Dermatopathology (Part 3 of 4)

Question 1

what is actinic keratosis (AK)?

Answer 1

usually occurs in sun-damaged skin and exhibits hyperkeratosis

Question 2

where does actinic keratosis usually occur?

Answer 2

face, arms, and dorsum of hands

Question 3

who is at risk for developing actinic keratosis (AK)?

Answer 3

lightly pigmented individuals, those exposed to ionizing radiation, industrial hydrocarbons, or arsenic

Question 4

what could happen to actinic keratosis lesions?

Answer 4

these lesions may show progressively worsening dysplastic changes that culminate in cutaneous squamous cell carcinoma

Question 5

how does actinic keratosis appear morphologically?

Answer 5

less than 1 cm, tan-brown, red or skin colored, rough sandpaper-like consistency

Question 6

some actinic keratosis lesions produce so much keratin that what happens?

Answer 6

a cutaneous horn develops

Question 7

what is it called when the lips develop actinic keratosis lesions?

Answer 7

actinic cheilitis

Question 8

what is the cytologic atypia seen in actinic keratosis?

Answer 8

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)

Question 9

what is elastosis caused from?

Answer 9

abnormal elastic fiber synthesis by sun-damaged fibroblasts

Question 10

what is parakeratosis?

Answer 10

seen in actinic keratosis; when the stratum corneum is thickened and unlike normal skin, the cells in this layer often retain their nuclei

Question 11

What is the second most common tumor arising in sun exposed sites in older people?

Answer 11

squamous cell carcinoma (basal cell carcinoma is first)

Question 12

who is more likely to get squamous cell carcinoma (SCC)?

Answer 12

men more likely than women except on legs then women more likely than men

Question 13

what is metastasis like of SCC?

Answer 13

less than 5% of these tumors metastasize to regional nodes; if there is metastasis then they are usually deeply invasive and involve the subQ

Question 14

what is the most important cause of SCC?

Answer 14

DNA damage induced by exposure to UV light; incidence proportional to degree of lifetime sun exposure

Question 15

besides DNA damage induced by UV light, what are two other important causes of SCC?

Answer 15

immunosuppression and epidermodysplasia verruciformis

Question 16

what patients are at risk of immunosuppression leading to SCC?

Answer 16

those undergoing chemotherapy or organ transplantation

Question 17

why are immunosuppressed individuals at risk for developing SCC?

Answer 17

there is a decrease in host surveillance and an increase in risk of infection by oncogenic virus

Question 18

what oncogenic viruses are especially associated with development of SCC?

Answer 18

HPV 5 and HPV 8

Question 19

what is epidermodysplasia verruciformis?

Answer 19

an autosomal recessive disorder- HPV is implicated and they are at an increased risk of cutaneous SCC

Question 20

besides sun damage, immunosuppression, and genetic disorders, what other factors put individuals at risk of developing SCC?

Answer 20

industrial carcinogens (tars and oils), chronic ulcers and draining osteomyelitis, old burn scars, ingestion of arsenicals, ionizing radiation, tobaccos and betel nut chewing

Question 21

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?

Answer 21

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

Question 22

in addition to p53 mutations, what other mutations can lead to SCC?

Answer 22

mutations in RAS signaling and decreased Notch signaling

Question 23

what is xeroderma pigmentosum?

Answer 23

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

Question 24

what are in situ lesions of SCC?

Answer 24

SCC that have not invaded through the basement membrane of the dermoepidermal junction

Question 25

how do in situ SCC lesions appear?

Answer 25

as sharply defined, red, scaling plaques with atypical (enlarged and hyperchromatic) nuclei involve all levels of the epidermis

Question 26

how do invasive SCC lesions appear?

Answer 26

nodular keratin production (hyperkeratotic scale) and they may ulcerate; they are anaplastic cells with dyskeratosis

Question 27

what is the most common invasive cancer?

Answer 27

basal cell carcinoma (BCC)

Question 28

what are the growth characteristics of BCC?

Answer 28

slow growing and rarely metastasizes; cured by local excision

Question 29

who is at risk of developing BCC?

Answer 29

sun exposed sites of lightly pigmented elderly adults, immunosuppressed individuals, and those with xeroderma pigmentosum

Question 30

what mutations are associated with BCC?

Answer 30

mutations that activate the Hedgehog signaling pathway–> leads to unbridled hedgehog signaling on the PTCH gene

Question 31

what is nevoid basal cell carcinoma syndrome/ Gorlin syndrome/ basal cell nevus syndrome?

Answer 31

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

Question 32

what is the gene associated with NBCCS/Gorlin/ basal cell nevus syndrome?

Answer 32

PTCH

Question 33

what are the morphological features of BCC? and what is the buzzword for BCC?

Answer 33

pearly papules, telangiectasias, rodent ulcers; buzzword= pearly

Question 34

how does BCC appear histologically?

Answer 34

the tumor cells resemble those in the normal basal cell layer of the epidermis; hyperchromatic nuclei, peripheral palisading; artificial clefts separate stroma from tumor

Question 35

what is peripheral palisading?

Answer 35

when cells are arranged radially with their long axes in parallel alignment

Question 36

What are benign Fibrous histiocytomas (dermatofibroma) and who is at risk of developing them?

Answer 36

they are benign dermal neoplasms of uncertain origin; adults, legs of young-middle aged women

Question 37

what is the presentation of benign fibrous histiocytomas?

Answer 37

asymptomatic or tender; +/- size over time, indolent; dimple sign: lateral pressure on the skin produces a depression

Question 38

what does a benign fibrous histiocytoma look like histologically?

Answer 38

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

Question 39

what is pseudoepitheliomatous hyperplasia?

Answer 39

many cases of benign fibrous histiocytoma demonstrate a peculiar form of overlying epidermal hyperplasia, characterized by downward elongation of hyperpigmented rete ridges

Question 40

what is the dimple sign seen in dermatofibromas?

Answer 40

lateral pressure on the skin produces a depression

Question 41

what is a dermatofibrosarcoma protuberans (DFSP)?

Answer 41

the malignant version of a dermatofibroma; well differentiated primary fibrosarcoma of the skin; slow growing, locally aggressive, can recur, but rarely metastasizes

Question 42

what mutation is associated with a dermatofibrosarcoma protuberans?

Answer 42

translocation collagen 1A1 (COL1A1) and PDGFB–> promotes tumor cell growth

Question 43

what are the morphological features of dermatofibrosarcoma protuberans?

Answer 43

a protuberant nodule, usually trunk, firm indurated plaque +/- ulceration

Question 44

how does a dermatofibrosarcoma protuberans appear histologically?

Answer 44

closely packed fibroblasts arranged radially–> storiform formation

Question 45

what does the overlying epidermis look like in a patient with dermatofibrosarcoma protuberans?

Answer 45

it is thinned (opposite of dermatofibroma)

Question 46

what is the honeycomb pattern?

Answer 46

seen in cases of dermatofibrosarcoma protuberans when there is deep extension from the dermis into the subQ fat