Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) is a reliable and accurate method for the diagnosis of mediastinal metastases in patients with pulmonary and extrathoracic neoplasms. We report the cytopathologic findings of a case of metastatic signet-ring cell carcinoma with abundant extracellular mucin production in the mediastinal lymph nodes of a 41-year-old woman, who presented with nausea, abdominal pain, and weight loss. Imaging studies showed a renal mass, numerous lung nodules, and mediastinal and retroperitoneal lymphadenopathy. EBUS-TBNA of level 4R and 7 lymph nodes showed abundant, thick, “clean” mucus with entrapped ciliated bronchial cells, rare histiocytes, and fragments of cartilage. No neoplastic cells could be identified in Diff-Quik®-stained smears during the rapid on-site evaluation, but rare signet-ring cells were identified in the Papanicolaou-stained smears and cellblock sections. A distinctive feature of the aspirates was the presence of large branching (arborizing), “spidery” stromal fiber meshwork fragments. These stained metachromatically (magenta) with Romanowsky-type stains and cyanophilic to orangeophilic with Papanicolaou stains and showed occasional attached bland spindle cells, but had no capillary lumina or CD31-staining endothelial cells. The tumor cells were strongly and diffusely positive for CEA, CDX2, CK7, CK20, and MUC2, supporting the diagnosis of a metastatic signet-ring cell adenocarcinoma, most likely of gastrointestinal origin. We believe that the presence of the large spidery stromal fiber fragments is a useful clue to the presence of a mucinous neoplasm in EBUS-TBNA and allows the differentiation of the neoplastic mucus from contaminating endobronchial mucus. Diagn. Cytopathol. 2012; © 2012 Wiley Periodicals, Inc.

Cytological diagnosis is a valuable method for detection of mediastinal tumors, and recent reports have shown the usefulness of fine-needle aspiration cytology for diagnosis of mediastinal tumors, including germ cell tumors. We report a case of mediastinal seminoma diagnosed intraoperatively by cytological examination of cystic fluid containing tumor cells.

An anterior mediastinal tumor with cystic component was incidentally found in a 28-year-old Japanese male. Cytological examination of the cystic fluid at the time of tumor resection showed single and loose aggregates of large round to polygonal cells with large round nuclei, vesicular chromatin and nucleoli, and mild to moderate amounts of PAS-positive cytoplasm admixed with mature lymphocytes. A diagnosis of seminoma was made intraoperatively. On subsequent immunostaining, the tumor cells showed nuclear positivity for SALL4, a recently recognized germ cell marker that, in the appropriate setting, can be helpful to distinguish germ cell tumors from other mediastinal neoplasms, such as malignant lymphoma, thymoma, and thymic carcinoma. Diagn. Cytopathol. 2012; © 2012 Wiley Periodicals, Inc.

Herpes simplex virus (HSV) infection is usually observed in the oral cavity and external genitals, and HSV peritonitis is extremely rare. Herein, we report a case of type II HSV peritonitis successfully diagnosed by ascitic cytology. A 66-year-old Japanese man, who had been treated with steroid inhalation for 5 years due to chronic obstructive pulmonary disease, was suspected to have acute cholecystitis. Laparoscopic cholecystectomy and intraoperative cytological examination of ascitic fluid were performed. Cytological study of ascitic fluid revealed that abundant granular cell debris, degenerative cells and apoptotic bodies were present, as well as some single or multinucleated cells with ground glass nuclei. However, vivid mesothelial cells were rarely seen. Immunocytochemical staining for type II HSV was positive in single or multinucleated cells with ground glass nuclei. Therefore, a diagnosis of type II HSV peritonitis was made. This is the first reported case of type II HSV peritonitis successfully diagnosed by ascitic cytology. This report highlights that the presence of abundant cell debris, degenerative cells and apoptotic bodies, and the absence of vivid mesothelial cells are the key cytological findings to suspect HSV peritonitis, and the diagnosis can be confirmed by careful surveillance for characteristic nuclear findings of single or multinucleated cells. The frequency of opportunistic infection is increased because of the increased numbers of iatrogenic immunocompromised patients as seen in this case, therefore, cytological examination is a useful method for early detection of the causative agent of peritonitis including HSV. Diagn. Cytopathol. 2011; © 2011 Wiley Periodicals, Inc.

This study was to clarify the nuclear features of “condensed clusters of stromal cells (EGBD-stromal cells)” and “metaplastic clumps with irregular protrusions (EGBD-metaplastic cells)” which may be recognized in endometrial glandular and stromal breakdown (EGBD) cases in liquid-based cytologic (LBC) preparations of endometrial brushings. The material consists of cytologic smears of 20 cases of proliferative endometrium (PE), 20 cases of EGBD, and 20 cases of endometrioid adenocarcinoma grade 1 (G1) for which histopathological diagnosis was obtained by endometrial curettage. Nuclear findings were examined in PE cells, EGBD-stromal cells, EGBD-metaplastic cells, and G1 cells, respectively.

It was examined about the following items: (1) Nuclear shape; (2) A long/minor axis ratio in cell nuclei; (3) An area of cell nuclei; (4) Overlapping nuclei; (5) The distribution pattern of nuclei within cell clusters.

The following observations were made: (1) In PE cells, round-oval nuclei appeared to predominate, overlapping nuclei were not observed, and a slightly abnormal distribution pattern of nuclei was recorded; (2) In EGBD-stromal cells, reniform nuclei were characteristically observed, nuclei had small size and a generally elongated appearance, overlapping nuclei were recognized, and a remarkable abnormal distribution pattern of nuclei was found; (3) In EGBD-metaplastic cells, spindle nuclei were a characteristic feature, nuclei were larger in size and had a bipolar appearance, overlapping nuclei with moderately abnormal distribution pattern of nuclei were identified; (4) In G1 cells round-oval nuclei predominated, overlapping nuclei with moderately abnormal distribution pattern of nuclei were found.

The study demonstrates that the analysis of selected nuclear findings appears to be very useful in the cytopathological assessment of endometrial lesions in LBC samples, especially for the discrimination of EGBD and G1. Diagn. Cytopathol. 2012; © 2012 Wiley Periodicals, Inc.

The patient is a 75-year-old man with axillary lymphadenopathy presenting an indurated papule on his buttock. Touch imprint cytology of the biopsied axillary lymph node revealed the monotonous appearance of medium-sized tumor cells. The nuclei had a slightly irregular contour, finely dispersed chromatin, and a conspicuous nucleolus. Some tumor cells had intracytoplasmic microvacuoles. Immunohistochemistry of the imprint specimens showed that the tumor cells were positive for CD56 and CD123. Histological diagnosis of the lesion was blastic plasmacytoid dendritic cell neoplasm (BPDCN). Epstein-Barr virus-encoded RNAs were not detected in the tumor cells. Neither immunoglobulin heavy chain genes nor T- cell receptor genes was clonally rearranged. BPDCN should be strongly considered during the differential diagnosis of CD56-positive neoplasms of the skin. We demonstrated a possible contribution of the cytomorphological and immunohistochemical findings of the touch imprint specimens to the diagnosis of BPDCN. Diagn. Cytopathol. 2012; © 2012 Wiley Periodicals, Inc.

Intrapancreatic accessory spleen is not an uncommon entity and usually located in the tail of the pancreas. Most of them are asymptomatic and incidental findings on radiologic study or at autopsy. On imaging study, it appears to be a well-defined, solitary, and hypervascular lesion; therefore, it may be confused with pancreatic neoplasms, such as neuroendocrine neoplasm, well-differentiated adenocarcinoma, solid pseudopapillary tumor, or metastatic tumor to the pancreas. As such, the diagnostic fine-needle aspiration biopsy of the lesion may be performed. Several case reports describing cytological features of the lesion have been published in recent years. Among them, the most commonly identified cytological findings are sheets of a heterogeneous population of lymphocytes and prominent traversing blood vessels. Herein, we report an unusual EUS-FNA case of intrapancreatic accessory spleen. In addition to above previously well-described cytological features, our case revealed many cells with fine granular chromatin and areas with pseudo rosette-like architecture, mimicking and engendering the differential diagnosis of pancreatic neuroendocrine tumors. Although cytological findings of our case are rare, they may extend our current knowledge and provide additional differential diagnostic information for this entity. Diagn. Cytopathol. 2012; © 2012 Wiley Periodicals, Inc.

Primary squamous cell carcinoma of the endometrium (PSCCE) is a rare entity, with fewer than 100 cases reported in the literature. We report two cases of PSCCE and review the literature regarding associated markers and treatment outcomes. Many different markers have been tested for association with PSCCE, with mixed results. Thus, it is likely that several etiologic factors are responsible for the development of PSCCE. Further, due to the rarity of the condition, the optimal postoperative management of patients with PSCCE remains to be defined. Diagn. Cytopathol. 2012; © 2012 Wiley Periodicals, Inc.

Primary strumal carcinoid tumor of the ovary (SCTO) is an extremely rare entity, though the survival rate is excellent if the disease is confined to one ovary. A case is presented here in which intraoperative squash smears in a 45-year-old woman with a left adnexal mass revealed dispersed or small clusters of neoplastic cells forming loosely cohesive gland-like structures with abundant cytoplasm. The nuclear chromatin was finely granular with a “salt and pepper” appearance and occasional tiny nucleoli. The position of the nucleus presented a vaguely plasmacytoid appearance. Small fragments of thyroidal colloid-like structures were also identified. A cytopathologic diagnosis of a SCTO was suggested. Further evaluation and immunohistochemical studies were conducted on formalin-fixed, paraffin-embedded material. Cords or nests of uniform cells with abundant cytoplasm, and eccentric nuclei with coarse chromatin and occasional colloidal tissue were identified on H&E sections. The tumor cells showed diffuse and strong cytoplasmic staining for chromogranin A, synaptophysin, CD56, and vimentin but were negative for calretinin, α-inhibin or CDX2. The proliferative index with MIB-1 was around 3%. Thyroidal colloid-like structures were immunoreactive for thyroglobulin and TTF-1 stains. The diagnosis of primary SCTO was confirmed based on cytopathologic, histopathological, and immunohistochemical results, and the location of the tumor. Awareness of the cytopathological findings of SCTO can assist in diagnosing this rare entity correctly. Diagn. Cytopathol. 2011; © 2011 Wiley Periodicals, Inc.

Psammoma bodies (PBs) in breast lesions are rare and little is known about the role of these structures in breast pathology. This study has looked in to the diagnostic significance of PBs in fine needle aspiration (FNAC) of breast lesions. Over a 5-year period, FNACs of the breast were done in 4,563 subjects, of which 1,678 were diagnosed to be malignant. On review of all breast aspirates including non-neoplastic lesions, 30 cases showed PBs to be associated with breast carcinoma (BC). Cytological features were correlated with clinical, radiological, histological, and immunohistochemical findings. All 30 aspirates and their corresponding histological sections showed varying number of PBs and nonpsammomatous bodies (NPBs). For comparison, 31 cases of age-matched BC without PBs and NPBs in both aspirates and sections were studied. Statistical analysis using Chi-square test was done to compare BC with and without PBs. BC with PBs was characterized by papillary pattern of malignant cells, mucin in the background, infiltration by macrophages, cellular degeneration, overexpression of estrogen receptor (ER), and progesterone receptor (PR) and moderate positivity (2+) for Her2/neu. Calcium deposition has long been implicated in the pathogenesis of many degenerative diseases; hence the formation of PBs may be relevant in breast oncology. The presence of PBs in FNAC of clinically suspected breast lesions which are cytologically negative for malignancy warrants further histological confirmation. Diagn. Cytopathol. 2011; © 2011 Wiley Periodicals, Inc.

Merkel cell carcinoma represents a highly aggressive cutaneous malignancy characterized by regional recurrences, lymph node metastases, distant metastases, and high mortality. As the cytomorphology of Merkel cell carcinoma can be mimicked by other malignancies, especially lymphoma and pulmonary small cell carcinoma, immunocytochemistry is often useful in confirming the diagnosis. Cell blocks, which are traditionally utilized for immunocytochemistry, occasionally exhibit insufficient cellularity. Hence, we prospectively investigated the application of CK20 immunocytochemistry to air-dried, unstained direct smears in the diagnosis of Merkel cell carcinoma fine needle aspirates (FNAs). Eight consecutive FNAs of Merkel cell carcinoma were prospectively examined in this series; seven (88%) cases exhibited immunoreactivity for CK20 in the tumor cells. The one CK20-negative Merkel cell carcinoma was immunoreactive for synaptophysin and CD56. This immunophenotype was identical to that of the original primary tumor. For comparison, air-dried direct smears prepared from three pulmonary small cell carcinoma FNAs were examined by CK20 immunocytochemistry. In all cases, no CK20 immunoreactivity was seen in any of the tumor cells. In conclusion, direct smears represent a feasible and robust source of cellular material for immunocytochemical studies to diagnose Merkel cell carcinoma. This methodology allows the cytologist to confirm on site that material for diagnostic immunocytochemistry is present thereby serving as a safeguard in instances where insufficient cell block cellularity is anticipated or encountered. Diagn. Cytopathol. 2011; © 2011 Wiley Periodicals, Inc.

