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
      • Bone sarcomas
      • Adrenal cortical carcinoma
    • Presents at young age
    • Multiple times of ca diagnosis


    • 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

    • 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


    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