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Hidradenoma Papilliferum: A Clinicopathologic Study of 264 Tumors From
261 Patients, With Emphasis on Mammary-Type Alterations
Konstantinova, Anastasia M; Michal, Michal; Kacerovska, Denisa; Spagnolo, Dominic V; Stewart, Colin
J; Kutzner, Heinz; Zelger, Bernhard; Plaza, Jose A; Denisjuk, Natalja; Hejda, Vaclav; Shelekhova,
Ksenya; Bisceglia, Michele; Danis, Dusan; Zamecnik, Michal; Kerl, Katrin; Guenova, Emmanuella;
Kazakov, Dmitry V
Abstract: Hidradenoma papilliferum (HP), also known as papillary hidradenoma, is the most common
benign lesion of the female anogenital area derived from anogenital mammary-like glands (AGMLG).
HP can be viewed conceptually as the cutaneous counterpart of mammary intraductal papilloma. The
authors have studied 264 cases of HP, detailing various changes in the tumor and adjacent AGMLG, with
emphasis on mammary-type alterations. In many HP, the authors noticed changes typical for benign
breast lesions, such as sclerosing adenosis-like changes, usual, and atypical ductal hyperplasia. Almost in
a third of cases, remnants of AGMLG adjacent to the lesion were evident, manifesting columnar changes
reminiscent of those seen in breast lesions. This study shows that the histopathological changes in HP
run a broad spectrum comparable with that in the mammary counterpart and benign breast disease.
DOI: https://doi.org/10.1097/DAD.0000000000000495
Posted at the Zurich Open Repository and Archive, University of Zurich
ZORA URL: https://doi.org/10.5167/uzh-130109
Published Version
Originally published at:
Konstantinova, Anastasia M; Michal, Michal; Kacerovska, Denisa; Spagnolo, Dominic V; Stewart, Colin
J; Kutzner, Heinz; Zelger, Bernhard; Plaza, Jose A; Denisjuk, Natalja; Hejda, Vaclav; Shelekhova,
Ksenya; Bisceglia, Michele; Danis, Dusan; Zamecnik, Michal; Kerl, Katrin; Guenova, Emmanuella;
Kazakov, Dmitry V (2016). Hidradenoma Papilliferum: A Clinicopathologic Study of 264 Tumors From
261 Patients, With Emphasis on Mammary-Type Alterations. American Journal of Dermatopathology,
38(8):598-607.
DOI: https://doi.org/10.1097/DAD.0000000000000495
ORIGINAL STUDY
Hidradenoma Papilliferum: A Clinicopathologic Study of
264 Tumors From 261 Patients, With Emphasis on
Mammary-Type Alterations
Anastasia M. Konstantinova, MD, PhD,*† Michal Michal, MD,‡§ Denisa Kacerovska, MD, PhD,‡§
Dominic V. Spagnolo, MBBS, FRCPA,¶k Colin J. Stewart, FRCPA,** Heinz Kutzner, MD,††
Bernhard Zelger, MD, MSc,‡‡ Jose A. Plaza, MD,§§ Natalja Denisjuk, MD,¶¶ Vaclav Hejda, MD,kk
Ksenya Shelekhova, MD, PhD,**** Michele Bisceglia, MD,††† Dusan Danis, MD,‡‡‡
Michal Zamecnik, MD,§§§ Katrin Kerl, MD,¶¶¶ Emmanuella Guenova, MD, PhD,¶¶¶
and Dmitry V. Kazakov, MD, PhD‡§
Abstract: Hidradenoma papilliferum (HP), also known as
papillary hidradenoma, is the most common benign lesion of the
female anogenital area derived from anogenital mammary-like
glands (AGMLG). HP can be viewed conceptually as the
cutaneous counterpart of mammary intraductal papilloma. The
authors have studied 264 cases of HP, detailing various changes in
the tumor and adjacent AGMLG, with emphasis on mammarytype alterations. In many HP, the authors noticed changes typical
for benign breast lesions, such as sclerosing adenosis-like
changes, usual, and atypical ductal hyperplasia. Almost in a third
of cases, remnants of AGMLG adjacent to the lesion were evident,
manifesting columnar changes reminiscent of those seen in breast
lesions. This study shows that the histopathological changes in HP
run a broad spectrum comparable with that in the mammary
counterpart and benign breast disease.
