undifferentiated pleomorphic sarcoma

UPS commonly presents as a deep-seated, rapidly enlarging, painless mass in individuals aged 50 to 70 years. These masses are rarely superficial lesions and rarely occur in the pediatric population. In a retrospective study of 266 individuals, UPS tumors ranged from 1–55 cm in greatest diameter (average 8.8 cm with 25%, 38%, and 38% having greatest diameters of 0–1, 5–9, and ≥10 cm, respectively).{{cite journal | vauthors = Vodanovich DA, Spelman T, May D, Slavin J, Choong PF | title = Predicting the prognosis of undifferentiated pleomorphic soft tissue sarcoma: a 20-year experience of 266 cases | journal = ANZ Journal of Surgery | volume = 89 | issue = 9 | pages = 1045–1050 | date = September 2019 | pmid = 31364245 | doi = 10.1111/ans.15348 | hdl = 11343/286224 | s2cid = 198997759 | url = | hdl-access = free }} 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. In rare cases, these tumors have also presented in other sites such as the retroperitoneal space,{{cite journal | vauthors = Chen S, Huang W, Luo P, Cai W, Yang L, Sun Z, Zheng B, Yan W, Wang C | title = Undifferentiated Pleomorphic Sarcoma: Long-Term Follow-Up from a Large Institution | journal = Cancer Management and Research | volume = 11 | issue = | pages = 10001–10009 | date = 2019 | pmid = 31819633 | pmc = 6885560 | doi = 10.2147/CMAR.S226896 | url = | doi-access = free }} liver,{{cite journal | vauthors = Wen J, Zhao W, Li C, Shen JY, Wen TF | title = High-grade myofibroblastic sarcoma in the liver: A case report | journal = World Journal of Gastroenterology | volume = 23 | issue = 38 | pages = 7054–7058 | date = October 2017 | pmid = 29097878 | pmc = 5658323 | doi = 10.3748/wjg.v23.i38.7054 | url = | doi-access = free }} pleura of the lung, heart,{{cite journal | vauthors = Oh SJ, Yeom SY, Kim KH | title = Clinical implication of surgical resection for the rare cardiac tumors involving heart and great vessels | journal = Journal of Korean Medical Science | volume = 28 | issue = 5 | pages = 717–24 | date = May 2013 | pmid = 23678263 | pmc = 3653084 | doi = 10.3346/jkms.2013.28.5.717 | url = }}{{cite journal | vauthors = Alam L, Agrawal K, Kankanala V, Fishberg R, Powell D | title = Primary Cardiac Undifferentiated High-Grade Intimal Pleomorphic Sarcoma: A Case Series Report | journal = Cardiology Research | volume = 11 | issue = 2 | pages = 129–133 | date = April 2020 | pmid = 32256920 | pmc = 7092767 | doi = 10.14740/cr1029 | url = }} and small intestine. In a retrospective study, distant metastases were detected at the time of initial diagnosis in 6.4% of 266 individuals. Overall, metastases have or will develop in up to 40% of individuals with UPS.{{cite journal | vauthors = Toulmonde M, Lucchesi C, Verbeke S, Crombe A, Adam J, Geneste D, Chaire V, Laroche-Clary A, Perret R, Bertucci F, Bertolo F, Bianchini L, Dadone-Montaudie B, Hembrough T, Sweet S, Kim YJ, Cecchi F, Le Loarer F, Italiano A | title = High throughput profiling of undifferentiated pleomorphic sarcomas identifies two main subgroups with distinct immune profile, clinical outcome and sensitivity to targeted therapies | journal = eBioMedicine | volume = 62 | issue = | pages = 103131 | date = December 2020 | pmid = 33254023 | pmc = 7708794 | doi = 10.1016/j.ebiom.2020.103131 | url = }} These metastases are reported to occur in lung (40% to 55% of cases) and less commonly in other sites such as lymph nodes near the primary tumor,{{cite journal | vauthors = Arora S, Rastogi S, Shamim SA, Barwad A, Sethi M | title = Good and sustained response to pembrolizumab and pazopanib in advanced undifferentiated pleomorphic sarcoma: a case report | journal = Clinical Sarcoma Research | volume = 10 | issue = | pages = 10 | date = 2020 | pmid = 32670543 | pmc = 7346343 | doi = 10.1186/s13569-020-00133-9 | url = | doi-access = free }} brain,{{cite journal | vauthors = Arnett AL, Smith TL, Gamez ME, Jhawar SR | title = Haemichorea-haemiballism secondary to brain metastasis from undifferentiated pleomorphic sarcoma | journal = BMJ Case Reports | volume = 14 | issue = 8 | pages = e242342| date = August 2021 | pmid = 34400423 | doi = 10.1136/bcr-2021-242342 | pmc = 8378830 | url = }} pancreas,{{cite journal | vauthors = Lee M, Song JS, Hong SM, Jang SJ, Kim J, Song KB, Lee JH, Cho KJ | title = Sarcoma metastasis to the pancreas: experience at a single institution | journal = Journal of Pathology and Translational Medicine | volume = 54 | issue = 3 | pages = 220–227 | date = May 2020 | pmid = 32311873 | pmc = 7253956 | doi = 10.4132/jptm.2020.03.04 | url = }} and heart.{{cite journal | vauthors = Xu G, Shi X, Shao G | title = An unusual case of metastasis of a pulmonary undifferentiated pleomorphic sarcoma to the right ventricle: a case report | journal = Journal of Medical Case Reports | volume = 7 | issue = | pages = 165 | date = June 2013 | pmid = 23805953 | pmc = 3750226 | doi = 10.1186/1752-1947-7-165 | url = | doi-access = free }}

