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Keywords:

  • serous cystadenoma;
  • pancreas;
  • cytology;
  • fine-needle aspiration;
  • endoscopic ultrasonography;
  • mucinous cystic neoplasm

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

BACKGROUND

The preoperative diagnosis of pancreatic serous cystadenoma (SCA) is important because as a typically benign tumor it can be treated expectantly, whereas many other cystic tumors require excision. This study examines the cytology, clinical and radiologic features, diagnostic accuracy of fine-needle aspiration (FNA), and potential pitfalls associated with this rare tumor.

METHODS

Cytomorphologic features were retrospectively reviewed from 28 FNAs of SCA from 21 patients. FNA biopsies were guided by percutaneous computed tomographic or ultrasonographic imaging in 10 cases and by endoscopic ultrasonographic imaging in 18 cases. Corresponding histology (14 tumors) and clinical/imaging findings were also evaluated.

RESULTS

Patients typically presented with upper abdominal discomfort or asymptomatically. Radiologically, a well-demarcated, multiloculated cystic mass involving the pancreatic head or uncinate process was common. Aspirates were sparsely cellular against a clean or granular, proteinaceous background. Tumor cells formed loose clusters or monolayered sheets composed of cuboidal cells with indistinct cell borders and granular or clear cytoplasm that was often stripped from the nucleus. Nuclei were small, round, with fine chromatin and indistinct nucleoli and devoid of mitotic activity. Seven (25%) of the aspirates were initially classified as “consistent with SCA,” 6 (21%) as “no malignant cells,” 3 (11%) as “nondiagnostic specimen,” 3 (11%) as “suspicious for malignancy,” 3 (11%) as “rare atypical cells,” and 6 (21%) as “probably or consistent with mucinous cystic neoplasm.” Features causing diagnostic difficulty were scant cellularity, papillary groups, nuclear atypia, and columnar cells mimicking those of mucinous neoplasms. Gastrointestinal (GI) epithelium and mucin also caused confusion. The detection of intracytoplasmic glycogen (3 of 6 cases) and cyst fluid analysis (2 of 2 cases) showing low viscosity and low or undetectable levels of carcinoembryonic antigen, CA 19.9, and amylase enhanced diagnostic confidence.

CONCLUSIONS

Diagnosing SCA by FNA is challenging. Familiarity with its morphologic spectrum, use of ancillary studies, and correlation with clinical/radiologic findings greatly improves diagnostic accuracy. Contaminating GI epithelium and mucin should be distinguished from components of a mucinous neoplasm. Cancer (Cancer Cytopathol) 2006. © 2006 American Cancer Society.

Serous cystadenoma (SCA) of the pancreas, encompassing serous microcystic adenoma (SMA) and serous oligocystic adenoma (SOA), accounts for 1% to 2% of exocrine pancreatic tumors.1 First described in 1978 by Compagno and Oertel,2 SCA is characterized histologically by multiloculated cysts separated by fibrous septae and lined with a single layer of flattened or cuboidal epithelium containing glycogen. SCA typically has an indolent clinical course and virtually no malignant potential.2–4 Although surgical excision is indicated in some patients,5–7 conservative management with clinical and radiologic follow-up is sufficient for asymptomatic patients and those who are poor surgical candidates.2, 4, 8 However, to our knowledge there are no completely reliable clinical or radiologic criteria for distinguishing SCA from other pancreatic cystic lesions. The latter include nonneoplastic lesions (inflammatory pseudocyst) and premalignant or malignant lesions (mucinous cystadenoma, intraductal papillary mucinous tumor, cystic islet cell tumor, solid pseudopapillary tumor, and adenocarcinoma with cystic degeneration).8–10 Whether surgery is needed and what procedure should be performed depend largely on the nature of the cyst. Therefore, a preoperative tissue diagnosis is highly desirable for determining appropriate management.