From the *Department of Pathology, Clinical Research and Practical Center for
Specialized Oncological Care, Saint–Petersburg, Russia; †Department of
Pathology, Medical Faculty, Saint–Petersburg State University, Saint–
Petersburg, Russia; ‡Sikl’s Department of Pathology, Medical Faculty in
Pilsen, Charles University in Prague, Pilsen, Czech Republic; §Bioptical
Laboratory, Pilsen, Czech Republic; ¶PathWest Laboratory Medicine WA,
QEII Medical Centre, Nedlands, Australia; kSchool of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Australia;
**PathWest Laboratory Medicine WA, King Edward Memorial Hospital,
Perth, Australia; ††Dermatopathologische Gemeinschaftspraxis, Friedrichshafen, Germany; ‡‡Clinical Department of Dermatology and Venereology, Medical University Innsbruck, Innsbruck, Austria; §§Division of
Dermatopathology, Department of Pathology, Medical College of Wisconsin, Milwaukee, WI; ¶¶Dermatopathology Institute, Zürich, Switzerland;
kkDepartment of Pathology, Institute for the Care of Mother and Child,
Prague, Czech Republic; ***Department of Pathology, Petrov’s Research
Institute of Oncology, Saint–Petersburg, Russia; †††Unit of Anatomic
Pathology, School of Biomedical Sciences, Etromapmacs Pole, Lesina
(FG), Italy; ‡‡‡Cytopathos Laboratory, Bratislava, Slovak Republic;
§§§Agel Laboratory of Pathology, Novy Jicin, Czech Republic; and
¶¶¶Department of Dermatology, Zurich University Hospital, Zurich, Switzerland.
The authors declare no conflicts of interest.
Reprints: Dmitry V. Kazakov, MD, Sikl’s Department of Pathology, Charles
University Medical Faculty Hospital, Alej Svobody 80, 304 60 Pilsen,
Czech Republic (e-mail: kazakov@medima.cz).
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Key Words: hidradenoma papilliferum, anogenital mammarylike glands, vulva, skin, sclerosing adenosis, extramammary
Paget disease
(Am J Dermatopathol 2016;38:598–607)
INTRODUCTION
Hidradenoma papilliferum (HP), also known as papillary hidradenoma, is the most common benign lesion of
female anogenital area derived from anogenital mammarylike glands (AGMLG). The latter are a normal constituent of
the anogenital area.1–5 Lesions affecting AGMLG are histopathologically very similar, if not identical, to those seen in
the breast.6–8 HP can be viewed conceptually as the cutaneous
counterpart of mammary intraductal papilloma.9–12 Previous
case reports and case series demonstrated a number of metaplastic and hyperplastic changes in HP and demonstrated
a relationship to AGMLG, but no systemic study on the morphological spectrum of this neoplasm has been performed. In
this report, we present a histopathological study of 264 cases
of HP, detailing various changes in the tumor and adjacent
AGMLG, with emphasis on mammary-type alterations.
MATERIAL AND METHODS
Case Inclusion/Exclusion
A search in the consultation and routine institutional
files of the authors between 1993 and 2015 years yielded 272
cases coded as HP involving the anogenital area. Hematoxylin–eosin-stained slides were reviewed to confirm the diagnosis. The histopathological findings were correlated with the
clinical data to confirm the location and appropriate clinicopathological context. Eight cases were excluded (3 fibroadenomas, 2 syringocystadenoma papillifera, 1 vulvar lesion
having features of mammary-type fibrocystic disease). Also,
excluded was a case showing mixed features of fibroadenoma, and HP and another previously published HP with a ductal in situ carcinoma component.13 Thus, 264 tumors from
261 patients were included in the study.
Am J Dermatopathol Volume 38, Number 8, August 2016
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Am J Dermatopathol Volume 38, Number 8, August 2016
TABLE 1. Age Distribution of Patients With HP
Age Group, yr*
20–29
30–39
40–49
50–59
60–69
70–79
80–89
Hidradenoma Papilliferum
TABLE 2. Distribution of HP in the Anogenital Area
No. Cases (%)
14
46
70
62
34
20
2
(5.7)
(18.5)
(28.2)
(25)
(13.7)
(8.1)
(0.7)
*At the time of HP excision.