A review study conducted in China of 183 individuals with UPS reported that 7 (3.83%) individuals (age 51 to 73 years; median age 62.8 years) had a subtype of the paraneoplastic syndrome termed neoplastic fever, i.e. these individuals suffered continuous, disabling fevers. Their tumors were located within a thigh muscle (4 cases), the upper arm (2 cases), or the lower leg (1 case). Compared to 89 individuals (median age 59.1 years) with a similar distribution of their UPS tumors, individuals with the neoplastic syndrome had similar tumor recurrence rates (57.14% vs 53.93% for the two respective groups) but a lower metastasis rate (14.29% vs 44.94%) and a higher 3-year survival rate (85.71% vs 59.55%). Fever symptoms disappeared in all patients after surgical removal of their tumors. It is suggested that individuals with UPS and neoplastic fever have a more favorable prognosis than individuals with UPS that do not evidence such fevers.

UPS is a diagnosis of exclusion (a diagnosis reached by the process of elimination) because the histopathology of this disorder's tumors is non-specific. UPS tumor cells are undifferentiated (i.e. do not resemble any particular cell type) and pleomorphic (i.e. highly variable in size, shape, and/or color) when examined microscopically. Therefore, the diagnosis of UPS is commonly based on detecting a specific set of proteins that are expressed by UPS tumor cells but not by the cells of other undifferentiated and pleomorphic tumors or visa versa (see Diagnosis section).

