Search

Objective: Atypical squamous cells of undetermined significance (ASCUS) and atypical glandular cells (AGC) reflect cellular abnormalities insufficient for clear diagnosis. We used cell pellets obtained from liquid-based cytology (LBC) to prepare cell blocks (CB) and clarify the initial diagnosis of ASCUS and AGC., Study Design: A total of 393 CBs with initial diagnosis of ASCUS or AGC were processed. Of those, 305 of the ASCUS and 20 of the AGC had adequate specimens. We compared results of CBs prepared from ASCUS and AGC to determine which had higher frequencies of higher-grade lesions., Results: A majority of specimens (83%) were adequate for evaluation. Compared with the initial diagnosis, 14% (42/305) of ASCUS were diagnosed with low-grade squamous intraepithelial lesion (LSIL) in CB, while 10% (2/20) of AGC were diagnosed with LSIL or adenocarcinoma. No statistical relationship between the initial diagnosis of ASCUS and AGC and results of higher-grade lesions in CB is evident as determined by p value greater than 0.05 (p = 0.228)., Conclusions: CBs prepared from Liqui-PREP cell pellets are, in most cases, assessable and can be useful as an adjunctive test to help clarify the initial diagnosis of ASCUS and AGC. Diagn. Cytopathol. 2017;45:520-525. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Myofibroblastoma (MFB) is a benign tumor of the mammary stroma with predominant myofibroblastic differention. The cytologic reports of MFB are very few in the available literature. From the cytodiagnostic point of view about 21 cases of MFB with cytological evaluation by fine-needle aspiration cytology (FNAC) have been encountered in the English-language literature: A 35-year-old woman presented with lump in the left breast. FNAC showed mild degree of pleomorphism with occasional groups with fibrous stroma and tumoral cells. A few benign epithelial cell groups were seen. Hematoxylin-eosin-stained sections of cell block preparation from the aspirate showed fascicles of spindle cells forming whorl structures. Three months later, excision biopsy was performed. The diagnosis was a classic variant of MFB. On immunohistochemical examination, sections were found to be highly positive for vimentin, CD34, and bcl- 2. In light of these findings, cell block material was retrospectively reviewed both morphologically and immunhistochemically. The findings of resection and cell block material were found to be very similar. MFB may cause a potential diagnostic pitfall while interpreting FNAC due to its wide differential diagnosis spectrum. We concluded that cytology and cell block findings complement each other. Diagn. Cytopathol. 2016;44:1064-1069. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Evaluation of ER, PR and Her 2 are routinely performed on breast carcinomas. For accurate detection of these markers, compliance with the ASCO/CAP guidelines is recommended. Our previous study showed that alcohol fixation did not affect ER results when alcohol-fixed cell block (CB) sections were compared to formalin-fixed tissue sections, while PR and Her2 showed less concordance. The aim of this study was to evaluate and to compare ER, PR and Her2 IHC results on formalin-fixed CB sections to those observed on subsequent surgical (needle core or resection) specimens (SS). Fifty cases of formalin fixed CB samples obtained from primary (18%) and metastatic (82%) breast carcinomas were studied, all of which had subsequent SS available. ER, PR, and Her2 IHC studies were done on all samples and results were compared. ER results on formalin-fixed CB samples showed excellent correlation with SS (correlation coefficient cc = 0.82). While there was minimal improvement in PR results (cc = 0.433), Her2 detection did not improve by formalin fixation (cc = 0.439). Formalin fixation for CB preparations does not significantly improve the already good detection of ER positive breast tumors. The concordance rate in PR and IHC results between formalin-fixed CB and SS samples showed improvement as compared with the alcohol-fixed CB results. However, there was no improvement in detection of Her2 overexpression by using formalin fixation on cytology specimens., (Copyright © 2012 Wiley Periodicals, Inc.)

We compared the results of smears to those of cytospin and cell block preparations from fine-needle aspirations to determine the cost effectiveness of each and to determine which should be routinely obtained. We reviewed 844 cases, 361 of which had both smears and cytospins, and 483 of which had both smears and cell blocks. Smears alone were diagnostic in 94% of cases (796/844 cases), cytospins alone diagnostic in 43% of cases (154/361 cases), and cell blocks alone diagnostic in 57% of cases (277/483 cases). Cytospins contributed additional information beyond that obtained from smears in 2% (7/361) and cell blocks in 12% (57/483) of cases. When smears were nondiagnostic, cytospins contributed additional information in 10% (2/21) of cases and cell blocks contributed additional information in 44% (12/27) of cases. The cost of providing a diagnosis from smear alone is $212, from cytospin alone is $352, and from cell block alone is $392. The cost for additional information established by cytospin is $7,736 and by cell block the cost is $1,906. Smears are superior to either cytospins or cell blocks in providing a diagnosis. It is not cost-effective to obtain either cytospins or cell blocks in addition to smears on all cases. However, it is cost-effective to obtain cell blocks when the immediate smear evaluation is nondiagnostic.

Serous tumors of low malignant potential are uncommon in women under 30-years-old peritoneal washings play an important role in the diagnosis and prognosis of ovarian neoplasms. Accurate diagnosis of peritoneal washings is important in determining therapeutic regimens and in determining patient prognosis. In peritoneal washings, these tumors can be difficult to distinguish from reactive benign mesothelial cells. The cases of four women with borderline serous ovarian tumors, all of whom were under the age of 25, and had peritoneal washings which were positive for papillary tumors were reviewed.

Background: Liquid-based cytology (LBC) allows immunohistochemistry (IHC), fluorescence in situ hybridization, and molecular testing to be performed in fixed cell materials. We examined the feasibility of subtyping and EGFR mutation testing of bronchoscopic samples from patients with lung cancer using cell blocks (CB) based on LBC fixation (LBC-CB)., Methods: We included 35 consecutive patients with peripheral lung nodules who underwent endobronchial ultrasonography with a guide sheath in our hospital. Thirty of these patients were diagnosed with lung cancer by obtaining cytological samples. Cytological subtyping was performed with IHC using LBC-CB, and the Cobas EGFR Mutation Test ver. 2 was performed using extracted genomic DNA from the LBC-CB, formalin-fixed paraffin-embedded (FFPE) tissue, and matched plasma., Results: Of the 30 cases, 25 were classified cytomorphologically as adenocarcinoma (ADC, n = 17) and squamous-cell carcinoma (SQCC, n = 8). The remaining five cases were classified by IHC as favor ADC (n = 3) and favor SQCC (n = 2) according to the WHO criteria. In the final ADC group (n = 20), EGFR mutations on the LBC-CB were identified in eight cases (40%; 1 exon 19 deletion, 6 L858R, and 1 L861Q). Mutations in FFPE samples were identified in seven cases (35%) at the same site in each case. Plasma EGFR mutations were identified in four cases (20%) at the same site. The CB detection rate was higher than for FFPE and plasma., Conclusion: LBC-CB is suitable for subtyping and EGFR mutation testing in lung cancers., (© 2020 Wiley Periodicals, Inc.)

Background: PD-L1 immunoexpression in head and neck squamous-cell carcinoma (HNSCC) determines immunotherapy eligibility. Patients are often diagnosed using fine-needle aspiration (FNA) of metastatic lymph nodes, however, the cytohistologic correlation of the combined positive score (CPS) is largely unknown., Methods: This study retrospectively identified 96 paired histologic (HS) and cytologic specimens (CyS), between 2016 and 2020, diagnosed with HNSCC. Cases with <100 tumor cells (n = 54) or missing block(s) (n = 8) were excluded. All 34 case pairs were scored with CPS using the PD-L1 22C3 pharmDx assay at clinically relevant cut-offs of <1%, 1%-19%, and ≥20% independently by three observers blinded to the case pairs (CyS with corresponding HS)., Results: The CPS (<1/1-19/≥20) for CyS and HS were as follows: 10(29.4%)/10(29.4%)/14(41.2%) and 2(5.9%)/13(38.2%)/19(55.9%), respectively. There was fair overall cytohistologic agreement (OA) of 76.5% (k = 0.261) at the CPS cut-off of 1. The OA did not differ significantly between site-matched (n = 13) and -unmatched (n = 21) case pairs (p = .4653). CyS has a specificity and positive predictive value (PPV) of 100% but a negative predictive value (NPV) of only 20% as compared to its paired HS., Conclusions: Our study demonstrates fair CPS cytohistologic correlation in HNSCC specimens using the PD-L1 IHC 22C3 pharmDx assay with high PPV but low NPV. This suggest that determining PD-L1 status in FNA specimens can play an important role in the clinical management of HNSCC patients., (© 2023 The Authors. Diagnostic Cytopathology published by Wiley Periodicals LLC.)

