Faculty Bibliography

Background: In mediastinal biopsies that show fibrosis, the differential diagnosis includes fibrosing mediastinitis, immunoglobulin G subclass 4-related disease, Hodgkin lymphoma, as well as reactive fibrotic and inflammatory changes adjacent to other processes including neoplasms. Cases Description: We report two cases of incidentally detected mediastinal seminoma that contained extensive areas of paucicellular fibrosis, which precluded accurate preoperative biopsy diagnosis. The fibrosis consisted of mildly inflamed, densely scarred tissue with thin dilated vessels, and was present to a significant extent that is suggestive of spontaneous regression. These features are not currently described in the World Health Organization Classification of Thoracic Tumors. In both patients, needle and open biopsies sampled only the fibrotic areas of the tumors, and the final diagnosis was not achieved until surgical excision was performed. After surgery, both patients received chemotherapy, and were alive without evidence of disease at 3.4 years and 1 year post-operatively, respectively. Tumor fibrosis composed approximately 95% and 50% of each patient"™s tumor, respectively. In one of the patients, correlation of the needle biopsy position with the positron emission tomography (PET) scan revealed that the biopsy needle had sampled a non-metabolically active portion of the tumor. Conclusions: While pathologic spontaneous regression is well-described in gonadal germ cell tumors, it is not well-reported in extragonadal locations. Prospective knowledge of this diagnostic pitfall and targeting PET-avid regions of the tumor may increase the diagnostic yield and help to avoid non-indicated surgical interventions.

BACKGROUND:A 64-year-old man presented with a 7.8 cm lipomatous thyroid mass discovered on magnetic resonance imaging. METHODS:After two non-diagnostic fine needle aspirations (FNAs) were performed, computed tomography (CT) revealed features concerning for malignancy including central necrosis and infiltrative borders. A third FNA was still non-diagnostic. Total thyroidectomy was performed. RESULTS:Upon pathologic examination, the final diagnosis was primary thyroid angiolipoma. The lesion contained central fat necrosis with ischemic features, attributable to the FNAs. CONCLUSION/CONCLUSIONS:Ours is the third published case report of this rare entity. To date, no lipomatous thyroid tumor has undergone extensive genomic testing. Next-generation sequencing of our case revealed multiple genetic alterations, supporting the concept of angiolipomas being true neoplasms. Whereas the two previously reported cases in the literature were radiographically much smaller and appeared indolent, the large tumor in our case exhibited radiographic features concerning for liposarcoma, which belied the benign final pathologic diagnosis. Our case demonstrates that conservative surgical management (partial thyroidectomy) may be considered for lipomatous thyroid tumors, with further interventions to be determined only after final pathologic diagnosis.

In the version of this article initially published, Giampaolo Merlini (IRCCS Foundation Policlinico San Matteo, Pavia, Italy) was shown with an incorrect affiliation, which has now been corrected in the HTML and PDF versions of the article.

OBJECTIVES/OBJECTIVE:Our study assesses whether the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) offers any benefit over the original cytology classification, and measures interobserver agreement. METHODS:Four cytopathologists retrospectively blindly classified preoperative cytology by MSRSGC from 101 resected salivary tumors. Consensus MSRSGC diagnoses were correlated with surgical pathology diagnoses and compared with the original cytology classification. Diagnostic parameters were calculated for both systems. Interobserver variability was assessed. RESULTS:The original cytology classification vs MSRSGC had sensitivity, specificity, positive predictive value, and negative predictive value of 75.0% vs 78.3%, 97.1% vs 98.0%, 91.2% vs 94.7%, and 90.1% vs 90.0%, respectively. The original cytology classification risk of neoplasm (RON) was 91.7% for "negative for malignancy" and 100.0% for other categories. The MSRSGC RON was 71.4% in category II (nonneoplastic) and 100.0% in all other categories. The original cytology classification risk of malignancy (ROM) ranged from 0.0% for "atypical" to 100.0% for "positive for malignancy." The MSRSGC ROM ranged from 0.0% in categories I (nondiagnostic) and III (nonneoplastic) to 100.0% in category VI (malignant). Weighted agreement using the MSRSGC was 92% (Gwet AC1, 0.84); unweighted agreement was 69% (Gwet AC1, 0.64). MSRSGC category IVA (benign neoplasm) was most likely to show interobserver agreement, with complete agreement in 67% of cases. CONCLUSIONS:The MSRSGC performs similarly to the original cytology classification and shows relatively high interobserver agreement.