A study of 52 individuals found that their UPS tumor cells expressed on their surface membranes PD-L1 protein (i.e. programmed death-ligand 1 protein) either focally (36.5% of cases) or strongly (9.62% of cases); 48.1% of these individuals had tumor cells which also expressed IDO1 protein (i.e. indoleamine 2,3-dioxygenase protein).{{cite journal | vauthors = Ishihara S, Yamada Y, Iwasaki T, Yoshimoto M, Toda Y, Kohashi K, Yamamoto H, Matsumoto Y, Nakashima Y, Oda Y | title = PD‑L1 and IDO‑1 expression in undifferentiated pleomorphic sarcoma: The associations with tumor infiltrating lymphocytes, dMMR and HLA class I | journal = Oncology Reports | volume = 45 | issue = 1 | pages = 379–389 | date = January 2021 | pmid = 33155664 | doi = 10.3892/or.2020.7837 | s2cid = 226270021 | url = | doi-access = free | hdl = 2324/4474987 | hdl-access = free }} Tumor cells that strongly expressed PD-L1 also expressed CMTM6 protein (i.e. CKLF like MARVEL transmembrane domain containing 6 protein).{{cite journal | vauthors = Liang J, Li S, Li W, Rao W, Xu S, Meng H, Zhu F, Zhai D, Cui M, Xu D, Cai J, Zhang B | title = CMTM6, a potential immunotherapy target | journal = Journal of Cancer Research and Clinical Oncology | volume = 148| issue = 1| pages = 47–56| date = November 2021 | pmid = 34783871 | doi = 10.1007/s00432-021-03835-9 | s2cid = 244132643 | url = }} Strong PD‑L1 expression proved to be a poor, while expression of IDO‑1 proved to be a favorable, prognostic factor for disease outcomes. Individuals with tumor cells that strongly expressed CMTM6 protein also had poor prognoses. Increases in the expression of CMTM6 protein were associated in some cases with mutations that increased the number of copies of its gene, i.e. CMTM6.{{cite journal | vauthors = Ishihara S, Iwasaki T, Kohashi K, Yamada Y, Toda Y, Ito Y, Susuki Y, Kawaguchi K, Takamatsu D, Kawatoko S, Kiyozawa D, Mori T, Kinoshita I, Yamamoto H, Fujiwara T, Setsu N, Endo M, Matsumoto Y, Nakashima Y, Oda Y | title = The association between the expression of PD-L1 and CMTM6 in undifferentiated pleomorphic sarcoma | journal = Journal of Cancer Research and Clinical Oncology | volume = 147 | issue = 7 | pages = 2003–2011 | date = July 2021 | pmid = 33811537 | doi = 10.1007/s00432-021-03616-4 | s2cid = 232773534 | url = }} In a later study that examined 83 individuals, 72.8% had UPS tumor cells that expressed PD-L1 with 53%, 35%, and 12% of these cases showing weak, intermediate, and strong PD-L1 expression, respectively. 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).{{cite journal | vauthors = Orth MF, Gerke JS, Knösel T, Altendorf-Hofmann A, Musa J, Alba-Rubio R, Stein S, Hölting TL, Cidre-Aranaz F, Romero-Pérez L, Dallmayer M, Baldauf MC, Marchetto A, Sannino G, Knott MM, Wehweck F, Ohmura S, Li J, Hakozaki M, Kirchner T, Dandekar T, Butt E, Grünewald TG | title = Functional genomics identifies AMPD2 as a new prognostic marker for undifferentiated pleomorphic sarcoma | journal = International Journal of Cancer | volume = 144 | issue = 4 | pages = 859–867 | date = February 2019 | pmid = 30267407 | doi = 10.1002/ijc.31903 | s2cid = 52883298 | url = | doi-access = free }} Other abnormalities found in some or isolated cases of UPS include: 1) Amplification of the Hippo signaling pathway, an intracellular cell signaling pathway that regulates cell proliferation and cell death;{{cite journal | title = Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas | journal = Cell | volume = 171 | issue = 4 | pages = 950–965.e28 | date = November 2017 | pmid = 29100075 | pmc = 5693358 | doi = 10.1016/j.cell.2017.10.014 | url = | last1 = Abeshouse | first1 = Adam | last2 = Adebamowo | first2 = Clement | last3 = Adebamowo | first3 = Sally N. | last4 = Akbani | first4 = Rehan | last5 = Akeredolu | first5 = Teniola | last6 = Ally | first6 = Adrian | last7 = Anderson | first7 = Matthew L. | last8 = Anur | first8 = Pavana | last9 = Appelbaum | first9 = Elizabeth L. | last10 = Armenia | first10 = Joshua | last11 = Auman | first11 = J. Todd | last12 = Bailey | first12 = Matthew H. | last13 = Baker | first13 = Laurence | last14 = Balasundaram | first14 = Miruna | last15 = Balu | first15 = Saianand | last16 = Barthel | first16 = Floris P. | last17 = Bartlett | first17 = John | last18 = Baylin | first18 = Stephen B. | last19 = Behera | first19 = Madhusmita | last20 = Belyaev | first20 = Dmitry | last21 = Bennett | first21 = Joesph | last22 = Benz | first22 = Christopher | last23 = Beroukhim | first23 = Rameen | last24 = Birrer | first24 = Michael | last25 = Bocklage | first25 = Thèrése | last26 = Bodenheimer | first26 = Tom | last27 = Boice | first27 = Lori | last28 = Bootwalla | first28 = Moiz S. | last29 = Bowen | first29 = Jay | last30 = Bowlby | first30 = Reanne | display-authors = 1 }} this amplification is associated with the overexpression of two proteins, vestigial-like family member 3 protein, a product of the VGLL3 gene, and YAP1, i.e. yes-associated protein 1, a product of the YAP1 gene, in the Hippo signaling pathway; 2) Abnormal activation of notch signaling pathways (this activation has been shown to promote the growth and survival of various types of cancer cells;{{cite journal | vauthors = Anusewicz D, Orzechowska M, Bednarek AK | title = Notch Signaling Pathway in Cancer-Review with Bioinformatic Analysis | journal = Cancers | volume = 13 | issue = 4 | date = February 2021 | page = 768 | pmid = 33673145 | pmc = 7918426 | doi = 10.3390/cancers13040768 | url = | doi-access = free }} and 3) Overexpression of DKK1, i.e. Dickkopf-related protein 1 (elevated in the tumor cells of various cancer types).{{cite journal | vauthors = Chu HY, Chen Z, Wang L, Zhang ZK, Tan X, Liu S, Zhang BT, Lu A, Yu Y, Zhang G | title = Dickkopf-1: A Promising Target for Cancer Immunotherapy | journal = Frontiers in Immunology | volume = 12 | issue = | pages = 658097 | date = 2021 | pmid = 34093545 | pmc = 8174842 | doi = 10.3389/fimmu.2021.658097 | url = | doi-access = free }}