Light Microscopic Studies
The number of tissue blocks available for review
varied from 1 to 3. The following histopathological
features were assessed: connection of the lesion with
a follicular infundibulum or with the overlying epidermis,
ulceration of the overlying epidermis/epithelium, pseudocarcinomatous hyperplasia, prominent tumor necrosis, and
cystic alteration.
For the epithelial and myoepithelial components,
the following features were evaluated: metaplasia (oxyphilic, mucinous, and squamous), clear cell change of the
luminal epithelial cells (so-called “lamprocytes”) and
Location (n = 264)
No. Cases
Vulva, NOS
Labium major
Labium minus
Sulcus interlabialis
Vulvar commissure
Vulvar introitus
Periclitoral
Perianal/anal
Perineum
Gluteal region
Anogenital, NOS
Unknown
100
48
26
9
3
2
1
37
10
1
18
9
NOS, not otherwise specified.
myoepithelial cells, myoepithelial cell hyperplasia, presence of intraluminal macrophages, or deposits of calcium.
Cases suspicious of mucinous metaplasia were stained
with alcian blue and mucicarmine. When the above
changes involved more than 25% of the neoplasm, they
were referred to as prominent.
Mammary-type ductal changes including usual ductal
hyperplasia and atypical ductal hyperplasia were defined
according to Rosai.14 Usual ductal hyperplasia was applied
for an intraluminal proliferation of cells without atypia;
some lesions show a solid pattern with “streaming” cellular
growth pattern.15 Atypical ductal hyperplasia was defined as
a marked intraluminal proliferation of cuboidal epithelial
cells with increased nuclear to cytoplasmic ratio, forming
TABLE 3. Clinical Diagnoses (When Available) in HP
Clinical Diagnoses (n = 143)
FIGURE 1. HP. A solitary nodule in the perianal area.
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No. Cases
Cyst
Fibroma
Atheroma
Lipoma
Verruca
Papilloma
Hidradenoma
Granuloma
Hemorrhoids
Polyp
Pyogenic granuloma
Vulvar cancer
Angiomyxoma
Apocrine gland carcinoma
Condyloma
Endometriosis
Fibrolipoma
Folliculitis
Hemangioma
Sebaceous cyst
Syringocystadenoma papilliferum
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28
25
5
4
3
3
2
2
2
2
2
1
1
1
1
1
1
1
1
1
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Am J Dermatopathol Volume 38, Number 8, August 2016
Konstantinova et al
TABLE 4. Histopathological Features of HP
Histopathological Features (n = 264)
Epithelial component changes
Metaplasia
Oxyphilic
Squamous
Mucinous
Mammary-type alterations
Lamprocyte-like cells
Usual ductal hyperplasia-like
changes
Atypical ductal hyperplasia-like
changes
Solid growth pattern
Streaming growth pattern
Adenosis-like changes
Sclerosing adenosis-like changes
Myoepithelial changes
Clear cell change
Hyperplasia
Stromal component changes
Sclerosis
Focal hyperplasia of myofibroblastlike cells
Foamy macrophages
Calcium deposits
Giant cells
Other features
Prominent cystic change
Association with EMPD
Connection with the overlying
epidermis (with/without plasma cell
stromal infiltrate)
Connection with follicular
infundibulum (with/without plasma
cell stromal infiltrate)
Ulceration of the epidermis
Pseudoepitheliomatous hyperplasia of
the epidermis
Foamy macrophages within the lumina
of the tubules
Calcium within the lumina of the
tubules
Tumor necrosis
Remnants of AGMLG
Normal
Columnar cell change
Columnar cell hyperplasia
With surrounding inflammation
Cystic change
Frequency
95 (36%), prominent—10 (4%)
3 (1%)
2 (,1%)
3 (1%)
60 (23%)
14 (5%)
37 (14%)
22 (8%)
16 (6%)
15 (6%)
45 (17%)
3 (1%)
myoepithelial cell layer, and which lie in a sclerotic
stroma.16,17
The following stromal features were evaluated: stromal
sclerosis, focal hyperplasia of myofibroblast-like cells, the
presence of foamy macrophages or giant cells, calcifications,
and abundant plasma cells.
