Dermatopathology (Part 3 of 4) Flashcards
what is actinic keratosis (AK)?
usually occurs in sun-damaged skin and exhibits hyperkeratosis
where does actinic keratosis usually occur?
face, arms, and dorsum of hands
who is at risk for developing actinic keratosis (AK)?
lightly pigmented individuals, those exposed to ionizing radiation, industrial hydrocarbons, or arsenic
what could happen to actinic keratosis lesions?
these lesions may show progressively worsening dysplastic changes that culminate in cutaneous squamous cell carcinoma
how does actinic keratosis appear morphologically?
less than 1 cm, tan-brown, red or skin colored, rough sandpaper-like consistency
some actinic keratosis lesions produce so much keratin that what happens?
a cutaneous horn develops
what is it called when the lips develop actinic keratosis lesions?
actinic cheilitis
what is the cytologic atypia seen in actinic keratosis?
cytologic atypia is seen in the lowermost layers of the epidermis and may associated with hyperplasia of basal cells; the atypical basal cells usually have pink or reddish cytoplasm due to dyskeratosis; intracellular bridges are present; the superficial dermis contains thickened, blue-gray elastic fibers (elastosis)
what is elastosis caused from?
abnormal elastic fiber synthesis by sun-damaged fibroblasts
what is parakeratosis?
seen in actinic keratosis; when the stratum corneum is thickened and unlike normal skin, the cells in this layer often retain their nuclei
What is the second most common tumor arising in sun exposed sites in older people?
squamous cell carcinoma (basal cell carcinoma is first)
who is more likely to get squamous cell carcinoma (SCC)?
men more likely than women except on legs then women more likely than men
what is metastasis like of SCC?
less than 5% of these tumors metastasize to regional nodes; if there is metastasis then they are usually deeply invasive and involve the subQ
what is the most important cause of SCC?
DNA damage induced by exposure to UV light; incidence proportional to degree of lifetime sun exposure
besides DNA damage induced by UV light, what are two other important causes of SCC?
immunosuppression and epidermodysplasia verruciformis
what patients are at risk of immunosuppression leading to SCC?
those undergoing chemotherapy or organ transplantation
why are immunosuppressed individuals at risk for developing SCC?
there is a decrease in host surveillance and an increase in risk of infection by oncogenic virus
what oncogenic viruses are especially associated with development of SCC?
HPV 5 and HPV 8
what is epidermodysplasia verruciformis?
an autosomal recessive disorder- HPV is implicated and they are at an increased risk of cutaneous SCC
besides sun damage, immunosuppression, and genetic disorders, what other factors put individuals at risk of developing SCC?
industrial carcinogens (tars and oils), chronic ulcers and draining osteomyelitis, old burn scars, ingestion of arsenicals, ionizing radiation, tobaccos and betel nut chewing
most studies on the genetics of squamous cell carcinoma have focused on acquired defects in sporadic tumors and their precursors (actinic keratosis) and the relationships between these defects and sun exposure; the incidence of what mutations in actinic keratosis is high in caucasians? and this suggests what?
TP53 mutations; this suggests that p53 dysfunction is an early event in the development of tumors induced by sunlight–> so there is an improper repair of UV damage
in addition to p53 mutations, what other mutations can lead to SCC?
mutations in RAS signaling and decreased Notch signaling
what is xeroderma pigmentosum?
an autosomal recessive disorder that affects the XPA gene leading to a mutation in the nucleotide excision repair pathway, which is required for accurate repair of pyrimidine dimers–> leading to an increase SCC risk
what are in situ lesions of SCC?
SCC that have not invaded through the basement membrane of the dermoepidermal junction
how do in situ SCC lesions appear?
as sharply defined, red, scaling plaques with atypical (enlarged and hyperchromatic) nuclei involve all levels of the epidermis
how do invasive SCC lesions appear?
nodular keratin production (hyperkeratotic scale) and they may ulcerate; they are anaplastic cells with dyskeratosis
what is the most common invasive cancer?
basal cell carcinoma (BCC)
what are the growth characteristics of BCC?
slow growing and rarely metastasizes; cured by local excision
who is at risk of developing BCC?
sun exposed sites of lightly pigmented elderly adults, immunosuppressed individuals, and those with xeroderma pigmentosum
what mutations are associated with BCC?
mutations that activate the Hedgehog signaling pathway–> leads to unbridled hedgehog signaling on the PTCH gene
what is nevoid basal cell carcinoma syndrome/ Gorlin syndrome/ basal cell nevus syndrome?
an autosomal dominant disorder that presents as multiple BCCs in people less than 20 years old; also accompanied by various other tumors especially medulloblastomas and ovarian fibromas; also odontogenic keratocytes, pits of palms and soles
what is the gene associated with NBCCS/Gorlin/ basal cell nevus syndrome?
PTCH
what are the morphological features of BCC? and what is the buzzword for BCC?
pearly papules, telangiectasias, rodent ulcers; buzzword= pearly
how does BCC appear histologically?
the tumor cells resemble those in the normal basal cell layer of the epidermis; hyperchromatic nuclei, peripheral palisading; artificial clefts separate stroma from tumor
what is peripheral palisading?
when cells are arranged radially with their long axes in parallel alignment
What are benign Fibrous histiocytomas (dermatofibroma) and who is at risk of developing them?
they are benign dermal neoplasms of uncertain origin; adults, legs of young-middle aged women
what is the presentation of benign fibrous histiocytomas?
asymptomatic or tender; +/- size over time, indolent; dimple sign: lateral pressure on the skin produces a depression
what does a benign fibrous histiocytoma look like histologically?
firm, tan-brown papules, less than 1 cm, become flattened over time; they are benign spindle-shaped cells with well-defined, non-encapsulated masses in the mid dermis
what is pseudoepitheliomatous hyperplasia?
many cases of benign fibrous histiocytoma demonstrate a peculiar form of overlying epidermal hyperplasia, characterized by downward elongation of hyperpigmented rete ridges
what is the dimple sign seen in dermatofibromas?
lateral pressure on the skin produces a depression
what is a dermatofibrosarcoma protuberans (DFSP)?
the malignant version of a dermatofibroma; well differentiated primary fibrosarcoma of the skin; slow growing, locally aggressive, can recur, but rarely metastasizes
what mutation is associated with a dermatofibrosarcoma protuberans?
translocation collagen 1A1 (COL1A1) and PDGFB–> promotes tumor cell growth
what are the morphological features of dermatofibrosarcoma protuberans?
a protuberant nodule, usually trunk, firm indurated plaque +/- ulceration
how does a dermatofibrosarcoma protuberans appear histologically?
closely packed fibroblasts arranged radially–> storiform formation
what does the overlying epidermis look like in a patient with dermatofibrosarcoma protuberans?
it is thinned (opposite of dermatofibroma)
what is the honeycomb pattern?
seen in cases of dermatofibrosarcoma protuberans when there is deep extension from the dermis into the subQ fat
