Undifferentiated pleomorphic sarcoma (UPS), also termed pleomorphic myofibrosarcoma,[1] high-grade myofibroblastic sarcoma, and high-grade myofibrosarcoma,[2] is characterized by the World Health Organization (WHO) as a rare, poorly differentiated neoplasm (i.e., an abnormal growth of cells that have an unclear identity and/or cell of origin).
[7] UPS is considered a diagnosis that defies formal sub-classification after thorough histologic, immunohistochemical, and ultrastructural examinations fail to identify the type of cells involved.
[1] MFH are now regarded as a wastebasket category of various sarcoma types including sarcoma-like carcinomas and melanomas.
[10] Because of their low incidence and frequent grouping with what are now considered to be other sarcoma types, past findings on the clinical behaviour, proper treatment, and prognosis of UPS may be revised with further study.
[8] The majority of UPS tumors are highly aggressive, often recur after surgical removal, and often metastasize.
[12] UPS commonly presents as a deep-seated, rapidly enlarging, painless mass in individuals aged 50 to 70 years.
[13] In a study of 205 individuals (median age 59 years) diagnosed with UPS, the tumors were located in the arm or leg (47.3% of cases), abdomen or pelvis (26.8%), thorax (17.6%), and head or neck (8.3%) areas.
[8] In rare cases, these tumors have also presented in other sites such as the retroperitoneal space,[14] liver,[15] pleura of the lung,[2] heart,[16][17] and small intestine.
[18] These metastases are reported to occur in lung (40%[13] to 55%[14] of cases) and less commonly in other sites such as lymph nodes near the primary tumor,[19] brain,[20] pancreas,[21] and heart.
[8] And, in a study of 73 patients with UPS, 39 cases showed no, 23 cases showed low, 10 showed intermediate, and 11 strong immunoreactivity for AMPD2, i.e. AMP deaminase 2 protein; the gains in AMPD2 protein immunoreactivity were associated with copy number gains in the AMPD2 gene and patients with higher AMPD2 levels had poorer prognoses (5 year survivals for AMPD2 positive versus AMPD2 negative cases were ~38 and 59%, respectively).
[38] In a retrospective study of 176 patients with localized UPS undergoing curative-intent treated with surgical resection or resection plus adjuvant treatment, disease-free survival rates at 120 months for patients with tumors in an extremity (leg or arm), heat/neck area, thorax, and abdomen/pelvis were about 70, 60, 50, and 0%, respectively; overall survival rates at 150 months for disease at these sites were about 90, 80, 75, and 35%, respectively.
Post-treatment local recurrences and metastases were observed in 15% and 38% of cases; 5- and 10-year overall survival rates were 60% and 48%, respectively; Overall median survival time were 10.1 years; and patients with tumors ≥10 cm in longest diameter had an almost 6-fold higher rate of developing metastases than patients with tumors 4 cm or smaller.
[12] Pembrolizumab is a manufactured IG4 therapeutic monoclonal antibody that binds to and inhibits stimulation of the PD-1 receptors expressed on the surface of activated T-cells.
[42] In a study of 16 patients with UPS, 5 achieved short-term (lasting 1.2 to 1.4 months) stable disease in response to a regimen of pembrolizumab combined with the chemotherapy drug, cyclophosphamide.