PEDIATRIC TUMORS Disease Age Retinoblastoma Commonly around age 2 (familial = earlier, multiple tumors) Neuroblastoma (also ganglioneuroblastoma, ganglioneuroma) 85% <5 yo, 50% <2 yo, but can arise in older children, rarely in adults. Page 1 of 6 Most Common Sites RETINA Clinical Symptoms Radiographic Features Pathologic Features Prognosis Genetics / Other Information Decreased visual acuity, strabismus, whitish hue to pupil, pain and tenderness in the eye N/A Primitive small blue cells (PSBC’s from here on) making rosettes around lumens (FlexnerWintersteiner Rosettes) Untreated, fatal. But, with early intervention, survival is common. Treatment = enucleation, radiation, chemo Anywhere along sympathetic chain, but 40% in adrenal medulla. Secrete catecholamines in >90%, therefore their breakdown products (VMA, HVA) can be detected in the urine. Other hormones may be produced. Because areas of widespread necrosis are common, these areas can calcify (dystrophic calcification), and these can be seen on radiographs. Cells range from PSBC’s to more differentiated cells with elongated cytoplasmic processes (primitive neurites). More differentiated tumors may contain (possibly entirely) mature ganglion cells or intermediate cells (ganglioneuroblasts). Rosettes may be present—processes oriented inward, no lumen (HomerWright rosettes). Degree of differentiation correlates with prognosis (more = better). Loss of tumor suppressor gene (Rb) on long arm of Chromosome 13. Can be sporadic (more common) or familial (in which case, more likely multiple tumors and bilateral) The most differentiated (mature ganglion cells) = ganglio-neuroma. It is benign. Intermediate = ganglioneuroblastoma. The prognosis is highly variable— infants with tumors limited to primary sites or metastasized to skin, liver, marrow: excellent, tumor may even spontaneously regress. Older children, especially if met to other sites, 90% fatal. Familial cases – uncommon, poor prognosis (1p abnl) Genetics: Chr 1p abnormality, N-myc amplification = poor prognosis PEDIATRIC TUMORS Disease Age Wilms’ Tumor Usually diagnosed between the ages of 2 and 5. Page 2 of 6 Most Common Sites KIDNEY Clinical Symptoms Radiographic Features Pathologic Features Prognosis Genetics / Other Information Most frequently detected by parents as an abdominal mass (asymptomatic at detection). Calcification not as prominent as neuroblastoma, so not as well seen on radiographs. Soft, encapsulated tumor. Histologically, 3 components: epithelium (tubules), stroma (usu fibroblast like, maybe skel muscle, cartilage), and blastema (PSBC’s). If spread beyong renal capsule, or if histologic anaplasia (tumor cells >3X size of neighboring cells, atypical mitoses) = poor prognosis. The two WT tumor suppressor genes = chromosome 11. Familial and sporadic forms. Prior to 1960’s, 5 yr survival 10-40%, now 90%). - BeckwithWiedemann (organomegaly, macroglossia, hemihypertrophy, inc. risk of hepatoblastoma, rhabdomyosarcoma, adrenocortical tumors, brain tumors) Associated with several syndromes: - WAGR complex (Wilms’, aniridia (no iris), GU malform., mental retardation) Rhabdomyosarcoma 2/3 <10 yo, also teens, rarely adults Head and neck region, GU tract, extremities, trunk. Palpable mass or symptoms due to a mass N/A Primitive cells w/ evidence of skeletal muscle differentiation. Actin/myosin Z-bands on EM, crossstriations possible on light micro. Other cases, PSBC’s. Good: embryonal, botyroid/spindle cell subtypes. (95, 88% 5yr surv) Intermediate: embryonal, not subtyped (MOST COMMON) – 66% 5yr surv) Poor: alveolar (common (31%), 53% 5 yr surv) - Denys-Drash (gonadal dysgenesis, nephropathy) Alveolar subtype = t(2;13) or t(1;13). PEDIATRIC TUMORS Disease Age Page 3 of 6 Most Common Sites Clinical Symptoms Radiographic Features Pathologic Features Prognosis Genetics / Other Information Rare, poor: anaplastic, diffuse; undifferentiated sarcoma (<50% 5 yr surv) Ewing’s Sarcoma (peripheral neuroepithelioma/PNET (primitive neuroectodermal tumor) Hemangioma Teratoma Second decade Most common tumor of infancy. Histologically similar to adult hemangiomas, but many will spontaneously regress. Congenital. Depends on age of discovery, not age of onset… Pelvis, femur, humerus Pain, fever, signs