Skin Pathology Flashcards
Traumatic lesion breaking the epidermis and causing a raw linear area (i.e., deep scratch); often self induced
Excoriation
5 Disorders of pigmentation and melanocytes
Freckle Lentigo Melanocytic nevus Dysplastic nevus Melanoma
Most common pigmented lesion of childhood; appear after sun exposure, typically fading and darkening cyclically with season changes and are caused by increased melanin pigment in basal keratinocytes
Freckle (ephelis)
_________, which are seen in neurofibromatosis, have similar histoogy to freckles but are larger and arise independently of sun exposure
Cafe au lait spots
Benign localized hyperplasia of melanocytes initiated in infancy and childhood but can occur in all ages; do NOT darken when exposed to sunlight. Histologically characterized by linear melanocytic hyperplasia restricted to cell layer immediately above basement membrane
Lentigo
_______ is a term describing linear melanocytic hyperplasia in the basal cell layer in melanocytic tumors
Lentiginous
[i.e., acral lentiginous melanoma]
Melanocytic nevi are benign growths usually acquired by activating mutations in components of the ______ signaling pathway
They are usually <6mm, tan-brown, and _____ pigmented; consisting of flat macules or elevated papules with well-defined rounded borders
Ras
Uniformly
3 types of nevi include:
________ = nests at dermoepidermal junction
________ = nests or cords grow into underlying dermis w/ nests in dermis and epidermis
_______ =no epidermal nests; usually older lesions
Junctional
Compound
Intradermal
Describe histology of melanocytic nevi (moles)
Benign histology with superficial nests of large-round cells with increased melanin
Deeper than that are cords or single cells, smaller cells, and decreased pigment
Deepest are fusiform, fascicles resembling neural tissue
[she explains it as maturing in opposite direction from normal epithelium— with larger more heavily pigmented cells being more superficially located, and smaller less pigmented cells as nevus goes deeper into dermis]
Autosomal dominant syndrome with 50% chance of progression to melanoma by age 60
Dysplastic nevus syndrome
T/F: all melanoma were at one time dysplastic nevi
False — not all dysplastic nevi become melanoma, and not all melanoma come from dysplastic nevi
Dysplastic nevi often acquire activating mutations in ____ and ____ genes
NRAS; BRAF
Histologically, dysplastic nevi are _____ than acquired nevi. They have ______ pigmentation with irregular borders. They have enlarged epidermal nests that may coalesce with other nests. _____ _____ occurs when single nevus cells replace basal cells along the epidermal-dermal junction. Atypia is signified by large nuclei, irregular angulated nuclear contour, and hyperchromasia. Lymphocytic infiltrate of superficial dermis may occur, as well as melanin incontinence. Linear ____ surrounds the epidermal rete ridges
Larger
Variegated
Lentiginous hyperplasia
Fibrosis
Melanoma is the most deadly of all skin cancers and is strongly linked to acquired mutations caused by exposure to __________ which causes _________
UV radiation in sunlight; DNA damage
Risk factors for melanoma
Light complexion, hair, eyes
History of blistering sunburn(s)
Proximity to the equator
Indoor occupation; outdoor hobbies
Family hx of melanoma or dysplastic nevi
Precursor lesions (congenital or dysplastic nevi)
Xeroderma pigmentosum
Most common sites of melanoma in men vs. women
Men — upper back
Women — legs
Although it is rare in blacks and asians, where is malignant melanoma most commonly found in these pt populations?
Soles
Mucous membranes
Palms
Nail beds
Clinical features of melanoma: ABCDEs
Asymmetry Irregular Borders Variegated Color Increasing Diameter Evolution/change over time (rapid)
Any pigmented lesion with diameter >6mm, any change, itching, or pain should raise suspicion for _____
Melanoma
Driver mutations in melanoma
Disruption in cell cycle control genes: CDKN2A, tumor suppressor genes p15/INK4b, p16/INK4a, p14/ARF
Activation of pro-growth signaling pathways: mutations in BRAF 40-50%, NRAS
Activation of telomerase: TERT in 70% of tumors (MOST COMMON)
Morphologic findings associated with melanoma
Epidermis: single abnormal cells and nests with aggregates of lymphocytic infiltration
Prominent red nucleoli
HMB-45+ staining = indicator of melanoma
The _____ growth phase of melanoma consists of horizontal spread within the epidermis and superficial dermis; tumor cells seem to lack the capacity to ________
Radial; metastasize
Radial growth melanoma; usually an indolent lesion on the face of older men, may remain in the radial growth phase for several decades
Lentigo maligna
Most common type of melanoma, usually involving sun exposed skin; radial growth phase
Superficial spreading melanoma
Type of radial growth melanoma that is UNRELATED to sun exposure
Acral/mucosal lentiginous melanoma
During _____ growth phase of melanoma, tumor cells invade downward into deeper dermal layers as an expansile mass, after a variable and unpredictable period of time following radial phase.
