Metastatic germ cell tumors in serous cavities and cerebrospinal fluid: A single-center experience.

BACKGROUND: Metastatic germ cell tumors (GCTs) involving body cavity effusions and cerebrospinal fluid (CSF) are rare. Diagnosis is challenging because of limited morphological and clinicopathological information in the literature. METHODS: A database search of our institution from 1990 to 2024 identified 27 cases of metastatic GCTs, comprising five pediatric and 22 adolescent and adult patients, in serous cavities or the CSF, including peritoneal (15), pleural (nine), CSF (two), and pericardial (one) fluid. RESULTS: The most common primary site was the testis (n = 10), followed by the ovaries (n = 7), mediastinum (n = 4), retroperitoneum (n = 3), pineal gland (n = 2), and sacrum/coccyx (n = 1). The primary tumors in 14 patients were mixed GCTs (six with a seminoma component), followed by immature teratomas (six), yolk sac tumors (three), embryonal carcinomas (two), pure seminomas (one), and postpubertal teratomas (one). The median interval between primary tumor diagnosis and diagnosis of fluid positivity was 7 months (range: 0-134 months). In nine cases, the malignant fluid was diagnosed simultaneously with or within 1 month of the primary tumor. GCT subtyping was performed on 23 of the 27 cytological specimens. Twenty-four patients (89%) also had metastases to other sites. Thirteen patients died of the disease (48%), with a median survival time of 4 months. CONCLUSIONS: Metastatic GCTs in serous effusions and CSF are often associated with disseminated disease and poor prognosis. Subtyping can be performed by cytomorphology combined with immunohistochemistry.

Comparison of endoscopic ultrasound-guided fine needle aspiration cytology versus endoscopic biopsy for the diagnosis of subepithelial lesions of the upper and lower gastrointestinal tract: A 10-year retrospective single institution analysis.

BACKGROUND: The aim of this study is to compare the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) versus endoscopic biopsy for the diagnosis of gastrointestinal (GI) subepithelial lesions (SELs) using surgical resection as the gold standard. METHODS: All patients who underwent EUS-FNA of upper and lower GI SELs over a 10-year period (2010 through 2019) were retrospectively reviewed. The medical records of all patients were reviewed and data extracted from the endoscopy, pathology, and surgical reports were analyzed. RESULTS: In total, 283 patients with ages ranging from 21 to 92 years underwent EUS-FNA for evaluation of GI SELs, 117 (41%) patients underwent endoscopic biopsy and 82 (29%) patients had concurrent surgical resection specimen. EUS-FNA was obtained from the stomach in 167 (59%) patients, duodenum in 51 (18%) patients, esophagus in 38 (13%) patients, and colorectum in 27 (10%) patients. It was found that the largest percentage of lesions originated in the muscularis propria (36%), followed by the submucosa (26%), deep mucosa (13%), and not specified in 21%. The concordance between EUS-FNA and endoscopic biopsy was good (correlation coefficient of 0.631, p < .001). EUS-FNA versus endoscopic biopsy in resected cases showed sensitivity and specificity of 78% versus 68% and 84% versus 100%, respectively. The EUS-FNA has an accuracy of 80% compared to 74% in biopsy. The diagnostic yield of EUS-FNA and endoscopic biopsy was 64% versus 55%. CONCLUSION: EUS-FNA is more sensitive and more accurate than endoscopic biopsy for diagnosing GI SELs with a good concordance between the two techniques.

The Role of Fluorescence In Situ Hybridization in Pancreatobiliary Brushing Cytology: A Large Retrospective Review with Histologic Correlation.

