2-15 Benign Neoplastic Lesions of Skin and Disorders of Pigmentation

Question 1

Explain the Fitzpatrick scale.

Answer 1

I Pale, light hair +/- freckles Burns very easily

II Light skin and hair Usually burns

III Creamy skin, any hair color Tans well +/- burns

IV Light brown (Mediterranean) Tans well, rarely burns

V Medium brown Tans well, rarely burns

VI Deep brown Very rarely burns

Question 2

What falls under the heading of benign neoplastic lesions of skin and disorders of pigmentation?

Answer 2

I.Benign epithelial tumors

A.Fibroepithelial polyp

B.Epithelial inclusion cyst

C.Seborrheic keratosis

II.Adnexal neoplasms

III.Dermal tumors

A.Hemangioma

B.Xanthoma

C.Dermatofibroma (fibrous histiocytoma)

IV.Disorders skin pigmentation, macular or patch type

V.Acanthosis nigricans

VI.Tattoos

VII.Benign melanocytic neoplasms, nevocellular nevi

A.Junctional, compound, intradermal nevi

B.Blue nevus

C.Dysplastic nevus

Question 3

What are FEPs/Fibroepithelial polyps?

Answer 3

•Also known as

–skin tags

–acrochordon

–fibroma molle

–squamous papilloma

–

• Occur in individuals usually age 30 or greater and particularly in obese individuals
• Associated with areas of rubbing by clothing; collar of neck or groin
• Has vascular supply and variable stroma from fatty to fibrous

Question 4

What is an epithelial inclusion cyst?

Answer 4

• Also known as an epidermal cyst, follicular infundibular cyst or a wen
• Occur where there are large numbers of hair follicles (face, scalp, trunk)
• Caused by obstruction of hair follicle at infundibulum (near where hair shaft extends beyond skin surface)
• Filled with keratinous debris
• Lined by squamous epithelium with a granular cell layer

–A similar cyst, but without a granular cell layer is the trichilemmal/pilar cyst

•If ruptured (trauma) →

foreign body granulomatous giant cell inflammatory reaction to the keratin debris and pain

Question 5

What is a trichilemmal cyst?

Answer 5

Epidermal cyst

A similar cyst, but without a granular cell layer is the trichilemmal/pilar cyst

Caused by obstruction of hair follicle at infundibulum (near where hair shaft extends beyond skin surface)

Filled with keratinous debris

Question 6

What is seborrheic keratosis/SK?

Answer 6

• Proliferation of epidermal basal cells
• Usually middle-aged or older
• “Postage stamp” appearance, can look like melanoma
• Round, flat but elevated, can have keratin popping out of pseudocysts
• On non-exposed skin (trunk, proximal extremities, lateral neck)
• Many have mutations in fibroblast growth factor receptor 3
• Removed for cosmetic reasons or because lesion may resemble a malignant melanoma
• Sign of Leser-Trélat – acute onset of SKs with malignancies (GI mostly)

Question 7

What is sign of Leser-Trelat?

Answer 7

Acute onset of SK/seborrheic keratosis with malignancies (GI mostly)

Question 8

What are adenxal neoplasms? Discuss origins, and benign versus malignant.

Answer 8

• Overwhelming majority (99%) are benign
• Arise from the ductal and glandular epithelial cells of adnexa

–Sweat glands & ducts; hair-bulb germinal epithelium and sebaceous glands; apocrine glands and ducts

• Benign adnexal tumors are
• Symmetrical, small (<1 cm), superficial, vertically orientated
• Malignant adnexal tumors are
• Asymmetrical, large, deep, wide

–Sebaceous carcinoma

•Most common type of malignant adnexal neoplasm, but quite uncommon

–Eccrine carcinoma

–Apocrine carcinoma

Question 9

What are the names of some adnexal neoplasms? Discuss some histo findings too.

Answer 9

Sebaceous adenoma/carcinoma

Look for foamy cytoplasm, noting sebum

Malignant cells are invasive and push into other cells

Pilomatrixoma

tumor of matrix of the hair follicle

no granular cell layer

Ghost cells undergo apoptosis

Apocrine Hydrocystoma

cyst with fluid in skin, lining with apocrine epithelium – fibrocystic change, anything that is apocrine has more fibers

can also have accrine hydrocystoma

Question 10

Where do cylindromas and trichoepitheliomas occur?

Answer 10

Cylindroma – nests of basaloid cells that look like jigsaw puzzles on forehead and scalp

Trichoepithelioma – full of hair shafts – tumor arising from hair follicle, looks like epitheliod basaloma

Both look like little tiny bumps

Question 11

What adnexal tumors arise from the hair follicles? What are the histologic features and clinical significance?

