(1)
Department of Dermatology, University of Pennsylvania, Penn Presbyterian Medical Center Medical Arts Building, Philadelphia, PA, USA
Abstract
Cutaneous neoplasms are either growths of cells normally in the skin or growths of cells that have abnormally migrated to the skin. Most neoplastic diseases fall under the dermal reaction pattern, but since it is such a large category, it is separated into its own section. Here neoplasms and tumors are divided by the type of proliferation.
Keywords
Skin neoplasmsSkin tumors7.1 Keratinocyte Neoplasms
Normally occurring cells of the epidermis include: keratinocytes, melanocytes, Langerhans cells, neuroendocrine cells
1.
Benign keratinocyte neoplasms/hyperplasias
(a)
Seborrheic keratosis
Path: flat-topped papillomatous epidermis, horned pseudocysts
See also Keratotic Diseases: Hyperkeratotic Eruptions
(b)
Benign lichenoid keratosis
Aka lichen planus-like keratosis (LPLK)
See also Keratotic Diseases: Hyperkeratotic Eruptions
(c)
Epidermal nevi
See also Keratotic Diseases: Hyperkeratotic Eruptions
(d)
Warts
HPV-induced keratinocyte proliferations including verruca vulgaris and condyloma acuminata
See also Infectious Diseases: Viral:DNA Viruses: Papovavirus
(e)
Warty dyskeratoma
Papule of focal acantholytic dermatosis
See also Vesiculobullous Diseases: Intraepidermal Blisters
(f)
Clear cell acanthoma/Pale cell acanthoma
On path, can appear very similar to psoriasis, except cells notably pale (from glycogen), and clinically it is usually a solitary
(g)
Chondrodermatitis nodularis helicis (CNH)
Chronic tender ulcerated nodule on helix of ear, ddx BCC and SCC
From pressure/friction, not a neoplasm
See also Keratotic Diseases: Lichen Simplex
2.
Premalignant keratinocyte neoplasms
(a)
Actinic keratosis (AK)
Aka solar keratosis
Path: partial-thickness keratinocyte atypia (starting at basement membrane), parakeratosis that spares areas over adnexae
For each AK, apparently 2–10 % chance of progression to SCC
On lips, can see actinic cheilitis/cheilosis (lower > upper lip)
(b)
Bowenoid papulosis
May represent an intermediate between condyloma and SCCIS
Papular HPV lesions most commonly on the penis that may have malignant potential
Most associated with HPV-16, 18
(c)
Leukoplakia
Cannot be removed (unlike thrush)
Associated with tobacco (smoked and chewed) and alcohol
This is different from oral hairy leukoplakia, which is caused by EBV, but has no malignant potential, and may be a sign of HIV infection
One type seen in dyskeratosis congenita, see also Vascular: Regional Erythema:Telangiectasia: Genodermatoses with early aging, telangiectasia, sun sensitivity
3.
Malignant keratinocyte neoplasms
Note: Collectively, squamous cell carcinomas and basal cell carcinomas are referred to as non-melanoma skin cancers (NMSCs). Others have used the term “keratinocyte carcinoma,” which may be a more specific and accurate term.
Note: in transplant/immunosuppressed patients, see increase in skin cancers estimated at: SCC (65X), BCC (5X), and MM (3X); SCC, by far, accounts for most. In HIV, skin cancer risk is increased, but at a much lower factor.
(a)
Basal cell carcinoma (BCC)
BCC is the most common cause of skin cancer in Caucasians and East Asians; most common cancer of all organs overall
Clinically, may see pearly papule, ulcer with “rolled borders,” dermoscopy with “arborizing vessels”
Gene most frequently mutated = PTCH (on Chr 9q)
PTCH’s product = Patched, the transmembrane sonic hedgehog (Shh) receptor); normally hedgehog regulates Patched, which inhibits Smoothened (SMO, a proto-oncogene). Thus, Patched inactivation mutation and Smoothened activation mutations would constitutively activate expression, causing BCCs.