(1) Background: Although the specificity of brush cytology for the detection of malignant pancreaticobiliary strictures is high, its sensitivity is low. Fluorescence in situ hybridization (FISH) can be used to detect chromosomal aneuploidy in biliary brushing specimens, and when used as an adjunct to routine cytology, it significantly improves diagnostic sensitivity. (2) Methods: We searched our laboratory information system to identify all bile duct brush cytology cases with follow-up surgical pathology between January 2001 and September 2019. Cytologic diagnoses were classified as negative, atypical, suspicious, or malignant. Correlated surgical pathological diagnoses were classified as benign or malignant. FISH test results were obtained for a subset of cytology cases with concurrent FISH testing, and the sensitivity, specificity, positive predictive value, and negative predictive value in identifying malignancy for cytology alone, FISH alone, and combined cytology and FISH were calculated. (3) Results: A total of 1017 brushing cytology cases with histologic correlation were identified. A total of 193 FISH tests were performed concurrently with cytological specimens. Malignant diagnoses were identified in 623 of 1017 patients, while 394 patients had benign strictures. The sensitivity, specificity, positive predictive, and negative predictive rate were 65%, 78%, 83%, and 49% for cytology alone; 72%, 67%, 63%, and 68% for FISH alone; and 85%, 42%, 60%, and 74% for combined cytology and FISH, respectively. Among FISH-positive cases, the risk of malignancy for polysomy was 82% and 32% for trisomy. (4) Conclusions: FISH improves the sensitivity and negative predictive rate of bile duct brush cytology. The combination of cytology and FISH has increased the sensitivity from 65% to 85% and the negative predictive rate from 49% to 74% when compared to cytology alone. A patient with a polysomy FISH result had a significantly higher risk of malignancy than a patient with a trisomy 7 result (82% vs. 32%, p < 0.00001).

The cytology of salivary gland neoplasms with globules of extracellular matrix: Case-based review of adenoid cystic carcinoma and its potential mimics.

Fine needle aspiration (FNA) cytology is an important tool for diagnosing salivary gland neoplasms and for guiding clinical management. The classic adenoid cystic carcinoma (AdCC) is a basaloid neoplasm with abundant extracellular matrix. The presence globules of extracellular matrix are quite characteristic of AdCC but not diagnostic. We selected from our files six FNA cases that contained at least some globules of amorphous matrix that are similar to the ones seen in AdCC. The aim of this case-based review is to discuss the pitfalls and some of the common differential diagnoses of AdCC in FNA cytology. By the end of this review, we hope to have shared with the readers the lessons we learned from these cases and to highlight the key criteria needed to make a correct diagnosis of AdCC based on cytomorphology. The importance of considering other entities, in addition to AdCC, whenever a salivary gland FNA presents with globules is emphasized.

Hepatic angiomyolipoma with predominant epithelioid component: Diagnostic clues on aspiration and core needle biopsies.

Hepatic angiomyolipoma (HAML) is a rare mesenchymal neoplasm that belongs to the perivascular epithelioid tumor family. Though it is characteristically, a triphasic tumor composed of smooth muscle, blood vessels, and adipocytes, the smooth muscle cells are often epithelioid and can represent the near-entirety of the tumor. A HAML composed predominantly of epithelioid smooth muscle cells occurring in the liver presents significant diagnostic challenges as many liver tumors are composed of large epithelioid cells. Furthermore, even if the tumor is not composed predominantly of epithelioid smooth muscle cells, this may be the only component present in a fine-needle aspiration (FNA) or core needle biopsy. A 38-year-old female with a 3 month history of abdominal pain, nausea, and diarrhea was found to have a 12 cm right hepatic lobe mass. FNA biopsy revealed a moderately cellular specimen composed of plump epithelioid cells with indistinct cell borders, low N:C ratio, round to oval nuclei, fine chromatin, occasional nucleoli, and abundant vacuolated to fibrillary cytoplasm. Rare intranuclear inclusions and occasional foamy macrophages were noted. Concurrent core biopsy revealed large polygonal cells with eccentric nuclei and clear, vacuolated to granular, eosinophilic cytoplasm that stained strongly for HMB45, confirming the diagnosis of HAML. Because HAML is a rare tumor, this diagnosis can be easily overlooked; cognizance of the typical cytologic, histologic, and immunophenotypic findings is crucial to establishing a diagnosis.

