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6.4 Adnexal Neoplasms and Hamartomas
Fig. 6.13 Syringocystadenoma papilliferum: this exophytic lesion developed
within a nevus sebaceus. Note that the surface is covered with squamous epithelium. (From Calonje E, Brenn T, Lazar AJ, Billings SD. Tumors of the sweat
glands. In: McKee’s Pathology of the Skin . 5th ed. Philadelphia: Elsevier;
2020:1611–1679.)
Fig. 6.14 Papillary eccrine adenoma: the lesion is composed of dilated ducts
and cysts dispersed in a brous stroma. (From Calonje E, Brenn T, Lazar AJ,
Billings SD. Tumors of the sweat glands. In: McKee’s Pathology of the Skin . 5th
ed. Philadelphia: Elsevier; 2020:1611–1679.)
Syringobroadenoma
• Rare, benign sweat gland proliferation (unclear if true
neoplasm or reactive); legs (#1)
• May be a/w:
■
Schöpf-Schulz-Passarge
■
Clouston syndrome
■
Chronic stasis dermatitis (reactive process), burns,
scarring
• Histology: thin, anastomosing strands of sweat duct-
containing epithelium projecting downward from
epidermis into mid dermis; rich brovascular stroma
(similar to poroma)
Microcystic adnexal carcinoma (MAC,
sclerosing sweat duct carcinoma)
• Locally aggressive adnexal carcinoma with divergent/
bi-lineage differentiation (follicular 1 sweat gland)
• Firm, indurated plaque on lip (.chin and cheek) of
middle-aged women (Fig. 6.15)
Fig. 6.15 Middle-aged woman with a typical microcystic adnexal carcinoma.
(From Prado R, Mellette JR. Uncommon malignant tumors of the skin. In:
Fitzpatrick JE, Morelli JG, eds. Dermatology Secrets Plus. 5th ed. Philadelphia:
Elsevier, 2016:425–433.)
• Treatment: Mohs (ToC) .. WLE (high recurrence rate)
• Histology: poorly-circumscribed, deeply-inltrative
sclerosing basaloid proliferation with divergent/bi-lineage
differentiation (mixture of small sweat ducts 1
keratinizing “microcysts”); typically has PNI and
prominent lymphoid aggregates (most helpful clues on
examination); cytologic atypia is minimal
Aggressive digital papillary
adenocarcinoma (ADPA)
• Rare, highly aggressive malignant sweat gland neoplasm
(14% metastatic rate even w/ amputation); affects volar
digits of middle-aged adults; M » F (7:1)
• Treatment: amputation
• Histology: solid and cystic proliferation with papillary
projections, deeply inltrative growth pattern, cytologic
atypia, and ↑ mitotic rate; may appear quite bland but all
cases should be treated aggressively
Primary cutaneous mucinous carcinoma
(PCMC)
• Very rare malignant sweat gland neoplasm; presents as a
slow-growing, soft nodule; most commonly on eyelid/
periocular region; average age 5 60 years old
• Two subtypes: non-neuroendocrine PCMC (aggressive;
30% recurrence rate, 11% overall metastatic rate with 4%
distant metastasis) and neuroendocrine PCMC (much
less aggressive; 0% metastatic rate; strongly associated
with endocrine mucin-producing sweat gland carcinoma)
• Treatment: Mohs (lower recurrence rates) recommended
over WLE
• Histology: basaloid epithelial tumor nodules “oating in
lakes of mucin” (sialomucin); intratumoral ducts give
rise to cribriform appearance (Fig. 6.16); CK71, CK20-
• Clinical pearl: mucinous carcinomas on the face are
almost always primary, whereas lesions arising on trunk
may represent metastasis of visceral malignancy (GI,
breast, lung, or ovarian); may be indistinguishable from
mucinous breast cancer metastasis
355
CHAPTER 6 • Neoplastic Dermatology
Fig. 6.16 Mucinous carcinoma. (From Elston DM. Sweat gland neoplasms. In:
Elston DM, Ferringer T, eds. Dermatopathology. 3rd ed. Philadelphia: Elsevier;
2019:83–100.)