Other mutated relevant genes may include p53, MCR1
Path = basaloid growth, nuclear debris, mucinous stroma, peripheral palisading clefting/retraction; ddx trichoepithelioma, MAC
Metastases in <0.55 %
Surgical excision of BCCs: < 2 cm = 3–4 mm margin, ≥2 cm = 6 mm margin or Mohs surgery
Evidence says imiquimod and 5-FU may be used as monotherapy for superficial BCC; limit these topicals to low-risk areas, and not for other types of BCC
Types:
I.
Superficial/Superficial multifocal
II.
Nodular
III.
Pigmented
IV.
Sclerosing
Aka morpheaform or sclerodermiform
Clinically may resemble a scar
Considered a more aggressive form of BCC; may extend farther histologically than is appreciable clinically
V.
Fibroepithelioma of Pinkus
Large tumor in lumbosacral area; may appear tag-like
Path: thin strands of anastamosing basal cells
VI.
Infundibulocystic
Controversial if different from basaloid follicular hamartoma
VII.
Syndromes that cause BCCs
See also Neoplastic: Syndromes with multiple tumors or multiple types of tumors
1.
BCC nevus syndrome
Aka Gorlin’s syndrome/Gorlin-Goltz/nevoid BCC syndrome
Multiple BCCs at young age, other tumors, congenital abnormalities including odontogenic keratocysts of the jaw, calcification of falx cerebri, palmar pits, ovarian fibromas (4–24 % of women)
Can be associated with medulloblastoma
PTCH (Patched) gene mutation, autosomal dominant
2.
Bazex-Dupré-Christol syndrome
Note: do not confuse with acrokeratosis paraneoplastica (also called Bazex syndrome)
Genodermatosis of follicular atrophoderma and the early onset of multiple BCCs, may have hypohidrosis
X-linked dominant
3.
Rombo syndrome
Similar to Bazex, but with KP-like lesions of cheeks that can form honeycombed, worm-eaten appearance (atrophoderma vermiculatum)
Hypotrichosis but not hypohidrosis (mnemonic Rambo must sweat), blepharitis, milia (break down into atrophoderma), peripheral vasodilation with cyanosis, BCCs
4.
Multiple hereditary infundibulocystic BCC syndrome
Several cases reported
(b)
Squamous cell carcinoma (SCC)
Primary risk factors: UV, HPV
Most common mutation = p53 (Chr 17). Others include CDKN2A and PTCH
Can occur at sites of chronic trauma/ulcers, scars (Marjolin’s ulcer), chronic inflammation (e.g. lichen planus, lichen sclerosus, discoid lupus), radiation, or chemical exposure
Arsenic is a well-defined cause of SCC; may see palmoplantar arsenical keratoses, multiple tumors as clue
SCC is the most common cause of skin cancer in African-Americans and Asian Indians; may be more aggressive
High-risk SCC generally defined as >2 cm diameter, >4 mm thickness, recurrent, high-grade or desmoplastic growth, presence of perineural invasion, certain high-risk locations (ear/near parotid gland, nose, lip, perianal, genital), immunosuppression (especially with organ transplant), lymphovascular invasion
Metastatic risk for SCC estimated at 0–10 %
Path = full-thickness keratinocyte atypia with invasion
Surgical excision of SCCs: generally, low-risk = 3–4 mm margin, high risk = 6 mm margin or Mohs surgery
(c)
Squamous cell carcinoma in situ (SCCIS)
Path = full-thickness keratinocyte atypia, confined by basement membrane; parakeratosis; may have loss of polarity (meaning that the superficial and deeper epidermis can no longer be distinguished), loss of proper maturation
Evidence says topical 5-FU may be used as monotherapy; limit topicals to low-risk areas, and not for invasive SCC
I.
Bowen’s disease
Some use the term “Bowen’s” to refer only to SCCIS on the penis, and others use the term Bowen’s as synonymous with all SCCIS
II.