resembling infection Bone lesion – often diaphyseal, lytic, permeative; prominent periosteal reaction, soft tissue mass common. Skin, usu head and neck region Some irregularly raised (strawberry hemangiomas); others flat and widespread (port wine stains). N/A Most in the sacrococcygeal area, others mediastinal, other midline locations. Can be extraordinarily large (largest tumor on record – 300 lb teratoma…) N/A PSBC tumor, usu arranged in sheets, nests, organoid patterns. PNET vs. Ewing’s? - PNET = greater neural differentiation (rosettes), Ewing’s = sheets, etc - Same translocation, so probably just variable histology of same tumor. Blood vessels of varying sizes, capillaries to larger vessels. Mostly cutaneous. Tissues from all three embryonal layers, all of which are generally mature/benign. In general, extent of disease is the most important prog indicator (site and subtype also play a role). Localized = 70-85% 5 yr surv; mets = 30%) 1960’s = 10% 5yr surv. Today, 50%, but metastatic = much worse. t(11;22) characteristic, less commonly t(7;22) or t(21;22). Benign. N/A Normally benign, but 10-15% contain areas of immaturity/ malignancy. Rather common tumor – 1/20,000 to 1/40,000 live births. Older children = more likely PEDIATRIC TUMORS Page 4 of 6 Disease Age Most Common Sites Clinical Symptoms Radiographic Features Pathologic Features Langerhans Cell Histiocytosis (LCH) (Histiocytosis X, Eosinophilic granuloma, Langerhans’ cell granulomatosis Any age may be affected, most are <5 yo at diagnosis. Isolated, lytic bone lesions, usually craniofacial. Bone lesions, may be associated with diabetes insipidus and exophthalmos (Hand-SchullerChristian Syndrome) or be disseminated (Leterrer-Siwe Syndrome). (both of these syndromes are rare – HSC <5%, L-S even less) Lytic bone lesions. If in long bones, usu in diaphysis. Clonal proliferation of Langerhans’ cell histiocytes (macrophages…), with variable amounts of inflammatory cells (principally eos, less often PMN/lymphs). Histiocytes = folded/grooved nuclei with abundant cytoplasm. EM = Birbeck granules (tennisracquet shaped) within cytoplasm. Prognosis malignant. Excellent. Adverse outcome correlated with: >3 bones involved hepatosplenomegaly thrombocytopenia young age at diagnosis (<3 yo) Genetics / Other Information Immunohistochemical markers: S-100 and CD1a. PEDIATRIC TUMORS Disease Age Osteosarcoma Predominantly second decade; secondary forms older (5th decade +) Page 5 of 6 Most Common Sites Distal femur and proximal tibia (knee bones), but virtually any bone possible. Clinical Symptoms Radiographic Features Pathologic Features Prognosis Pain, swelling or mass, frequent pathologic fracture. Permeative, destructive, maybe lytic/blastic, Codman’s triangle (periosteal reaction – elevated s.t. triangular area between cortex & periosteum), frequent soft tissue extension Strict definition: malignant tumor in which the tumor cells produce malignant osteoid/bone. Chondroid and hyaline cartilage may also be seen. Traditionally treated by amputation or disarticulation of affected limb; but 5 yr surv <=20%. Now, chemo + limbsparing surgery – 5 yr surv <= 60%. Histologic subtypes: Prognosis is correlated with postchemotherapy necrosis. If >= 90% of tumor has necrosed, good prognosis. <90%, bad. (Necrosis = tumor cell dropout – bone with holes where tumor used to be) Intramedullary (within bone): - conventional – osteoblastic, chondroblastic, fibroblastic. MOST COMMON. - well-differentiated – resembles fibrous dysplasia w/o typical clinical/radiologic features. - small cell – resembles Ewing’s but assoc with malignant bone production - telangiectatic – may resemble an aneurysmal bone cyst, but obvious anaplastic malignant cells. Juxtacortical (arises from bone surface): - parosteal – welldifferentiated involving cortical bone surface. - periosteal – chondroblastic Genetics / Other Information PEDIATRIC TUMORS Disease Age Page 6 of 6 Most Common Sites Clinical Symptoms Radiographic Features Pathologic Features involving cortical bone surface - high grade surface – conventional osteosarcoma involving cortical bone surface. Secondary: - irradiation, Paget’s disease, fibrous dysplasia – all usually high grade conventional OS. Prognosis Genetics / Other Information