Endocrine mucin-producing sweat gland
carcinoma (EMPSGC)
• Rare, low-grade sweat gland carcinoma that presents as a
slow-growing nodule/cyst; exclusively eyelid/periocular
region; F . M (2:1); average age 5 60 to 70 years
• Often occurs in conjunction with primary cutaneous
mucinous carcinoma (neuroendocrine subtype) → thought
to be a precursor lesion (mucinous carcinoma in situ)
• Histology: dermally based, multilobular tumor with solid,
cystic, cribriform, and papillary areas; small mucinous
pseudocysts (vs. “LARGE lakes of extracellular mucin” in
PCMC); bland cytology; expresses neuroendocrine markers
■
Mnemonic: “essentially looks like the epithelial areas
of PCMC but without huge lakes of mucin”
■
IHC: must be positive for one or more
neuroendocrine marker (synaptophysin,
chromogranin, NSE, or CD57); usually positive for
low-molecular cytokeratins (Cam5.2 and CK7), EMA
(luminal cells), and ER/PR; negative for CK20 and
S100. Myoepithelial markers (SMA, calponin, p63/p40,
SOX10, and S100) may be used to identify the
periphery of in situ component n if present, supports
a primary cutaneous (vs. metastatic) origin
• Prognosis/treatment: excision is curative; rarely recurs and
never metastasizes; may progress to mucinous carcinoma
(specically, neuroendocrine PCMC)
w/ cribriform appearance; extends into SQ fat w/
prominent PNI; lacks epidermal connection
■
May have brotic or mucinous stroma (but no large
“lakes of mucin”)
■
Contains myoepithelial cells (lining ducts; stains positive
for SMA, calponin, p63/p40, SOX10, and S100)
■
Fusions/mutations in MYB, NFIB, and MYBL1 seen in
nearly all cases
Comparative dermatopathologic features of sweat gland neoplasms for Board Exam purposes
Poroma (classic juxtaepidermal type)
• Critical histologic features
■
Circumscribed endophytic proliferation with broad,
multifocal epidermal connections; monomorphous
“poroid cells”; variably sized sweat ducts; highlyvascularized stroma
■
Immunostains: CEA, EMA, and PAS highlight ducts
and intracytoplasmic lumina
• Most commonly encountered differential diagnosis
(DDx)
■
Trichilemmoma: similar endophytic growth pattern,
but has peripheral palisade with thick pink BMZ,
prominent clear cell change, and lacks small poroid
cells and sweat ducts
■
Hidradenoma: almost entirely conned to dermis, w/
minimal epidermal connection (vs. broad multifocal
connection in poroma); has three cell types (poroid 1
clear cells 1 squamoid cells); has prominent stromal
sclerosis w/ hyalinized or keloidal collagen
Hidroacanthoma simplex
• Critical histologic features
■
Wholly intraepidermal poroma variant; multiple welldemarcated nests of small poroid cells within the
epidermis; sweat ducts may not be easily visualized
• Most commonly encountered DDx
■
Clonal SK, or SK with Borst-Jadassohn effect: cells are
at least same size as (often larger than) surrounding
keratinocytes
■
Bowenoid SCCIS: keratinocytes are highly atypical,
↑ mitoses, and ↑ dyskeratotic keratocytes
Dermal duct tumor
Adenoid cystic carcinoma (ACC)
• May arise as a primary adnexal carcinoma or cutaneous
metastasis from salivary gland
■
Primary cutaneous ACC: indolent tumor; most
commonly on the scalp of middle-aged adults;
minimal metastatic risk, but up to 70% local
recurrence rate (as a result of extensive PNI)
■
Salivary gland ACC: highly-aggressive (50% metastatic
rate and high mortality)
• Histology: poorly-circumscribed proliferation of small-
to medium-sized basaloid cuboidal tumor nodules
356
• Critical histologic features
■
Wholly dermal poroma variant; well-circumscribed
“blue balls within dermis”; tumor nodules composed
of rounded poroid cells with same appearance as
classic poroma; lacks epidermal connection
• Most commonly encountered DDx
■
Hidradenoma: both may look like “big blue balls” in
the dermis with sweat ducts; however, hidradenoma
is composed of three cell types (poroid 1 squamoid
1 clear cells), has prominent stromal sclerosis/
keloidal collagen around tumor, and has dilated
cystic spaces
6.4 Adnexal Neoplasms and Hamartomas
■
Trichoblastoma: both may look like “big blue balls” in
the dermis and are composed of small blue cells, but
trichoblastoma has hair follicle differentiation with
rudimentary hair shafts, papillary mesenchymal
bodies, keratin debris, and dystrophic calcication
(none of which are seen with dermal duct tumor);
trichoblastoma lacks sweat ducts
■
Cylindroma: both appear as blue balls in dermis
with sweat ducts, but cylindroma has thick pink BMZ
material around tumor lobules, hyaline deposits
within tumor lobules, and biphasic cell types
(Dermal duct tumor is composed only of small blue
poroid cells)
■
Spiradenoma: both appear as blue balls in dermis with
sweat ducts, but spiradenoma has hyaline deposits
within tumor lobules, and biphasic cell types (Dermal
duct tumor is composed only of small blue poroid
cells), and large cystic spaces
Hidradenoma
• Critical histologic features
■
Circumscribed, large tumor nodules composed of three
main cell types: (1) squamoid cells, (2) poroid cells,
(3) clear cells; 1/– large cystic spaces (“solid-cystic
hidradenoma”); lesion occupies entire dermis; scattered
sweat ducts; prominent dermal sclerosis w/ keloidal
collagen (major clue!); minimal to no epidermal
connection
• Most commonly encountered DDx
■
Classic poroma (see above)
■
Dermal duct tumor (see above)
■
Trichoblastoma: both may look like “big blue balls” in
the dermis, but trichoblastoma has hair follicle
differentiation w/ rudimentary hair shafts, papillary
mesenchymal bodies, keratin debris, and dystrophic
calcication; lacks sweat ducts
■
Cylindroma: both appear as blue balls in dermis with
sweat ducts, but cylindroma has thick pink BMZ
material around tumor lobules, hyaline deposits
within tumor lobules, and biphasic cell types;
cylindroma lacks the three cell types characteristic of
hidradenoma; also lacks stromal sclerosis/
hyalinization/keloidal collagen
■
Spiradenoma: both appear as blue balls in dermis with
sweat ducts and dilated cystic spaces; but spiradenoma
has hyaline deposits within tumor lobules, biphasic
cell types, “lymphocytes peppered” within tumor;
spiradenoma lacks the three cell types (squamoid,
poroid, and clear cells) of hidradenoma and lacks
stromal sclerosis/keloidal collagen
■
Mixed Tumor: both tumors have ducts, a mixture of
