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</li> <li>Individuals with FAP develop hundred to thousands of benign colonic polyps during their early adulthood</li> <li>If not removed by surgery —>develop into adenocarcinomas</li> <li>Autosomal Dominant <ul> <li>100% Penetrance, 100% progress to carcinoma, most by age 30</li> </ul> </li> <li>Gene on chromosome 5 q21 <ul> <li>Adenomatous Polyposis Coli (APC)</li> <li>Tumor suppressor gene</li> <li>APC also plays a role in sporadic CRC</li> <li>In FAP —> Germline gene is mutated</li> <li>In sporadic —> somatic cell gene is mutated</li> </ul> </li> <li>Also get desmoid tumors</li> </ul> Hereditary non-polyposis colorectal cancer (HNPCC) <ul> <li>Lynch Syndrome</li> <li>Predisposition to Colorectal Ca <ul> <li>Also increased risk for Endometrium, ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin.</li> </ul> </li> </ul>

<li>Autosomal Dominant, but has incomplete penetrance</li> <li> Earlier than sporadic, later than FAP: 45 years (vs 63 for sporadic)</li> <li>Less severe than in FAP <ul> <li>Few tumors later in life</li> </ul> </li> <ul> <li>Genetic instability <ul> <li>Expansion or contraction of the length of microsatellites</li> <li>Microsatellite instable (MSI+)</li> </ul> </li> <li>Genes involved: <ul> <li>MSH2 (Mut S Homolog 2) <ul> <li>Encodes a protein that is required for recognition and repair of DNA mismatches</li> </ul> </li> <li>MLH1</li> <li>MSH6 (Mut S Homolog 6)</li> <li>PMS2 (Post-meiotic segregation 2)</li> <li>Mut L homolog 3 (MLH3)</li> </ul> </li> <li>~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</li> </ul> Cowden Syndrome See PTEN <ul> <li>Lifetime risk for developing CRC: 10%</li> <li>Risk of breast cancer: 50%</li> <li>Other lesions: <ul> <li>Lipomas</li> <li>Fibromas</li> <li>Ganglioneuromas</li> <li>Hamartomas</li> <li>specific cutaneous lesions (facial trichilemmomas and acral verrucous papules)</li> <li>Benign breast fibroadenomas, neurofibromas, lipomas</li> <li>Uterine leiomyomas</li> <li>Meningiomas</li> </ul> </li> </ul> <ul> <li>Germline mutations in PTEN <ul> <li>Tumor suppressor gene <ul> <li>Encoding the phosphatase and tensin homolog</li> <li>On chromosome 10 </li> </ul> </li> </ul> </li> </ul> Turcot Syndrome See Turcot Syndrome Syndromes associated with Pituitary adenoma MEN-1 Syndrome <ul> <li>Autosomal dominant</li> <li>Tumors of <ul> <li>Pituitary <ul> <li>in 25% of patients with MEN-1 syn.</li> </ul> </li> <li>Parathyroid glands</li> <li>Pancreatic islet cells. Pituitary adenomas develop in 25% of patients with MEN type-1.</li> </ul> </li> </ul> Carney complex <ul> <li>rare</li> <li>spotty skin pigmentation</li> <li>myxomas</li> <li>endocrine overactivity</li> <li>schwannomas</li> <li>Pituitary adenoma</li> </ul> Syndromes associated with Thyroid Papillary Ca <ul> <li>Turcot Syndrome</li> <li>Gardner Syndrome</li> <li>Familial Polyposis</li> <li>Familial Papillary Syn.</li> </ul> Syndromes associated with Soft Tissue Sarcoma Li Fraumeni Syndrome See Li Fraumeni <li>Rare</li> <li>Autosomal Dominant</li> <li>Linked with germline mutations <ul> <li>germline p53 tumor suppressor gene mutation <ul> <li>Detects damaged DNA and helps for repair or arranged cell death ( apoptosis )</li> </ul> </li> </ul> </li> <li>CHEK2 mutations <ul> <li>Controls p53</li> </ul> </li> <li>Is activated by ATM</li> <li>High susceptibly to CANCER <ul> <li>Breast Ca</li> <li>Gastric Ca</li> <li>Brain tumors</li> <li>Acute leukemia</li> <li>Soft tissue sarcomas <ul> <li>Pediatric Rhabdomyosarcoma</li> </ul> </li> <li><ul> <li>Bone sarcomas</li> <li>Adrenal cortical carcinoma</li> </ul> </li> <li>Presents at young age</li> <li>Multiple times of ca diagnosis</li> </ul>

