Expression of insulinoma-associated protein 1 in non-small cell lung cancers: a diagnostic pitfall for neuroendocrine tumors.

Insulinoma-associated protein 1 (INSM1) has been reported as a highly sensitive and specific marker of neuroendocrine tumors. INSM1 expression has also been reported, although uncommonly, in non-neuroendocrine tumors. This study aimed to elucidate potential nonspecific INSM1 expression in non-small cell non-neuroendocrine lung cancers (NSCNELCs), especially in squamous cell carcinomas (SqCCs) with basaloid features to avoid diagnostic pitfalls. Tissue microarrays (TMAs) were constructed for 324 NSCNELCs, including 196 adenocarcinomas (AdCs), 86 SqCCs, and 42 other NSCNELCs. In addition, 38 whole-tissue sections of SqCCs with basaloid features were examined. INSM1 immunostain was semiquantitively evaluated based on the percentage of nuclear staining in tumor cells, categorized as negative, focal (<10% tumor cells), and positive (>10% tumor cells). Among 324 TMAs, 6.2% (20/324) were positive for INSM1, 4.9% (16/324) were focal, and 88.9% (289/34) were negative. Of 196 AdCs, 5.1% (10/196) were positive for INSM1, 4.7% (9/196) were focal, and 90.3% (177/196) were negative. Of 86 SqCCs, 9.3% (8/86) were positive for INSM1, 5.8% (5/86) were focal, and 84.9% (73/86) were negative. Of the remaining 42 NSCNELCs, 4.8% (2/42) were positive for INSM1, 4.8% (2/42) were focal, and 90.4% (38/44) were negative. Among 38 cases of whole-tissue sections of SqCCs with basaloid features, 15.8% (6/38) were positive for INSM1, 18.4% (7/38) were focal, and 65.8% (25/38) were negative. Our study demonstrates that INSM1 is expressed in a significant subset of NSCNELCs, suggesting caution in interpreting INSM1 staining, especially with limited samples. INSM1 should not be used as a stand-alone neuroendocrine marker in differentiating primary lung tumors.

Applicability of the Paris System for veterans: high rates of undiagnosed low-grade urothelial neoplasia.

BACKGROUND: The Paris System for Reporting Urinary Cytology (TPS) is a recently developed standardized terminology system. It is well-established that urine cytology has low sensitivity for detecting low-grade urothelial neoplasia (LGUN). Though the majority of tumors are low-grade, surveillance of these lesions is important to monitor for possible progression. Herein, we compared TPS to our veteran integrated system network (VISN) to assess its applicability. We also introduced semi-quantitative scoring to further evaluate cytomorphologic features of high-grade urothelial carcinoma (HGUC). MATERIALS AND METHODS: Voided and instrumented urine cytology specimens and concurrent biopsies were reviewed from Sept 2018 - Jan 2020. Cytologic diagnoses reported using the VISN institutional system were reevaluated by staff cytopathologists and categorized according to TPS. A semi-quantitative scoring system to evaluate cytomorphologic features was devised. RESULTS: Cytology and surgical specimens from 105 patients were reviewed. The VISN and TPS reporting systems were compared and showed similar sensitivities and specificities for the detection of HGUC. Rates of biopsy-proven LGUN were high for the negative for high-grade urothelial carcinoma category (NHGUC; 27/53, 50.9%) and atypical urothelial cells (AUC; 14/30; 46.7%) compared to suspicious/positive (0/22, 0%) categories. Major and minor criteria as outlined in TPS were evaluated semi-quantitatively. CONCLUSIONS: Urine cytology has limited sensitivity for LGUN regardless of the cytologic reporting system used. There was a high rate of LGUN following NHGUC/AUC diagnoses in the Veteran population. Coarse chromatin was determined to be the least sensitive criterion for the detection of high-grade lesions and irregular chromatin rim was most specific.

A Nervous Recipient of a "Tongue Lashing".

A veteran with a history of mental illness and drug and alcohol misuse developed a bleeding lesion on his tongue, which raised concerns of self-injury.

Diagnosis of Infectious Diseases in the Lower Respiratory Tract: A Cytopathologist's Perspective.

CONTEXT.­: Respiratory cytology continues to play an important role in the diagnosis of lower respiratory tract infections. Prompt, accurate diagnosis of causative organisms is of paramount importance, particularly in immunosuppressed patients. In addition, a rapidly expanding arsenal of ancillary testing is now available, aiding tremendously in organism identification. OBJECTIVE.­: To provide an updated review on the cytomorphologic features of common organisms in lower respiratory tract infection. Relevant ancillary tests, differential diagnoses, and potential pitfalls of organism identification will also be discussed. DATA SOURCES.­: Data for this review were gathered from PubMed searches of infectious diseases of the lower respiratory tract, especially related to the diagnoses. CONCLUSIONS.­: The lower respiratory tract is subject to infection by a wide variety of infectious agents. Pathologists should be familiar with common organisms, including their general clinical characteristics, cytomorphologic features, differential diagnoses, and ancillary methods of detection. Above all, correlation with microbiologic and clinical information is necessary to make a confident diagnosis of infection.

A rare 'incidentaloma' found on low-dose CT screening for lung cancer: 'scanner beware'.

Screening for lung cancer with low-dose computed tomography (LDCT) has been shown to reduce mortality and has been recommended by the U.S. Preventive Services Task Force for adults 55 to 80 years of age with a 30 pack-year smoking history who are either current smokers or those that quit within 15 years. However, the overwhelming majority of abnormalities detected are not from malignancy. We report a case of pulmonary Langerhans' cell histiocytosis, here-to-fore thought of as extremely uncommon, and make readers aware that this may be increasingly found as LDCT is more widely adopted.

Detection and genotype of high-risk human papillomavirus in fine-needle aspirates of patients with metastatic squamous cell carcinoma is helpful in determining tumor origin.

OBJECTIVES: Recent studies have shown that human papillomavirus (HPV) is associated with a certain subset of head and neck squamous cell carcinoma (HNSCC)-namely, those arising in the oropharynx. The objective of this study is to determine the efficacy, detection, and genotype of high-risk (HR) HPV using the Roche cobas 4800 system (Roche Molecular System, Pleasanton, CA). METHODS: Forty-two fine-needle aspirate (FNA) specimens from 37 patients with cervical (n = 36) or mediastinal (n = 5) lymphadenopathy or a left parapharyngeal mass (n =1) were included in this prospective study. HR-HPV testing was performed on residual FNA material after direct smear preparation and, if positive, was further delineated into HPV 16/18 genotypes using the Roche cobas 4800 system. Follow-up included review of histologic material and/or electronic health records. RESULTS: Among those HNSCCs that were positive for HR-HPV, 18 (100%) of 18 originated from the oropharynx, whereas only two (13%) of 15 HR-HPV-negative HNSCCs originated from the oropharynx (χ(2) test, P < .05). p16 immunohistochemical assay and HPV 16 in situ hybridization on corresponding histologic specimens were concordant with cytologic HR-HPV results. CONCLUSIONS: HR-HPV detection and genotyping can be performed on lymph node FNAs with metastatic squamous cell carcinoma using the Roche cobas 4800 system. The presence of HR-HPV and/or HPV 16 is a reliable indicator of the metastatic squamous cell carcinoma originating from the oropharynx.