ThinPrep vs. conventional smear cytologic preparations in analyzing fine-needle aspiration specimens from palpable breast masses.

Limited data exist concerning the cellular features of the ThinPrep (Cytyc Corp., Boxborough, MA) technique in the analysis of breast fine-needle aspiration specimens. Therefore, we analyzed a series of 75 surgically excised palpable breast masses and compared ThinPrep and conventional smear fine-needle aspiration preparations. Each mass was aspirated twice. The first sample was used for two alcohol-fixed conventional smears, and the second sample was rinsed into CytoLyt (Cytyc Corp., Boxborough, MA) solution for processing into a ThinPrep slide. The paired slides were separated and independently analyzed for adequacy, overall cellularity, single epithelial cells (absent, rare, moderate, or numerous), epithelial architecture (sheets or three-dimensional clusters), myoepithelial cells and stripped bipolar nuclei (present or absent), and nuclear detail (poor, satisfactory, or excellent). Each sample was classified as negative, negative consistent with fibroadenoma, atypical favoring benign, atypical favoring malignant, or positive for malignant cells. The 75 breast masses included 32 carcinomas and 43 benign lesions. Four conventional smears and one ThinPrep were unsatisfactory. Significantly, more conventional smears were limited by drying artifact (9 vs. 0). ThinPrep aspirates of carcinomas had better nuclear detail (P = 0.03) and greater cellularity (P = 0.05). ThinPrep aspirates of benign masses had greater epithelial cellularity (P = 0.007) and better nuclear detail (P < 0.001), and more specimens had myoepithelial cells (P = 0.007). The ThinPrep interpretation classified 29 of 32 carcinomas (91%) as positive and three as atypical favoring malignant (sensitivity = 100%). The conventional smear interpretation classified 28 of 31 carcinomas (90%) as positive and three as atypical favoring malignant (sensitivity = 100%). The ThinPrep interpretation classified 42 benign lesions as negative (23 cases), negative consistent with fibroadenoma (8 cases), atypical favoring benign (10 cases), and atypical favoring malignant (1 case) (specificity = 74%). The conventional smear interpretation classified 40 benign lesions as negative (25 cases), negative consistent with fibroadenoma (12 cases), and atypical favoring benign (3 cases) (specificity = 93%). ThinPrep was less specific, but the difference was not statistically significant (P = 0.065). In summary, ThinPrep aspirates had greater cellularity and better nuclear detail than conventional smears, and were just as sensitive in identifying the carcinomas. The difference in specificity between the two techniques was not statistically significant (P = 0.065). Diagn. Cytopathol. 1999;21:137-141.     

Identification of factors predictive of malignancy in patients with atypical biliary brushing results obtained via ERCP

Biliary brushings obtained during ERCP can have one of three cellular interpretations: benign, malignant, or “atypical.” Atypical interpretations usually result in further testing, and may cause controversy over management and increases in cost. We evaluated a large cohort of patients with atypical biliary brushings for analysis and risk stratification. All biliary brushing specimens collected between January 1, 2001 and December 31, 2010 that had an atypical result were included. Hospital electronic records were reviewed for these patients to include: demographics, indication for ERCP, endoscopist/pathologist impressions, serologic testing, stricture site, and information relating to the final clinical diagnosis. Eighty‐six patients were included. Totally, 60/86 patients (70%) had malignancies while 26/86 (30%) had no evidence of malignancy during long term follow up. Univariate analysis showed that the risk of malignant outcomes was significantly associated with older age, suspicious/malignant endoscopic impression, pancreatic mass, indications including jaundice and/or dilated bile ducts, stricture location within the common bile duct, PSC, and CA 19‐9 levels >300 U/mL. We created a novel scoring system for prediction of malignancy based on clinical and endoscopic factors. We identified parameters that are typically available to the clinician to categorize patients with an “atypical” bile duct brushing results into “high risk” and “lower risk” classifications. Our proposed scoring system would allow such risk stratification to take place. Diagn. Cytopathol. 2013;41:682–688. © 2013 Wiley Periodicals, Inc.     

