Activation of STAT3 signaling pathway in the kidney of COVID-19 patients.

BACKGROUND: Acute kidney injury is common in patients with COVID-19, however mechanisms of kidney injury remain unclear. Since cytokine storm is likely a cause of AKI and glomerular disease, we investigated the two major transcription factors, STAT3 and NF-kB, which are known to be activated by cytokines. METHODS: This is an observational study of the postmortem kidneys of 50 patients who died with COVID-19 in the Mount Sinai Hospital during the first pandemic surge. All samples were reviewed under light microscopy, electron microscopy, and immunofluorescence by trained renal pathologists. In situ hybridization evaluation for SARS-CoV-2 and immunostaining of transcription factors STAT3 and NF-kB were performed. RESULTS: Consistent with previous findings, acute tubular injury was the major pathological finding, together with global or focal glomerulosclerosis. We were not able to detect SARS-CoV-2 in kidney cells. ACE2 expression was reduced in the tubular cells of patients who died with COVID-19 and did not co-localize with TMPRSS2. SARS-CoV-2 was identified occasionally in the mononuclear cells in the peritubular capillary and interstitium. STAT3 phosphorylation at Tyr705 was increased in 2 cases in the glomeruli and in 3 cases in the tubulointerstitial compartments. Interestingly, STAT3 phosphorylation at Ser727 increased in 9 cases but only in the tubulointerstitial compartment. A significant increase in NF-kB phosphorylation at Ser276 was also found in the tubulointerstitium of the two patients with increased p-STAT3 (Tyr705). CONCLUSIONS: Our findings suggest that, instead of tyrosine phosphorylation, serine phosphorylation of STAT3 is commonly activated in the kidney of patients with COVID-19.

Molecular Alterations in Thyroid Carcinoma.

Thyroid carcinoma is the most common cancer in the endocrine system. Recent advances, using next-generation sequencing, have shed light on the molecular pathogenesis of thyroid cancer. Constitutional activation of the mitogen-activated protein kinase pathway through RAS mutation, BRAF mutation, and/or fusions involving receptor tyrosine kinase (eg, (REarranged during Transfection) RET-PTC) plays a central role in tumorigenesis and opens doors to promising tyrosine kinase inhibitor therapy. Several molecular signatures, such as TERT promoter mutation and TP53 mutation, are associated with tumor progression. This article provides a concise and updated summary of the main genetic alterations in thyroid carcinoma.

Androgen receptor immunohistochemistry in salivary duct carcinoma: a retrospective study of 188 cases focusing on tumoral heterogeneity and temporal concordance.

Salivary duct carcinoma (SDC) is a high-grade salivary gland carcinoma that is associated with frequent metastasis and poor outcome. Androgen receptor (AR) immunoexpression in SDC is reported in 69% to 100% of SDC. Androgen deprivation therapy (ADT) has shown a response rate of 18% to 42% in SDC. Therefore, AR immunoexpression may serve as a diagnostic and predictive marker for ADT response in SDC. We investigated AR immunopositivity and staining pattern in a large retrospective cohort of 188 SDCs from 163 patients, including 22 paired primary and metastatic SDCs from the same patients, focusing specifically on staining heterogeneity and concordance. A control cohort of 61 non-SDC salivary gland carcinomas was also included. AR immunopositivity defined as ≥1% of tumor cell nuclear staining was found in 94% (177/188) of SDCs, including 95% of primary tumors, 100% of regional metastases, and 90% of distant metastases. Most of the cases (75%, 86/114) showed homogeneous and diffuse AR positivity. However, a subset (25%) exhibited focal or heterogeneous AR staining pattern. Although most metastases (21/22, 95%) had concordant AR expression with the primary tumors, one treatment-naïve tumor (5%) had complete loss of AR immunoexpression in the metastasis without detectable molecular alterations in AR or AR co-regulators. AR positive staining in non-SDC salivary carcinomas was infrequent (15%, 9/61), and mostly heterogeneous or focal. AR immunoexpression is highly prevalent in SDC, in both primary (94%) and metastatic tumors (93%). The cumulative AR immunopositivity rate in SDC is 90% based on data from the current study and previous literature. A small subset may show intratumoral AR heterogeneity and discordant AR expression in metastasis. AR immunoexpression may be seen in non-SDC salivary gland carcinomas but it is uncommon and usually focal.

Encapsulated follicular variant of papillary thyroid carcinoma/noninvasive follicular thyroid neoplasm with papillary-like nuclear features with Spindle Cell Metaplasia: Case report and review of literature.

Spindle cell lesions of the thyroid are rare overall, and span a wide clinical spectrum that ranges from spindle cell metaplasia (SCM1) to anaplastic carcinoma. Their differentiation is only seldom straightforward, and usually requires the integration of the clinical, histological and immunohistochemical data. Only a handful of publications have described cases of SCM in the thyroid and we add to that literature by reporting a unique case of encapsulated follicular variant of papillary thyroid carcinoma/noninvasive follicular thyroid neoplasm with papillary-like nuclear features with SCM. In addition, we review the literature on the relationship between SCM and different thyroid lesions, summarizing the morphological and immunohistochemical features that aid in its differentiation from more aggressive spindle cell proliferations.

Angiosarcoma of the hand associated with pseudoaneurysm.

Angiosarcoma is a rare malignancy of vascular endothelial origin. We describe a case of angiosarcoma of the hand initially histopathologically diagnosed as a pseudoaneurysm, emphasizing the diagnostic importance of radiological pathologic concordance. Here we highlight the distinctive imaging and the histopathologic features of angiosarcoma, invaluable to its accurate and timely diagnosis.

Renal Angiomyolipoma With Sarcoid Granulomas: Report of a Unique Case.

Angiomyolipoma is a mesenchymal neoplasm characterized by the coexpression of melanocytic and smooth muscle markers. Sarcoidosis is a multisystem disorder of unknown etiology, which presents with characteristic nonnecrotizing granulomas and rarely involves the kidney. The coexistence of renal sarcoidosis with renal neoplasms is exceedingly rare and was reported only with renal cell carcinoma. Renal sarcoidosis associated with a nonepithelial renal neoplasm, such as an angiomyolipoma has never been reported. We present the first reported case of sarcoid granulomas in a renal angiomyolipoma, including morphologic and immunohistochemical features.

A Rare Case of Sarcina ventriculi of the Stomach in an Asymptomatic Patient.

Sarcina ventriculi is a gram-positive coccus that grows in a tetrad arrangement in the stomach. In the past 35 years, less than 20 cases have been reported in the literature, and it has been associated with life-threatening complications such as emphysematous gastritis and perforation. Treatment of S ventriculi generally consists of proton pump inhibitors with or without adjuvant antibiotic therapy. We report the first ever case of S ventriculi, including the morphological and immunohistochemical features, occurring in an asymptomatic patient with a history of Helicobacter pylori gastric ulcers.