The Utility and Challenges of Histopathologic Evaluation in the Diagnosis of Non-malignant Skin Ulcers

Background: Histopathologic evaluation of cutaneous ulcers is indicated when the clinical diagnosis is not well established or when ulcers have not responded to standard of care. Many non-malignant skin ulcers lack specific histologic findings on biopsy and pose a diagnostic challenge. While the usefulness of skin biopsies to diagnose underlying malignancy in ulcerated lesions has been demonstrated in previous studies, their utility in the diagnosis of ulcers of other etiologies has not been reported.

Objectives: To evaluate the role of skin biopsies in the definitive diagnosis of non-malignant ulcers and to assess the level of inter-observer variability in the histological diagnosis.

Methods: The study was conducted with random histologic specimens of 45 patients between 2015 and 2018 that included skin biopsies of non-malignant ulcers such as vascular ulcers, autoimmune/inflammatory ulcers, infectious and dermatitis artefacta. The slides were independently reviewed by three dermatopathologists who were blinded to clinical information. These diagnoses were then compared to an independent clincopathologic consensus diagnosis.

Results: The leading diagnosis from each of the three raters agreed with the final clinical diagnosis, on average, for 29.6% of the cases (average pairwise kappa = 0.15). When asked to provide up to three differential diagnoses, any of the raters’ diagnoses and the final clinical diagnosis agreed on average for 25.2% of diagnoses compared (average pairwise kappa = 0.10).

Conclusions:  Skin biopsies alone are useful in the evaluation of non-malignant ulcers but not sufficient to establish a definitive diagnosis. The low concordance in the histopathologic diagnosis among dermatopathologist also reflects the real-world challenges when assessing these ulcers. Additional workup and clinicopathologic correlation is necessary in the assessment of non-malignant ulcers. Future research endeavors should explore alternative approaches to more efficiently diagnose non-malignant ulcers.