Sonographic and cyst fluid cytologic changes after EUS-guided pancreatic cyst ablation.

BACKGROUND AND AIMS: The effect of EUS-guided pancreatic cyst ablation (PCA) on sonographic morphology and cyst fluid cytology is unknown. The aim of this study was to evaluate morphologic, cytologic, and change in cyst fluid DNA after PCA. METHODS: In a prospective single-center study, consecutive patients with suspected benign 10- to 50-mm pancreatic cysts underwent baseline EUS-FNA and EUS-PCA followed 2 to 3 months later by repeat EUS, cyst fluid analysis, and possible repeat PCA. Surveillance imaging after ablation was performed at least annually and classified as complete response (CR), partial response, or persistent, with <5%, 5% to 25%, and 25% of the original cyst volume, respectively. RESULTS: Thirty-six patients underwent EUS-PCA with ethanol alone (n = 8) or ethanol and paclitaxel (n = 28), and CR occurred in 19 patients (56%). After EUS-PCA, EUS showed an increase in wall diameter in 68%, decreased number of septations in 24%, increased debris in 24%, loss of mural nodule or novel calcification in 21%, and alteration of fluid viscosity in 48%. Follow-up cytology showed increased epithelial cellularity in 27%, loss or decreased cellular atypia in 15%, increased or appearance of macrophages in 24%, and inflammatory cells in 15%. Postablation DNA amount increased and quality decreased in 71% each. Between the CR and non-CR patients, there was no significant difference in frequency of sonographic or cytologic features. In the CR group, mean DNA quantity was significantly increased after ablation (P = .023) without a change in quality (P = .136). CONCLUSIONS: EUS-PCA induces morphologic and cytologic changes of pancreatic cysts, none of which appears to predict overall imaging-defined response to ablation. (Clinical trial registration numbers: NCT00233038 and NCT01643460.).

Anaplastic Lymphoma Kinase Immunocytochemistry on Cell-Transferred Cytologic Smears of Lung Adenocarcinoma.

BACKGROUND: Anaplastic lymphoma kinase (ALK) immunohistochemical staining on formalin-fixed paraffin-embedded tissue or cell blocks (CB) has been reported as an effective alternative to fluorescence hybridization in situ (FISH) for the detection of ALK gene rearrangement. However, CB frequently lack adequate cellularity even when the direct smears are cellular. This study aims to assess the utility of ALK immunocytochemical (ICC) staining on direct smears using the cell transfer (CT) technique for the detection of ALK rearrangement. METHODS: Fine-needle aspiration (FNA) cases of lung adenocarcinoma in which the ALK status had been determined by FISH on CB or a concurrent biopsy were identified. ICC staining for ALK was performed on alcohol-fixed Papanicolaou-stained direct smears using the CT technique. ALK immunoreactivity was evaluated using a modified semiquantitative scale. Results were compared with those of FISH. RESULTS: A total of 47 FNA specimens were included. Five of 7 FISH-positive cases showed positive ALK ICC staining (71.4%), and 39 of 40 FISH-negative cases were negative on ALK ICC staining (97.5%). The overall correlation between ALK ICC and FISH was 93.6%. CONCLUSION: ICC performed on FNA smears using the CT technique is an alternative method for the assessment of ALK rearrangement, especially when CB lack adequate cellularity.

Utilization of cell-transferred cytologic smears in detection of EGFR and KRAS mutation on adenocarcinoma of lung.

Cell-transfer technique has been proven useful for performing immunocytochemistry on fine-needle aspiration smears. However, its utility for EGFR and KRAS molecular testing has not been validated. Molecular testing was performed using the cell-transfer technique on both Papanicolaou-stained ethanol-fixed and Hema 3-stained air-dried smears from 32 fine-needle aspiration samples that had diagnoses of adenocarcinoma of the lung, and then was compared to the results of the corresponding formalin-fixed paraffin-embedded tissues. The molecular testing was successfully performed on 32 of 32 ethanol-fixed and 31 of 32 air-dried samples. The molecular results on ethanol-fixed and air-dried smears showed 100% agreement. There is 100% (32/32) agreement for the EGFR and 97% (31/32) agreement for the KRAS between the cell-transfer technique and formalin-fixed paraffin-embedded tissues. One discrepant case was due to low percentage of tumor cells on the smears. Cell-transfer technique is a reliable alternative method for EGFR and KRAS testing if the cell blocks lack adequate cellularity.

Cystic neoplasms of the pancreas; findings on magnetic resonance imaging with pathological, surgical, and clinical correlation.

Pancreatic cysts are increasingly being identified by cross-sectional imaging studies. Pancreatic cystic lesions comprise a spectrum of underlying pathologies ranging from benign and pre-malignant lesions to frank malignancies. Magnetic resonance imaging with cholangiopancreatography is a non-invasive imaging modality used for the characterization of cystic pancreatic lesions. This article will review the most common pancreatic cystic neoplasms and the utility of MR imaging in the characterization of these cysts.

Hürthle cell neoplasms diagnosed by fine needle aspiration are not associated with an increased risk of malignancy.

