Cutaneous Adnexal Tumors

17-05-2020 Cutaneous adnexal tumors - UpToDate
Official reprint from UpToDate®

www.uptodate.com ©2020 UpToDate, Inc. and/or its affiliates. All Rights Reserved.
Cutaneous adnexal tumors

Authors: Jeffrey P North, MD, Timothy H McCalmont, MD, Beth S Ruben, MD
Section Editor: June K Robinson, MD
Deputy Editor: Rosamaria Corona, MD, DSc
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2020. | This topic last updated: Mar 04, 2020.
INTRODUCTION
Cutaneous adnexal tumors are a large group of benign and malignant neoplasms that exhibit morphologic
differentiation towards one of the four primary adnexal structures present in normal skin: hair follicles,
sebaceous glands, apocrine glands, and eccrine glands [1,2]. They may occur sporadically or may be markers
of rare genetic syndromes, including Birt-Hogg-Dubé syndrome, Brooke-Spiegler syndrome, Cowden
syndrome, and Muir-Torre syndrome [3].
This topic will review the clinical features, diagnosis, and treatment of cutaneous adnexal tumors and
associated syndromes. Brooke-Spiegler syndrome, microcystic adnexal carcinoma, sebaceous carcinoma,
Muir-Torre syndrome, and Cowden syndrome are discussed separately.
● (See "Brooke-Spiegler syndrome (CYLD cutaneous syndrome)".)

● (See "Microcystic adnexal carcinoma".)
● (See "Sebaceous carcinoma".)
● (See "Muir-Torre syndrome".)
● (See "PTEN hamartoma tumor syndromes, including Cowden syndrome".)
CLASSIFICATION
Cutaneous adnexal tumors are classified based upon their differentiation toward one of the primary
appendageal skin structures (table 1) [1]. Some tumors display differentiation toward more than one cell
lineage, making their precise classification difficult. However, it is important to remember that hair follicles,
sebaceous glands, and apocrine glands derive from the same epidermal bud in fetal development, explaining
why some adnexal tumors show differentiation of some or all of these adnexal structures in the same
neoplasm. Eccrine glands develop from a distinct embryologic anlage.
https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage_… 1/102

EPIDEMIOLOGY
Adnexal tumors represent a minority of cutaneous neoplasms. Data on their incidence and prevalence in the
general population are lacking. With the exception of patients with syndromes associated with adnexal tumors
and adnexal tumors arising in nevus sebaceus, most adnexal tumors occur in the fourth to sixth decade [4-6].
A female predilection has been noted for sweat duct tumors [4,7].
Malignant cutaneous adnexal tumors are rare. A retrospective study of the patients registered in the
Surveillance, Epidemiology, and End Results (SEER) database in the United States from 1988 to 2006, found
4032 malignant cutaneous adnexal tumors [8]. The median age at diagnosis was 70 with a slight male
predominance. Lesions were located on the head and neck in 65 percent of cases. The 10-year disease-
specific survival was 97 percent.
A higher incidence of malignant adnexal tumors occurs in patients with germline mutations predisposing to
such tumors. As an example, 5 to 10 percent of patients with Brooke-Spiegler syndrome develop malignant
adnexal tumors [6]. (See 'Brooke-Spiegler syndrome' below.)
CLINICAL FEATURES
Adnexal tumors typically present as pink, skin-colored, or slightly bluish papules or nodules ranging in size
from a few millimeters to several centimeters (picture 1A-C). Lesions are typically asymptomatic and slow-
growing over several years. Malignant adnexal tumors have a similar clinical appearance, but exhibit rapid
growth and can ulcerate. Adnexal tumors can be pigmented and may clinically resemble a melanocytic tumor.
Follicular and sebaceous neoplasms occur most frequently on the head and neck, where the greatest density
of folliculosebaceous units is found. Eccrine neoplasms can arise in any area of skin, but are most frequently
found on the palms and soles. Apocrine tumors have a predilection for the axilla, anogenital region, and
eyelids.
Patients with multiple adnexal tumors should be evaluated for possible syndromes associated with adnexal
tumors. (See 'Syndromes associated with cutaneous adnexal tumors' below.)
DIAGNOSIS
Biopsy — Because of the extensive overlap in clinical features of cutaneous adnexal tumors, biopsy is
essential for proper diagnosis. Excisional or punch biopsies are preferred to shave biopsies for the diagnosis
because superficial shave biopsies may miss important diagnostic findings. As an example, the surface of
fibrofolliculomas and trichodiscomas can resemble angiofibroma, and a superficial shave biopsy may lead to a
misdiagnosis. However, a deep-shave biopsy that captures a majority of the dermis with the lesion may be
acceptable. (See "Skin biopsy techniques".)

Pathology — The histopathologic characteristics of benign and malignant adnexal tumors are discussed in
the sections on specific tumor types below.
● (See 'Eccrine and apocrine tumors' below.)

● (See 'Follicular tumors' below.)
● (See 'Tumors with sebaceous differentiation' below.)
Immunoperoxidase stains — Most adnexal tumors can be diagnosed accurately with routine hematoxylin
and eosin-stained (H&E) sections from an adequate biopsy. When small, partial biopsies are performed or
tumors have ambiguous histopathologic features, immunohistochemical stains are a valuable adjunct:
● Ber-Ep4, cytokeratin 15, and T cell death-associated gene 51 (TDAG51) – Markers of hair follicle
differentiation, but also variably positive in some eccrine and apocrine tumors.
● Cytokeratin 20 and androgen receptor – The presence of cytokeratin 20 positive-Merkel cells colonizing
benign hair follicle tumors (eg, trichoblastoma) and absence of androgen receptor positivity helps
distinguish those tumors from basal cell carcinoma. Androgen receptor is frequently expressed in
sebaceous carcinoma as well.
● CD34 – Marker of trichilemmal differentiation and positive in the stroma in trichodiscoma.
● Epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA) – Useful markers of sweat
gland/ductal differentiation.
● Myoepithelial markers (eg, smooth muscle actin, p63, S100, SOX10, calponin) – Used to assess for loss
of myoepithelial cells in invasive adenocarcinomas or to assess for myoepithelial differentiation in
cutaneous mixed tumors.
● Beta-catenin – Positive in hair matrical tumors (eg, pilomatricoma).
● PTEN – Complete loss of PTEN staining occurs in >80 percent of trichilemmomas in patients with
Cowden syndrome and in only 3 percent of sporadic trichilemmomas [9].
● Adipophilin – Marker of sebocytic lineage.
● CD117 (c-kit) and MYB – Positive markers for adenoid cystic carcinoma. Also expressed in cylindroma
and spiradenoma.
● Phosphohistone H3 and Ki-67 (MIB-1) – Immunostains to assess the mitotic and proliferative rate of
tumors, respectively.
● Cytokeratin 7 or CAM 5.2 – Positive in many sweat gland tumors, including extramammary Paget
disease.
● MSH2, MLH1, MSH6, and PMS2 – Screening stains for loss of protein expression in sebaceous tumors
associated with Muir-Torre syndrome.

Differentiation of primary cutaneous adnexal carcinoma from metastatic adenocarcinoma — Significant

histopathologic overlap exists between primary cutaneous adenocarcinomas of apocrine or eccrine derivation
and various internal adenocarcinomas that metastasize to the skin. Clinical history of prior cancer is the most
useful information when confronted with this differential diagnosis.
Immunostaining can also be helpful in distinguishing primary cutaneous tumors from cutaneous metastases.
Since no single stain is fully sensitive or specific, a combination of these stains provides the best results.
Positive staining for p63, D2-40 (podoplanin), cytokeratin 5/6, and cytokeratin 15 is supportive of primary
cutaneous origin [10,11]. Additional staining with cytokeratin 7, cytokeratin 20, estrogen receptor,
progesterone receptor, thyroid transcription factor 1, prostate specific antigen, renal cell carcinoma antigen,
and various other stains can be used in appropriate settings to exclude various forms of metastatic
carcinomas. (See "Adenocarcinoma of unknown primary site", section on 'Immunohistochemistry'.)
In cases of cutaneous metastases of unknown origin, molecular assays that assess gene expression profiles
can also be used to identify potential candidates for the primary site of the tumor. (See "Adenocarcinoma of
unknown primary site", section on 'Molecular cancer classifier assays'.)
ECCRINE AND APOCRINE TUMORS
Benign
Syringoma — Syringomas are small tumors of eccrine or apocrine origin that present as multiple discrete,
skin-colored papules 2 to 4 mm in diameter [12,13]. They occur most frequently in the periorbital area (picture
2) but they may involve any body site. Eruptive syringomas appear during childhood or early adulthood on the
anterior neck (picture 3A-B), chest, shoulders (picture 4), abdomen, and genital areas (picture 5).
Multiple or eruptive syringomas may be associated with Down's syndrome [14], anti-epileptic medications [15],
and hyperthyroidism [16]. Reports of eruptive syringomas at the sites of prior inflammatory lesions [17] or hair
waxing [18] have led to discussion of a reactive rather than neoplastic etiology in some cases. Multiple clear
cell syringomas have been reported in patients with diabetes mellitus [19].
Histologically, syringomas are characterized by multiple small epithelial collections with central ducts
surrounded by a bilayer of cuboidal cells in the superficial dermis (picture 6). Frequently, a tapering, comma-
shaped edge is present at one edge of the epithelial collections with an encompassing fibrotic stroma [14-19].
Poroma — Poroid tumors, including hidroacanthoma simplex, classic poroma, dermal duct tumor, and
poroid hidradenoma, are benign adnexal tumors characterized by small round, monomorphous cells with
small amounts of cytoplasm (poroid cells) that exhibit ductal differentiation. Originally regarded as a purely
eccrine tumor, it is now clear that both eccrine and apocrine poromas occur. HRAS mutations have been
reported in a small percentage of poromas [20]. RNA sequencing has identified recurrent YAP1-MAML2 and
YAP1-NUTM1 fusions in approximately 90 percent of poromas and approximately 65 percent of
porocarcinomas [21].

The classic variant of poroma presents as a skin-colored or erythematous papule with a predilection for the
palms and soles (picture 7A-B). The other variants are found on the trunk and limbs (picture 1A). The average
age at diagnosis for poroid tumors is the fifth and sixth decade of life with no sex predilection [22,23]. Multiple
poromas (poromatosis) can occur sporadically but have also been associated with pregnancy, hidrotic
ectodermal dysplasia, bone marrow transplant, radiation exposure, chemotherapy, or radiation therapy [24-
28].
Histologically, the intraepidermal variant of poroma (hidroacanthoma simplex) resembles a seborrheic

keratosis, but is distinguished by duct formation (picture 8). Classic poroma consists of a superficial dermal
proliferation of poroid cells with multiple epidermal connections and a highly vascular stroma (picture 9). A
purely dermal variant of poroma (dermal duct tumor) is composed of multiple small nodular aggregations
(picture 10). Poroid hidradenoma consists of one or a few large aggregations of poroid cells in the dermis,
often extending into the subcutaneous fat (picture 11).
Cytologic atypia is typically minimal. Tumor necrosis and mitotic activity are often present in benign poroid
neoplasms and should not be mistaken for an indication of malignancy. Porocarcinoma is distinguished by
nuclear atypia, infiltrative growth pattern, and rapid growth. (See 'Porocarcinoma' below.)
Cylindroma and spiradenoma — Cylindromas and spiradenomas are sweat duct tumors centered in the
dermis that often show overlapping features in the same tumor (spiradenocylindroma). They occur
sporadically in the older adult population, typically as a solitary papule or nodule on the head or neck or, less
commonly, on the trunk and extremities (picture 1B, 1D). Detection of multiple cylindromas (picture 12) or
spiradenomas should raise the suspicion of Brooke-Spiegler syndrome or familial cylindromatosis caused by
mutation of CYLD. (See 'Syndromes associated with cutaneous adnexal tumors' below.)
Sporadic cylindromas and spiradenomas also have frequent CYLD mutations. In addition to CYLD mutations,
some cylindromas harbor t(6;9) MYB-NFIB gene fusions and mutations in DNMT3A [29,30]. Spiradenomas
frequently have ALPK1 mutations, which appear to be mutually exclusive from CYLD mutations [30].
Histologically, cylindroma consists of small, irregularly shaped aggregations of basaloid keratinocytes closely
opposed to one another in a pattern resembling interconnecting pieces of a jigsaw puzzle (picture 13).
Scattered lymphocytes and small ducts are present within the neoplastic clusters of cells. Hyalinized
basement membrane material surrounds the individual clusters and forms small circular collections between
cells within the clusters.
Spiradenomas have a similar appearance, with basaloid keratinocytes, interspersed lymphocytes, ductal
differentiation, and hyalinized basement membrane material, but form one or a few large nodules in the
dermis with a trabecular pattern (picture 14), as opposed to the many small clusters in cylindroma.
Cutaneous mixed tumor — Mixed tumors of the skin, also called chondroid syringoma, are rare apocrine
or eccrine tumors with mixed epithelial and stromal components. They usually present in older adults as
asymptomatic, slow-growing firm nodules, most frequently located in the head and neck region (picture 15)
[5]. Cutaneous mixed tumors and myoepitheliomas frequently have PLAG1 or EWSR1 gene rearrangements

similar to pleomorphic adenomas of the salivary gland [31,32]. PHF1-TFE3 fusion has been reported in a
malignant mixed tumor [33].
Histologically, mixed tumors of the skin resemble mixed tumors of the salivary gland (pleomorphic adenoma).
Follicular and sebaceous elements may also be observed. Mixed tumors form large, well-circumscribed,
nodular aggregations of epithelial cells with focal ductal differentiation in the dermis and upper subcutis. A
prominent myxoid, chondroid, or fibrous stroma surrounds the epithelial cells and distinguishes this variant of
sweat gland tumor (picture 16). Prominent myoepithelial differentiation is frequently present and can be
demonstrated with myoepithelial markers such as smooth muscle actin or calponin. When myoepithelial
differentiation is the dominant pattern, a diagnosis of myoepithelioma is rendered. The presence of
decapitation secretion or concurrent folliculosebaceous differentiation confirms apocrine lineage.
Syringofibroadenoma — Typically regarded as an eccrine tumor, syringofibroadenoma is a superficial