ThinPrep evaluation of fluid samples aspirated from cystic ovarian masses

The cytological evaluation of ovarian cystic fluid using ThinPrep has not been reported. To determine the diagnostic accuracy of ThinPrep cytology in distinguishing between benign and nonbenign ovarian cystic lesions, we examined 65 fluid samples aspirated during intraoperative consultation with subsequent histologic correlation. One ThinPrep slide was prepared from each sample aspirated from surgically removed ovarian cystic masses and reviewed blindly by a panel of three cytopathologists. The parameters used in cytological evaluation were cellularity, cell types, cellular arrangement, and background. Four samples were acellular and excluded from the study. The consensus cytologic diagnoses were compiled for 61 cases which were assigned to one of the following diagnostic categories: negative for malignant cells (40 cases), atypical cytology (13 cases), and suspicious or positive for malignancy (8 cases). Histologic correlation of the cytological benign/negative cases showed that 26/40 (65%) were histologically benign and 14/40 were false-negative (35%, 5 carcinomas and 9 borderline tumors) with 10 of these cases being mucinous tumors. Most false-negative cytologic samples (11/14 or 79%) did not have an epithelial component. Of the 21 cytological nonbenign diagnoses (atypical/suspicious/positive), 15 (71%) were confirmed on histology (10 carcinomas and 5 borderline tumors). However, a nonbenign cytologic diagnosis was rendered in 6 histologically benign cases, including 2 serous cystadenomas, 1 mucinous cystadenoma, 1 serous cystadenofibroma, 1 endometriosis, and 1 corpus luteal cyst. The diagnostic sensitivity by ThinPrep evaluation of ovarian cystic masses is 81% (26/32) for benign and 52% (15/29) for nonbenign lesions. Our results concluded that ThinPrep examination of ovarian cystic fluid is not accurate in distinguishing benign from malignant cysts, given the significant number of false-negative diagnoses. Major contributing factors include sparse cellularity of the fluid samples and mucinous differentiation of the tumors.     

Comparison of ThinPrep and conventional preparations in pancreatic fine-needle aspiration biopsy

Use of ThinPrep preparation for fine-needle aspiration biopsy (FNA) is gaining popularity. However, there may be a difference in the morphology and the operating characteristics between ThinPrep and conventional methods. The objective of this study was to compare the accuracy of the two methods and to address the pitfalls of ThinPrep preparation in pancreatic FNA. A computer search identified 67 pancreatic FNAs with both conventional smears and ThinPrep preparation during a 19-mo period. These cases, obtained under endoscopic ultrasound-guidance, consisted of 47 malignant neoplasms (44 ductal carcinomas, two mucinous neoplasms, and one islet cell tumor) and 20 benign lesions. Direct smears were prepared first and the remaining material was then put into PreservCyt Solution for ThinPrep slides. All slides were reviewed and the cytologic diagnoses were correlated with histologic and clinical follow-up. Five conventional and 16 ThinPrep specimens were unsatisfactory due to insufficient cellularity. These cases were excluded from the analysis. Among the 62 cases evaluated by conventional preparation, 77% (34) were diagnosed as positive and 14% (seven) atypical/suspicious by conventional smears. For the 51 ThinPrep specimens, 58% (22) were interpreted as positive and 31% (12) atypical/suspicious. The sensitivity, specificity, and accuracy of diagnosing a malignancy were 77%, 100%, and 84% for conventional smears and 58%, 100%, and 67% for ThinPrep preparation, respectively. There were no false positives with either method. However, three benign lesions were interpreted as atypical/suspicious with ThinPrep preparation because of the presence of single atypical cells with distinct nucleoli. One of the two mucinous neoplasms was incorrectly diagnosed with ThinPrep preparation because of lack of mucin. The diagnostic accuracy of pancreatic FNA using ThinPrep is inferior to that of conventional smears. This may be partly due to the use of split sample technique resulting in scant cellularity in ThinPrep preparation and partly due to the differences in morphology between the two preparations. Therefore, the current morphologic criteria may need modification for ThinPrep preparation in pancreatic FNA.     

Diagnostic accuracy and clinical utility of endoscopic bile duct brushing in the evaluation of biliary strictures.

