Radiation Oncology/Cancer Syndromes/Syndromes You Should Know

Syndrome associated with Esophageal Ca Plummer-Vinson Syndrome Patterson Kelly Syndrome = Sideropenia (iron deficiency) syn. Increase chance of Ca in: Esophagus Oral Cavity Hypopharynx Syndromes associated with Colorectal Ca Familial Adenomatous Polyposis (FAP) Gardner Syndrome Individuals with FAP develop hundred to thousands of benign colonic polyps during their early adulthood If not removed by surgery —>develop into adenocarcinomas Autosomal Dominant 100% Penetrance, 100% progress to carcinoma, most by age 30 Gene on chromosome 5q21 Adenomatous Polyposis Coli (APC) Tumor suppressor gene APC also plays a role in sporadic CRC In FAP —> Germline gene is mutated In sporadic —> somatic cell gene is mutated Also get desmoid tumors Hereditary non-polyposis colorectal cancer (HNPCC) Lynch Syndrome Predisposition to Colorectal Ca Also increased risk for Endometrium, ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin. Autosomal Dominant, but has incomplete penetrance Earlier than sporadic, later than FAP: 45 years (vs 63 for sporadic) Less severe than in FAP Few tumors later in life Genetic instability Expansion or contraction of the length of microsatellites Microsatellite instable (MSI+) Genes involved: MSH2 (Mut S Homolog 2) Encodes a protein that is required for recognition and repair of DNA mismatches MLH1 MSH6 (Mut S Homolog 6) PMS2 (Post-meiotic segregation 2) Mut L homolog 3 (MLH3) ~3% of population. Estimated to be responsible for ~5% of colorectal cancer; conversely, patients with HNPCC have ~80% risk of colon cancer and 30-50% risk of endometrial cancer Cowden Syndrome See PTEN Lifetime risk for developing CRC: 10% Risk of breast cancer: 50% Other lesions: Lipomas Fibromas Ganglioneuromas Hamartomas specific cutaneous lesions (facial trichilemmomas and acral verrucous papules) Benign breast fibroadenomas, neurofibromas, lipomas Uterine leiomyomas Meningiomas Germline mutations in PTEN Tumor suppressor gene Encoding the phosphatase and tensin homolog On chromosome 10 Turcot Syndrome See Turcot Syndrome Syndromes associated with Pituitary adenoma MEN-1 Syndrome Autosomal dominant Tumors of Pituitary in 25% of patients with MEN-1 syn. Parathyroid glands Pancreatic islet cells. Pituitary adenomas develop in 25% of patients with MEN type-1. Carney complex rare spotty skin pigmentation myxomas endocrine overactivity schwannomas Pituitary adenoma Syndromes associated with Thyroid Papillary Ca Turcot Syndrome Gardner Syndrome Familial Polyposis Familial Papillary Syn. Syndromes associated with Soft Tissue Sarcoma Li Fraumeni Syndrome See Li Fraumeni Rare Autosomal Dominant Linked with germline mutations germline p53 tumor suppressor gene mutation Detects damaged DNA and helps for repair or arranged cell death ( apoptosis ) CHEK2 mutations Controls p53 Is activated by ATM High susceptibly to CANCER Breast Ca Gastric Ca Brain tumors Acute leukemia Soft tissue sarcomas Pediatric Rhabdomyosarcoma Bone sarcomas Adrenal cortical carcinoma Presents at young age Multiple times of ca diagnosis Neurofibromatosis Autosomal Dominant Nerve tissue grows tumor Neural crest cells Schwann cells Melanocytes Endoneural fibroblast Syndromes associated with Thymoma Good's Syndrome Thymoma with immunodeficiency Combined B and T cell immunodeficiency in adults Increased susceptibility infections Bacterial encapsulated organisms Opportunistic viral Opportunistic fungal Most consistent immunological abnormalities Hypogammaglobulinemia Reduced or absent B cells Treatment: Resection of the thymoma Immunoglobulin replacement to maintain adequate trough IgG. Myasthenia Gravis Autoimmune neuromuscular junction disorder Presence of anti-acetylcholine receptor antibodies ==> Acetylcholine receptor deficiency at the motor end plate Rapid exhaustion of voluntary muscular contractions, with a slow return to the normal state Syndromes associated with Cutaneous malignancy Gorlin Syndrome See Nevoid Basal Cell Carcinoma Syndrome (NBCCS)Autosomal Dominant Nevoid Basal Cell Carcinoma Syndrome Defects within multiple body systems such as the skin, nervous system, eyes, endocrine system, and bones PTCH mutation Medulloblastoma Turcot Syndrome Mismatch repair cancer syndrome Rare Alternative form of two other syndromes associated with polyp formation: Hereditary non-polyposis colorectal cancer (HNPCC) Familial Adenomatose Polyposis (FAP) Multiple adenomatous colon polyps Increased risk of Brain and Colon Ca GBM Medulloblastoma Thyroid Ca Autosomal Dominant MLH1 PMS2 Von Hippel Lindau Rare Autosomal dominant Mutation in the von Hippel–Lindau tumor suppressor gene on chromosome 3 Increase risk benign and malignant tumors Cafe au lait spots Most common tumors: CNS CNS tumor Retinal hemangioblastomas Kidney RCC (Clear cell) Pheochromocytomas Pancreas Pancreatic neuroendocrine tumors Pancreatic cysts Albinism Xeroderma Pigmentosum See Xeroderma pigmentosum defect in base excision repair (NER pathway) Ultra sensitive to light and radiation SCC and melanoma skin autosomal recessive Rothmund–Thomson syndrome Fanconi anemia See Fanconi Anemia Autosomal recessive/X-linked disorder Causes congenital marrow failure, poor growth, morphologic abnormalities, and usually macrocytic anemia. Most common cause of congenital aplastic anemia --> Most patients are diagnosed by the age of 16 and have a predisposition for developing cancer Dx is made by chromosomal breaks on genetic analysis along with clinical findings: Middle ear abnormalities + deafness, abnormal/absent thumbs (Hypoplastic thumbs), cafe au lait spots, etc