Dermatopathology (Part 2 of 4) Flashcards
what are some risk factors for melanoma?
light complexion, hair, and eyes (Scandinavian descent), history of blistering sunburn, proximity to the equator, indoor occupation with outdoor hobbies, family history of melanoma or dysplastic nevi
where is a common site for melanoma- especially for males?
upper back
where is a common site for melanoma-especially for females?
legs
where are common sites for malignant melanoma in blacks and asians?
soles, mucous membranes, palms, and nail beds
What are the ABCDEs of melanoma?
A: asymmetry B: irregular Borders; C: variegated Color; D: increasing Diameter; E: Evolution/ change over time
besides the ABCDEs of melanoma, what is another clinical feature of melanoma?
any pigmented lesion with a diameter greater than 6mm, any change, itching, or pain
what is the driver mutation in melanoma that disrupts the cell cycle control genes?
CDKN2A
what does CDKN2A encode?
3 tumor suppressor genes: p15, p16, and ARF
which driver mutation in melanoma is responsible for activating the pro-growth signaling pathways?
RAS and P13K/AKT; and BRAF
which driver mutation in melanoma is responsible for activating telomerase?
TERT
what is the most commonly mutated gene in melanoma?
TERT
what do the cells’ nuclei look like in melanoma?
the nucleus has margination of the chromatin- it tends to go towards the edges of the nucleus- tends to have this bright red nucleolus in the center- these are classic cells that we see with melanoma
what does radial growth mean?
horizontal spread of melanoma within the epidermis and superficial dermis; tumor cells seem to lack the capacity to metastasize
what is lentigo maligna?
usually an indolent lesion on the face of older men- may remain in the radial growth phase for several decades
what is superficial spreading?
the most common type of melanoma; usually involves sun-exposed skin
what is acral/mucosal lentiginous melanoma?
melanoma that is unrelated to sun exposure
what are three different types of radial growth of melanoma?
lentigo maligna, superficial spreading, and acral/mucosal lentiginous
what is the most common type of melanoma?
superficial spreading
what is the vertical growth phase of melanoma?
when tumor cells invade downward into the deeper dermal layers as an expansile mass, after a variable (and unpredictable) period of time following radial phase
what is the vertical growth phase heralded by?
by the appearance of a nodule and correlates with the emergence of a tumor subclone with metastatic potential
what is present in melanocytic nevi but absent in melanoma?
neurotization
the probability of metastasis in vertical growth melanoma lesions correlates with what?
the depth of the invasion
how is the depth of invasion in the vertical growth phase measured? what is this measurement known as?
it is the distance from the superficial epidermal granular cell layer to the deepest intradermal tumor cells; the BRESLOW THICKNESS
what are 5 criteria for a favorable prognosis of melanoma?
thinner tumor depth; no mitosis (no mitotic figures); brisk tumor infiltrating lymphocyte response; no regression; and lack of ulceration
what are 2 criteria for a poor prognosis of melanoma?
metastases (even micrometastases), and # and degree of LN involvement
what are 4 examples of benign epithelial tumors?
seborrheic keratoses, acanthosis nigricans, fibroepithelial polyp, and epithelial or follicular inclusion cyst (wen)
who is most likely to get seborrheic keratoses (Seb K)?
middle age or older individuals
how and where do seborrheic keratoses arise?
arise spontaneously and primarily on the trunk but can also be on the extremities, head, and neck
what is dermatosis papulosa nigra?
a subtype of seborrheic keratoses that affects people of color (multiple small lesions on the face- think morgan freeman)
what are the morphological features of Seb K? and what is the buzz-word for Seb K?
round, flat, coin-like, waxy papules; tan-dark brown; velvety or granular surface buzzword: WAXY
how can you differentiate between melanoma/dysplastic nevi and Seb K lesions?