The presence of normal AGMLG remnants adjacent to
the lesion was recorded, and also columnar cell change or
columnar cell hyperplasia in these glands. Columnar cell
change was defined as variably dilated lumina lined by 1–2
cell layers of elongated to ovoid columnar epithelial cells
oriented perpendicularly to the basement membrane, having
apical cytoplasmic blebs or snouts.7 Columnar cell hyperplasia appeared as variably dilated lumina lined by more than 2
cell layers of elongated to ovoid columnar epithelial cells
oriented perpendicularly to the basement membrane, having
apical cytoplasmic blebs or snouts.7
Any other unusual features, if present, were also
recorded. The size of the tumor was recorded in all patients
either from medical charts or, when not available, measured
on histopathological slides directly.
37 (14%)
6 (2%)
18 (7%)
1 (,1%)
1 (,1%)
19 (7%)
2 (,1%)
39/5 (15/2%)
3/8 (1/3%)
14 (5%)
1 (,1%)
61 (23%)
2 (,1%)
6
72
40
27
13
2
1
(2%)
(27%)
(56%)
(38%)
(18%)
(3%)
(1%)
RESULTS
Clinical Data
All patients were women, whose ages at the time of
diagnosis ranged from 25 to 82 years (median: 49 years;
mean: 49.9 years) (Table 1). In 13 cases, the age of patients
was unknown. The duration was known in 25 cases, ranging
from 2 to 120 months (median: 12 months; mean: 22.8
months). In almost half of the patients (44%), the tumor
had been present for less than 1 year. In all but 1 case, the
lesions were solitary and occurred in the anogenital area (Fig.
1). One patient presented with 4 tumors. The location was
unknown in 9 cases. Most involved the vulva (71.6%) and
less frequently the perianal (14%) and perineal (3.8%) regions
(Table 2). The neoplasms ranged in size from 2 to 20 mm in
largest dimension (median: 7 mm; mean: 7.3 mm). The clinical diagnosis was suggested in 143 cases (Table 3); the most
frequent diagnoses were a cyst (39.2%), fibroma (19.6%),
atheroma (17.5%), lipoma (3.5%), and verruca (2.8%). None
of these 143 lesions was suspected to be a HP.
Histopathological Data
complex architectural patterns including micropapillae, true
papillae, and cribriform spaces with Roman bridges, but
with mild or no cytological atypia. Mammary-type adenosis-like changes were also recorded and whenever possible
classified into sclerosing adenosis or other forms. Sclerosing adenosis was defined as a compact proliferation of small
ductal structures with luminal epithelial cells, which are
often atrophic and attenuated, have a preserved peripheral
All tumors had a similar microscopic appearance
(Table 4). They were intradermal solid–cystic nodules with
a complex pattern of branching and anastomosing tubules
interconnected in a labyrinthine manner, with bands of
fibrous tissue between them, focally forming papillae (Fig.
2A). The tubules and papillae were by a luminal layer of epithelial cells surrounded by a layer of myoepithelial cells. Decapitation secretion was a common feature. Nineteen cases (7.2%)
were predominantly and markedly cystic (Fig. 2B). In 44
(16.7%) specimens, a connection with the overlying epidermis
was noted and in the overwhelming majority of these (39/44,
89%), there was a dense plasma cell stromal infiltrate (Fig. 3A).
Less frequently (11 cases, 4.2%), there was a connection with
a follicular infundibulum (Fig. 3B). Ulceration of the epidermis
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Hidradenoma Papilliferum
FIGURE 2. HP. Intradermal solid–
cystic neoplasm with a complex
pattern of branching and anastomosing tubules and papillae (A).
Prominent cystic change (B).
FIGURE 3. HP. Connection to the
overlying epidermis. Note a plasma
cell-rich
infiltrate
occasioning
a resemblance to syringocystadenoma papilliferum (A). Connection
to the follicular infundibulum (B).
FIGURE 4. HP with oxyphilic metaplasia (A, B), streaming growth
pattern and foamy macrophages
within the lumina of the tubules (B).
Note multiple areas with oxyphilic
metaplasia (A).