Background: Immunotherapy based on disruption of the PD-1/PD-L1 axis is standard of care for many high stage malignancies including melanomas, non-small cell carcinomas of the lung, triple negative breast carcinomas, and squamous cell carcinomas of the head and neck. Eligibility for immunotherapy requires immunohistochemical assessment of PD-L1 expression. Currently, many high stage malignancies are diagnosed by cytology and cytologic material is the only specimen available for ancillary testing. Formal guidelines do not currently exist defining the optimal specimen type, antibody to be used or the best scoring system for cytologic material. Significant information has been published for PD-L1 testing of pulmonary specimens but much less data exists for the reproducibility, accuracy and best practices for material obtained from other body sites and types of malignancy., Methods: We searched the PubMed data base for manuscripts relating to PD-L1 testing of cytologic specimens. The search period was between 2016 and 2022. The search terms used were PD-L1, cytology, FNA, immunotherapy, immunohistochemistry, immunocytochemistry, cytology-histology correlation. Cross referencing techniques were used to screen for the most relevant manuscripts. The abstracts of these were then reviewed for final data collection and analysis., Results: A total of 86 studies were identified conforming to study relevancy. These were reviewed in their entirety by two authors (LJL, TZ) for extraction of data. The majority of studies involved pulmonary specimens (79) with three relating to PD-L1 testing of head and neck cytologic specimens and one each for PD-L1 testing of cytology specimens from melanomas, pancreas, pleural fluids, and triple negative breast carcinomas. While smears could be used, most studies found cell blocks optimal for testing., Summary: Currently, four drugs are approved for immunotherapy based on PD-L1 status. These drugs require specific antibody clones as well as scoring systems. Scoring systems and cut points vary with the type of neoplasm being treated. Cytology specimens from the lung, head and neck and melanomas can all be used for PD-L1 testing with good agreement with corresponding histology specimens., (© 2022 Wiley Periodicals LLC.)

Malignant mesothelioma (MM) is a rare and highly lethal tumor that arises from mesothelial tissue on the surface of the chest and abdominal cavity. Cytological examination of body fluids, including pleural fluid and ascites, is essential for the differentiation of malignant mesothelioma from other carcinomas, such as lung and gastrointestinal carcinomas and metastatic tumors. To evaluate the effectiveness of cell block preparation procedures, which are used for immunocytochemical staining and genetic panel analysis of tumor-specific gene mutations, we used various fixatives. We also evaluated the effects of immunostaining, and the quality of nucleic acids for genetic analysis., Methods: Cell blocks were prepared using the malignant mesothelioma cell lines MESO4 and H226 and non-small cell lung carcinoma cell line HCC78. The cells were fixed using 10% neutral buffered formalin and four different fixatives for liquid cytology. Fixed cells were formed into cell clusters using sodium alginate or centrifugation, and paraffin-embedded cell blocks were prepared., Results: Cell blocks were morphologically evaluated by hematoxylin and eosin and immunocytological staining, and the nucleic acid quality was evaluated by DNA/RNA extraction, qPCR, and next-generation sequence analysis. D2-40 and WT1 staining differed depending on the fixation solution and the cell cluster formation method; however, the degree of nucleic acid degradation was not impaired by any method., Conclusion: Although the morphological evaluation of cytology specimens is affected by the method of cell block preparation, it is still useful for nucleic acid extraction and gene panel analysis, as long as there are sufficient amounts of tumor cells., (© 2022 Wiley Periodicals LLC.)

Background: The cytologic evaluation of serous effusions to distinguish malignant cells from reactive mesothelial cells (RMCs)was an enormous challenge. The purpose of this study was to investigate the diagnostic value of glucose transporter 1 (GLUT1) and calretinin (CR) in serous effusions of patients with malignant and in order to significantly ameliorate the diagnostic accuracy., Methods: The expressions of GLUT1 and CR were measured by streptavidin-peroxidase (S-P) immunocytochemical technique in serous effusions of 183 patients with malignant and in 95 patients with benign diseases., Results: The positive ratio of GLUT1 was 91.8% (168/183) in serous effusions from patients with malignant and 5.3% (5/95) in benign diseases, they had a significant difference (P < .01). CR was expressed 89.5% (85/95) in benign diseases and 6.6% (12/183) in malignant, it also showed an important difference (P < 0.01). The combination of GLUT1 + CR revealed the best efficiency: the sensitivity and specificity were 100% and 98.9%, respectively., Conclusion: Immunocytochemical staining for GLUT1 and CR may be used as a complementary tool for the detection of malignant effusions and help to make a distinction between cancer cells and RMCs. The combination of GLUT1 and CR with immunocytochemistry stained can be achieved a higher diagnostic performance., (© 2021 Wiley Periodicals LLC.)

The differential diagnosis in cellular effusions with cytological atypia often includes malignant mesothelioma (MM), reactive mesothelial proliferation, and malignancies of metastatic origin, particularly carcinomas. The International Reporting System for Serous Fluid recently established guidelines for reporting MM. In conjunction with the cytomorphologic evaluation, the role of immunochemistry (IC) was emphasized as a very useful tool in the workup of serous fluids, especially with the availability of novel markers. Utilizing a panel of markers, IC allows the characterization of the cells, whether mesothelial or not, and when mesothelial origin is established, IC can frequently assist in delineating its benign or malignant nature. IC can also confirm metastatic disease, allowing the identification of the primary origin in most cases. This review summarizes the current status of IC and its role in the diagnosis of MM and its differential diagnosis in serous fluids., (© 2021 Wiley Periodicals LLC.)

Myofibroblastoma (MFB) is a rare benign spindle cell tumor originating from myofibroblasts in the breast stroma. MFB typically presents as a slow-growing, well-circumscribed, solitary mass ranging from 1 to 4 cm in size. It has been reported in adults, and frequently seen in older males and in postmenopausal females. The lesion is composed of stromal cells showing fibroblastic and myofibroblastic differentiation at the morphological, immunohistochemical and ultrastructural levels. To date, the literature includes only about 24 MFB cases confirmed via fine-needle aspiration and cytological evaluation. Here, we present a patient with MFB that was diagnosed via conventional smear slides and cell block, in addition to immunohistochemical analysis., (© 2020 Wiley Periodicals LLC.)

Background: PD-L1 immunohistochemistry is currently performed in patients with advanced non-small cell lung carcinoma (NSCLC) to identify responders to immune checkpoint inhibitors. Cell blocks from fine needle aspiration of NSCLC are frequently used for diagnostic purposes. The aims of the study are to analyze: (a) the distribution of PD-L1 in cell blocks, in comparison to biopsies and surgical specimens; (b) the concordance of PD-L1 in specimens of the same patients., Methods: PD-L1 analyses conducted in NSCLCs were retrieved. Cell blocks were prepared with the self-clotting method. PD-L1 was performed with Dako 22C3 on the Ventana BenchMark ULTRA platform. Results were divided by tumor proportion score (TPS) in 3 categories: <1%; 1% to 49%; ≥50%., Results: A total of 483 samples from 456 patients was collected: 120 cell blocks (24.8%), 307 endoscopic or transthoracic biopsies (63.6%), 56 surgical specimens (11.6%). TPS was: <1% in 230 samples (47.8%), 1% to -49% in 136 (28.3%) and ≥ 50% in 115 (23.9%); in two samples material was insufficient. Statistics did not reveal significant differences in PD-L1 expression among the various materials (χ 2 = 2.905; P = .574). In 50 samples from 25 patients, PD-L1 was carried out in two samples of the same patients, with moderate agreement (concordance rate: 68.0%, k = 0.469)., Conclusion: (a) PD-L1 is similarly distributed in the different materials; (b) PD-L1 shows moderate concordance in different samples of the same patients. PD-L1 may be routinely tested in cell blocks, but interpreted with caution and repeated whenever possible., (© 2020 Wiley Periodicals LLC.)

