CMM 520 Ca syndromes and key clinical characteristics

Li Fraumeni

Bone, brain, blood, breast cancers

Hereditary diffuse gastric cancer

diffuse gastric/signet ring cancer

MEN1

3 P's: parathyroid, pancreas, pituitary neuroendocrine tumors

-Hyperparathyroidism

-skin findings: CALMS, inguinal or genital freckling, neurofibromas, Lisch nodules

-neurodevelopmental disabilities

MEN1 vs. MEN4 phenotype differences

MEN4 has lower penetrance and later ages at diagnosis

Nevoid basal cell carcinoma syndrome (Gorlin-Goltz)

-numerous BCC

-palmar pits

-odontogenic keratocysts in the jaw

-skeletal abnormalities

Cowden syndrome

-Mucocutaneous lesions (trichilimmomas, papillomas of face, acral keratosis)

-Macrocephaly

-Hamartomas

Muir-Torre syndrome

-uncommon Lynch variant phenotype

-Sebaceous neoplasms

Peutz-Jeghers syndrome

-Pigmented mucotaneous macules

-polyps in GI tract

-adenomas in GI tract

Birt-Hogg-Dube

-Skin (Fibrofolliculomas, Angiofibromas, Acrochordons)

-Lung cysts and spontaneous pneumothorax

-Renal cell carcinoma

NF1, NF2

-Neurofibroma

-Cafe-au-lait, axillary or inguinal freckling

MEN2

-Medullary thyroid carcinoma

-pheochromocytoma

-hyperparathyroidism

BAPI

-mealnocytic BAPI-mutated atypical intraderma tumors

-Spitz tumors

-ocular melanoma

Lynch

-CRC and endometrial ca

-polyps at younger age (<50 y)

-tumors show MMR deficiency and microsatellite instability

-CRC occurs in transverse and ascending colon (as opposed to descending and sigmoid)

Classic FAP

->100 adenomatous colon polyps and polyps develop early

-congenital hypertrophy of retinal pigment epithelium (eye lesion)

-osteomas

-adrenal masses

Von Hippel-Lindau syndrome

-hemangioblastomas

-renal cysts and RCC

-pheo/PGLs

-pancreatic cysts

-neuroendocrine tumors

-endolymphatic sac tumors

-epidydymal and broad ligament cystadenomas

Beckwith-Wiedemann syndrome

-macroglossia

-omphalocele

-Wilms tumors

-hyperinsulinemia/hypoglycemia

-abnormal growth

Carney complex

-Myxomas

-Thyroid tumors

-Skin pigment abnormalities

-Acromegaly

-Large cell calcifying Sertoli cell tumor

-Primary pigmented nodular adrenocortical disease (causes Cushing syndrome)

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC)

-Skin leiomyomas

-Uterine fibroids

-Renal cell cancers (type 2 papillary RCC)

Rothmund-Thomson Syndrome

-poikiloderma

-short stature

-skeletal abnormalities

-cataracts

Hereditary retinoblastoma

-leukocoria

-strabismus

Ataxia telangiectasia (AT)

-ataxia

-oculomotor apraxia

-choreoathetosis (writhing movements)

-eye and ear telangiectasias

-hypersensitivity to radiation

Tuberous sclerosis complex

-skin findings (Facial angiofibromas, fibromas, Ash leaf spots, Shagreen patch)

-CNS tumors

-neurological and behavioral differences

-kidney disease

-lung disease

Bloom syndrome

-growth deficiency

-sun sensitivity, facial erythema, telangiectasia

-immune deficiency

-distinct facial features (malar hypoplasia, nasal prominence, small mandible, dolichocephalic skull)

Fanconi anemia

-aplastic anemia/bone marrow failure

-microcephaly

-abnormal skin pigmentation

-renal malformations

Constitutional MMR deficiency (genes and features)

biallelic pathogenic variants in MLH1, MSH2, MSH6, and PMS2

hematologic cancer, brain cancer, and CALMs

Xeroderma pigmentosum

-UV sensitivity

-hyper and hypopigmentation

-neurologic abnormalities

Autoimmune lymphoproliferative syndrome

-autoimmune disease

-urticarial skin rashes

-non-malignant lymphoproliferation

What type of genetic testing is recommended in ALL cases of medullary thyroid cancer?

RET gene

What is a paraganglioma

neuroendocrine tumor in the adrenal medulla or ganglia of the sympathetic or parasympathetic nervous system

What is the difference between a paraganglioma and a pheochromocytoma?

a pheochromocytoma is a type of paraganglioma that is IN the adrenal gland

What is an extra-adrenal paraganglioma?

a paraganglioma that is located in the thoracic cavity, outside the adrenal glands

What type of paragangliomas are typically nonfunctional?

paragangliomas of the parasympathetic system (head and neck paragangliomas)

What type of paragangliomas are typically functional?

paragangliomas of the sympathetic nervous system (extra-adrenal paragangliomas and pheochromocytomas)

What do functional paragangliomas produce that cause the "fight or flight" response?

catecholamines

How are paragangliomas and pheochromocytomas treated?

surgery