Detection of GNAS mutations in intramuscular / cellular myxomas as diagnostic tool in the classification of myxoid soft tissue tumors

Abstract

Background: Intramuscular / cellular myxomas and low-grade myxofibrosarcomas are two different tumor entities with a significant histological overlap, especially if dealing with small biopsies. Despite the morphological similarities, they differ considerably in their biological behaviour. Intramuscular / cellular myxoma rarely shows signs of recurrence and never metastasizes, in contrast to myxofibrosarcoma that tends to recur more aggressively and to metastasize haematologically. Therefore, it is of great importance to distinguish these lesions - evaluation of GNAS mutation status could be of tremendous help.

Methods: We reviewed 13 cases with intramuscular / cellular myxomas. The 13 cases included 5 men and 8 women, aged from 33 to 71 years (mean age 55.5 years). Immunohistochemistry was performed as well as next generation sequencing. Ten cases were located in the lower extremities and three cases were located in the upper extremities. Two lesions were initially misdiagnosed as a low-grade myxofibrosarcoma.

Results: Performing next generation sequencing 12 out of 13 specimens showed a GNAS mutation.

Conclusions: Our findings demonstrate that GNAS mutations are more common in intramuscular / cellular myxomas, than had been reported in literature in the past. Next generation sequencing for determining GNAS mutation status on small biopsies or diagnostically challenging cases facilitates the diagnosis of intramuscular / cellular myxoma and separates this tumor entity from its mimics.

Keywords: GNAS mutation; Intramuscular / cellular myxoma; Myxofibrosarcoma; Soft tissue pathology.

Fig. 1

a Shows a hypocellular lesion with small bland cells, with oval nuclei and inconspicuous nucleoli and abundant myxoid stroma. b Embedded in the myxoid matrix are scattered blood vessels and small bland cells. c At the periphery of this lesion muscle fibers are split up by the mucoid matrix. d This lesion shows an increase in cellularity, accompanied by an increase in vascularity and collagenous stroma. e Area with spindled cells showing cytonuclear atypia. f Immunohistochemistry reveals focal CD34 expression

Fig. 2

a Low-grade myxofibrosarcoma shows an abundant myxoid matrix with prominent curvilinear vessels and a few spindled or stellate cells with eosinophilic cytoplasm. b Low-grade myxofibrosarcoma shows spindled cells with hyperchromatic nuclei and eosinophilic cytoplasm mitotic figures are hardly to find