Squamous metaplasia (SM) occurs in a variety of thyroid conditions, both neoplastic and non-neoplastic. In a small subset of benign thyroid lesions, SM can create a diagnostic pitfall by mimicking a malignant process. Here, we describe the case of a 52-year-old male with a 1.5 cm right thyroid nodule. Ultrasound-guided fine-needle aspiration biopsy showed markedly atypical, mitotically active epithelial cells which were suspicious for high-grade carcinoma. Resection of the nodule demonstrated a follicular adenoma with cystic changes and atypical SM of the cyst-lining component. As illustrated here, SM of the thyroid represents an important diagnostic pitfall for the cytopathologist, and should be included in the differential diagnosis of thyroid nodules, particularly those with potentially benign cystic changes. Diagn. Cytopathol. 2011; © 2011 Wiley Periodicals, Inc.

Calcitonin (CT) measurement on fine-needle aspiration cytology (FNAC) washouts (FNAC-CT) is a promising tool in the diagnosis of medullary thyroid carcinoma (MTC). Guidelines for the method with codified cut-off are needed to use this technique in clinical routine. This study was undertaken to assess the best pre-analytical procedure and to define a reliable reference value for FNAC-CT. Fifty-four patients underwent thyroid surgery, so MTC was excluded by surgical pathology examination and CT immunostains. Before surgery, FNAC-CT was measured on 78 thyroid nodules from such 54 patients. Needles were rinsed by normal saline and specific CT-free dilution buffer, and CT was measured by a fully automated immunochemiluminometric assay. FNAC-CT levels were not significantly different in normal saline or specific buffer. The calculated 97.5th upper FNAC-CT value was 8.5 pg/mL (saline) and 7.43 pg/mL (buffer), respectively. Seeing its relatively large sample size, rigorous selection criteria and inclusion of CT immunostaining of thyroid nodules, the present study provides a reliable guideline and a clinically relevant reference value for FNAC-CT measurement in thyroid nodules. Diagn. Cytopathol. 2011; © 2011 Wiley Periodicals, Inc.

On fine-needle aspiration (FNA) biopsy, clear cell parathyroid lesions can be misdiagnosed as thyroid neoplasms, salivary gland neoplasms, paraganglioma, or even metastatic renal cell carcinoma. We report the clinicopathological, cytologic, and histologic findings of a clear cell parathyroid tumor in a 64-year-old HIV-positive patient. A computed tomography (CT) scan with contrast showed a heterogeneous and enhancing mass at the inferolateral aspect of the left thyroid lobe. FNA showed a cellular smear with many single and loosely clustered tumor cells with finely granular and vacuolated light-purple cytoplasm and central nuclei. Occasional microfollicular structures were noted. No colloid was seen. This FNA was misdiagnosed as a follicular neoplasm of the thyroid. Sections of the excised mass showed large polyhedral cells with well-defined cell membranes and clear cytoplasm with a small amount of eosinophilic granular material. These clear cells were positive for pancytokeratin and PTH immunohistochemical stains. These results favored a diagnosis of parathyroid Water Clear Cell Adenoma. This brief report highlights the cytologic findings of clear cell parathyroid lesions and their potential diagnostic pitfalls. Diagn. Cytopathol. 2011; © 2011 Wiley Periodicals, Inc.

Serum calcitonin is a tumor marker used in the diagnosis and follow-up of medullary thyroid carcinoma. Calcitonin washout evaluation is a new method used for suspicious thyroid nodules and lymph nodes. Limited clinical data are present about the efficacy of this method. A 61-year-old female patient with known Hashimoto's thyroditis and an 8-mm hypoechoic nodule was presented with one previously benign fine-needle aspiration cytology (FNAC). On referral to our department, she had a moderately high-serum calcitonin level, and we repeated the FNAC that was reported as nondiagnostic. We performed FNAC for the third time together with calcitonin washout evaluation from the thyroid nodule. The FNAC was again nondiagnostic, but the calcitonin washout level from the thyroid nodule was 152.569 pg/mL. Total thyroidectomy was performed, and the diagnosis was confirmed as medullary thyroid carcinoma. Calcitonin washout evaluation may be a useful method in the differential diagnosis of patients with thyroid nodules having moderately high-serum calcitonin levels. Diagn. Cytopathol. 2011; © 2011 Wiley Periodicals, Inc.

Epidermal growth factor receptor (EGFR) mutation status has been shown to predict response to anti-EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). In patients with advanced-stage NSCLC, evaluation of mutational status is increasingly requested on biopsy or fine-needle aspiration specimens, which often have limited material. There are limited data on the suitability of cytology cell blocks (CB) for EGFR mutation testing. In this study, we report our institutional experience with cytology cell block material for EGFR mutation testing. We retrospectively reviewed EGFR mutation analyses performed on 234 surgical (SP) and cytology (CB) from October 2007 to May 2010. One hundred ninety-two SP specimens and 42 CB specimens were evaluated for EGFR mutation. CB specimens were evaluated for overall specimen size based on aggregate cellularity in comparison to small biopsy specimens, and percent tumor. Of the 192 SP and 42 CB specimens, 31 (16.1%) and 11 (26.2%) were positive for EGFR mutation, respectively; there does not appear to be an association between mutation detection rate and the source of the specimen (P = 0.124). Limited DNA was obtained from 70.0% (29/42), including 81.8% (9/11) of those which were mutation positive. Additionally, 45.4% (5/11) of mutation positive specimens had extremely low DNA yields. Although 16.6% (7/42) of CB specimens had <10% tumor, all 11 mutation positive CB cases had >10% tumor. These data indicate that CB specimens provide an alternative source for molecular evaluation of NSCLC, and that tumor percentage may be more important than specimen size and/or DNA yield in determining the suitability of these specimens for testing. Diagn. Cytopathol. 2011; © 2011 Wiley Periodicals, Inc.

The cytopathologic diagnosis of basaloid squamous cell carcinoma can be problematic as there are several components of the differential diagnosis that share common cytomorphologic features. In this study, we report the fine-needle aspiration (FNA) findings of 16 basaloid squamous cell carcinoma cases and compare those cases to 16 cases of small cell carcinoma. To our knowledge, this is the largest series of basaloid squamous cell carcinoma FNA cases ever reported. The following cytomorphologic features were compared for both tumors: cohesive tissue fragments, single cells, adenoid cystic-like features (cribriform pseudoglandular lumina with hyaline materials), necrosis, nuclear size, nuclear molding, nucleoli, cytoplasm, and the presence of single keratinized cells. Adenoid cystic-like features and the presence of single keratinized cells were specific for basaloid squamous cell carcinoma (P < 0.05). Diagn. Cytopathol. 2011; © 2011 Wiley Periodicals, Inc.

Chordomas are rare tumors that are usually located in the sacrococcygeal and sphenooccipital region. Their cytologic diagnosis is rather straightforward when sampled by fine-needle aspiration (FNA) from these characteristic locations, especially when physalipherous cells are present. However, chordomas may pose difficult diagnostic challenges when encountered in unusual locations, such as the parapharyngeal region. We report the cytologic findings of a recurrent chordoma sampled through transoral FNA from the parapharyngeal space of a 66-year-old woman. As the prior history of chordoma was not available during the rapid onsite evaluation, the presence of bland epithelioid nonvacuolated cells and spindle cells intimately admixed with a fibrillary, intensely metachromatic material led to an initial diagnosis of pleomorphic adenoma. Review of the patient's prior pathology specimen and of the Papanicolaou-stained smears and cellblock sections showing rare multivacuolated (physalipherous) cells led to the correct diagnosis, which was supported by immunoperoxidase stains (cytokeratin AE1/AE3+, S100+, GFAP−). A review of the literature found no previous instances in which chordomas mimicked pleomorphic adenoma on FNA. However, since the two tumors show significant cytomorphologic overlap, including the presence of abundant fibrillary matrix with embedded neoplastic cells and single bland spindle and epithelioid tumor cells with occasional intranuclear pseudoinclusions, we compared their cytologic features. A review of the FNA cytologic features of this case of chordoma and of 17 consecutive cases of pleomorphic adenoma found that the presence of a more abundant, focally vacuolated cytoplasm favors chordoma over pleomorphic adenoma. Diagn. Cytopathol. 2011. © 2011 Wiley Periodicals, Inc.

Herein, we described a case of a 29-year-old female with a large ovarian mass. Fine needle aspiration cytology (FNAC) of the mass showed discrete round to oval cells in a fatty vacuolated background. FNAC diagnosis of dysgerminoma was suggested. The histology of the tumors showed features of poorly differentiated Sertoli–Leydig cell tumors. We discussed the diagnostic pitfalls of this case on FNAC. Diagn. Cytopathol. 2011. © 2011 Wiley Periodicals, Inc.

There is a paucity of prospective data on flexible bronchoscopy with rapid on-site evaluation (ROSE) in the setting of superior vena cava (SVC) syndrome. The aims of this prospective study were to assess the diagnostic yield and safety of these investigations and specifically to evaluate the role of ROSE in limiting the need for tissue biopsies. Over a 5-year period 48 patients (57.4 ± 9.7 years) with SVC syndrome secondary to intrathoracic tumors underwent flexible bronchoscopy with TBNA and ROSE. Endobronchial Forceps biopsy was reserved for visible endobronchial tumors with no on-site confirmation of diagnostic material. ROSE confirmed diagnostic material in 41 cases (85.4%), and in only one of the remaining cases did the addition of a forceps biopsy increase the diagnostic yield (overall diagnostic yield of 87.5%). No serious complications were noted. The final diagnoses made included nonsmall lung cancer (n = 27), small cell lung cancer (n = 16), and metastatic carcinoma (n = 3). Two undiagnosed cases died of suspected advanced neoplasms (unknown primary tumors). We conclude that TBNA has a high diagnostic yield and is safe in the setting of SVC syndrome. With the addition of ROSE, tissue biopsy is required in the minority of cases. Diagn. Cytopathol. 2011. © 2011 Wiley Periodicals, Inc.

Gangliocytic paragangliomas are rare tumors primarily found in the duodenum. We report a case of a woman who presented with a retroperitoneal lymph node involved by metastatic gangliocytic paraganglioma. Subsequently, fine-needle aspiration (FNA) cytology was used to identify the primary duodenal gangliocytic paraganglioma. The smears of the aspirate material were highly cellular and contained a dominant population of epithelioid cells, a second population of ganglion cells and a third population of small, bland spindled cells. To our knowledge, the cytologic features of gangliocytic paraganglioma have not previously been documented. Diagn. Cytopathol. 2011. © 2011 Wiley Periodicals, Inc.

Extramedullary hematopoiesis (EMH) is the production of mature blood elements outside of the bone marrow and can occur as a compensatory result of a marrow replacing process or from marrow space occupying lesions such as tumor or marrow fibrosis. EMH can also be induced by factors elicited by neoplasms, such as vascular endothelial growth factor (VEGF). Usually, EMH is a diffuse process most commonly observed in lymph nodes, liver, and spleen. Rarely, EMH can form a mass lesion. Although the spleen is a common site for diffuse EMH, it is a rare location for a mass forming EMH. Hemangiomas are the most common benign tumors of the spleen.

A case of a discrete, 8 cm lesion was noted incidentally on CT scan in a 59-year-old man with no significant past medical history. Endoscopic ultrasound guided fine-needle aspiration (EUS FNA) biopsy was performed and cytologic examination revealed trilinear hematopoiesis, with the most distinctive elements being megakaryocytes and erythroid precursors. A diagnosis of EMH was made. On resection, the mass was a hemangioma with EMH.

EUS guided FNA is a useful tool for diagnosing splenic masses. Awareness of EMH, both as a mass forming lesion and a feature associated with benign and malignant vascular lesions is important, especially in patients with hematologic malignancies or marrow replacing processes. Diagn. Cytopathol. 2011. © 2011 Wiley Periodicals, Inc.

Reporting of benign appearing endometrial cells (BECs) in the Papanicolaou smears of women aging 40 years or older was mandated in the Bethesda System 2001 aiming at predicting the uterine pathology. The purpose of this study was to determine the clinical significance of the BECs in patients in our Medical Center. A two-arm study was designed in ≥40-years-old women with BECs and without BECs in their Pap smears from January 2002 to December 2004. Of 21,965 patients, 882 had BECs in their Pap smears and the rest did not. Among the patients with BECs, 186 (study group) and among those without BECs, 2,064 (control group) had histopathologic follow-ups. There were 4 patients in the study and 47 in the control groups who had uterine adenocarcinoma. The Chi-square P-value for adenocarcinoma between the two groups was 0.91; indicating insignificant differences between the two groups. We conclude that presence of BECs in the Pap smears of ≥40-years-old women signal no significance as a harbinger of endometrial adenocarcinoma. Diagn. Cytopathol. 2011;. © 2011 Wiley Periodicals, Inc.

Tumor cytology has proven to be inadequate for precise diagnosis of thyroid follicular adenoma. This suggests the need for a molecular approach for its diagnosis.

