Soft Tissue Tumors - II PDF

Soft Tissue Tumors - II Robbins &Cotran Pathologic Basis of Disease, 10th Edition Eds: Kumar, Abbas, Aster Robbins Basic Pathology, 11th Edition Eds: Vinay Kumar Abul K. Abbas Nelson Fausto , Richard N. Mitchell PERIPHERAL NERVE SHEATH TUMORS https://drawittoknowit.com Schwannoma Neurofibroma Malign...

Soft Tissue Tumors - II Robbins &Cotran Pathologic Basis of Disease, 10th Edition Eds: Kumar, Abbas, Aster Robbins Basic Pathology, 11th Edition Eds: Vinay Kumar Abul K. Abbas Nelson Fausto , Richard N. Mitchell PERIPHERAL NERVE SHEATH TUMORS https://drawittoknowit.com Schwannoma Neurofibroma Malignant Peripheral Nerve Sheath Tumor Schwannomas Benign encapsulated tumors that may occur in soft tissues, internal organs, or spinal nerve roots. The most commonly affected cranial nerve is the vestibular portion of the eighth nerve. Tumors arising in a nerve root or the vestibular nerve may be associated with symptoms related to nerve root compression, which includes hearing loss in the case of vestibular schwannomas. Most schwannomas appear originating from a nerve. as a circumscribed mass, A) dense- cellular areas, B) loose- hypocellular areas (Antoni A and Antoni B) uniform proliferation of neoplastic Schwann cells Bland spindle cells align to produce nuclear palisading, resulting in alternating bands of nuclear and anuclear areas called Verocay bodies. No or very few Axons. Benign peripheral nerve sheath tumors. 1. Localized cutaneous neurofibromas: superficial nodular or polypoid tumors. Solitary sporadic lesions or often as multiple lesions in the context of neurofbromatosis 1 (NF1). neurofibrom a 2. Plexiform neurofibromas: grow diffusely within a nerve. Plexiform neurofibromas are virtually pathognomonic for NF1. Unlike other benign nerve sheath tumors, these tumors are associated with a small but real risk of malignant transformation. 3. Diffuse neurofibromas are infiltrative proliferations that can take the form of large, diffusely growing subcutaneous masses. These also are often associated with NF1. Unlike schwannomas, neurofibromas are not encapsulated. They may appear circumscribed, as in localized cutaneous neurofbromas, or Also in contrast to schwannomas, the neoplastic Schwann cells in neurofibroma are admixed with other cell types, including mast cells, fbroblast like cells, and perineurial-like cells. The background stroma often contains loose wavy collagen bundles Plexiform neurofbromas involve multiple fascicles of individual affected nerves Diffuse neurofbromas show an extensive infltrative pattern of growth within the dermis and subcutis of the skin m Neurofibromatosis-1 NF1 is an autosomal dominant disorder caused by mutations in the tumor suppressor neurofibromin, encoded on the long arm of chromosome 17 (17q). Neurofibromin - negative regulator of the potent oncoprotein Ras. Loss of function -> Ras hyperactivity -> Tumors Neurofibromas of all three main types Malignant peripheral nerve sheath tumors Optic gliomas and other glial tumors learning disabilities, seizures, skeletal abnormalities, vascular abnormalities with arterial stenoses, pigmented nodules of the iris (Lisch nodules), and pigmented skin lesions (axillary freckling and café-au-lait spots) in various degrees. Neurofibromatosis -1 Neurofibromatosis-2 ~10% of schwannomas are associated with familial neurofibromatosis type 2 (NF2). Despite the name, neurofibromas are not found in NF2 patients. Dominant loss of function mutation of merlin gene on chromosome 22. Merlin is a cytoskeletal protein that functions as a tumor suppressor by facilitating E-cadherin–mediated contact inhibition. Loss of merlin function-> contact inhibition is lost-> tumor cells proliferate Multiple schwannomas, meningiomas, and ependymomas The presence of bilateral vestibular schwannomas is a hallmark of NF2; Neurofibromatosis-2 Occurs in adults Evidence of Schwann cell derivation in tumor cells Malignant They may arise from transformation of a neurofibroma, usually of the plexiform type. About one-half of such tumors arise in patients with NF Peripheral Nerve Sheath High cellularity, anaplasia, necrosis, infltrative growth pattern, pleomorphism, and high proliferative activity Tu Skeletal muscle tumors Almost all is malignant. Rhabdomyoma, rare - heart. Rhabdomyosarcoma Most common soft tissue sarcoma of childhood and adolescence Head and neck or genitourinary tract (very few skeletal muscle?!) Histologic types: Spindle, embryonal, alveolar