Intramuscular myxoma
Gross findings:
- Single round/globular well-circumscribed soft whitish soft tissue mass with thin fibrous capsule, measures around 5.5x4x4 cm in size.
- Cut surface appears as homogenous solid glistening/shiny with attached muscle tissue (marked with red arrow).
- Microcystic changes are not seen in this case, which are otherwise are not uncommon.
Histopathology:
- Circumscribed tumor with overall hypocellularity
- The interface between tumor and skeletal muscle is sharp and distinct but with irregularity and infiltrative appearance (Myxoid substance dissects the adjacent attached muscle tissue)
- Tumor shows very sparse stellate to bland small ovoid to spindle cells with poorly defined pale eosinophilic cytoplasm, in a abundant myxoid rich stroma
- Occasional thin walled blood vessels are seen. Not arborising type and not curvilinear type.
- No evidence of cellular areas, pleomorphism and mitotic activity.
Practical Points of Pathoclinics:
- Intramuscular myxoma is a benign mesenchymal neoplasm of uncertain histogenesis, arising within deep skeletal muscle. Intramuscular myxomas affect commonly middle and old age female. The thigh (most common site), pelvic girdle/buttock, shoulder, upper arm are the other common sites. It is a slow growing (months to years), solitary painless or dull ache painful mass.
- Most cases of intramuscular myxomas are sporadic. Presence of multiple lesions should be evaluated for coexistent fibrous dysplasia (polyostotic) of bone (Mazabraud syndrome). Multiple myxomas are common in the same anatomic region as fibrous dysplasia lesion. It can be associated with Albright syndrome (polyostotic fibrous dysplasia, café au lait spots on the skin, and endocrine abnormalities).
- Gross Features: Intramuscular myxomas are round ovoid lobulated circumscribed mass within the skeletal muscle or adjacent fascia. Its size is variable ranges from 5 cm to 10 cm. Cut surface has a soft, gelatinous, grey-white mucoid consistency with mucin filled microcysts. Though it is a circumscribed tumor, myxoid stroma infiltrating into surrounding skeletal muscle is commonly seen on close inspection.
- On microscopic examination, intramuscular myxoma is characterized by hypocellular, haphazard proliferation of uniform scattered, bland spindled and stellate-shaped cells with sparse and inconspicuous small vessels and numerous thin collagen fibers in an abundant myxoid matrix. Blood vessels are non-arborizing and thin capillary sized. Peripheral infiltration of skeletal muscle fibers (sometimes with atrophic changes) is frequently seen. Fat cells are commonly interspersed in the skeletal muscle. The spindled and stellate-shaped cells have a small bland nucleus and inconspicuous nucleoli and tapered, eosinophilic, ill-defined fibrillary cytoplasm. Cytoplasmic processes of cells are often continuous with thin collagen. Large thick collagen fibers are uncommon in myxomas but may be seen around the periphery of the lesion. The mitotic activity and necrosis are not seen. Microcystic spaces contain hyaluronic acid–rich, mucinous stroma. Small histiocytes and foamy vacuolated macrophages may be encountered in intramuscular myxoma. Mast cells are rarely seen in intramuscular myxomas.
- Cellular variant of intramuscular myxoma has focal or diffuse increased cellularity (at least more than 20% of total tumor areas), more collagen bands, and an increase in the number of vessels. The growth pattern of cellular areas is more organized rather than haphazard or pattern-less growth of conventional intramuscular myxoma. Cellular variants lack mitotic activity, cytologic atypia, branching vascular network, and necrosis characteristic of a sarcoma. Low-grade fibromyxoid sarcoma should always be considered before rendering a diagnosis of intramuscular cellular myxoma.
- Diagnostic issues with needle biopsies: Biopsies are commonly fragmented due to abundant myxoid stroma. Intramuscular myxomas can be readily recognized on small needle biopsies. However, the major pitfall is a misinterpretation of myxoma as a low-grade fibromyxoid sarcomas (LGFMS) and vice versa in small biopsies. Obtaining several cores with radiology co-relation may help to sort out issues in a good extent. Clinically both lesions are slow-growing and deep seated. The imaging commonly shows a relatively uniform myxoid lesion located in the muscular plane.
