Head and Neck

Vania Nosé, MD, PhD

Familial Cancer Syndromes With Head and Neck Neoplasms
Syndrome	Gene	Head and Neck Tumor	Other Manifestations
Dyskeratosis congenita	TERT, TERC, DKC1, TINF2; other genes involved in telomere maintenance	SCCa of head and neck, SCCa of tongue	Skin cancer, anorectal carcinoma, gastric carcinoma, lung carcinoma, colon carcinoma, esophageal carcinoma, Hodgkin lymphoma, retinoblastoma, and others
Fanconi anemia	13 separate genes comprising the “Fanconi anemia pathway”: FANCx	SCCa of head and neck	Short stature, eye abnormalities, Wilms tumor and other solid tumors, SCCa of cervix; hematologic neoplasms (by age 45, cumulative incidence of hematologic malignancy is 25%; median diagnosis age: 11-14 years); predominantly myeloid malignancies, acute myeloid leukemia, and other hematopoietic abnormalities, (600x increased risk of AML; 5,000x increased risk of MDS); solid tumors such as SCCa (esophageal, anogenital), hepatocellular carcinoma, brain tumors; breast cancer susceptibility
XP	Genes involved in nucleotide excision repair of ultraviolet light-induced damage (XPA-XPG)	SCCa of tongue (increase 100,000x in XP patients < 20 years compared to general population)	Carcinomas and sarcomas of skin, melanomas, ocular cancer, and other internal malignancies, such as brain tumors (medulloblastomas and glioblastomas); spinal cord astrocytomas; carcinomas of lung, uterus, breast, stomach, kidney, and testicles; leukemias; and multiple benign tumors
Bloom syndrome	BLM (a tumor-suppressor gene belonging to the family of RecQ DNA helicase)	SCCa of head and neck	Up to 50% of patients will develop a malignancy; ˜ 10% of patients have ≥ 2 primary cancers, with fewer patients reported to have 3, 4, or even 5 primary neoplasms; hematolymphoid malignancies predominant in the first 2 decades of life; carcinomas predominant after the first 2 decades of life and arise in varied sites, e.g., skin, head and neck, gastrointestinal tract (including esophagus [both squamous cell carcinoma and adenocarcinoma], stomach, and colon), lung, uterus, and breast; medulloblastoma, Wilms tumor, osteogenic sarcoma
Retinoblastoma	RB	Carcinoma of nasal cavity	Retinoblastoma; 2nd cancers common in patients with RB mutations (i.e., osteosarcoma, leiomyosarcoma, fibrosarcoma, chondrosarcoma, rhabdomyosarcoma, Ewing sarcoma, melanoma, pinealoblastoma, Hodgkin lymphoma, breast carcinoma)
NF2	NF2	Vestibular schwannoma: Bilateral vestibular schwannomas a hallmark of NF2 (90-95% of patients)	Plexiform schwannoma (features occurring more frequently in NF2-associated schwannomas include whorl formation, multiple tumors involving a single nerve, and juxtaposition to meningioma), neurofibroma, meningoma, ependymoma, conventional MPNST and MPNST ex-schwannomas reported in NF2 but very rare
Basal cell nevus syndrome (Gorlin syndrome)	PTCH1	Odontogenic cysts, dentigerous cysts	Triggers that should prompt evaluation for Gorlin syndrome: Odontogenic keratocysts if age < 20 years old, basal cell carcinoma if age < 20 years old, palmar or plantar pits, lamellar calcification of falx cerebri, medulloblastoma, desmoplastic, characteristic facies with broad nasal root (and hypertelorism), numerous tumors, including basal cell carcinoma, medulloblastoma, meningoma, ovarian fibroma, cardiac fibroma
HPTH-jaw tumor syndrome	HRPT2	Fibroma of the jaw, ossifying fibroma of the jaw	Hyperparathyroidism develops late in adolescence in > 80% of patients: Parathyroid hyperplasia, adenoma, and carcinoma; renal cysts, hamartomas, and cortical adenomas; Wilms tumor; testicular germ cell tumor; papillary thyroid carcinoma, and other neoplasms
FAP	APC	Juvenile nasopharyngeal angiofibroma	≥ 100 colorectal adenomas (classical FAP), fundic gland polyps, antral adenomas, gastric cancer (rare), hepatoblastomas in male infants, hepatic adenomas and hepatocellular carcinomas, pancreatic adenocarcinoma and intraductal mucinous neoplasms of pancreas, adenocarcinoma of gallbladder, fibromatosis, multiple osteomas, congenital hypertrophy of the retinal pigmented epithelium, cribriform-morular variant of papillary thyroid carcinoma
AML: Acute myeloid leukemia; FAP: Familial adenomatous polyposis; HPTH: Hyperparathyroidism; MDS: Myelodysplastic syndrome; MPNST: Malignant peripheral nerve sheath tumor; NF2: Neurofibromatosis type 2; SCCa: Squamous cell carcinoma; XP: Xeroderma pigmentosum.