Date of Award

January 2026

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Sean R. Christensen

Abstract

Background:Cutaneous sarcomas exhibit a broad spectrum of clinical behavior, ranging from indolent tumors to lesions with significant metastatic potential. In atypical fibroxanthoma, pleomorphic dermal sarcoma, and cutaneous leiomyosarcoma predictors of recurrence and metastasis are not always apparent at initial diagnosis. Improved understanding of clinicopathologic features associated with adverse outcomes is needed to guide risk stratification and management.

Objectives:To identify clinical and pathologic factors associated with poor outcomes in AFX, PDS, and cutaneous leiomyosarcoma and to evaluate the relationship between initial biopsy, definitive excision findings, and clinical outcomes.

Methods:This thesis comprises three retrospective cohort studies conducted at a single academic institution. The first study evaluated predictors of major poor outcomes, defined as metastasis and or disease-specific death, in 126 patients with AFX or PDS. The second study assessed diagnostic concordance between initial biopsy and final excisional pathology and examined the association between diagnostic reclassification and clinical outcomes. The final study evaluated factors associated with recurrence and metastasis in 43 patients with primary cutaneous leiomyosarcoma.

Results:In AFX and PDS, depth of invasion was the strongest predictor of major poor outcomes. Tumors confined to the dermis demonstrated an indolent course. In contrast, invasion beyond the dermis was associated with significantly increased risks of recurrence, metastasis, and disease-specific death. Immunosuppression independently increased the risk of adverse outcomes. Tumor diameter lost significance after adjustment for depth of invasion. Diagnostic reclassification between biopsy and excision was common, and tumors upstaged from AFX or indeterminate diagnoses on biopsy to PDS on excision experienced significantly higher rates of major poor outcomes. Among cases with a final diagnosis of PDS, incorrect initial biopsy diagnoses were associated with worse outcomes than uncertain diagnoses. In cutaneous leiomyosarcoma, adverse outcomes occurred exclusively in tumors with subcutaneous or deeper invasion and were associated with higher histologic grade and incomplete initial excision.

Conclusions:Across atypical fibroxanthoma, pleomorphic dermal sarcoma, and cutaneous leiomyosarcoma, depth of invasion emerged as the most consistent predictor of recurrence, metastasis, and disease-specific death. These findings highlight the limitations of biopsy-based risk assessment in tumors where depth defines prognosis and demonstrates the importance of complete excision for accurate classification and risk stratification. Improved recognition of high-risk features may inform surgical management, surveillance strategies, and patient counseling in cutaneous sarcomas.

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This is an Open Access Thesis.

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