Erythroplasia of Queyrat
Bowen’s disease on the glans penis
III.
Erythroplakia
Like erythroplasia of Queyrat, but in the mouth
(d)
Keratoacanthoma (KA)
Clinical: cutaneous horn, Path: keratin-filled crater/keratotic plug surrounded by proliferation of atypical keratinocytes/mitoses
Usually considered a form of SCC or benign with a small risk of progression to invasive SCC
Typical history = sudden onset (weeks)
Should regress on own, but usually treated as SCC
I.
Muir-Torre syndrome
Subtype of hereditary nonpolyposis colorectal cancer (HNPCC) syndrome (aka Lynch syndrome), prone to colon, breast, GU cancers
Sebaceous neoplasms (adenoma, epithelioma, or carcinoma), keratoacanthomas, and internal malignancies; sebaceous adenoma is a unique hallmark
Mutations in MSH2, MLH1 (DNA mismatch repair gene)
See also Neoplastic/Tumors: Syndromes with multiple tumors or multiple types of tumors
II.
Ferguson-Smith syndrome
Multiple spontaneously regressing KAs in sun-exposed areas, autosomal dominant
III.
Grzybowski syndrome
Generalized eruptive KAs, thousands of papules resembling milia
IV.
Side effect of BRAF inhibitors
Multiple eruptive keratoacanthomas and SCCs have been reported in association with BRAF inhibitors in treatment for metastatic melanoma
(e)
Verrucous carcinoma
A well-differentiated variant of SCC that is large, and pale and glassy on pathology; not simply an SCC with a warty appearance
1.
Giant condyloma acuminata (Buschke-Löwenstein tumor)
Large, locally destructive verrucous plaque, usually on penis > other anogenital
May be associated with HPV-6, 11
2.
Oral florid papillomatosis (Ackerman tumor)
Warts in oral cavity, nasal sinuses
May be promoted by smoking, radiation
3.
Epithelioma cuniculatum
Verrucous carcinoma arising from a plantar wart on the foot
(f)
Adenoid SCC (pseudoglandular)
May have acantholysis, so remember to consider acantholytic SCC in ddx of herpes and acantholytic dermatoses (e.g. pemphigus)
7.2 Melanocytic Neoplasms
1.
Benign melanocytic neoplasms
(a)
Common acquired melanocytic nevi
Nests of melanocytes, predominantly in rete ridges
On path: remember to evaluate size, symmetry, circumscription; need full lesion (shave or excision)
I.
Intradermal nevus
Nest of melanocytes in dermis
Clinically usually exophytic
Clinical ddx acrochordon, neurofibroma
II.
Compound nevus
Nests of melanocytes in epidermis and dermis
Path: center with melanocytes in dermis/junction, may have surrounding rim of junctional melanocytes = shouldering (creates fried egg appearance clinically)
III.
Junctional nevus
Nests of melanocytes at D-E junction
Clinically macular
IV.
Recurrent nevus
Recurrence after biopsy or excision, may look more concerning given altered appearance
Path: melanocytic proliferation over a scar
V.
Acral nevi
Benign dermoscopic patterns = parallel furrow (most common), lattice-like, and fibrillar patterns
Concerning dermoscopic patterns include parallel ridge and multicomponent
(b)
Dysplastic/atypical nevus
Aka Clark’s nevus
On path, these characteristics may be seen:
1.
Bridging of rete ridges
2.
Shouldering
3.
Lamellar fibroplasia (fibrosis around basement membrane)
4.
Slight atypia
Other atypical features include asymmetry, poor circumscription, Pagetoid spread
Recent description of nevi with features of Spitz and dysplastic (Clark’s) nevi was called “Spark’s nevus”
In general, dysplastic nevi are not considered premalignant lesions. They represent a patient risk factor for melanoma and are re-excised less because of concern that they will evolve into a melanoma and more because of concern that a melanoma diagnosis was missed.