dermal tumor presenting as a hyperkeratotic or verrucous plaque usually found on the extremities and, less
commonly, on the eyelid [34] or in a nevus sebaceus [35]. An association with ectodermal dysplasia
syndromes has also been reported [36].
Histologically, syringofibroadenoma is composed of thin, interconnecting strands of keratinocytes in a lattice

pattern that connects with the undersurface of the epidermis (picture 17). Small ducts are present in variable
numbers in the thin strands [34-36]. Syringofibroadenomatosis is a reactive hyperplasia of eccrine ducts seen
in areas of trauma or inflammation that histopathologically resembles syringofibroadenoma [37].
Syringocystadenoma papilliferum — Syringocystadenoma papilliferum (SCAP) is an adnexal tumor

affecting a much younger patient population than most adnexal tumors, with an average age of 15 at
diagnosis [6]. SCAP presents as a warty plaque most often located on the scalp. Less commonly, lesions can
be found on the face, chest, arms, or thighs. SCAP may occur sporadically, but approximately one-third of
cases are associated with a nevus sebaceus [38]. (See "Nevus sebaceus and nevus sebaceus syndrome".)
Histologically, SCAP is a tumor of apocrine derivation characterized by cuboidal and columnar epithelial cells
lining ducts that invaginate from the epidermis into the superficial dermis. Dilated, cystic ducts are frequently
present, some of which have papillary projections into their lumens. An inflammatory infiltrate with many
plasma cells surrounds the tumor (picture 18). Frequently, apocrine (decapitation) secretion is visible in some
parts of the tumor. Most SCAPs harbor RAS or BRAF mutations [39].
Hidradenoma papilliferum — Hidradenoma papilliferum usually occurs on the vulvar region of middle-
aged women (picture 19) [40]. It displays some histopathologic overlap with syringocystadenoma papilliferum,
but resides in the deeper dermis and subcutis with a more nodular configuration, lacks a plasmacytic infiltrate,
and is found almost exclusively in the anogenital region. It has been suggested that hidradenoma papilliferum
may derive from anogenital mammary-like glands [41-43]. Mutations in PIK3CA and AKT1 have been
detected [44,45]. Rare cases occurring outside the anogenital region have been reported [46-48]. (See "Vulvar
lesions: Differential diagnosis based on morphology".)

Hidradenoma — Hidradenoma is a benign adnexal tumor related to poroma that presents as a solitary
nodule, typically ranging from 1 to 3 cm in size. It occurs in all areas of the body, usually in adults.
Hidradenoma can be either apocrine or eccrine, with variants including solid-cystic, clear (pale) cell, nodular,
and poroid types. The term "acrospiroma" has also been used for the spectrum of hidradenoma and poroma.
Approximately 50 percent of hidradenomas harbor a t(11;19) translocation causing a MECT1-MAML2 gene
fusion [49].
Histopathologic examination shows a circumscribed dermal tumor with variable extension into the subcutis,
composed of one or more large nodules of epithelial cells with areas of ductal differentiation (picture 20).
Epidermal connection is present in 25 percent of cases.
Tubular/papillary adenoma, including papillary cystadenoma — Numerous reports have described

benign apocrine or eccrine tumors with a papillary, tubular, and/or cystic pattern under various names,
including papillary eccrine adenoma, tubular apocrine adenoma, and papillary apocrine fibroadenoma. These
tumors have no sex predilection and are most frequently seen on the head and extremities [6]. BRAF V600E
mutations have been identified in >50 percent of these tumors, and KRAS mutations occur in a small percent
[50].
Histologically, tubular/papillary adenomas are well-circumscribed proliferations of small epithelial aggregations

exhibiting ductal differentiation. They form round, cystic, or tubular structures in the dermis (picture 21).
Papillary projections into cystically-dilated ducts are sometimes prominent.
Malignant — Malignant adnexal tumors are rare and typically affect older adults or individuals with familial
tumor syndromes. For nearly all of the benign apocrine and eccrine tumors listed above, there is a malignant
counterpart (eg, poroma and porocarcinoma) which is differentiated from the benign form by clinicopathologic
features including larger size, infiltrative growth pattern (poor circumscription), nuclear enlargement and
pleomorphism, increased mitotic activity, necrosis, and ulceration.
Porocarcinoma — Eccrine porocarcinoma or malignant eccrine poroma is a rare tumor that occurs most
often on the head and neck or lower extremities of older individuals (mean age 68) and sometimes arises in a
pre-existent poroma [51,52]. A meta-analysis of 453 cases showed equal gender distribution and progression
to metastasis in 31 percent of cases, with lymph node being the most common site of metastasis [52].
Histologically, porocarcinoma is characterized by infiltrative growth pattern, nuclear atypia, increased mitotic
activity, and necrosis (picture 22). The presence of an adjacent benign poroid component is helpful in
establishing the diagnosis.
DNA sequencing data have shown mutations in EGFR, HRAS, TP53, RB1, ATM, ARID1A, PIK3CA, and
CDKN2A [20]. RNA sequencing has identified recurrent YAP1 gene fusions in approximately 65 percent of
porocarcinomas [21]. Retrospective analysis of the National Cancer Database found 5- and 10-year survival
rates of 69 and 54 percent, respectively, for porocarcinoma [53]. Large tumor size (particularly >4 cm) is
associated with a poor prognosis. Wide local excision is the mainstay of treatment. Data are lacking to support
sentinel lymph node biopsy, though lymph node dissection is typically utilized when lymph node involvement is

detected [52]. Chemotherapy and/or radiation have been reported for treatment of advanced stages of
porocarcinoma.
Adenoid cystic carcinoma — Adenoid cystic carcinoma (ACC) is a variant of adenocarcinoma that can
arise in multiple organ types. Salivary gland ACC is the most frequent type, but primary ACC has been
reported in skin, breast, lung, prostate, lacrimal gland, female genital tract, and gastrointestinal tract. (See
"Salivary gland tumors: Epidemiology, diagnosis, evaluation, and staging".)
A characteristic t(6;9) MYB-NFIB gene fusion is present in cutaneous as well as noncutaneous ACC [54].
MYBL1 rearrangements occur in a small minority of cases [55]. Primary cutaneous ACC has a more favorable
prognosis than its salivary counterpart [56].
The average age of onset for primary cutaneous ACC is approximately 60 years [56]. The tumor can occur on
the scalp, trunk, and extremities, and typically presents as a slow-growing, nondescript nodule on the skin.
Diagnosis of ACC on the lower half of the face should prompt evaluation for local spread of salivary gland
ACC.
ACC exhibits three primary histopathologic growth patterns (ie, cribriform, solid, tubular). The cribriform
pattern is the most unique of the three, with clusters of epithelial cells with both true ducts and duct-like
collections of mucin interspersed in a sieve-like pattern (picture 23). Solid and tubular patterns are also
observed, with multiple patterns frequently present in the same tumor. Perineural invasion is frequently
present.
Mucinous carcinoma and endocrine mucin-producing sweat gland carcinoma — Mucinous

carcinoma is a type of adenocarcinoma that occurs in multiple organ systems including breast, skin, ovary,
lung, and gastrointestinal tract. Cutaneous mucinous carcinoma presents as a slow-growing blue or reddish
nodule ranging from 0.5 to 8 cm with a predilection for the scalp, eyelids, and axilla. The mean age of onset is
approximately 60 years [57]. Endocrine mucin-producing sweat gland carcinoma (EMPSGC) represents a low-
grade adnexal carcinoma that can be a precursor to mucinous carcinoma and typically occurs on or near the
eyelid [58].
Histologically, mucinous carcinoma consists of islands of epithelial cells seemingly floating within large pools
of mucin in the dermis and/or subcutis. Sometimes apocrine decapitation secretion and ductal differentiation is
apparent. Biopsy findings in EMPSGC include rounded aggregations of epithelial cells with mild to moderate
cytologic atypia in the dermis that express neuroendocrine markers and estrogen and progesterone hormone
receptors. Mucin deposition is present but to a lesser degree than mucinous carcinoma.
Microcystic adnexal carcinoma — Microcystic adnexal carcinoma (MAC), also known as sclerosing
sweat duct carcinoma, is a locally aggressive malignancy that typically occurs on the central face, although
extra-facial cases have been reported [59,60]. MAC presents as a slowly expanding scar-like plaque or firm
nodule (picture 24A-D) [60]. Recurrent TP53 and JAK1 mutations have been identified with next-generation
sequencing [61].

Histologically, MAC shows divergent differentiation, with follicular elements of keratin cysts in the upper dermis
and infiltrating strands of epithelial cells with sweat ductal differentiation that often extends into the subcutis,
and an associated fibrotic stroma (picture 25).
The clinical presentation, diagnosis, and treatment of MAC are discussed in detail separately. (See
"Microcystic adnexal carcinoma".)
(Aggressive) digital papillary adenocarcinoma — Digital papillary adenocarcinoma (DPA), also called
aggressive digital papillary adnexal carcinoma or aggressive digital papillary tumor, is a malignant adnexal
tumor presenting as a nodule on the volar surface of the digits of the hands and, less often, of the feet [62,63].
DPA is a rare tumor, with an estimated incidence of 0.08 per million person-years [64]. It usually occurs in
adult individuals, with a male predominance [63]. Rarely, patients present with metastatic disease to the lymph
nodes and lungs. Sequencing analysis from one study showed BRAF V600E mutations in one out of nine
tumors [65]. Gene expression profiling of eight cases showed overexpression of FGFR2, indicating that
pathway as a potentially treatment-targetable genetic alteration [66].
Histopathologically, the tumor displays a multinodular, sometimes infiltrative configuration of epithelial cells
with glandular and ductal differentiation. Frequently, papillary projections within cystic ductal spaces are
present (picture 26). Cytologic atypia is variable, ranging from mild to severe, and does not appear to correlate
with prognosis [63].
Wide local excision or digital amputation is the treatment of choice for digital papillary adenocarcinoma
[62,63]. Local recurrence rates range from 16 to 50 percent. In one study, local recurrence was reported in 1
of 21 patients treated with re-excision or amputation after the initial excision and in 11 of 22 patients who did
not undergo additional procedures after the initial excision, after an average follow-up time of six years [62].
Metastasis occurs in approximately 15 to 30 percent of cases [62-64].
Extramammary Paget disease — Extramammary Paget disease (EMPD) can be either a primary
cutaneous adenocarcinoma or a tumor with secondary cutaneous involvement via extension from a lower
gastrointestinal or urinary tract carcinoma. The cell of origin for primary cutaneous EMPD is controversial.
While some cases of EMPD represent epidermal extension of an adenocarcinoma arising from underlying
apocrine or eccrine glands, EMPD may also arise from pluripotent stem cells or Toker cells [67,68]. PIK3CA,
AKT1, ERBB2, and RAS/RAF pathway mutations have been reported in EMPD [45,69].
EMPD usually presents with well-demarcated, eczematous plaques predominantly located in the anogenital
region and, less commonly, in the axillae. Multifocal and bilateral tumors have been reported.
Histopathologically, EMPD mimics Paget disease of the breast with a poorly circumscribed proliferation of
large epithelial cells distributed singly and in small clusters between normal keratinocytes in the epidermis (ie,
pagetoid scatter) with variable ductal differentiation (picture 27). HER2 overexpression in some cases may
indicate potential therapeutic response to trastuzumab [70].
The diagnosis, differential diagnosis, and treatment of extramammary Paget disease are discussed
separately. (See "Vulvar cancer: Epidemiology, diagnosis, histopathology, and treatment", section on 'Paget

disease of the vulva'.)
Cutaneous cribriform carcinoma — Cutaneous cribriform carcinoma (cutaneous apocrine cribriform

carcinoma) is a rare, low-grade sweat gland carcinoma with frequent apocrine differentiation that occurs in
adults of all ages and has a predilection for the upper and lower extremities [71]. It presents as a solitary,
slow-growing, skin-colored nodule ranging from 1 to 3 cm in size. Surgical excision is the primary treatment,
and no metastases have been reported.
Biopsy findings for cutaneous cribriform carcinoma include a relatively well-circumscribed, nodular growth
pattern centered in the dermis with peripheral lymphoid aggregates (picture 28). Subcutaneous extension can
be seen. The tumor is composed of interconnecting aggregations of epithelial cells with irregular, dilated
ductal spaces forming a cribriform pattern (picture 29). The thin, thread-like strands seen in cribriform areas
are characteristic. Mitotic figures are frequently present but typically low in number.
Cutaneous secretory carcinoma — Cutaneous secretory carcinoma, also known as cutaneous mammary
analogue secretory carcinoma, is a low-grade sweat duct carcinoma caused by a t(12;15) translocation
resulting in ETV6-NTRK3 fusion [72]. These are rare tumors analogous by histopathology and molecular
origins to secretory carcinoma of the breast and salivary glands. Twelve cases have been reported with no
metastatic cases [73]. Histopathologically, they have a nodular, relatively well-circumscribed pattern with
characteristic eosinophilic secretions in ducts.
FOLLICULAR TUMORS
Benign
Trichoblastoma and trichoepithelioma — Trichoblastoma and trichoepithelioma are benign epithelial

tumors composed of follicular germinative cells resembling those seen in the embryologic buds of primitive
folliculosebaceous units. They present as smooth, nonulcerated, skin-colored papules, sometimes with
associated telangiectasias usually located on the head and neck (picture 1C, 1E). The majority of cases occur
in adults after the age of 40. The presence of multiple trichoepitheliomas should raise the suspicion of Brooke-
Spiegler syndrome or multiple familial trichoepithelioma. (See 'Brooke-Spiegler syndrome' below.)
Histologically, trichoblastoma shows large and small aggregations of basaloid keratinocytes surrounded by a
fibrous stroma rich in fibroblasts and mesenchymal cells that often form densely cellular aggregations
(papillary mesenchymal bodies) closely opposed to the epithelial cells in a pattern recapitulating embryologic
hair follicle development (picture 30). Trichoepithelioma represents a subset of trichoblastoma composed of
smaller islands of basaloid cells, sometimes only one to two cells thick, with marked fibrosis (desmoplastic
trichoepithelioma). Numerous histopathologic variants of trichoblastoma have been described, including
nodular, retiform, cribriform, racemiform, columnar, and adamantinoid (lymphadenoma) [6].
Trichoadenoma — Trichoadenoma presents as a slow-growing, skin-colored papule on the face.