Fine-needle aspiration (FNA), a simple, safe, and cost-effective diagnostic tool, is often used as an initial procedure for this purpose. Traditionally, FNA is performed under percutaneous imaging (computed tomography [CT] or ultrasonography) guidance. Currently, endoscopic ultrasonography (EUS) is favored because its imaging resolution is higher and it has fewer complications.8, 11–14 EUS-guided FNA (EUS-FNA) does, however, require the needle to pass through the gastrointestinal (GI) wall into the pancreatic mass. The value of FNA in diagnosing SCA is somewhat controversial. Previous studies describing the cytologic features of this tumor are single case reports,15–20 or contain only a small series21–25 and demonstrate diagnostic accuracies ranging widely from 10% to 100%.21–27 The reported experience with EUS-FNA in diagnosing this tumor is even more limited.19, 20, 27, 28 The current study examines our experience with this unusual entity by reviewing the cytologic features of 28 FNA cases (18 sampled via EUS-FNA), correlating with histologic findings and discussing diagnostic pitfalls.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Twenty-eight FNA cases of SCA from 21 patients between January 1991 and March 2005 were identified in the pathology files of the University of Texas M. D. Anderson Cancer Center. Clinical and radiologic information for all patients was available for our review. Five tumors had been reaspirated because of a failure to obtain a diagnostic specimen on initial FNA; 1 tumor had been aspirated 4 times. The results of each biopsy were considered individually because each result was documented in a separate report.

Aspirates were obtained using a 20-gauge or 22-gauge biopsy needle. Ten FNA biopsies had been performed under percutaneous imaging (CT or ultrasonography) guidance and 18 under EUS imaging guidance. An average of 3 FNA passes was made for each case. Direct smears were air-dried for Diff-Quik staining (Stat Lab, Lewisville, TX) or fixed in modified Carnoy fixative (a 6:1 ratio of 70% ethanol and glacial acetic acid) for Papanicolaou staining. Frosted slides were used for Papanicolaou-stained smears. Smears were assessed immediately by a cytopathologist for specimen adequacy. Cells from needle rinses were collected in RPMI medium and centrifuged. The sediment was fixed in a 50:50 mixture of 95% ethanol and 10% formalin and embedded in paraffin (i.e., cell block preparation). The cell blocks were then sectioned and stained with hematoxylin and eosin (H & E; available for 18 cases). Detection of intracytoplasmic glycogen was attempted for 6 cases (2 cell blocks and 4 smears). Positive periodic acid-Schiff staining that is abolished by diastase digestion and negative mucicarmine staining indicate the presence of glycogen. For 2 cases, aspirated fluid was analyzed for carcinoembryonic antigen, CA 19.9, amylase, and viscosity.

The FNA features of SCA were retrospectively analyzed for the background content, cellularity, architecture, cytoplasmic, and nuclear features. These features were correlated with available histologic specimens (14 tumors: 12 resections and 2 core biopsy specimens). To determine the diagnostic accuracy of FNA, initial FNA diagnoses were compared with final diagnoses. Final diagnoses were based on histologic findings or, for the 7 cases without histologic tissue, based on combined clinical and radiologic findings, cytologic features comparable to those of FNA cases confirmed by histologic examination, positive glycogen staining, analysis of aspirated fluid, and clinical follow-up data.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Clinical Findings

The clinical characteristics and follow-up data of the 21 patients with SCA are summarized in Table 1. The mean age at presentation was 61 years (range, 40-80 years) and the male-to-female ratio was 1:3.1. A prior cancer history was found in 4 patients. Twelve (57%) of the patients presented with symptoms; of these, 10 presented with upper abdominal discomfort or pain, 1 with diarrhea, and 1 with obstructive jaundice. The remaining 9 patients (43%) were asymptomatic and their tumors were discovered incidentally during imaging workups for other indications. Twelve patients underwent tumor excision for definitive diagnosis and/or relief of symptoms and 2 patients underwent core biopsy for definitive diagnosis. The other 7 patients were followed up with close observation because combined clinical, radiologic, and cytologic findings were thought to be in keeping with SCA.