epithelial cell types, and stromal changes; however,
MT has much more chondroid/myxoid stromal
changes (vs. sclerotic collagen/keloidal stroma in
hidradenoma)
Spiradenoma
• Critical histologic features
■
Well-circumscribed, nodulo-cystic proliferation of “blue
balls in the dermis” with ductal formation (often
cystically dilated); biphasic epithelial cell population;
intratumoral lymphocytes (“lymphocytes peppered in
the tumor”); PAS1 eosinophilic hyaline droplets
composed of BMZ material (type IV collagen) found
within tumor (same material as in cylindromas, but
usually located within the tumor, rather than encircling
the tumor to form separate jigsaw pieces); very
vascular-appearing because of the widely ectatic
vessels around periphery of tumor
• Most commonly encountered DDx
■
Cylindroma: thick hyaline BMZ material
predominantly encircles nodules (vs. droplets found
within nodules, as in spiradenoma) and separates them
into small jigsaw puzzle pieces; lacks “lymphocyte
peppering,” also lacks large cystically dilated ducts and
ectatic vascular spaces of spiradenoma
■
Hidradenoma (see above)
■
Dermal duct tumor (see above)
Cylindroma
• Critical histologic features
■
Well-circumscribed proliferation of multiple small- to
medium-sized blue tumor lobules encircled by thick
hyaline BMZ material (type IV collagen mainly) →
leads to “jigsaw puzzle” pattern; scattered small ducts;
biphasic cell population
• Most commonly encountered DDx
■
Spiradenoma (see above)
■
Dermal duct tumor (see above)
■
Hidradenoma (see above)
Syringoma
• Critical histologic features
■
Circumscribed proliferation of small tadpole or
comma-shaped sweat ducts w/ eosinophilic cuticle
and amorphous sweat within lumen; sclerotic stroma;
conned to upper half of dermis
■
Boards fodder: you should never see follicular
differentiation or multiple horn cysts in a syringoma
→ if you see either → more likely desmoplastic
trichoepithelioma (DTE) or MAC!
• Most commonly encountered DDx
■
DTE: follicular differentiation, lots of horn cysts, and
dystrophic calcication; lacks sweat ducts
■
Morpheaform BCC: follicular differentiation, 1/– horn
cysts (fewer than in DTE), atypical cells w/ ↑ mitoses,
and apoptotic cells; lacks sweat ducts
■
MAC: like syringoma has sweat ducts, but has
concomitant follicular differentiation w/ horn cysts
(divergent/bi-lineage differentiation is a key feature
of MAC!), more deeply inltrative into deep dermis/
SQ, PNI w/ lymphoid aggregates (not seen in
syringoma)
Mixed tumor (MT; “chondroid syringoma”)
• Critical histologic features
■
Tumor of mixed epithelial and mesenchymal
derivation (hence the name); circumscribed
dermal/SQ tumor consisting of glandular structures,
357
CHAPTER 6 • Neoplastic Dermatology
ducts, and epithelial strands with myxoid/chondroid
stroma
• Most commonly encountered DDx
■
Hidradenoma (see above)
■
Syringoma: lacks chondroid/myxoid stroma
Hidradenoma papilliferum (HPAP)
• Critical histologic features
■
Well-circumscribed cystic proliferation in dermis with
innumerable papillary projections invaginating into
central cyst-like spaces; has “maze-like” appearance;
lacks epidermal connection
• Most commonly encountered DDx
■
SPAP (SCAP): has broad epidermal connection;
↑ plasma cells in peritumoral stroma; lacks maze-like
quality of HPAP
■
Nipple adenoma/erosive adenomatosis: arises on
nipple rather than vulva; typically has connection to
overlying epidermis; less maze-like
■
TAA/PEA: dermal-based proliferation of multiple small
ducts w/ papillary projections into lumen; lacks mazelike appearance of HPAP
Syringocystadenoma papilliferum (SPAP, SCAP)
• Critical histologic features
■
Verrucous epidermal hyperplasia w/ endophytic growth
into dermis; broadly opens onto epidermis; papillary
projections lined by two cell layers (inner
myoepithelial and outer apocrine layer with
decapitation secretion); abundant plasma cells in
peritumoral stroma
• Most commonly encountered DDx
■
HPAP: maze-like quality; lacks epidermal connection
Papillary eccrine adenoma (PEA)
• Critical histologic features
■
Favors legs of Black women; well-circumscribed
proliferation of small- to medium-sized sweat ducts
w/ papillary projections extending into the lumen
• Most commonly encountered DDx
■
TAA: nearly identical appearance, but favors scalp; has
decapitation secretion and ↓ papillary projections
■
ADPA: more inltrative growth pattern; solid and
cystic architecture; ↑ mitoses and atypia; occurs on
digits
Tubular apocrine adenoma (TAA)
• Critical histologic features
■
Similar to PEA, but favors scalp; apocrine
differentiation w/ decapitation secretion and fewer
papillary projections
• Most commonly encountered DDx
■
PEA: see above
■
ADPA: occurs on ngertips; more inltrative; solid and
cystic architecture; ↑ atypia and mitoses
Porokeratotic eccrine ostial and dermal duct nevus
• Critical histologic features
■
Punctate epidermal hyperkeratosis with cornoid
lamellae arising from acrosyringium
• Most commonly encountered DDx
■
Porokeratosis: cornoid lamellae arise from epidermal
epithelium, not acrosyringium
Syringobroadenoma
• Critical histologic features
■
Thin, anastomosing strands of sweat duct-containing
epithelium extending down from the epidermis into
the mid dermis; rich brovascular stroma surrounds
tumor
• Most commonly encountered DDx
■
Tumor of follicular infundibulum: follicular
differentiation (lacks sweat ducts); grows laterally in
supercial dermis in a “plate-like” fashion; multiple
connections to overlying epidermis with brotic stroma
(architecture resembles supercial BCC)
■
Fibroepithelioma of Pinkus: endophytic, bulbous
architecture, w/ multiple connections to the overlying
epidermis and BCC-like stromal changes; lacks sweat
ducts
Microcystic adnexal carcinoma (MAC)
• Critical histologic features
■
Sclerosing basaloid proliferation with divergent/
bi-lineage differentiation (follicular and sweat),
giving rise to proliferation of small sweat ducts
and “follicular microcysts”; minimal cytologic
atypia; deeply inltrative throughout dermis, SQ
and into muscle; typically has PNI and lymphoid
aggregates
■
Boards fodder: mixture of sweat and follicular
differentiation (divergent/bi-lineage differentiation) is a
very useful clue for MAC; typically do not see this w/
syringoma, DTE, or BCC!