and pleomorphic. Alveolar variant: t(2;13) PAX3 – FOX01A fusion %60 Aggressive! Tx: combination of surgery, CT, RT. Embryonal variant Alveolar variant Spindle cell/ sclerosing variant Pleomorphic variant The malignancy is curable in almost two thirds of children; the prognosis is much less favorable in adults with the pleomorphic type. The rhabdomyoblast is the diagnostic cell in all histologic types. It has granular eosinophilic cytoplasm rich in filaments. Demonstration of skeletal muscle differentiation necessary (myogenin and MYOD-1, desmin) Sarcoma botryoides: Embryonal variant arising near the mucosal surfaces of the bladder or vagina and manifest as soft, grapelike masses. It has a better prognosis. Smooth Muscle Tumors Leiomyoma Benign smooth muscle tumors Well-circumscribed neoplasms anywhere in the body. Most frequent in the uterus and the skin. Leiomyosarcoma Malignant. Adults Histologic examination: spindle cells in interwoven fascicles. Smooth muscle origin should be shown (Immunohistochemistry- SMA, desmin, h-caldesmon) Superficial or cutaneous leiomyosarcomas usually are small and carry a good prognosis Retroperitoneal tumors are large and difficult to excise and cause death by both local extension and metastatic spread. Tumors of uncertain Origin. Undifferentiated Sarcoma Pleomorphic Fibroblastic Sarcoma/Pleomorphic Undifferentiated Sarcoma Aneuploid tumors with complex caryotype Poorly differentiated sarcomas: cytologic pleomorphism, the presence of bizarre multinucleate cells, and storiform architecture. Frequent mitosis and necrosis. They usually are large (5 cm to 20 cm), Unencapsulated Musculature of the proximal extremities or in the retroperitoneum. Extremely aggressive, recur unless widely excised, and have a metastatic rate of 30% to 50%. Synovial Sarcoma Phenotype of the neoplastic cells bears no resemblance to a synoviocyte, and less than 10% of tumors are intra-articular. Age: 20s to 40s. Deep soft tissues around the large joints of the extremities. Express both epithelial and mesenchymal markers by IHC (Cytokeratins and vimentin) Most show t(X;18)=> fusion gene encoding a chimeric transcription factor. Aggressive tumors, so is the treatment: radical surgery and chemotherapy. Common metastatic sites are lung, bone, and regional lymph nodes. 5-year survival rates: ~%50 Joint Tumors and Tumor-Like Lesions Reactive tumor-like lesions such as ganglions and synovial cysts are much more common than neoplasms these typically result from trauma or degenerative processes - Ganglion and Synovial Cysts - Tenosynovial Giant Cell Tumor Ganglion and Synovial Cysts Ganglion is a small cyst (less than 1.5 cm in diameter) Near a joint capsule or tendon sheath- the wrist Fluid-filled spaces that lack a true cell lining, Stem from cystic degeneration of connective tissue Completely asymptomatic. Synovial cyst: Herniation of synovium through a joint capsule or massive enlargement of a bursa (Baker cyst in the popliteal fossa) Tenosynovial Giant Cell Tumor Consistently associated with an acquired t(1;2) Age: 20s to 40s. Diffuse TGCT affects the knee in 80% of cases Aggressive lesions erode into adjacent bones and soft tissues. Localized TGCT Wrist and finger tendon sheaths. Well circumscribed The most common soft tissue tumor of the hand. Both lesions are amenable to surgical resection, but also prone to local recurrence, especially diffuse type. Tenosynovial Giant Cell Tumor https://www.tgcthcp.com/en/mechanis m-of-disease https://www.tgcthcp.com/en/mechanism-of-disease SUMMARY The category of soft tissue neoplasia describes tumors that arise from non-epithelial tissues, excluding the skeleton, joints, central nervous system, and hematopoietic and lymphoid tissues. A sarcoma is a malignant mesenchymal tumor. Although all soft tissue tumors probably arise from pluripotent mesenchymal stem cells, rather than mature cells, they can be classified as: - Tumors that recapitulate a mature mesenchymal tissue (e.g., fat). These can be further subdivided into benign and malignant forms. - Tumors composed of cells for which there is no "normal" counterpart (e.g., synovial sarcoma, UPS). Sarcomas with simple karyotypes demonstrate reproducible, chromosomal, and molecular abnormalities that contribute to pathogenesis and are sufficiently specific to have diagnostic use. Most adult (elderly) sarcomas have complex karyotypes, tend to be pleomorphic, and are genetically heterogeneous with a poor prognosis.