Pediatric Pathology 2 PDF

Pediatric Pathology II Ana Yuil-Valdes, M.D. Department of Pathology and Microbiology, UNMC  Learning Objectives Be able to list the most common pediatric neoplasms Understand the definitions of hamartomas and heterotopias Be able to discuss the common presentation of retinob...

Pediatric Pathology II Ana Yuil-Valdes, M.D. Department of Pathology and Microbiology, UNMC  Learning Objectives Be able to list the most common pediatric neoplasms Understand the definitions of hamartomas and heterotopias Be able to discuss the common presentation of retinoblastomas Know the common syndromes associated with Wilms tumors  Childhood neoplasms Children are susceptible to a number of tumors that are less commonly seen in adults. Childhood tumors are often associated with certain syndromes After accidents, cancer is the second leading cause of childhood death  Tumors and Tumor-like lesions  Tumor/neoplasm = swelling; growth (L. “tumere” = to swell)  Tumor-like lesion = an abnormal collection of tissue with limited growth potential.  Benign Tumor = not able to metastasize  Malignant Tumor = capable of metastasis  Metastasis = transfer of disease from one organ or part to another not directly connected with it.  Tumor-like lesions Hamartoma– focal overgrowth of cells that are native to the organ site. – E.g. bile duct hamartoma in liver Heterotopia/choristoma/rest- growth of cells that are NOT native to the organ site. – E.g. pancreatic rest in gallbladder wall  Most common Benign Tumors of Childhood Hemangioma Lymphangioma Sacrococcygeal teratoma  Hemangioma A benign tumor of capillaries, often congenital and on the skin – “port-wine stain” – Associated with von-Hippel Lindau and Sturge Weber diseases Some do grow with the child, but most regress during childhood and are completely gone by adolescence.  Hemangioma Lesion at birth Lesion at 2 years  Lymphangioma A benign tumor of lymphatics – Found in most commonly in the neck or axilla, but can be found internally as well – “cystic hygroma” – Associated with Turner’s syndrome Lymphangioma (Cystic Hygroma)  Sacrococcygeal Teratoma A tumor of primitive cells, usually with different histologic types reflecting all three germ cell layers – Usually in sacrococcygeal area, but can be found anywhere, congenital – 75% benign, but some behave in a malignant fashion (immature teratomas) – Often associated with other developmental abnormalities like spina bifida, choanal atresia, etc. Sacrococcygeal Teratoma  Malignant tumors of childhood  Derived from the tissues/cells that are actively growing (bone marrow, brain, soft tissue).  Childhood malignancies differ biologically from adults.  Close relationship between abnormal development and tumor induction  Constitutional genetic abnormalities or syndromes  Tendency to spontaneously regress or differentiate from immature tissue into mature elements  Improved survival or cure  Common Malignant Neoplasms of Infancy and Childhood 0-4 Age Yr 5-9 Age Yr 10-14 Age Yr Leukemia Leukemia Leukemia Retinoblastoma Retinoblastoma Soft tissue sarcoma Neuroblastoma Neuroblastoma Osteogenic sarcoma Wilms’ tumor Hepatocellular carcinoma Thyroid carcinoma Hepatoblastoma Soft tissue sarcoma Hodgkin disease Soft tissue sarcoma (esp. Ewing tumor rhabdomyosarcoma) Teratoma Lymphoma CNS tumors Modified from Table 7-12, pg. 268  Neuroblastoma  Malignant tumor that arises from the cells of the sympathetic nervous system  Second most common solid malignancy of childhood  Usually in the abdomen, most commonly from the adrenal gland.  Can present with hypertension (90% make catecholamines - VMA & HVA) or “blueberry-muffin baby” (cutaneous metastases).  Neuroblastoma Neuroblastoma within adrenal gland Homer Wright pseudo-rosettes  Neuroblastoma Prognosis: – Stage: infiltration, lymph node status (ipsilateral vs bilateral), distant metastasis. – Differentiation (maturation) Neuroblastoma  ganglioneuroblastoma  ganglioneuroma Schwannian stroma (stroma-rich vs. stroma-poor) – Age: < 12 months do better – MYCN status (amplified MYCN is associated with advanced stage disease and treatment failure) – International Neuroblastoma Risk Group (INRG) classification system*. Have a tendency to widely spread (via mets and direct extension), but even with this disease, patients do well *Maris JM et al. Neuroblastoma. Lancet (2007);369:2106-20.  Retinoblastoma Most common childhood tumor of the eye Clinically presents with poor vision, strabismus, leukocoria, pain and tenderness Median age at presentation = 2 yrs. Arises from retinal epithelium Fatal without treatment, therapy includes enucleation, radiation, and chemotherapy Also spontaneously regresses. Leukocoria is an abnormal white reflection from the retina Sporadic vs. Familial Retinoblastoma Sporadic retinoblastoma – unilateral, unifocal, and present at a slightly older age Familial retinoblastoma – Germline RB1 gene mutation (60-70% of cases) – bilateral, multifocal, and presents at a younger age. – Increased risk of osteosarcoma Retinoblastoma  Wilms’ Tumor (Nephroblastoma) The most common primary kidney tumor in kids Seen most frequently from 2-5 years of age Usually presents as a palpable abdominal mass that can extend across the midline and into pelvis, hematuria, flank pain, or fever Prognosis with multidisciplinary therapy is good, even with lung metastasis. Associated with several maldevelopment syndromes – Most cases are sporadic  Wilms’ Tumor Kidney with Wilms’ Tumor Triphasic growth pattern: - blastema - stroma - epithelium – abortive tubules or glomeruli  WAGR Syndrome Wilms’ tumor (1/3), Aniridia Genitourinary anomalies, mental Retardation; Deletions involving WT-1 (11p13) Aniridia is an eye disorder characterized by a complete or partial absence of the colored part of the eye (the iris).  Denys-Drash Syndrome gonadal dysgenesis (male pseudohermaphroditism) renal abnormalities most develop Wilms’ (90 %); WT-1 (11p13) dominant negative missense mutation, NOT a deletion  Beckwith-Wiedemann syndrome Organomegaly (enlargement of body organs) adrenal cytomegaly (enlargement of adrenal cortex cells) Hemihypertrophy Macroglossia exophthalmos gigantism renal medullary cysts Hypoglycemia Perilobular nephrogenic rests  Increased risk for hepatoblastoma, adrenocortical tumors, rhabdomyosarcomas, pancreatic tumors.  Childhood neoplasms– a review The types of tumors common in kids are different than those seen in adults They are often of primitive cell types They are often associated with syndromes– if you see a tumor, look for the other findings Even “aggressive” tumors have a good prognosis with therapy Leukemias are the most common childhood neoplasms QUESTIONS