Soft tissue sarcoma

1. Soft tissue sarcoma Ibtisam albader FRCSC Mubarak hospital

2. Sarcomas are a rare and heterogeneous group of malignant tumors of mesenchymal origin that comprise approximately 1 percent of all adult malignancies and 12 percent of pediatric cancers . • 80 percent of sarcomas originate from soft tissue and 20 percent from bone.

3. After GIST, the most common soft tissue sarcoma subtypes in adults are pleomorphic sarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor (MPNST)

5. Desmoid tumor/deep fibromatosis • Not sarcomas but they represent neoplasms of fibroblastic tissue that lack the ability to metastasize. However, desmoid tumors have a propensity for local recurrence, even after complete resection, and they have the capacity to cause local morbidity and death in rare cases

6. Desmoid tumor/deep fibromatosis Typically arise • in the extremity in sporadic cases • in the abdominal wall in association with pregnancy (where they usually improve post-partum) • in the mesenteric root in the setting of familial adenomatouspolyposis (FAP). FAP is characterized by loss of expression of the gene APC. The development of desmoid tumor in the setting of FAP is a characteristic of Gardner syndrome, a specific version of FAP. Mesenteric desmoids are those with the highest degree of mortality.

7. Soft tissue sarcoma • arise de novo and not from a preexisting benign lesion. • no clearly defined etiology, • Associated / predisposing factors • genetic predisposition (eg, Li Fraumeni syndrome, neurofibromatosis type I) • exposure to radiation therapy or chemotherapy, • chemical carcinogens • chronic irritation • lymphedema. • human immunodeficiency virus and human herpes virus 8 (Kaposi's sarcoma).

8. Soft tissue sarcoma • Distant metastatic disease after successful treatment primary tumor25 %. • Incidence increases to 40 to 50 % : tumors that are >5 cm in size deep to the fascia intermediate or high grade • In 70 to 80 percent of cases, metastasis is to the lungs • Spread to regional nodes is infrequent except for : rhabdomyosarcoma, synovial sarcoma, epithelioid sarcoma, clear cell sarcoma, and the vascular sarcomas (including angiosarcomas) • Rare sites of metastatic dis. : skin, soft tissues, bone, liver, brain. • Exceptions : • In round cell/myxoidliposarcomas: extrapulmonary metastases to the retroperitoneum, abdomen, bone (particularly the spine), and paraspinal soft tissue is common . • Retroperitoneal sarcomas, in particular leiomyosarcomas, metastasize to the liver as well as lung. • Retroperitoneal liposarcomas, nearly all the well differentiated/dedifferentiated subtype, recur local-regionally instead of with metastatic disease.

9. Differential diagnosis • Benign soft tissue tumors: lipoma • Malignant tumors including sarcoma, metastatic carcinoma, melanoma, or lymphoma.   • Given that benign soft tissue masses are at least 100 times more common than malignant soft tissue sarcomas : The United Kingdom Department of Health has published criteria for urgent referral of a patient with a soft tissue lesion : • Soft tissue mass >5 cm (golf ball size or larger) • Painful lump • Lump that is increasing in size • A lump of any size that is deep to the muscle fascia • Recurrence of a lump after previous excision

10. Imaging • Plain radiography : useful to rule out soft tissue masses that arise from bone and to detect intratumoral calcifications such as those that appear within soft tissue (extraskeletal) osteosarcomas and synovial sarcomas.   • MRI and CT: • MRI is the preferred imaging modality for the evaluation of soft tissue masses of the extremities, trunk, and head and neck, delineating the extent of the neoplasm and relation to surrounding structures, especially individual muscle involvement • CT is the most commonly used imaging technique for retroperitoneal sarcomas. • PET and PET/CT : not routinely recommended

11. biopsy Diagnostic biopsy should be carefully planned to ensure that adequate tissue is obtained in a manner that does not compromise definitive or subsequent therapy : subsequent surgical resection, preparation of flaps, and/or cosmetic repair, or result in the need for a more extensive surgery to encompass the biopsy site at the time of definitive resection.

12. biopsy •  Core needle biopsy is considered the preferred method: In a study of 530 patients with suspected soft tissue tumors, core needle biopsy differentiated malignant soft tissue sarcomas from benign soft tissue tumors in 97.6 percent of patients. Histologic grade was accurately determined in 86.3 percent of patients, and the subtype was accurately identified in 88 percent (J SurgOncol. 2010;102(5):523). • CT or ultrasound guidance assist biopsy of deep lesions, improve and lesions with cystic areas and necrosis by allowing the operator to select the site to be biopsied . • In cases where core needle biopsy is unsuccessful in obtaining adequate material for diagnosis, a subsequent incisional biopsy is usually considered. The incidence of follow-up biopsy has been reported as high as 20 percent .

13. Fine needle aspiration •  FNA is not recommended in the initial diagnostic evaluation of a suspicious soft tissue mass, has lower diagnostic accuracy than core needle biopsy . • Does not provide subtype or grade of the sarcoma. • FNA can be useful in confirming disease recurrence.

15. Prognosis • Tumor stage • Histologic grade • Tumor size • High grade tumors as a function of tumor size : Tumors ≤2.5 cm – 6 percent Tumors > 20 cm – 83 percent

16. Surgery • Main stay of therapy IS Surgical resection of the primary tumor • Periosteal stripping should be avoided, if possible, because it increases the risk of radiation induced #. • widely resect the tumor with negative margins = cuff of normal tissue completely surrounding the tumor. Thickness debatable (traditionally 1 cm margins were recommended). • One cm margins seldom occur accepted , the type of tissue is important: thinner (1 to 2 mm) margins of fascia are likely adequate, whereas wider margins that consist of fat or muscle are suggested.

