Tumor Syndromes Flashcards
What is the gene and inheritance pattern of Basal cell nevus syndrome (Gorlin syndrome)
PTCH (patched tumor suppressor protein)
AD
What is the underlying pathophysiology in basal cell nevus syndrome (Gorlin syndrome)?
Patched normally inhibits smoothened (when uninhibited signals intracellularly and activates GLI1/2 which is a transcription factor to promote transcription of genes involved in cellular growth) –> basal cell nevus syndrome results from a mutation in the Patched gene
What are the major criteria of Basal cell nevus syndrome (Gorlin syndrome)?
Needs 2 for confirmation (or one major and 2 minor)
- >2 BCC or 1 before the age of 20
- Palmoplantar pits (>3)
- Odontogenic keratocyts of the jaw, histologically proven
- Calcification of the falx cerebri
- Medulloblastoma
- First degree relatives with Basal cell nevus syndrome (Gorlin syndrome)
What are the minor criteria for Basal cell nevus syndrome (Gorlin syndrome)?
Rib anomalies (bifid most commonly, also fused, or markedly splayed)
- Cleft lip/palate
- Skeletal anomalies (pectus excavatum or pectus carinatum, polydactyly, syndactyly, kyphoscoliosis, Sprengel deformity, or other vertebral anomalies
- Macrocephaly
- Ovarian/cardiac fibroma
- Lyphomesenteric cysts
- Ocular abnormalities (strabismus, hypertelorism, congenital cataracts, glaucoma, and colobomas
What are the clinical findings in Basal cell nevus syndrome (Gorlin syndrome)?
Multiple, early-onset (usually around puberty), BCC [*Note: these can look like nevi milia, SK). These also favor sun-exposed areas like the face, neck and upper torso, but can occur in non-sun-exposed skin too
- Medulloblastoma usually presents in the first 3 yrs of life
- The palmoplantar pits are present in childhood
- The odontogenic keratocyst of the jaw need to be histologically proven, usually asymptomatic and then present late in the first decade of life
- All abnormalities listed as minor criteria (they like to test on bifid ribs, frontal bossing, ovarian/cardiac fibroma) can occur
- Also, can see an increased risk of fibrosarcoma, rhabdomyosarcoma, cryptorchidism, gynecomastia, agenesis of corpus callosum, ovarian fibromas, and cardiac fibromas
What is the treatment of Basal cell nevus syndrome (Gorlin syndrome)?
Standard BCC treatments plus you can use targeted therapy with vismodegib (acts as an artificial patched, inhibits smoothened
What syndromes are associated with increased basal cells?
Gorlin, Bazex-Dupré-Christol, Rombo, Brooke-Spiegler, xeroderma pigmentosum, and Schöpf-Schulz-Passarge
What is the gene and the mode of inheritance for Birt-Hogg-Dubé syndrome?
BHD gene (folliculin)
AD
When do the manifestations of Birt-Hogg-Dubé begin?
Third decade or later
What are the cutaneous findings of Birt-Hogg-Dubé?
Fibrofolliculomas, trichodiscomas, and acrochordons
- Clinically these looks like multiple tiny skin-colored to white papules on the face
What is the histology of the fibrofolliculomas’s / trichodiscomas seen in Birt-Hogg-Dubé?
These have slender strands of basophilic cells radiating from a follicular unit, surrounded by a fibrous stroma, can have a “bat-wing” appearance
What are the systemic findings in Brooke-Spiegler syndrome?
Salivary and parotid gland tumors
What are the extracutaneous findings in Birt-Hogg-Dubé?
Renal cell carcinoma and spontaneous recurrent pneumothorax (w/ lung cysts and bullous emphysema)
What is the gene and mode of inheritance for Brooke-Spiegler syndrome?
Gene: CYLD (tumor suppressor, is a deubiquitinating enzyme which interacts w/ NEMO to downregulate NFkappaB expression)
- AD
What are the skin findings in Brooke-Spiegler syndrome?
Presents in adolescence/early adulthood
- Cylindromas (Papules/nodules on scalp)
- Trichoepitheliomas (skin-colored to white small facial papules)
- Spiradenomas (Painful nodules on head/neck and elsewehre)
- Multiple BCC
- Can also see malignant degeneration into cylindro- and spiradenocarcinoma
What is the gene and mode of inheritance for multiple endocrine neoplasia (MEN) syndrome I (MEN1)?
MEN1 gene mutation (menin)
AD
What are the tumors seen in multiple endocrine neoplasia (MEN) syndrome I (MEN1)?
3 p’s
Pituitary (prolactinoma most common)
- Parathyroid (can present w/ kidney stones from calcium/phosphate derangements as the tumor is hyperplasia/adenoma)
- Pancreas (Zollinger elison sometimes, stomach ulcers) [tumors are usually islet cell hyperplasia, adenomas, or carcinoma]
Cutaneous findings in multiple endocrine neoplasia (MEN) syndrome I (MEN1)?