Pathologic evidence of malignancy in biliary strictures is useful in the preoperative setting because it helps define therapeutic planning and prognosis. The purpose of this study was to assess the diagnostic accuracy and clinical utility of endoscopic bile duct brushings in the evaluation of bile duct strictures. We retrospectively evaluated 34 endoscopic biliary brushings derived from 31 patients with bile duct strictures. Relevant clinical and follow-up data were collected. Histologic specimens were reviewed in patients undergoing subsequent biopsies. Patients included 18 men and 13 women with an age range of 25 to 79 years (mean, 52 years). All patients had histologic and/or clinical follow-up. Cytologic diagnosis included cholangiocarcinoma (14.7%), suspicious for cholangiocarcinoma (5.9%), atypical hyperplasia (17.6%), and negative for malignancy (61.7%). All positive diagnoses were confirmed by histologic testing (false-positive rate, 0%). The cases that were suspicious for cholangiocarcinoma and the 5 atypical hyperplasia cases were also subsequently diagnosed as cholangiocarcinoma by biopsy. One atypical case was diagnosed as pancreatic carcinoma. All 21 negative cases were confirmed by biopsies (15) and clinical follow-up (6) (false-negative rate, 20%). Endoscopic bile duct brushing is diagnostically accurate and hence clinically useful in the management of patients with bile duct strictures. Atypical hyperplasias may contribute to diagnostic pitfalls leading to false-positive and false-negative diagnoses.     

Cytodiagnosis of hepatocellular carcinoma in fine-needle aspirates of the liver: its differentiation from reactive hepatocytes and metastatic adenocarcinoma

Fine-needle aspiration (FNA) cytology is a useful tool for diagnosis of primary malignancies and metastatic lesions of the liver. However, well-differentiated hepatocellular carcinoma (HCC) may resemble benign/reactive hepatocytes, and less differentiated HCC may simulate poorly differentiated adenocarcinoma, leading to difficulties in interpretation of aspirates from liver. To determine the subtle cytomorphological features which can differentiate these lesions, ultrasound-guided FNA smears from 86 cases of liver malignancy were subjected to detailed cytologic assessment. These included 20 cases of HCC, 38 cases of metastatic adenocarcinoma, and 28 cases of benign/reactive hepatocytes. The important features for separating HCC or well-differentiated HCC from benign/reactive hepatocytes were excessive cellularity, trabecular pattern vs. thin cords of hepatocytes, nuclear pleomorphism, atypical stripped nuclei, and macronucleoli (P < 0.001 to < 0.0001). The most significant features for differentiating HCC from metastatic adenocarcinoma were trabecular growth pattern, hepatocytic cells vs. columnar/cuboidal cells, eosinophilic granular cytoplasm, lipid vacuoles, bile pigments, and atypical stripped nuclei (P < 0.001 to < 0.0001). The cytomorphological features which may distinguish poorly differentiated HCC from poorly differentiated adenocarcinoma were polygonal (hepatocytic) cells, eosinophilic granular cytoplasm and lipid vacuoles in HCC, and columnar/cuboidal cells and acinar/glandular formation in adenocarcinoma (P < 0.05 to < 0.001). Diagn. Cytopathol. 1999;21:370-377.     

Significance of atypia in pancreatic and bile duct brushings: Follow‐Up analysis of the categories atypical and suspicious for malignancy

Brushing cytology is frequently utilized for the investigation of pancreatic and biliary strictures but is associated with low diagnostic sensitivity. The Papanicolaou Society of Cytopathology has presented a system for diagnostic classification which includes the categories benign, atypical, suspicious for malignancy and malignant. We studied a series of 216 pancreatic and biliary brushings with either histologic follow‐up or a minimum of 6 months clinical follow‐up to determine outcomes for the diagnostic categories (“benign,” “atypical, favor reactive,” “atypical, not otherwise specified,” “atypical, suspicious” and “malignant”). Eighty‐six of the 216 (39.8%) were designated “atypical” with 10 of these designated as “atypical favor reactive.” Forty‐five were called “atypical not otherwise specified” and 31 were interpreted as “atypical suspicious for malignancy.” On follow‐up, 2 of 10 (20%) “atypical favor reactive” were eventually associated with a malignant diagnosis and 23 of 31 (74.2%) “atypical, suspicious for malignancy” demonstrated a malignant outcome. The remaining 45 brushings in the “atypical” category were “atypical not otherwise specified,” and 62% of these were associated with malignancy on follow‐up. Stratification of the “atypical” category into “atypical favor reactive,” “atypical, not otherwise specified” and “atypical, suspicious for malignancy” improves diagnostic accuracy. The “atypical suspicious for malignancy” category has a follow‐up similar to the “malignant” category while the “atypical favor reactive” category is associated with a clinical outcome similar to that of the “benign” category. Diagn. Cytopathol. 2014;42:285–291. © 2013 Wiley Periodicals, Inc.     

