Uveal melanoma is the most common intraocular malignancy and has a poor prognosis compared to other melanoma subtypes with a median overall survival of 6–10 months. With immune checkpoint inhibitor therapy, either PD-1 inhibitor alone or combination ipilimumab/nivolumab (anti-CTLA-4/anti-PD-1), responses are rare and often not durable. We present a case report of a now 66-year-old woman with diffuse metastatic uveal melanoma previously treated with a combination of ipilimumab/nivolumab, followed by maintenance nivolumab. Almost complete resolution of all sites of metastatic disease was observed except for one liver metastasis which regressed partially on immunotherapy. Notably, the patient had a significantly elevated BMI and developed widespread vitiligo on treatment. Whole-genome and transcriptome analysis was performed on the residual liver biopsy and molecular markers that may have contributed to the exceptional response were investigated. Several alterations were observed in genes involved in T-cell responses. Estimates of tumour infiltrating immune cells indicated a high level of plasma cells compared to other uveal melanoma cases, a finding previously associated with indolent disease. The patient also carried several germline SNPs that may have contributed to her treatment response as well as widespread vitiligo. Whole-genome and transcriptome sequencing have provided insight into potential molecular underpinnings of an exceptional treatment response in a tumour type typically associated with poor prognosis. Immunological findings suggest a role for plasma cells in the tumour microenvironment. Elevated BMI and the development of vitiligo may be clinically relevant factors for predicting response to immune checkpoint inhibitor therapy, warranting further studies in patients with uveal melanoma.

BackgroundMarijuana use has become more common since its legalization, as have reports of marijuana-associated spontaneous pneumomediastinum. Non-spontaneous causes such as esophageal perforation are often ruled out on presentation due to the severe consequences of untreated disease. Here we seek to characterize the presentation of marijuana-associated spontaneous pneumomediastinum and explore whether esophageal imaging is necessary in the setting of an often benign course and rising healthcare costs.Materials and MethodsRetrospective review was performed for all 18–55 year old patients evaluated at a tertiary care hospital between 1/1/2008 and 12/31/2018 for pneumomediastinum. Iatrogenic and traumatic causes were excluded. Patients were divided into marijuana and control groups.Results30 patients met criteria, with 13 patients in the marijuana group. The most common presenting symptoms were chest pain/discomfort and shortness of breath. Other symptoms included neck/throat pain, wheezing, and back pain. Emesis was more common in the control group but cough was equally prevalent. Leukocytosis was present in most patients. Four out of eight of computed tomography esophagarams in the control group showed a leak requiring intervention, while only one out of five in the marijuana group showed even a possible subtle extravasation of contrast but this patient ultimately was managed conservatively given the clinical picture. All standard esophagrams were negative. All marijuana patients were managed without intervention.DiscussionMarijuana-associated spontaneous pneumomediastinum appears to have a more benign clinical course compared to non-spontaneous pneumomediastinum. Esophageal imaging did not change management for any marijuana cases. Perhaps such imaging could be deferred if clinical presentation of pneumomediastinum in the setting of marijuana use is not suggestive of esophageal perforation. Further research into this area is certainly worth pursuing.

Crohn's disease typically affects the small bowel and colon, and it predisposes to an increased risk of various cancers, including small bowel, colorectal, and lymphoma. Ileostomy adenocarcinoma, although technically a cancer of the small bowel despite any skin involvement, is often thought of as a distinct and separate entity from small bowel adenocarcinoma given its different disease course and prognosis. Furthermore, in Crohn's disease, it is an uncommon complication; to date, there are only five reported cases in the literature.Here, we present a 73-year-old female who was diagnosed with adenocarcinoma of her ileostomy approximately 44 years after her last ostomy revision. Her medical history included Crohn's disease, which was in remission at the time of presentation, diabetes, anemia, asthma, and chronic kidney disease stage 3. She was initially diagnosed with Crohn's disease in 1969. She subsequently underwent proctocolectomy with end ileostomy for acute Crohn's colitis. Afterward she underwent approximately 30 additional surgical procedures due to subsequent infection, wound dehiscence, and hernias. Her ileostomy required two revisions, with the most recent performed for stoma necrosis in 1977.She first started to notice peristomal changes in 2008. These persisted despite topical therapies. In 2020, she noted that she was having difficulty pouching her ostomy, initially thought to be due to a skin fold. In 2021, she presented for evaluation after developing purulent drainage from a peristomal skin lesion, followed by development of multiple nodules (Figure 1). An incisional biopsy was performed in the office, which demonstrated moderately differentiated adenocarcinoma, gastrointestinal in origin. Staging workup revealed no evidence of metastatic disease. She underwent en bloc resection of the ileostomy with relocation of the ostomy. Final pathology demonstrated moderately to poorly differentiated adenocarcinoma with extensive invasion of the surrounding soft tissue and the skin at the stoma site. Margins were negative, but no lymph nodes were identified in the specimen. She was discussed in a multidisciplinary group and referred for chemotherapy.