Histologically, trichoadenoma is composed of multiple cystic collections of keratinocytes with differentiation
toward the follicular infundibulum (picture 31).
https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage… 10/102
Trichofolliculoma — Trichofolliculoma is a rare hamartomatous lesion with follicular differentiation that

typically occurs on the face (picture 32A-C). Histologically, trichofolliculoma is composed of a large central
follicle from which multiple small (vellus) hair follicles emanate (picture 33). The vellus follicles sometimes
produce fully developed hair, resulting in a clinical appearance of multiple hairs growing centrally from a small
papule. A sebaceous variant without fully developed hair shafts has also been described [74].
Trichilemmoma — Trichilemmoma (also known as tricholemmoma) is a benign follicular tumor with

differentiation toward the outer root sheath of the hair follicle. It has been hypothesized that human
papillomavirus (HPV) may have a pathogenetic role. However, polymerase chain reaction studies for HPV
detection in trichilemmomas provided conflicting results [75-78]. The discovery of frequent HRAS mutations
supports a neoplastic etiology [79].
Solitary trichilemmomas usually occur in older adults without sex predilection [1]. They present as a small
skin-colored papule or verrucous lesion, most often located on the central face (picture 34). Trichilemmoma is
a frequent secondary tumor found in nevus sebaceous, and multiple facial trichilemmomas are seen in
patients with Cowden syndrome (picture 35). (See 'Cowden syndrome (multiple hamartoma syndrome)'
below.)
Histopathologically, trichilemmoma exhibits a papillated, well-circumscribed, exo-endophytic growth pattern

(picture 36). Lobules of keratinocytes with pale cytoplasm predominate centrally, with smaller basaloid
keratinocytes with peripheral palisading forming a peripheral rim around the tumor. Focal hypergranulosis
resembling koilocytic changes of HPV is frequently present at the periphery.
Trichodiscoma and fibrofolliculoma — Although originally described as distinct entities, evidence

suggests that trichodiscomas and fibrofolliculomas represent a spectrum of the same neoplastic process [80].
There is also overlap with perifollicular fibroma (angiofibroma). Both fibrofolliculoma and trichodiscoma
present as small, 2 to 4 mm, dome-shaped, skin-colored papules on the face, scalp, ears, or upper trunk.
They occur sporadically in adults and are seen in multiplicity in patients with Birt-Hogg-Dubé syndrome
(picture 37). (See 'Birt-Hogg-Dubé syndrome' below.)
Histologically, trichodiscomas and fibrofolliculomas are tumors of the follicular mantle with both stromal and
epithelial components. In trichodiscoma, a central zone of fibromucinous stroma predominates, with
surrounding sebaceous glands in a "mitt-like" configuration (picture 38). In fibrofolliculoma, thin
interconnecting strands of keratinocytes punctuated by small collections of mature sebocytes radiate from a
dilated follicular infundibulum and are accompanied by a variably fibrotic and mucinous stroma (picture 39).
Tumor of the follicular infundibulum — Tumors of the follicular infundibulum (TFI) are rare adnexal
tumors that usually present as solitary keratotic papules resembling basal cell carcinoma or actinic keratosis.
They usually occur in older adults and are located on the head and neck in the majority of cases [81]. Multiple
or eruptive TFIs may present as hypopigmented, scar-like macules or flat papules [82,83]. Microscopic TFIs
are often discovered as incidental findings in skin biopsies and excisions.

Despite its name, TFI is a follicular tumor with predominantly follicular isthmic differentiation and a superficial,
plate-like growth pattern running parallel to the overlying epidermis. Keratinocytes with bright pink cytoplasm
that contrast sharply with the darker pink epidermal keratinocytes descend from and reconnect with the
undersurface of the epidermis (picture 40). Peripheral palisading, small keratin cysts, and ducts are
sometimes present.
Panfolliculoma — Panfolliculoma is a very rare adnexal neoplasm that occurs predominantly on the head
and neck of older individuals with a male predilection [84]. Panfolliculoma exhibits follicular upper and lower
segment (infundibular, isthmic, germinative, and matrical) differentiation within the same tumor (picture 41).
Intraepidermal and cystic variants have been described.
Pilomatricoma — Pilomatricoma, also called pilomatrixoma or calcifying epithelioma of Malherbe exhibits

differentiation toward the hair matrix portion of the lower segment (stem) of hair follicles. Activating mutations
in beta-catenin in the WNT-signaling pathway appear to be involved in the pathogenesis of these tumors
[85,86].
Pilomatricomas occur at any age without gender predilection and exhibit a bimodal distribution with the
highest incidence in children and adults over 50. Fifty percent occur on the head and neck [87]. They present
as firm, skin-colored to bluish papules or nodules (picture 42A-B). Transepidermal elimination (perforation)
sometimes occurs with extrusion of calcified/ossified portions of the neoplasm. Most lesions are <3 cm, but
giant lesions up to 15 cm have been reported [88].
Multiple pilomatricomas are associated with myotonic dystrophy (Steinert's disease) [89], Gardner's syndrome
[90], Turner syndrome [91], trisomy 9 [92], Kabuki syndrome [93], Rubinstein-Taybi Syndrome [94], and
glioblastoma [95].
Histologically, pilomatricomas appear as well-circumscribed nodular collections of basaloid epithelial cells that
transition centrally into pink keratinized cells without nuclei (ghost/shadow cells). Early tumors have a larger
proportion of basaloid matrical cells with abundant mitotic activity. Late-stage pilomatricomas may be
composed almost exclusively of shadow cells with areas of calcification and ossification (picture 43).
Proliferating trichilemmal tumor — Proliferating trichilemmal tumor (also called proliferating pilar tumor,
proliferating trichilemmal cyst, or proliferating follicular-cystic neoplasm) encompasses a spectrum of rare
tumors with follicular isthmic differentiation and varying degree of atypia. The extreme end of the spectrum
has been considered a variant of squamous cell carcinoma, but is better classified as a form of follicular
adnexal carcinoma (the designation "proliferating follicular-cystic carcinoma" has been proposed) [96].
Most proliferating pilar tumors present as solitary, asymptomatic nodules ranging from 2 to 5 cm with a broad
age range and slight female predilection [6]. Over 85 percent are found on the scalp.
On histology, these neoplasms have a multinodular configuration that fills the dermis, with frequent extension
into the subcutis. Brightly eosinophilic keratinocytes are present in the outer portion of tumor aggregates and
cornify abruptly into compact keratin-filled cystic spaces with frequent calcification (picture 44). The degree of

cytologic atypia and mitotic activity, as well as the presence of a more infiltrative growth pattern, are indicators
of potential malignancy.
Malignant — Basal cell carcinoma is the most common cutaneous malignancy that exhibits follicular
differentiation. The remainder of malignant tumors with hair follicle differentiation includes rare tumors seen
more frequently in patients with germline mutations that predispose to adnexal tumors. (See "Epidemiology,
pathogenesis, and clinical features of basal cell carcinoma" and 'Syndromes associated with cutaneous
adnexal tumors' below.)
Trichoblastic carcinoma — Malignant transformation of trichoblastoma is rare. The diagnosis is based

upon the histopathologic finding of atypical basaloid keratinocytes with crowded, hyperchromatic nuclei and
increased mitotic activity adjacent to a benign trichoblastoma.
Outside this setting, the diagnosis of trichoblastic carcinoma is controversial, with some experts arguing that it
represents a variant of basal cell carcinoma [97]. However, the presence of hypercellular stroma that can also
exhibit malignant changes (so-called trichoblastic carcinosarcoma) distinguishes trichoblastic carcinoma from
basal cell carcinoma.
Trichilemmal carcinoma — Trichilemmal carcinoma is a rare malignant counterpart of trichilemmoma with

approximately 100 cases reported [98]. However, the number of cases of trichilemmal carcinoma may be
overestimated, due to significant histopathologic overlap with clear cell squamous cell carcinoma [99,100].
Trichilemmal carcinomas are usually found on sun-exposed surfaces of older adult patients, suggesting that
ultraviolet radiation plays a pathogenic role. The tumor is composed of infiltrative aggregations of pale
keratinocytes with outer root sheath differentiation, cytologic atypia, and brisk mitotic activity (picture 45).
Surgical excision, with or without the Mohs micrographic technique, provides high cure rates and should be
considered first-line treatment [98,101]. In a review of 35 cases with follow-up data, local recurrence occurred
in 3 cases and metastatic disease in 1 after an average follow-up of 33 months [98].
Pilomatrix (matrical) carcinoma — Pilomatrix carcinoma is an extremely rare tumor derived from follicular
matrix cells with a high rate of local recurrence. It usually occurs on the head and neck of middle-aged and
older men [102]. Pilomatrix carcinoma shares the same activating mutations in beta-catenin seen in
pilomatricoma [86]. However, a component of benign pilomatricoma is not found in the majority of cases,
suggesting that most pilomatrix carcinomas arise de novo.
Histologically, both pilomatricoma and pilomatrix carcinoma consist of nodular aggregations of basaloid
keratinocytes that transition to shadow (ghost) cells. Poor circumscription, tumor necrosis, cellular
pleomorphism, and asymmetry help distinguish pilomatrix carcinoma from its benign counterpart. Mitotic
activity can be high in both benign and malignant tumors.
Wide local excision (≥2 cm margins) or Mohs micrographic surgery are the treatments of choice for pilomatrix
carcinoma [86,103]. There are isolated reports of therapeutic response of metastatic pilomatrix carcinoma to
cyclophosphamide and etoposide (complete response) and radiation therapy (partial response) [104,105].

TUMORS WITH SEBACEOUS DIFFERENTIATION
Tumors with sebaceous differentiation may occur sporadically or in association with Muir-Torre syndrome.
Inactivating mutations in lymphoid enhancer factor 1 (LEF1) and mismatch repair genes (MSH2, MLH1, and
MSH6) have been implicated in this family of tumors [106-108]. (See "Sebaceous carcinoma".)
Sebaceous hyperplasia — Sebaceous hyperplasia is a relatively common lesion resulting from the
enlargement of normal sebaceous glands. Sebaceous hyperplasia is not a true tumor, but shares clinical and
histopathologic features with sebaceous adenoma. It typically presents as 2- to 6-mm umbilicated, skin-
colored to yellowish or brownish papules on the forehead, nose, and cheeks of older individuals (picture 46A-
B). Rarely, lesions can occur on the areola, genitalia, and anterior chest, sometimes in a linear configuration
("juxtaclavicular beaded lines") [109-112].
Sebaceous hyperplasia has been reported in 15 to 30 percent of transplant patients treated with cyclosporine
[113,114]. The so-called premature sebaceous hyperplasia presents with multiple discrete or plaque-like
lesions in children and adolescents and is considered a hamartomatous lesion related to nevus sebaceous
[115-117].
Visualization with a dermatoscope reveals individual whitish-yellow aggregations with a rim of dilated blood
vessels in "crown" configuration (picture 47). Biopsy shows a dome-shaped lesion with numerous mature
sebaceous lobules composed of mature sebocytes, frequently radiating from a central dilated hair follicle
(picture 48).
Treatment is for cosmetic reasons and includes electrosurgery, cryosurgery, shave removal, dermabrasion,
laser therapy, and oral isotretinoin [118-123].
Sebaceous adenoma and sebaceoma — Sebaceous adenomas are benign, well-differentiated sebaceous
tumors typically located in the upper dermis. They are often connected directly with the overlying epidermis
instead of a central follicle, as in sebaceous hyperplasia. Sebaceoma is a variant of sebaceous adenoma that
is typically located deeper in the dermis [124].
Sebaceous adenomas and sebaceomas share similar clinical characteristics with sebaceous hyperplasia, but
are typically solitary and larger than sebaceous hyperplasia. They present as yellowish or brownish papules,
usually <1 cm in diameter, almost exclusively located on the head and neck (picture 49).
Sebaceous adenomas are the most common sebaceous neoplasm associated with Muir-Torre syndrome
[125]. In contrast with sporadic cases, sebaceous adenomas in Muir-Torre syndrome occur frequently on the
trunk, as well as the head and neck, and can have a cystic pattern [126]. (See "Muir-Torre syndrome".)
Histologically, sebaceous adenoma is composed of well-circumscribed, round aggregations of predominantly

mature, lipid-filled sebocytes with a rim of basaloid, germinative cells at the periphery (picture 50). Maturation
of the central sebocytes is less orderly than in sebaceous hyperplasia. In sebaceoma, the basaloid
germinative sebocytes predominate (>50 percent) and tend to be centered deeper in the dermis. Sometimes,

mature sebocytes are few in number and easily overlooked (picture 51). Limited mitotic activity is often
present in both sebaceous adenoma and sebaceoma.
Sebaceous carcinoma — Sebaceous carcinoma is a rare malignant tumor most commonly occurring in the
head and neck region, particularly in the periocular area (picture 52) [127]. It is distinguished from sebaceous
adenoma and sebaceoma by an infiltrative growth pattern, cytologic atypia, high mitotic rate, and necrosis
(picture 53). Sebaceous carcinomas are genetically heterogenous with three main genetic types, including
tumors with a microsatellite instability pattern, tumors with an ultraviolet signature pattern, and paucimutational
tumors that include ocular sebaceous carcinomas [128]. The clinical presentation, diagnosis, and treatment of
sebaceous carcinoma are discussed separately. (See "Sebaceous carcinoma".)
TREATMENT
Benign adnexal tumors — The treatment of choice for benign adnexal tumors is simple excision. Some
experts advocate full excision after partial biopsies of benign adnexal tumors to prevent local persistence and
to eliminate the chance of future malignant transformation. However, given the excellent prognosis of these
benign tumors and extremely low rate of malignant transformation, clinical follow-up may be preferable for
patients not desiring additional surgery.
In patients with syndromes causing multiple adnexal tumors, the tumors can be disfiguring and cause
significant psychosocial effects. Although surgical excision of large tumors is often used, excision of all tumors
is impractical and other measures can be used to help these patients. Such treatment modalities include
superficial shave removal, electrocautery, and laser ablation using erbium-doped yttrium aluminum garnet
(Er:YAG) or fractional carbon dioxide (CO2) lasers [129].
Malignant adnexal tumors — General treatment recommendations are discussed in this section.
Patient evaluation and staging — Patients diagnosed with a malignant cutaneous adnexal tumor should
receive a complete skin examination that includes palpation of regional lymph nodes to evaluate for clinical
signs of regional metastasis. If enlarged lymph nodes are detected, lymph node biopsy via fine needle
aspiration or surgical removal of the enlarged lymph node is indicated.
In patients with large tumors (eg, ≥2 cm) in the head and neck region and particularly in the periorbital area,
imaging studies with computerized tomography (CT) or magnetic resonance imaging (MRI) are useful to
evaluate for invasion of bone, other deep structures, or the orbit.
The staging for malignant cutaneous adnexal tumors is consolidated with the staging system for cutaneous
squamous cell carcinoma in the 2017 eighth edition of the American Joint Committee on Cancer (AJCC)
Cancer Staging Manual (table 2) [130].
Local disease

