SOX9 Immunohistochemistry in the Distinction of Angiomatoid Fibrous Histiocytoma From Histologic Mimics: Diagnostic Utility and Pitfalls

Abstract

Angiomatoid fibrous histiocytoma (AFH) can be diagnostically difficult because of its varied histologic appearance and potential to occur at unusual sites. The identification of recurrent rearrangements (EWSR1-CREB1, EWSR1-ATF1, and FUS-ATF1) is a helpful diagnostic tool. Additional immunohistochemical markers in AFH could aid in restricting the differential diagnosis and selecting appropriate cases for targeted molecular studies. SOX9 is a transcription factor that is crucial for chondrogenesis and is expressed in neoplasms with chondroid differentiation, and other malignant bone and soft tissue tumors. Recently a role of EWS in regulation of SOX9 expression has been reported, the rearrangements typical of AFH may play a role in SOX9 expression. In this study, we analyzed SOX9 expression in 13 pediatric AFH with varying histology, and an additional 80 cases of other myofibroblastic or fibrohistiocytic lesions. SOX9 expression was present in 11 of 13 AFH, 2 of 53 dermatofibroma (1 aneurysmal and 1 cellular) and 1 calcifying aponeurotic fibroma. The remaining tumors were negative. SOX9 is selectively expressed in AFH and may be a useful maker in combination with desmin, CD99, CD68, and EMA in small biopsies, especially in cases with unusual morphologic features. SOX9 appears to be highly specific for AFH, being weakly expressed in a subset of aneurysmal dermatofibroma and absent in other myofibroblastic lesions, except calcifying aponeurotic fibroma. It should be used with caution when differentiating AFH from malignant neoplasms such as Ewing sarcoma.

Angiomatoid Fibrous Histiocytoma, A Great Mimicker – A Short Series of 3 Cases with EWSR1 Fusion

“…So, whenever a relatively wellcircumscribed fibrohistiocytic lesion is encountered in the extremities, a diagnosis of AFH should also be considered in the differential, keeping in mind its varied histological patterns and immunoreactivity. SOX9, a transcription factor involved in the embryogenesis of cartilage and gonadal tissue, has been expressed in 85% of AFH and is quite specific for it (18).…”

“…SOX9, a transcription factor involved in the embryogenesis of cartilage and gonadal tissue, has been expressed in 85% of AFH and is quite specific for it ( 18 ).…”

Distinct clinicopathological features of pulmonary primary angiomatoid fibrous histiocytoma: A report of four new cases and review of the literature

“…ALK expression was observed in 5/7 cases, 8,24 and it is a pitfall that PPAFH might be misdiagnosed to be a pulmonary ALKoma tumor, 25,26 especially inflammatory myofibroblastic tumor (IMTs) in the lung; on the other hand, it becomes one of the common IHC biomarkers for diagnosis of PPAFH. Recently, SOX9 and MUC4 was verified to be positive in AFH cases and suggested as useful markers for PPAFH differential diagnosis 27,28 …”