• Most commonly encountered DDx
■
Syringoma: both have basaloid tadpole appearance, but
syringoma is circumscribed (vs. inltrative), conned
to upper half of dermis, only has sweat duct
differentiation (lacks follicular elements)
■
Morpheaform BCC: cells more atypical, w/ ↑ mitoses,
apoptosis, and myxoid stroma (vs. sclerotic in MAC);
only demonstrates follicular differentiation (lacks
sweat ducts)
■
DTE: follicular differentiation only (lacks sweat
ducts)
Aggressive digital papillary adenocarcinoma (ADPA)
• Critical histologic features
■
Solid and cystic proliferation w/ papillary projections;
deeply inltrative, cytologic atypia, and ↑ mitotic rate
358
• Most commonly encountered DDx
■
PEA, HPAP, and TAA: may have similar low-power
appearance, but inltrative growth pattern and
anatomic site is critical to diagnosis of ADPA!
Primary cutaneous mucinous carcinoma
(PCMC)
• Critical histologic features
■
Mnemonic: “blue tumor islands oating in lakes of
mucin”
■
Immunostaining pattern:
Positive: AE1/AE3, CAM5.2, EMA, CEA, CK7, ER,
PR, and 1/– neuroendocrine markers (neuron-
specic enolase [NSE], chromogranin, and
synaptophysin)
Negative: CK20
■
Important note: PCMC frequently has an in situ
component that is identied by nding a myoepithelial
layer (p63/p401, SMA1, calponin1, SOX101, and
S1001) surrounding the tumor → this conrms primary
cutaneous origin (rules out metastatic adenocarcinoma
from internal organs, since a myoepithelial layer is never
present in metastatic tumors)
• Most commonly encountered DDx
■
Metastatic mucinous carcinoma from breast: can be
ruled out if in situ component of PCMC is found
(unfortunately, not always present); otherwise, appears
identical to PCMC by histologic and
immunohistologic studies → need history,
examination, and imaging studies; most likely to arise
on trunk (vs. face, which is highly suggestive of PCMC)
■
Metastatic mucinous carcinoma from colon: CK7 /
CK201 (vs. CK71/CK20 in PCMC); GI tumors also
have a different mucin type than PCMC → can
distinguish with mucin histochemistry:
GI tumors 5 sulfomucin (Alcian blue positive at
pH 1.0 and 0.4)
PCMC 5 sialomucin (Alcian blue positive at pH 2.5)
♦ Also may be ruled out if in situ component of
PCMC is found
6.5 Hair Follicle Neoplasms/Hamartomas
6.5 HAIR FOLLICLE NEOPLASMS/
HAMARTOMAS
Folliculo-sebaceous-apocrine hamartomas
Trichofolliculoma
• Clinical and histopathologic features
■
Benign follicular hamartoma; skin colored papule w/
central follicular punctum from which numerous
tufted vellus hairs emerge
■
Histology: dilated central cystic follicle connected to
multiple fully formed vellus follicles (Fig. 6.17);
background brous stroma
■
Sebaceous trichofolliculoma (variant): radiating
follicles are accompanied by sebaceous glands
■
Folliculosebaceous cystic hamartoma: likely same entity
as sebaceous trichofolliculoma; often embedded in a
stroma containing supercial fat
• Histologic DDx
■
Fibrofolliculoma: both have a large central follicle with
numerous emanating epithelial attachments; however,
brofolliculoma only has thin strands of primitive
follicular epithelium (lacks hair shafts)
■
Pilar sheath acanthoma: cystically dilated central
follicle with radiating acanthotic epithelium; no hair
shafts in acanthotic buds
• Other high-yield facts/comments
■
Mnemonic: “multiple baby hairs connected to a large
mama hair”
Small mature follicles
Adenoid cystic carcinoma (ACC)
• Critical histologic features
■
Poorly circumscribed, inltrative proliferation of
multiple small- to medium-sized cribriform “blue
balls in dermis” with intratumoral ducts; typically has
extension into SQ fat and PNI; lacks large “lakes of
mucin”
• Most commonly encountered DDx
■
Mucinous carcinoma: epithelial tumor nodules are
oating in huge lakes of mucin
■
Trichoblastoma: also appears as “blue balls within
dermis” and may also have cribriform appearance,
but has follicular differentiation; lacks sweat ducts
and PNI
■
Dermal duct tumor: also appears as “blue balls within
dermis,” but the proliferation is well-circumscribed;
lacks PNI and cribriform appearance
Comedo
Fig. 6.17 Trichofolliculoma (low mag). (From Rapini RP. Follicular neoplasms.