Cytopathology of malignant mesothelioma: a stepwise logistic regression analysis.

Twenty-four cytologic features, previously reported to be useful in the distinction of malignant mesothelioma, adenocarcinoma, and benign mesothelial proliferation in serous effusions were assessed. Forty-four cases of malignant mesotheliomas, 46 cases of metastatic adenocarcinomas, and 30 cases of benign mesothelial proliferations were examined for these parameters. When these cytologic features were subjected to a stepwise logistic regression analysis, five features were selected to distinguish malignant mesothelioma from adenocarcinoma. These were true papillary aggregates, multinucleation with atypia, cell-to-cell apposition, acinus-like structures, and balloon-like vacuolation, the latter two features being characteristic of adenocarcinoma. The four variables selected to distinguish malignant mesothelioma from benign mesothelial proliferations were nuclear pleomorphism, macronucleoli, cell-in-cell engulfment, and monolayer cell groups, the latter being a feature of benign proliferations. Using these selected variables, the logistic model correctly predicted 95.4% of cases of malignant mesothelioma versus 100% of adenocarcinoma and 100% of malignant mesotheliomas versus 90% of benign mesothelial proliferations. The results of regression analysis suggest that many of the previously described cytologic features are not important diagnostic discriminators.     

Endoscopic bile duct brushing of malignant pancreatic biliary strictures: retrospective study with comparison of conventional smear and ThinPrep techniques

Endoscopic bile duct brushing (EBDB) is carried out to differentiate benign from malignant biliary strictures in patients who have pancreaticobiliary disease. The sensitivity of this method for the diagnosis of malignancy is relatively low. The aim of this study is to analyze the cytomorphologic features that are helpful in increasing the sensitivity of detecting these lesions on cytologic samples. These features are compared with slides prepared with the ThinPrep technique. The study included 142 patients with bile duct obstruction or pancreatic mass who underwent EBDB and follow-up surgery or biopsy between 1997 to 2000. Twenty-five (18%) of these cases were positive for malignancy in both EBDB and follow-up surgical biopsy; 20 of these cases were used as positive controls (PC). Sixty-one (43%) were negative in both EBDB and follow-up surgical biopsy specimens, and 21 of those cases were used as negative controls (NC). Fifty-six (39%) cases were negative/atypical in EBDB cytology but were suspicious or positive in the surgical or biopsy specimens (false-negative). We identified the cytologic criteria that were helpful in differentiating our positive and negative control groups and applied these criteria to our false-negative group to see whether our sensitivity could be increased, using well-defined cytologic criteria alone. Of the 56 false-negative cases, 9 (16%) were upgraded to suspicious/positive based on the presence of the following features: three-dimensional (3D) micropapillae (95% PC vs 19% NC, P < 0.0001), anisonucleosis (90% PC vs 5% NC, P < 0.0001), high nuclear-to-cytoplasmic (N/C) ratio (95% PC vs 9% NC, P < 0.0001), nuclear contour irregularity (65% PC vs 24% NC, P = 0.0079), and prominent nucleoli (70% PC vs 38% NC, P = 0.0406). Cytomorphologic features which were not helpful in distinguishing positive and negative cases were: single naked nuclei (50% PC vs 28% NC, P = 0.1597), chromatin granularity (50% PC vs 62% NC, P = 0.54), and necrosis (10% PC vs 5% NC, P = 0.5197). Improvement in diagnostic sensitivity for carcinoma of pancreaticobiliary tract in EBDB samples may be achieved by identifying the key malignant cytomorphologic features: 3D micropapillae, anisonucleosis, nuclear contour irregularity, prominent nucleoli, and high N/C ratio. The sensitivity in detecting malignant biliary strictures increased from 31% to 42% based on these criteria in our current study.     