Table 1. Clinical Features of 21 Patients with Serous Cystadenomas of the Pancreas
Patient No.Age, YearsSexSiteSize, cmHistory of MalignancyClinical PresentationSurgical ProcedureFollowup, Months
  • M indicates male; DP, distal pancreatectomy; F, female; Abd., abdominal; UP, uncinate process; Whipple: pancreaticoduodenectomy with or without pylorus-preserving.

  • *

    Died of prostate cancer.

  • Lost to follow-up.

  • Died of unknown cause, but other than serous cystadenoma.

164MBody4.5Prostate carcinomaIncidental findingDP24, Dead*
269FBody3.9NoneAbd. discomfortDP41, Alive
374FUP4.5Renal cell carcinomaIncidental findingResection90, Alive
464MHead4NoneIncidental findingWhipple11, Alive
546FTail2.5NoneDiarrheaDP26, Alive
652FBody3.5NoneAbd. discomfortDP15, Alive
740FHead1.5NoneAbd. discomfortWhippleUnknown
856MHead8NoneJaundiceWhipple28, Alive
956FUP4NoneAbd. discomfortWhipple22, Alive
1043FHead2NoneIncidental findingWhipple12, Alive
1175FHead2.5NoneAbd. discomfortWhipple57, Alive
1256FDiffuse10NoneAbd. discomfortWhipple20, Alive
1378FHead8NoneIncidental findingCore biopsy10, Alive
1476FTail4NoneIncidental findingCore biopsy36, Alive
1571FBody5NoneAbd. discomfortNone13, Alive
1652FTail2.5Breast carcinomaAbd. discomfortNone38, Alive
1743FBody2NoneAbd. discomfortNone64, Alive
1868MHead3NoneIncidental findingNone14, Alive
1974FHead4NoneAbd. discomfortNone42, Dead
2040FBody2.5NoneIncidental findingNone9, Alive
2180MTail1.5Prostate and gastric carcinomaIncidental findingNone7, Alive

The mean duration of follow-up for all FNA procedures was 29 months (range, 7-90 months). Two patients died of unrelated causes and 1 patient was lost to follow-up. The remaining 18 patients were alive and well at the time of last follow-up.

Radiologic Findings

Radiographically, lesions were generally well demarcated, multiloculated cysts. They appeared hypoechoic on ultrasonographic images or hypodense on CT images. Central scars were found in 2 tumors and focal calcifications in 4. A characteristic sunburst-type calcification3 was suggested in 1 tumor. Lesions ranged from 1.5 to 10 cm in dimension (mean, 4.0 cm) (Table 1). Ten lesions (47%) were located in the pancreatic head or uncinate process, 6 (29%) in the pancreatic body, 4 (19%) in the pancreatic tail, and 1 (5%) diffusely involved the whole pancreas. “Microcystic adenoma” was suggested for 8 tumors and “cystadenoma” or “cystic tumor” for another 10 tumors (Table 2). Other differential diagnostic considerations included pseudocyst, neuroendocrine tumor, intraductal papillary mucinous tumor, primary adenocarcinoma, and metastasis.

Table 2. Imaging, FNA, and Histologic Findings of 21 Patients with Serous Cystadenomas of the Pancreas
Patient No.Imaging ImpressionFNA CytologyHistologic Diagnosis
Mode*Initial DiagnosisGlycogen StainingFluid Analysis
  • FNA indicates fine-needle aspiration; PUS, percutaneous ultrasonography; SMA, serous microcystic adenoma; PCT, percutaneous computed tomography; S/O, suggestive of; EUS, endoscopic ultrasonography; C/W, consistent with; SOA, serous oligocystic adenoma.

  • *

    Cases with multiple FNA biopsies were labeled chronologically from to .