In: Practical Dermatopathology . 2nd ed. Philadelphia: Elsevier; 2012:
311–319.)
359
CHAPTER 6 • Neoplastic Dermatology
Fibrofolliculoma
• Clinical and histopathologic features
■
Benign hamartoma; nondistinctive, small, skin-colored
papules involving head/neck; treatment: none required
but may try dermabrasion or CO
■
Histology: central follicle/cyst with numerous thin
laser ablation
2
strands of follicular epithelium radiating from it;
lacks hair formation; lesion surrounded by delicate,
loose bromyxoid stroma (Fig. 6.18)
■
Variants (perifollicular broma, trichodiscoma, and
acrochordons): likely same entity, just viewed in
different histologic sections; may not visualize the thin
strands of follicular epithelium
• Histologic DDx
■
Trichofolliculoma: has similar central cyst, but
attached structures are fully formed vellus hairs
w/ hair shafts
• Other high-yield facts/comments
■
Birt-Hogg-Dubé syndrome: Mutation in FLCN (encodes
folliculin, a tumor suppressor), AD inheritance; triad
of skin lesions (brofolliculomas, trichodiscomas, and
acrochordons); a/w RCC (oncocytic or chromophobe),
spontaneous pneumothorax, pulmonary cysts, and
medullary carcinoma of thyroid
Nevus sebaceus
• Clinical and histopathologic features
■
Benign hamartoma with follicular, apocrine, and
sebaceous components; present at birth along
Blaschko lines; becomes more yellow and verrucous
after puberty; scalp/face most common sites (.trunk
and neck); alopecia of affected area
■
Histology: verrucous epidermis with malformed,
diminutive hairs, lacks fully formed terminal hairs
within lesion; sebaceous glands open directly onto
skin surface; dilated apocrine glands
• Histologic DDx
■
Epidermal nevus: appears similar histologically
■
Sebaceous hyperplasia: nodular architecture; lacks
dilated apocrine glands and malformed/diminutive
hairs
• Other high-yield facts/comments
■
If extensive, may be a/w Schimmelpenning syndrome
or phakomatosis pigmentokeratotica
■
Secondary adnexal neoplasms arising within nevus
sebaceus: trichoblastoma (#1) . SPAP .
trichilemmoma, poroma, TAA, and BCC
Neoplasms with follicular germinative differentiation
Trichoepithelioma
• Clinical and histopathologic features
■
Benign; solitary or multiple (a/w inherited syndromes)
smooth, skin-to-pearly colored, dome-shaped papules
w/ telangiectasias; central face (nose #1, nasolabial
folds, upper cutaneous lip, and scalp)
■
Histology: well-circumscribed follicular basaloid
proliferation; well-organized nodules with epithelial
fronds, reticulated strands, and cribriform nodules
(“Swiss cheese”) (Fig. 6.19); numerous horn cysts (much
more than BCC); peripheral palisading; papillary
mesenchymal bodies; highly-cellular brotic pink
stroma (broblasts account for 50% of tumor’s overall
cellularity); almost entirely intradermal w/ minimal to no
epidermal connection; rarely ulcerates; no clefting
between tumor cells and stroma (stroma is tightly attached
to epithelial cells; may have stromal-stromal retraction)
■
IHC: scattered CK201 Merkel cells within tumor;
PHLDA11; stroma is CD341 and CD101; BCL-2 only
stains periphery of trichoepithelioma (vs. diffuse in BCC);
androgen receptor negative (vs. AR1 in most BCC)
• Histologic DDx
■
BCC: ↑ cytologic atypia, ↑ apoptosis, and ↑ mitoses;
myxoid stroma (vs. collagenous w/ ↑ broblasts);
lacks cribriform or reticulated architecture; retraction
from surrounding stroma; lacks papillary mesenchymal
bodies; far fewer horn cysts; has more connection to
epidermis; stains: BCL-21 (diffuse), CK20 negative,
PHLDA1 negative; stroma is CD10 negative
■
Trichoblastoma: may refer to large trichoeps or
follicular neoplasms w/ exclusively bulbar
differentiation (immature blue cells)
Thin follicular extensions
Sebaceous gland
Pale fibrotic stroma
Fig. 6.18 Fibrofolliculoma histology—hair follicle with thin extensions of epithelium into surrounding mucinous stroma. (From Rapini RP. Follicular neoplasms. In: Rapini
RP, ed. Practical Dermatopathology. 3rd ed. Philadelphia: Elsevier; 2021:321–329.)
