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Introduction: p16 immunostaining is considered as a surrogate marker for human papillomavirus (HPV)-related head and neck squamous cell carcinomas (HNSCC). Herein, the utility of p16 is evaluated in cytology specimens., Material and Methods: The electronic data of a large academic institution was searched for cytology cases accompanied by p16 (2014-2018). Cases were categorized based on body sites. P16 staining was quantified (negative [0%], focal/patchy, or diffusely positive [>70%]). HPV testing was correlated where available., Results: A total of 372 cases were included (male:female, 239:133). The largest differences in application of p16 between men and women were in head/neck cases (209 versus 59) and the abdominal cases (1 versus 33), respectively. p16 diffuse staining is seen in most squamous cell carcinomas, small cell carcinomas, and gynecologic serous carcinomas. p16 expression was patchy or negative in most adenocarcinoma, neuroendocrine carcinoma, spindle cell neoplasms, and benign conditions. HPV testing was done on 217 cases including 138 cases with strong p16 (127 HPV+/11 HPV-), 20 cases with focal/patchy P16 staining (6 HPV+/14 HPV-) and 59 cases with negative p16 staining (3 HPV+/56 HPV-)., Conclusions: Diffuse p16 staining aids in the diagnosis of HPV-related carcinomas, particularly HPV-related HNSCC, across the body and according to sex. In contrast, focal/patchy p16 staining does not correlate with HPV status across various body sites. In conclusion, intensity of p16 matters and should be correlated with cytomorphology, clinical history, and ancillary studies (eg, p40 immunostaining) for an accurate diagnosis and preventing diagnostic pitfalls., (Copyright © 2020 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Objectives: A definitive diagnosis of malignancy may not be possible in pleural effusions. We report our experience with the diagnosis of suspicious for malignancy (SFM) in pleural effusion., Methods: A search for pleural effusions diagnosed as SFM (2008-2018) was performed. Patient records and pathology reports were reviewed. Specimens were subdivided into groups depending on volume (<75, 75-400, >400 mL). Diagnoses of malignant pleural effusion (MPE) served as controls., Results: We identified 90 patients, with a mean age of 60.6 years. Diagnoses included suspicious for involvement by carcinoma/adenocarcinoma in 64.4%, leukemia/lymphoma in 15.6%, melanoma in 2.2%, sarcoma in 3.3%, germ cell tumor in 1.1%, and not otherwise specified in 13.3%. Immunostains were performed in 47.8% and considered inconclusive in 24%. Average sample volume was 419 mL. There was a statistically significant difference between the SFM vs MPE groups for volumes greater than 75 mL (P = .001, χ 2 test), with SFM having increased proportion of volumes  greater than 400 mL, compared with the MPE group. There was no statistically significant difference in mean overall survival when the groups were compared (P = .49)., Conclusions: Samples with low cellularity, scant cell blocks, and inconclusive immunostains may contribute to a suspicious category diagnosis in pleural effusions., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Sclerosing pneumocytoma (SP) is a rare, benign pulmonary neoplasm. To the authors' knowledge, the current study is the first to evaluate the cytomorphology and immunoprofile of SP in a series., Methods: A total of 9 fine-needle aspiration cases of SP (7 of which were computed tomography guided and 2 of which were endobronchial ultrasound guided) including histopathology and immunohistochemistry were collected from 5 institutions., Results: The female-to-male ratio was 3.5:1, and the mean age of the patients was 54 years (range, 27-73 years). All cases presented as lung nodules, with a mean size of 2.2 cm (range, 1.1-5 cm), and were interpreted as atypical on rapid on-site evaluation. The final diagnoses were favor adenocarcinoma (1 case), well-differentiated lung adenocarcinoma (2 cases), low-grade epithelial neoplasm (2 cases), and sclerosing pneumocytoma (4 cases). Samples were moderately cellular, and consisted of round epithelioid cells with clear cell features, columnar cells, and spindle cells. A papillary arrangement with prominent hyalinized fibrovascular cores was the most common architectural pattern, followed by flat sheets and acinar formations. Tumor cells demonstrated mild, focally moderate nuclear pleomorphism with prominent nucleoli, hyperchromasia, nuclear elongation, nuclear overlap, and occasional nuclear inclusions and grooves. The background consisted of foamy macrophages (9 cases), hemosiderin pigment (6 cases), and lymphoid aggregates (3 cases) with no mitoses and/or necrosis. The surface cells and underlying round cells were positive for both thyroid transcription factor 1 and epithelial membrane antigen in all cases, which was the most notable immunohistochemical finding., Conclusions: Cytomorphological findings of SP overlap with those of well-differentiated lung adenocarcinoma. Awareness of these cytomorphologic findings and the distinct immunoprofile of the 2 cell types found in SP should prevent a misdiagnosis and aggressive treatment., (© 2020 American Cancer Society.)