1Primary cystic tumor vs. metastasisPUSSuspicious for metastatic prostate carcinoma  SMA
  PCTRare atypical cells   
2S/O microcystic adenomaPCTNondiagnostic specimen  SMA
3Primary tumor vs. metastasisPCTSuspicious for metastatic renal cell carcinoma  SMA
4S/O microcystic adenomaEUSProbably mucinous cystic neoplasm  SMA
  EUSC/W mucinous cystic neoplasm   
5Probably cystadenomaEUSC/W mucinous cystic neoplasm  SMA
6Adenocarcinoma vs. neuroendocrine tumor vs. simple cyst vs. mucinous tumorEUSNo malignant cells  SMA
  EUSNondiagnostic specimen   
7Microcystic adenoma vs. intraductal papillary mucinous tumorEUSProbably mucinous cystic neoplasm  SMA
8Probably microcystic adenoma with pancreatitisEUSRare atypical cells with inflammation  SMA
  PCTNo malignant cells   
  EUS§No malignant cells   
  EUSC/W pancreatitis   
9Cystic tumor vs. pseudocystEUSC/W mucinous cystic neoplasmEquivocal SOA
10Cystic tumor vs. complex pseudocystEUSNondiagnostic specimen  SMA
11Cystic tumor vs. neuroendocrine tumorEUSRare atypical cells  SMA
12Multicystic massPCTC/W microcystic adenoma  SMA
13Cystadenoma vs. adenocarcinoma vs. neuroendocrine lesionPCTSuspicious for adenocarcinoma  SMA
  PUSC/W microcystic adenomaEquivocal  
14C/W microcystic adenomaEUSNo malignant cells  SMA
15Microcystic tumor vs. neuroendocrine tumorEUSC/W microcystic adenoma  None
16S/O multilocular cystic tumorEUSS/O microcystic adenomaPositive None
17Cystic tumor vs. pseudocystEUSBenign cystPositive None
18Cystic tumor vs. pseudocystPCTS/O microcystic adenoma C/W serous tumorNone
19S/O microcystic adenomaPCTS/O microcystic adenomaPositive None
20S/O microcystic adenomaEUSProbably mucinous cystic neoplasmEquivocalC/W serous tumorNone
21Complex cystic tumorEUSC/W microcystic adenoma  None

Pathologic Findings

The initial diagnoses of the 28 FNA samples and those of 14 corresponding histologic samples are listed in Table 2. The cytologic features of the 28 FNA samples are summarized in Table 3. Most aspiration samples were hypocellular and composed of tumor cells arranged singly, in loose clusters with a focal vaguely acinar pattern, in strips, or in monolayered sheets (Fig. 1A, left and right). Tumor cells were rather uniform: cuboidal with indistinct cell borders and a scant to moderate amount of clear or finely granular cytoplasm. Centrally located round to oval nuclei displayed smooth nuclear contours, evenly dispersed chromatin, and indistinct nucleoli. Bare nuclei were frequently noted (Fig. 1B and 1C). Mitosis, necrosis, and significant nuclear atypia were not found. Most cases had a nonmucinous (clean or finely granular proteinaceous) background. Mucinous material with normal GI epithelium was identified in most samples aspirated via EUS-FNA. Collagenous stromal fragments with loosely attached tumor cells were found in 14 cases (50%) (Fig. 1C). These cytologic findings agreed well with the histologic features found in resection or core biopsy samples. The latter revealed numerous, variably sized small cysts (13 microcystic adenomas) or few larger cysts (one oligocystic adenoma) containing proteinaceous fluid. These cysts were separated by hyalinized fibrous septae and were lined by a single layer of flat or cuboidal epithelial cells with clear cytoplasm. Nuclei were round with minimal nuclear atypia and no mitotic activity. Foci of inflammatory cell infiltration and hemosiderin-laden histiocytes were present.

Table 3. Cytologic Features of 28 FNA Cases of Serous Cystadenoma of the Pancreas
Cytologic FeatureNo.Percent
  • FNA indicates fine-needle aspiration; GI, gastrointestinal.

  • *

    Encompassing enlargement, pleomorphism, and overlap.

