A new Cylindromatosis (CYLD) gene mutation in a case of Brooke-Spiegler syndrome masquerading as basal cell carcinoma of the eyelids.

A 70-year-old woman sought treatment for confluent flesh-colored papules on all 4 eyelids. Sixteen family members were reported to have similar lesions involving the face and scalp. Initial histopathologic examination of the lesions was interpreted as basal cell carcinoma, but on further review, the lesions were deemed to be consistent with trichoepitheliomas as seen in Brooke-Spiegler syndrome. Cylindromatosis gene mutation analysis confirmed this unique presentation of Brooke-Spiegler syndrome, and revealed a previously unidentified mutation in the cylindromatosis gene.

Small cell carcinoma presenting as a biatrial mass with obstructive physiology: a case report.

BACKGROUND: Small cell carcinoma is a highly aggressive and often fatal cancer that most commonly arises in the lung, although it can occasionally arise from other sites, such as the gastrointestinal tract, prostate or cervix. Cardiac involvement, however, is extremely uncommon and therefore has been poorly documented in the literature. CASE PRESENTATION: We describe a rare case of a 31-year-old male with small cell carcinoma presenting as a massive, 15-cm cardiac tumor invading the bilateral atria, interatrial septum, and pericardium without an apparent primary malignancy on PET CT and cardiac MRI. With extensive tissue necrosis, traditional methods of obtaining a right atrial endomyocardial biopsy via internal jugular venous access failed and a diagnosis was made via endoscopic ultrasound guided transesophageal fine needle aspiration of the left atrial mass. Due to the extensive tumor invasion, the patient was not a suitable candidate for surgical resection, debulking, or heart transplant. The patient was treated with etoposide, carboplatin, atezolizumab, and radiation therapy with initial monitoring in the intensive care unit due to concern that tumor lysis may cause rapid cardiac decompensation. Unfortunately, 4 months after chemoradiation therapy, the malignancy progressed and the patient passed away 6 months after the initial diagnosis. CONCLUSION: We describe a rare occurrence of small cell carcinoma presenting as a massive cardiac tumor without apparent primary malignancy. This case demonstrates useful alternative diagnostic strategies and treatment considerations for patients presenting with a rare cardiac mass.

Prevalence of Homologous Recombination Pathway Gene Mutations in Melanoma: Rationale for a New Targeted Therapeutic Approach.

Homologous recombination DNA damage repair (HR-DDR) deficient patients with various solid tumors have been treated with PARP inhibitors. However, the clinical characteristics of patients with melanoma who have HR-DDR gene mutations and the consequences of PARP inhibition are poorly understood. We compared the commercially available next-generation sequencing data from 84 patients with melanomas from our institution with a dataset of 1,986 patients as well as 1,088 patients profiled in cBioportal. In total, 21.4% of patients had ≥1 functional HR-DDR mutation, most commonly involving BRCA1, ARID1A, ATM, ATR, and FANCA. Concurrent NF1, BRAF, and NRAS mutations were found in 39%, 39%, and 22% of cases, respectively. HR-DDR gene mutation was associated with high tumor mutational burden and clinical response to checkpoint blockade. A higher prevalence of HR-DDR mutations was observed in the datasets from Foundation Medicine (Cambridge, CA) and those from the Cancer Genome Atlas. Treatment of HR-DDR‒mutated patient-derived xenograft models of melanoma with PARP inhibitor produced significant antitumor activity in vivo and was associated with increased apoptotic activity. RNA sequencing analysis of PARP inhibitor-treated tumors indicated alterations in the pathways involving extracellular matrix remodeling, cell adhesion, and cell-cycle progression. Melanomas with HR-DDR mutations represent a unique subset, which is more likely to benefit from checkpoint blockade and may be targeted with PARP inhibitor.

Intra-lacrimal gland cavernous hemangioma.

Orbital cavernous hemangioma usually has a typical clinical and imagery pattern. We present a patient with an enlarged lacrimal gland due to an intra-gland cavernous hemangioma.

Alteration of gene expression in normal-appearing colon mucosa of APC(min) mice and human cancer patients.

The expression of many genes is altered in colon cancer, but the roles of these genes in carcinogenesis are unclear. Using real-time quantitative PCR, we demonstrated that several genes previously implicated in human colon cancer undergo altered expression in the APC(min) mouse adenomatous polyp, a precursor of cancer, as well as in normal-appearing surrounding mucosa. The five genes that were most highly up-regulated in mouse polyp were also significantly up-regulated in polyp-free colon mucosa. Similar changes occurred in morphologically normal mucosa of surgical sections taken from human cancer patients, frequently extending to the margins. Thus, morphologically normal colon mucosa in APC(min) mice and in human cancer patients is not metabolically normal. Altered gene expression in this tissue does not appear to result from a field effect because there was no correlation between extent of altered regulation and distance from polyp or tumor. Our data suggest that alterations of expression levels of these genes may be an early event in carcinogenesis and a marker of risk for the development of colon cancer.

Multiple significant bortezomib-related toxicities in one patient: case report and literature review.

Bortezomib has shown significant efficacy in the treatment of patients with relapsed multiple myeloma (MM) and is generally well tolerated. We report a 65-year-old male patient undergoing bortezomib therapy for MM who, with the addition of liposomal doxorubicin, presented with severe paralytic ileus, peripheral neuropathy, pruritic rash, and testicular pain. Each of these toxicities was temporally related to the bortezomib-based therapy and the administration of concomitant liposomal doxorubicin. Herein, we discuss the patient's course and briefly review the literature on these bortezomib combination-related toxicities.

Cystic orbital metastasis from endometrial carcinoma.

PURPOSE: To describe a rare orbital metastasis with atypical presentation. DESIGN AND METHODS: Retrospective case report. RESULTS: The patient presented with a rapid onset of a cystic orbital lesion after a presumptive diagnosis of endometrial carcinoma that had been completely excised eight months ago. This was the initial presentation of widespread metastasis. CONCLUSIONS: Endometrial carcinomas can metastasize to the orbit and may have a very atypical presentation.