Prostatic aspirates. A cytomorphologic analysis with emphasis on well-differentiated carcinoma

In this retrospective evaluation of 72 cases of fine needle aspiration biopsy of the prostate, 25 aspirates from well-differentiated carcinoma were compared with 27 aspirates from benign prostatic enlargement and 20 aspirates from moderately to poorly differentiated carcinoma. Each case was examined by a single observer (V.K.) for multiple parameters including cellularity, dyshesion, nuclear membrane irregularity, anisonucleosis, macronucleoli (major criteria of malignancy), cell and nuclear enlargement, and altered nuclear/cytoplasmic ratio. Cellularity was the most significant indicator, but all major and minor criteria of malignancy were consistently important for distinguishing well-differentiated carcinoma from benign lesions. Systematic use of these meaningful standards enhances diagnostic sensitivity.     

Fine-needle aspiration cytology of sclerosing adenosis of the breast: a retrospective review of cytologic features in conjunction with corresponding histologic features and radiologic findings

We retrospectively reviewed 25 fine-needle aspiration cases of sclerosing adenosis of the breast in conjunction with histologic features of the paired core-needle biopsy and radiologic findings. The original cytologic diagnoses were benign (n = 19), focally atypical (n = 3), and suspicious for carcinoma (n = 3). The frequent features, although not specific, were low-to-moderate cellularity, bland epithelial cells that focally formed cohesive groups/tubules or occasionally discohesive clusters or individual cells, and fragments of dense fibrous stroma. Some tubules had an angulated configuration. Myoepithelial cells were present in all cases but were scant or absent in small epithelial groups. These cytologic features closely reflected the histologic appearances (ie, compressed and attenuated tubules and sclerotic stroma), but may cause overinterpretation on cytologic smears, especially when angulated tubules, discohesive or individual epithelial cells, scanty myoepithelial cells, and nuclear atypia are noted concurrently. Familiarity with its cytologic features may prevent false-positive diagnosis. Histologic confirmation is recommended for difficult cases.     

Cutaneous malignant melanoma in teenagers

Of 57 reviewed cases of malignant melanoma in teenagers, 51 had a minimum follow-up of 5 years. The histological and some clinical features of the 51 cases were compared for diagnostic and prognostic significance with those of 19 Spitz naevi and 10 other benign naevi using the SPSS-X computer program. The overall crude survival was 71% (males 64%, females 81%). Five patients with regional metastases survived more than 5 years, three of these more than 10 years. The main statistically significant features associated with a poor prognosis were Breslow thickness, diameter of ulcer, abnormal mitoses, pushing dermal borders and marginal (deep) mitoses. In comparison with Spitz naevi, features favouring malignancy were Breslow thickness, fine dusty cytoplasmic melanin pigment, marginal or abnormal mitoses, epithelioid intra-epidermal melanocytes below parakeratosis, dermal nests larger than junctional nests and the mitotic rate in the papillary dermis. Features favouring a benign lesion were diffuse maturation, spindle cells, spindle nuclei and Kamino bodies, especially if numerous or clustered. In comparison with the atypical benign naevi, significant features favouring malignancy were marginal or abnormal mitoses, single cell epidermal invasion below parakeratosis, large nuclei and irregular nuclei.     

Atypical meningioma: morphometric analysis of nuclear pleomorphism

The revised edition of the WHO classification of brain tumours now includes the "atypical" meningioma (grade II) which should be placed between the common type (grade I) and anaplastic type (grade III) according to histomorphological features and prognosis. However, diagnostic criteria for atypical meningioma are vague and the significance of brain invasion in the determination of malignancy is controversial. Nuclear pleomorphism and mitoses are usually considered the most important parameters to distinguish atypical and malignant meningiomas. According to WHO classification we selected eight cases of meningioma diagnosed as atypical (3 cases) and malignant (5 cases). All the tumours were supratentorially located. Nine cases of benign meningiomas were also studied as a control group. Morphometrical analysis was carried out by S.A.M. (Shape Analytical Morphometry) system. S.A.M. logical architecture assumes that each irregular shape contains elements of two distinct logical domains: gross distortions that interest the contour and its local perturbations. These features were investigated separately by analytical procedures to acquire independent parameters both on the logical and the numerical level. The results, statistically evaluated, show that nuclear pleomorphism is not a satisfactory criterion, if used alone, to distinguish atypical from malignant meningioma (Discriminant Analysis: 19% of minimum error).     

