PAX7 Is a Sensitive Marker of Skeletal Muscle Differentiation in Rhabdomyosarcoma and Tumors With Rhabdomyosarcomatous Differentiation in the Female Genital Tract

Abstract

In the female genital tract, rhabdomyosarcoma may occur in “pure” form or as a heterologous constituent of a biphasic neoplasm such as carcinosarcoma or adenosarcoma. Discriminating rhabdomyosarcoma from its histologic mimics relies on confirmation of skeletal muscle differentiation by morphology or immunohistochemistry (IHC), which can be challenging to interpret in some cases owing to limited expression. PAX7, a transcription factor expressed in mammalian muscle progenitor cells, has been reported in up to 86% of soft tissue rhabdomyosarcomas by IHC. To determine whether PAX7 IHC could augment current approaches to identify rhabdomyosarcoma in gynecologic malignancies, we assessed PAX7, myogenin, and MyoD1 IHC on whole tissue sections from 100 gynecologic tumors: 50 with rhabdomyosarcomatous differentiation and 50 with features mimicking rhabdomyosarcoma. PAX7 expression was present in 96% (48/50) of gynecologic tumors with rhabdomyosarcomatous differentiation and was absent in all rhabdomyosarcoma mimics; it was more diffusely expressed than myogenin in 16 cases and was positive in a greater percentage of tumor cells in 28 cases. PAX7 and myogenin were typically coexpressed, and no rhabdomyosarcoma exhibited complete absence of both markers; however, 2 myogenin-negative tumors were PAX7-postive. Morphologically, PAX7 localized to the nuclei of primitive-appearing cells, whereas myogenin was observed in maturing rhabdomyoblasts including strap cells. Our findings highlight the utility of PAX7 as a complementary diagnostic marker of rhabdomyosarcomatous differentiation in gynecologic tumors. PAX7 should be used in combination with other markers of skeletal muscle differentiation, namely myogenin, and may be particularly helpful in cases where myogenin and/or MyoD1 expression is limited.

DICER1-associated Tumors in the Female Genital Tract: Molecular Basis, Clinicopathologic Features, and Differential Diagnosis

“…The tumor cells are positive to a varying degree for markers of skeletal muscle differentiation including desmin, myogenin, MyoD1, and PAX7 and generally lack expression of hormone receptors. 54,56,58,60 ERMS has a generally favorable prognosis and among the rhabdomyosarcoma family, ERMS has the best prognosis. 61 The overall survival rate is ∼70% at 5 years and only 10% of patients die of this disease.…”

“…Immunohistochemical stains can be helpful in confirming the diagnosis. The tumor cells are positive to a varying degree for markers of skeletal muscle differentiation including desmin, myogenin, MyoD1, and PAX7 and generally lack expression of hormone receptors 54,56,58,60…”

Spindle cell rhabdomyosarcomas: With TFCP2 rearrangements, and novel EWSR1::ZBTB41 and PLOD2::RBM6 gene fusions. A study of five cases and review of the literature

“…1 Most recently, PAX7 has been described as a sensitive IHC marker for skeletal muscle differentiation. 2 RMS are divided into four basic types according to the latest 5th edition of the WHO classification of soft tissue and bone tumours, 3 which includes embryonal RMS, alveolar RMS, pleomorphic RMS, and spindle cell/sclerosing RMS (SS-RMS). 4 SS-RMS was first described as a histological subtype of embryonal RMS, but since the 2013 the WHO classification of soft tissue and bone tumours, they have been classified separately.…”

“…Immunohistochemistry (IHC) using the myogenic nuclear regulatory proteins MyoD1 (MYF3) and myogenin (MYF4) with variable desmin expression across RMS subtypes is essential to achieve a diagnosis of RMS 1 . Most recently, PAX7 has been described as a sensitive IHC marker for skeletal muscle differentiation 2 …”