Cellularity  
 Low2693
 Moderate27
Arrangement  
 Loose clusters or monolayered sheets2589
 Papillae, focal14
 Honeycomb sheet311
Background  
 Clean or granular2279
 Inflammatory, focal414
 Mucinous (from GI tract)621
Cell shape  
 Flat or cuboidal2589
 Low columnar, focal311
Cell border  
 Indistinct2589
 Distinct, relatively311
Cytoplasm  
 Finely granular2279
 Clear621
 Stripped off2693
Nucleus  
 Bare2693
 Bland, round or oval2693
 Atypia,* focal518
 Invisible or indistinct nucleolus28100
 Absent of mitotic figure28100
Stromal fragments1450
Calcification414
thumbnail image

Figure 1. Fine-needle aspiration samples showing cytologic features typical of most serous cystadenomas. (A) Small clusters of uniform cuboidal epithelial cells with finely granular cytoplasm and round nuclei, evenly distributed chromatin, smooth nuclear membranes, and indistinct nucleoli; background is clean (left panel, Papanicolaou stain). Tumor cells arranged in a monolayered sheet with minimal nuclear pleomorphism (right panel, Diff-Quik stain). (B) Strips of tumor cells with numerous bare nuclei in a finely granular proteinaceous background (Papanicolaou stain). Inset: vague acinar pattern in some cell groups (Papanicolaou stain). (C) Fragments of collagenous stroma with loosely attached tumor cells (Papanicolaou stain). Original magnification ×400 (A, C); ×200 (B); ×100 (inset).

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In addition to low cellularity, 3 additional cytologic features caused difficulty in arriving at a correct diagnosis. One feature was variable nuclear atypia, seen in 5 (18%) FNA cases from 4 tumors (Patients 1, 8, 11, and 13). Most of these cases demonstrated only minimal nuclear enlargement and pleomorphism, often with an associated inflammatory background. However, in Patient 13 some tumor cells demonstrated prominent nuclear pleomorphism, hyperchromasia, and overlap (Fig. 2A). Similar nuclear changes, caused by focal nuclear degeneration, were present in the corresponding histologic tumor specimen (Fig. 2B). The histologic diagnosis of microcystic adenoma for this patient was supported by positive glycogen staining. Second, the presence of papillary groups, as seen in Patient 3 (Fig. 3A), in a background of bare nuclei. Intracystic micropapillary projections were focally present in the histologic counterpart, which otherwise demonstrated classic SCA morphologic features. No fibrovascular stalks were seen within these papillae (Fig. 3B). Lastly, in 3 FNA samples from Patients 4 and 5, tumor cells appeared columnar, with moderate amounts of cytoplasm and relatively well-defined cell borders, giving a honeycomb-like pattern and thereby suggesting mucin-producing cells (Fig. 4A). In corresponding resected tumor sections, some neoplastic cysts were lined by columnar cells with clear cytoplasm (Fig. 4B). In light of this unusual finding, special stains were performed on tissue sections and the diagnosis of SCA was supported by positive glycogen and negative mucicarmine staining.

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Figure 2. Patient 13 had an initial fine-needle aspiration diagnosis of suspicious for carcinoma. (A) Tumor cells in the cytologic smear show nuclear pleomorphism, overlap, and hyperchromasia (Papanicolaou stain). (B) Corresponding histologic section shows similar nuclear changes (H & E stain). Original magnification ×400 (A); ×200 (B).

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thumbnail image

Figure 3. Patient 3 had an initial fine-needle aspiration diagnosis of suspicious for metastatic renal cell carcinoma. (A) Aspirate shows cuboidal tumor cells forming papillary-like clusters with numerous bare nuclei in the background (Papanicolaou stain). (B) Corresponding histologic section shows a classic microcystic pattern with focal intracystic papillae without fibrovascular cores (H & E stain). Original magnification ×100 (A, B).

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thumbnail image

Figure 4. Patient 4 had an initial fine-needle aspiration diagnosis of “consistent with mucinous cystic neoplasm.” (A) Columnar-shaped tumor cells are arranged in a monolayer honeycomb-like pattern with a moderate amount of cytoplasm and distinct cell borders. Numerous bare nuclei are seen in the background (Papanicolaou stain). (B) Corresponding histologic section shows cystic spaces lined by a single layer of columnar cells with bland, centrally located round nuclei, and clear cytoplasm (H & E stain). Original magnification ×200 (A); ×400 (B).