Clear-cell sarcoma diagnosis by fine-needle aspiration: cytologic, histologic, and ultrastructural features; potential pitfalls; and literature review

A definitive diagnosis of clear-cell sarcoma of soft parts (CCSSP) is possible by fine-needle aspiration (FNA) biopsy alone. The aspirates are markedly cellular, consisting predominantly of discohesive cells but also of cohesive cells. The cytoplasm is eosinophilic and eccentric. The nuclei are round and contain macronucleoli. CCSSP should be considered when FNA of a soft-tissue tumor shows uncharacteristically high cellularity and relatively uniform cells with macronucleoli. Cohesion of some tumor cells does not rule out CCSSP. Melanin pigment and cytoplasmic clearing are infrequent and not necessary for the diagnosis. Sufficient material should always be procured for immunohistochemical studies on the cell block. Seven other cases are found in the literature, all correctly diagnosed by FNA. Although it is rare, CCSSP is a highly malignant tumor that can be diagnosed readily by FNA without resorting to incisional biopsy.     

Bilateral cystosarcoma phyllodes of the breast: a case report of malignant form with contralateral benign form

Bilateral cystosarcoma phyllode is uncommon; bilateral tumors, either synchronous or metachronous, are generally either benign or malignant. We report one case of bilateral synchronous cystosarcoma phyllode in a 32-year-old pregnant woman. The left breast mass, measuring 21 x 17 x 10 cm, was classified as malignant cystosarcoma phyllode (high cellularity, stromal overgrowth, marked nuclear atypia, necrosis, mitotic rate = 4 mitoses/10 high power field, infiltrative margin). The right 9 x 9 cm mass was a benign cystosarcoma phyllode tumor (low to moderate cellularity, discrete nuclear atypia, mitotic rate = 1 mitoses/10 high power field, no necrosis, pushing margin). The patient had a left-sided mastectomy and a complete local excision with clear margin of the right breast mass. The patient is free of disease with a 17-month follow-up.     

Epithelial repair versus carcinoma in esophageal brush cytology

The distinction between repair atypia and carcinoma in esophageal brushings is often difficult. To establish criteria for making this distinction, the cytologic smears from 121 consecutive esophageal brushings and the companion biopsies were reviewed. The most reliable criteria for malignancy included sharply angulated nuclear rims, a high nuclear/cytoplasmic ratio, and coarsely granular chromatin. Nuclei bearing these features were not numerous and had to be carefully sought. Nuclear pleomorphism was a more consistent feature, but it showed considerable overlap with epithelial repair. Cytologic features of multiple nucleoli, macronucleoli, and loss of polarity were common to both repair and carcinoma. Adherence to the criteria established in this study permits the distinction between repair atypia and carcinoma in almost all cases; however, there are lesions of the esophagus with such overlap between the features of repair and carcinoma that it may not be possible to reach a definitive diagnosis. Specific examples, with illustrations, are discussed as diagnostic guides.     

Interobserver and intraobserver variation among experts in the diagnosis of thyroid follicular lesions with borderline nuclear features of papillary carcinoma

Distinguishing follicular variant of papillary carcinoma (FVPC) from follicular adenoma and follicular carcinoma can be difficult if nuclear features of papillary carcinoma are not well developed or only focally present. We assessed interobserver and intraobserver agreement among 6 thyroid experts by using 15 cases in which original pathologists suspected FVPC. There was unanimous expert agreement in diagnosing FVPC in only 2 cases (13%) and majority agreement in 6 cases (40%). Unanimous agreement on benign and malignant diagnoses was seen in 4 cases (27%) and majority agreement on malignancy in 8 cases (53%). Intraobserver agreement ranged from 17% to 100%. Histologic features considered most helpful in diagnosing FVPC were nuclear clearing, nuclear grooves, nuclear overlapping and crowding, nuclear membrane irregularity, and nuclear enlargement. This considerable interobserver and intraobserver variability in the diagnosis of FVPC seems to result from lack of agreement on the minimal criteria needed to diagnose FVPC, even among experts.     