UPS tumors also show gene and chromosome abnormalities that further studies may find contribute to the development and/or progression of UPS. These abnormalities, which have not yet been reported to be helpful in diagnosing UPS, include the following. 1) Deletion and/or inactivation or the RB1 gene that encodes (i.e. is responsible for production of) the retinoblastoma protein that functions as a tumor suppressor protein; 2) deletions and/or mutations in the TP53 gene that encodes tumor protein P53 (a protein which regulates cell proliferation and cell death); 3) mutations in the ATRX gene that encodes transcriptional regulator ATRX protein which contributes to regulating the expression of various genes;{{cite journal | vauthors = Delespaul L, Lesluyes T, Pérot G, Brulard C, Lartigue L, Baud J, Lagarde P, Le Guellec S, Neuville A, Terrier P, Vince-Ranchère D, Schmidt S, Debant A, Coindre JM, Chibon F | title = Recurrent TRIO Fusion in Nontranslocation-Related Sarcomas | journal = Clinical Cancer Research | volume = 23 | issue = 3 | pages = 857–867 | date = February 2017 | pmid = 27528700 | doi = 10.1158/1078-0432.CCR-16-0290 | s2cid = 3756473 | url = | doi-access = free }}{{cite journal | vauthors = Zheng B, Qu Y, Wang J, Shi Y, Yan W | title = Pathogenic and Targetable Genetic Alterations in Resected Recurrent Undifferentiated Pleomorphic Sarcomas Identified by Targeted Next-generation Sequencing | journal = Cancer Genomics & Proteomics | volume = 16 | issue = 3 | pages = 221–228 | date = 2019 | pmid = 31018952 | pmc = 6542646 | doi = 10.21873/cgp.20127 | url = }}{{cite journal | vauthors = Ali NM, Niada S, Brini AT, Morris MR, Kurusamy S, Alholle A, Huen D, Antonescu CR, Tirode F, Sumathi V, Latif F | title = Genomic and transcriptomic characterisation of undifferentiated pleomorphic sarcoma of bone | journal = The Journal of Pathology | volume = 247 | issue = 2 | pages = 166–176 | date = February 2019 | pmid = 30281149 | pmc = 8033574 | doi = 10.1002/path.5176 | url = }} 4) mutations in the KMT2C gene which encodes lysine N-methyltransferase 2C protein (the KMT2C gene is mutated in various cancer types{{cite journal | vauthors = Fagan RJ, Dingwall AK | title = COMPASS Ascending: Emerging clues regarding the roles of MLL3/KMT2C and MLL2/KMT2D proteins in cancer | journal = Cancer Letters | volume = 458 | issue = | pages = 56–65 | date = August 2019 | pmid = 31128216 | pmc = 6638576 | doi = 10.1016/j.canlet.2019.05.024 | url = }}); 5) amplification of the IL7R gene which encodes Interleukin-7 receptor-α protein (mutations in the IL7R gene are commonly found in acute lymphoblastic leukemia{{cite journal | vauthors = Rodrigues GO, Cramer SD, Winer HY, Hixon JA, Li W, Yunes JA, Durum SK | title = Mutations that collaborate with IL-7Ra signaling pathways to drive ALL | journal = Advances in Biological Regulation | volume = 80 | issue = | pages = 100788 | date = May 2021 | pmid = 33578108 | doi = 10.1016/j.jbior.2021.100788 | s2cid = 231908606 | url = }}){{cite journal | vauthors = Zheng B, Qu Y, Wang J, Shi Y, Yan W | title = Pathogenic and Targetable Genetic Alterations in Resected Recurrent Undifferentiated Pleomorphic Sarcomas Identified by Targeted Next-generation Sequencing | journal = Cancer Genomics & Proteomics | volume = 16 | issue = 3 | pages = 221–228 | date = 2019 | pmid = 31018952 | pmc = 6542646 | doi = 10.21873/cgp.20127 | url = }} and 6) expression of a fusion gene (i.e. a hybrid gene formed from two previously independent genes as a result of a mutation) that merges TRIO with other genes and is often found in other sarcoma subtypes.)

