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.

• 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

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

Xeroderma Pigmentosum

See Xeroderma pigmentosum

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