Expression of CD26/DPPIV (dipeptidyl peptidas IV), p53, and PTEN was analyzed in smears or sections obtained from 19 patients with histologically proven thyroid follicular adenoma. Papanicolaou staining, CD26/DPPIV activity staining, and HE staining were performed and the specimens were observed morphologically. Immunohistochemical analysis using antibodies against p53 and PTEN was performed. Genetic mutation of PTEN exons was performed using the laser capture microdissection method.

The nuclear area of the CD26/DPPIV-positive cells was significantly larger than that of the CD26/DPPIV-negative cells. p53 expression was not observed any specimen. PTEN expression was observed in 18 of 19 cases. DNA sequence analysis did not reveal mutations in exons 5–9 of PTEN in the immunohistochemically PTEN-negative case.

In accordance with our previous reports, we found that observation of concomitant CD26-positive and PTEN-negative status in cases of follicular adenoma suggests a state close to follicular carcinoma or progression to cancer, thus warranting careful follow-up. Diagn. Cytopathol. 2011;. © 2011 Wiley Periodicals, Inc.

Angiomatoid fibrous histiocytoma (AFH) is an uncommon and mostly indolent soft tissue neoplasm, which usually occurs in the subcutaneous tissue of the extremities in children and young adults. Although the histologic features of AFH are well established, reports of its cytomorphology are very limited. This report characterizes the cytomorphologic features of five cases of AFH, with correlation to clinical, histology, and cytogenetic findings.

Smears of fine needle aspiration (FNA; four cases) and intraoperative scrape (one case) were reviewed from five patients with a histologically confirmed diagnosis of AFH. A review of six previously reported AFH cases with cytomorphology was also performed.

The tumor presented as a cystic, deep dermal mass in three pediatric cases and as a solid, deeply seated mass in two adults. The cytomorphologic features are mostly nondistinctive and include cellular smears with ovoid to spindled histiocytoid cells that may be isolated or in clusters. Some of these cells are atypical and others contain hemosiderin. Large cellular clusters with a capillary structure and a whorled arrangement of tumor cells can be appreciated in some cases. There is always a bloody background, but a lymphoplasmacytic infiltrate is uncommon. The presences of EWSR1 rearrangement in one case and three copies of FUS gene in another case were detected by fluorescence in situ hybridization.

Diagnosing AFH by FNA cytology alone can be challenging because of its rarity and usually nonspecific cytologic findings. Clinical correlation and ancillary studies are essential to reach a specific diagnosis of AFH in small needle biopsies. Diagn. Cytopathol. 2011;. © 2011 Wiley Periodicals, Inc.

Intrapancreatic and intraabdominal accessory spleens (IPIASs) are rarely encountered in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsies. However, as incidentally discovered IPIAS can mimic a benign or malignant pancreatic neoplasm on imaging studies, a definitive diagnosis made by EUS-FNA can avert an unnecessary surgical intervention or additional radiologic follow-up. We report five cases of intrapancreatic splenules and one case of accessory spleen (AS) in which a definitive diagnosis was made on EUS-FNA. Previously recognized FNA cytomorphologic features of splenic tissue, including ASs and splenosis, are endothelial cells and polymorphous lymphocytes admixed with neutrophils, eosinophils, plasma cells, histiocytes, and lymphoglandular bodies. We describe the additional finding of abundant large platelet aggregates as another distinguishing feature of splenic tissue on FNA. In all six cases, large platelet aggregates were identified along with polymorphous lymphoid cells, lymphoglandular bodies, loose aggregates of endothelial cells and scattered or aggregated bland spindle cells. A review of 10 consecutive cases of EUS-FNA-sampled benign intraabdominal lymph nodes showed that the presence of large platelet aggregates, three-dimensional aggregates of lymphoid cells and of bland slender spindle cells and the absence of follicular germinal cell components (tingible body macrophages and lymphohistiocytic aggregates) are useful in differentiating IPIASs from reactive lymph nodes. Immunoperoxidase stains were useful to confirm a suspected IPIASs by showing CD31-positive acellular flocculent material, consistent with large platelet aggregates and a rich CD8-positive endothelial cell network between CD45-positive lymphoid cells and CD68-positive histiocytes in all six cases. Diagn. Cytopathol. 2011;. © 2011 Wiley Periodicals, Inc.

The assessment of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2) status in the fine needle aspirates of metastatic breast carcinomas has prognostic and therapeutic implications. In this study, expression of ER, PR, and HER2 was assessed by immunohistochemical study in 70 cases of metastatic breast carcinomas and HER2 gene amplification was further evaluated by fluorescence in situ hybridization (FISH) in 38 (54%) cases. Positive expression of ER and PR was seen in 42 (60%) and 16 (23%) cases of metastatic breast carcinomas, respectively. HER2 immunoreactivity was scored as 0/1+ in 39 (56%), 2+ in 10 (14%), and 3+ in 21 (30%) cases. HER2 gene amplification was seen in 20% of HER2 2+ and 64% of HER2 3+ cases. ER, PR, and HER2 status in primary breast cancers were available to comparison in 31 cases (44%). The concordance rates between metastatic and primary breast carcinomas were 81% for ER, 65% for PR and 71% for HER2. Our study demonstrates that ER, PR, and HER2 status can be assessed in the fine needle aspirates of metastatic breast carcinomas and ER has a higher concordance rate between metastatic and primary breast carcinomas than PR and HER2. The addition of HER2 gene amplification FISH test helps in accurate assessment of HER2 status in metastatic breast carcinomas. Diagn. Cytopathol. 2011;. © 2011 Wiley Periodicals, Inc.

BD FocalPoint GS™ computer-assisted screening of BD SurePath® liquid-based cervical cytology slides (SP + FP) was compared with screening an accompanying conventional cervical Papanicolaou (Pap) smear (CON) in a split sample trial of 2,198 routine specimens. The rate of unsatisfactory specimens in the SP + FP arm was 0.2% compared with 4.1% in the conventional Pap smear, a significant reduction. There was no statistically significant difference between SP + FP and CON for the detection of histologically confirmed high-grade (HG) lesions in the routine split sample specimens (n = 9). To further test the sensitivity of SP + FP for HG lesions, 38 SurePath slides from confirmed HG cases, without an accompanying CON, were interpolated among the routine smears. In every one of the 47 confirmed HG cases, either HG cells were present in the microscope fields selected by FocalPointGS™ for review by the screening cytologist (46 of 47), or full screening of the slide was indicated by the FocalPointGS™ (1 of 47), confirming the effectiveness of SP + FP technology for primary screening. In a small number of cases, the screening cytologist did not recognize the abnormality even though on review HG cells were present in fields selected by FocalPointGS™. The overall detection rate was 93% for HG squamous lesions; 89% for known HG endocervical glandular lesions; and 91% for known endometrial carcinoma. In conclusion, the SP + FP detected 100% of HG abnormalities in the trial set; significantly reduced the rate of unsatisfactory specimens; and improved the overall screening rate of detection of HG abnormalities particularly of glandular lesions when compared with other screening technologies. Diagn. Cytopathol. 2011;. © 2011 Wiley Periodicals, Inc.

No absract.

Vaginal lactobacilli assessed by PCR-based microarray and PCR-based genotyping of HPV in South African women at risk for HIV and BV.

Vaginal lactobacilli can be defined by microarray techniques in fixed cervical samples of South African women. Cervical brush samples suspended in the coagulant fixative BoonFix of one hundred women attending a health centre for HIV testing in South Africa were available for this study. In the Ndlovu Medical Centre in Elandsdoorn, South Africa, identification of 18 hr-HPV genotypes was done using the INNO-LiPA method. An inventory of lactobacilli organisms was performed using microarray technology.

On the basis of the Lactobacillus and Lactobacillus biofilm scoring, the cases were identified as Leiden bacterial vaginosis (BV) negative (BV-; n = 41), Leiden BV intermediate (BV±; n = 25), and Leiden BV positive (BV+; n = 34).

Fifty-one women were HIV positive and 49 HIV negative. Out of the 51 HIV positive women, 35 were HPV infected. These 51 HIV positive women were frequently infected with HPV16 and HPV18. In addition, HPV35, HPV52, HPV33, and HPV66 were often detected in these samples. Lactobacillus salivarius and Lactobacillus iners were the most prevalent lactobacilli as established by the microarray technique. In women with HPV infection, the prevalence of Lactobacillus crispatus was significantly reduced. In both HIV and HPV infection, a similar (but not identical) shift in the composition of the lactobacillus flora was observed. We conclude that there is a shift in the composition of vaginal lactobacilli in HIV-infected women. Because of the prominence of HPV35, HPV52, HPV33, and HPV66, vaccination for exclusively HPV16 and HPV18 might be insufficient in South African HIV+ women. © 2011 Wiley Periodicals, Inc.

There are limited studies on the utility of immunostaining in cytologic specimens suspected of melanoma. In this study, we examined the performance of the most commonly used antibodies including monoclonal antibodies against Melan-A (A103), S-100, and HMB-45 antigens. Immunostains were performed on formalin-fixed, paraffin-embedded cell blocks prepared from 100 cytologic specimens. The specimens consisted of 57 melanomas and 43 nonmelanocytic neoplasms. Of 57 melanomas, 53 showed positive reaction to Melan-A antibody while 51 and 41 revealed positive immunostaining for S-100 and HMB-45, respectively. Of 43 nonmelanocytic neoplasms, 10, 4, and 8 specimens stained positive with an antibody against S-100, HMB-45, and Melan-A, respectively. However, the false-positive immunostaining for Melan-A was eliminated in seven of the eight specimens after applying the pretreatment with avidin/biotin blocking reagents. Overall, the highest sensitivity and negative predictive value (NPV) were achieved in Melan-A antibody (93 and 90%) compared with antibodies to S-100 (89 and 85%), and HMB-45 (72 and 71%). Initially, an intermediate specificity and positive predictive value (PPV) were obtained for Melan-A antibody (81 and 87%) that were greater than S-100 (77 and 84%), and lower than HMB-45 (91 and 91%). However, the aforementioned treatment with avidin/biotin blocking reagents improved both specificity (98%) and PPV (98%) for Melan-A antibody. In conclusion, by blocking endogenous biotin, Melan-A antibody offers the greatest performance. In terms of cost-effectiveness, we suggested that Melan-A antibody should be used as the first-line antibody for detecting melanoma in the cytologic specimens. © 2011 Wiley Periodicals, Inc.

Intraparotid spindle cell lipoma (SCL) of the salivary gland is a rare entity. Review of the literature revealed only two previous reports describing its cytological features. We report a case of a 44-year-old man who complained for a slowly growing, asymptomatic mass in the left parotid gland that since 12 months. Fine needle aspiration biopsy (FNAB) showed a loose collections of bland-appearing spindle cells in a myxoid background admixed with capillary fragments and some mature fat cells suggesting a diagnosis of SCL. A cytological diagnosis of mesenchymal myxoid spindle cell tumor with lipomatous differentiation, possibly an intraparotideal SCL was performed. Histological examination of the mass and the positive immunostaining for CD34 and negativity for S-100, CK-cocktail, and actin confirmed the diagnosis of SCL. The diagnosis of intraparotid SCL can be made by examining cytologic material containing mature fat with bland spindle cells in a myxoid background. FNAB diagnosis on SCL also allows to rule out other primary salivary gland tumors that may be clinically and instrumentally indistinguishable and thereby permits an appropriate surgical procedure to ensue. © 2011 Wiley Periodicals, Inc.

Lymphohistiocytoid malignant mesothelioma is an infrequent variant of sarcomatoid mesothelioma representing approximately 0.5–3.3% of malignant mesotheliomas. It has been related to asbestos exposure. The tumor is characterized by a diffuse large histiocyte-like cells proliferation mixed with an inflammatory infiltrate of lymphocytes and plasma cells. Its cytological diagnosis is difficult. We present a case of a 67-year-old female with lymphohistiocytoid mesothelioma involving the left pleura. The cytological, histological, and immunohistochemical features are discussed. © 2011 Wiley Periodicals, Inc.

