Uterine smooth muscle tumors (USMT) are the most common neoplasms of the uterus, categorized into benign, uncertain malignant potential, and malignant subtypes based on histopathologic features, including mitotic index, presence of coagulative necrosis, and degree of nuclear atypia [1]. Although leiomyoma (LM) accounts for the vast majority of these tumors, leiomyosarcoma (LMS) contributes to a significant proportion of uterine cancer mortality, with an incidence of only 2–5 % of all uterine malignancies [2,3]. Smooth muscle tumor of uncertain malignant potential (STUMP) is an umbrella term given to tumors with atypical features without fulfilling the criteria of LMS. As the name suggests, this entity is associated with ambiguity regarding its clinical behavior and prognosis.

The clinical manifestations of these tumors are nonspecific, and the most reliable pre-operative diagnostic modality is magnetic resonance imaging (MRI) [4]. However, imaging findings can also be non-specific, overlapping with cellular, atypical, and degenerated leiomyomas [5,6].

Uterine leiomyomas and leiomyosarcomas represent opposite ends of the spectrum of uterine smooth muscle tumors. Histologically, most of the conventional leiomyomas reveal bland nuclei with low mitosis and no evidence of coagulative necrosis. However, diagnosis of leiomyoma variants, including leiomyoma with bizarre nuclei (LBN), mitotically active leiomyoma (MLM), and in some cases, distinction of ischemic versus coagulative necrosis, could be problematic. Smooth muscle tumors with diffuse significant nuclear atypia, unequivocal coagulative necrosis, and more than 10 mitosis per 10 HPF or two of the described criteria are easily diagnosed as leiomyosarcoma. But the diagnosis of leiomyosarcoma variants, including epithelioid or myxoid subtypes, could be difficult [7,8]. Leiomyomas with fumarate hydratase deficiency (FH-LM) are a recently recognized entity, typically affecting a younger demographic and arising in either syndromic or sporadic forms. The histopathological features of FH-LM include staghorn vessels, alveolar edema, scattered bizarre nuclei, eosinophilic cytoplasmic inclusions, and large eosinophilic nucleoli surrounded by a perinuclear halo [9,10]. These features may result in misdiagnosis as STUMP or LMS. Considering the overlapping morphological features, the use of ancillary studies, including an IHC study, is an area of interest in previous research [7].

Immunohistochemical differentiation of uterine LMS from its benign counterpart is limited to markers of cellular differentiation and proliferation [11,12]. The most common marker for distinguishing suspicious and borderline cases is Ki-67 [13]. Additionally, the overexpression of P53 and P16 has been reported in leiomyosarcomas, although their use in clinical practice is not recommended due to limited studies [[14], [15], [16]]. Recently, the Duchenne muscular dystrophy gene (DMD) mutation has been reported in approximately 63 % of high-grade myogenic cancers, including leiomyosarcoma, rhabdomyosarcoma, and gastrointestinal stromal tumor (GIST) [17,18]. DMD expression in the benign counterparts and normal tissue of these tumors, and its inactivation in 63–100 % of their metastases, confirmed its role as a tumor suppressor and possibly an anti-metastatic factor. The DMD gene encodes dystrophin, a protein primarily expressed in skeletal and cardiac muscle cells, as well as in some neurons. This protein connects the cytoplasmic cytoskeleton to the extracellular matrix, thereby contributing to the structural stability of muscle cells. Some studies suggest that dystrophin may play a role in cell division, adhesion, and metastasis. Therefore, changes in dystrophin expression or function can alter cell behavior, including increased invasion, metastasis, and resistance to treatment [[19], [20], [21], [22]]. Similarly, decreased or lost dystrophin expression is observed in LMS, correlating with the tumor's aggressive and metastatic behavior. On the other hand, dystrophin expression is preserved in normal myometrium and LMs [8,23].

Thus far, studies on the pattern of dystrophin expression in USMTs remain limited. We designed this study to evaluate and compare dystrophin expression in a wide range of uterine smooth muscle tumors to determine its value in diagnosing suspicious cases and enhancing the sensitivity and specificity of immunohistochemical panels for USMTs.