Background: Although fine needle aspiration cytology (FNAC) is highly accurate for detecting breast malignancies, concerns remain among cytopathologists about false-positive and false-negative diagnoses. Cell block (CB) preparations have been advocated by some cytopathologists as one of the methods to improve and consolidate the diagnostic accuracy of FNAC. The aim of this study was to determine the diagnostic utility of CB in FNAC of palpable breast lesions among female patients., Methods: Following FNA, CBs were prepared using 10% neutral-buffered formalin from the residual breast aspirates of 100 consecutive female patients attending the FNAC clinic. The slides of the conventional smears, CB and excisional biopsies were examined, and results were analysed using the SPSS., Results: Of the 100 patients that had FNAC, 44 (44%) had excisional biopsy performed. An additional 13% diagnostic yield for malignancy was obtained with the use of CB preparations. CB reduced equivocal diagnoses by 25%, corresponding with 90.9% improvement on definitive diagnoses., Conclusion: In our setting, the addition of CB to smear remarkably improved the diagnostic utility of breast FNAC by minimising atypical and suspicious for malignancy diagnostic categories., (© 2020 Wiley Periodicals LLC.)

Background: This study was conducted to evaluate the diagnostic utility of cell block material in fine needle aspiration (FNA) of thyroid nodules., Design: A total of 242 thyroid fine need aspirations (FNAs) were performed between January 2015 and December 2015. Of those, all consecutive thyroid FNA cases with cell blocks (n = 140) from 129 patients (age: 58.9 ± 12.8 years) are included in this study. Cytology slides and cell blocks are reviewed for adequacy assessment based on the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) and then categorizing them into TBSRTC diagnostic categories. These cases are divided into two groups, combined cytology and cell block (C + CB) and cytology without cell block (C)., Results: In the first group (C + CB), a total 140 cases are categorized in TBSRTC as follows: I: 13 (9.3%) cases, II: 78 (55.7%) cases, III: 7 (5%), IV: 16 (11.4%), V: 3(2.2%) and VI: 23 (16.4%). In the second group (C), the cases are classified in TBSRTC as follows: I: 23 (16.4%) cases, II: 70 (50%), III: 7 (5%), IV: 16 (11.4%), V: 3 (2.2%) and VI: 21 (15%). Nondiagnostic rate was 7.1% lower in the first group (C + CB) as compared with second group (C) (First group: 9.3% vs second group: 16.4%, P = .0764)., Conclusions: Combined use of cytology slides and cell block decreases the nondiagnostic rate up to 7.1% as compared with cytology without cell block., (© 2019 Wiley Periodicals, Inc.)

The Uniform Approach to Breast Fine Needle Aspiration Biopsy was put forward by a learned group of breast physicians in 1997. This landmark manuscript focused predominantly on diagnosis and reporting of mammary epithelial lesions. Today, most American practitioners turn initially to core biopsy rather than aspiration biopsy for the first line diagnosis of solid breast lesions; however, recent efforts from the International Academy of Cytology have produced a system called the Standardized Reporting of Breast Fine Needle Aspiration Biopsy Cytology (colloquially labeled in 2017 as the "Yokohama System"), suggesting a new interest in breast fine needle aspiration (FNA), especially in resource limited settings or clinical practice settings with experienced breast cytopathologists. Fibroepithelial lesions of the breast comprise a heterogeneous group of biphasic tumors with epithelial and stromal elements. Mesenchymal lesions of the breast include a variety of neoplasms of fibroblastic, myofibroblastic, endothelial, neural, adipocytic, muscular, and osteo-cartilaginous derivations. The cytology of mesenchymal breast lesions is infrequently described in the literature and is mainly limited to case reports and small series. This illustrated review highlights the cytologic features of fibroepithelial and mesenchymal mammary proliferations and discusses differential diagnoses and histomorphologic correlates., (© 2019 Wiley Periodicals, Inc.)

Aberrant expression of high mobility group box 1 (HMGB1) is associated with tumor development and progression. The current study was conducted to evaluate the significance of HMGB1 immunostaining on cell block (CB) preparations in the diagnosis of neoplastic and preneoplastic lesions of the cervix. The CBs were prepared from 157 residual liquid-based gynecologic cytology specimens which were collected from women whose cervical lesions had been confirmed by histopathology. The expression of HMGB1 and p16INK4A (p16) was visualized by immunocytochemistry on the CB preparations, and the association of their expression patterns was correlated with the severity of cervical lesions. HeLa cells were used as positive control. HMGB1 expression was observed in dysplastic and neoplastic cells and increased along with the progression of cervical neoplasia. The rates of positive staining for HMGB1 in cervical intraepithelial neoplasia 1 (CIN-1), CIN-2, CIN-3, and invasive squamous cell carcinomas (ISCCs) were 69.4, 96.9, 100.0, and 100.0%, respectively. The differences between positive rates of patients with chronic cervicitis and various CINs as well as ISCCs were significant (P < 0.005). The differences in positive staining rates between each two CIN groups, and differences between CIN-1/2 and ISCCs, were also significant (P < 0.005). The expression pattern of HMGB1 was generally correlated with that of p16 (P < 0.001). HMGB1 staining was observed in some p16-negative specimens. HMGB1 immunostaining on a CB from gynecologic cytology specimens is potentially valuable for the screening of cervical lesions in cases with questionable cytology., (Copyright © 2014 Wiley Periodicals, Inc.)

Introduction: Claudin-4 has been described as a highly sensitive immunocytochemical marker for detection of metastatic carcinoma cells in effusion cytology specimens. This study aims to challenge the performance of claudin-4 in different types of malignancies and low cellularity specimens, by comparison with other markers in a large cohort of carcinomatous effusion specimens., Methodology: Cell block preparations from peritoneal and pleural fluid specimens were retrieved, with malignant (carcinoma) diagnoses confirmed by review of hospital diagnosis code and pathology reports. Claudin-4, BerEP4, CEA, and MOC31 immunocytochemistry were performed and scored by expression proportion and intensity. Tumor cellularity was assessed for subgroup analysis of low cellularity specimens., Results: Totally 147 specimens (70 pleural, 77 peritoneal) of 68 lung, 62 breast, 9 gynecological, and 7 gastrointestinal carcinomas were retrieved. The average proportion expression of claudin-4 was highest (89.6%, vs. CEA 40.5%, BerEp4 18.6%, MOC31 16.8%) and the percentage of strong expression was highest for claudin-4 (72.1%). Expression levels of claudin-4 were consistently higher than other markers in subgroups of all primary sites. The difference was more significant for low cellularity specimens. High (≥50%) proportion expression was seen for 96.61% of cases for claudin-4 (vs. BerEp4 8.77%, CEA 46.55%, MOC31 8.77%, p < 0.001). These factors contributed to a low concordance between claudin-4 and BerEp4, CEA and MOC31 (K = 0.010-0.043)., Conclusion: Claudin-4 is more sensitive than CEA, BerEp4 and MOC31, suitable for low cellularity specimens of most types of metastatic carcinoma and is a robust immunocytochemical marker for carcinoma that can be used solitarily., (© 2024 The Author(s). Diagnostic Cytopathology published by Wiley Periodicals LLC.)

