Soft Tissue Tumors Flashcards
What are soft tissue tumors?
They are non epithelial tissue excluding the bones, joints, CNS, hematopoietic and lymphoid tissue. They are mainly benign apart from skeletal muscle neoplasms. Most of these tumors are sporadic and have no known predisposing cause, a small number are associated to mutations in tumor suppressor genes and environmental exposures. It has been hypothesized that these tumors arise from pluripotent mesenchymal stem cells which acquire oncogenes and tumor suppressor genes. According to WHO there are 160 different types of STTs.
What are some useful IHC markers used to identify the cell of origin in STTs?
• CD34 is a useful marker that is expressed by progenitor cells in the BM, epithelial cells and solitary fibrous tumors (lesions found in pleural cavity). It can be used also as a vascular marker. Since CD34
is very common, negative control is done with ERG, a transcription factor present in endothelium, many vascular tumors and prostate malignancy (60% of prostate carcinomas);
• S100 protein is one of the fist markers used in IHC because immunogenic and abundant in the nervous system. It is present also in melanomas, nevi and nerve tissue tumors.
• MDM2 amplification is a useful marker for liposarcoma (especially for atypical lipoma). Its expression in normal tissue is low, while it is expressed at high levels in Reed-Sternberg cells and
liposarcomas.
• CDK4 (cyclin dependent kinase) a gene involved in the cell cycle.
• Actin is a component present in all cells, but there are different isoforms and some are specific for certain cell types (smooth muscle cells, skeletal muscles, cardiac muscles). In case of mutation, it
may be lost or expressed by just few cells. Actin is a useful marker to identify the cell of origin;
• Markers of intermediate filaments, that are different for each tissue (for example desmin for
muscles);
• CD31 is a vascular marker;
• Factor VIII is a vascular marker as it is expressed by endothelial cells.
What are some tumors of adipose tissue?
Lipoma : Benign tumor of fat. They are soft, mobile and painless and usually cured by excision. It is composed of mature, monomoprhic adipocytes with small nuclei. Usually arises in the subcutis of the proximal extremities and trunk.
Liposarcoma : Arises in 50/60 yr olds in deep soft tissue. Histologically they are divided in three morphological subtypes ; well differentiated liposarcoma, de differentiated liposarcoma and myxoid liposarcoma.
What is the difference between the morphological types of Liposarcomas?
Well differentiated : Indolent with locally aggressive behavior. Adipocytes vary in size and shape and present scattered atypical spindle cells. Involves the MDM2 gene which encodes for a potent P53 inhibitor.
De differentiated : Loss of normal adipocyte morphology. There are lipoblasts. Macroscopically the lesion is thick with white nodules. These tumors metastasize.
Myxoid : Contains basophilic extracellular matrix, arborizing capillaries and lymphoblasts. It is called myxoid because of the gelatinous appearance and it is intermediate in malignancy but is able to metastasize.
What are some fibrous tumors?
Nodular fascitis : It is a benign self limited fibroblastic and myofibroblastic proliferation that occurs in young adults in the upper extremities. The tumor grows rapidly and reaches a well- circumscribed or slightly infiltrative lesion no larger than 5 cm. It spontaneously regresses. Histologically it is highly cellular and contains immature fibroblast and myofibroblasts which varie in shape.
Fibromatoses : Which can be superficial, deep or dermatofibrosarcoma protuberans.
What are the different types of fibromatoses?
Superficial : Is an infiltrative fibroblastic proliferation that can cause local deformity but has an innocuous clinical course. They are characterized by nodular or poorly defined broad fascicles of long fascicles, surrounded by abundant dense collagen. Can be palmar and cause progressive flexion of the fourth and fifth finger, plantar or penile.
Deep : Desmoid tumors are large, infiltrative masses that frequently recur but do not metastasize. Macroscopically, fibromatoses are gray-white, firm, poorly demarcated masses. They are rubbery and tough with a marked inflammation of surrounding muscle, nerve and fat. Microscopically, fibroblasts are arranged in broad sweeping fascicles together with dense collagen, resembling a scar.
Dermatofibrosarcoma protuberans : A tumor that involves deeply the skin. It is characterized by spindle cells with some mitotic activity and organized in an altered way. CD34 is positive. These lesions recur after excision.
What are some skeletal muscle tumors?
Rhabdomyosarcoma : It is a malignant mesenchymal tumor with skeletal muscle differentiation. Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood and adolescence. The pediatric form usually arises in sinuses, head and neck and genitourinary tract. There are three subtypes:
Alveolar : 20%, microscopically, it is traversed by a network of fibrous septae, creating a crude resemblance to pulmonary alveoli.
Embryonal : 60%, presents as soft gray infiltrative mass. It has the best prognosis among rhabdomyosarcomas. The tumor cells mimic skeletal muscle at various stages of embryogenesis and consist of sheets of both primitive round and spindle cells in a myxoid stroma.
Pleomorphic : 20%, It is characterized by numerous large, sometimes multinucleated, bizarre eosinophilic tumor cells. IHC (e.g. myogenin) is necessary to confirm rhabdomyoblastic differentiation. It is often fatal.
What are some smooth muscles tumors?
Leiomyoma : Benign tumors of SM often arising in the uterus. Multiple leiomyomas can be associated to hereditary leiomyomatosis. They are 1-2 cm in dimension and mainly composed of fascicles of densely eosinophilic spindle cells that tend to intersect each other at right angles. The tumor cells have elongated nuclei and show minimal atypia and few mitotic figures.
Leiomyosarcoma : Occur mainly in adult women and develops in sof tissues of the extremities, retroperitoneum and great vessels. They consist of eosinophilic spindle cells with nuclei arranged in interweaving fascicles.
What are some peripheral nerve sheath tumors?
Schwannomas : They are encapsulated benign tumors with Schwann cell differentiation arising directly from peripheral nerves. They are well circumscribed, do not invade the nerve and allow for easy surgical excision. Loss of expression of NF2 product merlin is a consistent finding.
Neurofibromas : They are benign nerve sheath tumors with a heterogeneous composition (neoplastic Schwann cells, fibroblasts, mast cells, CD34+ spindle cells, perineural-like cells). Neurofibromas can be either sporadic or NF1-associated. Different types can be distinguished according to growth pattern.
Malignant peripheral nerve sheath tumors : They are high-grade tumors, but low-grade variants are recognized. 50% occur in NF1 patients because of malignant transformation from a plexiform neurofibroma. Sporadic cases may arise de novo. Most are associated with larger peripheral nerves in the chest, abdomen, pelvis, neck or limb-girdle. They exhibit complex chromosomal aberrations. From the morphological point of view, the lesions are poorly defined tumor masses that frequently infiltrates along the axis of the parent nerve and invade adjacent soft tissue. Mitoses, necrosis and nuclear anaplasia are common
What are the different types of neurofibromas?
Superficial cutaneous neurofibroma : Small, well-delineated pedunculated nodule that arise in the dermis or subcutaneous fat. They can be isolated (if sporadic) or multiple (if NF1 associated). They have low cellularity and bland Schwann cells mixed with stromal cells. Adnexal structures can be involved.
Diffuse neurofibroma : A large plaque-like elevation of skin, typically NF1-associated. It infiltrates the dermis and subcutaneous tissue and appendage structures. Focal collections of cells mimic the appearance of Meissner corpuscles.
Plexiform neurofibroma : Found in deep or superficial locations in association with nerve roots or large nerves. The external perineurial layer is preserved, giving individual nodules an encapsulated appearance. The thickening of multiple nerve fascicles results in a “bag of worms” appearance. They are usually associated with NF1. They may transform into MPNST.