Can look like tuberous sclerosis: facial angiofibromas, gingival papules, hypopigmented macules and CALM
What is the gene and mode of inheritance for MEN IIA?
RET proto-oncogene
AD
What neoplasias are seen in MEN IIA?
Parathyroid hyperplasia (not in IIB)
- Medullary thyroid carcinoma (everyone)
- Pheochromocytoma
What are the skin findings in MEN IIA?
Lichen amyloidosis and macular amyloidosis
This get’s asked a bit
What is the gene and mode of inheritance for MEN IIB?
RET gene as well
AD
Skin findings in MEN IIB?
Remember that this is also called multiple neuroma syndrome, so:
- Mucosal neuromas on tongue/lips
- thickened lips
- Marfanoid habitus
What are the endocrine findings in MEN IIB?
Ganglioneuromatosis –> megacolon, diarrhea, and constipation
What is the gene and mode of inheritance for Cowden syndrome (multiple hamartoma syndrome)?
PTEN
- AD
What is the pathophysiology of Cowden syndrome (multiple hamartoma syndrome)?
PTEN is a tumor suppressor gene, loss of it leads to a proliferation of cutaneous/GI/mucosal/thyroid/breast tissues
What syndrome is PTEN also mutated in?
Bannayan-Riley-Ruvalcaba which is like Cowden syndrome + pigmented macules on the glans penis, lipomas, macrocephaly, and mental retardation.
Some rarer forms of Proteus syndrome can also be PTEN but usually AKT1
What are the cutaneous findings in Cowden syndrome (multiple hamartoma syndrome)?
Sclerotic fibromas, facial tricholemmomas (skin-colored to light brown small papules), punctate palmoplantar keratoses, keratotic papules (acral keratoses) [These acral keratoses occur on the dorsal hands/feet/forearms/legs], lipomas, skin tags, and inverted follicular keratoses
What are the oral findings in Cowden syndrome (multiple hamartoma syndrome)?
Small skin-colored grouped papillomas leading to a “cobblestone” appearance on the lips and gingival/buccal/labial mucosa
- These are effectively fibrofolliculomas of the mouth
What are the thyroid findings in Cowden syndrome (multiple hamartoma syndrome)?
Goiter, adenomas, and carcinoma (follicular carcinoma most commonly)
Breast findings in Cowden syndrome (multiple hamartoma syndrome)?
Fibrocystic disease, fibroadenomas, and adenocarcinoma (most common malignancy in Cowden’s overall, up to 50% of female pts)
What are the GI findings in Cowden syndrome (multiple hamartoma syndrome)?
Hamartomatous polyps along GI tract, low risk of malignancy
In general what cancers are seen in Cowden syndrome (multiple hamartoma syndrome)?
#1 Breast cancer (in women)
- Follicular thyroid cancer
- Endometrial carcinoma (10% of female pts)
- GU carcinomas/cysts
What MSK abnormalities can be seen w/ Cowden syndrome (multiple hamartoma syndrome)?
Craniomegaly (80% of pts), adenoid facies, kyphoscoliosis, bone cysts, large hands/feet
What is Lhermitte-Duclos disease?
Dysplastic gangliocytoma of the cerebellum
Presents w/ overgrowth of cerebellar ganglion cells leading to ataxia, seizures and increased intracranial pressure
this is pathognomonic criterion for Cowden’s
What is the gene involved and the method of inheritance for Gardner syndrome?
APC gene (adematous polyposis coli)
AD
Pathogenesis of Gardner syndrome?
APC is a tumor suppressor gene that regulates Beta-catenin
What are the cutaneous manifestations of Gardner syndrome?
Epidermoid cysts (classically w/ pilomatricoma changes), fibromas (in the skin subcutaneous and mesentery/retroperitoneal areas), lipomas
What are the GI manifestations of of Gardner syndrome?
Premalignant polyposis throughout the GI tract
- Also see desmoid tumors, locally aggressive but don’t metastasize female>male can occur post-surgically after resection and these can lead to obstruction
Huge increase in the risk of adenocarcinoma, especially high in the colon/rectum where 100% of affected pts get it
What are the ocular manifestations of Gardner syndrome?
congenital hypertrophy of retinal pigment epithelium (CHRPE; 70%)
What are the other tumors that can be seen in Gardner syndrome?
Osteomas (skull/mandible/maxilla; 80% of pts, painless), odontomas of teeth, supernumerary teeth, papillary thyroid carcinoma in women, hepatoblastoma, adrenal adenomas, sarcomas, pancreatic carcinomas, and brain tumors
What is Turcot syndrome?
Gardners but w/ glioblastomas and medulloblastomas
What is the treatment for Gardner syndrome?
Prophylactic colectomy when polyp formation is first evident, usually in the 2-3rd decade