The importance of risk of neoplasm as an outcome in cytologic-histologic correlation studies on thyroid fine needle aspiration.

BACKGROUND: The introduction of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) altered the practice of thyroid pathology and reduced the risk of malignancy (ROM) associated with the indeterminate categories in the Bethesda system for reporting thyroid cytopathology (TBSRTC). It has been proposed that the evaluation of the risk of neoplasm (RON) is important in cytologic-histologic correlation studies. METHODS: A total of 5224 thyroid aspirates were performed at our institution during an 8-year period. Of the 1475 cases (28%) with surgical follow-up, the histologic diagnoses comprised benign non-neoplastic (BNN, n = 669), follicular adenoma (FA, n = 188), NIFTP (n = 42), papillary microcarcinoma (PMC) (n = 223), and malignant neoplasm excluding PMC (n = 353). The RON was calculated to include neoplasia with low risk biologic behavior (FA, NIFTP, PMC) and malignant neoplasms. In contrast, the ROM was reserved for malignant neoplasms excluding PMC. RESULTS: The RON for each TBSRTC category was: nondiagnostic (ND) 38.3%, benign 20.9%, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) 63.2%, follicular neoplasm or suspicious for follicular neoplasm (FN/SFN) 83.9%, suspicious for malignancy (SFM) 94%, and malignant 100%. The ROM excluding PMC was: ND 14%, benign 1.6%, AUS/FLUS 17.8%, FN/SFN 28.4%, SFM 84.4%, and malignant 99.5%. CONCLUSIONS: The RON and ROM support the recommended management guidelines from TBSRTC for all categories, except for FN/SFN. Histopathologic follow-up of FN/SFN aspirates in our study contain a very high rate of neoplasm (83.9%), which might support the management preference of conservative surgery.

Risk of malignancy in "atypia of undetermined significance" category of salivary gland fine-needle aspiration: A bi-institutional experience.

BACKGROUND: Many prior institutional and multi-institutional studies have applied the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) retrospectively to their specimens to determine the risk of malignancy (ROM) of each category. Most of these studies focused on general assessment of the system and risk classification. However, there seems to be less focus on the category of atypia of undetermined significance (AUS) that could be attributed to the low number of cases that could fit into this category. Herein, we present a bi-institutional experience with this category. METHODS: A computerized search of the databases was performed to identify all salivary gland fine-needle aspiration (FNA) in two institutions over a period of 12 years. The final diagnosis of each case was reclassified based on MSRSGC, and histology follow-up was retrieved. RESULTS: Sixty AUS cases (out of 1560 salivary gland FNA) were identified with a rate of 3.8%. Forty cases (66%) had a subsequent tissue material. Correlation with histology revealed that the estimated ROM is 37.5% (15/40) and the overall ROM is 25% (15/60). Fifty percent of the cases had a prominent lymphoid component and most commonly represented lymphomas, reactive lymph node or sialadenitis. CONCLUSION: The AUS category is a heterogeneous group of lesions with predominant lymphoid-rich entities. Some variability exists between institutions with most having higher ROM than the suggested 20% by the MSRSGC atlas.

Risk of malignancy and neoplasia predicted by three molecular testing platforms in indeterminate thyroid nodules on fine-needle aspiration.