Typically, DNs are reported as having mild, moderate, or severe atypia; the risk of melanomas being misclassified as mild or moderate DNs appears to be extremely small to none. Severe DNs are uniformly re-excised (as they are borderline to MMIS). However, many are comfortable (and some evidence supports) not re-excising mild and moderate DNs, especially if margins were clear on biopsy.
I.
“Dysplastic nevus syndrome”
Patients with multiple DNs with increased risk for MM; not a well-defined syndrome
II.
Familial atypical multiple mole melanoma (FAMMM) syndrome
An autosomal dominant disease, from mutation in CDKN2A (or p16) gene, or CDK4 gene
Predisposition to >50 atypical nevi and multiple melanomas
70 % will develop at least one melanoma, 30 % will have multiple
Increased risk for pancreatic cancer (20X), with lifetime risk of 15–20 %
(c)
Congenital melanocytic nevus
Small <1.5 cm, Medium = 1.5–20 cm
Large/giant >20 cm (or >5 % TBSA in prepubertal), can have “bathing trunk” distribution
Path: “congenital pattern” = wraps around adnexal structures
Increased risk of MM, neurocutaneous melanosis (NCM) = syndrome of large congenital melanocytic nevi with meningeal melanosis or melanoma
Greatest risk for NCM in axial lesions with satellite nevi, screen with MRI
50 % with NCM get leptomeningeal MM
(d)
Spitz nevus
Aka “benign juvenile melanoma”
In kids, clinical ddx JXG, mastocytoma
Dermoscopy: starburst pattern
Path: circumscribed elongated nests (may look like bananas), separated from adjacent keratinocytes (clefting around nests), with Kamino bodies (pink globules)
Many Spitz have HRAS mutation associated
“Spitzoid features” of other nevi include: nests that are vertical, epithelioid appearance, spindle cells
(e)
Pigmented spindle cell nevus of Reed
Classically a recently developed well-circumscribed black lesion on thigh of young woman (without other pigmented lesions on body)
Some classify this as a subtype of Spitz nevus
Path: fascicles of uniform, slender spindle cells with melanin
(f)
Deep penetrating nevus
Aka plexiform spindle cell nevus
Dark papule/nodule typically on head/neck in first few decades
Path: sharply demarcated wedge-shaped pigmented proliferation
Shares features with both Spitz nevi and blue nevi, and can mimic melanoma
(g)
Halo nevus
A nevus with a surrounding white halo, caused by an immune response to nevus cells (infiltrating lymphocytes on path); repigments if remove nevus
(h)
Balloon cell nevus
Variant of nevus with predominance of altered, large melanocytes with vacuolated cytoplasm
(i)
Becker’s nevus/melanosis
Unilateral, hyperpigmented patch, often with hypertrichosis
On path, acanthosis, features of smooth muscle hamartoma, basilar hyperpigmentation; ddx accessory nipple (papillomatous)
See also Neoplastic: Spindle Cell Tumors: Smooth Muscle
(j)
Nevus spilus
Speckled lentiginous nevus
Can see in phakomatosis pigmentovascularis (with capillary malformation), phakomatosis pigmentokeratotica (with nevus sebaceus)
(k)
Dermal melanocytosis
Note: Melanocytes may remain in dermis (stalled migration from neural crest during in utero development) most commonly in three areas: head/neck, lumbosacral, distal dorsal extremities
I.
Mongolian spot
On lumbosacral
Multiple can be associated with lysosomal storage diseases
II.
Nevus of Ota
By eye
Laser tx = q-switched Ruby or Alexandrite
III.
Nevus of Ito
On shoulder
IV.
Acquired dermal melanocytosis
Not congenital; might represent reactivation of existing dermal melanocytes
V.
Blue nevus (dermal melanocytoma)
GNAQ mutations may be associated
1.
Common blue nevus
Path: elongated, wavy melanocytes, melanophages
2.
Cellular blue nevus
Path: dendritic melanocytes associated with nests of spindle cells
Atypical cellular blue nevi hard to distinguish from melanoma
l.
