Chapter 25: Skin - Pigmentation/Melanocytes and Tumors Flashcards

1
Q

A circumscribed, flat skin lesion distinguished from surrounding skin by color, either <5mm or >5mm in diameter describes what?

A
  • Macules are <5mm
  • Patches are >5mm
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2
Q

Elevated dome-shaped or flat-topped skin lesion, either <5mm across or >5mm across describes what?

A
  • Papules = <5mm
  • Nodule = >5mm
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3
Q

Surface elevation caused by hyperplasia and enlargement of contiguous dermal papillae describes what?

A

Papillomatosis

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4
Q

What is Parakeratosis and where is it a normal finding?

A
  • Keratinization with retained nuclei in the stratum corneum
  • Normal on mucous membranes
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5
Q

A traumatic lesion breaking the epidermis and causing a raw linear area (i.e., deep scratch) describes what?

A

Excoriation

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6
Q

Multiple trichilemmomas may be seen with what syndrome that is associated with an increased risk of endometrial cancer, breast cancer, and many other tumors?

A

Cowden syndrome –> loss-of-function in PTEN

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7
Q

Differentiate Freckles from Café au lait spots.

A
  • Freckles: appear after sun exposure; fade and darken cyclically w/ season
  • Café au lait: seen in neurofibromatosis; larger than freckles; arise independent of sun exposure
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8
Q

Linear (nonnested) melanocytic hyperplasia restricted to the cell layer immediately above the basement membrane that produces a hyperpigmented basal cell layer, describes what?

A

Lentigo

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9
Q

What is the histology of superficial nevi, deeper nevi, and the deepest nevi which are helpful in differentiating benign nevi from melanoma?

A
  • Superficial: nests, large-round cells, ↑ melanin
  • Deeper: cords or single cells, smaller, ↓ pigment
  • Deepest: fusiform, fascicles resembled neural tissue
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10
Q

What is the clinical significance of spindle and epitheliod cell nevus (Spitz nevus)?

A

Common in children; red-pink nodule; often confused with hemangioma clinically

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11
Q

Clinically how do compound and dermal nevi differ in appearance from junctional nevi?

A

Often more elevated

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12
Q

Inheritance pattern of dysplastic nevus syndrome and chance of melanoma?

A

Autosomal dominant; >50% chance dev. melanoma by age 60

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13
Q

What are some of the distinguishing histologic features of dysplastic nevi?

A
  • Typically larger than acquired nevi, >5mm, can be hundreds
  • Lentiginous hyperplasia: single nevus cells replace basal cell at E-D jct
  • Architectural and cellular atypia
  • Lymphocytic infiltrate of superf. dermis, melanin incontinence
  • Linear fibrosis surrounds epidermal rete ridges
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14
Q

Activating mutations in which downstream serine/threonine kinase from RAS is seen in 40-50% of melanomas?

A

BRAF

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15
Q

What is the most commonly mutated gene identified in melanomas?

A

TERT expression (activation of telomerase)

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16
Q

In which growth phase of melanoma do tumor cells seem to lack the capacity to metastasize?

A

Radial growth –> horizontal spread of melanoma within the epidermis and superficial dermis

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17
Q

Melanomas in radial growth phase fall into what 3 clinicopathologic classes; which is most common?

A
  • Lentigo maligna: usually indolent lesion on face of older men
  • Superficial spreading: most common type of melanoma, usually involving sun-exposed skin
  • Acral/mucosal lentiginous: melanoma unrelated to sun exposure
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18
Q

Which phase of melanoma growth is often heralded by the appearance of a nodule and correlates with the emergence of a tumor subclone with metastatic potential?

A

Vertical growth phase: tumor cells invade downward into deeper dermal layers as an expansile mass

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19
Q

Which feature of melanocytic nevi is absent from the deep invasive portion of melanoma?

A

Neurotization

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20
Q

Which measurement is the distance from the superficial epidermal granular cell layer to the deepest intradermal tumor cells; what does this correlate with in melanoma?

A
  • Breslow thickness
  • Depth of invasion correlates with probability of metastasis
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21
Q

Staining for which melanocytic marker can be useful in distinguishing melanoma cells?

A

HMB-45 (+)

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22
Q

Which nuclei and nucleolus findings are seen histologically with melanoma?

A
  • Nuclei with irregular contours + clumped chromatin at periphery
  • Prominent red (eosinophilic) nucleoli
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23
Q

What are 5 determinants of a more favorable prognosis with melanoma?

A
  • Thinner tumor depth (Breslow thickness)
  • NO (<1 per mm2) mitosis
  • Brisk tumor infiltrating lymphocyte response
  • NO regression
  • Lack of ulceration
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24
Q

Where do most melanomas initially metastasize and how does this affect the clinical handling of these lesions?