Seb K lesions have a pore-like ostia impacted with keratin
what causes Seb K?
activating mutations in fibroblast growth factor receptor-3 (FGFR-3)- thought to drive the growth of the tumor
what is Leser-Trelat sign?
it is a paraneoplastic syndrome; a sudden appearance of large numbers of Seb K’s; associated with carcinomas of the GI tract
what are 3 characteristic features of Seb Ks?
exuberant keratin production (hyperkeratosis) and small keratin-filled cysts (horn cysts) and invaginations of keratin into the main mass (invagination cysts)
what is acanthosis nigricans? and what are the morphological features?
cutaneous sign of several underlying benign and malignant conditions; thickened hyperpigmented skin with velvet-like texture in flexural areas; intertriginous areas (two skin surfaces that rub together)
what is acanthosis nigricans associated with?
obesity and diabetes
besides being asosciated with obesity and diabetes, what else could acanthosis nigricans be associated with?
cancers, especially GI adenocarcinomas in middle age or older individuals (it is a paraneoplastic process–> growth factors released from tumors)
what is the pathogenesis of acanthosis nigricans?
increased growth factor receptor signaling in the skin: familial: FGFR-3
DM2: hyperinsulinemia believed to increase stimulation of insulin-like growth factor receptor-1
what is the histology like of acanthosis nigricans?
the epidermis and underlying enlarged dermal papillae undulate sharply–> numerous repeating peaks and valleys; NO MELANOCYTIC HYPERPLASIA
what is the medical term for skin tag?
fibroepithelial polyp or acrochordon
what age is more like to develop a fibroepithelial polyp?
middle age- elderly
what are fibroepithelial polyps associated with?
diabetes, obesity, and intestinal polyposis
what is a rare syndrome of polyps and perifollicular mesenchymal tumors (fibroblasts associated with hair bulb)?
Birt-Hogg-Dube syndrome
what is Birt-Hogg-Dube syndrome?
rare, polyps and perifollicular mesenchymal tumors
how do fibroepithelial polyps look morphologically?
soft, flesh-colored, bag-like tumors; often attached by slender stalk
what do fibroepithelial polyps look like histologically?
fibrovascular cores covered by benign squamous epithelium
how can you remove fibroepithelial polyps?
torsion- which leads to ischemic necrosis, which ultimately leads to their removal
what are epithelial or follicular inclusion cysts (Wen)?
invagination and cystic expansion of the epidermis or hair follicle (common in the scalp region)
what could happen to epithelial or follicular inclusion cysts (Wen)?
they are subject to traumatic rupture, which would cause a spill of keratin into the dermis leading to a painful granulomatous inflammatory response
what are adnexal (appendage) tumors?
hundreds of neoplasms arising from or showing differentiation toward cutaneous appendages; benign tumors that may be confused with basal cell carcinoma (BCC)
what is Cowden syndrome? and what is it caused by?
multiple trichilemmomas; a disorder caused by germline mutations in the tumor suppressor gene PTEN
what are people with Cowden syndrome at risk for?
endometrial cancer and breast cancer
what is a cylindroma?
ductal differentiation “jigsaw puzzle”; turban tumor: coalesce, hat-like growth
what gene is mutated in a cylindroma: turban tumor?
CYLD
what is the CYLD normal function?
it is a tumor suppressor gene
what are two CYLD associated genetic syndromes?
Familial Trichoepithelioma and Brooke-Spiegler
what is an eccrine poroma?
an adnexal (appendage) tumor of the palms and soles and anywhere where there are lots of sweat glands
what is a Syringoma?
eccrine differentiation, small tan papules, usually affects the lower eyelids
What can sebaceous adenomas be associated with?
internal malignancy in Muir-Torre syndrome and also a subset of cases with hereditary nonpolyposis colorectal carcinoma syndrome (aka Lynch Syndrome)
what is lynch syndrome caused by?
germline defects in DNA mismatch repair genes
What is a pilomatricoma and what is it associated with?
an adnexal (appendage) tumor showing hair follicle differentiation, associated with activating mutations in CTNNB1 (the gene encoding Beta-catenin)
What is beta-catenin important for?
early hair development and it regulates hair growth and maintenance
what is the buzzword for cylindromas?
jigsaw puzzle
what is a trichoepithelioma?
proliferation of basaloid cells that forms primitive structures resembling hair follicles
what is a cylindroma composed of?
islands of cells resembling the normal epidermal or adnexal basal cell layer (basaloid cells)
what does a sebaceous adenoma look like histologically?
bubbly due to the lipid
what are pilomatrixomas composed of?
basaloid cells that show trichilemmal or hair-like differentiation; ghost cells: no nucleus
what is the mutated gene in nevoid basal cell carcinoma syndrome?
PTCH
what is the mutated gene in cowden syndrome?
PTEN
what is the mutated gene associated with familial melanoma syndrome?
CDKN2
What is the manifestation of muir-torre syndrome?
internal malignancy (colon and others)
what is the mutated gene associated with Xeroderma pigmentosum?
XPA