Metastatic urothelial carcinoma is a rare cause of pleural effusions. We report a case of urothelial carcinoma of the upper urinary tract in an oldest-old male patient, a smoker, with situs inversus totalis, that presented uniquely with malignant pleural effusion at presentation without evidence of a primary tumor on imaging. Cytological smears of the massive left pleural effusion revealed epithelioid neoplastic cells arranged in short cords, small-to-large clusters, and raspberry-like morules, mimicking mesothelioma; cell block preparations highlighted the presence of tubules and nest-like structures. The tumor cells showed a high nuclear-to-cytoplasmic ratio, nuclear grooves, and mitotic figures. Cytomorphologic features coupled with the immunophenotype of neoplastic cells (p63, GATA3, and uroplakin II positive) allowed the diagnosis of metastatic urothelial carcinoma and a possible nested subtype. These findings were supported by a total body computed tomography (CT) showing no evidence of a mass in the bladder or elsewhere in the urinary tract but a concentric parietal thickening of the proximal left ureter, suggesting malignancy. To our knowledge, a malignant effusion as a primary manifestation of urothelial carcinoma with nest-like features originating in the upper urinary tract has never been described previously. Our case focuses on the value of cell block in the working-up of neoplastic effusions by revealing the architectural pattern of an uncommon malignancy and the correlation between cytopathology and imaging gross findings to reach an accurate diagnosis., (© 2024 Wiley Periodicals LLC.)

Objective: Squamous metaplasia is not uncommonly observed in salivary gland neoplasms, including pleomorphic adenomas (PAs). It poses as a diagnostic pitfall with cytomorphologic features overlapping with low-grade epithelial malignances and carcinoma ex-PA. We report series of aspirates of PAs with squamous metaplasia and review the literature for the clinicopathological and cytologic features of this diagnostically challenging entity., Methods: Three cases including index aspiration cytology, post-aspiration specimen cytology, cell block immunohistochemistry (IHC), histologic correlation, and clinical data were reviewed. Literature search was performed for cases of PAs with squamous metaplasia, yielding 22 case reports including 11 with aspiration cytology performed., Results: Metaplastic squamous components were seen in all index aspirations, but foreign body reaction and cystic changes were observed only after aspiration or in irritated lesions. PLAG1 IHC demonstrated reliable immunoreactivity in cell block preparations. Summarizing cases in this series and in the literature, cytologic features reported were variable and no consistent diagnostic feature was identified. Most reported cases were initially diagnosed as suspicious or malignant, but all ran a benign clinical course. Significant morbidity was reported only in one case due extensive surgery based on a malignant diagnosis., Conclusions: Squamous metaplasia in PAs is not associated with adverse outcomes, but may induce reactive changes upon aspiration/irritation, resulting in worrisome cytologic features. PLAG1 IHC is a useful adjunct when characteristic cytologic features for PAs are absent or obscured. Prudent use of the diagnostic category salivary gland neoplasm of uncertain malignant potential (SUMP) in the Milan system can avoid overtreatment., (© 2021 Wiley Periodicals LLC.)

Extramedullary multiple myeloma (EMM) involving the liver as a focal space-occupying lesion is very rare, especially in the patients with cirrhosis. Here, we report a case of EMM in the liver and periportal lymph node, diagnosed by endoscopic ultrasound guided-fine-needle aspiration (EUS-FNA). A 57-year-old male patient, with history of cirrhosis, presented with abdominal pain and pancytopenia. The abdominal magnetic resonance imaging (MRI) demonstrated a 6.5 cm left hepatic mass with a 1.1 cm malignant-appearing periportal lymph node and diffuse osseous lesions. The cytology specimens from the hepatic mass and the periportal lymph node were obtained through EUS-FNA without rapid on-site evaluation (ROSE). The thin-layer preparations (ThinPrep) showed abundant plasmacytoid cells, which were confirmed to be Kappa-restricted neoplastic plasma cells by the cell block preparations. Later, his serum level of Kappa light chain was found significantly elevated by flow cytometry, which was identified as monoclonal IgA Kappa light chain by serum protein electrophoresis (SPEP) with immunofixation. The patient was diagnosed as IgA multiple myeloma with extramedullary involvement of the liver and periportal lymph node. This is the first case showing the ThinPrep cytomorphologic features of EMM in the liver and periportal lymph node. This case highlights the importance of distinguishing plasma cells from being hepatocytes and lymphocytes on the ThinPrep and also emphasizes the utility of the cell block in the diagnosis of plasma cell neoplasm., (© 2020 Wiley Periodicals, Inc.)

Background: With the continuous development of new antibodies, the use of immunohistochemistry (IHC) is becoming more often a requirement. IHC is frequently necessary for establishing cancer diagnosis and making therapeutic decisions. However, cytology specimens such as effusion fluid and fine-needle aspiration are highly variable in cellularity and contain background inflammatory and mesothelial cells. Compared to biopsy or excision specimens, tissue exhaustion and levels of sections not matching are more commonly encountered. We present a method of integrating whole-slide cell block image of multiple antibodies by digital image processing and reconstructing a virtual multiplex IHC image for enhanced interpretation., Methods: Historic archived cell block preparations of carcinomas (n = 19) and melanoma (n = 1) and IHC performed with 3,3'-diaminobenzidine chromogen were reviewed. The slides were digitized by a whole-slide image scanner. Using ImageJ and self-developed code, the slides were aligned by image registration, layered, and recolored to reconstruct a virtual multiplex image, simulating a multiplex preparation with multiple chromogens. To quantity the performance of the image registration, the mean distance between the same cell clusters in aligned images were measured., Results: All 20 cases were successfully registered. The mean distance between cell clusters after image registration was 8.40 +/- 5.52 μm. The reconstructed images were able to demonstrate coexpression of membranous, cytoplasmic, and nuclear antibodies., Conclusion: With virtual multiplex IHC, we were able to visualize coexpression of multiple antibodies without the added cost of multiplex IHC. Routine and historic slides, without additional tissue consumption, can be retrieved for image reconstruction. This technique is a low-cost adjunct to diagnosis in cytology for more efficient and accurate assessment of antibody coexpression and histochemical stains., (© 2020 Wiley Periodicals, Inc.)

Serous cystadenoma (SCA) is an uncommon benign pancreatic neoplasm that is most often managed conservatively with follow-up rather than surgical excision. Therefore, to avoid the serious complications of pancreatic surgery, SCA should be diagnosed accurately at the preoperative level. Preoperative SCA diagnosis requires a multimodal diagnostic approach that includes imaging, cystic fluid biochemical analysis and/or endoscopic ultrasound fine-needle aspiration (EUS-FNA). In this brief report, we describe six EUS-FNA cases from five patients that were reported as "benign, consistent with serous cystadenoma". Samples were hypocellular, composed of loose clusters and single cuboidal, bland-looking cells among epithelial sheets representing gastrointestinal contamination. Cell blocks were prepared and all six FNA cases revealed cuboidal cells with a positive α-inhibin immunophenotype, consistent with a diagnosis of SCA. As EUS-FNAs of SCA commonly result in non-diagnostic interpretations, cell block preparations with subsequent immunochemistry can increase their diagnostic accuracy and guide patient management., (© 2019 Wiley Periodicals, Inc.)

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors that can affect any part of the body. They can be sporadic or arise in the setting of tuberous sclerosis (TSC). In this article, we report a series of three hepatic and two pancreatic PEComas diagnosed preoperatively with ultrasound-guided fine needle aspiration (FNA). All patients were female (age range 28-70), had no personal history of TSC and presented with a single, localized painless mass. Rapid on-site evaluation (ROSE) of cytologic samples was performed for all cases to evaluate for cellular content and adequacy of specimens. Direct smears and cell block preparations revealed a proliferation of medium to large polygonal epithelioid cells, with abundant eosinophilic and vacuolated cytoplasm, arranged in sheets and nests. On immunohistochemistry (IHC), neoplastic cells showed co-expression of melanocytic and smooth muscle markers and a diagnosis of PEComa was rendered. PEComas of the pancreas and liver are rare neoplasms, but should always be considered when examining "clear cell" neoplasms, especially in young female patients. If good quality cytologic samples are obtained by FNA, a correct diagnosis can be achieved with the help of IHC. This is of particular importance in order to plan adequate surgical strategy and to avoid overtreatment., (© 2018 Wiley Periodicals, Inc.)