Large three-dimensional cell aggregates and psammoma bodies are usually encountered in benign serous effusions (mesothelial hyperplasia and endosalpingiosis), mesotheliomas, and metastatic papillary carcinomas. We report a case of pulmonary small-cell carcinoma occurring in an 88-year-old woman that initially presented with a malignant pleural effusion characterized cytologically by a predominance of large three-dimensional neoplastic cell aggregates (“cannonballs”), associated with rare psammoma bodies. Although the crowded three-dimensional tumor-cell aggregates did not allow detailed cytologic examination, the diagnosis of metastatic small-cell carcinoma could be established noting the characteristic chromatin features of the occasional single neoplastic cells and the characteristic “cell-in-cell” and “stack-of-coins” arrangements of rare small clusters of neoplastic cells. Immunoperoxidase stains showing positivity of the tumor cells for CD56, synaptophysin, and TTF1 further supported this diagnosis. Endobronchial ultrasound-guided fine-needle aspiration of a mediastinal lymph node subsequently confirmed the diagnosis of pulmonary small-cell carcinoma. Metastatic pulmonary small-cell carcinoma should be considered in the differential diagnosis of serous effusions showing large three-dimensional neoplastic cell aggregates and psammoma bodies to prevent a potential diagnostic pitfall. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

In this study, we applied artificial neural network (ANN) for the diagnosis of lobular carcinoma in fine-needle aspiration cytology (FNAC) material. We selected a total of 64 cases of histology proven breast lesions consisting of 20 fibroadenomas, 28 infiltrating ductal carcinomas (IDC), and 16 infiltrating lobular carcinomas (ILC). Detailed cytomorphological features were studied on representative Haematoxylin–Eosin (H&E) and May-Grunwald Giemsa stained slides. Image morphometric analysis was performed on Haematoxylin–Eosin stained smears to study nuclear area, diameter, perimeter, roundness, convex area, and convex perimeter. Both the qualitative cytological features and objective morphometric data were collected and a total of 18 variables were studied. Back propagation ANN was designed and this data were used as input values. ANN network was designed as 34-17-3. There were a total of 34 first layers neurons, 17 hidden neurons and three output neurons. The total cases were randomly divided automatically by the program into three groups: training set (40), validation set (8), and test set (16). After the successful training, the program was able to differentiate all the benign and lobular carcinoma cases and majority of the ductal carcinoma cases. In test set, the ANN program successfully classified all the cases of benign, and ILC cases and six of seven IDC cases. A suitably designed ANN may be able to diagnose the lobular carcinoma of breast on FNAC material. ANN is an efficient software program with immense potential. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

This study investigates the distribution of human papillomavirus (HPV) in women with abnormal cervical cytology in Kuwait. Two hundred and ninety-eight (298) abnormal ThinPreps were taken from women seeking routine gynecological care and screened for HPV DNA by real-time PCR. HPV genotyping was determined by PCR-based sequencing. HPV DNA was detected in 152 women (51%), and 29 different HPV genotypes were detected, comprising 16 high-risk (HR) (16, 18, 31, 33, 35, 39, 45, 51, 53, 56, 58, 59, 66, 68, 73, 97), nine low-risk (LR) (6, 11, 54, 61, 74, 81, 90, 102, 106), and four intermediate-risk (IR) (62, 67, 84, 87). HPV16 had the highest prevalence (24.3%), followed by HPV11 (13.8%), HPV66 (11.2%), HPV33 (9.9%), HPV53 (9.2%), HPV81 (9.2%), HPV56 (7.9%) and HPV18 (6.6%). HPV prevalence was 86, 67, and 89% in women with invasive cervical carcinoma (ICC), high-grade squamous intraepithelial lesion (HSIL) and low-grade squamous intraepithelial lesion (LSIL), respectively. As for age distribution, 69% of all HPVs were found in women aged 20–29 years, and the HPV incidence rate deceased with increasing age. The proportion of single infections decreased as the severity of the cytological diagnosis increased, while the proportion of multiple infections increased. This study is the first of its type in Kuwait and one of few in the Middle East. The findings are consistent with the hypothesis that HPV infection is the primary cause of cervical neoplasia. They support HPV vaccine research to prevent cervical cancer and efforts to develop HPV DNA diagnostic tests. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

While about 15% of menstruating women develop endometriosis, abdominal wall endometriosis is relatively rare. We present 10 cases of abdominal wall endometriosis diagnosed by fine-needle aspiration (FNA) cytology and confirmed by subsequent surgical excision. A palpable abdominal wall mass was the most common symptom, followed by pain. Nine cases were associated with previous surgery. The smear showed glandular epithelial cells and spindle or ovoid stromal cells accompanied by macrophages in eight cases. The nucleus was round-to-oval and the nucleolus was inconspicuous. Mitosis was not observed in any case. In two cases, which were suspicious of malignancy on FNA, the epithelial cells showed anisonucleosis, hyperchromasia, and small conspicuous nucleoli. The stromal cells were spindle or ovoid in shape, without metaplastic changes. Histiocytes were noted in nine cases and hemosiderin-laden histiocytes were noted in two cases. The proportion of inflammatory cells varied. FNA diagnosis of abdominal wall endometriosis is possible when the cytological features are interpreted cautiously, together with the patient's clinical history. An accurate diagnosis on FNA will prevent unnecessary surgery. Diagn. Cytopathol.2011;. © 2011 Wiley-Liss, Inc.

T-cell prolymphocytic leukemia (T-PLL) is a very unusual form of chronic lymphoproliferative disorder, which has rarely been diagnosed by fine needle aspiration (FNA) cytology. We report one such case with some overlapping cytomorphological features with chronic lymphocytic leukemia and acute lymphoblastic leukemia. A 91-year-old man presented with generalized lymphadenopathy, pleural effusion, ascites, and an ulcerated growth in rectum. FNA smears from the left cervical lymph node showed a monotonous population of small lymphoid cells having small but distinct nucleoli that was initially diagnosed as chronic lymphocytic leukemia (CLL). Smears from the left axillary lymph node contained both small and medium-sized lymphoid cells with frequent hand-mirror cell appearance, which has been described in acute lymphoblatic leukemia (ALL). Immunocyto/histochemical stainings on smears and cell block preparations of the aspirate showed the following immunophenotype: CD3+, CD4+, CD5+, CD7+, CD8-, CD20-, CD23-, and Tdt-. Total peripheral blood leukocyte count was 26.4 × 10⁹/L and total lymphocyte count, 8.3 × 10⁹/L with predominance of small lymphocytes. T-cell nature of the neoplasm was confirmed by biopsies from the cervical lymph node (T-cell lymphoma), bone marrow (T-cell lymphoid neoplasm/chronic lymphocytic leukemia), and the ulcerated rectal lesion (atypical T-cell lymphoproliferative disorder). The patient developed deep vein thrombosis, heparin-induced thrombocytopenia and bleeding from duodenal ulcer. By the time the reports of all the investigations were ready, the patient succumbed to bronchopneumonia. To the best of our knowledge, this T-CLL/T-PLL which was diagnosed initially by FNA cytology with immunocytochemical support is first of its kind to be reported. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Invasive breast cancer is divided into luminal A, luminal B, HER2 overexpression, basal-like (BL) and normal-like subtypes, among which the BL subtype has the worst prognosis. The purpose of this study was to determine the clinicopathological and cytological characteristics of BL breast cancer (BLBC). Fine-needle aspiration cytology samples from 17 patients with consecutive BLBC were investigated, and the findings were compared with those of other subtypes (10 cases each) for the following cytomorphological features: necrosis; lymphocyte infiltration; mitotic index; apoptosis; naked nuclei; nuclear/cytoplasmic ratio; nuclear margin, size and pleomorphism; chromatin granularity and density; and nucleolar appearance. Histologically, the BLBCs were heterogeneous, and included medullary carcinoma and metaplastic carcinoma, in addition to invasive ductal carcinoma. Cytologically, high mitotic index, naked nuclei, and irregular nuclear margin were significantly observed when compared with both the luminal A and B subtypes. Large nuclei with nucleoli and lymphocyte infiltration were frequently seen compared with the luminal A and B subtypes, respectively. Squamous nodules were seen in all metaplastic cases, but not in the HER2 overexpression subtype. Lymphocyte infiltration, squamous metaplasia, and nuclear findings such as a high mitotic index, naked or large nuclei, an irregular nuclear margin and the presence of nucleoli, may be clues indicating BLBC. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Histoplasmosis is usually an opportunistic fungal infection in patients with defective cell mediated immunity, and has been considered as one of the acquired immunodeficiency syndrome (AIDS) defining illness. However, cutaneous involvement in human immunodeficiency virus (HIV) positive patients is less common, and very rarely can be the initial presenting symptom for the diagnosis of AIDS. We present here an unusual case of multiple diffuse cutaneous nodular lesions predominantly in face, trunk, and upper extremities diagnosed initially on aspiration cytology as histoplasmosis. Subsequent serological test revealed positivity for HIV 1 and 2, along with a low CD4 count and low CD4:CD3 ratio. The cytomorphological features were further corroborated by histology and histochemical stains. Hence, cutaneous histoplasmosis can cause multiple wide spread nodular or umbilicated lesions in AIDS patients as the initial presentation. Fine needle aspiration cytology (FNAC) is a rapid, cost effective tool for diagnosis of the fungi from such lesions and initiating work up for immunocompromised states including AIDS. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

The urine fluorescence in situ hybridization (FISH) assay (UroVysion™), with the current scoring criteria, has a higher sensitivity than routine cytopathology but a lower specificity. Among 215 urine FISH tests we performed, 45 had associated histopathology and clinical follow up. In this study, a cell with four signals for each probe was classified as a uniform tetraploid cell (UTC); a presumed reparative cell which is currently classified as an abnormal cell in the FDA approved assay. By using the existing criteria, the tests were scored as positive or negative before and after exclusion of the UTCs. Before the exclusion, 24 positive, 13 negative, seven false positive, and one false negative result were obtained with 96% sensitivity and 65% specificity. After the exclusion, the results changed to 22 positive, 19 negative, one false positive, and three false negatives resulting in a 88% sensitivity of 88% and a 95% specificity; a significant improvement in the specificity. We conclude that exclusion of the UTCs as abnormal cells would result in a more solid performance of the FISH assay. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is a rare tumor. Moreover, there are only three reports to date that have focused on the cytologic findings of cervical LCNEC. We report the case of a 59-year-old Japanese woman with cervical LCNEC combined with small cell carcinoma (SmCC). Cytologic specimens from the uterine cervix demonstrated large cells with coarse chromatin and prominent nucleoli. Frequent mitotic figures were also observed. Curettage of the uterine endometrium revealed an endometrioid adenocarcinoma with squamous differentiation; i.e., an adenoacanthoma. Histologic examination of surgically resected uterine cervical tissue revealed LCNEC with minor foci of SmCC. Neuroendocrine differentiation in LCNEC was confirmed by immunohistochemistry for synaptophysin and CD56. Cytotechnologists or pathologists need to consider a differential diagnosis of LCNEC while examining cervical cytologic specimens; therefore, it is important to correctly identify the cytologic characteristics of this tumor. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Chromosomal instabilities (CIN) manifesting as structural or numerical alterations in the chromosomes are common in malignancies like breast cancer. Assessment of CIN in breast cancer may help to understand its etiopathogenesis. Micronucleus (MN) scoring and aneuploidy have been used to assess the presence of CIN in lymphocytes of various malignancies in the past. In this study, spontaneously occurring MN were counted in epithelial cells on fine needle aspiration cytology (FNAC) smears from 50 patients with benign and malignant breast lesions. Further, the ploidy status and S-phase fraction (SPF) of the samples was determined by flow cytometry. All these were then correlated with grades of breast cancer at cytology. Most IDC cases showed variable number of MN (n = 16, MN mean = 9.3), in contrast to the benign lesions (n = 26) where they were consistently absent. Aneuploidy and SPF analysis also showed a significant difference between benign (n = 10, mean DNA index [DI] = 0.96 ± 0.04, mean SPF= 8.07% ± 2.93) and malignant (n = 10, mean DI = 1.5 ± 0.41, mean SPF = 25.05% ± 10.35) lesions. On statistical analysis, a positive correlation was observed between the grades of IDC and presence of aneuploidy and high SPF (P-values < 0.05); however, the difference between the MN scores of grade 2 and 3 cancers was not significant. The study suggests that MN scoring and aneuploidy may be used to assess the presence of underlying CIN in IDC on FNAC smears. Further, collectively they may be explored for their role as biomarkers for predicting the tumor behavior in the breast cancer patients. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Primary clear cell carcinoma (CLCC) of the lung is an extremely rare disease and is a subtype of large cell carcinoma, according to the World Health Organization (WHO) classification. A case is presented here in which intraoperative squash smears in a 53-year-old man revealed sheet and small clusters or tumor cells with prominent nucleoli and fine granular chromatin. Abundant translucent cytoplasm with occasional cytoplasmic vacuoles and intracytoplasmic eosinophilic inclusions was also identified. A cytopathologic diagnosis of a CLCC was suggested. Further evaluation and immunohistochemical studies were conducted on formalin-fixed, paraffin-embedded material. Nests of slightly acidophilic clear tumor cells with a prominent cellular membrane and an alveolar growth pattern were identified on H&E sections. Immunohistochemically, the tumor cells showed diffuse and strong membranous staining for CK(AE1/AE3), CK7, and CA19-9 but were negative for Napsin A, CK20, CDX2, TTF-1, alpha-fetoprotein, chromogranin A, synaptophysin, CD10, and CD56. The diagnosis of primary CLCC of the lung was confirmed based on cytopathologic, histopathologic, immunohistochemical results, and a detailed systemic examination to exclude a possible extrapulmonary origin. We report here the cytopathological features of CLCC of the lung with an emphasis on differential diagnostic considerations. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