Objectives: Define if the presence of morphologic features of adenocarcinoma (ACA) in non-small cell lung carcinoma (NSCLC) on cytology specimens correlates with clinical and biologic features., Methods: A total of 209 cases of NSCLC diagnosed on fine-needle aspiration in a 3-year period were included., Results: After morphologic review, the cases were classified as ACA (n = 115), NSCLC favor ACA (n = 43), and NSCLC-not otherwise specified (NOS) (n = 18). Squamous cell (SCC) (n = 14) and NSCLC favor SCC (n = 19) were excluded from further analysis. Patients with EGFR-mutated tumors had longer overall survival than those with EGFR wild-type tumors (P = .01). When comparing cases with morphologic features of ACA, NSCLC favor ACA, and NSCLC-NOS, there were no differences in the presence or absence of tested mutations, clinical stage, or survival., Conclusion: Patients diagnosed with pulmonary ACA, NSCLC favor ACA, or NSCLC-NOS in cytology specimens have similar clinical stage, survival, and molecular alterations.

Objectives: We analyzed the morphologic features and clinical characteristics of lung adenocarcinomas (ACAs) harboring mutated BRAF., Study Design: A review of the histology/cytology of BRAF-mutated lung ACAs was performed at the Johns Hopkins Hospital from January 1, 2013, to January 1, 2015. Patient demographics, clinical history, and ACA morphology were assessed., Results: Thirty-six cases were identified with a median age of 66 years (range 44-87), 58% (21/36) were female, and 94% (34/36) were current or former smokers. In total, 28% (10/36) had a BRAF-V600E mutation. Concurrent mutations were identified in KRAS in 4 cases (11%), PIK3CA in 2 cases (6%), and AKT1 in 2 cases (6%). No cases tested for ALK rearrangement were positive. The tumor grading varied from well to poorly differentiated, and the architecture assumed various patterns, including papillary, micropapillary, solid/cribriform, lepidic, and acinar. Of the cases with immunostains, 90% (18/20) were TTF-1 positive, 88% (14/16) were napsin-A positive, and 100% (8/8) were P63 negative., Conclusion: Mutated-BRAF lung ACA arose on average in the seventh decade of life in patients who were current or former smokers and was infrequently found in combination with other common lung ACA driver mutations. The actionable V600E mutation was present in <30% of cases, more commonly in females. The histologic grade and architecture of these tumors varied significantly., (© 2018 S. Karger AG, Basel.)

Objectives: The aim of this study was to report cytologic and molecular features of pulmonary adenocarcinoma patients presenting with a malignant pleural effusion at the first diagnosis., Study Design: Patients who had a cytopathologic diagnosis conclusive for lung adenocarcinoma for the first time on their pleural fluid specimen, and molecular testing done, were studied. The control group consisted of patients with a malignant pleural effusion that developed during disease progression., Results: We identified 18 patients (9 males and 9 females). Micropapillary and/or solid adenocarcinoma type features predominated among cytologic specimens (n = 15), while acinar patterns predominated in controls. Survival was not significantly different from that of the control group (mean 13.8 vs. 13.9 months, respectively; p = 0.61). Ten (55%) cases had mutations in EGFR (n = 6; 60%), KRAS (n = 3; 30%), or ALK translocation (n = 1; 10%). No mutations were identified in BRAF, AKT, ERBB2, NRAS, or PIK3CA (tested in 7 patients). Patients positive for the tested mutations had a better overall survival than patients negative for the mutations (mean survival 16.2 vs. 6.05 months, respectively; p = 0.006, log-rank test). Ten (84%) control patients were positive for mutations in EGFR (n = 5; 42%), KRAS (n = 4; 34%), or ALK translocation (n = 1; 8.4%)., Conclusion: In our series, a micropapillary-like and solid-like morphology, common in cytologic specimens, and alterations in EGFR were the most frequent identifiable molecular changes., (© 2017 S. Karger AG, Basel.)

Thyroid carcinomas and lung adenocarcinoma share cytomorphological features yet have different prognoses. Thyroid Transcription Factor-1 (TTF-1) is an immunohistochemical (IHC) marker used to confirm pulmonary and thyroid carcinoma, while Thyroglobulin (TGB) is expressed by thyroid carcinoma. The cytopathology archive of The Johns Hopkins Hospital was searched for cases of lung adenocarcinoma versus thyroid carcinoma with TTF-1 and TGB IHC. Forty-four cases of lung adenocarcinoma (25) and thyroid carcinoma (19) were retrieved. One was metastatic lung adenocarcinoma to the thyroid and three were metastatic papillary thyroid carcinoma (PTC) to the lung. The initial interpretation of two cases from bony lesions was metastatic lung adenocarcinoma. In light of additional clinical information and TGB immunostain, the diagnoses of these two cases changed to metastatic thyroid carcinoma. TTF-1 and TGB is a small immunostain panel that can differentiate lung adenocarcinoma from thyroid carcinoma and prevent misdiagnosis and its consequences., (Copyright © 2013 Wiley Periodicals, Inc.)