OBJECTIVES: The aim of this study is to determine the risk of neoplasm and malignancy in thyroid fine needle aspiration (FNA) diagnosed as atypia of undetermined significance with Hürthle cell change (AUS-H) or Hürthle cell neoplasm (HCN). STUDY DESIGN: A computerized search of our laboratory information system was performed to identify all thyroid FNA and correlating surgical pathology diagnoses including Hürthle cell or oncocyte in the diagnostic nomenclature. The risks of neoplasm and malignancy were calculated for AUS-H and HCN categories separately. RESULTS: For the 29 AUS-H cases, the follow-up histology demonstrated 15 benign lesions, 4 follicular adenomas, 7 Hürthle cell adenomas, 1 papillary microcarcinoma (PMC), 1 follicular carcinoma and 1 Hürthle cell carcinoma. For the 93 HCN cases, the follow-up histology demonstrated 28 benign lesions, 9 follicular adenomas, 32 Hürthle cell adenomas, 2 PMCs, 2 papillary thyroid carcinomas, 6 follicular carcinomas and 14 Hürthle cell carcinomas. CONCLUSIONS: The risks of neoplasm and malignancy were 62 and 7% for the AUS-H category and 73 and 24% for the HCN category, respectively. The risk of malignancy for the AUS-H patients is within the 5- to 15-percent range suggested by the Bethesda System for Reporting Thyroid Cytology and within the 15- to 30-percent range suggested for follicular neoplasms.

Detection of BRAF mutation in metastatic melanoma utilizing cell-transferred cytological smears.

OBJECTIVES: Fine-needle aspiration (FNA) is frequently used to diagnose metastatic melanoma. In this study, we validated the use of cell-transferred cytological smears for BRAF molecular testing. STUDY DESIGN: We conducted a search of our laboratory information system for the period 2011-2013 in order to identify surgical pathology cases of either primary or metastatic melanomas in which BRAF mutation analyses had already been performed. Thirty FNA cases with diagnoses of metastatic melanoma from the same patients were identified. Direct smears from each FNA case were selected for mutation analyses using the cell transfer technique. RESULTS: Mutation analyses were successfully performed on 28 of 30 FNA cases (93%) using the cell-transferred cytological smears. In 25 cases (8 BRAF mutations and 17 BRAF wild types), there was 100% agreement for the BRAF mutation between the cell-transferred cytological smears and the formalin-fixed paraffin-embedded tissues. Three FNA cases showed BRAF mutations that had not been detected in the correlated surgical specimens which were tested twice, and 2 cases failed to work. CONCLUSIONS: Cell-transferred cytological smears are a reliable and alternative resource for detecting BRAF mutations in metastatic melanoma.

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.

Molecular pathology of lung cancer: key to personalized medicine.

The majority of lung adenocarcinoma patients with epidermal growth factor receptor- (EGFR) mutated or EML4-ALK rearrangement-positive tumors are sensitive to tyrosine kinase inhibitors. Both primary and acquired resistance in a significant number of those patients to these therapies remains a major clinical problem. The specific molecular mechanisms associated with tyrosine kinase inhibitor resistance are not fully understood. Clinicopathological observations suggest that molecular alterations involving so-called 'driver mutations' could be used as markers that aid in the selection of patients most likely to benefit from targeted therapies. In this review, we summarize recent developments involving the specific molecular mechanisms and markers that have been associated with primary and acquired resistance to EGFR-targeted therapy in lung adenocarcinomas. Understanding these mechanisms may provide new treatment avenues and improve current treatment algorithms.

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.

Role of endoscopic ultrasound-guided fine-needle aspiration with flow cytometry to diagnose lymphoma: a single center experience.

BACKGROUND AND AIM: The use of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) +/- flow cytometry (FC) for the diagnosis of suspected lymphoma remains controversial. We report our experience and diagnostic yield for EUS +/- FC for suspected lymphoma. METHODS: Databases were queried for those who underwent EUS-FNA +/- FC for suspected lymphoma. Hospital charts were reviewed to confirm the final cytological diagnosis, follow up and FC results if obtained. The final diagnosis was confirmed by the results of EUS-FNA +/- FC, other biopsy and/or follow up. RESULTS: In total, 54 patients underwent EUS-FNA of 72 lesions. The final diagnosis of lymphoma was made in 38 of the 54 (70%) patients, and 33 of the 54 (61%) patients relied on EUS-FNA. Cytopathology in 41 patients using EUS-FNA + FC showed lymphoma in 24 patients, atypical lymphoid cells in six and reactive lymph node in 11. In 9 of the 24 with lymphoma by EUS + FC, the diagnosis was confirmed by another diagnostic modality, like surgery, bone marrow biopsy and computed tomography-guided biopsy. Of the six with atypical lymphoid cells, additional diagnostic methods confirmed lymphoma in three. The remaining 13 of the 54 patients underwent EUS-FNA without FC due to insufficient sample (n = 5) or operator choice (n = 8). Cytopathology in these 13 patients without FC showed lymphoma (9), atypical lymphoid cells (3) and reactive node (1). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of EUS-FNA for lymphoma in all 54 patients ranged from 80% to 87%, 92% to 93%, 97%, 60% to 75% and 83% to 89%, respectively. CONCLUSIONS: EUS-FNA is sensitive and specific for the diagnosis of suspected lymphoma. Confirmatory or further testing should be performed when EUS-FNA with or without FC is indeterminate and or non-diagnostic.

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.

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.

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.