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MSKII Exam I + Gene decks > Chapter 25: Skin - Pigmentation/Melanocytes and Tumors > Flashcards

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
What are the ABCDEs of melanoma which correlate with the warning signs?
- **_A_**symmetry - Irregular **_B_**orders - Variegated **_C_**olor - ↑ **_D_**iameter - **_E_**volution/change over time (esp. rapid) \***_ANY_** pigmented lesion w/ diameter \>6mm, any change, itching or pain**\***
26
Seborrheic keratoses may suddenly appear in large numbers as part of which paraneoplastic syndrome; associated with what malignancy?
**Leser-Trélat** **sign**; most commonly **carcinoma** of **GI tract**
27
Round, flat, coinlike, **waxy** plaques that are tan-brown describes what?
Seborrheic Keratoses
28
Which morphological feature is helpful in distinguishing seborrheic keratoses from melanoma?
**Pore-like _ostia impacted with keratin_**
29
Activating mutation in what are seen in many sporadic seborrheic keratoses?
**FGFR3**
30
Small-keratin filled cysts (**horn cysts**) and invaginations of keratin into the main mass (**invagination cysts**) are characteristic features of what benign tumor?
Seborrheic keratoses
31
Benign tumor of skin described as "coin-like" or "stuck-on" is characteristic of what?
Seborrheic keratoses
32
What are the 2 most common associations with acanthosis nigricans?
**Obesity** and **diabetes**
33
Epidermis with underlying enlarged dermal papillae undulating sharply to form numerous peaks and valleys describes the histology of what?
Acanthosis nigricans
34
Sebaceous adenomas can be associated with internal malignancy in which syndrome?
**Muir-Torre syndrome**, subset of **HNPPC** (deficit in DNA mismatch repair)
35
Cylindromas are appendage tumors with what kind of differentiation and where do they arise?
- **Ductal (apocrine** or **eccrine****) differentiation** - Usually arise on **forehead** and **scalp** - With time may produce **turban tumor**
36
Characteristic histology of cylindromas?
**Islands** of **cells** resembling normal epidermal or adnexal basal cell layer (basaloid cells) which **fit together** like **pieces of a jigsaw puzzle**
37
Actinic keratosis can progressively worsen over time finally culminating into what?
Cutaneous **SCC**
38
What is the gross morphology of Actinic Keratosis?
- **\<1cm**, tan-brown, red or skin colored, rough **_sandpaper_**-like consistency - Excess **keratin** prod. ---\> **cutaneous horns**
39
Histologically what is seen with Actinic Keratosis?
- **Atypical basal cells** w/ _pink_ or _red_ cytoplasm due to **_dyskeratosis_** - **Intracellular bridges** (not seen in bcc) - Superficial dermis w/ _thickened_, **blue**-**gray** elastic fibers (**elastosis**) - **Stratum corneum** is _thickened_, cells retaining their **nuclei** = **Parakeratosis\***
40
Cutaneous SCC and BCC incidence is proportional to what?
**Degree** of **lifetime sun exposure**
41
Immunosuppression such as chemotherapy or organ transplantation ↑ the risk of cutaneous SCC due ↑ risk of infection by what?
**HPV** subtypes **5** and **8**
42
Which rare AR condition is marked by a high susceptibility to cutaneous SCCs and assoc. with HPV types 5 and8?
Epidermodysplasia verruciformis
43
Which acquired defect in precursor actinic keratosis has a high incidence in Caucasians and is an early event in development of cutaneous SCC?
***TP53*** mutations --\> improper repair of UV damage
44
Xeroderma pigmentosum is an inherited mutation in what; leads to very increased susceptibility to SCC?
- Inherited mutation in **nucleotide excision repair** pathway, required for accurate repair of **pyrimidine dimers** - ↑ risk of **cutaneous SCC** and **basal cell carcinoma**
45
How do in situ cutaneous SCC's appear morphologically?
**Sharply defined**, _red_, **scaling _plaques_**
46
How do more advanced, invasive lesions of cutaneous SCC appear?
**Nodular**, variable **keratin** production (**hyperkeratotic scale**) and may **ulcerate**
47
How do cutaneous SCC's differ from actinic keratosis histologically?
**Cells** with **atypical** (**enlarged** and **hyperchromatic**) **nuclei** involve **_ALL_** levels of the **epidermis**
48
Highly anaplastic cells that exhibit only abortive, single-cell keratinization seen with some cutaneous SCC is known as what?
Dyskeratosis
49
What is typical behavior of basal cell carcinoma and risk of metastases?
**_Slow_** growing, **rarely metastasize**; if caught early --\> **cured by local excision**
50