The diagnosis of UPS depends on finding non-specific, undifferentiated tumor cells that have features suggestive of UPS and not features of other tumor types that also consist of pleomorphic, undifferentiated cells. The features primarily involve the expression of certain proteins by the tumor cells. The identifying proteins for UPS tumor cells are given in the preceding section. Identification proteins for tumors that have been confused with UPS inlclude:

• Pleomorphic leimyosarcoma: Desmin and h-caldesmon (i.e. high molecular form of caldesmon.{{cite journal | vauthors = Watanabe K, Tajino T, Sekiguchi M, Suzuki T | title = h-Caldesmon as a specific marker for smooth muscle tumors. Comparison with other smooth muscle markers in bone tumors | journal = American Journal of Clinical Pathology | volume = 113 | issue = 5 | pages = 663–8 | date = May 2000 | pmid = 10800398 | doi = 10.1309/jnqx-f4km-q0q0-7xk8 | url = | doi-access = free }}) proteins
• Pleomorphic rhabdomyosarcoma: Desmin and myogenin proteins.
• Defifferentiated liposarcoma: MDM2 and CDK4 proteins.
• Poorly differentiated carcinoma (i.e. grade 3 or 4 carcinoma): MUC1 (also termed EMA), TP63 (also termed p63; which is detected with the p40 antibody{{cite journal | vauthors = Alomari AK, Glusac EJ, McNiff JM | title = p40 is a more specific marker than p63 for cutaneous poorly differentiated squamous cell carcinoma | journal = Journal of Cutaneous Pathology | volume = 41 | issue = 11 | pages = 839–45 | date = November 2014 | pmid = 25263848 | doi = 10.1111/cup.12388 | s2cid = 9053425 | url = }}), and various members of the keratin family of proteins.
• Melanoma: MLANA (i.e. melanoma antigen recognized by T cells 1 protein), S100, and PMEL (a product of the PMEL gene which is detected using an antibody termed HMB-45.{{cite journal | vauthors = Gleason BC, Nascimento AF | title = HMB-45 and Melan-A are useful in the differential diagnosis between granular cell tumor and malignant melanoma | journal = The American Journal of Dermatopathology | volume = 29 | issue = 1 | pages = 22–7 | date = February 2007 | pmid = 17284958 | doi = 10.1097/01.dad.0000249888.41884.6c | s2cid = 20167145 | url = }}) proteins

Two other tumors that may be confused with UPS have microscopic histopathological and/or other features that help make this distinction. These tumors and features are:

• Pleomorphic liposarcoma: At least some tumor cells have features of pleomorphic lipoblasts, i.e. variable shaped immature fat cells.
• Malignant peripheral nerve sheath tumor: Typically occurs in young children, often develops in a preexisting inoperable plexiform neurofibroma, and often associated with neural tissue. These tumors typically show undifferentiated, pleomorphic cells that are arranged in whorls, parallel bundles, or rosettes (i.e. circular arrangement resembling leaves in a flowering plant) and often contain large areas of necrosis (i.e. dead or dying cells).