Surgery — Wide local excision with negative surgical margins or Mohs micrographic surgery is the
recommended treatment for the majority of malignant adnexal tumors. Mohs micrographic surgery, a surgical
technique that offers complete circumferential intraoperative margin monitoring, is the preferred treatment for
malignant adnexal tumors located on the head and neck and has also been recommended as an appropriate
treatment for tumors at all anatomic sites by the American Academy of Dermatology guidelines for Mohs
micrographic surgery [131]. However, wide local excision is a reasonable alternative for tumors on the trunk
and extremities. Because of the rarity of these tumors, the width of safety margins has not been evaluated in
clinical trials or large observational studies. In general, 1 to 2 cm clinical margins are used [132]. Partial
amputation may be necessary in malignant adnexal tumors on the digits.
Radiation therapy — Retrospective reviews and single case reports have reported successful
treatment of sebaceous carcinoma with radiation therapy [133,134]. A retrospective review of 1045 patients
with a histologic diagnosis of cutaneous adnexal carcinoma with eccrine differentiation showed no survival
benefit in patients receiving adjuvant radiation therapy versus surgery alone [135]. Radiation therapy should
be reserved for patients in which surgery is not an option or as a postsurgical adjuvant treatment when
surgical margins cannot be cleared.
Sentinel lymph node biopsy — Because of the rarity of these tumors and the relatively low rate of
nodal involvement [8,136], the role of sentinel lymph node biopsy (SLNB) in patients without clinical lymph
node involvement has not been established and cannot be recommended in routine practice.
Metastatic disease — There is very limited evidence on the treatment of metastatic adnexal tumors from
single case reports [105,137]. The choice of treatment is made on a case-by-case basis. An increasing
number of reports detailing mutations in the MAP kinase pathway (eg, BRAF, RAS) and PIK3CA/AKT1
pathway indicate targeted therapies may be of use in selected aggressive adnexal carcinomas. Some
apocrine and eccrine carcinomas express estrogen and progesterone receptors. Case reports detailing
response to hormone-directed therapies (eg, tamoxifen) indicate another potential path of treatment in these
tumors [138]. Reports of HER2 amplification and response to trastuzumab have been reported as well [139]. A
few cases have been successfully treated with adjuvant chemoradiation [140,141].
PROGNOSIS
Malignant cutaneous adnexal tumors are primarily locally aggressive tumors. Tumor recurrence resulting from
incomplete removal of the tumor is a major prognostic concern. Local recurrence rates range from 10 to 50
percent among patients treated with wide local excision or Mohs micrographic surgery [62,98,142]. Routine
postsurgical follow-up visits are advisable to monitor for recurrence.
In a large retrospective study of malignant cutaneous adnexal tumors using the SEER database, distant
metastases occurred in 12 percent of patients [8]. This may overestimate the actual incidence of metastasis,
due to underreporting of early-stage malignant cutaneous adnexal tumors to the SEER database. The overall
five-year survival and the five-year disease-specific survival were 73 and 98 percent, respectively. Increasing

age, T3 tumors, presence of nodal or distant metastases, and nonsurgical treatment are unfavorable
prognostic factors.
SYNDROMES ASSOCIATED WITH CUTANEOUS ADNEXAL TUMORS
Brooke-Spiegler syndrome — Brooke-Spiegler syndrome (BSS; MIM #605041) is a rare autosomal

dominant syndrome characterized by the development of multiple cylindromas, trichoepitheliomas, and
spiradenomas. BSS is caused by germline mutations in the CYLD gene on chromosome 16q12-q13, encoding
a highly conserved deubiquitinating enzyme involved in the regulation of cell proliferation through multiple cell
signaling pathways, including NF-kB and c-Jun N-terminal kinase (JNK) [143]. BSS, familial cylindromatosis,
and multiple familial trichoepithelioma-1 are allelic and, therefore, may be considered phenotypic variants or a
spectrum of the same disease [144,145]. (See "Brooke-Spiegler syndrome (CYLD cutaneous syndrome)".)
Patients with BSS present with numerous pink, translucent papules and nodules with telangiectasias ranging
from 0.5 to 3 cm located on the face, scalp, and neck (picture 54). Tumors appear in late childhood to early
adulthood and gradually increase in size and number throughout life. There is wide variation in the number of
tumors, with some patients developing less than 30 and some in the hundreds.
Malignant transformation of these adnexal tumors occurs in 5 to 10 percent of patients [6]. Rapid growth in a
lesion should raise concern for malignant change.
Multiple familial trichoepithelioma 1 (MFT1; MIM #601606) is an autosomal dominant syndrome caused by
mutations in the CYLD gene and allelic to Brooke-Spiegler syndrome [145]. Patients develop multiple
trichoepitheliomas concentrated on the face and scalp.
Familial cylindromatosis (FC; MIM #132700) is an autosomal dominant syndrome allelic to BSS and MFT1,
caused by mutations in the CYLD gene. FC is characterized by the occurrence of multiple cylindromas in the
head and neck region. Some patients may develop large, confluent tumors on the scalp known as turban
tumors (picture 55).
Cowden syndrome (multiple hamartoma syndrome) — Cowden syndrome (MIM #158350) is an autosomal
dominant syndrome associated with multiple cutaneous trichilemmomas (picture 35), oral fibromas, sclerotic
fibromas, lipomas, acral verrucous hyperkeratosis, intestinal polyps, penile freckling, macrocephaly, and
benign and malignant breast, uterine, and thyroid tumors [146]. Cowden syndrome is discussed in detail
elsewhere. (See "PTEN hamartoma tumor syndromes, including Cowden syndrome".)
Birt-Hogg-Dubé syndrome — Birt-Hogg-Dubé syndrome (BHDS; MIM #135150) is an autosomal dominant

syndrome caused by mutations in the FLCN (folliculin) gene and characterized by cutaneous fibrofolliculomas,
trichodiscomas, and acrochordons; multiple lung cysts, which can lead to spontaneous pneumothorax; and
renal tumors [129]. Over 90 percent of BHDS patients present in the third to fourth decade of life with multiple
facial fibrofolliculomas or trichodiscomas (picture 37) [6]. The presence of at least five adult-onset
fibrofolliculomas, with at least one histologically confirmed, and the detection of pathogenic FLCN germline
mutations are major diagnostic criteria for BHDS [129]. (See "Hereditary kidney cancer syndromes".)
Muir-Torre syndrome — Muir-Torre syndrome (MIM #158320) is an autosomal dominant variant of hereditary
nonpolyposis colorectal carcinoma syndrome (Lynch syndrome), characterized by the association with both
benign and malignant sebaceous tumors (sebaceous adenoma, sebaceoma, and sebaceous carcinoma), as
well as keratoacanthomas [147]. Muir-Torre syndrome is discussed separately. (See "Muir-Torre syndrome".)
SUMMARY AND RECOMMENDATIONS
● Cutaneous adnexal tumors are a large group of benign and malignant neoplasms that exhibit morphologic
differentiation towards one of the four primary adnexal structures present in normal skin: hair follicles,
sebaceous glands, apocrine glands, and eccrine glands (table 1). (See 'Introduction' above and
'Classification' above.)
● Adnexal tumors typically present as pink, skin-colored, or slightly bluish papules or nodules ranging in
size from a few millimeters to several centimeters, most often located on the head and neck (picture 1A-
C). Lesions are typically asymptomatic and slow-growing over several years. Malignant adnexal tumors
have a similar clinical appearance, but exhibit rapid growth and can ulcerate. (See 'Clinical features'
above.)
● Because of the extensive overlap in clinical features of cutaneous adnexal tumors, biopsy is essential for
diagnosis. Immunohistochemical stains may be useful for the diagnosis of tumors with ambiguous
histopathologic features. (See 'Diagnosis' above.)
● The treatment of choice for benign adnexal tumors is simple excision. In patients with genetic syndromes
associated with multiple adnexal tumors, excision of all lesions may not be feasible. For these patients,
alternative treatment modalities include superficial shave removal, electrocautery, and laser ablation.
(See 'Benign adnexal tumors' above.)
● For patients with malignant adnexal tumors, we suggest treatment with Mohs micrographic surgery
(Grade 2C). Wide local excision with pathologic margin assessment is a reasonable alternative if Mohs
surgery is not available. Because of the rarity of these tumors, the width of safety margins has not been
evaluated in high-quality studies. In general, 1 to 2 cm clinical margins are used. (See 'Malignant adnexal
tumors' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
REFERENCES
1. Alsaad KO, Obaidat NA, Ghazarian D. Skin adnexal neoplasms--part 1: an approach to tumours of the
pilosebaceous unit. J Clin Pathol 2007; 60:129.

2. Obaidat NA, Alsaad KO, Ghazarian D. Skin adnexal neoplasms--part 2: an approach to tumours of
cutaneous sweat glands. J Clin Pathol 2007; 60:145.
3. Lee DA, Grossman ME, Schneiderman P, Celebi JT. Genetics of skin appendage neoplasms and related
syndromes. J Med Genet 2005; 42:811.
4. Winkelmann RK, Wolff K. Solid-cystic hidradenoma of the skin. Clinical and histopathologic study. Arch
Dermatol 1968; 97:651.
5. Kazakov DV, Kacerovska D, Hantschke M, et al. Cutaneous mixed tumor, eccrine variant: a
clinicopathologic and immunohistochemical study of 50 cases, with emphasis on unusual histopathologic
features. Am J Dermatopathol 2011; 33:557.
6. Kazakov DV, McKee PH, Michal M, Kacerovska D. Cutaneous Adnexal Tumors, 1st ed, Lippincott Willia
ms & Wilkins Health, Philadelphia 2012.
7. Mayer I. Zur Histologie der Hidradenoma. Frankf Z Path 1941; 55:548.
8. Martinez SR, Barr KL, Canter RJ. Rare tumors through the looking glass: an examination of malignant
cutaneous adnexal tumors. Arch Dermatol 2011; 147:1058.
9. Al-Zaid T, Ditelberg JS, Prieto VG, et al. Trichilemmomas show loss of PTEN in Cowden syndrome but
only rarely in sporadic tumors. J Cutan Pathol 2012; 39:493.
10. Sariya D, Ruth K, Adams-McDonnell R, et al. Clinicopathologic correlation of cutaneous metastases:

experience from a cancer center. Arch Dermatol 2007; 143:613.
11. Mahalingam M, Nguyen LP, Richards JE, et al. The diagnostic utility of immunohistochemistry in
distinguishing primary skin adnexal carcinomas from metastatic adenocarcinoma to skin: an
immunohistochemical reappraisal using cytokeratin 15, nestin, p63, D2-40, and calretinin. Mod Pathol
2010; 23:713.
12. Williams K, Shinkai K. Evaluation and management of the patient with multiple syringomas: A systematic
review of the literature. J Am Acad Dermatol 2016; 74:1234.
13. Ciarloni L, Frouin E, Bodin F, Cribier B. Syringoma: A clinicopathological study of 244 cases. Ann
Dermatol Venereol 2016; 143:521.
14. Urban CD, Cannon JR, Cole RD. Eruptive syringomas in Down's syndrome. Arch Dermatol 1981;
117:374.
15. Oztürk F, Ermertcan AT, Bilaç C, Temiz P. A case report of postpubertal eruptive syringoma triggered
with antiepileptic drugs. J Drugs Dermatol 2010; 9:707.
16. Polat M, Pelitli A, Oztaş P, et al. Eruptive syringoma associated with hyperthyroidism. Skinmed 2010;
8:124.
17. Guitart J, Rosenbaum MM, Requena L. 'Eruptive syringoma': a misnomer for a reactive eccrine gland
ductal proliferation? J Cutan Pathol 2003; 30:202.
18. Garrido-Ruiz MC, Enguita AB, Navas R, et al. Eruptive syringoma developed over a waxing skin area.
Am J Dermatopathol 2008; 30:377.
19. Yoshimi N, Kurokawa I, Kakuno A, et al. Case of generalized eruptive clear cell syringoma with diabetes
mellitus. J Dermatol 2012; 39:744.
20. Harms PW, Hovelson DH, Cani AK, et al. Porocarcinomas harbor recurrent HRAS-activating mutations
and tumor suppressor inactivating mutations. Hum Pathol 2016; 51:25.
21. Sekine S, Kiyono T, Ryo E, et al. Recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poroma and
porocarcinoma. J Clin Invest 2019; 130:3827.
22. Battistella M, Langbein L, Peltre B, Cribier B. From hidroacanthoma simplex to poroid hidradenoma:
clinicopathologic and immunohistochemic study of poroid neoplasms and reappraisal of their
histogenesis. Am J Dermatopathol 2010; 32:459.
23. Betti R, Bombonato C, Cerri A, et al. Unusual sites for poromas are not very unusual: a survey of 101
cases. Clin Exp Dermatol 2014; 39:119.
24. Wilkinson RD, Schopflocher P, Rozenfeld M. Hidrotic ectodermal dysplasia with diffuse eccrine
poromatosis. Arch Dermatol 1977; 113:472.
25. Ullah K, Pichler E, Fritsch P. Multiple eccrine poromas arising in chronic radiation dermatitis. Acta Derm
Venereol 1989; 69:70.
26. Nguyen BT, Lortscher DN, Lee RA. Multiple poromas in a bone marrow transplant recipient: A case
report. Dermatol Online J 2012; 18:9.
27. North JP, Lo J, Landers M. Poromatosis in pregnancy: a case of 8 eruptive poromas in the third
trimester. Cutis 2012; 89:81.
28. Fujii K, Aochi S, Takeshima C, et al. Eccrine poromatosis associated with polychemotherapy. Acta Derm
Venereol 2012; 92:687.
29. Fehr A, Kovács A, Löning T, et al. The MYB-NFIB gene fusion-a novel genetic link between adenoid
cystic carcinoma and dermal cylindroma. J Pathol 2011; 224:322.
30. Rashid M, van der Horst M, Mentzel T, et al. ALPK1 hotspot mutation as a driver of human spiradenoma
and spiradenocarcinoma. Nat Commun 2019; 10:2213.
31. Bahrami A, Dalton JD, Krane JF, Fletcher CD. A subset of cutaneous and soft tissue mixed tumors are
genetically linked to their salivary gland counterpart. Genes Chromosomes Cancer 2012; 51:140.

