Cutaneous Vascular Neoplasms of Uncertain Biological Behavior

Neoplasms of uncertain biological behavior present physicians with a genuine conundrum in practice. Cutaneous vascular neoplasms within this category are exceedingly rare, possessing significant gaps and uncertainty in many facets of clinical practice. Firstly, lesions were selected for review based on their categorization as indeterminate behavior, indicating the potential for local recurrence and rarely metastasize. After identification of the target lesions, a comprehensive review of the literature using national databases produced several landmark studies and case series regarding these neoplasms. Limiting the review to only cutaneous limited tumors narrowed the pool of studies; however, quite a large sum of papers remained. Examination of each paper yielded beneficial results on diagnosing, effective treatments, follow-up findings, and prognosis for each indeterminate lesion discussed. Overall, the literature search combined the molecular, histologic, immunohistochemical, surgical strategies to develop an up-to-date and comprehensive framework to guide physicians when encountering such lesions. The tumors reviewed include: kaposiform hemangioendothelioma, endovascular papillary angioendothelioma, pseudomyogenic hemangioendothelioma, retiform hemangioendothelioma, epithelioid hemangioendothelioma, and composite hemangioendothelioma.

A novel SERPINE1-FOSB fusion gene in a case of pseudomyogenic hemangioendothelioma results in activation of intact FOSB and the PI3K-AKT-mTOR signaling pathway and responsiveness to sirolimus

Pseudomyogenic hemangioendothelioma (PHE) is an extremely rare disease that affects mainly the young and more men than women. PHE are multicentric, locally aggressive, have low metastatic potential, and affect multiple tissue planes. Genetic aberrations are frequently detected in PHE and may play important roles in the occurrence, development, and treatment of this disease. In this study, we report a case of PHE with a novel SERPINE1-FOSB fusion gene. The fusion introduced a strong promoter near the coding region of FOSB, resulting in overexpression of intact FOSB. Immunohistochemical analysis showed overexpression of pAKT and mTOR in tumor cells, suggesting activation of the PI3K-AKT-mTOR signaling pathway. The patient responded well to targeted therapy with sirolimus, an mTOR inhibitor. Our study correlated dysregulation of a specific signaling pathway and the effectiveness of a targeted therapy to a specific genetic aberration. This information may be useful for future investigations of targeted therapeutics and provide a potential predictive biomarker for therapeutic effectiveness in cases of PHE with this genetic aberration.

Unclassified mesenchymal sarcoma with NTRK1-KHDRBS1 gene fusion: a case report of long-term tumor-free survival with crizotinib treatment

Background Mesenchymal sarcomas are tumors that originate from mesenchymal tissue. Most mesenchymal sarcomas can be accurately classified, but some are unclassifiable in clinical practice. Molecular detection methods enable patients to benefit from molecular-targeted therapies for many cancers, including lung, breast, and bowel cancers. Further, even unclassified tumors can have therapeutic targets. NTRK gene fusions are sporadic genetic alterations that occur across tumor entities. If NTRK gene fusions are detected, TRK inhibitors can be used regardless of the tumor entity. Case presentation This report describes a case with an unclassifiable mesenchymal sarcoma carrying a neurotrophic tyrosine receptor kinase NTRK1-KHDRBS1 gene fusion that was diagnosed and treated at multiple hospitals. Diagnostic work-up included pathological and immunohistochemical analysis, which excluded angiosarcoma, dendritic cell sarcoma, and pseudomyogenic hemangioendothelioma. The patient achieved a long-term survival without tumor relapse after treatment with crizotinib. Conclusions This case will be of significant interest to pathologists because, despite the tumor being unclassified, a molecular target was identified. Although the FDA does not currently approve crizotinib for treatment of patients harboring NTRK gene fusions, this case provides new insights for diagnosis and treatment of mesenchymal sarcomas with NTRK1 gene translocations. Similar to ALKomas, which can be successfully treated using NTRK molecular-targeted therapy, tumors with NTRK gene translocations can be classified as NTRKomas, even when they occur at different organ sites, and with varying histological morphologies, and immunophenotypes.