360
Fig. 6.19 Trichoepithelioma. Groups of basaloid cells surrounded by broblasts forming a broepithelial lesion. (From Prieto VG, Shea CR, Celebi JT, Busam KJ. Adnexal
tumors. In: Busam KJ, ed. Dermatopathology: A Volume in the Series: Foundations
in Diagnostic Pathology. 2nd ed. Philadelphia: Elsevier; 2016:388–446.)
6.5 Hair Follicle Neoplasms/Hamartomas
Fig. 6.20 Desmoplastic trichoepithelioma. Characteristic low-power view showing epithelial strands, cysts, and foci of calcication. There are multiple points of
continuity within the epidermis. (From Brinster NK, Liu V, Diwan H, McKee PH.
Desmoplastic trichoepithelioma. In: Dermatopathology: A Volume in the High
Yield Pathology Series. Philadelphia: Elsevier; 2011:390.)
• Other high-yield facts/comments
■
Benign follicular tumors are CK201 and PHLDA11
(new stain) → distinguishes from BCC
■
Syndromes a/w multiple trichoepitheliomas:
Brooke-Spiegler syndrome: CYLD mutation,
multiple trichoepitheliomas, trichoblastomas,
spiradenomas, and cylindromas
Rombo syndrome: atrophoderma vermiculatum,
hypotrichosis, acro-facial vasodilation and cyanosis,
milia, and multiple BCCs
Desmoplastic trichoepithelioma (DTE)
• Clinical and histopathologic features
■
Young adult F . M; always solitary; almost always on
face (cheek #1); rm annular plaque w/ central dell
■
Histology: well-circumscribed proliferation contained
within upper half of dermis; thin cords of basaloid
cells (two to three cell layers thick) within sclerotic/
thickened collagenous stroma; numerous horn cysts,
keratin granulomas (from ruptured microcysts) and
dystrophic calcication (Fig. 6.20)
Granulomatous
inflammation
• Histologic DDx
■
Morpheaform BCC: atypical cells w/ ↑ mitoses,
↑ apoptosis, sharply angled nests, and fewer horn cysts
• Other high-yield facts/comments
■
Not a/w inherited syndromes
■
CK201 and PHLDA11 (vs. negative in morpheaform BCC)
Neoplasms with follicular matrix differentiation
Pilomatricoma (calcifying epithelioma of Malherbe)
• Clinical and histopathologic features
■
Solitary, rm, esh-colored nodule with white-chalky
hue from calcication; cheek (#1); children . adults;
caused by a mutation in the CTNNB1 gene (encodes
b-catenin, involved in WNT pathway)
■
Histology: well-circumscribed; complex cystic
proliferation with internal “rolls and scrolls”
appearance (Fig. 6.21); matrical (basaloid) cells w/
abrupt transition to fully keratinized, anucleate
Basaloid cells
Shadow cells within "cyst"
Fig. 6.21 Pilomatrixoma (low mag). (From Rapini RP. Follicular neoplasms. In: Practical Dermatopathology. 2nd ed. Philadelphia: Elsevier; 2012:311–319.)
361
CHAPTER 6 • Neoplastic Dermatology
“shadow/ghost cells” (eosinophilic); keratin
production leads to intense granulomatous
inammation; calcication in 80% (ossication
in 20%)
• Histologic DDx
■
Proliferating pilar tumor: similar convoluted cystic
architecture (“rolls and scrolls”), but has dense
eosinophilic trichilemmal keratin in cyst cavity rather
than ghost cells; lacks basaloid matrical cells
■
Pilomatrical carcinoma: adults on head/neck; basaloid
cells predominate over ghost cells; numerous mitoses
and inltrative architecture
• Other high-yield facts/comments
■
Old pilomatricomas may be composed entirely of
ghost cells, with calcication and ossication
■
Conditions a/w multiple pilomatricomas:
Myotonic dystrophy
Turner syndrome
Gardner syndrome (usually multiple hybrid
epidermoid cysts w/ pilomatrical differentiation)
Rubinstein-Taybi (broad thumbs)
Neoplasms with follicular sheath (trichilemmal) differentiation
A
Trichilemmoma
• Clinical and histopathologic features
■
Benign; smooth, skin-colored, verrucous papule on
central face (nose or upper lip most commonly); may
arise within nevus sebaceus
■
Histology: circumscribed lobular proliferation of pale
to clear staining cells containing abundant glycogen
(resemble outer root sheath cells); broad epidermal
connection, warty surface w/ hypergranulosis, and
peripheral palisading with eosinophilic/hyalinized
BMZ (PAS1) (Fig. 6.22)
■
Immunostains: pan-keratin1 and CD341 (marker of
outer root sheath differentiation)
• Histologic DDx
■
Clear cell acanthoma: both are clear cell proliferations
arising from epidermis; however, CCA is not endophytic/
lobular → instead, has regular psoriasiform hyperplasia
1 neutrophils in stratum corneum (mnemonic: “looks
like psoriasis w/ clear cells”)
■
Poroma: similar endophytic/lobular architecture, but is
composed of small blue poroid cells w/ rounded
nuclei, 1 sweat ducts 1 highly vascular stroma
■
Verruca vulgaris: lacks clear cells and hyalinized BMZ
• Other high-yield facts/comments
■
Multiple trichilemmomas → diagnostic of Cowden
syndrome
Desmoplastic trichilemmoma (DTL)
• Clinical and histopathologic features
■
Always solitary; slow-growing esh-colored papule on
face (#1 site); often arises within nevus sebaceus
■
Histology: mistaken for invasive SCC because has
angulated, pseudoinltrative epithelial strands in
center of lesion, accompanied by sclerotic/desmoplastic
B
Fig. 6.22 Trichilemmoma. A supercial dermal nodule of small cuboidal keratinocytes with a lobular growth pattern is associated with a follicle. (A) Low power
(B) high power. (From Prieto VG, Shea CR, Celebi JT, Busam KJ. Adnexal tumors.