BACKGROUND: The management of thyroid nodules with indeterminate cytology is challenging. Recently, molecular testing on fine-needle aspirates (FNAs) has been advocated to determine whether clinical follow-up or surgery is warranted for patients. Three different testing platforms were performed on aspirates from our institution (Afirma Thyroid FNA Analysis, RosettaGX Reveal, and Interpace ThyGenX/ThyraMIR). This study compares their diagnostic efficacy. METHODS: We conducted a retrospective analysis of indeterminate thyroid FNAs with correlating molecular testing over 4 years (2015-2018). The aspirates included diagnoses of follicular lesion of undetermined significance, follicular neoplasm, or suspicious for malignancy (SM). Based on cases that underwent surgical resection (Afirma, n = 37; Rosetta, n = 19; Interpace, n = 14), we calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for risk of malignancy and neoplasia. RESULTS: The three tests performed similarly when predicting risk of malignancy. They showed high sensitivity (80-100%) and NPV (90-100%) but lower specificity (10-64%) and PPV (21-44%). When assessing their value to predict neoplasia, each test had a high PPV (76-89%) but low NPV (20-33%). The sensitivity for neoplasm was intermediate to high (50-93%), and the specificity remained extremely variable (11-67%). CONCLUSION: Overall, these molecular platforms performed similarly, displaying high NPV but low to intermediate PPV for malignancy and low NPV but high PPV for neoplasm. The risk of neoplasm is a good index for surgery, and we argue that many of the neoplasms are low-risk tumors. We endorse conservative treatment with lobectomy for cases that are indeterminate at FNA but suspicious by molecular testing.

Cytomorphologic comparison of type 1 and type 2 papillary renal cell carcinoma: A retrospective analysis of 28 cases.

BACKGROUND: Papillary renal cell carcinoma (pRCC) is classified as type 1 or type 2 on the basis of histomorphologic features. Type 1 pRCC typically carries a better prognosis, and renal cell carcinoma is often diagnosed by fine-needle aspiration (FNA). Thus, this study was designed to characterize cytomorphologic features present in FNA cases that could be used to discriminate between type 1 and type 2 pRCC. METHODS: Electronic records of Indiana University were searched for pRCC FNA cases (2007-2018). Corresponding surgical pathology reports were reviewed to classify patients as having type 1 or type 2 pRCC. FNA slides were reviewed to assess cytomorphologic features (ie, nuclear grade; cell size; cytoplasmic volume and quality; and the presence of single cells, papillary clusters, nuclear grooves, foamy histiocytes, hemosiderin pigment, psammoma bodies, and hyaline globules). A semiquantitative score was assigned to each feature. The nuclear grade was assigned with the World Health Organization/International Society of Urological Pathology grading system. The cytomorphologic features of type 1 and type 2 pRCC were compared. RESULTS: Sixteen patients with type 1 pRCC and 12 patients with type 2 pRCC were included in the study. Type 2 pRCC had a higher nuclear grade, a higher volume of cytoplasm, and more granular cytoplasm. Type 1 pRCC more frequently had nuclear grooves and clear cytoplasm. The remaining features (ie, cell size, papillary clusters, single cells, foamy histiocytes, hemosiderin pigment, psammoma bodies, and hyaline globules) were not statistically significant. CONCLUSIONS: Nuclear grade, cytoplasmic volume and granularity or clarity, and nuclear grooves are cytomorphologic features that may aid in the distinction between type 1 and type 2 pRCC.

Application of the Milan System for Reporting Salivary Gland Cytopathology: A Retrospective 12-Year Bi-institutional Study.

OBJECTIVES: Multi-institutional studies are required for the validation of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC). METHODS: A total of 1,560 fine-needle aspirations of the salivary glands were retrieved from two institutions for a 12-year period. The diagnoses were reclassified based on the MSRSGC. Risk of malignancy (ROM) for each category was calculated based on 694 histologic follow-up cases. RESULTS: The ROM for each category was: 18.3% for nondiagnostic, 8.9% for nonneoplastic, 37.5% for atypia of undetermined significance (AUS), 2.9% for benign neoplasm, 40.7% for salivary gland neoplasm of uncertain malignant potential (SUMP), 100% for suspicious for malignancy, and 98.3% for malignant. The sensitivity, specificity, positive predictive rate, and negative predictive rates were 89%, 99%, 98%, and 96%, respectively. CONCLUSIONS: The results of the current study are in keeping with the MSRSGC. The indeterminate categories of AUS and SUMP showed intermediate ROMs at 37.5% and 40.7%, respectively.