The aims of this study were to determine the expression of Ki-67 in type I and type II endometrial adenocarcinomas as well as normal endometrium in imprint smears and to correlate the results with clinicopathologic parameters of primary untreated endometrial cancer patients. During a 29-month period, 255 patients were evaluated with entometrial imprint cytology. Endometrial samples freshly resected from women who underwent total abdominal hysterectomy were studied. One hundred twenty-six patients had endometrial carcinoma and 129 cases were diagnosed as normal endometrium. The expression of Ki-67 was assessed by immunocytochemistry. Positive staining was correlated with increased stage, grade and lymph node metastases. High expression was more frequent in type II than type I endometrial adenocarcinoma and high-grade endometrial carcinoma had higher proportions of Ki-67 positive immunostaining compared with low-grade carcinoma. Proliferative endometrium showed high Ki-67 expression level, even higher than those of grade 1 and type I. On the other hand, secretory endometrium Ki-67 positive cells were markedly diminished and even disappeared. Completely negative staining was found to be related to atrophic endometrium. Immunocytochemical findings from Ki-67 stain, in addition to cytomorphologic features, appeared to be useful for the diagnosis of endometrial carcinoma in endometrial cytology with imprint smears. High Ki-67 expression correlates with morphologic features of aggressiveness and the expression pattern of Ki-67 correspond to the expected cyclic/atrophic pattern in normal endometrium. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

Fine-needle aspiration (FNA) diagnosis of oncocytic lesions is challenging. In fact, oncocytic changes occur in inflammatory, hyperplastic, and neoplastic settings, including both benign and malignant tumors. The rare oncocytic variant of papillary thyroid carcinoma (PTC), shows papillae composed by cells with large oncocytic granular cytoplasm featuring clear PTC nuclear features. A morphological similar, but biologically distinct lesion, is the encapsulated papillary oncocytic neoplasia. Here, we first report on FNA, its cytological features together with histological, immunohistochemical, and molecular correlates. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

The diagnosis of nodular sclerosing classical Hodgkin lymphoma (NSCHL) by fine-needle aspiration (FNA) biopsy has historically been a diagnostic challenge due to the usual paucicellularity of the specimen. This case report, and other previously published reports, suggests that there is another facet to the potentially challenging diagnosis of this particular variant of Hodgkin lymphoma (HL): the presence of suppurative-necrotizing changes mimicking an infectious etiology. The patient presented here underwent FNA biopsy of an acutely enlarged supraclavicular lymph node and cytologic smears showed marked acute inflammation in a background of necrosis. A diagnosis of infectious suppurative lymphadenitis was made at that time. After a negative infectious work-up with infectious disease consultation, an excisional biopsy was performed and the patient was definitively diagnosed with NSCHL. The presence of neoplastic Hodgkin and Reed-Sternberg cells in the purulent exudate was minimal and only appropriately identified after retrospective review. This particular subtype of classical HL represents a potential pitfall in FNA biopsy cytology. Consequently, the cytopathologist and surgeon should always consider this entity in the differential diagnosis of a suppurative, lymphadenitis-like aspirate, and pursue repeat FNA or an excisional biopsy if there is any clinical index of suspicion. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Hepatocellular carcinoma (HCC) with atypical cytomorphological features and presenting with bone and soft tissue metastasis is very rare. We report a 65-year-old male patient of HCC who presented with bone and soft tissue metastases and was clinically and radiologically suspected to have a soft tissue sarcoma. The patient presented with severe cervical pain with palpable masses in right scapular, nape of neck, and occiput area of scalp. Radiologically, these were large, bulky soft tissue masses expansile, destructive, and lytic in nature. Cytomorphologic studies revealed HCC with uncommon features of multinucleated osteoclast-like giant cell and very prominent intracytoplasmic hyaline bodies (IHBs). Cytology, immunohistochemistry on cell block preparation, rising serum α-fetoprotein (AFP) levels (1121.93–5000 ng/ml), and PIVKA II levels confirmed the diagnosis. The patient has been on follow-up on sorafinib for 2 months and is doing well. This case emphasizes the need for systematic approach in cases of HCC with atypical clinical presentation and unusual cytomorphology. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Interinstitutional consultation in pathology has shown to improve patient safety by detecting interpretive errors that may significantly impact clinical management. We conducted a study of 922 cases of thyroid FNAC slides, referred to our institution over a 2-year period, to assess the magnitude of discrepancies and determine the clinical impact of second opinion. Disagreements were categorized as none, minor or major, the latter two defined as one- or two-step deviations respectively on the NCI diagnostic categories scale. There were 122 disagreements (13%), including 44 major and 78 minor. Seventy-five patients underwent a change in management based on second opinion, in conjunction with clinical and radiologic findings (age, size of nodule, family history, ultrasonographic appearance, and solitary versus multiple nodules). The second opinion was supported on follow-up in 57% of major discrepancies, and the initial diagnosis was concurrent with the surgical diagnosis in 7% cases. The remainder (36%) of major discrepancy cases did not undergo surgery, precluding tissue confirmation. Critics have alleged increased costs due to interinstitutional consultations. However, cost avoidance from lost wages, potential surgical complications, and litigation is not easily quantified. Using a simplified calculation to objectively measure the costs associated with changed diagnoses, we estimate that second opinion of these 922 cases resulted in potential cost saving of $940,166 based on current Medicare reimbursement codes. Our study indicates the need for a quality-control program of outside thyroid FNA slides, especially in “high discrepancy categories” as discussed in the article. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

Gallbladder cancer is an aggressive cancer with extremely poor prognosis. Over 90% of patients are diagnosed at an advanced, inoperable stage with metastasis and invasion to other organs. In this study, the expression of metadherin (MTDH) and erythropoietin-producing hepatoma-amplified sequence (Eph) receptor A7 (EphA7) in 96 benign and 108 malignant lesions of gallbladder was determined by immunohistochemistry, and their correlations with pathological features and prognosis were analyzed. Positive expression of EphA7 and MTDH was significantly higher in gallbladder adenocarcinoma than in benign lesions. In adenocarcinoma, the positive expression of EphA7 and MTDH was significantly associated with differentiation, tumor mass, lymphnode metastasis, invasion, and overall survival. Multivariate Cox regression analysis suggested that positive expression of EphA7 and MTDH was an independent poor-prognostic predictor in gallbladder adenocarcinoma. The elevated expression of EphA7 and/or MTDH is closely related to carcinogenesis, progression, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

Strongyloidiasis is an infectious disease caused by the nematode helminth, Strogyloides stercoralis. Subjects immunosuppressed, immunocomprised, or on steroids are susceptible to hyperinfection and dissemination. Early detection of parasitic infection in such individuals is extremely important as disseminated Strongyloidiasis is potentially fatal. Here, we present a case of Strongyloidiasis initially detected by Prussian blue stain of bronchoalveolar lavage (BAL) specimen from an immunosuppressed patient who was treated with prednisone for acute interstitial nephritis and developed hemoptysis. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

Ameloblastoma is an odontogenic tumor with aggressive biological behavior, high recurrence rate, and a complex microscopic appearance with many different histologic patterns. Primary ameloblastoma is also described in extragnathic locations. Because of its wide morphologic spectrum, which is mirrored also in cytologic smears, a thorough study of distinctive features is required to reach a reliable diagnosis. Twelve cases of ameloblastoma were examined both cytologically and histologically. The patients were seven women and five men 24–85 years old, mean age being 64 years. Eleven cases were primary tumors of the mandible and maxilla, and one case was a lung tumor metastatic from the tibia. The epithelial element in the cytologic smears of the various cases was morphologically diverse. The basaloid pattern and minimal nuclear atypia were rather constant findings, and the most helpful features toward reaching a cytological diagnosis. However in most cases, careful consideration of the clinical, radiological, cytological, and occasionally immunocytochemical data was required to rule out other entities with similar cytological findings. In some cases, the final diagnosis was only possible by histologic examination. Due to their variable microscopic morphology, ameloblastomas are quite often misdiagnosed for other entities, both benign and malignant. Nevertheless, when one is aware of their distinctive features, an accurate diagnosis can be made by fine-needle aspiration cytology, in conjunction with clinical and radiological findings. Both the preoperative surgical planning and the postoperative follow-up of the patients benefit significantly from this method. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

We present a rare occurrence of metastatic proximal epithelioid sarcoma (PES) in the pleural effusion of a 23-year-old man, developed within one year of diagnosis in his gluteal soft tissue. The cytologic and immunoperoxidase findings are described. PES, due to its epithelioid morphology, can be confused with more common cancers in effusions such as adenocarcinoma and mesothelioma. PES is an aggressive neoplasm that differs clinically and pathologically from conventional epithelioid sarcoma. Knowledge of its cytomorphology in serous cavity effusions, a patient's clinical history and ancillary studies may lead to an accurate diagnosis. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

Kikuchi-Fujimoto disease (KFD) is cytologically characterized by a polymorphous lymphoid cell population, abundant karyorrhectic debris and histiocytes, many of which are crescentic (Kikuchi histiocytes). As per reviewed literature, KFD may be confused with tuberculosis, lymphoma, and reactive hyperplasia of lymph nodes (RHLN). Since RHLN was found to be a major challenging factor during routine cytodiagnosis of KFD in our material, we tried to find out the differentiating clinico-cytologic features between 76 KFD and 684 RHLN cases seen in Kuwait. 63.2% of KFD were in 3rd and 4th decades of life as compared to 40.2% of RHLN (P = 0.0002). Male to female ratio was 1: 2.45 for KFD and 1:1.09 for RHLN (P = 0.0022). Kuwaiti:non-Kuwaiti ratio was 1:2.04 for KFD and 1.31:1 for RHLN (P < 0.0001). Capillary networks was present in 71.1% of KFD smears and 52.6% of RHLN (P = 0.0023). Tingible body macrophages and dendritic reticulum cells were detected in 17.1% and 22.4%, respectively, in KFD as opposed to 50.1% and 58.8%, respectively, in RHLN (P < 0.0001). Kikuchi histiocyte count ranged from 2 to 36% in KFD and was ≥10% in 31 (40.8%). Rare Kikuchi histiocytes were detected in 16 (2.3%) of RHLN cases but in none of them the count exceeded 1%, whereas their count was >1% in all KFD cases (P < 0.0001). Thus, KFD cases differed significantly from RHLN in respect of age and sex distribution, Kuwaiti:non-Kuwaiti ratio, and cytomorphologic features such as capillary networks, Kikuchi histiocyte count, dendritic reticulum cells, and tingible body macrophages. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

Indications of fine-needle aspiration (FNA) of spleen have increased as more splenic lesions are detected because of advanced imaging techniques. A retrospective analysis of cytological material of 36 patients on whom ultrasound-guided splenic FNA was performed was done. No complications were noted. There were 16 inflammatory lesions, 12 neoplastic and 8 cases were reported as descriptive either because of scant cellularity, blood only, or normal splenic cytology. Inflammatory lesions included nine cases of acute abscess, five cases of tuberculosis, and one case each of leishmaniasis and infarct. Neoplastic lesions included two benign (benign cyst and inflammatory pseudotumor) and 10 malignant lesions. Among malignant lesions, eight were non-Hodgkin lymphoma (NHL), one suspicious of NHL, and one desmoplastic small round cell tumor. FNA proved to be an effective procedure for reaching a microscopic tissue diagnosis and thus a splenectomy could be avoided in cases where it was not required. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

Malignant lymphomas of the female genital tract are very uncommon, and the development of a diffuse large B-cell lymphoma involving the vagina following treatment for classic Hodgkin lymphoma is extremely rare. Clinically and morphologically, this entity represents a challenge. We herein report such a case with liquid-based Pap test and tissue biopsy findings. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

Sarcomatoid carcinoma of the urinary bladder is a rare entity, whose histogenesis and biological behavior remain controversial. The cytological literature on sarcomatoid carcinoma in voided urine is very scarce. Clinically, the diagnosis of this tumor can be made by computed tomography (CT), magnetic resonance imaging (MRI), cytology, and biopsy material. In this study, cytology, histopathology, and radiological imaging were employed in order to reach a diagnosis of sarcomatoid carcinoma. CT imaging showed increased thickness of the bladder wall associated to a polypoid mass. MRI showed a 4-cm sized, broadly necked polypoid mass with calcification and ulceration at the right side of the bladder wall. T2W1 imaging showed low signal. Voided urinary cytology showed a scattered cellular presentation. The tumor cells had a high nucleo- cytoplasmic ratio, with elongated cytoplasm with faint with indistinct cytoplasm border. The nucleus was oval to round, with large and irregular nucleoli and irregular nuclear membrane. These tumor cells were positive for cytokeratin (CKAE1/AE3), vimentin, p53, carcinoembryonic antigen (CEA), α1-smooth muscle actin (SMA) by the immunoperoxidase staining. Histopathology showed spindle-shaped and clumped large tumor cells with abundant cytoplasm. Mitotic figures were frequently seen and varied from area to area (50% of the tumor cells were positive for MIB1). Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

It is well known that “condensed cluster of stromal cells (CCSC)” and “metaplastic clumps with irregular protrusion (MCIP)” in endometrial glandular and stromal breakdown (EGBD) cases may simulate “clumps of cancer cells (CCC)” in endometrioid adenocarcinoma grade 1 (G1), leading to difficulty in cytological interpretation. The aim of this study was undertaken to clarify the cytological immunoreactivity of nuclear findings about CCSC and MCIP which may be recognized in EGBD cases by using p53 protein and cyclin A in liquid-based cytologic (LBC) preparations. The material consists of cytologic smears of 20 cases of EGBD and 20 cases of G1 for which histopathological diagnosis was obtained by endometrial curettage at the JA Suzuka General Hospital. The evaluation of immunoreactivity was performed by using the intensity of nuclear staining and the nuclear labeling index (N-LI). The intensity of nuclear staining was scored as negative (0), weak (1), moderate (2), or strong (3). The N-LI was scored as less than 10% (0), from 10 to 25% (1), from 26 to 50% (2), or greater than 50% (3). The final score was calculated of the addition of both partial scores.