Skeletal muscle metastasis from breast carcinoma is a relatively rare clinical entity. We report two cases of breast cancer metastatic to the skeletal muscle, diagnosed by ultrasound guided fine needle aspiration (US-FNA) biopsy done by interventional cytopathologists at an outpatient cytopathology center. Our two patients presented with lower anterior neck firmness and chest wall mass, respectively. Ultrasound evaluation of our first case demonstrated hypo-echoic thickened anterior strap muscles while in the second case there was significant distortion of the anatomy from previous surgeries. It was necessary to proceed with FNA biopsy even when their ultrasound findings were equivocal, to establish a definite rapid diagnosis. The immediate onsite evaluation findings were suggestive of malignancy in both cases with subsequent core biopsy confirming the diagnosis of metastatic breast carcinoma. In cytopathology, point-of-care (POC) ultrasound is used as an adjunct tool that offers visual guidance during FNA of nonpalpable masses and enables sampling of lesional "hot" spots to ensure specimen adequacy. Studies have demonstrated a reduction in FNA nondiagnostic rates with the use of ultrasound-guidance consequently reducing health care costs associated with nondiagnostic FNAs. US-FNA also provides adequate samples for cell block preparations. Metastatic lobular carcinoma of the breast has a wide range of clinical presentations and a high level of suspicion is advised. Cytopathologists-performed US-FNA is a proven, less-invasive, cost-effective tool that provides timely cytologic diagnosis., (© 2018 Wiley Periodicals, Inc.)

Background: Women treated for breast cancer are at increased risk of developing pulmonary nodules which could represent new primary lung carcinomas or metastatic breast carcinoma. The FNA biopsy is frequently the first diagnostic choice in determining the primary site of the tumor. Estrogen receptor (ER) positivity in diagnostic tissue is generally used to favor breast over lung primary. However, the recent studies have shown a wide range of ER antibody cross reactivity with lung adenocarcinoma. We studied the frequency of ER expression in cytology samples of lung adenocarcinoma using antibodies to three different ER clones., Methods: Cytology cell block preparations, including 22 lung FNAs and 19 malignant pleural effusions (PE) from 41 patients, with clinically documented primary lung adenocarcinomas were selected for this study. All cases were stained with monoclonal antibodies to ER clones 6F11 and 1D5. Twenty nine cases with remaining available material (15 FNA and 14 PE) were stained with a third antibody to ER clone SP1. The extent of ER nuclear staining was scored as 3+ (50%-100% of tumor cells), 2+ (11%-49%), and 1+ (≤10%)., Results: Positivity for ER-6F11 clone was present in 4 of 22 lung FNAs (18.2%, 2+ staining). Two of the four 6F11 positive FNAs also co-expressed ER-1D5 (9.1%, 2+ staining). No immunoreactivity was observed for ER clones 6F11 and 1D5 in all 19 malignant PEs. In addition, none of the remaining 15 FNAs and 14 PEs showed immunoreactivity for ER-SP1 clone., Conclusions: A small subset of pulmonary adenocarcinomas shows immunoreactivity for ER clones 6F11 and 1D5 in FNA samples (18.2% and 9.1%, respectively). The absence of immunoreactivity for ER-SP1 clone indicates higher specificity of this clone in non-breast tissue. The differential diagnostic value of all ER clones in malignant PEs appears to be secure. Larger studies are necessary to validate this observation., (© 2018 Wiley Periodicals, Inc.)

Background: Pancreatic tumors often represent primary neoplasms, however organ involvement with metastatic disease can occur. The use of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) to determine the underlying pathology provides guidance of clinical management., Methods: 25 cases were identified in a retrospective review of our institution's records from 2006 to 2016. Clinical parameters and prognosis are described., Results: Metastatic lesions to the pancreas diagnosed by EUS-FNA accounted for 4.2% of all pancreatic neoplastic diagnoses, each lesion had a median greatest dimension of 1.5 cm, were most often located in the head of the pancreas, and by EUS were typically hypoechoic masses with variably defined borders. Patients were of a median age of 64 years old at diagnosis of the metastatic lesion(s) and the mean interval from primary diagnosis to the diagnosis of metastasis to the pancreas was 58.7 months (95% confidence interval, CI, 35.4 to 82.0 months). The rates of 24-month overall survival after diagnoses of metastatic renal cell carcinoma or all other neoplasms to the pancreas were 90% and 7% respectively. The origin of the neoplasms included the kidney (n = 10), colon (n = 4), ovary (n = 3), lung (n = 2), et al. Smear-based cytomorphology, and a combination of histomorphology and immunohistochemical studies from cell block preparations showed features consistent with the neoplasm of derivation., Conclusion: Metastases to the pancreas can be diagnosed via EUS-FNA, with enough specimen to conduct immunohistochemical studies if necessary to delineate origin. The determination of metastatic disease to the pancreas alters management and prognosis of the patient. Diagn. Cytopathol. 2017;45:418-425. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

This study reviewed the clinical presentation, cytologic findings, and the immunophenotype of 69 Merkel cell carcinoma (MCC) cases sampled by fine-needle aspiration (FNA).  Demographic and clinical data, the cytology findings, and results of ancillary testing were reviewed.  Median patient age was 78 years (37-104) with a 1:1.8 female to male ratio. The most common FNA sites sampled included lymph nodes in the neck, the axillary region, the inguinal region and the parotid gland. Most patients had a history of MCC (68%) and/or non-MCC malignancy (70%).  The common cytologic pattern was a cellular smear with malignant cells arranged in a dispersed pattern with variable numbers of disorganized groups of cells. Cytoplasm was scant or absent and nuclei showed mild to moderate anisokaryosis, stippled chromatin, inconspicuous nucleoli, and nuclear molding. Numerous apoptotic bodies were often present.  Cell block samples (28 cases) were usually positive for cytokeratins in a perinuclear dot pattern, including 88% of cases with CK20 positivity. CD56 was the most sensitive (95%) neuroendocrine marker on cell blocks and was also positive with flow cytometry in nine cases tested.  MCC is most commonly seen in FNA specimens from the head and neck of elderly patients, often with a history of previous skin lesions. Occasional cases present in younger patients and some may be mistaken for other round blue cell tumors, such as lymphoma. CD 56 may be a useful marker in cell block preparations and in flow cytometric analysis of MCC., (© 2014 Wiley Periodicals, Inc.)

The diagnosis of metastatic prostate carcinoma frequently requires the use of immunohistochemical adjuncts. Immunohistochemistry for prostate-specific antigen (PSA) is commonly used for this purpose but can be of limited utility. Recently, prostate-specific membrane antigen (PSMA) has been shown to be a promising marker for the identification of metastatic prostate carcinoma in surgical specimens. The utility of this marker has yet to be reported for cytology specimens. We sought to compare the sensitivities of PSMA and PSA immunohistochemistry and investigate the specificity of PSMA by utilizing cell block preparations from cytologic cases of metastatic prostate carcinoma (n = 19) and carcinomas of nonprostatic origin (n = 33). The sensitivity of PSMA immunohistochemistry was higher (16/19; 84%) in detecting metastatic prostate carcinomas than that of PSA immunohistochemistry (11/19; 58%). Strong, diffuse staining for PSMA was seen in 13 (81%) of 16 PSMA-positive cases whereas strong, diffuse staining for PSA was observed in six (55%) of 11 PSA-positive cases. Positivity for either PSMA or PSA was seen in 17 of 19 cases of metastatic prostate carcinoma for a combined sensitivity of 89%. PSMA immunohistochemistry was completely negative in 32 of 33 cytology cases of nonprostatic carcinomas. Therefore, the specificity of this marker was 97% in this study. In conclusion, our results indicate that PSMA is a highly sensitive and specific immunomarker for the detection of metastatic prostate carcinoma in cytology specimens., (© 2013 Wiley Periodicals, 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 × 10(9) /L and total lymphocyte count, 8.3 × 10(9) /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., (Copyright © 2011 Wiley Periodicals, Inc.)

