Cancer Cytopathology

Pancreatic endoscopic ultrasound-guided fine-needle aspiration (FNA) cytopathologic diagnosis has a very low false-positive rate, but has a relatively high false-negative rate when using matched surgical resections as the gold standard. The major cause of a false-negative result in FNA is due to sampling error.

A 10-year experience diagnosing histoplasmosis using ultrasound-guided fine-needle aspiration revealed that contrary to recent reports, histoplasmosis was frequently diagnosed in immunocompetent patients when the differential diagnosis commonly included malignancy. In the current study, the cytomorphologic, clinical, and laboratory findings pertinent to the diagnosis are reviewed.

The results from this investigation are consistent with prior reports indicating a decrease or loss of E-cadherin expression in poorly differentiated pancreatic adenocarcinoma. However, zeste homolog 2 (EZH2) expression does not always inversely correlate with E-cadherin expression and is more heterogeneous.

Endosalpingiosis in peritoneal washings displays morphologic and immunophenotypic characteristics that should allow its distinction from reactive mesothelial hyperplasia or serous/endometrioid neoplasms. Peritoneal washings are best interpreted with complete knowledge of the operative technique and surgical biopsy findings.

Observed changes over time in the proportion of unsatisfactory Papanicolaou tests after conversion to liquid-based technology vary across participating sites and depend on the type of technology used. The changes are influenced by the proportion of unsatisfactory studies before the implementation of liquid-based technology.

Numerous clinical studies have demonstrated that fluorescence in situ hybridization increases the diagnostic sensitivity of routine cytology for detecting pancreatobiliary tract malignancy with minimal decreases in clinical specificity. The improved ability to detect pancreatobiliary tract cancers offers the possibility of earlier detection when patients are amenable to surgical intervention and can decrease health care costs by reducing the amount of clinical evaluation required to arrive at a cancer diagnosis.

Application of the ThinPrep Imaging System for urine cytology is as reliable as conventional screening for the detection of abnormal urine cells. There is good correlation between both methods with almost equal sensitivity and specificity.

The application of standard cytologic examination of the urine specimen can now be augmented by using ThinPrep technology and other automatic screening devices. The technical and preparation adjustments required for these new technologies notwithstanding, the potential for shorter screening times and the possibility of greater diagnostic accuracy may provide great diagnostic promise for this very common specimen.

To the best of our knowledge, the current study, which used pooled analysis from multiple studies performed in China and included large numbers of women with abnormal cytology results, is the first report of a large-scale population-based study to assess liquid-based cytology for the detection of biopsy-confirmed cervical intraepithelial neoplasia and cancer in China. The findings indicated that the performance of liquid-based cytology can effectively predict a risk of existing cervical intraepithelial neoplasia of type 2 or worse and has higher accuracy than Hybrid Capture 2 in population-based cervical cancer screening practice.

The neoplastic cell enrichment in touch imprints and matched frozen whole-tumor tissue samples were compared in 11 adenocarcinomas harboring KRAS mutations using light microscopy of hematoxylin and eosin-stainedslides and the height ratio between the mutant and wild-type peaks on the sequencing electropherograms. The authors found that procurement of carcinomas by touch imprinting is superior to the procurement of frozen whole-tumor tissue when tumor DNA is needed for molecular analysis.

Familiarity with cytologic features, correlation with clinical/radiologic information, and ancillary studies are important for the diagnosis of lymphoma with signet ring cell features and for making the distinction from other lesions with signet ring cell features in fine-needle aspiration samples.

Standardized protocols for the fixation and handling of cytological specimens are required for reliable, consistent, and robust molecular test results for the assessment of biomarkers to direct patient selection for targeted therapies. This editorial discusses the strengths and limitations of the article by Dejmek et al with regard to this topic.

The authors demonstrate that cytologic direct smear preparations of lung adenocarcinoma can be effectively used for the analysis of anaplastic lymphoma kinase (ALK) rearrangement by fluorescence in situ hybridization. This approach can complement the use of cell blocks for such testing, especially for situations in which insufficient cell block cellularity is encountered or anticipated.

In a retrospective review of 1320 atypical urine samples from 851 patients collected from January 2000 to December 2011, upper tract urine specimens had the highest rate of progression to high-grade urothelial carcinoma at a rate of 55%. Thus, the authors postulate that the diagnosis of atypia in this specimen group has higher clinical significance, and these patients should be managed more aggressively.

Molecular testing has profound therapeutic implications in the systemic management of patients with lung adenocarcinoma. The results of the current study demonstrate the successful identification of epidermal growth factor receptor (EGFR) mutation, Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, and anaplastic lymphoma kinase (ALK) gene rearrangement in cytological specimens and suggest the need to repeat molecular testing in those patients with metastatic/recurrent tumors.

In the current study, the value of the uCyt1/ImmunoCyt test in the follow-up of patients with superficial urothelial carcinoma is confirmed. This could potentially reduce the number and cost of routine cystoscopic examinations performed in patients followed for bladder carcinoma.

Thyroglobulin levels in ultrasound-guided fine-needle aspiration specimens demonstrate a strong negative predictive value (93%-99%). They may be particularly useful for difficult cytological cases.