Lentigines (lentigo simplex)
Increased number of melanocytes and melanin (but not a neoplastic proliferation)
Essentially the same as café-au-lait macules, but <5 mm
Labial lentigo: path = mucosal, ectatic, broad rete ridges, basilar hyperpigmentation
Can be seen in many syndromes:
I.
Peutz-Jeghers syndrome
Perioral and oral mucosal lentigines prominent
Intestinal polyposis, risk of intussusseption
Mutation in STK11 (LKB1), a serine-threonine kinase
Increased cancers (93 % have cancer, 50 % have died from cancer by age 57!), especially GI cancers, breast, ovarian
II.
Laugier-Hunziker syndrome
Only lentigines, no other findings or risks
III.
LEOPARD syndrome
Lentigines, Electrocardiographic conduction defects, Ocular hypertelorism, Pulmonary stenosis, Abnormalities of genitalia, Retardation of growth and Deafness (need lentigines and ≥2 others for dx)
Autosomal dominant, PTPN11 gene; defect in same gene causes Noonan syndrome
IV.
Carney complex
Aka LAMB/NAME syndrome
Lentigines, Atrial myxoma, Mucocutaneous myxoma, Blue nevi
Nevi, Atrial myxoma, Myxoid neurofibroma, Ephelides
Essentially 3 main components: 1. Myxomas (skin, heart, breast), 2. Lentigines (spotty skin pigmentation), 3. Endocrine tumors/abnormalities
Associated with PRKAR1A gene mutation (tumor suppressor gene that encodes a cAMP-dependent kinase important in many endocrine processes), autosomal dominant – Less common components include large-cell calcifying Sertoli cell tumor of the testis (sexual precocity), psammomatous melanotic schwannoma, epithelioid blue nevus. Also, growth hormone-producing pituitary adenomas.
V.
Cronkhite-Canada syndrome
Polyposis associated with lentigines of buccal mucosa, face, acral sites; nail dystrophy, alopecia
Usually in older men
(m)
Café-au-lait macules (CALMs)
Essentially the same as lentigines, but >5 mm
Path: increased melanin/melanosomes, but not increased melanocytes
I.
Neurofibromatosis – types I and II
“Coast of California”-type CALMs
Axillary freckling “Crowe’s sign”
Dx criteria for NF require ≥6 CALMs of 5 mm (prepubertal) 1.5 cm (postpubertal)
See also Neoplastic: Syndromes with Multiple Tumors or Multiple Types of Tumors
II.
McCune-Albright syndrome
Precocious puberty and CALMs
“Coast of Maine”-like CALMs
(n)
Solar lentigines (liver spots/solar lentigo)
See in older patients; may be precursors for macular seborrheic keratoses
From UV exposure
Path: club-shaped rete ridges with pigmentation, solar elastosis
(o)
Ephelides (freckles)
Only in sun-exposed areas, can see in kids
2.
Malignant melanocytic neoplasms
(a)
Melanoma (MM)
Melanoma represents less than 2 % of skin cancers, but accounts for the majority of skin cancer deaths (about 10,000/year)
Sixth most common cancer diagnosis in US and the most common cancer in Caucasian women age 25–29
Path: atypical features as described in dysplastic nevi, neoplastic proliferation of melanocytes beyond nests, Pagetoid spread, artifactual splitting in epidermis from lack of cellular adhesions (desmosomes) with melanocyte infiltrate, regression
Risk factors include: exposure to sun (intermittent sun exposure significant rather than total sun exposure seems more important), use of sun beds/tanning bed, skin phenotype/pigmentation (Fitzpatrick skin type), number of melanocytic nevi and dysplastic nevi, family history of melanoma, personal history of melanoma
Despite association of melanoma with ultraviolet radiation (exemplified by xeroderma pigmentosum with defects in nucleotide excision repair), it is not clear how UVR causes melanoma; melanomas lack the UVB signature mutations seen in NMSCs. It is clear, however, that melanoma can occur without sun exposure.
