Perivascular epithelioid cell neoplasms (PEComas)
PEComas include angiomyolipoma, lymphangioleiomyomatosis, and clear cell "sugar" tumor. Benign PEComas are common in tuberous sclerosis, an autosomal dominant syndrome that also predisposes to renal cell cancer and brain tumors. Tuberous sclerosis is caused by germline inactivation of either TSC1 (9q34) or TSC2 (16p13.3), and the same tumor suppressor genes are inactivated somatically in sporadic PEComas. Inactivation of either gene results in stimulation of the mTOR pathway, providing the basis for the treatment of non-surgically curable PEComas with mTOR inhibitors.[54,55]
PEComas occur in various rare gastrointestinal, pulmonary, gynecologic, and genitourinary sites. Soft tissue, visceral, and gynecologic PEComas are more commonly seen in middle-aged female patients and are usually not associated with the tuberous sclerosis complex. Most PEComas have a benign clinical course, but malignant behavior has been reported and can be predicted based on the size of the tumor, mitotic rate, and presence of necrosis.
Plexiform histiocytic tumor
Plexiform histiocytic tumor is a low to intermediate grade tumor. It most commonly arises in the skin or subcutaneous tissue of children and young adults.[58,59,60] Treatment is limited to surgical resection. There are rare reports of spread to regional lymph nodes or the lung. The majority of patients are cured by surgery, but local recurrence has been reported in 10% to 40% of cases.
Synovial sarcoma is considered to be more chemotherapy responsive than many other soft tissue sarcomas. There is ample documentation of objective response of synovial sarcoma to systemic chemotherapy.[41,61,62,63] The value of adjuvant chemotherapy following resection of localized disease has not been conclusively supported in prospective trials, but most pediatric oncologists favor adjuvant chemotherapy for all but the smallest, completely resected tumors.[62,64,65,66]
Diagnosis of synovial sarcoma is made by immunohistochemical analysis, ultrastructural findings, and demonstration of the specific chromosomal translocation t(x;18)(p11.2;q11.2). This abnormality is specific for synovial sarcoma and is found in all morphologic subtypes. Synovial sarcoma results in rearrangement of the SYT gene on chromosome 18 with one of the subtypes (1, 2, or 4) of the SSX gene on chromosome X.[67,68] Synovial sarcoma can be subclassified as monophasic fibrous type, biphasic type with distinct epithelial and spindle cell components, or poorly differentiated. Poorly differentiated synovial sarcoma has features of monophasic or biphasic synovial sarcoma but also a variable proportion of poorly differentiated areas characterized by high cellularity, pleomorphism, and polygonal or small round-cell morphology, numerous mitoses, and often necrosis.
Undifferentiated soft tissue sarcoma
Patients with undifferentiated sarcoma were eligible for participation in rhabdomyosarcoma (RMS) trials coordinated by the Intergroup Rhabdomyosarcoma Study Group and the Children's Oncology Group (COG) from 1972 to 2006. The rationale was the observation that patients with undifferentiated sarcoma had similar sites of disease and outcome compared with those with alveolar RMS. Therapeutic trials for adults with soft tissue sarcoma include patients with undifferentiated sarcoma and other histologies, which are treated similarly, utilizing ifosfamide and doxorubicin, sometimes with other chemotherapy agents, surgery, and radiation therapy. The COG is studying the use of a combination of surgery and/or radiation therapy, with or without ifosfamide and doxorubicin, for patients with undifferentiated sarcoma of soft tissue in its open protocol COG-ARST0332 for patients with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS).