Faculty Bibliography

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4d-UT) is an uncommon, aggressive lung neoplasm associated with smoking and characterized by loss of SMARCA4 (BRG-1) expression. Although originally considered to be a primary sarcoma, there is growing evidence that these lesions may represent transformation of conventional non-small cell carcinoma. In this study, we probe this relationship based on the clinical, histologic and molecular findings of 18 SMARCA4-deficient malignancies of the lung. Cases diagnosed as SMARCA4d-UT and SMARCA4-deficient carcinoma were retrospectively reviewed, including histologic and immunophenotypic features, and next generation sequencing studies. Of the 18 tumors, 5 were considered to represent undifferentiated SMARCA4d-UT, and 13 SMARCA4-deficient carcinomas, including 11 adenocarcinomas, 1 squamous cell carcinoma, and 1 poorly differentiated non-small cell carcinoma. All 13 carcinomas had a morphologically identifiable undifferentiated component. Survival outcomes were similar in both SMARCA4d-UT and carcinomas. Genetic alterations often seen in lung cancer were identified in 8 cases, including mutations in EGFR (in 2 SMARCA4-deficient adenocarcinomas), KRAS (1 SMARCA4d-UT and 1 SMARCA4-deficient adenocarcinoma), MAP2K1 (1 SMARCA4-deficient adenocarcinoma), and a gene fusion involving EML4::ALK (1 SMARCA4d-UT). The patient with EML4::ALK fusion was treated with alectinib with partial response. Fusions involving BRAF::CHCHD3 and FGFR1::FILIP1 were identified in 2 SMARCA4-deficient adenocarcinomas. High expression of PD-L1 (TPS >50 %) was seen in 12 cases (67 %). These finding further suggest that SMARCA4d-UT and carcinomas with SMARCA4 loss may be on the same spectrum of disease, and accurate histologic distinction between these lesions may be challenging. A unified terminology may be beneficial for appropriate diagnosis and treatment.

With the advancement of tissue procurement techniques, in-depth knowledge of morphology is crucial for cytopathologists to diagnose neoplastic and nonneoplastic lung diseases optimally. Cytopathologists must also be well versed in immunohistochemistry/immunocytochemistry markers and their interpretation for an accurate diagnosis.

Small biopsies of lung are routinely obtained by many methods, including several that result in cytologic specimens. Because lung cancer is often diagnosed at a stage for which primary resection is not an option, it is critical that all diagnostic, predictive, and prognostic information be derived from such small biopsy specimens. As the number of available diagnostic and predictive markers expands, cytopathologists must familiarize themselves with current requirements for specimen acquisition, handling, results reporting, and molecular and other ancillary testing, all of which are reviewed here.

Benign adrenal cysts are relatively uncommon variants of all adrenal incidentalomas. When identified, most benign adrenal cysts are asymptomatic, which differentiates them from other functional adrenal lesions. There are various types of adrenal cysts, although the most common being an endothelial cyst. Ultimately, evaluation and management approaches are aimed at ruling out a functional adrenal mass and management of symptoms if present. We present a unique presentation of an otherwise healthy male with a large incidental adrenal cyst, later identified as a benign endothelial cyst, who presented with classic symptoms of catecholamine excess. The patient had a negative hormonal evaluation, and his episodic symptoms were resolved with surgical removal of the adrenal mass. This case report and brief review provides valuable insight into the evaluation and management of a unique clinical scenario, where a benign cystic mass led to compression-related symptoms of catecholamine excess that were resolved after removal of the nonfunctional, cystic, mass.

Medical practice requires physicians to have a broad understanding of the basic sciences, have competent clinical skills, and have an ability to practice in evolving health systems in a cost-effective and evidence-based manner. Essential to the practice of medicine is an understanding of the common laboratory tests and the ability to use them effectively. The Essential Laboratory Tests for Medical Education (ELTME) is a concise document explaining the pathophysiology of common laboratory tests and clinical context for each test and was developed in response to an expressed need from medical students, residents and fellows, and medical educators. The ELTME is linked to the Pathology Competencies in Medical Education and its third competency of diagnostic medicine and therapeutic pathology. The ELTME table is a document of common laboratory tests in alphabetical listing. Laboratory tests may be easily queried by name or organ system, and with simple editing tools, new tables may be constructed to fit the needs of individual curricula or learners. Furthermore, the table may be easily expanded by educators who wish to add specific tests to complement their curricula.

BACKGROUND:In the ongoing COVID-19 pandemic, there is an urgent need for comprehensive performance evaluation and clinical utility assessment of serological assays to understand the immune response to SARS-CoV-2. METHODS:IgM/IgG and total antibodies against SARS-CoV-2 were measured by a cyclic enhanced fluorescence assay (CEFA) and a microsphere immunoassay (MIA), respectively. Independent performance evaluation included imprecision, reproducibility, specificity and cross-reactivity (CEFA n = 320, MIA n = 364). Clinical utility was evaluated by both methods in 87 patients at initial emergency department visit, 28 during subsequent hospitalizations (106 serial samples), and 145 convalescent patients. Totally 916 patients and 994 samples were evaluated. RESULTS:Agreement of CEFA and MIA was 90.4%-94.5% (Kappa: 0.81-0.89) in 302 samples. CEFA and MIA detected SARS-CoV-2 antibodies in 26.2% and 26.3%, respectively, of ED patients. Detection rates increased over time reaching 100% after 21 days post-symptom onset. Longitudinal antibody kinetic changes by CEFA and MIA measurements correlated well and exhibited three types of seroconversion. Convalescent sera showed a wide range of antibody levels. CONCLUSION/CONCLUSIONS:Rigorously validated CEFA and MIA assays are reliable for detecting antibodies to SARS-CoV-2 and show promising clinical utility when evaluating immune response in hospitalized and convalescent patients, but are not useful for early screening at patient's initial ED visit.