17. The combination of surgery and radiation therapy achieves better local control than either modality alone for the majority of STS; however, no improvement in survival has been demonstrated

18. IMPORTANCE OF MULTIDISCIPLINARY EVALUATION AND MANAGEMENT

19. GIST • Stromal or mesenchymalneoplasms affecting the gastrointestinal (GI) tract • divided into two groups. • most common gastrointestinal stromal tumors (GISTs) most often located in the stomach and proximal small intestine, any portion of the alimentary tract and occasionally in the omentum, mesentery, and peritoneum . • A far less common group are soft tissue sarcomas

20. CLASSIFICATION AND MOLECULAR PATHOGENESIS • Aided by identification of the near-universal expression of the CD117 antigen by GISTs, in contrast to leiomyomas, true leiomyosarcomas, and other spindle-cell tumors of the GI tract, which are typically CD117-negative • The CD117 antigen is part of the KIT transmembrane receptor tyrosine kinase (RTK) that is the product of the KIT (also denoted c-kit) protooncogene. • In more than 80 percent of GIST cases, a mutation in the KIT gene leads to a structural variant of the KIT protein which is abnormally activated and enables oncogenic signaling in the cell. • In some KIT-negative GISTs, the platelet-derived growth factor receptor alpha (PDGFRA) is present.

21. KIT or PDGFR immunoreactivity is thought to define a group of tumors showing differentiation toward or derived from the interstitial cells of Cajal (ICC). (the GI pacemaker cells) • Most KIT gene mutations (approximately 75 percent) in GISTs affect exon 11 (which codes for the intracellular juxtamembrane domain) and result in spontaneous (ligand-independent) receptor dimerization and receptor activation. • However, in some cases, a mutation is present in exon 9, 13, or 17, with a different structural biological mechanism that results in uncontrolled KIT signaling.

22. management of GISTs, leiomyomas, and leiomyosarcomas involving the GI tract depends the preoperative diagnosis, tumor location and size, extent of spread, and clinical presentation (evidence of tumor obstruction, perforation, or uncontrolled hemorrhage) • Overt GI bleeding — 40 percent • Abdominal mass — 40 percent • Abdominal pain — 20 percent

23. GISTs frequently metastasize to liver and peritoneum and rarely to regional lymph nodes. • Uncommonly metastasize to the lungs, the most common site of metastasis for most soft tissue sarcomas.

24. Preoperative biopsy or endoscopic ultrasound (EUS)-guided fine needle aspiration biopsy (FNA) may not be necessary if a mesenchymal GI tumor is strongly suspected, resectable, and the patient is otherwise operable. • a biopsy is preferred to confirm the diagnosis if metastatic disease is suspected or if preoperative imatinib is considered prior to attempted resection in a patient who has a large locally advanced lesion thought to represent a GIST.

25. All GISTs ≥2 cm in size should be resected • GISTs between 1 and 2 cm, including their growth rate and metastatic potential, remains unknown. Although these small GISTs may be followed endoscopically until they grow or become symptomatic, the optimal frequency of follow-up and specific risks of this strategy is uncertain • Successful endoscopic resection is reported, but it remains controversial because of the risk of positive margins, tumor spillage, and perforation . Because GISTs are submucosal, standard techniques of endoscopic mucosal not adequate , submucosal resection is needed to guarantee removal of all the deep tissue.

26. Tumour size and mitotic rate predicts malignant potential • Number of mitosis in 50 hpf (=5mm2) of tissue (>10)

27. Surgical resection is the treatment of choice for potentially resectable tumors; however, initial therapy with imatinib(tyrosinekinase inhibitors) may be preferred if a tumor is borderline resectable, or if resection would necessitate extensive organ disruption. • Five year survival have been reported.

28. POSTTREATMENT FOLLOW-UP • Guidelines from the National Comprehensive Cancer Network (NCCN) suggest the following: • For a completely resected GIST tumor, history and physical examination every three to six months for five years, then annually. A CT scan is recommended every three to six months for three to five years, then annually. • For patients with more locally advanced or metastatic disease who are receiving imatinib, history and physical examination as well as abdominopelvic CT scan are recommended every three to six months.

29. Sources • Uptodate • Nccn guidelines

30. Thank you

31. Gardner's syndrome is associated with all the following EXCEPT: a) multiple colorectal adenomasb) sebaceous and dermoid cystsc) osteomas of the mandible or skulld) desmoidtumours of the abdominal walle) no malignant potential

32. A 47 year old gentleman was found to have a subepithelial mass at OGD. A subsequent EUS revealed a hypoechoic mass arising from the muscle layer. FNA of the lesion was performed. Cytology and immunohistochemistry was diagnostic of a GIST. The following is true about a GIST tumour except: a) Any symptomatic GIST is potentially aggressiveb) GIST usually metastasizes to lungs c) Imatinib (Gleevac) is the treatment of choice d) GIST almost uniformly express c-kit (CD117)

33. Which is the most common organ of origin for Gastrointestinal stromal tumor (GIST) a) Esophagus b) Jenunum c) Colon d) Stomach