Molecular Testing for EGFR Mutations and ALK Rearrangements in the Cytological Specimens From the Patients With Non-Small Cell Lung Cancer.

OBJECTIVE: The aim of this study was to investigate epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK) gene rearrangements using cytological specimens from the patients with a diagnosis of primary or metastatic lung non-small cell carcinoma. MATERIALS AND METHODS: A total 307 cases were submitted for EGFR mutational analysis and 265 cases for ALK analysis. The cytological specimen sources included lung, lymph node, liver, bone, adrenal gland, mesentery mass, and body fluids/bronchial brushing. EGFR mutations in the exons 18 to 21 were analyzed with Qiagen EGFR Pyro Kits. Fluorescence in situ hybridization (FISH) studies for ALK rearrangement inv(2)(p21; p23) were performed on the paraffin-embedded cell block sections utilizing dual-color Vysis LSI ALK Break Apart Probe Kit. RESULTS: Among 307 fine needle aspirate cases for EGFR analysis, 302 cases (269 from cell blocks, 33 from direct smears) had sufficient material for EGFR test. Five cases failed due to inadequate cellularity. Twenty six of 302 (8.6%) cases were positive for EGFR mutations. A total of 265 cases submitted for ALK analysis included 240 cases of fine needle aspirate, 25 cases of pleural fluid/pericardial fluid/bronchial washings. Eight cases failed because of low cellularity, whereas 257 of 265 cases had sufficient material for ALK FISH study. Nine of 257 cases (3.5%) revealed ALK rearrangement by FISH. CONCLUSIONS: The current study demonstrates that cytological specimens can yield sufficient material for EGFR mutations and ALK rearrangement test. Our study reveals that 8.6% of EGFR mutation rate and 3.5% of ALK rearrangement rate in the cytology specimens from the patients with primary or metastatic lung non-small cell carcinoma.

World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading in fine-needle aspiration biopsies of renal masses.

BACKGROUND: Utilization of fine-needle aspiration (FNA) biopsy for the evaluation of renal masses has been increasing at our institution. At times diagnostic material on direct smears is superior to that in the cell block/core biopsy, therefore assigning an accurate nuclear grade in the cytopathology report would provide useful prognostic information. METHODS: Search of the pathology database identified renal FNAs performed during an 11-year period (2006-2017). Corresponding core biopsies and resections were identified. Cases with a diagnosis of primary renal neoplasia on FNA, core biopsy, and/or resection were included. Two pathologists reviewed all cases and assigned a World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade to each FNA, core biopsy, and resection case. RESULTS: A total of 162 kidney FNAs were identified. Primary renal neoplasia was diagnosed in 137 cases on core biopsy/resection. Among diagnostic FNAs of clear cell RCC and papillary RCC with core biopsy/resection specimens for re-review (n = 52), reviewers assigned a concordant WHO/ISUP grade to 83% (43/52) of cases. Among 9 cases with discrepant scores, all had a discrepancy of 1 grade and were undergraded on FNA. Using a two tier grading system (low vs. high grade), reviewers assigned a concordant grade to 88% (46/52) of cases. Among 6 cases with discrepant scores, all were classified as low grade (WHO/ISUP grade 2) on FNA versus high grade (WHO/ISUP grade 3) on resection. CONCLUSION: The WHO/ISUP grade assigned on FNA shows good concordance with subsequent resection/core specimens (83%), with all discrepant cases being undergraded by one grade.

Death within 30 days of fine needle aspiration: Post-mortem confirmation of FNA diagnoses and the contribution of FNA to patient mortality.