Results are as follows: As for the p53 protein immunoreactivity, CCC (2.4 ± 1.4) was a significantly higher value in comparison with CCSC (0) and MCIP (0.8 ± 0.4), respectively. As for the cyclin A immunoreactivity, CCC (2.8 ± 1.1) was a significantly higher value in comparison with CCSC (0) and MCIP (0.6 ± 0.5), respectively. CCSC and MCIP in EGBD are misunderstood as cellular atypia and structural atypia on occasion; but, as for results of the immunoreactivity scores of p53 protein and cyclin A in our study, it seemed that those biochemical characters proved that the biological activity level was low (or degenerative).

The results of the current study demonstrated that the cytological immunoreactivity of nuclear findings by p53 and cyclin A appear to be more useful for the LBC assessment of endometrial lesions, especially for the discrimination of EGBD and G1.Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

Although uncommon, Hurthle cell neoplasms have a characteristic histologic and cytologic features which often aid in the diagnosis of these lesions. In fine needle aspiration biopsies, determining malignant potential on cytologic features is challenging unless other evidence of malignancy (such as metastases) are known. The role of EUS-guided FNA in diagnosing superior mediastinal masses has been described previously. It's role in evaluating subcarinal metastases from lung cancer primaries have also heen studied. However we describe metastatic thyroid Hurthle cell carcinoma to the subcarina diagnosed through EUS-guided FNA combining the unique cytologic features o Hurthle cell neoplasms and the versatility ofthe endoscopic ultrasound to reach a diagnosis in this unusual neoplasm. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

Malignant small round cell tumors represent a diagnostic challenge for cytologists and pathologists. This case series describes four cases of unusual metastasis of small round cell tumors subtypes into body cavities generating effusions in which fluid cytological examination suggested the neuroendocrine origin of the tumors. Tumor diagnosis (Ewing sarcoma/primitive neuroectodermal tumor and desmoplastic small round cell tumors) were unknown at the cytological evaluation. We can highlight the importance of the accurate analyses of body fluids, both for early diagnosis of metastatic disease, and for the diagnosis of primary tumor when serous effusion is the first manifestation of the neoplasia. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

The efficacy of thyroid (FNAB) processed by liquid-based cytology (LBC) in Hashimoto's Thyroiditis (HT) in two reference periods, is evaluated. The morphologic features of 820 cases with both methods and the cyto-histological comparison are analyzed. The diagnosis of hyperplastic nodules (HN) in HT, its mimickers especially in presence of oxyphilic cells and the role of immunocytochemistry (IHC) are studied.

150 cases of HT processed by conventional smear (CS) in 1996–98 and 670 with LBC in 2005–2007,were included. The majority of FNAB were carried out under USguidance and fixed with ethyl alcohol for the CS. LBC material was rinsed in the Cytolit solution, processed according to the manufacturer's recommendations. Among the 150 CS, 83 were HT while 67 were HN in HT; in the second triennium 245 LBC were HT and 425 were HN in HT. In the first period a follow-up (including a second FNA or surgery) was done in 92 cases, in the second period in 116.

In the surgical group 97.1% in the first period were benign (all HT and 34/36 HN) and 2.8% malignant(all HN). In 2005–2007, 94% were benign (15 HT and 45/49 HN) and 6%malignant. Thirty HN from the second triennium had ICC for HBME-1 and Galectin-3 resulting negative in 93.5%. Among these cases, 10 had a benign histology and a concordant negative ICC.

LBC can be used as a valid method for HT, especially for the possible application of ICC to HN, and it allows a correct preoperative selection of lesions Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Erythema nodosum leprosum (ENL) or type 2 lepra reaction is an inflammatory reaction, which may occur in the course of hanseniasis, may compel the patient to seek medical attention and may result in nerve function impairment and subsequent disability. Thus, recognition and timely management of these patients is critical in order to avoid permanent disability. Fine-needle aspiration cytology is simple and effective tool that aids in the correct diagnosis and management of ENL. Herein, we present two cases of ENL, one with typical and another with atypical presentation. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Liposarcoma (LS) represents the most common type of soft tissue sarcoma. LS is subdivided into four distinct subtypes: well-differentiated, myxoid/round cell, pleomorphic, and mixed LS. In addition to distinctive morphology, each of the subgroups has a different prognosis and treatment strategy. While subgrouping has traditionally been based on conventional morphology, recent molecular and cytogenetic findings have validated the current classification system. Well-differentiated LS is characterized by overexpression of MDM2, which blocks the tumor suppressor function of p53. Myxoid/round cell LS is characterized by a specific translocation resulting in a fusion protein which interferes with adipocyte differentiation. Pleomorphic LS, like other high grade sarcomas, is characterized by multiple chromosomal abnormalities. Each of these distinctive molecular signatures can be exploited to aid in the subtyping of LS and in distinguishing true sarcomas of lipogenic derivation from benign mimics. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Fine-needle aspiration (FNA) is a screening and diagnostic tool used to triage the management of thyroid nodules. While FNA has proved to be a sensitive means of detecting common thyroid malignancies, less is known about the sensitivity and positive predictive value (PPV) of FNA for uncommon thyroid malignancies, including anaplastic thyroid carcinomas, medullary thyroid carcinomas, lymphomas, metastatic carcinomas, and other malignancies. We reviewed our experience with these uncommon malignancies sampled by thyroid FNA and recorded interpretations according to the Bethesda System. We compared the FNA interpretations to the follow-up cytology, histology, and flow cytometry. The sensitivity and PPV were as follows: anaplastic thyroid carcinoma (sensitivity 100%, PPV 89%), lymphoma (sensitivity 100%, PPV 100%), medullary thyroid carcinoma (sensitivity 83%, PPV 100%), metastatic carcinoma (sensitivity 80%, PPV 80%), and other malignancy (sensitivity 100%, PPV 100%). Four false-negative and two false-positive diagnoses were identified. While cases were nearly always triaged correctly, occasional pitfalls were encountered. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Histoplasmosis has emerged as an important opportunistic fungal infection in immunocompromised patients. Histoplasma is a dimorphic fungus that primarily involves lung and the environmental reservoir is soil. Although several cases of histoplasmosis have been reported in India but cytological diagnosis was made in a few cases. We are presenting two cases of histoplasmosis diagnosed on fine-needle aspiration cytology. In the first case, pulmonary histoplasmosis was diagnosed on transbronchial needle aspiration of lung in a 41-year-old immunocompetent male, while second case was of disseminated histoplasmosis in 40-year-old immunocompromised female diagnosed on cytology of cervical lymph node. FNAC is a simple, safe, and rapid technique to establish the initial diagnosis, thus promoting early treatment and favorable outcome especially in the immunocompromised patients. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

The objective of this study is to assess the utility of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in the diagnosis and staging of colorectal cancer. The study includes patients who underwent EUS-FNA at our institution for staging of colorectal carcinoma or for evaluation peri-rectal masses or distal metastases from August 2000 to November 2010. We assessed the frequency with which EUS-FNA procedure confirms the diagnosis of malignancy and the percent of cases in which it modifies staging of colorectal carcinoma. Using histology as a reference standard, we also assessed the diagnostic performance. We identified 79 cases of EUS-FNA from 77 patients, mean (SD) age of 60 (12.5), 44 males. Twenty-seven (34%) aspirates were from patients with primary rectal/peri-rectal masses, 15 (19%) were from patients with suspected regional lymph node metastasis, and 37 (47%) were cases of suspected of distal metastasis. All lesions were clinically suspicious for primary or metastatic colorectal carcinoma. On cytologic examinations, 43 (54%) cases were confirmed as malignant, 6 (8%) were benign neoplasms, 4 (5%) were suspicious for malignant neoplasm, 2 (3%) showed atypical cells, and the rest 24 (30%) were negative for neoplasms. Fourteen of 27 (52%) of the local rectal masses were confirmed as colorectal carcinoma. Eleven of 15 (73%) regional lymph nodes were positive for metastasis—all, but two of these metastases, were of colorectal origin. Twenty of 37(54%) distal lesions were metastatic neoplasms and 15 of those were colorectal in origin. Diagnosis of primary colorectal carcinoma was confirmed in 52% of the clinically suspicious primary lesions and in 42% regional or distal metastatic lesions. Using histology as a reference standard in 27 of 79 (29%) cases, we calculated an overall sensitivity, specificity, and positive and negative predictive values (C.I) of EUS-FNA of 89% (74–100%), 79% (50–100%) 89% (74–100%), and 79% (51–100%). EUS-FNA is useful for assessing primary and metastatic colorectal lesion. This technique improves staging of suspected nodal or distant metastases. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

Mesoblastic nephroma (MN) is the most common renal tumor diagnosed in infancy. A case of congenital MN was diagnosed in a 6-month old child by fine-needle aspiration cytology. The smears were cellular and consisted of plump spindle cells arranged in clusters along with scattered naked nuclei in the background. Blastemal, epithelial, or glomeruloid structures were not seen. Considering the age and the cytomorphology, a diagnosis of cellular variant of MN was offered which was confirmed on histopathology. Unlike Wilms tumor, preoperative chemotherapy is not required for MN. Hence cytologic diagnosis is important. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

The aim of this study was to assess the utility of liquid-based cytologic preparation (LP) compared with conventional preparation (CP) for the assessment of nuclear findings in endometrial glandular and stromal breakdown (EGBD) which may be misdiagnosed as carcinoma in EGBD cases. The material consists of cytologic smears including 20 cases of proliferative endometrium (PE), 20 cases of EGBD, and 20 cases of endometrioid adenocarcinoma grade1 (G1) for which histopathological diagnosis was obtained by endometrial curettage at the JA Suzuka General Hospital. Nuclear findings were examined in PE cells, EGBD-stromal cells, EGBD-metaplastic cells, and G1 cells, respectively. It was examined about the following items; (1) nuclear shape; (2) A long/minor axis ratio in cell nuclei; (3) an area of cell nuclei; (4) overlapping nuclei. Results are as follows: (1) nuclear shape; as for the reniform shape of EGBD-stromal cells and spindle shape of EGBD-metaplastic cells, the ratio of the LP method was a higher value than the CP method. (2) The long axis and area of cell nuclei; LP in all groups was a recognizable tendency for nuclear shrinkage. (3) The long/minor axis ratio in cell nuclei; only EGBD-metaplastic cells recognize a significant difference between CP and LP. (4) Overlapping nuclei; LP was a higher value in comparison with CP in the other groups except PE cells, and the degree of overlapping nuclei was enhanced about three times. Therefore, although a cell of LP has a shrinking tendency, (1) it is excellent that LP preserves a characteristic of nuclear shape than CP; (2) a cellular characteristic becomes clearer, because three-dimensional architecture of LP is preserved of than CP. As for the standard preparation method for endometrial cytology samples, we considered that a concrete introduction of the LP method poses no problems. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

Distinguishing malignant mesothelioma (MM) from reactive mesothelial hyperplasia (RM) may be difficult in effusions. This study tested the hypothesis that immunocytochemistry (IC) in effusion cell blocks (CB) can distinguish MM from RM and that the results may be applied to individual specimens. External validation of a risk score (RS) model associating sensitivity and specificity was applied to an external set of MM and RM specimens from a separate institution.

Forty three effusion cytology CBs of 25 confirmed malignant mesotheliomas were compared to CBs of 23 benign mesothelial effusions without inflammation and 13 reactive mesothelial proliferations associated with inflammation. Glut-1, EMA, and Desmin expression were evaluated by immunocytochemistry on CBs. Each antibody was compared using ROC values, where the area under the curve (AUC) was 0.90, 0.82, and 0.84 for Glut-1, EMA, and Desmin, respectively. Logistic regression (LR) analysis was applied to a combination of Glut-1 and EMA. A combined ROC curve was modeled for Glut-1 and EMA (AUC = 0.93). A RS = 2 × (Glut-1%) + 1 × (EMA%) was created from this ROC curve. When applied to an external set of MM and RM, the RS resulted in an ROC with AUC = 0.91.