This phase is often heralded by the appearance of a _____ and correlates with the emergence of a tumor subclone with _______ potential. Unlike melanocytic nevi, “______” is absent
Vertical
Nodule; metastatic; neurotization
What indicates the probability of metastasis in melanoma?
Correlated with depth of invasion, which is the distance from superficial epidermal granular cell layer to the deepest intradermal tumor cells — aka the BRESLOW THICKNESS
No mitosis, brisk tumor infiltrating lymphocyte response, no regression, and lack of ulceration are indications of a _____ prognosis in melanoma
Favorable
4 types of benign epithelial tumors
Seborrheic keratoses
Acanthosis nigricans
Fibroepithelial polyp
Epithelial or Follicular Inclusion Cyst (Wen)
Benign epithelial tumors arising in middle age, or older individuals, forming round flat waxy papules with tan-brown color that have velvety or granular surface, pore-like ostia impacted with keratin, and possibly hyperkeratosis with horn cysts
Seborrheic keratoses
[dermatosis papulosa nigra when there are multiple small lesions on face — think morgan freeman]
________ = paraneoplastic syndrome in which there is sudden appearance of large numbers of seborrheic keratoses
Leser-trelat sign
Adnexal (appendage) tumors may consist of hundreds of neoplasms arising from or showing differentiation toward cutaneous appendages. They are benign, nondescript, flesh-colored, solitary or multiple papules and nodules.
________ _______ consists of multiple trichilemmomas d/t loss of function in PTEN leading to increased risk for endometrial cancer, breast cancer, etc
Cowden syndrome
Adnexal tumor with ductal differentiation on forehead or scalpe showing “jigsaw puzzle” pattern
Cylindroma
[turban tumor is when these coalesce with hat-like growth; related to CYLD]
Adnexal tumor found on palms and soles where sweat glands are numerous
Eccrine poroma
Adnexal tumor with eccrine differentiation of lower eyelids
Syringoma
Sebaceous adenoma is associated with ________ syndrome — hereditary nonpolyposis colorectal carcinoma syndrome with DNA mismatch repair protein defects
Muir-Torre
Adnexal tumor with follicular differentiation, CTNNB1 encodes Beta catenin
Pilomatricoma
Inheritance and gene/protein affected in neurofibromatosis I
AD inheritance
Loss of NF1/neurofibromin (normally negatively regulates RAS signaling/neurofibromas)
Inheritance and gene/protein affected in neurofibromatosis II
AD inheritance
NF2/merlin (normally integrates signaling/neurofibromas and acoustic neuromas)
Inheritance and gene/protein affected in xeroderma pigmentosum
AR inheritance
Affects XPA (normally participates in nucleotide excision repair — loss may result in melanoma and nonmelanoma skin cancers)
_____ _____ occurs with sun damaged skin, particularly in lightly pigmented individuals, ionizing radiation exposure, industrial hydrocarbons, arsenic, etc. and progressively worsen with the potential to become ________ with time. They tend to be <1cm, tan-brown, red, or skin colored with rough sandpaper-like consistency
Actinic keratosis; SCC
Actinic keratosis may present grossly as a ______ _______ due to excessive keratin production. Morphologic features include ______ (single-cell keratinization, pink cytoplasm), intracellular bridges, blue-gray _______ (sun damage), and parakeratosis
Cutaneous horn; dyskeratosis; elastosis
Lesions of actinic keratosis that develop on the lips
Actinic cheilitis
Second most common tumor arising in sun exposed sites in older people; occurring more frequently in males than females (except on the legs), and <5% metastasize to regional LNs
SCC
Pathogenesis of SCC
DNA damage induced by UV light; incidence is proportional to degree of lifetime sun exposure
Other factors include immunosuppression (including oncogenic viruses, especially HPV 5 and 8), industrial carcinogen exposure, chronic ulcers and draining osteomyelitis, old burns, tobacco and betel nut chewing, etc