In: Busam KJ, ed. Dermatopathology: A Volume in the Series: Foundations in
Diagnostic Pathology. 2nd ed. Philadelphia: Elsevier; 2016:388–446.)
stroma; conventional trichilemmoma almost always
present at periphery (key to Dx!); tumor is pan-keratin1
and CD341 (marker of outer root sheath
differentiation)
• Histologic DDx
■
Invasive SCC/BCC: lacks conventional trichilemmoma
at periphery, cells appear atypical, w/ ↑ mitoses,
pleomorphism, and apoptosis
• Other high-yield facts/comments
■
Boards relevance: they mostly want to see if you can
differentiate from SCC
■
Hint: look at periphery to identify conventional
trichilemmoma features
Neoplasms with supercial follicular
(isthmus and infundibular) differentiation
Tumor of the follicular infundibulum (TFI)
• Clinical and histopathologic features
■
Benign; scaly plaque on head/neck
■
Histology: plate-like proliferation of eosinophilic
isthmic keratinocytes arranged in a reticulate fashion in
362
6.6 Sebaceous Proliferations
supercial dermis; has broad but intermittent
epidermal connections; peripheral palisading, brous
stroma
• Histologic DDx
■
Supercial BCC: both have broad, intermittent
epidermal connections and peripheral palisade, but
BCC has clefting, mucinous stroma, and single-cell
necrosis
■
Eccrine syringobroadenoma: both have anastomosing
or reticulated architecture, but ES has prominent sweat
ducts, highly vascular stroma, and deeper extension
into dermis
• Other high-yield facts/comments
■
Boards: not commonly tested; only the histology is
testable
Trichoadenoma (TA; of Nikolowski)
• Clinical and histopathologic features
■
Benign follicular neoplasm on spectrum with DTE:
whereas DTEs have a 50/50 mixture of basaloid
follicular epithelial structures and keratin-lled
microcysts, TAs are composed almost entirely of the
small, keratin-lled microcysts, with minimal to no
basaloid follicular epithelial structures
■
Histology: well-circumscribed, supercial dermal
proliferation composed of small keratinizing milia-
like cysts (“microcysts”) 1 sclerotic stroma (similar to
DTE stroma)
• Histologic DDx
■
DTE: (see above)
■
Milia: the microcysts of TA individually look identical to
milia, but simple milia lack the sclerotic stroma of TA
• Other high-yield facts/comments
■
Mnemonic: “trichoadenomas look like DTEs that are
composed purely of keratin microcysts”
■
Mnemonic: “trichoadenoma looks like dozens of small
milia crammed together in a small biopsy”
granular than would be expected for a mature sebocyte
(should be very white)
• Other high-yield facts/comments
■
May assume a linear conguration on clavicle/neck →
“juxtaclavicular beaded lines”
Sebaceous adenoma
• Clinicopathologic features
■
Benign, small yellowish papule on head/neck
■
Histology: well-circumscribed, endophytic proliferation
with dilated, direct opening that dumps sebaceous
debris onto skin surface → debris forms impetiginized
crust; tumor conned to supercial dermis; tumor is
composed of sebaceous glands w/ ↑ peripheral basaloid
seboblasts (30%–50% of tumor) 1 slightly immature
central sebocytes (cytoplasm is pinker and more granular
than fully mature, white sebocytes); lacks necrosis,
atypical mitoses, and inltrative growth (Fig. 6.23)
• Histologic DDx
■
Sebaceous carcinoma: ↑ seboblasts, ↑ mitoses, atypical
mitoses, inltrative growth, necrosis
■
Sebaceoma: purely intradermal in almost all cases
(limited to no connection to skin surface); well-
circumscribed nodule composed of ↑↑ seboblasts
(.50%); lacks normal sebaceous gland architecture
(vs. sebaceous adenoma, which has the same
architecture as normal sebaceous glands, but just too
many seboblasts)
• Other high-yield facts/comments
■
Most common sebaceous neoplasm a/w Muir-Torre
syndrome
■
Muir-Torre: AD inheritance; mutation in MSH2 .
MLH1 . MSH6, and PMS2; characterized by multiple
sebaceous neoplasms; multiple KAs; ↑ risk of colon
(#1) and GU (#2) cancer
Sebaceoma (sebaceous epithelioma)
Proliferating pilar (trichilemmal) tumor
• Discussed in Cyst section
6.6 SEBACEOUS PROLIFERATIONS
Sebaceous hyperplasia
• Clinicopathologic features
■
Common, benign enlargement of normal sebaceous
glands; p/w multiple yellow papules with central dell
on face and upper trunk
■
Histology: enlarged sebaceous glands with normal
internal architecture (peripheral thin layer of
immature basaloid seboblasts surrounding central,
mature, white sebocytes); enlarged sebaceous lobules
circumferentially surround a central infundibulum
• Histologic DDx
■
Sebaceous adenoma: thicker layer of immature,
peripheral, basaloid seboblasts; the central sebocytes
have cytoplasm that is slightly pinker and more
• Clinicopathologic features
■
Benign; more deeply-seated than sebaceous adenoma
Fig. 6.23 Sebaceous adenoma. Part of a well-circumscribed tumor with surface
continuity. (From Brinster NK, Liu V, Diwan H, McKee PH. Sebaceous adenoma.