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Cell-block preparations were obtained in 18 FNA cases. Only 2 cases had cell blocks that provided adequate material for diagnostic interpretation. The cell blocks in the other 16 cases contained no cells or rare clusters of tumor cells entrapped in fibrin blood clots without apparent cystic spaces. Of the 6 FNA samples for which glycogen staining was attempted, only 3 unequivocally demonstrated cytoplasmic glycogen. Chemical analysis of aspirated fluid was performed for 2 tumors. Both fluids showed low viscosity, normal values of carcinoembryonic antigen, CA 19.9, and undetectable amylase, findings consistent with SCA.

For the 7 FNA cases without histologic follow-up, the final diagnosis of SCA was made using a multidisciplinary approach. All 7 tumors had radiologic features favoring microcystic adenoma or cystic tumor; 5 of them were initially diagnosed on FNA samples as microcystic adenoma, and this diagnosis was supported by positive glycogen staining in 2 cases and aspirated fluid analysis in 1 case. The sixth case, which was originally diagnosed as a benign cyst, showed cytologic features comparable to FNA cases that had histologic follow-up. This case also stained positive for cytoplasmic glycogen. The seventh FNA sample contained tumor cells in a background of abundant extracellular mucin, raising a concern for mucinous cystic neoplasm (MCN) in the initial interpretation. The result of glycogen staining was equivocal. On retrospective review, the tumor cells in this case displayed features compatible with SCA, and the extracellular mucin represented GI contamination. The radiologic findings and aspirated fluid analysis also favored a diagnosis of SCA. Follow-up has disclosed that 6 of these patients were doing well clinically and 1 has died of an unrelated cause.

Diagnostic Accuracy of SCA by FNA

In the current series, 7 (25%) of the 28 FNA cases (33% of the 21 tumors) were interpreted as “consistent with microcystic adenoma” (Table 4). Three cases (11%) were considered “nondiagnostic specimen” and 6 (21%) as “no malignant cells” without rendering a specific diagnosis. In the remaining cases, the diagnosis rendered was “rare atypical cells” for 3 (11%), “suspicious for carcinoma” for 3 (11%), and “probably or consistent with MCN” for 6 (21%). Of the 5 tumors that were reaspirated, only 1 finally yielded a correct diagnosis.

Table 4. Comparison of Diagnostic Accuracy by FNA for SCA in the Literature and the Current Study
ReferenceFNA ModeNo. of CasesInitial Cytologic Diagnosis
SCA (%)Other (%)
  1. FNA indicates fine-needle aspiration; SCA, serous cystadenoma; PI, guidance by percutaneous image, either computed tomography or ultrasonography; EUS, endoscopic ultrasonography; NA, not available.

Current study, 2005PI and EUS287 (25)6 mucinous cystic neoplasm (21)
    3 suspicious for carcinoma (11)
    3 rare atypical cells (11)
    6 negative for malignancy (21)
    3 nondiagnostic (11)
Lewandrowski et al.21PI31 (33)2 inflammatory process
Centeno et al.22PI53 (60)1 nondiagnostic
    1 inflammatory process
Nguyen et al.25PI72 (29)5 nondiagnostic
Centeno et al.23NA41 (25)3 inflammatory process
Carlson et al.24PI and intraoperative62 (33)2 negative for malignancy
    2 nondiagnostic
Le Borgne et al.26NA323 (9)29 nondiagnostic
Frossard et al.28EUS1414 (100) 
Lal et al.27PI and EUS11Unclear1 mucinous cystadenoma

With regard to the diagnostic accuracy in samples obtained via EUS-FNA, only 3 (17%) of the 18 cases were diagnosed as “consistent with SCA.” Other interpretations were “probably or consistent with MCN” for 6 (33%), “cellular atypia” for 2 (11%), “negative for malignant cells” for 5 (28%), and “nondiagnostic specimen” for 2 (11%).

