Genodermatoses-Adults Flashcards
What is the function of the gene mutated in BSS
Tumor supressor gene that regulates proteins involved in cell growth, specifically it is a deubiquinating enzyme
What genes is mutated in Brooke-Spiegler?
Cylindromatosis gene (CYLD) on chromosome 16
Mode inheritance Brooke-Spiegler
AD
What are the main skin findings in Brooke Spiegler
Trichoepitheliomas (trichoepithelioma papulosum multiplex)
Cylindromas
Spiradenomas
Less frequently milia, epidermoid cysts
Cancers associated with Brooke-Spiegler?
Parotid and salivary gland
BCC transformation from trichoepithelioma
Spiradenocarcinoma
Cylindromcarcinoma
What are the limited forms of Brooke Spiegler
1) Multiple familial trichoepitheliomas
2) Familial cylindromatosis
Malignant transformation of spiradenoma? cyclindroma? Trichoepithelioma?
Spiradenoma–> spiradenocarcinoma
Cylindroma–> cylindromacarcinoma
Trichoepithelioma–> BCC
How do trichoepitheliomas present?
- multiple skin coloured, cystic or solid papules or nodule on face most often with predilection for nose, upper lip and mesolabial folds and eyes
- lesions often grouped but discrete
- 2-4mm
- often symmetric
other locations include scalp, neck, trunk
Lineage of spiradenoma?
Apocrine
*has never been on glabrous/non-hair bearing skin
How do spiradenomas present
solitary (mostly), deep seated 1 cm nodule, painful, often blue or pink hue with normal overlying skin
*biopsy diagnosis
Upper half body, ventral surface
How to cylindromas present
Typically present on the head and neck, especially scalp,
- single or multiples
- firm, rubber like
- pink to blue
- Can coalesce to form giant tumor on the scalp (turban tumor)
What is this?
Cylindroma
How does Brook Spiegler present generally
Multiple tumors, often head and neck predominant, usually around puberty
Can be trichoepithelioma predominant, cylindroma predominant, or multiple adnexal tumors
-Can be 0.5cm-3 cm or larger
-Can become confluent on scalp
-10-30 or hundreds
-Slow growing (if rapid growing then suspect malignant transformation)
What are some treatment options Brooke-Spiegler
electrosurgery, dermabrasion, and laser therapy
What % patients with BSS develop malignant transformation
5-10%
What is Muir Torre syndrome
AD inherited condition characterized by sebaceous tumors, KAs and internal malignancies, subset of Lynch syndrome
What % Lynch syndrome have Muir-Torre
around 30%
What gene is mutated in Muir-Torre
MSH2 > MLH1>MSH6
What is type of gene is MSH2, MLH1, MSH6
DNA mismatch repair
When is onset muir-torre?
Mid 50s
Skin findings of Muir Torre?
Sebaceous tumors: Sebaceous adenoma, sebaceous carcinoma, sebaceous, seboacanthoma, cystic sebaceous tumors
Keratoacanthomas: Sometimes have sebaceous differentiation
What is typical distribution sebaceous tumors? Distribution in Muir torre
Head/neck
Periocular for sebaceous carcinoma
Muir torre tend to be numerous (>2), extremities/trunk>h/n
What internal malignancies are associated with Muir-Torre
Colorectal MC
GU-bladder, upper tract
Gyne-Endometrial, ovarian
Others:
- Breast
- stomach
- small intestine
- head/neck
- hematolocial
What screening is needed in Lynch syndrome
Colonoscopy EGD UA + cytology TVUS Endo bx Hysterectomy and bilateral salpingo-oophorectomy
MENI internal organ findings
Parathyroid (think nephrolithiasis)
Pancreatic-duodenal (neuroendocrine)
Pituitary
3 P’s and NO M (no medullary thyroid)
MEN1 skin findings
Collagenomas Lipomas Angiofibromas CALMS hypo pigmented macules Gingival fibromas
MEN IIA internal organ
MTC (medullary thyroid cancer)
Adrenal
Parathyroid
MAP
Skin findings MEN IIA
Lichen and macular amyloidosis
MENIIB internal organs
MTC
Adrenal
GI ganglionneuromatosis
MAG
MENIIB skin findings
Mucosal neuromas
Enlarged lips
Marfanoid habitus
Unibrow (synophyrs)
MEN4
MTC Adrenal Parathyroid Pituitary Pancreatic
MAPPP*
MEN4 skin findings
maybe combo of both
MENI gene?
MEN1 -AD
MENII gene?
RET-AD
MEN4 gene
CDKN1B-AR
What is another name for Cowdens syndrome
Multiple hamartoma syndrome
Gene and inheritance pattern Cowdens
AD
Incomplete penetrance, Variable expressivity,
PTEN
What pathway affected in Cowdens
m-TOR
What non skin features characterize Cowdens
Breast cancer (also fibrocystic changes, fibroadenomas, adenocarcinoma Thyroid cancer Endometrial cancer
Others: Thyroid nodules fibrocystic breasts GI polyposis (hamartomatous polyps) Cerebellar hamartoma