Answer 11

Trichoepithelioma

Trichofolliculoma

Tricholemmoma

Pilomatricoma

Histologic features:

Hair matrix, outer root sheath differentiation

Clinical significance:

Cowden syndrome: Multiple tricholemmomas with dominant inheritance

Question 12

What adnexal tumors arise from the sebaceous glands? What are the histologic features and clinical significance?

Answer 12

Sebaceous adenoma

Sebaceous epithelioma

Histo: Cytoplasmic lipid vacuoles

Clinical:

Muir-Torre Syndrome: sebaceous adenomas with association colorectal malignancy (variant of Lynch)

Question 13

What adnexal tumors arise from apocrine glands? What are the histologic features and clinical significance?

Answer 13

Syringocystadenoma papilliferum

histo: Apocrine type “decapitation” secretion

Clinical: May develop in mixed epidermal-adnexal hamartomas of face and scalp termed nevus sebaceous

Question 14

What adnexal tumors arise from eccrine glands? What are the histologic features and clinical significance?

Answer 14

Syringoma

(lower eyelids)

Cylindroma

(forehead and scalp)

Poroma

(palmar or plantar regions)

histo: Eccrine ducts lined by membranous eosinophilic cuticles; tadpole-like epithelial structures

Clinical: may be confused with basal cell carcinoma clinically

Turban tumor :

Massive confluent cylindromas (basal cell origin)

Question 15

What are the dermal ‘lumps and bumps’?

Answer 15

• Hemangioma - Red
• Xanthomas – Yellow
• Fibrohistiocytic lesions – normal tan-brown skin tone or darker (darker d/t fibrocystic or reactive change in pigmentation over the top of them.)

These are from the deeper layers - the dermis, from mesenchyme.

Question 16

What do hemangiomas look like on gross and histo?

Answer 16

gross: well vascularized papules/macules, reddish to reddish brown in color

histo:

cavernous has more big open spaces

Lobular is more common, if ulcerated, inflamed and full of neutrophils it can be a pyogenic granuloma

Question 17

What do xanthomas look like on gross and histo?

Answer 17

gross: yellowish papules
histo: macrophages full of lipid, large cells with clear/slightly foamy cytoplasm

Question 18

What is a benign fibrous histiocytoma?

Answer 18

AKA dermatofibroma

Benign

In adults, frequently on the legs of young – middle aged women

Tan-brown, usually <1.0 cm

May occasionally be tender

(Benign and full of big bundles of fibrogenous tissue

• tend to push everything away (unlike neurofibromas, which encircle things)

Can cause hyperplasia of epithelium overlying it)

Question 19

What are some benign skin pigment disorders?

Answer 19

•Increased melanin in keratinocytes: NO increase in number of melanocytes

–Sun tan

–Freckles

–Café au lait spots

–Melasma

•Increased melanin in keratinocytes: small increase in number of melanocytes

–Solar lentigo

•Loss of Melanin in keratinocytes

–Acute transient vitiligo

–Albinism

•Loss of Melanocytes

–Chronic vitiligo

•Acquired Pigmentation

–Skin tattoo

–Amalgam tattoo

Question 20

What is a suntan?

Answer 20

• Due to ultraviolet light exposure
• UVB exposure →

–Melanocyte melanosome production →

–Increased melanin per keratinocyte→

–Increased protection against solar radiation (mid-UV [UVB] spectrum)

•Chronic skin damage and neoplasia also induced by exposure to ultraviolet radiation

(Tan is a protective mechanism/irritation for skin, to protect skin from UVB damage)

Question 21

What are the benign hypermelanosis abnormalities?

Answer 21

Freckles - Ephelides (sounds like an elf from LOTR)

Cafe au Lait spot

Hypermelanosis in both abnormalities

Small spots = freckles

Large area = café au lait spot

(Both represent an increase in melanin, become more prominent with sun exposure.

Mult café au lait spots – worry about Neurofibromatosis type I)

Question 22

What is found in neurofibromatosis Type I?

Answer 22

• Autosomal dominant disorder
• NF1 gene mutation that blocks encoding of neurofibromin (RAS inhibitor)
• Neurofibromas (including plexiform)

–Can develop malignant nerve sheath tumors

• Café au lait spots (macules)
• Freckles in axilla
• Optic nerve gliomas
• Lisch nodules on iris

(melanotic hamartomas)

• Macrocephaly
• Scoliosis

Question 23

What is found in neurofibromatosis Type II?