32. Antonescu CR, Zhang L, Shao SY, et al. Frequent PLAG1 gene rearrangements in skin and soft tissue
myoepithelioma with ductal differentiation. Genes Chromosomes Cancer 2013; 52:675.
33. Panagopoulos I, Gorunova L, Lund-Iversen M, et al. Fusion of the Genes PHF1 and TFE3 in Malignant
Chondroid Syringoma. Cancer Genomics Proteomics 2019; 16:345.
34. Guerin M, Droney T, Keohane C, Fenton S. Eccrine syringofibroadenoma of the eyelid in association
with eye prosthesis. Eye (Lond) 2011; 25:1102.
35. Noguchi M, Akiyama M, Kawakami M, et al. Eccrine syringofibroadenoma developing in a sebaceous

naevus. Br J Dermatol 2000; 142:1050.
36. Poonawalla T, Xia L, Patten S, Stratman EJ. Clouston syndrome and eccrine syringofibroadenomas. Am
J Dermatopathol 2009; 31:157.
37. Heng YK, Pan JY, Tan SH, Tey HL. Eccrine syringofibroadenomatosis of the reactive subtype occurring
in chronic poorly-controlled psoriasis. Indian J Dermatol Venereol Leprol 2014; 80:534.
38. HELWIG EB, HACKNEY VC. Syringadenoma papilliferum; lesions with and without naevus sebaceous
and basal cell carcinoma. AMA Arch Derm 1955; 71:361.
39. Shen AS, Peterhof E, Kind P, et al. Activating mutations in the RAS/mitogen-activated protein kinase
signaling pathway in sporadic trichoblastoma and syringocystadenoma papilliferum. Hum Pathol 2015;
46:272.
40. Baker GM, Selim MA, Hoang MP. Vulvar adnexal lesions: a 32-year, single-institution review from
Massachusetts General Hospital. Arch Pathol Lab Med 2013; 137:1237.
41. Konstantinova AM, Michal M, Kacerovska D, et al. Hidradenoma Papilliferum: A Clinicopathologic Study
of 264 Tumors From 261 Patients, With Emphasis on Mammary-Type Alterations. Am J Dermatopathol
2016; 38:598.
42. El-Khoury J, Renald MH, Plantier F, et al. Vulvar hidradenoma papilliferum (HP) is located on the sites of
mammary-like anogenital glands (MLAGs): Analysis of the photographs of 52 tumors. J Am Acad
Dermatol 2016; 75:380.
43. Kazakov DV, Spagnolo DV, Kacerovska D, Michal M. Lesions of anogenital mammary-like glands: an
update. Adv Anat Pathol 2011; 18:1.
44. Pfarr N, Sinn HP, Klauschen F, et al. Mutations in genes encoding PI3K-AKT and MAPK signaling define
anogenital papillary hidradenoma. Genes Chromosomes Cancer 2016; 55:113.
45. Konstantinova AM, Vanecek T, Martinek P, et al. Molecular alterations in lesions of anogenital mammary-
like glands and their mammary counterparts including hidradenoma papilliferum, intraductal papilloma,
fibroadenoma and phyllodes tumor. Ann Diagn Pathol 2017; 28:12.

46. Morimura S, Kadono T, Sugaya M, Sato S. Ectopic hidradenoma papilliferum on the abdomen. Eur J
Dermatol 2011; 21:278.
47. Jain D, Siraj F, Grover AK, Garg KK. Hidradenoma papilliferum presenting as an eyelid mass. Ophthal
Plast Reconstr Surg 2012; 28:e152.
48. Rosmaninho AD, de Almeida MT, Costa V, et al. Ectopic hidradenoma papilliferum. Dermatol Res Pract
2010; 2010:709371.
49. Behboudi A, Winnes M, Gorunova L, et al. Clear cell hidradenoma of the skin-a third tumor type with a
t(11;19)--associated TORC1-MAML2 gene fusion. Genes Chromosomes Cancer 2005; 43:202.
50. Liau JY, Tsai JH, Huang WC, et al. BRAF and KRAS mutations in tubular apocrine adenoma and
papillary eccrine adenoma of the skin. Hum Pathol 2018; 73:59.
51. Nazemi A, Higgins S, Swift R, et al. Eccrine Porocarcinoma: New Insights and a Systematic Review of
the Literature. Dermatol Surg 2018; 44:1247.
52. Salih AM, Kakamad FH, Baba HO, et al. Porocarcinoma; presentation and management, a meta-
analysis of 453 cases. Ann Med Surg (Lond) 2017; 20:74.
53. Behbahani S, Malerba S, Karanfilian KM, et al. Demographics and outcomes of eccrine porocarcinoma:
results from the National Cancer Database. Br J Dermatol 2020.
54. North JP, McCalmont TH, Fehr A, et al. Detection of MYB Alterations and Other Immunohistochemical
Markers in Primary Cutaneous Adenoid Cystic Carcinoma. Am J Surg Pathol 2015; 39:1347.
55. Kyrpychova L, Vanecek T, Grossmann P, et al. Small Subset of Adenoid Cystic Carcinoma of the Skin Is
Associated With Alterations of the MYBL1 Gene Similar to Their Extracutaneous Counterparts. Am J
Dermatopathol 2018; 40:721.
56. Ramakrishnan R, Chaudhry IH, Ramdial P, et al. Primary cutaneous adenoid cystic carcinoma: a
clinicopathologic and immunohistochemical study of 27 cases. Am J Surg Pathol 2013; 37:1603.
57. Kamalpour L, Brindise RT, Nodzenski M, et al. Primary cutaneous mucinous carcinoma: a systematic
review and meta-analysis of outcomes after surgery. JAMA Dermatol 2014; 150:380.
58. Zembowicz A, Garcia CF, Tannous ZS, et al. Endocrine mucin-producing sweat gland carcinoma: twelve
new cases suggest that it is a precursor of some invasive mucinous carcinomas. Am J Surg Pathol
2005; 29:1330.
59. Hansen T, Kingsley M, Mallatt BD, Krishnan R. Extrafacial microcystic adnexal carcinoma: case report
and review of the literature. Dermatol Surg 2009; 35:1835.
60. Chiller K, Passaro D, Scheuller M, et al. Microcystic adnexal carcinoma: forty-eight cases, their
treatment, and their outcome. Arch Dermatol 2000; 136:1355.
61. Chan MP, Plouffe KR, Liu CJ, et al. Next-generation sequencing implicates oncogenic roles for p53 and
JAK/STAT signaling in microcystic adnexal carcinomas. Mod Pathol 2019.
62. Duke WH, Sherrod TT, Lupton GP. Aggressive digital papillary adenocarcinoma (aggressive digital
papillary adenoma and adenocarcinoma revisited). Am J Surg Pathol 2000; 24:775.
63. Suchak R, Wang WL, Prieto VG, et al. Cutaneous digital papillary adenocarcinoma: a clinicopathologic
study of 31 cases of a rare neoplasm with new observations. Am J Surg Pathol 2012; 36:1883.
64. Rismiller K, Knackstedt TJ. Aggressive Digital Papillary Adenocarcinoma: Population-Based Analysis of
Incidence, Demographics, Treatment, and Outcomes. Dermatol Surg 2018; 44:911.
65. Bell D, Aung P, Prieto VG, Ivan D. Next-generation sequencing reveals rare genomic alterations in
aggressive digital papillary adenocarcinoma. Ann Diagn Pathol 2015; 19:381.
66. Surowy HM, Giesen AK, Otte J, et al. Gene expression profiling in aggressive digital papillary
adenocarcinoma sheds light on the architecture of a rare sweat gland carcinoma. Br J Dermatol 2019;
180:1150.
67. Regauer S. Extramammary Paget's disease--a proliferation of adnexal origin? Histopathology 2006;
48:723.
68. Chen YH, Wong TW, Lee JY. Depigmented genital extramammary Paget's disease: a possible
histogenetic link to Toker's clear cells and clear cell papulosis. J Cutan Pathol 2001; 28:105.
69. Nordmann TM, Messerli-Odermatt O, Meier L, et al. Sequential somatic mutations upon secondary anti-
HER2 treatment resistance in metastatic ERBB2S310F mutated extramammary Paget's disease.
Oncotarget 2019; 10:6647.
70. Barth P, Dulaimi Al-Saleem E, Edwards KW, et al. Metastatic Extramammary Paget's Disease of
Scrotum Responds Completely to Single Agent Trastuzumab in a Hemodialysis Patient: Case Report,
Molecular Profiling and Brief Review of the Literature. Case Rep Oncol Med 2015; 2015:895151.
71. Rütten A, Kutzner H, Mentzel T, et al. Primary cutaneous cribriform apocrine carcinoma: a
clinicopathologic and immunohistochemical study of 26 cases of an under-recognized cutaneous
adnexal neoplasm. J Am Acad Dermatol 2009; 61:644.
72. Bishop JA, Taube JM, Su A, et al. Secretory Carcinoma of the Skin Harboring ETV6 Gene Fusions: A
Cutaneous Analogue to Secretory Carcinomas of the Breast and Salivary Glands. Am J Surg Pathol
2017; 41:62.
73. Llamas-Velasco M, Mentzel T, Rütten A. Primary cutaneous secretory carcinoma: A previously

overlooked low-grade sweat gland carcinoma. J Cutan Pathol 2018; 45:240.
74. Plewig G. Sebaceous trichofolliculoma. J Cutan Pathol 1980; 7:394.

75. Rohwedder A, Keminer O, Hendricks C, Schaller J. Detection of HPV DNA in trichilemmomas by

polymerase chain reaction. J Med Virol 1997; 51:119.
76. Stierman S, Chen S, Nuovo G, Thomas J. Detection of human papillomavirus infection in

trichilemmomas and verrucae using in situ hybridization. J Cutan Pathol 2010; 37:75.
77. Leonardi CL, Zhu WY, Kinsey WH, Penneys NS. Trichilemmomas are not associated with human
papillomavirus DNA. J Cutan Pathol 1991; 18:193.
78. Kambiz KH, Kaveh D, Maede D, et al. Human Papillomavirus Deoxyribonucleic Acid may not be
Detected in Non-genital Benign Papillomatous Skin Lesions by Polymerase Chain Reaction. Indian J
Dermatol 2014; 59:334.
79. Tsai JH, Huang WC, Jhuang JY, et al. Frequent activating HRAS mutations in trichilemmoma. Br J
Dermatol 2014; 171:1073.
80. Ackerman AB, Reddy VB, Soyer HP. Neoplasms with Follicular Differentiation, 2nd ed, Ardor Scribendi P
ublishers, New York 2000.
81. Alomari A, Subtil A, Owen CE, McNiff JM. Solitary and multiple tumors of follicular infundibulum: a
review of 168 cases with emphasis on staining patterns and clinical variants. J Cutan Pathol 2013;
40:532.
82. Kubba A, Batrani M, Taneja A, Jain V. Tumor of follicular infundibulum: an unsuspected cause of
macular hypopigmentation. Indian J Dermatol Venereol Leprol 2014; 80:141.
83. Cheng AC, Chang YL, Wu YY, et al. Multiple tumors of the follicular infundibulum. Dermatol Surg 2004;
30:1246.
84. Shan SJ, Guo Y. Panfolliculoma and histopathologic variants: a study of 19 cases. Am J Dermatopathol
2014; 36:965.
85. Chan EF, Gat U, McNiff JM, Fuchs E. A common human skin tumour is caused by activating mutations
in beta-catenin. Nat Genet 1999; 21:410.
86. Lazar AJ, Calonje E, Grayson W, et al. Pilomatrix carcinomas contain mutations in CTNNB1, the gene
encoding beta-catenin. J Cutan Pathol 2005; 32:148.
87. Hernández-Núñez A, Nájera Botello L, Romero Maté A, et al. Retrospective study of pilomatricoma: 261
tumors in 239 patients. Actas Dermosifiliogr 2014; 105:699.
88. Rothman D, Kendall AB, Baldi A. Giant pilomatrixoma (Malherbe calcifying epithelioma). Arch Surg
1976; 111:86.