Most melanomas occur de novo; less than 1/4 in association with nevi; dysplastic nevi no more likely to develop MM than other common nevi
Breslow depth (from top of granular layer to deepest point) relates to prognosis; Clark level was another measure of depth that was found to be poorly reproducible and thus has fallen out of favor
Hutchinson’s sign = melanonychia with pigment on proximal nail fold, suggestive of melanoma
2010 AJCC criteria (T/N/M staging):
Tis = MMIS
T1 <1 mm thickness
(a)
without ulceration and mitosis <1/mm2
(b)
with ulceration or mitoses ≥1/mm2
T2 1.01–2.00 mm thickness
(a)
without ulceration
(b)
with ulceration
T3 2.01–4.00 mm thickness
(a)
without ulceration
(b)
with ulceration
T4 >4.00 mm thickness
(a)
without ulceration
(b)
with ulceration
N1 a: Micrometastasis, b: Macrometastasis
Staging:
Stage 0 = Tis, N0, M0
Stage IA = T1a; IB = T1b, T2a;
Stage IIA = T2b, T3a; IIB = T3b, T4a; IIC = T4b
Stage III = any T, N > N0, M0
Stage IV = any T, any N, M1
Increased LDH signifies poor prognosis
In-transit metastases are defined as lesions >2 cm from primary tumor, but not to the nodes
Satellite lesions are lesions within 2 cm of primary tumor; local recurrence typically defined as lesion within 2 cm of surgical scar
Sentinel lymph node biopsy controversial; quickly becoming standard of care since informs staging, but no mortality benefit to patients found; generally considered in stage III, IV, and even in any tumor with Breslow depth >1 mm
CDKN2A (Chr 9p) is the most common gene mutated in familial melanoma
CDKN2A = tumor suppressor, encodes p14 and p16 which allow p53 and Rb respectively to function
Most common gene mutation = BRAF, associated more with sun-protected area MM; codes for a kinase, BRAF, and also associated with papillary thyroid carcinoma and colorectal carcinoma; 90 % of BRAF mutations are V600E (glutamic acid for valine)
Majority of melanomas have BRAF (60 %) or NRAS (20 %) mutations (would not expect in same tumor)
Increased c-KIT mutations in MM from mucosal, acral, and chronically sun-damaged skin; imatinib (Gleevec) is potential therapy
Patients with history of MM should have GYN, ophtho, and dental f/u (for screening of areas where melanoma may occur that dermatologists may not evaluate well)
Treatment for metastatic melanoma: Currently no truly effective treatment. Standard chemotherapy has included dacarbazine (DTIC) and IL-2 despite response rates of only 15–25 %
New treatments include:
1.
BRAF inhibitors: sorafenib (nonselective, and not very efficacious in trials), PLX4032/vemurafenib, inhibits BRAF with V600E mutation (these may increase keratoacanthoma-type SCCs, however)
2.
Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte antigen 4 (CTLA-4), potentiates T-cell anti- tumor response
3.
Imatinib (Gleevec) – potential for patients with c-KIT mutation (acral and mucosal)
4.
Newest focus has been on MEK inhibitors in combination with BRAF inhibitors; also, PD-1 inhibitors (see also Basic Science: Genes in Melanoma)
NSAIDs/ASA may decrease melanoma incidence
Melanoma appears to occur more frequently on L > R (perhaps from sitting in car on driver’s side?)
Important immunohistochemistry stains:
S100 = sensitive, not specific
Stains melanocytes, dendritic cells, neural cells, adipocytes, sweat glands, breast epithelium
Good for desmoplastic MM
HMB-45 = specific, not sensitive
Stains only superficial
Poor staining in spindle cell/desmoplastic MM
Gradient pattern might help ddx MM vs. Spitz
Melan-A/MART-1 = current standard
Most sensitive/specific marker for demonstrating melanocytes
Target of cytotoxic cells; role in formation of type II melanosomes
May upstage MMIS
Surgical margins by depth (in general):
MMIS = 0.5 cm
MM <1 mm = 1 cm
MM <1–4 mm = 2 cm
MM >4 mm = 2–3 cm
I.