BACKGROUND: Fine needle aspiration (FNA) diagnoses are usually confirmed via surgical pathology or via evaluation of clinical outcomes. However, such confirmation may not occur for patients who die shortly after FNA, and autopsy may be a useful quality assessment tool in these cases. Also, there is little data investigating the relationship between FNA and mortality. We sought to demonstrate the autopsy as a quality assessment tool for the FNA and assess the contribution of FNA to mortality in patients who die soon after the procedure. METHODS: A search of our database was performed from 1992 to 2016 for patients who were autopsied after dying within 30 d of an FNA. Concordance between findings from FNA, autopsy, and any intervening surgical pathology material was determined. Finally, a subjective determination of the likelihood that FNAs contributed to deaths was made by reviewing autopsy reports. The contribution was categorised as either "unlikely", "possible", or "probable". RESULTS: Fifty-eight patients (average age = 58 y) met the search criteria. Thirty-six (62%) patients had malignancies. Surgical pathology material was obtained concurrently or following FNA in 20 cases (34%). There was 73% concordance between FNA and autopsy findings, which compares to 80% concordance between FNA and surgical pathology diagnoses. The FNA was determined to be at least possibly contributory to death in 7/58 cases (3 cases designated as "probable," and 4 as "possible"). CONCLUSION: Autopsy can be used to validate FNA diagnoses and, like surgical pathology, confirms that FNA diagnoses are mostly accurate. However, in a small number of patients, FNA can precipitate death.

Utilization of direct smears of thyroid fine-needle aspirates for ancillary molecular testing: A comparison of two proprietary testing platforms.

BACKGROUND: Ancillary molecular testing has been recommended for thyroid fine-needle aspirates (FNA) with indeterminate cytologic diagnoses. Rosetta Genomics and Interpace Diagnostics have developed assays that can utilize direct smears as the testing substrate. METHODS: A retrospective study of indeterminate thyroid FNAs with known histologic follow-up was performed. One Diff-Quik-stained smear and one Papanicolaou-stained smear with similar cellularity (at least 60-100 lesional cells) from each case were sent to Rosetta and Interpace, respectively, for analysis. The results were directly compared and correlated with the final histopathology. Neither company was aware of the follow-up histologic findings in these cases. RESULTS: A total of 10 thyroid FNAs were identified from our 2015 files. The cytologic diagnoses included follicular lesion of undetermined significance (FLUS, n = 5), follicular neoplasm/suspicious for follicular neoplasm (FN/SFN, n = 4), and suspicious for malignancy (SM, n = 1). Of the seven cases with benign histology, six smears were classified as benign by the RosettaGX microRNA classifier, and one case was designated as suspicious. Five cases were negative by both ThyGenX oncogene panel and ThyraMIR microRNA classifier. One case was negative by ThyGenX and positive on follow-up ThyraMIR, and one case was positive for KRAS mutation and positive on ThyraMIR. Both the RosettaGX and ThyGenX/ThyraMIR tests demonstrated positive results for the three histologically malignant cases. CONCLUSION: This study demonstrates that two molecular testing platforms performed equally well using our stained direct smears. Both molecular tests revealed a 100% negative predictive rate. RosettaGX showed a 75% positive predictive value in comparison to 60% for ThyGenX/ThyraMIR.

Homologous Recombination Deficiency in Patients With Pancreatic Ductal Adenocarcinoma and Response to Chemotherapy.