A
  • Regional lymph nodes
  • Should perform sentinel lymph node biopsy; microscopic involvement of a sentinel node by even a small # of melanoma cells = worse prognosis
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25
Q

What are the ABCDEs of melanoma which correlate with the warning signs?

A
  • Asymmetry
  • Irregular Borders
  • Variegated Color
  • Diameter
  • Evolution/change over time (esp. rapid)

*ANY pigmented lesion w/ diameter >6mm, any change, itching or pain*

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26
Q

Seborrheic keratoses may suddenly appear in large numbers as part of which paraneoplastic syndrome; associated with what malignancy?

A

Leser-Trélat sign; most commonly carcinoma of GI tract

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27
Q

Round, flat, coinlike, waxy plaques that are tan-brown describes what?

A

Seborrheic Keratoses

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28
Q

Which morphological feature is helpful in distinguishing seborrheic keratoses from melanoma?

A

Pore-like ostia impacted with keratin

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29
Q

Activating mutation in what are seen in many sporadic seborrheic keratoses?

A

FGFR3

30
Q

Small-keratin filled cysts (horn cysts) and invaginations of keratin into the main mass (invagination cysts) are characteristic features of what benign tumor?

A

Seborrheic keratoses

31
Q

Benign tumor of skin described as “coin-like” or “stuck-on” is characteristic of what?

A

Seborrheic keratoses

32
Q

What are the 2 most common associations with acanthosis nigricans?

A

Obesity and diabetes

33
Q

Epidermis with underlying enlarged dermal papillae undulating sharply to form numerous peaks and valleys describes the histology of what?

A

Acanthosis nigricans

34
Q

Sebaceous adenomas can be associated with internal malignancy in which syndrome?

A

Muir-Torre syndrome, subset of HNPPC (deficit in DNA mismatch repair)

35
Q

Cylindromas are appendage tumors with what kind of differentiation and where do they arise?

A
  • Ductal (apocrine or eccrine) differentiation
  • Usually arise on forehead and scalp
  • With time may produce turban tumor
36
Q

Characteristic histology of cylindromas?

A

Islands of cells resembling normal epidermal or adnexal basal cell layer (basaloid cells) which fit together like pieces of a jigsaw puzzle

37
Q

Actinic keratosis can progressively worsen over time finally culminating into what?

A

Cutaneous SCC

38
Q

What is the gross morphology of Actinic Keratosis?

A
  • <1cm, tan-brown, red or skin colored, rough sandpaper-like consistency
  • Excess keratin prod. —> cutaneous horns
39
Q

Histologically what is seen with Actinic Keratosis?

A
  • Atypical basal cells w/ pink or red cytoplasm due to dyskeratosis
  • Intracellular bridges
  • Superficial dermis w/ thickened, blue-gray elastic fibers (elastosis)
  • Stratum corneum is thickened, cells retaining their nuclei = Parakeratosis*
40
Q

Cutaneous SCC and BCC incidence is proportional to what?

A

Degree of lifetime sun exposure

41
Q

Immunosuppression such as chemotherapy or organ transplantation ↑ the risk of cutaneous SCC due ↑ risk of infection by what?

A

HPV subtypes 5 and 8

42
Q

Which rare AR condition is marked by a high susceptibility to cutaneous SCCs and assoc. with HPV types 5 and8?

A

Epidermodysplasia verruciformis

43
Q

Which acquired defect in precursor actinic keratosis has a high incidence in Caucasians and is an early event in development of cutaneous SCC?

A

TP53 mutations –> improper repair of UV damage

44
Q

Xeroderma pigmentosum is an inherited mutation in what; leads to very increased susceptibility to SCC?

A
  • Inherited mutation in nucleotide excision repair pathway, required for accurate repair of pyrimidine dimers
  • ↑ risk of cutaneous SCC and basal cell carcinoma
45
Q

How do in situ cutaneous SCC’s appear morphologically?

A

Sharply defined, red, scaling plaques

46
Q

How do more advanced, invasive lesions of cutaneous SCC appear?

A

Nodular, variable keratin production (hyperkeratotic scale) and may ulcerate

47
Q

How do cutaneous SCC’s differ from actinic keratosis histologically?

A

Cells with atypical (enlarged and hyperchromatic) nuclei involve ALL levels of the epidermis

48
Q

Highly anaplastic cells that exhibit only abortive, single-cell keratinization seen with some cutaneous SCC is known as what?

A

Dyskeratosis

49
Q

What is typical behavior of basal cell carcinoma and risk of metastases?

A

Slow growing, rarely metastasize; if caught early –> cured by local excision

50
Q

Which distinctive locally aggressive cutaneous tumor is associated with mutations that activate the Hedgehog pathways signaling?

A

Basal Cell Carcinoma

51
Q

Nevoid basal cell carcioma syndrome aka Gorlin syndrome aka basal cell nevus syndrome is inherited how and what is seen?