89. Chiaramonti A, Gilgor RS. Pilomatricomas associated with myotonic dystrophy. Arch Dermatol 1978;
114:1363.
90. Pujol RM, Casanova JM, Egido R, et al. Multiple familial pilomatricomas: a cutaneous marker for
Gardner syndrome? Pediatr Dermatol 1995; 12:331.
91. Maeda D, Kubo T, Miwa H, et al. Multiple pilomatricomas in a patient with Turner syndrome. J Dermatol
2014; 41:563.
92. Blaya B, Gonzalez-Hermosa R, Gardeazabal J, Diaz-Perez JL. Multiple pilomatricomas in association

with trisomy 9. Pediatr Dermatol 2009; 26:482.
93. Hamahata A, Kamei W, Ishikawa M, et al. Multiple pilomatricomas in Kabuki syndrome. Pediatr Dermatol
2013; 30:253.
94. Cambiaghi S, Ermacora E, Brusasco A, et al. Multiple pilomatricomas in Rubinstein-Taybi syndrome: a

case report. Pediatr Dermatol 1994; 11:21.
95. Hollmig ST, Tollefson MM, Kim J, Khuu P. Multiple eruptive pilomatricomas in a 9-year-old boy with
glioblastoma. Pediatr Dermatol 2013; 30:756.
96. Park BS, Yang SG, Cho KH. Malignant proliferating trichilemmal tumor showing distant metastases. Am
J Dermatopathol 1997; 19:536.
97. Sellheyer K, Krahl D. Basal cell (trichoblastic) carcinoma common expression pattern for epithelial cell
adhesion molecule links basal cell carcinoma to early follicular embryogenesis, secondary hair germ,
and outer root sheath of the vellus hair follicle: A clue to the adnexal nature of basal cell carcinoma? J
Am Acad Dermatol 2008; 58:158.
98. Hamman MS, Brian Jiang SI. Management of trichilemmal carcinoma: an update and comprehensive
review of the literature. Dermatol Surg 2014; 40:711.
99. Dalton SR, LeBoit PE. Squamous cell carcinoma with clear cells: how often is there evidence of
tricholemmal differentiation? Am J Dermatopathol 2008; 30:333.
100. Misago N, Toda S, Narisawa Y. Tricholemmoma and clear cell squamous cell carcinoma (associated
with Bowen's disease): immunohistochemical profile in comparison to normal hair follicles. Am J
Dermatopathol 2012; 34:394.
101. Tolkachjov SN, Hocker TL, Camilleri MJ, Baum CL. Mohs micrographic surgery in the treatment of
trichilemmal carcinoma: the Mayo Clinic experience. J Am Acad Dermatol 2015; 72:195.
102. Herrmann JL, Allan A, Trapp KM, Morgan MB. Pilomatrix carcinoma: 13 new cases and review of the
literature with emphasis on predictors of metastasis. J Am Acad Dermatol 2014; 71:38.

103. Melancon JM, Tom WL, Lee RA, et al. Management of pilomatrix carcinoma: a case report of successful
treatment with Mohs micrographic surgery and review of the literature. Dermatol Surg 2011; 37:1798.
104. Tselis N, Heyd R, Vogt HG, Zamboglou N. Pilomatrix carcinoma with lymph node and pulmonary
metastases. Strahlenther Onkol 2006; 182:727.
105. Arslan D, Gündüz S, Avci F, et al. Pilomatrix carcinoma of the scalp with pulmonary metastasis: A case
report of a complete response to oral endoxan and etoposide. Oncol Lett 2014; 7:1959.
106. Takeda H, Lyle S, Lazar AJ, et al. Human sebaceous tumors harbor inactivating mutations in LEF1. Nat
Med 2006; 12:395.
107. Boennelycke M, Thomsen BM, Holck S. Sebaceous neoplasms and the immunoprofile of mismatch-
repair proteins as a screening target for syndromic cases. Pathol Res Pract 2015; 211:78.
108. Everett JN, Raymond VM, Dandapani M, et al. Screening for germline mismatch repair mutations
following diagnosis of sebaceous neoplasm. JAMA Dermatol 2014; 150:1315.
109. Sato T, Tanaka M. Linear sebaceous hyperplasia on the chest. Dermatol Pract Concept 2014; 4:93.
110. Vergara G, Belinchón I, Silvestre JF, et al. Linear sebaceous gland hyperplasia of the penis: a case
report. J Am Acad Dermatol 2003; 48:149.
111. Franco G, Donati P, Muscardin L, et al. Juxta-clavicular beaded lines. Australas J Dermatol 2006;
47:204.
112. Woldow AB, Houk LD, Samie FH. Juxtaclavicular beaded lines: a presentation of sebaceous gland
hyperplasia. Dermatol Online J 2009; 15:14.
113. de Berker DA, Taylor AE, Quinn AG, Simpson NB. Sebaceous hyperplasia in organ transplant recipients:
shared aspects of hyperplastic and dysplastic processes? J Am Acad Dermatol 1996; 35:696.
114. Salim A, Reece SM, Smith AG, et al. Sebaceous hyperplasia and skin cancer in patients undergoing
renal transplant. J Am Acad Dermatol 2006; 55:878.
115. Wang Q, Liu JM, Zhang YZ. Premature sebaceous hyperplasia in an adolescent boy. Pediatr Dermatol
2011; 28:198.
116. Turan H, Erdem H, Turan A, et al. Premature sebaceous hyperplasia with pre-pubertal onset. Int J
Dermatol 2014; 53:e224.
117. Sener S, Sasmaz S, Dogan DG, Ciralik H. Is "premature sebaceous hyperplasia" really a sebaceous
hamartoma? Report of a case with neonatal onset. Pediatr Dermatol 2011; 28:732.
118. McDonald SK, Goh MS, Chong AH. Successful treatment of cyclosporine-induced sebaceous
hyperplasia with oral isotretinoin in two renal transplant recipients. Australas J Dermatol 2011; 52:227.

119. Noh S, Shin JU, Jung JY, Lee JH. A case of sebaceous hyperplasia maintained on low-dose isotretinoin
after carbon dioxide laser treatment. Int J Dermatol 2014; 53:e151.
120. Richey DF. Aminolevulinic acid photodynamic therapy for sebaceous gland hyperplasia. Dermatol Clin
2007; 25:59.
121. Wheeland RG, Wiley MD. Q-tip cryosurgery for the treatment of senile sebaceous hyperplasia. J
Dermatol Surg Oncol 1987; 13:729.
122. Bader RS, Scarborough DA. Surgical pearl: intralesional electrodesiccation of sebaceous hyperplasia. J
Am Acad Dermatol 2000; 42:127.
123. No D, McClaren M, Chotzen V, Kilmer SL. Sebaceous hyperplasia treated with a 1450-nm diode laser.
Dermatol Surg 2004; 30:382.
124. Troy JL, Ackerman AB. Sebaceoma. A distinctive benign neoplasm of adnexal epithelium differentiating
toward sebaceous cells. Am J Dermatopathol 1984; 6:7.
125. Bhaijee F, Brown AS. Muir-Torre syndrome. Arch Pathol Lab Med 2014; 138:1685.
126. Singh RS, Grayson W, Redston M, et al. Site and tumor type predicts DNA mismatch repair status in
cutaneous sebaceous neoplasia. Am J Surg Pathol 2008; 32:936.
127. Dasgupta T, Wilson LD, Yu JB. A retrospective review of 1349 cases of sebaceous carcinoma. Cancer
2009; 115:158.
128. North JP, Golovato J, Vaske CJ, et al. Cell of origin and mutation pattern define three clinically distinct
classes of sebaceous carcinoma. Nat Commun 2018; 9:1894.
129. Menko FH, van Steensel MA, Giraud S, et al. Birt-Hogg-Dubé syndrome: diagnosis and management.
Lancet Oncol 2009; 10:1199.
130. Part II Head and Neck. In: AJCC Cancer Staging Manual, 8th ed, Amid MB (Ed), Springer, New York 20
17. p.53., corrected at 4th printing, 2018.
131. Ad Hoc Task Force, Connolly SM, Baker DR, et al. AAD/ACMS/ASDSA/ASMS 2012 appropriate use
criteria for Mohs micrographic surgery: a report of the American Academy of Dermatology, American
College of Mohs Surgery, American Society for Dermatologic Surgery Association, and the American
Society for Mohs Surgery. J Am Acad Dermatol 2012; 67:531.
132. Xu B, Wang T, Liao Z. Surgical Treatment of Trichilemmal Carcinoma. World J Oncol 2018; 9:141.
133. Conill C, Toscas I, Morilla I, Mascaró JM Jr. Radiation therapy as a curative treatment in extraocular
sebaceous carcinoma. Br J Dermatol 2003; 149:441.

134. Pardo FS, Wang CC, Albert D, Stracher MA. Sebaceous carcinoma of the ocular adnexa:
radiotherapeutic management. Int J Radiat Oncol Biol Phys 1989; 17:643.
135. Avraham JB, Villines D, Maker VK, et al. Survival after resection of cutaneous adnexal carcinomas with
eccrine differentiation: risk factors and trends in outcomes. J Surg Oncol 2013; 108:57.
136. Barnes M, Hestley A, Murray DR, et al. The risk of lymph node involvement in malignant cutaneous
adnexal tumors. Am Surg 2014; 80:270.
137. De Iuliis F, Amoroso L, Taglieri L, et al. Chemotherapy of rare skin adnexal tumors: a review of literature.
Anticancer Res 2014; 34:5263.
138. Schröder U, Dries V, Klussmann JP, et al. Successful adjuvant tamoxifen therapy for estrogen receptor-
positive metastasizing sweat gland adenocarcinoma: need for a clinical trial? Ann Otol Rhinol Laryngol
2004; 113:242.
139. Brown TJ, Sher DJ, Nedzi LA, et al. Cutaneous adnexal adenocarcinoma with exquisite sensitivity to
trastuzumab. Head Neck 2017; 39:E69.
140. Miller DH, Peterson JL, Buskirk SJ, et al. Management of Metastatic Apocrine Hidradenocarcinoma with
Chemotherapy and Radiation. Rare Tumors 2015; 7:6082.
141. Hibler BP, Barker CA, Hollmann TJ, Rossi AM. Metastatic cutaneous apocrine carcinoma:
Multidisciplinary approach achieving complete response with adjuvant chemoradiation. JAAD Case Rep
2017; 3:259.
142. Snow SN, Larson PO, Lucarelli MJ, et al. Sebaceous carcinoma of the eyelids treated by mohs
micrographic surgery: report of nine cases with review of the literature. Dermatol Surg 2002; 28:623.
143. Blake PW, Toro JR. Update of cylindromatosis gene (CYLD) mutations in Brooke-Spiegler syndrome:
novel insights into the role of deubiquitination in cell signaling. Hum Mutat 2009; 30:1025.
144. Bowen S, Gill M, Lee DA, et al. Mutations in the CYLD gene in Brooke-Spiegler syndrome, familial
cylindromatosis, and multiple familial trichoepithelioma: lack of genotype-phenotype correlation. J Invest
Dermatol 2005; 124:919.
145. Young AL, Kellermayer R, Szigeti R, et al. CYLD mutations underlie Brooke-Spiegler, familial
cylindromatosis, and multiple familial trichoepithelioma syndromes. Clin Genet 2006; 70:246.
146. Nelen MR, van Staveren WC, Peeters EA, et al. Germline mutations in the PTEN/MMAC1 gene in
patients with Cowden disease. Hum Mol Genet 1997; 6:1383.
147. Ponti G, Ponz de Leon M. Muir-Torre syndrome. Lancet Oncol 2005; 6:980.
Topic 16910 Version 13.0


GRAPHICS
Cutaneous adnexal tumors [1-8]
Sweat gland tumors, benign Derivation Genetic abnormalities
Poroma (classic poroma, hidroacanthoma Eccrine or apocrine HRAS mutation, LOH in APC
simplex, dermal duct tumor)
Hidradenoma Eccrine or apocrine t(11;19) MAML2;MECT1
Hidradenoma papilliferum Anogenital apocrine PIK3CA mutation
Spiradenoma/cylindroma Eccrine or apocrine CYLD mutation/LOH; t(6;9) MYB-NFIB
Mixed tumor Sweat duct ± follicular
Syringofibroadenoma Eccrine
Syringoma Eccrine or apocrine
Syringocystadenoma papilliferum Apocrine RAS, BRAF mutation; 9p21 deletion; 9q22

LOH
Tubular/papillary adenoma Eccrine or apocrine BRAF V600E
Sweat gland tumors,

malignant
Porocarcinoma Eccrine or apocrine EGFR, HRAS, TP53, RB1, ATM, ARID1A,

CDKN2A, PIK3CA mutations
(Aggressive) digital papillary Eccrine or apocrine BRAF mutation

adenocarcinoma
Adenoid cystic carcinoma Eccrine or apocrine t(6;9) MYB-NFIB
Apocrine adenocarcinoma Apocrine
Syringomatous carcinoma Eccrine or apocrine
Hidradenocarcinoma Eccrine or apocrine
Malignant mixed tumor Eccrine or apocrine
Cylindrocarcinoma/spiradenocarcinoma Eccrine or apocrine CYLD mutation/LOH
Mucinous carcinoma Eccrine or apocrine
Microcystic adnexal carcinoma Sweat duct and follicular
Extramammary Paget disease Multiple possibilities PIK3CA mutation; Chr 19 and X

amplification; 10q loss
Cutaneous (mammary analog) secretory Apocrine (possibly eccrine) ETV6-NTRK3 fusion

carcinoma
Cutaneous cribriform carcinoma Apocrine
Follicular and sebaceous

tumors, benign
Trichoblastoma/trichoepithelioma Follicular CTNNB1, CYLD, and PTCH1 mutation
Trichofolliculoma Follicular
Panfolliculoma Follicular
Proliferating follicular-cystic acanthoma Follicular (outer root sheath)

(proliferating pilar tumor)
Trichilemmoma Follicular (outer root sheath) HRAS, PTEN mutation
Trichoadenoma Follicular (infundibulum)
Tumor of the follicular infundibulum Follicular (isthmus)
Pilar sheath acanthoma Follicular (isthmus/infundibulum)
Pilomatricoma Follicular (matrix) CTNNB1 mutation; trisomy 18
Sebaceous adenoma Sebaceous gland LEF1, MLH1, MSH2, MSH6 mutation