Morphological analysis of 9p21 deletion-positive malignant pleural mesothelioma cells reveals cytological characteristics useful for differentiation from reactive mesothelial cells. In addition, the novel technique of a combination of virtual microscopy and fluorescent in situ hybridization is introduced for tumor morphological analysis.

There is a small but significant subset of adolescents with extensive sexual and obstetric history who harbor grade 3 cervical intraepithelial neoplasia, and the high-risk adolescents with these lesions have higher parity (term deliveries). The current findings indicate that some high-risk adolescents may benefit from cervical cancer screening before age 21 years.

Mean levels of human epidermal growth factor receptor 2 (HER)2/neu, CYFRA 21-1, and carcinoembryonic antigen were found to be significantly higher in lung adenocarcinoma-associated cytologically negative pleural effusions than in benign pleural effusions. The results of the current study indicate that combining carcinoembryonic antigen with CYFRA 21-1 will provide the best differentiation between lung adenocarcinoma-associated cytologically negative pleural effusions and benign pleural effusions using 2 tumor markers, and allows for the early diagnosis and early treatment of approximately two-thirds of affected patients.

EGFR (epidermal growth factor receptor) mutations and EML4-ALK (echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase) translocations were analyzed in archived cytological/histological sample pairs obtained from lung adenocarcinomas. Archived hematoxylin and eosin-stained smears and paraffin-embedded tissue blocks demonstrated similar performance both in terms of success rates for DNA/RNA isolation and for the ability to detect gene alterations.

Acinar cell carcinoma has a distinctive cytological appearance, but is frequently misdiagnosed on cytology. Immunocytochemistry is useful for identifying acinar differentiation.

The effect of various clinically used techniques for the fixation, staining, and mounting of cytological samples on DNA yield and quality were tested using cultured cells treated as routine cytological samples. All the methods tested were found to result in analyzable DNA, but clear differences were observed, especially in liquid-based cytology samples.

A multicolor fluorescence in situ hybridization assay for the detection of human papillomavirus and gene copy numbers of TERC (telomerase RNA component) and MYC was assessed in liquid-based cytology specimens of preinvasive lesions of the uterine cervix. The analysis of TERC gene copy number can help to predict the clinical course of patients with low-grade squamous intraepithelial lesions.

Nonanalytic reasoning in cytopathology image interpretation can be as accurate as traditional feature-based reasoning. Instructions to combine analytic and nonanalytic reasoning were not effective.

A combination of urine cytology and cystoscopic findings at the time of diagnosis of low-grade urothelial carcinoma is examined. Cystoscopic findings, including the presence of multiple lesions, as well as positive urine cytology at or shortly before the time of diagnosis of low-grade urothelial carcinoma predicts disease recurrence or progression.

Epidermal growth factor receptor (EGFR) mutation status, which is used to qualify patients with nonsmall cell lung cancer for tyrosine kinase inhibitor therapy, depends on assay and platform selection as well as specimen type. Cytology smears can be used successfully as a specimen source for EGFR gene mutation analysis and can produce results comparable to those achieved with surgical specimens on both polymerase chain reaction and sequencing platforms.

ProExC antibody cocktail is introduced as an adjunct immunocytochemical marker that significantly improves sensitivity and specificity of urine cytological analysis.

EZH2 (enhancer of zeste homolog 2) and CD79B (B cell antigen receptor complex-associated protein beta chain) mutations were detected over time by a MassARRAY spectrometry customized assay in B-cell non-Hodgkin lymphomas using samples on FTA cards as well as biopsies, archived smears and cytospin preparations. Mutations varied in positive cases supporting that therapy should be based on results at the time of treatment and that testing minimal samples by high-throughput assays might facilitate studies in molecular events related to tumor progression and increase the material suitable for molecular analysis.

The past 10 years have witnessed extraordinary advances in the field of cytogenetics with the discovery that a multitude of neoplasms is characterized by identifiable chromosomal changes. Cytology has recognized cytogenetics as a welcome companion in the evaluation of soft tissue tumors, lymphomas, renal and urothelial tumors, and mesothelioma.

A multi-institutional review of endoscopic ultrasound-guided fine-needle aspirates from 18 pancreatic solid pseudopapillary neoplasms, 20 pancreatic endocrine neoplasms, and 4 acinar cell carcinomas indicates that these neoplasms share the following cytologic features: single cells and rosettes/acinar cell groups, round-to-plasmacytoid cells, pale-to-granular cytoplasm, fine vacuoles, and binucleated cells. Cytologic features favoring the diagnosis of solid pseudopapillary neoplasm are papillary structures, cercariform cells, large cytoplasmic vacuoles, reniform nuclei, hyaline globules/magenta-colored material, and degenerative features (cholesterol crystals, calcifications, foam cells, or giant cells).

Most patients with nonsmall cell lung carcinoma present with advanced-stage disease at the time of diagnosis, and cytologic samples represent the only material available for subsequent molecular analysis. This study demonstrates that cytologic specimens from patients with lung cancer can serve as reliable samples for the effective assessment of EGFR mutation status.

The authors explore the possible application of a molecular technique to liquid-based cytology and demonstrate its simplicity and feasibility, producing good results. They also explore the role of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene mutations in predicting the outcome of patients who have small (≤1 cm) thyroid papillary carcinomas diagnosed on liquid-based cytology and, hence, in guiding their clinical and surgical management.