PURPOSE: Mutations or copy number abnormalities of genes involved in homologous recombination (HR) occur in pancreatic ductal adenocarcinoma (PDAC). DNA-based measures of HR deficiency (HRD) have been developed and may help identify tumors with better response to DNA-damaging agents. This study aimed to describe the HR pathway mutations and HRD status and determine their association with treatment response and outcome in patients with PDAC. PATIENTS AND METHODS: We performed a retrospective analysis of tumor samples from patients treated at Indiana University for locally advanced or metastatic PDAC. Patients were included if they received gemcitabine plus nanoparticle albumin-bound paclitaxel (control) or fluorouracil, oxaliplatin, leucovorin, and irinotecan (FOLFIRINOX) and had adequate follow-up to assess survival and response to therapy. Tumor analysis generated a three-biomarker HRD score and mutation data for 44 genes. RESULTS: Ninety-one samples met inclusion criteria, and 78 samples (formalin-fixed paraffin-embedded, n = 15; fine-needle aspiration, n = 63) generated mutation data. HRD analysis was successful for 57 samples (HRD score: median, 18; range, 5 to 61); the primary cause of failure was low tumor cellularity. Six BRCA1/2 mutations were detected, four with HRD scores in the top decile (P = .011). There was no statistically significant correlation between HRD score and radiographic response (odds ratio per interquartile range, 1.40; P = .32 adjusted for treatment) in either treatment group. In patients treated with FOLFIRINOX, HRD score dichotomized at the median was not associated with progression-free survival (median, 5.3 v 9.4 months for low v high HRD score, respectively; P = .083) or overall survival (median, 11.9 v 10.7 months for low v high HRD score, respectively; P = .76). CONCLUSION: Mutations in DNA repair genes occur in PDAC, and HRD scores can be generated in the majority of patients. The HRD score was not significantly associated with higher response rate or prolonged survival in patients treated with FOLFIRINOX.

Fine needle aspiration cytology of hepatic metastases of neuroendocrine tumors: A 20-year retrospective, single institutional study.

BACKGROUND: Fine needle aspiration (FNA) is considered an excellent technique for documenting metastatic neuroendocrine tumors (NETs). This study aims to evaluate the accuracy of FNA in diagnosing metastatic NETs to the liver and determining the grade and origin of these metastases. METHODS: Our laboratory information system was searched from 1997 to 2016 to identify all cases of metastatic NETs to the liver that were sampled by FNA. The cytopathology and surgical pathology reports as well as the patients' electronic medical records were reviewed. The cytohistologic type and grade of the metastatic NETs, as well as the site of the patient's primary were recorded. RESULTS: High-grade NETs, including small cell and poorly differentiated neuroendocrine carcinomas, constituted 62% (167/271) of the cases, while low-grade NETs, including well differentiated NET (grade1 and grade 2), pheochromocytomas, paragangliomas, and carcinoid tumors of lung, constituted 38% (104/271) of cases. The most common diagnosis was metastatic small cell carcinoma accounting for 45% (122/271) of cases. The most common primary sites were lung (44%; 119/271) followed by pancreas (19%; 51/271). The FNA diagnosis was confirmed by histopathology in 121 cases that had a concurrent biopsies or resection specimens. CONCLUSIONS: FNA is an accurate method for diagnosing metastatic NETs to the liver. There were significantly more high-grade (62%) than low-grade (38%) metastatic NETs to the liver. In our practice, lung (44%) and pancreas (19%) were the most common primary sites of metastatic NETs involving the liver. In 16% of the cases, a primary site could not be established.

Fine needle aspiration evaluation of pancreatic lymphoma: A retrospective study of 25 cases in a single institution.

BACKGROUND: Accurate diagnosis of pancreatic lymphoma is crucial for clinical management. We evaluate the role of fine-needle aspiration (FNA) in the diagnosis of pancreatic lymphoma with the aid of flow cytometry and/or immunohistochemistry on the cell block. METHODS: Cases of pancreatic lymphoma were collected by searching our pathology laboratory information system over a period of 16 years. The clinical findings, cytologic features, and immunophenotypic results were reviewed. The diagnoses of FNA were correlated with surgical specimens in a subset of FNA cases. RESULTS: A total of 25 FNA cases of pancreatic lymphoma were included. The most common type of pancreatic lymphoma was large B cell lymphoma followed by follicular lymphoma. With the aid of flow cytometry and immunohistochemical work-up on cell block, 72% (18/25) of the cases were diagnosed as lymphoma and 16% of the cases (4/25) were diagnosed as suspicious for lymphoma by FNA. Only two cases (8%) including one false negative and one nondiagnostic aspirate missed the lymphoma diagnosis and 1 case (4%) was indeterminate by FNA evaluation. CONCLUSION: FNA demonstrated high accuracy in rendering diagnosis of pancreatic lymphoma. The overall sensitivity is 88% and the false negative and nondiagnostic rates are 4%, respectively. Further subtyping of certain lymphomas can be difficult due to the lack of architectural features of FNA specimens.