Fine-needle aspiration (FNA) is frequently used as the initial diagnostic procedure for the investigation of bone and soft tissue masses. The majority of the lesions detected will represent metastatic carcinoma. Amyloid is a rare cause of a bone mass, with less than 15 published reports describing amyloid deposition within bone. The majority of reported cases involve the vertebral column. We report the finding of a massive amyloidoma of the iliac wing in a 46-year-old man. FNA smears and cell block preparations demonstrated fragments of waxy acellular material misinterpreted as necrotic debris. Subsequent open biopsy established the diagnosis of amyloid with congo red staining demonstrating apple green birefringence. Subsequent workup disclosed the patient to have anemia, hypogammaglobulinemia and trace monoclonal light chain gammopathy. Bone marrow examination revealed CD138a positive lambda restricted plasma cells consistent with plasma cell dyscrasia. Careful attention to the staining characteristics of amyloid in FNA derived material should allow the diagnosis of amyloidoma., (Copyright © 2011 Wiley Periodicals, Inc.)

Morphologic distinction of Müllerian carcinomas from non-Müllerian carcinomas in effusion specimens by cytomorphology alone can be diagnostically challenging. Therefore, immunohistochemical adjuncts can be useful in differentiating Müllerian from non-Müllerian metastases. In this study, we evaluated the expression of PAX8 and PAX2 in malignant effusions collected from patients with known Müllerian and non-Müllerian carcinomas. Sections from cell blocks prepared from 152 effusion specimens (54 and 98 cases representing metastases from Müllerian and non-Müllerian primaries, respectively) were immunostained with rabbit polyclonal antibodies against PAX8 and PAX2. Immunopositivity was defined as the presence of strong nuclear staining in at least 25% of the tumor cells. Fifty-two (96%) and 13 (24%) of the 54 Müllerian carcinomas were positive for PAX8 and PAX2, respectively. PAX8 positivity was seen in only four (4%) of 98 non-Müllerian carcinomas; these represented metastasis from a large cell neuroendocrine lung carcinoma, papillary thyroid carcinoma, renal cell carcinoma, and acinic cell carcinoma of the parotid gland. PAX2 positivity was not seen in any of the non-Müllerian carcinomas. The results demonstrate that both PAX8 and PAX2 are highly specific markers for metastatic Müllerian carcinomas in cell block preparations from effusion specimens (96% and 100%, respectively). PAX8, however, is more sensitive than PAX2 in identifying Müllerian carcinomas in fluids (96% versus 24%). Overall, immunohistochemistry for PAX8 and PAX2 represent diagnostically useful adjuncts in identifying a Müllerian carcinoma as a source of a malignant effusion., (Copyright © 2010 Wiley-Liss, Inc.)

To evaluate a cell-block preparation using glucomannan, which was extracted from Amorphophallus konjac. Ten specimens were centrifuged at 1,500 rpm for 5 minutes, the supernatant was removed; the remnant after the preparation of smear specimens for routine cytological examination was fixed with 20% formalin. The specimen was recentrifuged at 1,500 rpm for 5 minutes, and the supernatant was removed. The residue was resuspended with 2 ml of eosin solution and 1-5 ml of 80% alcohol, and stirred well. After further centrifugation, the supernatant was removed, and one drop of a glucomannan-formalin water solution was added gently. After immersion in methanol for 2 hours, glucomannan is solidified and becomes gelatinous. The obtained cell block was placed in the cassette for the preparation of tissue specimens, dehydrated by the routine method, infiltrated with paraffin, and a paraffin-embedded block was prepared. Thin sections were prepared from the paraffin-embedded cell block, and hematoxylin-eosin (H&E) stain with immunological stains was performed. H&E stain, periodic acid-Schiff reaction, Alcian blue, and immunohistochemical stain were clearly demonstrated.We evaluated a new modality of cell-block preparation using a glucomannan-formalin water solution. We found that the method was easy to perform and thought it could be useful as an alternative technique for cell-block preparations. Thus, this novel technique should find wide application in the future., (Copyright 2009 Wiley-Liss, Inc.)

Müllerian papilloma is a rare benign tumor of the cervix and/or vagina that occurs predominantly in young children. The cytologic features of benign müllerian papilloma have never been described. We report for the first time, to our knowledge, the cytologic findings of a benign müllerian papilloma from the vaginal fluid specimen of a 15-mo-old girl using touch prep, ThinPrep, and cell block preparations. The deceptive cytologic features of a cellular specimen with complex papillary fronds composed of overlapping and crowded small hyperchromatic cells, with a high nuclear:cytoplasmic ratio, and feathering in this case resembled a malignant neoplasm. The clinical findings and cytomorphology of a benign müllerian papilloma can mimic those of malignant lesions of the female lower genital tract such as sarcoma botryoides and adenocarcinoma. An awareness of this entity and its potential to mimic these more aggressive neoplasms is essential for accurate diagnosis and to avoid over-treatment., ((c) 2007 Wiley-Liss, Inc.)

Cell blocks (CBs) are often prepared with fine-needle aspirates (FNAs) from multiple organs as an adjunct to smears in the diagnosis of aspirated lesions. However, the literature contains few reports on their utility with regard to specific organ sites. At our institution, CBs are made routinely on FNAs when there is sufficient material remaining after smear preparation, with thyroid representing the largest volume. The aim of this study was to determine the utility of CBs in the diagnosis of thyroid lesions. From January 2002 to April 2004, 546 thyroid FNAs were performed. Eighty-two (15%) cases, from 60 females and 20 males (age range, 17-88 yr; mean, 50 yr), had CBs and formed the basis of this study. Seventy-four (90%) of the cases were performed by the radiologist or the clinician and 8 (10%) by the pathologist, all of which had an immediate assessment for adequacy. One to 7 passes were performed with an average of 3/case. The needles were immediately rinsed in Hanks' Balanced Salt Solution after smear preparation. CBs were made on bloody specimens/those with tissue fragments. Cell-block slides were reviewed for the presence of cellular elements and classified into three categories: (1) contributory, (2) noncontributory, or (3) provides additional information. Of the 82 cases, 23 (28%) were neoplastic, 51 (62%) were nonneoplastic, and 8 (10%) were nondiagnostic. Fifteen of the neoplastic cases had confirmatory biopsies, 9 of which were papillary carcinoma. The overall cellularity of the CBs was low, varying from 0 to 2 follicular groups in the noncontributory CBs and 3 to 6 follicular groups or papillary formations in the contributory CBs. CBs were contributory in 25 (31%) cases: 5 neoplastic (1 follicular neoplasm, 3 papillary carcinoma, and 1 suspicious for papillary carcinoma), 18 nonneoplastic, and 2 nondiagnostic. CBs were noncontributory in 56 (68%) cases: 18 neoplastic (4 papillary carcinomas, 1 suspicious for papillary carcinoma, 4 Hürthle cell neoplasms, and 9 follicular neoplasms), 33 nonneoplastic, and 5 nondiagnostic. One case was categorized as provided additional information because the CB showed material that was not present on the slides; however, it was still nondiagnostic. In summary, CBs did not help in the majority of cases. They were contributory in only 25 (31%) of the 82 cases, and of the 23 neoplastic cases, only 5 (22%) CBs were contributory. The contribution of the CBs in the diagnosis of thyroid lesions was minimal because of the low cellularity. On-site assessment of specimen adequacy often results in fewer passes, thus contributing to the low cellularity present in cell-block preparations. Ancillary studies may require additional passes., (2006 Wiley-Liss, Inc.)

