September 2023 – Cytopathology

A 4 cm well-circumscribed intramuscular mass was incidentally identified within the right psoas muscle of a 68-year-old man who was undergoing workup for elevated PSA. This fusiform mass demonstrated a globular enhancement pattern and showed no obvious intralesional fat on T1 images. The patient denied any weakness or pain with flexion of the right hip. Orthopedic oncology was consulted, and targeted right psoas muscle mass biopsy (combined FNA/core biopsy) was performed.

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What is the best diagnosis based upon combined cytomorphology, core histomorphology, clinical setting and imaging findings? 

  • Metastatic mucinous adenocarcinoma of gastric origin
  • Intramuscular myxoma
  • Myxoid chondrosarcoma
  • Myxoid liposarcoma

The correct answer is ...

Intramuscular myxoma.

Papanicolaou-stained direct smears showed a paucicellular spindle cell proliferation with myxoid and finely fibrillar background material. The lesional cells showed low nuclear/cytoplasmic ratios and were cytologically bland with small, elongated nuclei and bipolar cytoplasmic processes. No significant pleomorphism, cellular atypia, or necrosis was evident. Hematoxylin and eosin-stained core biopsy histology slides showed findings identical to the smears, confirming a hypocellular and hypovascular lesion comprised of bland spindle cells lacking atypia and dispersed in variably fibrillar to myxoid backgrounds. Entrapped skeletal muscle fibers were focally noted. As in the cytology, characteristic long and slender cytoplasmic processes were noted. The combined clinical setting, imaging findings, cytomorphology, and core histomorphology were those of an intramuscular myxoma.

Intramuscular myxomas are most often diagnosed in middle-aged to older individuals (40–70 years) and are more common in females (M:F ratio: ~0.3:1). Most lesions are sporadic, but a minority are associated with fibrous dysplasia, which is most often polyostotic (Mazabraud syndrome). Clinical features are only occasionally sufficient to distinguish benign from malignant tumors of soft tissue. Most soft tissue sarcomas of the extremities and trunk present as a large, painless, incidentally noted mass that patients sometimes associate with an episode of injury. Conversely, some patients present with rapidly growing tumors that are occasionally painful, leading to a rapid medical opinion. The seemingly innocent presentation and the rarity of sarcomas often leads to their initial misinterpretation as benign conditions. All superficial soft tissue lesions measuring >5 cm, and all deep-seated lesions, are statistically likely to be sarcomas. Intramuscular myxoma is an exception to this rule. It is a benign but deep-seated soft tissue lesion. Classic intramuscular myxoma is typically a nonrecurrent tumor, whereas the cellular subtype has a small risk for local nondestructive recurrence. Malignant transformation does not occur.

The differential diagnosis of intramuscular myxoma is subdivided into three categories, including nonneoplastic conditions, benign neoplasms, and malignancies. Relevant nonneoplastic differentials include intramuscular ganglion cyst and focal mucinosis. Potential benign neoplastic conditions in the differential diagnosis include myxoid nerve sheath tumors, myxoid leiomyomata, and angiomyxomas. Malignant differential diagnostic entities include diseases such as malignant peripheral nerve sheath tumor, low-grade fibromyxoid sarcoma, myxoid chondrosarcoma, myxoid liposarcoma, and metastatic mucinous carcinomas.

The current case lacks the branching capillary vasculature and lipoblasts expected in myxoid liposarcoma. The myxoid backgrounds in this case should not be mistaken for epithelial mucin, and no floating neoplastic epithelial cells or cell groups are present, making the diagnosis of a metastatic mucinous carcinoma unlikely. Myxoid chondrosarcomas arising in extraskeletal locations would typically show polygonal or oval lesional cells arranged in clusters and cords and dispersed in myxoid backgrounds. The majority of intramuscular myxomas are associated with GNAS1 mutations, while different molecular/genetic findings would be expected in the various entities in the differential diagnosis.


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Mariana Usatii, M.D., C.M., M.S.

Fellow, Cytopathology 
Mayo Clinic

Charles Sturgis, M.D.

Consultant, Anatomic Pathology
Mayo Clinic
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

MCL Education

This post was developed by our Education and Technical Publications Team.