Superficial spreading
60–70 % of melanomas
II.
Nodular
No radial growth phase, 15–30 %
III.
Acral lentiginous
5–10 %
Noted in darker skin patients, not because increased incidence, but all other types decreased incidence
IV.
Lentigo maligna melanoma
5–15 %, slow growing on sun-exposed skin
V.
Amelanotic
Ddx pyogenic granuloma, BCC, SCC, purple plums
May have worse prognosis, but also often with delays in diagnosis
VI.
Desmoplastic/Spindle cell melanoma
May have tendency to locally recur, but less likely to metastasize
VII.
Ocular
Melanocytes found in the posterior uveal tract; posterior uveal chamber MM can metastasize to liver (hematogenous spread)
VIII.
Mucosal
IX.
Melanoma in situ
Includes lentigo maligna
7.3 Adnexal Tumors
Note: some tumors appear to have either eccrine or apocrine derivation (may be controversial), but this is generally not clinically relevant
1.
Eccrine
Primary function of eccrine glands is thermoregulation; also electrolyte balance
Ketoconazole, griseofulvin, and chemotherapeutic agents may be secreted in sweat
Eccrine sweat = 99 % water plus electrolytes, secreted by merocrine (eccrine) secretion
Innervated by sympathetic postgangliotic innervation, but functionally cholinergic (neurotransmitter = acetylcholine)
(a)
Poroma
A papule or nodule, often on palms/soles, can be on scalp
Clinical ddx: pyogenic granuloma, amelanotic melanoma
Path: downward grown of blue basaloid cells with ducts
Three benign variants (and one malignant):
I.
Eccrine poroma (both epidermal and dermal)
II.
Hidroacanthoma simplex (epidermal)
III.
Dermal duct tumor (dermal)
IV.
Porocarcinoma
(b)
Syringoma
Typically around eyes, but can be on abdomen/thighs/genitals
Path: multiple small ducts in fibrous stroma, nests may resemble commas or tadpoles
Can be eruptive in Down syndrome
Variants include:
I.
Clear cell syringoma
May be associated with DM
II.
Chondroid syringoma (aka mixed tumor)
Tubular/epithelial layers, mucoid stroma, Alcian blue (+)
Can see ghost cells (pink), but no basaloid cells, ddx pilomatricoma
(c)
Eccrine hidrocystoma
Glistening papule, typically infraorbital, see also Neoplastic: Cysts
(d)
Eccrine spiradenoma
In the painful tumor ddx
Actually thought to be apocrine-derived by most now
(e)
Clear cell hidradenoma (nodular hidradenoma)
(f)
Eccrine carcinoma
(g)
Other eccrine disorders
I.
Hyperhidrosis
Treatment = antiperspirants (aluminum chloride hexahydrate), glycopyrrolate, Botox, and last resort = surgery
1.
Frey’s syndrome (auriculotemporal syndrome or gustatory sweating)
Common after parotid surgery or trauma
II.
Hypohidrosis
1.
Hypohidrotic ectodermal dysplasia (HED)
Aka anhidrotic ectodermal dysplasia, Christ-Siemens-Touraine syndrome
Thin, sparse, or absent hair, missing or peg-shaped teeth, inability to sweat correctly
Primarily X-linked recessive
See also Alopecia: Non-scarring alopecia: Ectodermal dysplasias
III.
Bromhidrosis
Eccrine sweat is odorless; however, maceration can allow bacterial colonization, and apocrine sweat can be decomposed by bacteria
1.
Trimethylaminuria (TMA)
Known for causing “fishy”-odor
Inherited deficiency of FMO3 (flavin-containing monooxygenase-3)
Tx = avoid eggs, kidney, liver, fish in diet
IV.
Chromhidrosis (colored sweat)
V.