Which distinctive locally aggressive cutaneous tumor is associated with mutations that activate the Hedgehog pathways signaling?
Basal Cell Carcinoma
51
Nevoid basal cell carcioma syndrome aka Gorlin syndrome aka basal cell nevus syndrome is inherited how and what is seen?
- Autosomal **_dominant_** - Development of **multiple BCC's** **\<20 y/o** + **medulloblastoma** and **ovarian fibromas**; odontogenic keratocysts, and pits of the palms and soles
52
Nevoid basal cell carcioma syndrome aka Gorlin syndrome is associated with with what germline mutation?
- Loss-of-function in one ***PTCH*** allele --\> **Two-hit hypothesis** - **PTCH** protein = **receptor** for **sonic hedgehog (SHH)**
53
Which DNA base substitution is considered the hallmark of UV damage and is seen in 1/3 of basal cell carcinomas?
**Cytosine (C)** --\> **Thymine (T) = pyrimidine dimers**
54
How do basal cell carcinomas typically present grossly?
**Pearly papules** w/ prominent _dilated_ subepidermal vessels (**telangiectasias**)
55
Why is the term rodent ulcers used with some forms of aggressive basal cell carcinomas?
May **ulcerate**, and _extensive_ local **invasion** of **bone** or **facial sinuses** may occur after many years of neglect or in unusually aggressive tumors
56
Which common and important variant of BCC presents as an erythematous, occasionally pigmented plaque that may resemble early forms of melanoma?
**Superficial basal cell carcinoma**
57
What are the 2 histological patterns of growth seen with BCC?
- **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
Benign Fibrous Histiocytomas (Dermatofibroma) most often occurs in whom and is seen on which parts of the body?
**Adults**; often on the **_legs_** of **young** and **middle-aged women**
59
Benign Fibrous Histiocytomas (Dermatofibroma) are composed at least partially of what?
**Factor XIIIa-**positive **dermal dendritic cells**
60
Many cases of Benign Fibrous Histiocytomas (Dermatofibroma) are associated with a history of what?
**Antecedent trauma**, suggesting an **_abnormal_** response to **injury** and **inflammation**
61
Dermatofibroma is the most common type of benign fibrous histiocytoma and appears how morphohistologically?
- 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
Which PE finding is benign fibrous histiocytoma (dermatofibroma) associated with?
**Dimple sign**: lateral pressure on the skin produces a _depression_
63
Dermatofibrosarcoma protuberans (DFSP) is best regarded as what; typical behavior?
**Malignant**, well-differentiated, primary **fibrosarcoma** of the skin which are **slow-growing**, **locally aggressive** and can **recur**; **_rarely_** _metz_
64
What is the molecular hallmark of dermatofibrosarcoma protuberans (DFSP); tumor cell growth is driven through what kind of loop?
- **Translocation** involving **collagen 1A1 (*COL1A1)*** and ***PDGFB*** - Leads to ↑ secretion of **PDGF**β - Tumor cell growth through an **_autocrine loop_**
65
Dermatofibrosarcoma protuberans (DFSP) most often presents how; what is the characteristic morphology seen?
- "**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
Lesions of mycosis fungoides usually involve truncal areas and include what type of lesions?
- Scaly, red-brown **_patches_** - Raised scaling **_plaques_** (can be confused w/ *psoriasis)* - Fungating **_nodules_**
67
What is the histologic hallmark of CTCL of the mycosis fungoides type?
- **Sezary-Lutzner cells** (**cerebriform nuclei**), forming _band-like_ aggregates with **superficial dermis** - Invade epidermis as single cells and small clusters = **_Pautrier Microabscesses_**
68
Prognosis of CTCL of the mycosis fungoides type is related to what?
**% of total body surface involved** and _progression_ from **_patch_** --\> **_plaque_** ---\> **_nodular_ forms**
69
Which cutaneous form of mastocytosis predominantly affects children and accounts for \>50% of all mastocytosis cases?
Urticaria pigmentosa
70
What can be a clue to the diagnosis of mastocytosis in both pre-menopausal women and in men?
**Osteoporosis** due to _excessive_ **histamine** release in the marrow microenviornment
71
Many cases of mastocytosis have acquired activating point mutation in what?
**KIT receptor tyrosine kinase**
72
Which stains can be helpful in identifying mast cells and mastocytomas?
- **Metachromatic stains** (**toluidine blue** or **_Giemsa_**) for their granules - Stains for **mast cell tryptase** and **KIT** if excessive degranulation has occurred

MSKII Exam I + Gene decks (16 decks)

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