The most often used treatment for localized (i.e. no metastases) UPS tumors is complete surgical removal with the object of leaving no tumor cells behind as evidenced by microscopic examinations. Adjuvant therapy combining radiotherapy or/and chemotherapy with surgical resection is employed to reduce the risk of developing recurrent and metastatic disease in cases with high-risk disease (e.g. large tumors, tumors deemed highly aggressive based on their pathology and/or local invasiveness, inoperable tumors, and resections that did not remove all tumor cells). A standard chemotherapy two-drug regimen (epirubicin plus ifosfamide) may be used in these cases.{{cite journal | vauthors = Gronchi A, Ferrari S, Quagliuolo V, Broto JM, Pousa AL, Grignani G, Basso U, Blay JY, Tendero O, Beveridge RD, Ferraresi V, Lugowska I, Merlo DF, Fontana V, Marchesi E, Donati DM, Palassini E, Palmerini E, De Sanctis R, Morosi C, Stacchiotti S, Bagué S, Coindre JM, Dei Tos AP, Picci P, Bruzzi P, Casali PG | title = Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial | journal = The Lancet. Oncology | volume = 18 | issue = 6 | pages = 812–822 | date = June 2017 | pmid = 28499583 | doi = 10.1016/S1470-2045(17)30334-0 | url = }} In place or combined with surgery and/or radiotherapy, severe and/or metastatic cases of UPS are commonly treated with epirubicin plus ifosfamide; doxorubicin alone or combined with ifosfamide, olaratumab, trabectedin, gemcitabine, or docetaxel; cyclophosphamide, vincristine, doxorubicin, plus dacarbazine or cisplatin; cyclophosphamide, doxorubicin, plus dacarbazine; high dose methotrexate; or etoposide, ifosfamide, and cisplatin. These treatment regimens have been reported to lower local recurrence rates, prolong disease-free survival rates (i.e. time after treatment when no disease is detected), and increase overall survival rates (i.e. time after treatment to death from any cause). However, other studies report that the addition of radiotherapy and/or chemotherapy to surgical resection does not improve recurrence or overall survival rates; addition of radiotherapy to surgery improves local control of UPS tumors but not disease-free survival rates (i.e. time from treatment to recurrence of disease); and adjuvant chemotherapy and radiotherapy have no significant effects on local recurrence-free survival rates, metastasis-free survival times, and overall survival rates. Further studies are needed to define the best treatments for UPS tumors.

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. Patients who received surgery alone or surgery plus adjuvant treatment had disease-free survival rates of about 50 and 40%, respectively. A retrospective analysis of 266 patients with UPS were treated with surgery alone (6% of cases), surgery plus radiotherapy (91% of cases), or surgery plus chemotherapy (3% of cases). 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. Poorer prognoses were seen in older patients; in patients with tumors that were large-sized, deep-seated, and/or located in a leg; in patients that presented with metastases; and in patients who had positive surgical margins and/or developed local recurrences after surgery. In another retrospective study, 203 individuals with UPS, 141 of whom had metastatic disease, were treated with regimens selected based on the severity of their disease. In this study, the overall 5 year survival rate was 4%. Patients with the most advanced disease had a median overall survival time 11 months.{{cite journal | vauthors = Savina M, Le Cesne A, Blay JY, Ray-Coquard I, Mir O, Toulmonde M, Cousin S, Terrier P, Ranchere-Vince D, Meeus P, Stoeckle E, Honoré C, Sargos P, Sunyach MP, Le Péchoux C, Giraud A, Bellera C, Le Loarer F, Italiano A | title = Patterns of care and outcomes of patients with METAstatic soft tissue SARComa in a real-life setting: the METASARC observational study | journal = BMC Medicine | volume = 15 | issue = 1 | pages = 78 | date = April 2017 | pmid = 28391775 | pmc = 5385590 | doi = 10.1186/s12916-017-0831-7 | url = | doi-access = free }}

