Low-grade myofibroblastic sarcoma (LGMS) is a subtype of the malignant sarcomas. As it is currently recognized, LGMS was first described as a rare, atypical myofibroblastic tumor (i.e. a tumor consisting of cells with the microscopic features of fibroblasts and smooth muscle cells) by Mentzel et al. in 1998. Myofibroblastic sarcomas had been divided into low-grade myofibroblastic sarcomas, intermediate‐grade myofibroblasic sarcomas, i.e. IGMS, and high‐grade myofibroblasic sarcomas, i.e. HGMS (also termed undifferentiated pleomorphic sarcoma and pleomorphic myofibrosarcoma [and formerly termed malignant fibrous histiocytoma]) based on their microscopic morphological, immunophenotypic, and malignancy features. LGMS and IGMS are now classified together by the World Health Organization (WHO), 2020, in the category of intermediate (rarely metastasizing) fibroblastic and myofibroblastic tumors. WHO, 2020, classifies HGMS (preferred name: undifferentiated pleomorphic sarcoma) as a soft tissue tumor in the category of tumors of uncertain differentiation. This article follows the WHO classification: here, LGMS includes IGMS but not HGMS which is a more aggressive and metastasizing tumor than LGMS and consists of cells of uncertain origin. LGMS tumors are typically painless lesions that develop in: 1) the subcutaneous tissues, i.e. the lowermost layer of the skin; 2) submucosa, i.e. the thin layer of tissue lying just below the mucous membranes that line passageways such as the gastrointestinal, respiratory, genitourinary tracts; 3) muscles; and 4) bones. They most often develop in middle-aged adults (average: 40 years old) but have been diagnosed in all age-groups. These tumors often recur at the sites of their surgical removal and may metastasize to nearby lymph nodes and distant tissues. LGMS's are commonly treated by surgical removal of the tumor along with all its cells, which if not removed increase the probability that the tumor will recur at the site of its removal. LGMS tumors typically show little or no sensitivity to radiotherapy and chemotherapy treatments.
Presentation LGMS present as single tumors that ranged in size from 0.4 to 24.0 cm in three literature review studies. In another study, 103 individuals diagnosed with LGMS were aged 2–75 years (median: 43 years) with 12.6% < 18 years, 65.1% 18–60 years, and 22.3% >60 years old. Eighty-two percent of their LGMS tumors were located in soft tissues (28.2% in mucous membranes, 21.8% in muscle, 19.2% in skin, and 12.9% in other soft tissues) and 18% were in bone. Overall, 51.5% of their tumors were in the head and neck areas (most commonly the tongue, followed by the larynx, gums, mandible, face, skull, and ear canal), 25.2% were in the trunk, and 23.3% were in an arm or leg. Bone tumors were located in the femurs, mandible, maxilla, tibias, or in one case each the hard palate and sacrum. In other reports, the tumors occurred in the oral mucosa, lip, groin, small intestine, greater omentum or lesser omentum (which omentum not defined), heart, eye socket (in an 11 month old infant), and chest wall/breast. While typically presenting as slow growing, painless masses, some individuals have presented with increasingly painful subcutaneous or submucosal masses (16 of 50 individuals reported pain in one retrospective study). Rare cases of submucosal LGMS tumors have presented with more serious symptoms such as partial bowel obstructions due to intrabdominal LGMS tumors, shortness of breath and palpitations due to a LGMS tumor in the heart, difficulty in swallowing and breathing due to a laryngeal LGMS tumor, and abdominal pain due to a pancreas LGMS tumor. A study of 96 individuals presenting for the first time with LGMS found that 51.0% had local disease, 25.0% had regional disease, 15.6% had metastases to the local lymph nodes, and 8.3% had distant metastases. (In the study 103 individuals, the distant metastasis rate was 4.4%.) Metastasis have been reported to develop in various sites including the lungs, pleura, lymph nodes, bones, thoracic cavity, abdominal cavity, peritoneum, heart, brain, and spinal cord.
Pathology Microscopic histopathological analyses of hematoxylin and eosin stained LGMS tissues generally show bundles of atypical spindle-shaped cells in a variably hyalinized (i.e. glassy appearing) stromal background containing collagen fibers. The tumors are not encapsulated and commonly infiltrate adjacent fibrous, fat, or skeletal muscle tissues. (The tumor's spindle-shaped cells may infiltrate between individual skeletal muscle fibers to create a characteristic checkerboard pattern.) LGMS tissues commonly have small or more extensive foci of epithelioid (i.e. epithelial-like) cells with a polygonal shape. In a minority of cases, the tumor tissues have scattered mast cells, sites of numerous neutrophils, and areas of necrosis (i.e. dead or dying cells). Immunohistochemical analyses find that the LGMS tumors' spindle-shaped cells commonly express ACTA2 (also known α-smooth muscle actin) and desmin (i.e. an intermediate filament protein found in all muscle forms including smooth muscle) proteins, with some tumors composed of cells expressing both of these proteins and other tumors composed of cells expressing only one of them. The tumor cells often express vimentin and SMARCB1 (also termed INI-1 and SNF5) proteins but typically fail to express CD34, S-100, CD34, STAT6, CD68, CD56, cytokeratin, ERG, β-catenin, or myogenin proteins. The epithelioid, polygonal-shaped cells express cytokeratin and TP63 proteins.
Chromosome and gene abnormalities Various chromosome abnormalities have been found in the tumor cells of a few LGMS cases. A ring chromosome and/or giant marker chromosome, which commonly occur in the cells of various mesenchymal tumors, were found in one case of LGMS. In addition, these tumor cells may, in rare cases, contain copy number variations such as gains in the genetic material on the short (i.e. 'p') arm of chromosomes 1, 12, and 5 and losses in genetic material on the long (i.e. 'q') arm of chromosome 15. These chromosome abnormalities are considered non-specific. Analysis of LGMS tumor cells for chromosome and gene abnormalities has not yet been helpful in understanding or diagnosing the disorder.
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