Sebaceoma Sebaceous gland LEF1, MLH1, MSH2, MSH6 mutation
Fibrofolliculoma/trichodiscoma Sebaceous mantle FLCN mutation
Follicular and sebaceous

tumors, malignant
Trichoblastic carcinoma Follicular
Trichilemmal carcinoma Follicular (outer root sheath)
Pilomatrix (matrical) carcinoma Follicular (matrix) CTNNB1 mutation
Sebaceous carcinoma Sebaceous LEF1, MLH1, MSH2, MSH6 mutation
LOH: loss of heterozygosity.
References:
1. Harms PW, Hovelson DH, Cani AK, et al. Porocarcinomas harbor recurrent HRAS-activating mutations and tumor suppressor
inactivating mutations. Hum Pathol 2016; 51:25.
2. Fehr A, Kovács A, Löning T, et al. The MYB-NFIB gene fusion-a novel genetic link between adenoid cystic carcinoma and dermal
cylindroma. J Pathol 2011; 224:322.
3. Shen AS, Peterhof E, Kind P, et al. Activating mutations in the RAS/mitogen-activated protein kinase signaling pathway in sporadic
trichoblastoma and syringocystadenoma papilliferum. Hum Pathol 2015; 46:272.
4. Pfarr N, Sinn HP, Klauschen F, et al. Mutations in genes encoding PI3K-AKT and MAPK signaling define anogenital papillary
hidradenoma. Genes Chromosomes Cancer 2016; 55:113.
5. Konstantinova AM, Vanecek T, Martinek P, et al. Molecular alterations in lesions of anogenital mammary-like glands and their
mammary counterparts including hidradenoma papilliferum, intraductal papilloma, fibroadenoma and phyllodes tumor. Ann Diagn
Pathol 2017; 28:12.
6. Behboudi A, Winnes M, Gorunova L, et al. Clear cell hidradenoma of the skin-a third tumor type with a t(11;19)--associated
TORC1-MAML2 gene fusion. Genes Chromosomes Cancer 2005; 43:202.
7. Liau JY, Tsai JH, Huang WC, et al. BRAF and KRAS mutations in tubular apocrine adenoma and papillary eccrine adenoma of the
skin. Hum Pathol 2018; 73:59.
8. North JP, McCalmont TH, Fehr A, et al. Detection of MYB Alterations and Other Immunohistochemical Markers in Primary
Cutaneous Adenoid Cystic Carcinoma. Am J Surg Pathol 2015; 39:1347.
Graphic 98212 Version 2.0

Poroma
Poroma presenting as a skin-colored papule on the leg.
Reproduced with permission from: www.visualdx.com. Copyright VisualDx. All rights reserved.

Spiradenoma
Spiradenomas present as shiny, pink to red papules or nodules, typically on the head and neck region. This example from
the scalp has prominent telangiectatic vessels.
Courtesy of Jeffrey P North, MD.

Trichoepithelioma
Cutaneous adnexal tumors present in a relatively non-specific pattern with pink, translucent, or slightly blue papules with
variable amounts of telangiectasia. Biopsy of this lesion revealed a trichoepithelioma.

Syringoma
Syringomas presenting as multiple small, skin-colored papules in the periocular area.

Eruptive syringoma
Multiple flesh-colored and erythematous small papules are present on the neck
and chest.
Reproduced with permission from: www.visualdx.com. Copyright VisualDx. All rights

reserved.

Syringoma
Syringomas presenting as multiple small, skin-colored papules on the anterior neck.

Eruptive syringoma
Multiple flesh-colored and hyperpigmented small papules are present on the

shoulder and chest.
Reproduced with permission from: www.visualdx.com. Copyright VisualDx. All rights

reserved.

Vulvar syringoma
Reproduced with permission from Lynne J Margesson, MD.

Histologic features of syringoma
Syringomas are characterized by numerous small collections of epithelial cells with central duct formation and associated
fibrotic stroma (H&E 100x).

Poroma
Poroma presenting as an erythematous papule on the palm.

Poroma
Poroma presenting as a skin-colored papule on the palm.

Histologic features of hidroacanthoma simplex
(A) Intraepidermal poroma (hidroacanthoma simplex) consists of well-demarcated collections of poroid cells within the
epidermis (H&E 40x).
(B) Hidroacanthoma simplex resemble seborrheic keratosis histopathologically, but are distinguished by the presence of ducts
within the neoplasm (H&E 200x).

Histologic features of classic poroma
Classic poromas form nodular collections of poroid keratinocytes in the upper dermis that connect with the overlying
epidermis in multiple areas. Ductal differentiation is focally present (H&E 40x).

Histologic features of poroma, dermal duct variant
The dermal duct variant of poroma consists of numerous small to medium-sized collections of poroid cells in the
dermis (H&E 40x).

Histologic features of poroid hidradenoma
Poroid hidradenoma consists of one or more large dermal nodules of poroid cells with ductal differentiation (H&E 20x).

Cylindroma
Cylindroma presenting as a small nodule on the helix of ear.

Cylindroma
Multiple cylindromas of the forehead and scalp presenting as red papules and nodules of varying sizes with superficial
telangiectasias.

Histologic features of cylindroma
(A) Cylindromas contain many small islands of basaloid keratinocytes closely opposed to
one another in a pattern resembling the pieces of a jigsaw puzzle (H&E 40x).
(B) Prominent pink, hyalinized basement membrane substance surrounds the individual
tumor aggregations and is present in drop-like fashion between the keratinocytes. Ductal
differentiation is present (H&E 200x).
H&E: hematoxylin and eosin.

Histologic features of spiradenoma
Spiradenomas lie on a spectrum with cylindromas but are composed of larger, nodular aggregations of basaloid keratinocytes
instead of small ones. Prominent deposition of basement membrane material and duct formation is present in both
spiradenoma and cylindroma (H&E 40x).

Mixed tumor of the skin (chondroid syringoma)
Chondroid syringoma presenting as an asymptomatic firm nodule in the nasolabial fold.

Histologic features of mixed tumor of the skin (chondroid syringoma)
Cutaneous mixed tumors have an epithelial and stromal component. The stromal component typically has areas with
abundant mucin and can have a chondroid appearance as depicted in this case. Mixed tumors can show apocrine or eccrine
differentiation, and they frequently have a prominent myoepithelial component. The epithelial component in this example is
minimal, but can be confirmed with a keratin stain (H&E 100x).

Histologic features of syringofibroadenoma
Syringofibroadenoma exhibits a unique pattern of thin interconnecting strands of keratinocytes extending from the epidermis
into the dermis. Small ducts are present in the strands in variable numbers (H&E 40x).

Syringocystadenoma papilliferum
Syringocystadenoma papilliferum is a superficial adnexal tumor. Cuboidal and columnar keratinocytes form interconnecting
ducts that interrupt the normal epidermis and extend into the dermis. Papillary projections into duct lumens and decapitation
secretion are typical. An inflammatory infiltrate rich in plasma cells surrounds the proliferation. Syringocystadenoma
papilliferum often arise within a nevus sebaceus, as is the case in this example (H&E 40x).

Hidradenoma papilliferum
Hidradenoma papilliferum presenting as a solitary, skin-colored nodule on the vulva.

Histologic features of hidradenoma
(A) Hidradenomas can exhibit both eccrine and apocrine differentiation and are
characterized by large, nodular collections of keratinocytes with variable duct
formation (H&E 40x).
(B) A variety of hidradenomas have been described. The pale/clear cell variant is
composed of a preponderance of keratinocytes with abundant pale cytoplasm
(H&E 200x).

Histologic features of tubular adenoma of the skin
(A) Tubular adenomas are benign sweat gland tumors with prominent ductal
differentiation (H&E 20x).
(B) Multiple collections of keratinocytes with central ducts form tubular structures that
may have papillary projections in their cystically-dilated lumens (H&E 100x).

Histologic features of porocarcinoma
Porocarcinoma is a rare tumor composed of keratinocytes with atypical nuclei present in a poorly circumscribed, infiltrative
growth pattern. Necrosis and mitotic activity can be present in both poroma and porocarcinoma, although they typically
occur in greater amount in the latter. This porocarcinoma arose within a preexistent poroma (well-circumscribed
aggregations of small poroid keratinocytes in the upper portion of the figure). (H&E100x).

Histologic features of adenoid cystic carcinoma of the skin
The hallmark histopathologic finding in adenoid cystic carcinoma is a cribriform architecture in which multiple circular
collections of mucin form within tumor aggregations in a sieve-like pattern (H&E 100x).

Microcystic adnexal carcinoma
Microcystic adnexal carcinoma presenting as a white-yellow plaque on the

cheek.

Microcystic adnexal carcinoma presenting as a white-yellow plaque on the cheek. The

palpable tumor is outlined. Note the asymmetrical extension.

Microcystic adnexal carcinoma presenting as a subtle papule beneath the eye.

Microcystic adnexal carcinoma presenting as a subtle white papule beneath the

eye. The palpable tumor is outlined.

Histologic features of microcystic adnexal carcinoma
(A) Microcystic adnexal carcinoma (MAC) is a locally aggressive adnexal carcinoma

with divergent differentiation. Follicular differentiation in the form of keratin (horn)
cysts is present in the superficial dermis (H&E 20x).
(B) Deeper in the dermis, smaller aggregations of keratinocytes with sweat duct
formation infiltrate between deep dermal collagen and into the subcutis. Dystrophic
calcium deposition (fragmented purple material) is common (H&E 100x).

Histologic features of digital papillary adenocarcinoma
(A) Digital papillary adenocarcinomas have a multi-nodular growth pattern with ductal
differentiation. Cystically-dilated areas are frequently present (H&E 40x).
(B) Papillary projections into dilated ductal spaces are a characteristic finding. This
example shows numerous mitotic figures, crowding of tumor nuclei, and prominent
cytologic atypia (H&E 200x).

Histopathologic features of extramammary Paget disease
Extramammary Paget disease (EMPD) is characterized by large keratinocytes with abundant pale pink cytoplasm and large
oval nuclei (pagetoid cytomorphology) that form nests in the epidermis. Solitary tumor cells can also be seen in the upper
epidermis between the normal epidermal keratinocytes (pagetoid architecture). Duct formation is helpful in identifying the
tumor, but is not always evident (H&E 200x).

Cutaneous cribriform carcinoma histopathology
Cutaneous cribriform carcinoma shows a nodular configuration in the dermis with a fibromyxoid stroma and peripheral lymphoid
aggregates. Irregular ductal spaces create focal cribriform architecture at the periphery of the tumor in this case (H&E 40x).

Cutaneous cribriform carcinoma histopathology
High magnification of cutaneous cribriform carcinoma showing characteristic clusters of epithelial cells with ducts of varying size
separated by thread-like septations (H&E 100x).

Trichoblastoma
Trichoblastoma presenting as a slightly erythematous papule with superficial telangiectasias in a 75-year-old woman.
Reproduced with permission from: Diepgen TL, Yihune G, et al. Dermatology Online Atlas. Published online at: www.dermis.net.
Copyright © 1996-2015 DermIS. All rights reserved.

Histologic features of trichoblastoma
(A) Trichoblastomas have large islands of basaloid keratinocytes with an associated hypercellular, fibrotic stroma (H&E 40x).
(B) Peripheral palisading of the outermost keratinocytes is present, and dense collections of mesenchymal cells directly
adjacent to the basaloid keratinocytes (papillary mesenchymal body) are identifiable (arrowhead) (H&E 200x).

Histologic features of trichoadenoma
Trichoadenomas are benign follicular tumors with multiple cystic structures of varying size in the dermis (H&E 40x).

Trichofolliculoma
Trichofolliculoma typically presents as a small follicular papule with multiple protruding vellus hairs.

Trichofolliculoma
Trichofolliculoma typically presents as a small follicular papule from which multiple vellus hairs emanate.

Trichofolliculoma
Trichofolliculoma presenting as a skin-colored confluent group of small follicular papules on the nose of an 83-year-old male
patient.
Reproduced with permission from: Diepgen TL, Yihune G, et al. Dermatology Online Atlas. Published online at: www.dermis.net.
Copyright © 1996-2015 DermIS. All rights reserved.

Histologic features of trichofolliculoma
Trichofolliculoma has a central dilated hair follicle from which multiple small vellus hair follicles emanate (H&E
40x).

Trichilemmoma
Trichilemmoma presenting as a small warty lesion in the mustache area of this patient.

Cowden syndrome
This patient with Cowden syndrome has numerous dome-shaped to verrucous pink papules on the face, several of which
were biopsied and diagnosed as trichilemmomas.

Histopathologic features of trichilemmoma
Trichilemmomas consist of lobular collections of keratinocytes with small nuclei and pink to pale cytoplasm. A rim of small,
palisaded cells lines some areas of the tumor, and there are frequently areas of hypergranulosis resembling the koilocytic
changes of human papillomavirus infection.
(A) H&E 40x.
(B) H&E 200x.

Trichodiscoma
Multiple small skin-colored papules on the chest of a patient with Birt-Hogg-Dubé syndrome. Histology revealed
trichodiscomas.

Histologic features of trichodiscoma
Trichodiscoma is composed of a central zone of spindled fibroblasts with mucin deposition (bluish substance) and a rim of
surrounding sebaceous glands arranged in what has been described as a mitt-like pattern (H&E 20x).

Histologic features of fibrofolliculoma
Fibrofolliculoma has cystically-dilated follicular infundibula from which thin strands of keratinocytes radiate. Sebaceous glands
can be found attached to the thin strands in some areas. A variably fibrotic and mucinous stroma is present (H&E 100x).

Histologic features of tumor of the follicular infundibulum
Tumor of the follicular infundibulum has a horizontal orientation to the tumor that parallels the epidermis. Keratinocytes with
pale pink cytoplasm that contrast sharply with the darker pink epidermal keratinocytes descend from and reconnect with the
undersurface of the epidermis. Small cyst and duct-like structures are focally present (H&E 40x).

Histologic features of panfolliculoma
(A) Solid aggregates in the dermis (H&E 20x).

(B) Aggregates with follicular differentiation. Note the fibrous stroma (H&E 100x).
(C) Aggregates composed of germinative cells, matrical cells, and cells with inner sheath differentiation (H&E 400x).
(D) Cells with eosinophilic trichohyalin granules and associated blue-gray corneocytes, indicating inner sheath differentiation.
Rudimentary papilla and inner sheath differentiation was evident (H&E 200x).
From: Shan SJ, Guo Y. Panfolliculoma and histopathologic variants: a study of 19 cases. Am J Dermatopathol 2014; 36:965. DOI:
10.1097/DAD.0000000000000108. Reproduced with permission from Lippincott Williams & Wilkins. Copyright © 2008 International
Society of Dermatopathology. Unauthorized reproduction of this material is prohibited.