Answer 23

Type 2 has bilateral acoustic nerveSchwannomas , CNS gliomas

(ependymomas of spinal cord),

and cataracts

Question 24

What is chloasma?

Answer 24

Melasma

• A.K.A. “Mask of Pregnancy” and “Chloasma”
• Blotchy hypermelanosis on face

–Symmetrical distribution over the cheeks and forehead

–Less frequently on upper lip and neck

• Appears in women>>>men
• Occurs: (due to estrogen)

–During pregnancy

–In women taking oral contraceptives

–At menopause

Question 25

What is acanthosis nigricans?

Answer 25

**•Epidermal hyperplasia of stratum spinosum & hyperpigmentation** **•Prefers flexural regions** –axillae, skin folds of neck, groin and anogenital regions •80% occur with benign conditions –Autosomal dominant forms with variable penetrance •Onset during childhood or puberty –Also occur with obesity or endocrine abnormalities **•20% are paraneoplastic** **–Malignancy (adenocarcinoma) signals the epidermis to undergo epidermal hyperplasia.** –Arises in middle-aged and older individuals

Question 26

What is a tattoo?

Answer 26

Tattoo = Acquired Pigmentation May be intentional or incidental (pencil “lead” breaking in skin or oral amalgam injury) May mimic pigmented lesions such as nevi and melanoma if incidental May “bleed” if pigment travels in dermis or as macrophages move Will fade over time as melanocytes move deeper into dermis and out of dermis

Question 27

What is solar lentigo?

Answer 27

AKA Lentigo Senilis, Lentigo Simplex •Benign, discrete hyperpigmented macule on chronically sun exposed skin –Back of the hands and the forehead in adults * Variable increase in number of junctional melanocytes & increased melanin pigment in keratinocytes * Note: “lentigo or lentiginous” means a proliferation of melanocytes **–Lentigo maligna is the name given to an in situ melanoma arising in sun exposed skin**

Question 28

What is macular/patch skin depigmentation?

Answer 28

•**Loss of melanin in keratinocytes** **–Acute transient vitiligo** •e.g. keratinolytic agents that remove layers of pigmented keratinocytes **–Albinism** * Defect in tyrosinase, an enzyme necessary for melanin production * **Permanent lack or loss of melanocytes** **–Chronic vitiligo** (Skin pigment is in keratinocytes, so if you slough off skin you can get acute transient vitiligo. - acute vitiligo – loss of skin - chronic vitiligo – loss of melanocyets Albinism – usu problems with tyrosine metabolism – photophobia, difficulty seeing)

Question 29

What are melanocytic/nevocellular nevi?

Answer 29

**•Neoplastic nested melanocyte proliferation (clusters)** –**Junctional: Basal epidermal nests** •Maculopapular –**Compound: Basal epidermal and dermal nests** •Papular –**Intradermal: Dermal nests** * Papular to nodular * **Acquired mutations in NRAS and BRAF** are commonly found –Mutations induce melanocyte neoplasia short of malignancy

Question 30

What is the postulated natural history of nevi?

Answer 30

Stage I Junctional nevus, with nests of melanocytes along base of epidermis Stage II Compound nevus, with nests of melanocytes at base of epidermis and dermis Stage III Intradermal/Dermal nevus, with nests of melanocytes present only in the dermis Stage IV Neurotized nevus, with melanocytes changing appearance from epitheliod to spindled shape (looks less like epithelium and more like neural tissue)

Question 31

What is a congenital nevus?

Answer 31

* Present at birth (birthmark) * Benign, but melanoma can arise in the larger congenital nevi * Extensive deep dermal to subcutaneous growth with proliferative nodules

Question 32

What is a blue nevus?

Answer 32

* Intradermal, roughly wedge-shaped and slightly raised skin surface * Thin, delicate melanocytes in a dense reactive fibrotic stroma * Melanin pigment in melanocytes, melanophages, or other adjacent structures cause the bluish color * Benign with no significant risk for development of melanoma

Question 33

What is a Spitz nevus?

Answer 33

Spitz nevus - AKA spindle & epitheliod cell nevus * Usually in children and young adults * Can be red like hemangioma or pigmented and can clinically & histologically mimic a melanoma (and melanomas can look like Spitz nevi) * Characteristic raining down melanocyte pattern and Kamino bodies (eosinophilic amorphous globules)

Question 34

What is a halo nevus?

Answer 34

•Involuting (regressing) nevus with extensive lymphocyte infiltration and depigmentation of surrounding skin