A
  • Autosomal dominant
  • Development of multiple BCC’s <20 y/o + medulloblastoma and ovarian fibromas; odontogenic keratocysts, and pits of the palms and soles
52
Q

Nevoid basal cell carcioma syndrome aka Gorlin syndrome is associated with with what germline mutation?

A
  • Loss-of-function in one PTCH allele –> Two-hit hypothesis
  • PTCH protein = receptor for sonic hedgehog (SHH)
53
Q

Which DNA base substitution is considered the hallmark of UV damage and is seen in 1/3 of basal cell carcinomas?

A

Cytosine (C) –> Thymine (T) = pyrimidine dimers

54
Q

How do basal cell carcinomas typically present grossly?

A

Pearly papules w/ prominent dilated subepidermal vessels (telangiectasias)

55
Q

Why is the term rodent ulcers used with some forms of aggressive basal cell carcinomas?

A

May ulcerate, and extensive local invasion of bone or facial sinuses may occur after many years of neglect or in unusually aggressive tumors

56
Q

Which common and important variant of BCC presents as an erythematous, occasionally pigmented plaque that may resemble early forms of melanoma?

A

Superficial basal cell carcinoma

57
Q

What are the 2 histological patterns of growth seen with BCC?

A
  • Multifocal growths: originate from epidermis and sometimes extend over several square cm’s or more of skin surface
  • Nodular: grow ↓ deeply into dermis as cords/islands of basophilic cells w/ hyperchromatic nuclei in a mucinous matrix w/ fibroblasts and lymphocytes –> cells at periphery arranged radially = palisading
58
Q

Benign Fibrous Histiocytomas (Dermatofibroma) most often occurs in whom and is seen on which parts of the body?

A

Adults; often on the legs of young and middle-aged women

59
Q

Benign Fibrous Histiocytomas (Dermatofibroma) are composed at least partially of what?

A

Factor XIIIa-positive dermal dendritic cells

60
Q

Many cases of Benign Fibrous Histiocytomas (Dermatofibroma) are associated with a history of what?

A

Antecedent trauma, suggesting an abnormal response to injury and inflammation

61
Q

Dermatofibroma is the most common type of benign fibrous histiocytoma and appears how morphohistologically?

A
  • Benign spindle-shaped cells, well-defined, non-encapsulated mass in the mid dermis
  • Overlying epidermal hyperplasia, downward elongation of hyperpigmented rete ridges = pseudoepitheliomatous hyperplasia
62
Q

Which PE finding is benign fibrous histiocytoma (dermatofibroma) associated with?

A

Dimple sign: lateral pressure on the skin produces a depression

63
Q

Dermatofibrosarcoma protuberans (DFSP) is best regarded as what; typical behavior?

A

Malignant, well-differentiated, primary fibrosarcoma of the skin which are slow-growing, locally aggressive and can recur; rarely metz

64
Q

What is the molecular hallmark of dermatofibrosarcoma protuberans (DFSP); tumor cell growth is driven through what kind of loop?

A
  • Translocation involving collagen 1A1 (COL1A1) and PDGFB
  • Leads to ↑ secretion of PDGFβ
  • Tumor cell growth through an autocrine loop
65
Q

Dermatofibrosarcoma protuberans (DFSP) most often presents how; what is the characteristic morphology seen?

A
  • Protuberant” nodule, most often on the trunk, within a firm (indurated) plaque that may sometimes ulcerate.
  • Closely packed fibroblasts arranged radially in storiform pattern, resembles blades of a pinwheel
  • Deep extension into SQ fat produces “honeycomb” pattern
66
Q

Lesions of mycosis fungoides usually involve truncal areas and include what type of lesions?

A
  • Scaly, red-brown patches
  • Raised scaling plaques (can be confused w/ psoriasis)
  • Fungating nodules
67
Q

What is the histologic hallmark of CTCL of the mycosis fungoides type?

A
  • Sezary-Lutzner cells (cerebriform nuclei), forming band-like aggregates with superficial dermis
  • Invade epidermis as single cells and small clusters = Pautrier Microabscesses
68
Q

Prognosis of CTCL of the mycosis fungoides type is related to what?

A

% of total body surface involved and progression from patch –> plaque —> nodular forms

69
Q

Which cutaneous form of mastocytosis predominantly affects children and accounts for >50% of all mastocytosis cases?

A

Urticaria pigmentosa

70
Q

What can be a clue to the diagnosis of mastocytosis in both pre-menopausal women and in men?

A

Osteoporosis due to excessive histamine release in the marrow microenviornment

71
Q

Many cases of mastocytosis have acquired activating point mutation in what?

A

KIT receptor tyrosine kinase

72
Q

Which stains can be helpful in identifying mast cells and mastocytomas?

A
  • Metachromatic stains (toluidine blue or Giemsa) for their granules
  • Stains for mast cell tryptase and KIT if excessive degranulation has occurred