CD138 (Syndecan-1) is a transmembrane heparan sulfate proteoglycan present on the surface of plasma cells and epithelial cells. CD138 is also expressed in some hematopoietic neoplasms and has recently been observed in carcinomas. We characterized CD138 expression in cell-block preparations of fluids/effusions, focusing on the distinction between carcinoma and mesothelioma. One hundred formalin-fixed, paraffin-embedded cell-block sections of fluids/effusions consisting of 58 metastatic carcinomas, 24 mesotheliomas, 11 reactive mesothelial cell proliferations, 3 lymphomas, 3 metastatic sarcomas, and 1 metastatic melanoma were stained with a monoclonal antibody against CD138. CD138 staining was observed in 32/58 (55%) metastatic carcinomas and 2/24 (8%) mesotheliomas; all reactive mesothelial cells, lymphomas, sarcomas, and melanoma were negative. CD138 is a highly specific marker in the differential diagnosis of carcinoma vs. mesothelioma. Distinct membranous staining without background staining of most inflammatory cells makes CD138 an ideal marker for cell-block preparations of fluids/effusions. It should be an integral component of the epithelial-mesothelial antibody panel., (Copyright 2005 Wiley-Liss, Inc.)

We describe the clinical, cytological, histological, and immunohistochemical features of primary and metastatic pancreatoblastoma (PBL), a rare primary pancreatic malignancy of both adults and children. An 18-yr-old male patient presented with abdominal pain, weight loss, and diarrhea and had a 9-cm pancreatic mass that was revealed by CT scan. The fine-needle aspiration biopsy (FNAB) smears from the pancreas specimen and the lung metastasis were cellular and were composed of a combination of solid sheets, three-dimensional, loosely cohesive epithelial groups, and primitive spindled mesenchymal tissue with focal cartilage formation. Acinar formations were best appreciated on cell block preparations, and squamoid corpuscles were seen only on cell block. Zymogen granules were demonstrated in a subset of the epithelial cells using periodic-acid Schiff stains with and without diastase and dual acinar-endocrine differentiation was evident using a focused panel of immunohistochemical stains. Acinar-cell carcinoma (ACC) is the most difficult neoplasm to distinguish from PBL, both clinically and cytologically, especially in young children. The key to distinguishing them is to note the presence of squamous corpuscles and/or heterologous elements such as cartilage. Given the increasing utility of FNAB in the investigation of pancreatic masses, it is important for the pathologist to be familiar with the morphological features of this tumor, especially because preoperative diagnosis provides an opportunity for preoperative therapy before resection., (copyright (c) 2004 Wiley-Liss, Inc.)

Angiomyolipoma is a benign mesenchymal lesion that occurs most commonly in the kidney. Its occurrence in the liver is relatively rare. We report two cases of hepatic angiomyolipoma diagnosed by ultrasound-guided, needle aspiration biopsy. One of the patients was a previously healthy 62-yr-old woman who presented with a hepatic mass incidentally during a healthy examination. The other patient was a 67-yr-old man, a victim of chronic hepatitis C, who was found to have a hepatic tumor in the right lobe during regular follow-up. Cytologic preparations of the two hepatic masses showed some mature adipocytes admixed with clusters of variable-sized mesenchyme-like cells with fibrillar cytoplasm and indistinct cytoplasmic borders. Some of the cells were round to oval and others were spindle shaped with oval, cigar-shaped or elongated nuclei. The nuclear chromatin was fine and some cells showed round nucleoli. No thick-walled blood vessels were noted in the cytological smears. In the cell block preparations, a mixture of thick-walled blood vessels, mature adipose tissue, and bundles of variable-sized smooth muscle cells were noted. The spindle or epithelioid smooth muscle cells were positive for vimentin, alpha-smooth muscle actin, and human melanoma black (HMB)-45 but negative for desmin and S100 protein in immunohistochemical stains. The purpose of the current study is to describe cytological features of this lesion with differential diagnosis because pathologists may be called on to render a diagnosis on needle aspiration. HMB-45 has been proved to be a sensitive marker for the smooth muscle component of angiomyolipoma. Cell block preparations assisted with immunohistochemical staining should be emphasized for definite diagnosis. Although a surgical procedure may still be necessary once a diagnosis of angiomyolipoma is made, treatment may be tailored for a less aggressive procedure than for malignant hepatic nodules., (2004 Wiley-Liss, Inc.)

Mesothelial cell hyperplasia, collagen balls, endometriosis, and endosalpingiosis are diagnostic pitfalls on peritoneal washing cytology in women who present with gynecologic lesions. Over an 8-month period, the peritoneal washings from 10 patients undergoing gynecologic surgery for presumed malignancy showed unusual cytologic findings, several of which posed diagnostic difficulties. The washings from four patients with ovarian carcinomas were cellular and contained clusters and strips of cells with cytologic atypia mimicking malignancy. Confirmation of their benign mesothelial origin was confirmed on immunohistochemistry utilizing cell block preparations. In two cases of endometrial endometrioid carcinoma, the washings contained several clusters of cells surrounding and/or admixed with a globular substance. Due to their similarity to endometrial cells, immunohistochemistry was performed on cell block preparations. The cells were positive for cytokeratin and negative for carcinoembryonic antigen and B72.3, confirming their mesothelial origin. In one case, clinically presumed to be a malignant mass, the washings contained tight clusters of cells with mild cytologic atypia admixed with hemosiderin-laden macrophages. In conjunction with the cell block findings, a diagnosis of endometriosis was made. Extensive endometriosis was found on the surgically resected specimen. In two cases, strips of ciliated epithelial cells resembling tubal epithelium were present on the cytologic and cell block preparations, consistent with endosalpingiosis. The peritoneal washings in one case contained several clusters and balls of atypical cells surrounding microcalcifications on cell block preparation. Since calcification within groups of cells in peritoneal washings always raised the possibility of malignancy, a serous carcinoma of the ovary, particularly of borderline malignancy, would have to be excluded. Fortunately, the resected specimen was free of tumor and showed calcified endosalpingiosis on the ovarian surface. Preparation of cell blocks from peritoneal washings is of value in the work-up and management of patients who present with cytologic mimickers of malignancy on fluid cytology., (Copyright 2003 Wiley-Liss, Inc.)

The ThinPrep Processor is gaining popularity in both gynecologic and nongynecologic cytologic samples, including effusion specimens. We compared immunocytochemical results on ThinPrep and cell-block preparations from the same effusion specimen with antibodies commonly used in effusion cytopathology. Samples from 17 reactive effusions and 79 effusions with metastatic adenocarcinomas were each prepared as monolayer ThinPreps and formalin-fixed, paraffin-embedded cell blocks. All slides were immunostained with antibodies against intermediate filaments (cytokeratins 8 and 18, and vimentin), cytoplasmic or membrane proteins (EMA, polyclonal CEA, B72.3, and BerEP4), and nuclear antigens (Ki67, PCNA, and p53), using the avidin-biotin procedure. ThinPrep and cell-block slides were stained simultaneously, using identical protocols. Both preparations showed similar results with respect to frequency of positivity, intensity, and distribution of stain for all nonnuclear markers tested. However, for the three nuclear markers Ki67, PCNA, and p53, the frequency and intensity of reaction with ThinPrep were significantly lower than with the cell-block preparation, particularly in malignant effusions. These findings suggest that immunocytochemical results obtained with ThinPrep match those of cell block for most markers tested. However, cell-block preparation are superior to ThinPrep for nuclear markers (Ki67, PCNA, and p53)., (Copyright 2003 Wiley-Liss, Inc.)

Rarely, spindle-cell lesions in liver fine-needle aspiration biopsies (FNABs) are encountered. A retrospective review of our experience with lesions that are mesenchymal in origin or appearance was undertaken to elucidate the frequency and spectrum of these lesions. Image-guided liver FNABs performed over a 3-year period (n = 585) at our institution (1996-1998) were retrospectively evaluated. Cytologic smears, cell block preparations, and clinical follow-up of lesions with spindle-cell morphology were reviewed. Twenty-nine of 585 cases were of spindle-cell morphology (5%). Hemangiomas (n = 12, 41%) and metastatic sarcomas (n = 6, 21%) comprised the largest categories, followed by granulomatous inflammation (n = 3, 10%). Other cases included primary angiosarcoma and fibrolamellar hepatocellular carcinoma. The most frequent spindle-cell liver lesion encountered is hemangioma, followed by metastatic leiomyosarcoma and granulomatous hepatitis. Awareness of diagnostic possibilities, special attention to specimen adequacy, and use of ancillary procedures can maximize diagnostic yield., (Copyright 2001 Wiley-Liss, Inc.)