BACKGROUND:Testosterone is one of the strategies that transmasculine persons can elect in order to align physical traits to their gender identity. Previous studies have shown morphologic changes in the genital tract associated with testosterone. Here, we aim to evaluate cervicovaginal cytology specimens (Pap tests) and high-risk HPV (HR-HPV) testing from transmasculine individuals receiving testosterone. METHODS:This is a retrospective cohort of 61 transmasculine individuals receiving testosterone from 2013 to 2021. Cytologic diagnoses from 65 Pap tests were correlated with HPV status and histologic follow-up and compared with the institutional data and a cohort of cisgender women with atrophic changes. RESULTS:The median age was 28 years and median time of testosterone use was 3 years. Transmasculine persons showed significantly higher rates of HSIL (2%) and unsatisfactory (16%) when compared with the institutional data and atrophic cohort of cisgender women. After reviewing slides of 46 cases, additional findings were noted: atrophy was present in 87%, glycogenated cells were seen in 30%, and Lactobacilli were substantially decreased in 89%. Among 32 available HPV tests, 19% were positive for HR-HPV and 81% were negative. On histologic follow-up, all HR-HPV-positive cases with abnormal cytology showed HSIL, while none of the HPV-negative cases revealed HSIL. CONCLUSION/CONCLUSIONS:Our study cohort demonstrated a high percentage of abnormal Pap tests in transmasculine persons receiving testosterone. Testosterone seems to induce changes in squamous cells and shifts in vaginal flora. HR-HPV testing can be a useful adjunct in the workup of abnormal Pap tests from transmasculine individuals.

T cell activation and function depend on Ca²⁺ signals mediated by store-operated Ca²⁺ entry (SOCE) through Ca²⁺ release-activated Ca²⁺ (CRAC) channels formed by ORAI1 proteins. We here investigated how SOCE controls T cell function in pulmonary inflammation during a T helper 1 (T_H1) cell-mediated response to influenza A virus (IAV) infection and T_H2 cell-mediated allergic airway inflammation. T cell-specific deletion of Orai1 did not exacerbate pulmonary inflammation and viral burdens following IAV infection but protected mice from house dust mite-induced allergic airway inflammation. ORAI1 controlled the expression of genes including p53 and E2F transcription factors that regulate the cell cycle in T_H2 cells in response to allergen stimulation and the expression of transcription factors and cytokines that regulate T_H2 cell function. Systemic application of a CRAC channel blocker suppressed allergic airway inflammation without compromising immunity to IAV infection, suggesting that inhibition of SOCE is a potential treatment for allergic airway disease.

Herein we present a case of an 80-year-old gentleman who presented with exertional dyspnea status post aortic valve replacement with #23 Trifecta pericardial St. Jude aortic bioprosthetic valve (BV) 12 years prior. He subsequently underwent valve re-replacement due cusp calcification. Histologically, the surgically explanted BV revealed Congophilic deposits with birefringence under cross-polarized light. Extensive work-up identified no systemic source of amyloid in this patient. Liquid chromatography-tandem mass spectrometry-based (LC-MS/MS) proteomics showed the amyloid was composed of human-origin amyloid signature proteins (apolipoprotein A4, apolipoprotein E, serum amyloid P) and human-origin mu heavy chains. Background bovine collagen was also present. Transmission electron microscopy (TEM) showed collections of 7.5-10 nm nonbranching fibrils, consistent with amyloid. Using these techniques, we classified the amyloid as Mu heavy chain, deposition of which is highly unusual in BV. Finally, we provide a review of the literature regarding isolated amyloid deposition in BV.

OBJECTIVE:Carcinosarcoma of the salivary gland is a rare malignant biphasic tumor. The present study investigates the epidemiology and clinical behavior of carcinosarcoma of the major salivary glands using the National Cancer Database (NCDB). STUDY DESIGN/METHODS:Historical cohort study. SETTING/METHODS:NCDB. METHODS:All tumors were selected between 2004 and 2018. Patient demographics, tumor characteristics, treatments, and survival were analyzed. Cox regression analysis was performed in surgically treated patients. RESULTS:= .008) remained significant. CONCLUSION/CONCLUSIONS:Carcinosarcoma is a rare salivary gland tumor that frequently presents at a locally advanced stage. Despite multimodality treatments, the outcomes are poor. In the absence of clinical trial data, these data from the NCDB could guide clinicians in the management of this rare disease.

OBJECTIVES/OBJECTIVE:Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may develop end-stage lung disease requiring lung transplantation. We report the clinical course, pulmonary pathology with radiographic correlation, and outcomes after lung transplantation in three patients who developed chronic respiratory failure due to postacute sequelae of SARS-CoV-2 infection. METHODS:A retrospective histologic evaluation of explanted lungs due to coronavirus disease 2019 was performed. RESULTS:None of the patients had known prior pulmonary disease. The major pathologic findings in the lung explants were proliferative and fibrotic phases of diffuse alveolar damage, interstitial capillary neoangiogenesis, and mononuclear inflammation, specifically macrophages, with varying numbers of T and B lymphocytes. The fibrosis varied from early collagen deposition to more pronounced interstitial collagen deposition; however, pulmonary remodeling with honeycomb change was not present. Other findings included peribronchiolar metaplasia, microvascular thrombosis, recanalized thrombi in muscular arteries, and pleural adhesions. No patients had either recurrence of SARS-CoV-2 infection or allograft rejection following transplant at this time. CONCLUSIONS:The major pathologic findings in the lung explants of patients with SARS-CoV-2 infection suggest ongoing fibrosis, prominent macrophage infiltration, neoangiogenesis, and microvascular thrombosis. Characterization of pathologic findings could help develop novel management strategies.