Myxoid Onychomatricoma with Unusual CD99 Expression: A Report of a Rare Case and Literature Review

Onychomatricoma (OM) is a rare, benign fibroepithelial tumor originating from the nail matrix, with different clinical and histological variants documented in existing studies. Myxoid OM is an even rarer subtype, characterized by a prominent fibromyxoid component in histopathology. We report a case of a 34-year-old male patient presenting with clinical manifestations consistent with typical OM. Histopathological examination revealed a biphasic tumor composed of an epithelial component and a prominent myxoid stroma, suggesting a diagnosis of myxoid OM. Notably, the tumor exhibited diffuse CD99 positivity, an extremely rare finding in OM. Histopathologically, myxoid OM shows considerable morphological overlap with superficial acral fibromyxoma (SAFM). Our case illustrates that CD99 positivity cannot serve as an absolute criterion to exclude OM; cautious interpretation of this marker is required to avoid diagnostic pitfalls in the differential diagnosis of these two entities. This case expands the immunophenotypic spectrum of myxoid OM and offers a valuable reference for its differential diagnosis. Furthermore, we include and provide a descriptive review to summarize the clinicopathological features and key differential diagnostic considerations of OM, with a focus on diagnostic pitfalls arising from rare histological variants and atypical immunophenotypes, to facilitate accurate differential diagnosis of subungual tumors.