Miliaria
See also Vesiculobullous: Other
VI.
Uremic frost
Rarely, see uric acid deposits on skin in ESRD
2.
Apocrine
Apocrine gland variants: Moll’s glands on the eyelids, cerumen producing glands of inner ear, milk-producing apocrine glands
Apocrine glands secrete via decapitation secretion
Apocrine tumors can be associated with increased plasma cells
(a)
Cylindroma
Clinical: “turban tumors”
Path: “jigsaw puzzle,” well-circumscribed pieces, two cell populations, glassy rim
I.
Brooke-Spiegler syndrome
Mutation in CYLD (a tumor supressor), which encodes a deubiquitinating enzyme (a protease), which inhibits the NF-κB pathway
Cylindromas, trichoepitheliomas, and spiradenomas
See also Neoplastic: Syndromes with Multiple Tumors or Multiple Types of Tumors
(b)
Spiradenoma
Related to cylindromas; can see in Brooke-Spiegler
Path: Round “blue balls” in the dermis, but not as well circumscribed as jigsaw of cylindroma; 3 cell types = 1. pale, 2. dark, and 3. lymphocytes (this may be why it is painful)
(c)
Hidradenoma (hidradenoma papilliferum)
Seen in vulvar and perianal areas
Path = partially cystic with papillary and glandular areas, no epidermal connection
(d)
Apocrine adenoma
I.
Syringocystadenoma papilliferum
Presents as warty papule/plaque, may ooze serosanguinous fluid
Almost exclusively on head/neck, 1/3 occur in nevus sebaceus
Path = irregular papillary projections protrude into invagination of surface epithelium; stroma with plasma cell infiltrate, often an epidermal connection
(e)
Apocrine hidrocystoma
Clinical: glistening cystic papule, typically on the eyelid, see also Neoplastic: Cysts
Path = dilated apocrine gland on eyelid skin, shows decapitation secretion, lined by two layers of cells
(f)
Microcystic adnexal carcinoma (MAC)
Most commonly occurs on the upper lip, locally aggressive
Path: poorly circumscribed, deeply infiltrative (subcutaneous to even muscle) with perineural invasion
(g)
Extramammary Paget’s disease
Most commonly in groin, perianal, scrotum, vulva
25–50 % associated with cutaneous malignancy
Path = atypical cells with abundant pale cytoplasm, can see Pagetoid spread
(h)
Syringoma (see eccrine)
(i)
Apocrine poroma
(j)
Apocrine carcinoma
3.
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Sebaceous
Remember association with Muir-Torre; in particular, the sebaceous adenoma is a unique hallmark
Note: nevus sebaceus is not a sebaceous neoplasm
For more detail on sebum, see also Basic Science: Sebum
Sebaceous gland variants:
Eyelids: Mebomian glands (inflamed = chalazion); Glands of Zeis (superficial margin, inflamed = hordeolum/stye); Mnemonic: Mebomian almost rhymes with chalazion, Zeis almost with stye.
Areolae: Montgomery tubercles
Vermillion, buccal mucosa: Fordyce spots
Genitalia: Tyson’s glands
(a)
Sebaceous hyperplasia
Yellow delled papules on face/chest
Path: large sebaceous lobules grouped around a central dilated duct (all connected to hair follicle)
(b)
Sebaceous adenoma
The hallmark lesion of Muir-Torre syndrome (MLH1, MSH2 defect)
Path: multiple sharply demarcated sebaceous lobules, separated and compressed connective tissue septa; classically, approximately half of the cells are mature sebocytes.
(c)
Sebaceoma (sebaceous epithelioma)
On a spectrum with sebaceous adenoma (some controversy about how to distinguish), may be associated with Muir-Torre
Path: similar to sebaceous adenoma, classically with a majority of sebocytes undifferentiated/germinative and only scattered clusters of mature sebocytes
(d)
Sebaceous carcinoma
Classically on eyelid, though BCC more likely in this location
Path: may see Pagetoid spread