- Diagnostic issues with cytology: Cytology diagnosis of myxoma is more challenging. It is better to co-relate with clinical and radiology details, like rapidity of growth and exact location of tumor mass. Other important pre-operative clues rest on shoulder of radiologist are findings of adjacent tissue infiltration, microcystic changes and presence or absence of hemorrhage and necrotic areas. In short, pathologist want gross findings from radiologist, to achieve good conclusion pre-operatively!!!!
- Immunohistochemistry findings are not specific. In general, IHC work-up is not required, provided good sampling has been done to rule out abnormal cellular solid areas. IHC is generally needed in small biopsies to rule out myxoid rich numbers of soft tissues tumor and tumor like lesions. The negativity of S100 protein (myxoid rich schwannomas), desmin (myxoid changes in rhabdomyosarcomas), keratin, EMA and claudin-1 (perineuromas), MUC4 (LGFMS) is important. Intramuscular myxomas are positive for SMA with a variable degree. A diffuse and strong expression of CD34 is a sensitive but non-specific marker for intramuscular myxoma.
- Most of Intramuscular myxomas have activating missense mutations of GNAS1 in codon 201. This mutation is seen in both sporadic and Mazabraud syndrome associated cases.
- Low-Grade Fibromyxoid Sarcoma is the closest differential. The affecting age group is young and middle age. Grossly most often, LGFMS is a lobulated circumscribed tumor. Low power show nodularity with alternating myxoid and collagenous areas. In LGFMS, vascularity is usually more prominent in myxoid areas, in contrast to myxoma. Presence of EMA and MUC4 positivity on IHC and characteristic t(7;16) with FUS-CREB3L2 helpful in small biopsies, where distinction of LGFMS from cellular intramuscular myxoma is difficult.
- Another close differential is Low-Grade Myxofibrosarcoma, which is common in old and elderly individuals with preferential superficial (subcutis and skin) location rather than deep tissue. Microscopically myxofibrosarcoma has easily appreciable nuclear atypia and pleomorphism, at least in some areas. In contrast to myxomas, curvilinear vessels are striking and increase in number in low-grade myxofibrosarcoma.
- Any benign and malignant peripheral nerve sheath tumors can show a variable degree of myxoid changes. When such changes are extensive in schwannian tumor, it easily mimic myxoma and other myxoid rich low-grade sarcomas. Positivity of S100 protein in wavy tapered cells (schwannian cells) is of great help in such scenario. Positivity for EMA and claudin-1 is seen in perineurioma, which show whorled architecture on a routine blue-pink stain.
- Occasionally, foamy histiocytes and macrophages within the myxoid matrix may mimic lipoblasts of Myxoid Liposarcoma, especially to young individuals. On scrutiny, the absence of plexiform chicken-wire/arborizing thin-walled blood vessels and “true” vacuolated lipoblasts rule out myxoid liposarcoma. The Positive MDM2 stain help to confirm the liposarcoma. Take note that CD34 stains both lipoblasts and myxoma. Common characteristic t(12;16) with FUS-DDIT3 fusion may be utilised in required cases.
- Aggressive angiomyxoma has predilection for pelvic and perineum soft tissue of young-middle aged female. In contrast to intramuscular myxoma, aggressive angiomyxoma is uncapsulated tumor with high rate of local recurrence. More stress given on blood vessels, otherwise both are same. Here the blood vessels are medium to large in size, with some have thick and hyalinized wall.
- No significant prognostic difference between cellular and conventional types. Simple surgical excision is the ideal management. Recurrence of intramuscular myxoma after complete excision is extremely uncommon. Also, recurrence is very rare even after an incompletely excised tumour. Intramuscular myxoma has no malignant or metastatic potential.
References: Libbrecht L, Bempt IV, Schubert T, Sciot R, Galant C. Next generation sequencing for GNAS uncovers CD34 as a sensitive marker for intramuscular myxoma. Ann Diagn Pathol. 2019 Dec;43:151409. doi: 10.1016/j.anndiagpath.2019.151409. Epub 2019 Oct 5. PMID: 31726379.