Improvements in cell block processing: The Cell-Gel method.

BACKGROUND: The ability to produce adequate cell blocks profoundly impacts the diagnostic usefulness of cytology specimens. Cell blocks are routinely processed from fine-needle aspiration specimens or concentrated fluid samples. Obtaining directed passes for the sole purpose of producing a cell block is common practice, particularly when the cytopathologist anticipates the need for ancillary immunocytochemical stains and/or molecular studies. METHODS: The authors developed an effective and inexpensive process for producing cell blocks that consistently yields abundant cellular material, which they have termed the Cell-Gel method. This method can be simplified into 3 main steps: 1) preparing the sample; 2) constructing the cell block; and 3) processing the cell block. Highlights of the protocol include using a hemolytic fixative for sample preparation and disposable base molds for cell block construction. RESULTS: The cell block failure rate in the current study decreased from 18% with the HistoGel Tube method (January 2014-December 2014) to 6% with the Cell-Gel method (January 2015-December 2016). The authors evaluated 110 cell blocks processed with the HistoGel Tube method and 110 cell blocks processed with the Cell-Gel method, for a total evaluation of 220 cell blocks. CONCLUSIONS: The authors have developed an effective and inexpensive protocol for producing cell blocks that consistently yields abundant cellular material. The Cell-Gel method uses a hemolytic fixative and disposable base molds to produce adequate cell blocks. When the method was implemented, the cell block failure rate of the study laboratory decreased by approximately 67%. Cancer Cytopathol 2017;125:267-276. © 2016 American Cancer Society.

Cytomorphological Features Useful to Prevent Errors in the Diagnosis of Pancreatic Adenocarcinoma by Fine Needle Aspiration Cytology.

OBJECTIVES: Endoscopic ultrasound-guided fine-needle aspiration (FNA) is now widely used as a primary tool to diagnose pancreatic neoplasms. However, criteria that can reduce the risk of overdiagnosing pancreatic adenocarcinoma by FNA have not been adequately defined in the literature. This study aims to identify characteristic cytomorphological features that are helpful in distinguishing pancreatic adenocarcinoma from its mimics. STUDY DESIGN: Five false-positive FNA cases (group A) diagnosed as adenocarcinoma (4 cases) and suspicious for adenocarcinoma (1 case) by FNA, were identified by searching our laboratory information system. Cytomorphological features of group A cases were compared to 12 true-positive, histologically confirmed FNA cases (group B). RESULTS: Subsequent histological follow-ups of 5 misdiagnosed FNA cases showed 2 cases of intraductal papillary mucinous neoplasm with focal high-grade dysplasia, 1 case attributed to tumor contamination from a gastroesophageal junction adenocarcinoma, and 2 cases of pancreatic intraepithelial neoplasia (PanIN1/reactive change and PanIN2, respectively). Cytomorphological features present in both groups A and B included nuclear enlargement/overlapping, mild to moderate anisonucleosis, granular chromatin and prominent nucleoli. However, 1 or more of these 4 characteristic morphological features such as 3-dimensional cluster with cell disorientation, isolated malignant cells, irregular nuclear contour/nuclear grooves/notches (>5% atypical cell population), and marked nuclear size variation 1:4 or higher was mainly present in adenocarcinoma. CONCLUSIONS: A combination of at least 2 of these 4 characteristic cytomorphological features needs to be present before rendering an unequivocal diagnosis of adenocarcinoma. Using these strict cytological criteria would have eliminated these false-positive diagnoses.