Pilomatricoma
Pilomatricomas present as firm nodules in the skin with varying degrees of pink, blue, and white color. Ulceration with
extrusion of calcified material can occasionally be seen.

Pilomatricoma
A firm blue-gray papule is present on the cheek of this 12-year-old girl.
Copyright © Bernard Cohen, MD, Dermatlas; http://www.dermatlas.org.

Histologic features of pilomatricoma
(A) Pilomatricoma is a well-circumscribed proliferation with basaloid keratinocytes

resembling those seen in the hair bulb/matrix that transition into large masses of
pink keratin material with focal calcification (H&E 20x).
(B) The basaloid matrical cells abruptly keratinize into large collections of pink
keratinocytes without nuclei (shadow cells) (H&E 200x).

Histologic features of proliferating cystic acanthoma

(proliferating pilar tumor)
Proliferating cystic acanthoma (proliferating pilar tumor) consists of multiple

small to large interconnecting collections of keratinocytes with abundant pink
cytoplasm that cornify centrally without a granular layer. Central calcification is
often present. Cytologic atypia is minimal in this case.
(A) H&E 20x.
(B) H&E 100x.

Histopathologic features of trichilemmal carcinoma
(A) Hematoxylin and eosin (original magnification x20), view showing lobular proliferation of atypical keratinocytes with areas
of peripheral palisading of basaloid cells. The spinous layer shows broad areas of pale staining cells with areas of abrupt
keratinization.
(B) Hematoxylin and eosin (original magnification x40), view showing enlarged keratinocytes with pleomorphic nuclei, and
abundant mitotic activity, including atypical mitoses.
From: Hamman MS, Brian Jiang SI. Management of trichilemmal carcinoma: an update and comprehensive review of the literature.
Dermatol Surg 2014; 40:711. DOI: 10.1111/dsu.0000000000000002. Reproduced with permission from Lippincott Williams & Wilkins.
Copyright © 2014 American Society for Dermatologic Surgery. Unauthorized reproduction of this material is prohibited.

Sebaceous hyperplasia
Sebaceous hyperplasia presenting as small, umbilicated, brownish papules on the nose and central face of this patient.

Sebaceous hyperplasia
Sebaceous hyperplasia presenting with multiple flesh-colored or yellowish papules on the cheek.

Dermoscopic image of sebaceous hyperplasia
On dermoscopic examination, sebaceous hyperplasia shows a structureless yellow to whitish center

surrounded by short linear vessels ("crown vessels") that do not cross the center.

Histologic features of sebaceous hyperplasia
Sebaceous hyperplasia has multiple enlarged but otherwise normal sebaceous glands present around a dilated follicle or
follicles in the upper dermis (H&E 20x).

Sebaceous adenoma
Sebaceous adenoma presenting as a solitary, skin-colored, dome-shaped lesion with a central dell on the forehead of this
patient.

Histologic features of sebaceous adenoma
Sebaceous adenomas can have overlapping histopathologic features with sebaceous hyperplasia, but typically lack a central
follicle and often connect directly to the epidermis. Architecturally, sebaceous adenomas have a more disorganized
appearance than sebaceous hyperplasia, with more basaloid germinative sebocytes (H&E 40x).

Histologic features of sebaceoma
Sebaceoma is a variant of sebaceous adenoma that is typically located deeper in the dermis and
has a predominance of germinative sebocytes over mature, lipidized sebocytes.
(A) H&E 20x.
(B) H&E 200x.

Sebaceous carcinoma of the eyelid
Mimic of blepharitis, but with only unilateral findings. Here the bump on the
medial upper lid is concerning due to its vascularity and alteration of both the lid
margin architecture and the lash line.

Histologic features of sebaceous carcinoma
Sebaceous carcinomas have variable numbers of fully lipidized sebocytes. They are
characterized by an infiltrative growth pattern, cytologic atypia, and mitotic figures.
(A) H&E 20x.
(B) H&E 100x.

Cutaneous squamous cell carcinoma of the head and neck TNM staging AJCC UICC 8th
edition
Primary tumor (T)

T category T criteria
TX Primary tumor cannot be assessed
Tis Carcinoma in situ
T1 Tumor smaller than or equal to 2 cm in greatest dimension
T2 Tumor larger than 2 cm, but smaller than or equal to 4 cm in greatest dimension
T3 Tumor larger than 4 cm in maximum dimension or minor bone erosion or perineural invasion or
deep invasion*
T4 Tumor with gross cortical bone/marrow, skull base invasion and/or skull base foramen invasion
T4a Tumor with gross cortical bone/marrow invasion
T4b Tumor with skull base invasion and/or skull base foramen involvement
* Deep invasion is defined as invasion beyond the subcutaneous fat or >6 mm (as measured from the granular layer of adjacent
normal epidermis to the base of the tumor); perineural invasion for T3 classification is defined as tumor cells within the nerve
sheath of a nerve lying deeper than the dermis or measuring 0.1 mm or larger in caliber, or presenting with clinical or
radiographic involvement of named nerves without skull base invasion or transgression.
Regional lymph nodes (N)

Clinical N (cN)
N category N criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(–)
N2 Metastasis in a single ipsilateral node larger than 3 cm but not larger than 6 cm in greatest
dimension and ENE(–); or
Metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and
ENE(–); or
In bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(–)
N2a Metastasis in a single ipsilateral node larger than 3 cm but not larger than 6 cm in greatest
dimension and ENE(–)
N2b Metastases in multiple ipsilateral nodes, none larger than 6 cm in greatest dimension and ENE(–)
N2c Metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension
and ENE(–)
N3 Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(–); or

Metastasis in any node(s) and clinically overt ENE [ENE(+)]
N3a Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(–)
N3b Metastasis in any node(s) and ENE(+)
NOTE: A designation of "U" or "L" may be used for any N category to indicate metastasis above the lower border of the
cricoid (U) or below the lower border of the cricoid (L).
Similarly, clinical and pathological ENE should be recorded as ENE(–) or ENE(+).
Pathological N (pN)
N category N criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(–)
N2 Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(+);
or
Larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(–); or
Metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and

ENE(–); or
In bilateral or contralateral lymph node(s), none larger than 6 cm in greatest dimension, ENE(–)
N2a Metastasis in a single ipsilateral lymph node 3 cm or smaller in greatest dimension and ENE(+);
or
A single ipsilateral node larger than 3 cm but not larger than 6 cm in greatest dimension and
ENE(–)
N2b Metastases in multiple ipsilateral nodes, none larger than 6 cm in greatest dimension and ENE(–)
N2c Metastases in bilateral or contralateral lymph node(s), none larger than 6 cm in greatest
dimension and ENE(–)
N3 Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(–); or

In a single ipsilateral node larger than 3 cm in greatest dimension and ENE(+); or
Multiple ipsilateral, contralateral, or bilateral nodes, any with ENE(+); or
A single contralateral node of any size and ENE(+)
N3a Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(–)
N3b Metastasis in a single ipsilateral node larger than 3 cm in greatest dimension and ENE(+); or
Multiple ipsilateral, contralateral, or bilateral nodes, any with ENE(+); or
A single contralateral node of any size and ENE(+)
NOTE: A designation of "U" or "L" may be used for any N category to indicate metastasis above the lower border of the
cricoid (U) or below the lower border of the cricoid (L).
Similarly, clinical and pathological ENE should be recorded as ENE(–) or ENE(+).
Distant metastasis (M)

M category M criteria
M0 No distant metastasis
M1 Distant metastasis
Prognostic stage groups

When T is... And N is... And M is... Then the stage group is...
Tis N0 M0 0
T1 N0 M0 I
T2 N0 M0 II
T3 N0 M0 III
T1 N1 M0 III
T2 N1 M0 III
T3 N1 M0 III
T1 N2 M0 IV
T2 N2 M0 IV
T3 N2 M0 IV
Any T N3 M0 IV
T4 Any N M0 IV
Any T Any N M1 IV
TNM: tumor, node, metastasis; AJCC: American Joint Committee on Cancer; UICC: Union for International Cancer Control; ENE:
extranodal extension.
Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the AJCC Cancer
Staging Manual, Eighth Edition (2017) published by Springer International Publishing. Corrected at 4th printing, 2018.

Brooke-Spiegler syndrome
(A) Adolescent patient with Brooke-Spiegler syndrome. This patient already has >50 papules on the temple and cheek ranging
from 1 to 6 mm in size.
(B) As patients with Brooke-Spiegler syndrome age, their adnexal tumors may increase in size to over 1 cm and develop
prominent telangiectasias.
https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usag… 100/102

Multiple cylindromas (turban tumor)
Large, confluent tumors in this patient with Brooke-Spiegler syndrome.

Contributor Disclosures
Jeffrey P North, MD Nothing to disclose Timothy H McCalmont, MD Nothing to disclose Beth S Ruben, MD Nothing to
disclose June K Robinson, MD Nothing to disclose Rosamaria Corona, MD, DSc Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by
vetting through a multi-level review process, and through requirements for references to be provided to support the
content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

Cutaneous Adnexal Tumors - UpToDate

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Cutaneous Adnexal Tumors - UpToDate

Uploaded by

Copyright:

Available Formats

17-05-2020 Cutaneous adnexal tumors - UpToDate

Official reprint from UpToDate®

● (See "Brooke-Spiegler syndrome (CYLD cutaneous syndrome)".)

https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage_… 1/102

https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage_… 2/102

● (See 'Eccrine and apocrine tumors' below.)

● CD34 – Marker of trichilemmal differentiation and positive in the stroma in trichodiscoma.

● Beta-catenin – Positive in hair matrical tumors (eg, pilomatricoma).

● Adipophilin – Marker of sebocytic lineage.

https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage_… 3/102

Differentiation of primary cutaneous adnexal carcinoma from metastatic adenocarcinoma — Significant

ECCRINE AND APOCRINE TUMORS

https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage_… 4/102

Histologically, the intraepidermal variant of poroma (hidroacanthoma simplex) resembles a seborrheic

https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage_… 5/102

Syringofibroadenoma — Typically regarded as an eccrine tumor, syringofibroadenoma is a superficial

Histologically, syringofibroadenoma is composed of thin, interconnecting strands of keratinocytes in a lattice

Syringocystadenoma papilliferum — Syringocystadenoma papilliferum (SCAP) is an adnexal tumor

https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage_… 6/102

Tubular/papillary adenoma, including papillary cystadenoma — Numerous reports have described

Histologically, tubular/papillary adenomas are well-circumscribed proliferations of small epithelial aggregations

https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage_… 7/102

Mucinous carcinoma and endocrine mucin-producing sweat gland carcinoma — Mucinous

https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage_… 8/102

https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage_… 9/102

disease of the vulva'.)

Cutaneous cribriform carcinoma — Cutaneous cribriform carcinoma (cutaneous apocrine cribriform

Trichoblastoma and trichoepithelioma — Trichoblastoma and trichoepithelioma are benign epithelial

Trichoadenoma — Trichoadenoma presents as a slow-growing, skin-colored papule on the face.

Trichofolliculoma — Trichofolliculoma is a rare hamartomatous lesion with follicular differentiation that

Trichilemmoma — Trichilemmoma (also known as tricholemmoma) is a benign follicular tumor with

Histopathologically, trichilemmoma exhibits a papillated, well-circumscribed, exo-endophytic growth pattern

Trichodiscoma and fibrofolliculoma — Although originally described as distinct entities, evidence

https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage… 11/102

Pilomatricoma — Pilomatricoma, also called pilomatrixoma or calcifying epithelioma of Malherbe exhibits

https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage… 12/102

Trichoblastic carcinoma — Malignant transformation of trichoblastoma is rare. The diagnosis is based

Trichilemmal carcinoma — Trichilemmal carcinoma is a rare malignant counterpart of trichilemmoma with

https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage… 13/102

TUMORS WITH SEBACEOUS DIFFERENTIATION

Histologically, sebaceous adenoma is composed of well-circumscribed, round aggregations of predominantly

https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage… 14/102

https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage… 15/102

https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage… 16/102

SYNDROMES ASSOCIATED WITH CUTANEOUS ADNEXAL TUMORS

Brooke-Spiegler syndrome — Brooke-Spiegler syndrome (BSS; MIM #605041) is a rare autosomal

Birt-Hogg-Dubé syndrome — Birt-Hogg-Dubé syndrome (BHDS; MIM #135150) is an autosomal dominant

SUMMARY AND RECOMMENDATIONS

Use of UpToDate is subject to the Subscription and License Agreement.

https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage… 18/102

7. Mayer I. Zur Histologie der Hidradenoma. Frankf Z Path 1941; 55:548.

10. Sariya D, Ruth K, Adams-McDonnell R, et al. Clinicopathologic correlation of cutaneous metastases:

https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage… 20/102

35. Noguchi M, Akiyama M, Kawakami M, et al. Eccrine syringofibroadenoma developing in a sebaceous

https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage… 21/102

73. Llamas-Velasco M, Mentzel T, Rütten A. Primary cutaneous secretory carcinoma: A previously

74. Plewig G. Sebaceous trichofolliculoma. J Cutan Pathol 1980; 7:394.

75. Rohwedder A, Keminer O, Hendricks C, Schaller J. Detection of HPV DNA in trichilemmomas by

76. Stierman S, Chen S, Nuovo G, Thomas J. Detection of human papillomavirus infection in

https://sibib2.ucm.cl:2141/contents/cutaneous-adnexal-tumors/print?search=patologia anexial&source=search_result&selectedTitle=4~150&usage… 24/102

92. Blaya B, Gonzalez-Hermosa R, Gardeazabal J, Diaz-Perez JL. Multiple pilomatricomas in association

94. Cambiaghi S, Ermacora E, Brusasco A, et al. Multiple pilomatricomas in Rubinstein-Taybi syndrome: a