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

The preoperative diagnosis of cystic lesions of the pancreas, which is essential for planning the best treatment, remains difficult despite recent improvements in imaging techniques. Data regarding the use of FNA in the diagnosis of SCA are limited because only a few studies with a small number of cases have explored its value. Reported accuracies are quite variable, most ranging between 10% to 60% (Table 4).21–26 A sensitivity of 100% has been reported in 1 study.28 In another series of 11 SCAs, only 1 FNA sample was misinterpreted as MCN27; however, it is unclear how many concurrent core biopsies had been obtained and whether the latter contributed to the interpretations of the FNA samples. In our series, 25% of the 28 FNA cases (33% of the 21 SCAs) were correctly classified and cytologic features were generally similar to those reported by other investigators.15, 16, 18, 19, 22, 25, 27–29 Factors that contributed to the low sensitivity of our study were retrospectively reviewed.

As reported by others,17–19, 22–28, 30 obtaining sufficient cells for the diagnosis of SCA is often difficult. In our study, 32% of the 28 cases were initially classified as “nondiagnostic specimen” or “no malignant cells.” Even in reaspirated specimens, the interpretations were mostly the same. It is important to note that low cellularity is intrinsically related to the cystic nature of SCA, especially if the lesion is oligocystic31, 32 or has epithelial denudation.9 A lack of familiarity with the cytologic features of SCA also contributes to false-negative results. Therefore, for a radiologically suggested cystic lesion, a careful search for epithelial cells and the assessment of their cytologic features would help minimize false-negative rates. When epithelial cells are not found, a diagnosis of SCA should not be excluded, although other cystic lesions, especially inflammatory pseudocyst, should also be considered.21, 22, 25

Significant cellular atypia is typically not found in SCA,3 although minimal nuclear atypia has been noted.18, 25, 27 We found variable degrees of atypia in 5 FNA cases from 4 tumors; 3 samples were initially classified as “atypia” and the other 2 as “suspicious for carcinoma.” The atypia was mostly mild and often seen in an inflammatory background. Of the 2 cases interpreted as suspicious for carcinoma, 1 was aspirated from a patient with a history of prostate carcinoma and the smears showed, in addition to slight nuclear enlargement, a vague acinar pattern. Another case was initially diagnosed as suspicious for adenocarcinoma due to the presence of focal prominent nuclear pleomorphism, overlap, and hyperchromasia. The corresponding surgically resected specimen showed similar nuclear features. In addition, focally, nuclear detail was not well preserved, showing dark and smudgy chromatin, probably representing a degenerated cell change. In 1 case there was no true cellular atypia on subsequent review, and metastatic renal cell carcinoma was initially considered mainly because of the presence of papillary groups of clear cells and the patient's prior history of renal cell carcinoma. Focal papillary cell groups have been previously reported in both the histologic2, 3 and cytologic literature19, 29 of SCA. It is noteworthy that in view of the presence of clear cells and glycogen in both SCA and renal cell carcinoma, the possibility of a renal origin deserves merit. In this case, the cytomorphologic features of the pancreatic lesion were classic SCA and dissimilar to that of the patient's prior renal tumor.

SCA and MCN account for 75% of cystic neoplasms of the pancreas.9 Differentiating them is crucial because of the different biologic characteristics of these 2 neoplasms. The choice of management for MCN is complete resection because even cytologically benign mucinous tumors may undergo malignant transformation,4, 6, 33, 34 whereas for a well-documented SCA, conservative management may be sufficient for patients who are asymptomatic or for whom surgical risk is high.2, 8 In our study, histologic follow-up was performed for 14 patients, mostly because of a nondefinitive FNA diagnosis or erroneous diagnosis of MCN. The 7 tumors that had no histologic follow-up but had clinical, radiologic, and FNA findings consistent with SCA were managed expectantly. Review of the 6 FNA cases from 5 tumors initially diagnosed as “probably or consistent with MCN” revealed that 3 specimens from 2 tumors had columnar tumor cells with a moderate to abundant amount of cytoplasm and distinct cell borders, reminiscent of mucin-producing cells in MCN. The diagnostic dilemma was further complicated by the presence of background mucin from the GI tract. Interestingly, the lining cells in corresponding histologic sections were also taller than typical SCA cells and contained more abundant cytoplasm, presumably representing a higher secreting status. The other 3 tumors, including 1 serous oligocystic adenoma, contained scanty tumor cells that were partially obscured by numerous fragments of normal GI epithelium and mucin. Stains for glycogen were performed in 2 of these 3 cases but were inconclusive due to equivocal results. In comparing SCAs with columnar cells to MCNs, we found that columnar cells in SCA tended to be shorter, the borders less distinct, and the cytoplasm less viscous. Image findings can provide additional information to separate these 2 entities. For example, well-circumscribed, thin wall masses with lobulated contour containing numerous small cysts, a central stellate scar, and/or sunburst calcifications are more suggestive of SCA.3, 4, 17, 35, 36