KOC (K homology domain containing protein overexpressed in cancer) and S100A4-protein immunoreactivity improves the diagnostic sensitivity of biliary brushing cytology for diagnosing pancreaticobiliary malignancies

Biliary tract brush cytology is one of the favored methods of evaluating lesions of the pancreatobiliary tract. However, although its specificity has been reported to be high (91-100%), the sensitivity is lower (30-88%). In this study we applied KOC and S100A4 protein immunocytochemistry to assess their potential use as adjunct markers in differentiating benign from malignant cells, and improve the diagnostic sensitivity of this method for pancreatobiliary malignancies. The authors examined KOC and S100A4 protein expression in 44 alcohol-fixed cytology specimens obtained by biliary brushings. Diagnoses included: (1) benign/atypical favor reactive (20 cases), (2) atypical/not diagnostic of malignancy (3 cases), and (3) suspicious for malignancy/malignant (21 cases). Alcohol-fixed Papanicolaou-stained slides (PAP) were stained with monoclonal antibody to KOC/L523S and polyclonal antibody to S100A4 protein. Results were recorded as negative or positive. Twenty-four cases were confirmed positive for adenocarcinoma and 20 cases were negative. The sensitivity and specificity of cytology was 83 and 95%, KOC showed a sensitivity of 92% and specificity of 95%. S100A4 protein showed a sensitivity of 79% and a specificity of 95%. The combined use of KOC and S100A4 protein showed a sensitivity of 100% and a specificity of 95%, respectively. The concurrent use of KOC and S100A4 protein improves the diagnostic sensitivity of biliary brushings cytology and demonstrates similar specificity as cytology alone in the diagnosis of pancreatobiliary malignancy.     

Cytologic diagnosis of metastatic malignant phyllodes tumor of the breast in pleural effusion

A 54‐year‐old woman presented with a left breast mass, discovered 4 years ago but was static until 2 months before presentation, when it showed a rapid increase in size and became painful. Mammography showed a large lobulated mass with internal cystic components (BI‐RADS 4B). A biopsy was performed, followed by modified radical mastectomy. The histologic diagnosis was malignant phyllodes tumor (PT). The patient developed local recurrence 4 months later while on adjuvant radiotherapy and she had a salvage resection. Two months later, she developed massive left pleural effusion. Pleural fluid cytology showed single discohesive markedly atypical cells with hyperchromatic and enlarged nuclei, irregular nuclear membrane, and distinct macronucleoli. Multinucleated forms were also seen. The mononuclear and multinucleated tumor cells cytomorphologically resembled that of the recurrent tumor, indicative of recurrence. Positron emission tomography/computed tomography confirmed recurrence at the left pleura. The patient opted for palliative care and succumbed 1 month later. The current case demonstrated a rare clinical presentation of recurrent malignant PT as massive unilateral malignant pleural effusion. Correlation with previous histologic and cytologic specimens may be useful as similar cytologic features could be identified in subsequent recurrent tumors.     

Lessons learned from mistakes and deferrals in the frozen section diagnosis of bronchioloalveolar carcinoma and well-differentiated pulmonary adenocarcinoma: an evidence-based pathology approach

The frozen section diagnosis of lung nodules is difficult because inflammatory atypia and histologic artifacts can simulate a malignancy. From a total of 2,405 frozen sections examined, 143 cases were misdiagnosed or deferred, including 65 with reactive atypia (RA) and 35 bronchioloalveolar carcinomas or well-differentiated adenocarcinomas (BAC-AC), resulting in deferral and error rates of 4.36% and 1.58%, respectively. The presence of 25 pathologic features was evaluated by using an evidence-based pathology (EBP) approach. Of the pathologic features, 11 were significant at a P value of less than .05 but exhibited variable incidence in AC and RA. Positive likelihood ratios allowed for identification of the 5 most useful pathologic features for the diagnosis of AC: multiple growth patterns, anisocytosis, atypia more than 75%, macronucleoli, and atypical mitoses. Granulomas favored the diagnosis of RA. An EBP approach is helpful to stratify pathologic features according to their clinical applicability.