The use of membrane filters to concentrate cytology specimens was first described by Seal (Cancer 1956; 9:866-868). We report on a technique in which a portion of Papanicolaou-stained Millipore filter (Millipore Corp, Bedford, MA) preparation can be converted into a paraffin block for hematoxylin-eosin (H&E) preparations and immunocytochemical analysis (ICC). Seven cases with moderate cellularity and no cell block preparation were retrieved from our cytopathology files. The specimens included: 4 pleural effusions with metastatic adenocarcinoma, and 3 FNA specimens (1 metastatic melanoma, 1 metastatic adenocarcinoma, and 1 thyroid/papillary carcinoma). The filter was removed from the slide, cut in half, and subjected to paraffin embedding in the usual fashion (postfixed in 10% neutral-buffered formalin). Four-micron-thick sections were cut onto Probe-On (Fisher Scientific, Pittsburgh, Pa) slides. ICC was performed using the avidin-biotin-peroxidase complex technique and capillary gap technology. Antibodies included CAM5.2, AE1/AE3, CEA, CD15, LCA, PanCK, S100, HMB45, and thyroglobulin. All cases showed excellent preservation of cellular morphology on H&E. ICC performed on Millipore filter cell block preparations showed specific antibody staining patterns with preservation of cellular details. All antibodies showed their specific staining patterns with clean background and lack of nonspecific staining. This technique has the following advantages: 1) offers an alternative to cell blocks in moderately cellular specimens; 2) clean background; 3) preservation of cytology specimens for future studies.

A 37-year-old white male with a large pancreatic mass was referred to our institution with a hypodense liver lesion detected on CT scan. A fine-needle aspiration (FNA) was performed on the liver lesion. Diff-Quik smears demonstrated scattered papillary structures and single neoplastic cells with abundant well-defined dense granular cytoplasm. Eccentrically located nuclei were noted with single prominent nucleoli. Cell block preparations showed papillary structures lined by cells with abundant pink granular cytoplasm, hyperchromatic nuclei, and prominent single nucleoli. Electron microscopic examination displayed numerous but poorly preserved mitochondria. The diagnosis of papillary carcinoma with oncocytic features was made. Only two previous cases of pancreatic oncocytic tumors diagnosed by FNA have been reported in the literature. We present an additional case, notable in that the diagnosis was made in a metastatic liver nodule.

Overlapping morphologic patterns that may be observed in goiter, follicular adenoma, and papillary carcinoma can limit the cytologic evaluation of the thyroid gland. In an attempt to develop a useful adjunctive test, the immunocytochemical reactivity of HBME-1, carcinoma antigen 19-9 (CA 19-9), and CD-15 (Leu-M1) was tested on 59 cell block preparations from fine-needle aspirations of the thyroid gland. HBME-1 monoclonal antibody was reactive in all 21 papillary carcinomas, in 4 of 18 adenomas, and in 5 of 20 goiters. CA 19-9 was identified in 13 of 21 carcinomas, 1 goiter, but none of the adenomas. CD-15 was present in 15 of 21 carcinomas, 1 goiter, and 1 adenoma. We conclude that HBME-1 is a sensitive marker of papillary thyroid carcinoma. CD-15 and CA 19-9 are less sensitive but more specific. This panel can be useful to help classify morphologically equivocal lesions. As with all immunocytochemical testing, caution must be exercised in the interpretation of results, and correlation made with morphologic and clinical data.

Myoepithelial cells play an important role in the interpretation of breast fine-needle aspiration biopsy, since these cells are believed to be a component of a benign process in breast lesions. Myoepithelial cells are usually easy to recognize, however, other cells can morphologically simulate myoepithelial cells and make the distinction difficult. To assess the feasibility of immunostaining as an adjunct to identify myoepithelial cells, we have used immunocytochemistry using monoclonal antibody against muscle specific actin (MSA) in our breast fine-needle aspirates. Herein, we report our experience in immunocytochemical detection of myoepithelial cells using labeled Streptavidin Biotin Detection System on destained Papanicolaou stained smears and cell block preparations obtained from breast aspirates.

Renal splenic heterotopia, a very rare benign occurrence of splenic tissue within the renal capsule, mimics organizing capsular hemorrhage, adenomyolipoma and renal cortical adenoma or carcinoma. It is found incidentally as a result of imaging asymptomatic kidneys for other reasons or may cause signs and symptoms due to mass effect and hypersplenism. When occurring in patients who had had splenectomy it has been classified as splenosis. When found in patients with intact spleens it is called splenorenal fusion and considered to be a developmental heterotopia. Renal splenic heterotopia can be diagnosed by 99mTc-sulfur colloid scan and confirmed with fine needle aspiration biopsy cell block preparations. Unnecessary nephrectomy can be avoided if splenic heterotopia is included in the differential diagnosis of renal lesions, particularly in splenectomized patients.

Pericellular lacunae are reported to be characteristic of adenocarcinoma cell clusters in cell block preparations of serous effusions. We examined the incidence of lacunae in cell blocks from 24 benign and 31 malignant effusions. The cases were classified as follows: group A with no pericellular lacunae, group B with < 50% of cell clusters in lacunae, and group C with > 50% of cell clusters in lacunae. Of the malignant effusions, 5% were in group A, 67% were in group B and 29% were in group C. Of the benign effusions, 50% were in group A, 50% were in group B, and 0% were in group C. The pericellular lacuna by itself is not a reliable diagnostic criterion. It could assist, however, in the overall evidence when evaluating a case, particularly if either there are no lacunae seen or the majority of cells are in lacunae. Furthermore, since lacunae are easily visible at low magnification, their recognition may help in screening cell blocks, using their presence to locate cell groups worthy of special attention.

We have reviewed our experience with 8,706 needle aspiration cytology (NAC) of the breast which were done from January 1983 to June 1991. During our study we diagnosed four cases of breast carcinomas (three ductal type and one with pleomorphic giant cells) in pregnant or lactating women; in all of these the cytologic findings corresponded with the subsequent tissue diagnosis and cell block preparations. Considering that carcinoma of breast during pregnancy and lactation is rare and is second only to cervical cancer, it was felt that its diagnosis by NAC was useful for timely management. In the case in which pleomorphic giant cells were present as an integral component of the tumour, immunohistochemical and electron microscopic study was done. This is discussed in view of our recent experience with this unusual tumour.

Hepatocellular carcinoma (HCC) may uncommonly present with distant metastasis in the absence of a documented neoplasm in the liver. The authors herein describe the case of a 60-year-old man with cirrhosis who developed unilateral enlargement of the breast and a subareolar mass. This problem was clinically thought to represent gynecomastia, but a mammary fine-needle aspiration biopsy demonstrated a malignant epithelial neoplasm composed of large granular amphophilic cells. Bile pigment was visualized in the tumor on aspirate smears and cell block preparations; immunostains showed reactivity for cytokeratin and alpha-fetoprotein, but there was no positivity for epithelial membrane antigen, gross cystic disease fluid protein-15, vimentin, estrogen receptors, progesterone receptors, or S100 protein. These results indicated a diagnosis of metastatic HCC, which was subsequently confirmed by computed tomography of the abdomen.

Peritoneal cytology has been well established as a diagnostic and staging tool in the management of the common epithelial tumors of ovary. Germ cell, mesenchymal, and sex-cord stromal tumors are much less frequently encountered in peritoneal specimens, often with cytologic features that may pose problems in differential diagnosis. This report presents the cytomorphology of the ascitic fluid in cases of endodermal sinus tumor, dysgerminoma, and Sertoli-Leydig-cell tumor, and peritoneal washings in a case of ovarian malignant mixed mullerian tumor. The cytologic features of Sertoli-Leydig-cell tumors have not been well described. Careful correlation of peritoneal cytologic findings, cell-block preparations, and immunocytochemistry with the cytohistologic features of these tumors is crucial for correct tumor classification.