Metastatic laryngeal large cell neuroendocrine carcinoma: A rare case of presentation and extreme tumor burden.

Large cell neuroendocrine carcinoma (LCNEC) of the larynx is an aggressive form of neuroendocrine carcinoma that affects smokers at an average age of 60 years. LCNEC is characterized by large cells with round to ovoid nuclei distributed in a trabecular or nested growth pattern. Previously, laryngeal LCNEC and atypical carcinoid tumors were considered identical; however, laryngeal LCNEC has been shown to have higher mitotic rates and worse prognosis, which has led to laryngeal LCNEC's being separated from atypical carcinoid and classified as a poorly differentiated neuroendocrine carcinoma in the most recent World Health Organization classification. We present a case of a 56-year-old female who presented with painful subcutaneous skin lesions that were diagnosed as metastatic carcinoma at an outside facility. Subsequent workup revealed a primary epiglottic lesion. Over the next 4 years, she continued to develop over 100 similar subcutaneous nodules. Additional workup confirmed neuroendocrine differentiation, thus clarifying the diagnosis of metastatic LCNEC. Review of literature has revealed only 1 reported case of LCNEC with skin metastasis. This is the first reported case in which skin metastasis was the initial presenting symptom; moreover, our case is unique with regard to the heavy metastatic burden to the skin.

NR3C2 microdeletions-an underrecognized cause of pseudohypoaldosteronism type 1A: a case report and literature review.

OBJECTIVES: Pseudohypoaldosteronism type 1A (PHA1A) is caused by haploinsufficiency of the mineralocorticoid receptor (MR). Heterozygous small insertions/deletions, transitions, and/or transversions within NR3C2 comprise the majority (85%-90%) of pathogenic copy number variants. Structural chromosomal abnormalities, contiguous gene deletion syndromes, and microdeletions are infrequent. We describe a neonate with PHA1A due to a novel NR3C2 microdeletion involving exons 1-2. METHODS: Literature review identified 39 individuals with PHA1A due to NR3C2 microdeletions. Transmission modality, variant description(s), testing method(s), exon(s) deleted, and affected functional domain(s) were characterized. RESULTS: In total, 40 individuals with NR3C2 microdeletions were described: 19 involved contiguous exons encoding a single MR domain; 21 involved contiguous exons encoding multiple MR domains. Transmission modality frequency was familial (65%), de novo (20%), or unknown (15%). Sequencing (Sanger or short-read next-generation) failed to detect microdeletions in 100% of tested individuals (n = 38). All were detected using deletion/duplication testing modalities. In 2 individuals, only microarray-based testing was performed; microdeletions were detected in both cases. CONCLUSION: Initial testing for PHA1A should rely on sequencing to detect the most common genetic alterations. Deletion/duplication analysis should be performed when initial testing is nondiagnostic. Most NR3C2 microdeletions are parentally transmitted, thus highlighting the importance of familial genetic testing and counseling.

Pheochromocytoma Multisystem Crisis and Masquerading Disseminated Histoplasmosis in a Neurofibromatosis Type 1 Patient With Bilateral Adrenal Tumors.

Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors that can occasionally progress to life-threatening disease, including a multisystem crisis. Patients with Neurofibromatosis type 1 (NF1) may develop pheochromocytomas, and the consequent chronic elevation of plasma catecholamine levels could further complicate various cardiovascular and pulmonary manifestations they may have. A 37-year-old African American female with NF1 presented with severe dyspnea, chills, myalgia, vomiting, and abdominal pain. Within several hours of hospital admission, she developed progressive agitation and died from circulatory collapse. An autopsy revealed disseminated histoplasmosis with necrotizing granulomatosis in her lungs, mediastinum, liver, and spleen, as well as bilateral pheochromocytomas with one tumor showing marked hemorrhage. Additionally, she had cardiac hypertrophy, myocarditis, pulmonary edema, apical bullae, features of pulmonary hypertension and interstitial fibrosis. Disseminated histoplasmosis caused by the fungal organism Histoplasma capsulatum is rarely described in immunocompetent individuals. This case is presented to illustrate that chronic hypercatecholaminemia caused by pheochromocytomas may potentially mask disseminated fungal infections which in turn could induce pheochromocytoma multisystem crisis in susceptible patients with neurofibromatosis.