Recent studies have treated UPS by targeting the immune system with pembrolizumab. 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. This inhibition blocks the PD-L1 and PL-L2 ligands located on the surface of normal tissue cells from binding to PD-1 receptors on activated T-cells and thereby blocks the T-cells from organizing an inflammatory response that kills the normal cells. Tumor cells may use this inflammation-evading tactic: they may express PD-L1/PD-L2 and thereby block the T-cell-mediated immune responses to them (see Immune checkpoint).{{cite journal | vauthors = Mazarico Gallego JM, Herrera Juárez M, Paz-Ares L | title = The safety and efficacy of pembrolizumab for the treatment of non-small cell lung cancer | journal = Expert Opinion on Drug Safety | volume = 19 | issue = 3 | pages = 233–242 | date = March 2020 | pmid = 32129104 | doi = 10.1080/14740338.2020.1736554 | s2cid = 212405175 | url = }} From ~47% to ~73% of UPS cases contain tumor cells that express PD-L1. In a retrospective review of 10 patients with UPS, 1 patient had a complete response, 3 had partial responses, and 6 had no response to pembrolizumab. (Further studies of the 4 pembrolizumab-responsive patients indicated that their tumor cells expressed PD-L1 in two cases but not in the other two cases.{{cite journal | vauthors = Keung EZ, Burgess M, Salazar R, Parra ER, Rodrigues-Canales J, Bolejack V, Van Tine BA, Schuetze SM, Attia S, Riedel RF, Hu J, Okuno SH, Priebat DA, Movva S, Davis LE, Reed DR, Reuben A, Roland CL, Reinke D, Lazar AJ, Wang WL, Wargo JA, Tawbi HA | title = Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab | journal = Clinical Cancer Research | volume = 26 | issue = 6 | pages = 1258–1266 | date = March 2020 | pmid = 31900276 | pmc = 7731262 | doi = 10.1158/1078-0432.CCR-19-1824 | url = }}) In a retrospective study of 25 patients (21 patients treated with pembrolizumab, 4 treated with other immunotherapy agents), 7 attained stable disease, 7 attained partial responses, and 1 attained a complete response.{{cite journal | vauthors = Monga V, Skubitz KM, Maliske S, Mott SL, Dietz H, Hirbe AC, Van Tine BA, Oppelt P, Okuno S, Robinson S, O'Connor M, Seetharam M, Attia S, Charlson J, Agulnik M, Milhem M | title = A Retrospective Analysis of the Efficacy of Immunotherapy in Metastatic Soft-Tissue Sarcomas | journal = Cancers | volume = 12 | issue = 7 | date = July 2020 | page = 1873 | pmid = 32664595 | pmc = 7408640 | doi = 10.3390/cancers12071873 | url = | doi-access = free }} 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.{{cite journal | vauthors = Toulmonde M, Penel N, Adam J, Chevreau C, Blay JY, Le Cesne A, Bompas E, Piperno-Neumann S, Cousin S, Grellety T, Ryckewaert T, Bessede A, Ghiringhelli F, Pulido M, Italiano A | title = Use of PD-1 Targeting, Macrophage Infiltration, and IDO Pathway Activation in Sarcomas: A Phase 2 Clinical Trial | journal = JAMA Oncology | volume = 4 | issue = 1 | pages = 93–97 | date = January 2018 | pmid = 28662235 | pmc = 5833654 | doi = 10.1001/jamaoncol.2017.1617 | url = }} It is clear that new treatment strategies{{cite journal | vauthors = Toulmonde M, Lucchesi C, Verbeke S, Crombe A, Adam J, Geneste D, Chaire V, Laroche-Clary A, Perret R, Bertucci F, Bertolo F, Bianchini L, Dadone-Montaudie B, Hembrough T, Sweet S, Kim YJ, Cecchi F, Le Loarer F, Italiano A | title = High throughput profiling of undifferentiated pleomorphic sarcomas identifies two main subgroups with distinct immune profile, clinical outcome and sensitivity to targeted therapies | journal = eBioMedicine | volume = 62 | issue = | pages = 103131 | date = December 2020 | pmid = 33254023 | pmc = 7708794 | doi = 10.1016/j.ebiom.2020.103131 | url = }} as well as further studies on the efficacy of pembrolizumab and similarly acting immunotherapy drugs used with or without radiotherapy and/or chemotherapy over longer time periods are needed to evaluate their usefulness in treating UPS.{{cite journal | vauthors = Keung EZ, Lazar AJ, Torres KE, Wang WL, Cormier JN, Ashleigh Guadagnolo B, Bishop AJ, Lin H, Hunt KK, Bird J, Lewis VO, Patel SR, Wargo JA, Somaiah N, Roland CL | title = Phase II study of neoadjuvant checkpoint blockade in patients with surgically resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma | journal = BMC Cancer | volume = 18 | issue = 1 | pages = 913 | date = September 2018 | pmid = 30249211 | pmc = 6154892 | doi = 10.1186/s12885-018-4829-0 | url = | doi-access = free }}

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{{Medical resources

| DiseasesDB = 31471

| ICD10 = {{ICD10|C|49||c|49}} (ILDS C49.M10)

| ICD9 =

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| eMedicineSubj = radio

| eMedicineTopic = 420

| MeshID = D051677

}}

{{Soft tissue tumors and sarcomas}}

{{Urologic neoplasia}}

Category:Dermal and subcutaneous growths

Category:Infectious causes of cancer

Category:Sarcoma