In conclusion, a RS derived from a LR of Glut-1 and EMA IC greatly improves the distinction between MM from RM cells in individual effusions. The study illustrates principles of evidence-based pathology concerning internal and external test performance in the differential diagnosis of MM versus RM. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

Squamous cell carcinoma with rhabdoid features (SCCRF) is a very rare and unusual cutaneous tumor. Here, we report an extraordinary case diagnosed by fine needle aspiration biopsy, in a 66-year-old man, status post multiple organ transplantation. The patient presented with a large ulcerating fungating mass in his forearm that had all the light microscopic and immunohistochemical features of a SCCRF. Previously six cases of SCCRF phenotype diagnosed by surgical pathology have been reported. This is the first case diagnosed cytologically. A review of the literature with emphasis on the differential diagnoses of such unusual rhabdoid-like tumors in fine-needle aspiration biopsy and the potential molecular mechanism for rhabdoid phenotype in transplant patients are discussed. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

The Bethesda 2007 Thyroid Cytology Classification defines follicular lesion of undetermined significance as a heterogeneous category of cases that are not convincingly benign nor sufficiently atypical for a diagnosis of follicular neoplasm or suspicious for malignancy. In our institution, we refer to these cases as indeterminate, and they are further sub-classified into two: (1) low cellularity with predominant microfollicular architecture and absence of colloid (IN_a) and (2) nuclear features not characteristic of benign lesions (nuclear atypia) (IN_b). We reviewed these indeterminate cases to document the follow-up trend using this two-tier classification. A search of the cytology records was performed for the period between January 2008 and June 2009. All thyroid fine-needle aspiration (FNA) cases were reviewed and the ones diagnosed as indeterminate were identified. Correlating follow-up FNA and/or surgical pathology reports were reviewed. The percentage of cases showing a malignancy was calculated. One hundred and seventy-one indeterminate cases were identified, representing 2.8% of the 6,205 thyroid FNA cases examined during the time under review (107 IN_a, 64 IN_b). Records of follow-up procedures were available in 106 (61%) cases. Malignancy was identified in 27% of all indeterminate cases. This was disproportionately more in the IN_b (56%) compared to the IN_a (7%) cases. A diagnosis of “IN_a” does not carry the same implication as that of “IN_b”. The IN_b category needs a more aggressive follow-up than the IN_a category and may justify an immediate referral for lobectomy. Despite the vague morphologic criteria for this diagnostic category, the indeterminate rate remains relatively low and falls within the NCI recommendation (<7%). Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

The t(9;22)(q34;q11) translocation between bcr and abl genes plays a pivotal role in the pathogenesis and diagnosis of chronic myelogenous leukemia (CML). Fluorescence in situ hybridization (FISH) using specific DNA probes provides a useful and accurate way for the detection of bcr/abl fusion gene in single cell. Here, we report an unusual case of a patient with no prior hematologic disease who initially manifested lymphadenopathy. The lymph node findings were suspicious for T-lineage lymphoblastic lymphoma, however, his blood and bone marrow at that time were in chronic phase of CML. This presented difficulty for accurate discrimination between CML blast crisis (BC) and non-Hodgkin's lymphomas (NHLs). To discern where the extramedullary nodal malignancy originated from, we cytologically analyzed lymph node biopsies and bone marrow with FISH to detect bcr/abl fusion signals. Together with the morphology, immunohistochemistry, cytogenetics as well as molecular analysis, the patient was diagnosed as extramedullary T-lymphoid BC of Ph+ CML. In conclusion, this case is unusual at three levels: first, extramedullary nodal BC as a presenting manifestation of CML is rare and the blasts are of precursor T lymphoblastic lineage, rather than the more common B-cell lineage; second, this case suggests that extramedullary lymphoid nodal BC of CML can exist independently without the bone marrow developing into BC; and third, FISH analysis on the single neoplastic cell is an accurate way to confirm that the neoplasm is either extramedullary localized blasts of CML or genetically distinct neoplasm. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

Laboratory contamination of clinical specimens submitted for cytological examination is an on-going threat that requires continuous vigilance and quality control. We recently were confronted with a suspected fungal infection in a bone aspirate that was found to derive from contaminated Hanks solution used in cytological preparation. Diff-Quik staining of air-dried cytocentrifuged preparations of Hanks fluid as well as any other suspect laboratory fluid is recommended as a routine quality control procedure. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

A case of metastatic mixed acinar-neuroendocrine carcinoma (MANEC) of the pancreas to the liver is reported. A diagnostic percutaneous US-guided FNA and core biopsy of a liver nodule was performed. The FNA smears were cellular and showed neoplastic cells in clusters with acinar formation, isolated single cells, and scattered naked nuclei. The cytoplasm was finely granular. The nuclei were relatively uniform, some with speckled chromatin and prominent nucleoli. The immunohistochemistry performed on the cell block showed strong positivity for cytokeratin AE1/AE3, chromogranin, and synaptophysin. Furthermore, the tumor cells were weakly positive for α1-antichymotrypsin. The Ki-67 mitotic index was up to 50%. Based on the morphology and supporting immunohistochemical stains, the final cytopathologic diagnosis rendered was “Positive for malignant cells. Carcinoma with mixed acinar and endocrine features.” To our knowledge, this is the first report of a metastatic MANEC to the liver diagnosed based on cytology with confirmatory histology. The difficulties in the cytopathologic diagnosis and differential diagnosis of MANEC are discussed in this article. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

Fine-needle aspiration biopsy is a reliable and accurate method for the diagnosis of nodal metastases of head and neck cancers. We report the cytopathologic findings of a case of metastatic sinonasal intestinal type adenocarcinoma (ITAC) in a 58-year-old man who presented with enlarged cervical lymph nodes on a follow-up imaging study, 5 months after resection of a sinonasal ITAC. Ultrasound-guided fine needle aspiration of the station 2B lymph node yielded moderately cellular smears with abundant background mucin pools, numerous naked, atypical nuclei, and rare cells with signet ring cell morphology. Rare mitoses, apoptotic bodies, and necrotic debris were also present. Occasional clusters of signet ring cells were also seen in the cell block sections. Immunoperoxidase stains showed these cells to be positive for CK20 and villin. The differential diagnosis included a metastatic signet ring cell adenocarcinoma from the gastrointestinal tract and a metastatic sinonasal ITAC. Review of the previously resected sinonasal ITAC revealed a similar morphology with signet ring cells and abundant extracellular mucin production; the immunostaining results were also similar to those obtained on previously resected sinonasal ITAC. This case emphasizes the importance of considering primary head and neck tumors with intestinal phenotype and immunophenotype in the differential diagnoses of cervical lymph node metastases with signet ring cell morphology. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

The CINtec PLUS® system is an immunohistochemical cocktail composed of antibodies against p16^INK4a (surrogate of HPV infection) and Ki-67 (proliferation marker) meant to improve the sensitivity and specificity for detecting high-grade dysplasia (HGD). In the presence of dysplasia, a red chromogen marks Ki-67 expression in the nucleus and a brown chromogen marks cytoplasmic p16^INK4a expression. Only cells showing dual staining are interpreted as positive. This retrospective study examined the performance of CINtec PLUS testing when performed on ASC-US diagnosed samples. Comparison was made to high-risk HPV DNA test results and colposcopic biopsy results. Technical considerations in the interpretation of this immunohistochemical stain are additionally discussed. CINtec PLUS showed modest sensitivity (64%) and specificity (53%) in identifying the presence of HGD at surgical biopsy. Positive and negative predictive values for HGD were 28% and 83%, respectively. HR-HPV DNA test yielded sensitivity of 100% and specificity of 21%. During interpretation, squamous metaplasia and endocervical cells were seen to show individual staining for p16^INK4a or Ki-67. Individual staining, when present within three dimensional cellular groups common to SurePath® preparations, can be time-intensive to interpret necessitating thoughtful examination at high power. The Pap test with HR-HPV DNA testing is a highly sensitive test. A specific test is needed to prevent false positives and over treatment. The CINtec® system provides a modest increase in specificity beyond HR-HPV DNA testing. Future study of its appropriateness and cost-ffectiveness in a treatment algorithm are warranted. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

We have built a database on the Internet managing z-axis video for cytology (Zavic), and report on a new style of case discussion supported by the Zavic database. Z-axis video for cytology is a movie file derived from the video recording of a microscopic field with changes in the focus. We used it for the case presentation of EUS-FNA of pancreatic lesions on the Internet prior to a training workshop. The attendees were asked to observe the Zavic and to make diagnoses of 20 cases before the workshop. Fourteen attendees also observed lesions under a microscope on that day, and the results were compared with those of Zavic observation. The evaluation of the Zavic database (DB) was surveyed by a questionnaire. The average number of accurate diagnoses by 46 Zavic observers was 10.8. These accuracies for those who observed both the Zavic and glass slides were 11.57 and 11.43, respectively, for the videos and slides. Compared with Zavic observation alone, the diagnoses with glass slide observation were shifted to a correct diagnosis in two cases, but were shifted to an incorrect diagnosis in two cases. Approximately 60% of Zavic observers replied in the questionnaire that the movies on Zavic DB started to play within 3–4 seconds after clicking the play button. We successfully carried out the new style of case discussion supported by the Zavic DB. It was evaluated favorably by many attendees, who were psychologically still dependent on the glass slide observation. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Urine cytopathology is a useful and noninvasive tool in the diagnosis and follow-up of urothelial neoplasia, which remains complementary to emerging molecular tests. These specimens may be challenging and there are numerous mimics and diagnostic pitfalls with which to contend. This review discusses these various entities and includes consideration of ancillary tests that may be useful in the diagnostic procedure. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Detection of cervical high-grade squamous intraepithelial lesions (HSIL) in patients with equivocal cytological abnormalities, such as atypical squamous cells (ASC) of undetermined significance (ASCUS) or inability to exclude high-grade squamous intraepithelial lesions (ASC-H) is still a challenge. This study tested the efficacy of PAX1 methylation analysis in the triage of cervical ASCUS and ASC-H and compared its performance with Hybrid Capture 2 (HC2) HPV test. A hospital-based case–control study was conducted. Cervical scrapings from patients with ASCUS or ASC-H were used for the quantitative methylation analysis of PAX1 methylation by MethyLight and HPV testing by HC2. Patients with ASC-H or ASCUS with repeated abnormal smears underwent colposcopic biopsy and subsequent therapies. Diagnoses were made by histopathology at a follow-up of 2 years. The efficacies of detecting high-grade lesions were compared. Fifty-eight cervical scrapings with cytological diagnosis of ASCUS (n = 41) and ASC-H (n = 17) were analyzed. One of the 41 (2.4%) ASCUS patients and seven of 17 (41.2%) ASC-H patients were confirmed to have HSIL. After dichotomy of the PMR, PAX1 methylation rates were significantly higher in ASC developing HSIL compared with those developing reactive atypia (87.5% vs. 12.5%, P < 0.001). Testing PAX1 methylation in cervical swabs of patients with ASC confers better sensitivity (87.5% vs. 62.5%) and specificity (98.0% vs. 86.0%) than HC2 HPV testing. We show for the first time that PAX1 hypermethylation analysis may be a better choice than HC2 in the triage of ASCUS and ASC-H. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Sclerosing hemangioma of the lung is a rare benign neoplasm. The majority of the literature published on sclerosing hemangioma has focused on the histologic features, while only a few case reports have described the cytologic features. We report two additional cases of sclerosing hemangioma of the lung in which the cytologic material was prepared at the time of frozen section. Because of the rarity of this lesion and the overlapping cytologic features with other primary malignant lung tumors, awareness of the cytologic features of sclerosing hemangioma may help to avoid a diagnosis of malignancy. This is especially true pre- and intraoperatively because a limited resection may suffice if a diagnosis of sclerosing hemangioma can be established. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

HPV detection in fine needle aspirates from suspected head and neck metastasis may be useful in clinching the diagnosis of HPV related oral squamous cell carcinoma. Ascertaining the HPV status of a particular tumor on cytological specimens could be useful for prognostication as HPV-related tumors appear to have a better prognosis and clinical outcome. The various techniques of detection are reviewed. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Epithelioid angiosarcomas (EAS) of kidney are rare and aggressive tumors with noncharacteristic imaging features that overlap with those of inflammatory conditions and renal cell carcinoma (RCC). We report the fine-needle aspiration (FNA) cytology findings of a case of EAS that involved the left kidney of an 83-year-old male. The smears and cell block sections showed pleomorphic epithelioid cells with ample cytoplasm, eccentric nuclei, occasional cytoplasmic hyaline globules, and rare intracytoplasmic lumina. Immunohistochemical stains performed on cellblock sections showed that the tumor cells were positive for vimentin, CD31, CD34, Factor VIII, and CD10, but showed no staining for cytokeratins AE1/AE3 and 8/18, HMB45, CD45, smooth muscle actin, and S100. The morphological and immunohistochemical distinction between EAS, primary tumors of the kidney, and other epithelioid and rhabdoid neoplasms is discussed. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Primary breast lymphoma (PBL) is a rare disease, which comprises 0.04–0.53% of all primary malignant tumors of the breast. The most frequent histological subtype is diffuse large B-cell type (DLBCL) (40–70%). Differentiation of PBLs from other breast tumors such as poorly differentiated carcinomas and lobular carcinoma may at times be difficult on cytomorphology alone. An audit of breast lymphomas diagnosed on fine needle aspiration cytology (FNAC) over a period of 9 years (2001–2009) was performed. Ten cases were retrieved and the cytomorphology was reviewed along with immunochemistry (IHC), flow cytometry as well as histopathology, wherever available. The age of patients ranged from 17 to 83 years. Eight cases were diagnosed as non-Hodgkin's lymphoma, high-grade on FNAC. Histopathology was available in four of these cases and cell block was available in one case. Lymphoid cells were positive for leukocyte-common antigen (LCA) and CD20 and negative for CD3 in these cases. The same was confirmed by flow cytometry on aspirated material in one case. A diagnosis of DLBCL was offered in these five cases. One case was a low-grade NHL and another case was a young male, a known case of acute leukemia and had leukemic infiltration in the breast lump. We wish to emphasize the potential importance of FNAC in breast lymphoma and the same can be helpful to avoid unnecessary surgery in these cases. The differential diagnostic entities have been discussed. IHC and flow cytometry can be performed on the aspirated material and provide valuable information. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Ciliated cells encountered outside of an expected anatomical location (e.g., the respiratory tract, fallopian tube, etc) can represent a diagnostic difficulty for the cytopathologist, especially during preliminary assessment of a fine needle aspiration (FNA) for adequacy or malignancy. We present the cytologic and histologic features of a FNA and needle core biopsy, respectively, of an abdominal mass, likely from a gastrointestinal duplication cyst, foregut cyst or a bronchogenic cyst. We also briefly review the differential diagnosis for ciliated cells encountered in abdominal or pelvic FNAs. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