Whereas EUS-FNA is gaining popularity for its ability to target small, intrapancreatic lesions, GI epithelium and mucin incidentally introduced by this procedure is a source of diagnostic pitfall and can be misinterpreted as MCN.20, 27, 37, 38 In the present study, all 6 cases that were erroneously interpreted as MCN were sampled via EUS-FNA. However, using the same FNA modality, Frossard et al.28 reported a sensitivity of 100% for 14 SCAs. The variation in diagnostic accuracy could be due to differences in sampling technique, the experience of the endoscopist or cytopathologist, and the thoroughness with which clinicopathologic correlation was accomplished. Several investigators have described distinctive features between GI contamination and MCN.20, 37, 39–41 In general, GI epithelial cells tend to form large cohesive monolayered sheets consisting of uniform, columnar cells without cytologic atypia and often with a luminal edge. These columnar cells usually do not contain abundant cytoplasmic mucin, and thus the cell border is not as prominent as that in MCN cells. Incarcerated mucin-producing goblet cells are a constant feature of incidentally sampled duodenal epithelium and the openings to the crypts of Lieberkuhn or the pits may be seen in some cell groups.41 In contrast, MCN cells are characterized by mucin-rich columnar epithelium with thick mucin in the background. Although MCN cells may appear extremely bland, they often exhibit, at least focally, some cytologic atypia and architectural complexity.40 The presence of background mucin warrants consideration of MCN.23 However, caution should be taken not to misinterpret GI mucin as the mucinous material of an MCN. Mucin from the GI tract tends to be thinner, wispier, and devoid of degenerated epithelial cells and inflammation compared with the mucin of MCN.37, 40 Unfortunately, this distinction is not always easy, as the features can overlap.

Cell block material and ancillary tests facilitate the differential diagnosis only if the results are informative. In our study, cell block material was available for 18 cases. Unfortunately, 8 cell blocks contained blood only, and 8 were composed of so few cells that architectural features were not present. Only 2 cell blocks showed cells with a diagnostic pattern. Similarly, results of stains for glycogen may vary depending on the amount of cytoplasmic glycogen and number of cells examined. Chemical analysis of aspirated cystic fluid can provide additional diagnostic clues. Low levels of carcinoembryonic antigen, amylase activity, and viscosity favor an interpretation of nonmucinous cystic lesion, whereas high levels of amylase and lipase suggest a pancreatic pseudocyst.14, 21, 30, 42, 43 However, this analysis alone is not entirely reliable.

In summary, SCA has a distinctive cytologic appearance, but the FNA diagnosis of this neoplasm can be challenging, especially when tumor cells are scant, or show atypical features. The presence of GI epithelium or mucin introduced by EUS-FNA is an additional source of potential error. We conclude that familiarity with the morphologic spectrum of SCA, in conjunction with using ancillary studies and correlation with clinical and radiologic findings, greatly improves the diagnostic certainty of SCA by FNA.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES
  • 1
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    Sarr MG, Kendrick ML, Nagorney DM, Thompson GB, Farley DR, Farnell MB. Cystic neoplasms of the pancreas: benign to malignant epithelial neoplasms. Surg Clin North Am. 2001; 81: 497509.
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    Pyke CM, van Heerden JA, Colby TV, Sarr MG, Weaver AL. The spectrum of serous cystadenoma of the pancreas. Clinical, pathologic, and surgical aspects. Ann Surg. 1992; 215: 132139.
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