Neurofibromatosis <ul> <li>Autosomal Dominant</li> <li>Nerve tissue grows tumor</li> <li>Neural crest cells</li> <li>Schwann cells</li> <li>Melanocytes</li> <li>Endoneural fibroblast</li> </ul> Syndromes associated with Thymoma Good's Syndrome <ul> <li>Thymoma with immunodeficiency</li> <li>Combined B and T cell immunodeficiency in adults</li> <li>Increased susceptibility infections <ul> <li>Bacterial encapsulated organisms</li> <li>Opportunistic viral</li> <li>Opportunistic fungal</li> </ul> </li> <li>Most consistent immunological abnormalities <ul> <li>Hypogammaglobulinemia</li> <li>Reduced or absent B cells</li> </ul> </li> <li>Treatment: <ul> <li>Resection of the thymoma</li> <li>Immunoglobulin replacement to maintain adequate trough IgG.</li> </ul> </li> </ul> Myasthenia Gravis <ul> <li>Autoimmune neuromuscular junction disorder</li> <li>Presence of anti-acetylcholine receptor antibodies <ul> <li>==&gt; Acetylcholine receptor deficiency at the motor end plate</li> </ul> </li> <li>Rapid exhaustion of voluntary muscular contractions, with a slow return to the normal state</li> </ul> Syndromes associated with Cutaneous malignancy Gorlin Syndrome See Nevoid Basal Cell Carcinoma Syndrome (NBCCS)<ul> <li>Autosomal Dominant</li> <li>Nevoid Basal Cell Carcinoma Syndrome</li> <li>Defects within multiple body systems such as the skin, nervous system, eyes, endocrine system, and bones</li> <li>PTCH mutation</li> <li>Medulloblastoma</li> </ul>

Turcot Syndrome <ul> <li>Mismatch repair cancer syndrome</li> <li>Rare</li> <li>Alternative form of two other syndromes associated with polyp formation: <ul> <li>Hereditary non-polyposis colorectal cancer (HNPCC)</li> <li>Familial Adenomatose Polyposis (FAP)</li> </ul> </li> </ul> <ul> <li>Multiple adenomatous colon polyps</li> <li>Increased risk of Brain and Colon Ca <ul> <li>GBM</li> <li>Medulloblastoma</li> </ul> </li> <li>Thyroid Ca</li> <li>Autosomal Dominant</li> <li>MLH1</li> <li>PMS2</li> </ul>

Von Hippel Lindau <ul> <li>Rare</li> <li>Autosomal dominant</li> <li>Mutation in the von Hippel–Lindau tumor suppressor gene on chromosome 3</li> <li>Increase risk benign and malignant tumors</li> <li>Cafe au lait spots</li> <li>Most common tumors: <ul> <li>CNS <ul> <li>CNS tumor</li> <li>Retinal hemangioblastomas</li> </ul> </li> <li>Kidney <ul> <li>RCC (Clear cell)</li> <li>Pheochromocytomas</li> </ul> </li> <li>Pancreas <ul> <li>Pancreatic neuroendocrine tumors</li> <li>Pancreatic cysts</li> </ul> </li> </ul> </li> </ul>

Albinism Xeroderma Pigmentosum See Xeroderma pigmentosum <ul> <li>defect in base excision repair (NER pathway)</li> <li>Ultra sensitive to light and radiation</li> <li>SCC and melanoma skin</li> <li>autosomal recessive</li> </ul>

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