The objective of this study is to assess the relationship between protozoa in spontaneously expectorated sputum samples and a range of clinical and immunological variables. Clinical details including age, gender, smoking status, and use of oral or inhaled steroids were recorded for a cohort of 199 patients whose spontaneously expectorated sputum samples were submitted to a Cytology Laboratory in Spain between January 2005 and December 2006. Slides were scanned for protozoa under light microscopy and scanned for monocytes/small macrophages highlighted by immunocytochemistry (CD68 monoclonal antibody). One hundred ninety-one patients provided adequate sputum samples, of whom 70 had protozoa in their sputum. There was a strong relationship between the presence of protozoa and monocytes/small macrophages identified under light microscopy (P < 0.001). A binary logistic regression model also indicated a relationship between protozoa and both smoking status and steroid use. The diagnoses in those with protozoa included infection (including tuberculosis), chronic obstructive pulmonary disease (COPD), lung fibrosis, asthma, chronic liver disease, immunosuppression, cancer, pancreatic or renal disease, heart failure, and AIDS. The identified association between protozoa and monocytes/small macrophages in sputum suggests an immune response and warrants further investigation to clarify whether or not these organisms have any pathological significance in this wide range of conditions. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has provided a set of uniform diagnostic terminology including benign (B), atypia of undetermined significance (AUS), follicular neoplasm (FN), suspicious for malignancy (SM), malignancy (M), and nondiagnostic (ND) for the interpretation of thyroid fine-needle aspiration (FNA). We applied this terminology on our 1,382 thyroid aspirates in a community practice setting, which included 539 cases of B (39%), 376 cases of AUS (27.2%), 116 cases of FN (8.4%), 37 cases of malignant (2.7%), 36 cases of SM (2.6%), and 278 cases of ND (20.1%). Two hundred twenty-one cases (16%) of thyroid FNA had corresponding follow-up thyroidectomies. Each diagnostic category represented a unique association with risk of malignancy and risk of neoplasm. Based on histologic follow-up, the risk of neoplasm (including benign and malignant neoplasm) was B 14%, AUS 44%, FN 67%, SM 77%, and M 100% and the risk of malignancy was B 3%, AUS 6%, FN 22%, SM 56%, and M 100%. The classification and follow-up recommendation of TBSRTC are appropriate for each category. Both B and AUS are low-risk lesions with low probability of malignancy. FN predicts a higher rate for neoplasm but an intermediate rate for malignancy while SM carries a high risk for malignancy. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Primary thyroid lymphoma is a very rare disease. Here, we present a case of primary diffuse large B-cell lymphoma (DLBCL) in a 48-year-old female involving thyroid gland. The patient had thyroid swelling for 15 years which rapidly increased during last 5 months. Fine needle aspiration cytology revealed monomorphic large cells arranged discretely. The cells have high nuclear-cytoplasmic ratio with prominent single to multiple nucleoli. Aggregates of thyroid follicular cells were absent in the smears. A cytodiagnosis of DLBCL was made and a differential diagnosis of lymphocytic thyroiditis was also included. Subsequent histologic examination revealed a high-grade non-Hodgkin lymphoma (NHL). Immunohistochemistry showed the tumor cells expressing CD45, CD20, BCl-6, and tumor cells were negative for cytokeratin, epithelial membrane antigen, CD3, CD5, and CD30. Proliferative index (Ki-67) was very high (70%). Thus, a final diagnosis of NHL of DLBCL subtype was established. The patient was treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristin, prednisone) and radiotherapy. The patient is under one-year follow-up which is uneventful. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Associations between bronchioloalveolar carcinoma (BAC), mucinous differentiation, and epidermal growth factor receptor (EGFR) and KRAS mutations have been previously reported in studies of surgical specimens. We present the cytomorphology of lung adenocarcinomas, including metastases that were diagnosed by cytologic methods and the relationship to both EGFR and KRAS mutational status. We retrospectively reviewed the clinical and cytomorphologic features of 50 lung adenocarcinomas that were tested for both EGFR and KRAS mutations. Cytomorphologic features evaluated included cell size, architectural pattern, nucleoli, intranuclear cytoplasmic inclusions (INCI), mucin, necrosis, squamoid features, lymphocytic response, and histologic features of BAC differentiation. DNA was extracted from a paraffin-embedded cell block or frozen needle core fragments. Exon 19 deletions and the L858R mutation in exon 21 of EGFR were detected using PCR followed by capillary electrophoresis for fragment sizing. KRAS mutational analysis was performed by real-time PCR using a set of seven different Taqman(r) allelic discrimination assays to detect six mutations in codon 12 and one mutation in codon 13. Six cases (12%) showed EGFR mutations, 12 (24%) showed KRAS mutations, and 38 (62%) contained neither EGFR nor KRAS mutations. The majority of patients had stage IV disease (78%); 20 samples (40%) were from metastatic sites. The presence of prominent INCI (P = 0.036), papillary fragments (P = 0.041), and histologic features of BAC on paraffin block (P = 0.039) correlated with the presence of EGFR mutations. The presence of necrosis (P = 0.030), squamoid features (P = 0.048), and poorly differentiated tumors (P = 0.025) were more likely to be identified in the KRAS positive group. Diagn. Cytopathol. 2011. © 2011 Wiley-Liss, Inc.

Palpable lesion(s) noticed in a patient with thoracic disease may be a useful diagnostic tool and it often gives a clue for further management. In this study, we searched the diagnostic value of palpable lesions in patients with thoracic pathology suspected clinically and/or radiologically. We prospectively examined the correlations of clinical/radiologic and pathologic findings of 72 palpable lesions from 68 patients who presented with suspect for a thoracic disease from two tertiary medical centers. Thirty-two lesions (44.4%) were diagnosed as malignant either by fine-needle aspiration (FNA) only or FNA with confirmatory biopsy. The most common malignancy was non-small-cell carcinoma (10) followed by adenocarcinoma (6), and small-cell carcinoma (5). The most common localization of the palpable lesions was cervical region (20.8%) followed by left supraclavicular (13.8%) and anterior chest wall (13.8%). FNA was effective in obtaining an accurate diagnosis in 66.6% of the patients. Tissue confirmation of FNA was performed in 54 patients. The sensitivity, specificity, negative predictive value, and positive predictive value of FNA in distinguishing a malignant lesion from a benign disease for these palpable lesions were 75, 97, 96, and 80, respectively. One false negativity and one false positivity were also found. Abnormal radiologic features were not correlated with having a malignant palpable lesion. Evaluation of the palpable lesions by FNA and tissue biopsy together is effective for initial triage of the patients with suspect for a thoracic pathology. FNA alone is a convenient and easy method for this purpose especially when the material is immediately assessed for specimen adequacy. Diagn. Cytopathol. 2011. © 2011 Wiley-Liss, Inc.

Bronchoalveolar lavage (BAL) is an established diagnostic tool in diffuse parenchyma lung disease. The objective of the present study was designed to investigate whether immunophenotyping affects BAL results and improves diagnostic accuracy.

BAL from 61 patients was included in the study. The patients were also submitted to transbronchial biopsy, with a final diagnosis of granulomatous disease [tuberculosis (TB), n = 20; sarcoidosis (SARC), n = 3; and hypersensitivity pneumonitis (HP), n = 4]; idiopathic interstitial pneumonias (IIPs) [idiopathic pulmonary fibrosis (IPF), n = 9; organizing pneumonia (OP), n = 17]; and lung cancer (LC), n = 8. Immunohistochemistry and histomorphometry were used to identify and quantify type 1 and type 2 alveolar epithelial cells, macrophages, CD3+T-cells, CD4+T-cells, CD8+T-cells, and CD20+B-cells in BAL. These markers were correlated with a database and pulmonary function tests.

The cellular, inflammatory, and immune components of BAL varied among the diagnostic groups and were negatively correlated with age and smoking history. An increased quantity of lymphocyte surface markers CD3 (P < 0.05) and CD20 (P = 0.01) was seen in IIPs. Patients with a pattern of OP had a higher proportion of type 2 alveolar epithelial cells; patients with SARC had a higher density of CD20+B-cells and CD4+T-helper cells; and patients with HP had a higher proportion of CD8+T-cytotoxic cells. A positive association was found between the density of type I alveolar epithelial cells and forced vital capacity.

The immunophenotyping affects the cellular, inflammatory, or immune constituents of BAL and improved the diagnostic accuracy in diffuse parenchymal lung disease. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Ultrasound-guided fine needle aspiration (USG-FNA) has enabled cytopathologists to accurately diagnose smaller or non-palpable lymph nodes (LN) on a regular basis. Pre-FNA clinical and ultrasonographic factors, such as a patient's age, ratio of short to long axis diameter (S/L ratio), internal echogenicity, and the vascular pattern of a LN, are reported to be able to predict the benign or malignant nature of a LN. This study is designed to test the formula “0.06 × (age) + 4.76 × (S/L ratio) + 2.15 × (internal echo) + 1.80 × (vascular pattern)” generated from the study of Liao et al. as a scoring system for predicting LN malignancy in a cytopathologist operated USG-FNA practice.

Eighty-three reports of USG-FNA of LNs issued between 7/1/2008 and 4/28/2010 were reviewed. Patient's age, S/L ratio, internal echo, and vascular pattern were used to generate scores based on the aforementioned formula. A score of seven was used as a cutoff for predicting benign (<7) and malignant (>7) LNs. FNA cytology diagnosis, flow cytometric analysis as well as subsequent surgical diagnosis in some cases served as gold standard for statistical analysis.

Among 46 USG-FNA of LNs with scores > 7, 38 were malignant and eight were benign. All 37 USG-FNA of LNs with scores < 7 were proven to be benign. The scoring system achieved 100% sensitivity, 82% specificity, 83% positive predictive value, 100% negative predictive value, and 90% accuracy. Further study of the eight “false-positive” cases revealed that three of them (37.5%) were found to be malignant in follow-up FNA and/or surgical biopsy.

This scoring system may serve as a complementary tool in determining how aggressive a FNA procedure should be performed, how a FNA sample of LN should be triaged for ancillary study, and how closely a patient with lymphadenopathy should be followed up. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

We report a case of isolated cervical leishmanial lymphadenopathy diagnosed by fine-needle aspiration cytology (FNAC) in apparently cured case of visceral leishmaniasis. A 28-year-old female presented with cervical lymphnode enlargement to surgery outpatient department and was subjected for FNAC. Smear showed numerous Leishmania donovani bodies in the cytoplasm of macrophages and giant cells, and extracellular spaces. She was treated by Amphotericin B for alternate 14 days and the size of the lymphnode regressed. She was found asymptomatic for 1 year of follow-up. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Giant-cell tumor (GCT) of bone arising from phalanx of a finger is extremely rare. Rizzoli Orthopedic Institute in their study on 900 treated cases of GCT from 1947–1997 reported only 0.9% incidence of GCT in bones of the hand. There was no case of GCT of the phalanges in that series. We report here a case of GCT of bone arising from phalanx of finger because of its very unusual location. The tumor was diagnosed on the basis of fine-needle aspiration cytology and confirmed by histopathology. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Most guidelines currently recommend the testing of human papillomavirus (HPV) in ASCUS cases. The most used method for this purpose is Hybrid Capture II (HCII), but PCR techniques with GP5+/6+ primers can be also applied. Furthermore, the HCII high-risk probe test for detection of HPV shows cross-reactivity with low-risk HPV. Although this cross-reactivity has been studied in screening populations, it has received little attention in ASCUS cases.

To compare the performance of the HCII high-risk probe test and PCR for the detection of HPV in ASCUS cases.

We randomly selected 83 ASCUS cases that were positive for high-risk HPV by HCII and applied the PCR test using MYO9-11 and GP5+/6+ primers to samples from these cases.

Our results show cross-reactivity with low-risk HPV in 25.3% (21/83) of the HCII+ PCR+ cases. Regarding the follow-up our results emphasize the importance of HPV typing, especially for HPV 16 infection.

We propose the use of PCR techniques using GP5+/6+ consensus primers for the screening of HPV in ASCUS. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

House paints, the industrial products of toxic chemicals are known to be linked with severe respiratory disturbances especially in inadequately ventilated places. In this study, we aimed to report a biopsy-proven case of extrinsic allergic alveolitis (EAA) who presented with nonspecific respiratory symptoms 1 month after having her whole house interior painted. At CT scanning, we observed the ground glass opacities and the micronodular pattern typ