In: Dermatopathology: A Volume in the High Yield Pathology Series. Philadelphia:
Elsevier; 2011:410.)
363
CHAPTER 6 • Neoplastic Dermatology
■
Histology: well-circumscribed, entirely intradermal
nodule with minimal to no connection to overlying
skin surface (vs. sebaceous adenoma which dumps
open to skin surface); seboblasts are the predominant
cell type (»50%), with a small number of randomly
scattered mature sebocytes; lacks the normal
sebaceous gland architecture (mature white sebocytes
are randomly scattered rather than concentrated
centrally); lacks malignant features (cytologic atypia,
mitoses, necrosis, and inltrative growth)
• Histologic DDx
■
Sebaceous adenoma: opens broadly onto skin surface,
dumping its contents/debris onto skin surface; retains
normal architecture of a sebaceous gland
■
Sebaceous carcinoma: malignant cytologic (nuclear
atypia, numerous/atypical mitoses) and architectural
(poorly circumscribed, inltrative) features
• Other high-yield facts/comments
■
Boards tip: if a sebaceous neoplasm has . 50%
basaloid cells (seboblasts) → must either be sebaceous
carcinoma or sebaceoma
Sebaceous carcinoma
• Clinicopathologic features
■
Malignant; signicant metastatic potential; separated
into ocular and extraocular types; most commonly
presents as a nonspecic red nodule 1/– ulceration;
most common sites: periorbital area . other sites on
head/neck . trunk
■
Histology: asymmetric, inltrative basaloid
proliferation (often . 50% seboblasts) w/ ↑ mitotic
rate, atypical mitoses, and tumor necrosis; arises from
epidermis, w/ extension into dermis; ocular sebaceous
carcinoma often has prominent pagetoid scatter
within epidermis (Fig. 6.24)
Can lose MSH2/MSH6, MLH1/PMS2 expression on
IHC, either as part of Muir-Torre syndrome or
sporadically
• Histologic DDx
■
Sebaceous adenoma: see above
■
Sebaceoma: although it also appears very basaloid with
↑ N:C ratio, sebaceoma lacks other malignant features
• Other high-yield facts/comments
■
May be a/w Muir-Torre syndrome or arise de novo
■
Ocular form most commonly misdiagnosed as
chalazion or blepharitis
6.7 NEURAL NEOPLASMS
Traumatic neuroma
• Reactive proliferation of nerve bers at sites of trauma →
arises from attempted regeneration of nerve
• Flesh-colored rm papule or nodule; painful
• Histology: variably sized/shaped, haphazardly distributed
small nerve bundles (resemble normal nerves, in that
Schwann cells and axonal components are present in a 1:1
ratio); background scar
■
S1001 and neurolaments1 (stains axons)
Palisaded encapsulated neuroma (PEN;
solitary circumscribed neuroma)
• Adults; most common on face (90%)
• Flesh-colored rm papule
• Histology: circumscribed dermal nodule w/ clefting at the
periphery (but lacks a true capsule); nodule composed of
tightly packed, fascicular bundles of plump, wavy spindle cells
(recapitulates normal nerve; Schwann cells: axons 5 1:1)
■
S1001 and neurolaments1 (stains axons)
• Histologic DDx:
■
Schwannoma: both are fascicular, but PEN is way more
supercial (schwannomas arise in deep fat/muscle near
large nerves), has axons (neurolament stain is
negative in schwannoma), and lacks a true capsule
(schwannoma has EMA1 perineurial capsule)
■
Neurobroma: individual cells are similar, but PEN is
much more sharply circumscribed and organized as
discrete fascicles
• Multiple mucosal neuromas of MEN 2B (similar
histologically): multiple pink papules in oral cavity,
conjunctiva, and nasal and laryngeal mucosa
Fig. 6.24 Sebaceous carcinoma. There is extensive epidermal involvement with
conspicuous sebocytes. (From Brinster NK, Liu V, Diwan H, McKee PH. Sebaceous carcinoma. In: Dermatopathology: A Volume in the High Yield Pathology
Series. Philadelphia: Elsevier; 2011:412–413.)
364
Schwannoma (neurilemmoma)
• Benign proliferation composed almost entirely of
Schwann cells (S1001) with perineurial capsule (EMA1)
• Solitary pink nodule most commonly on exural
extremities (.head/neck)
• Histology: deep (arises in SQ near large nerves), well-
circumscribed, encapsulated proliferation of plump wavy
cells (Schwann cells) with hypercellular (Antoni A) areas
containing Verocay bodies (palisaded nuclei around
acellular pink material), and hypocellular (Antoni B)
myxoid areas; lacks axons (vs. NF, PEN, traumatic
neuromas); may see large nerve from which it arose at
periphery (Fig. 6.25)
■
S1001 (stains Schwann cells), EMA1 (stains
perineurial capsule); negative for neurolaments
(lacks axons)