Management of intramuscular melanoma metastases to the psoas.

We detail a case of a woman in her 40s with isolated melanoma skeletal muscle metastasis (MSMM) to the right psoas muscle. This patient underwent R0 surgical resection through a novel pelvic approach. She received subsequent adjuvant immunotherapy with Braftovi/Mektov along with adjuvant radiation. She is currently disease free at 9 months post surgery. Here, we describe our novel surgical approach including description of the tumour pathology. We explain our multidisciplinary management of MSMM consisting of a multidisciplinary surgical approach by surgical oncology, gynecological oncology and urology as well as multidisciplinary medical management by oncology, radiation oncology and pathology. Finally, we discuss best current options for therapeutic management.

Pan-cancer Genomic Analysis of AXL Mutations Reveals a Novel, Recurrent, Functionally Activating AXL W451C Alteration Specific to Myxofibrosarcoma.

Myxofibrosarcoma (MFS) is a common soft tissue sarcoma of the elderly that typically shows low tumor mutational burden, with mutations in TP53 and in genes associated with cell cycle checkpoints ( RB1 , CDKN2A ). Unfortunately, no alterations or markers specific to MFS have been identified and, as a consequence, there are no effective targeted therapies. The receptor tyrosine kinase AXL, which drives cellular proliferation, is targetable by new antibody-based therapeutics. Expression of AXL messenger RNA is elevated in a variety of sarcoma types, with the highest levels reported in MFS, but the pathogenic significance of this finding remains unknown. To assess a role for AXL abnormalities in MFS, we undertook a search for AXL genomic alterations in a comprehensive genomic profiling database of 463,546 unique tumors (including 19,879 sarcomas, of which 315 were MFS) interrogated by targeted next-generation DNA and/or RNA sequencing. Notably, the only genomic alterations recurrent in a specific sarcoma subtype were AXL W451C (n = 8) and AXL W450C (n = 2) mutations. The tumors involved predominantly older adults (age: 44 to 81 [median: 72] y) and histologically showed epithelioid and spindle-shaped cells in a variably myxoid stroma, with 6 cases diagnosed as MFS, 3 as undifferentiated pleomorphic sarcoma (UPS), and 1 as low-grade sarcoma. The AXL W451C mutation was not identified in any non-sarcoma malignancy. A review of publicly available data sets revealed a single AXL W451C-mutant case of UPS that clustered with MFS/UPS by methylation profiling. Functional studies revealed a novel activation mechanism: the W451C mutation causes abnormal unregulated dimerization of the AXL receptor tyrosine kinase through disulfide bond formation between pairs of mutant proteins expressing ectopic cysteine residues. This dimerization triggers AXL autophosphorylation and activation of downstream ERK signaling. We further report sarcomas of diverse histologic subtypes with AXL gene amplifications, with the highest frequency of amplification identified in MFS cases without the W451C mutation. In summary, the activating AXL W451C mutation appears highly specific to MFS, with a novel mechanism to drive unregulated signaling. Moreover, AXL gene amplifications and messenger RNA overexpression are far more frequent in MFS than in other sarcoma subtypes. We conclude that these aberrations in AXL are distinct features of MFS and may aid diagnosis, as well as the selection of available targeted therapies.

The autopsy is not dead: ongoing relevance of the autopsy

ABSTRACT Background Autopsy requests have been trending downward for a variety of factors. There are differences between pre- and postmortem diagnoses. Autopsies remain a tool for education, public health research, quality control, and closure for families. Objective We report two cases that illustrate the utility of autopsy for uncovering contributing factors in the death of these patients and highlight their ongoing importance. Design Clinical and autopsy investigation of two individuals and illustration of the importance of autopsy findings which, had they been diagnosed premortem, could have changed the outcome. Cases were evaluated using the Goldman criteria for discrepancies between premortem clinical diagnoses and postmortem autopsy findings. Results In the first case, the patient had been previously admitted due to a non-ST elevation myocardial infarction months before the fatal event. The autopsy showed an undiagnosed clear cell carcinoma of the ovary. She expired due to a massive myocardial infarction secondary to neoplasm induced hypercoagulable state. The degree of pre-mortem/postmortem diagnostic discrepancy makes this a Goldman Class I error. In the second case, the patient presented to the emergency department with symptoms of Guillain-Barré Syndrome (GBS), for which he was treated. Abdominal masses were discovered; however, the patient decompensated before workup was completed. A high-grade B-cell lymphoma was confirmed but would not have altered the outcome, making this a Goldman class II error. Conclusions The autopsy remains a relevant and necessary tool for physicians and society. It assists in the establishment of diagnoses, measurement of treatment quality, the providence of public health metrics, and closure to the survivors.