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Konstantinova et al
FIGURE 5. Mucinous metaplasia in HP.
FIGURE 6. Clear cell change of the luminal epithelial cells.
was encountered in 14 cases (5.3%) and a single case manifested pseudoepitheliomatous hyperplasia. In 6 cases (2.3%),
there was considerable necrosis.
The most common type of metaplasia of the epithelium
was oxyphilic (Fig. 4A, B), which was usually multifocal and,
in 10 cases (3.8%), it involved more than half of the lesion.
The metaplastic cells had brightly eosinophilic cytoplasm,
sometimes with discernable intracytoplasmic zymogen granules. Focally, these cells sometimes showed moderate cellular
and nuclear pleomorphism with conspicuous nucleoli. Squamous and mucinous metaplasia (Fig. 5) were found only in 3
and 2 cases, respectively. The presence of intracellular mucin
Am J Dermatopathol Volume 38, Number 8, August 2016
was confirmed by positive staining with alcian blue and mucicarmine. Three lesions exhibited clear cell change of the
luminal epithelial cells (so-called lamprocytes—a rare benign
finding in the breast described by Skorpil) (Fig. 6),10 whereas
focal clear cell change in the abluminal myoepithelial cells
was a more common feature (17% of cases) (Fig. 7A, B).10,18
Fifteen (5.7%) HP showed changes resembling mammary sclerosing adenosis (Fig. 8A, B). So-called usual ductal
hyperplasia was always a focal finding and occurred in 60
cases (22.7%) (Fig. 9A). In 36 cases with usual ductal hyperplasia, prominent intraluminal proliferation resulted in a focal
solid growth pattern, with features of the so-called “streaming
growth pattern” seen in mammary epitheliosis (as defined by
Azzopardi) identified in 22 cases (Fig. 10).15 Atypical ductal
hyperplasia was observed in 14 cases (5.3%) (Fig. 9B).
With respect to changes in the stromal component,
sclerosis was observed in 37 cases (14.0%), whereas focal
hyperplasia of myofibroblast-like cells was seen in 6 cases
(2.3%) (Fig. 11). The presence of foamy macrophages was
not an uncommon finding; in 61 cases (23.1%), they were
seen within the lumina of the tubules (Fig. 3A), and in 18
cases (6.8%), they were in the stroma.
Almost in a third of cases, remnants of AGMLG
adjacent to the lesion were evident (Fig. 12A). In more than
half of cases (40 cases), the epithelium lining these glands
appeared normal; rarely, it manifested columnar cell change
(27 cases) (Fig. 12B) or columnar cell hyperplasia (13 cases)
(Fig. 12C). Occasionally, combinations of normal epithelium
and columnar cell change were seen within 1 slide.
Two cases in our study were unusual in that they
showed a combination of HP and extramammary Paget
disease (EMPD), with large carcinoma cells having abundant
pale cytoplasm infiltrating the overlying epidermis (Fig. 13).
DISCUSSION
HP is the most frequent benign neoplasm involving
AGMLG. It was first described in 1878 by Werth.19 Since that
time, different authors have suggested various theories relating to pathogenesis and origins of the tumor, including sweat
gland origin, association with, or resemblance to, the Wolffian apparatus, cystadenoma, and intraductal papilloma of the
breast.9,20 Van der Putte proposed the existence of AGMLG
as a normal constituent of the anogenital area, in contrast to
the traditional view that these represented ectopic breast
FIGURE 7. Clear cell change of the
abluminal myoepithelial cells (A, B).
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Am J Dermatopathol Volume 38, Number 8, August 2016
Hidradenoma Papilliferum
FIGURE 8. Sclerosing adenosis in
HP (A, B).
FIGURE 9. HP with usual (A) and
atypical (B) ductal hyperplasia.
FIGURE 10. HP with solid and streaming growth pattern.
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FIGURE 11. HP with a prominent hyperplasia of stromal myofibroblast-like cells.
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Konstantinova et al
Am J Dermatopathol Volume 38, Number 8, August 2016
FIGURE 12. HP with adjacent remnants of AGMLG, a feature recognized in a third of cases (A).
Columnar cell change (B) and
columnar cell hyperplasia (C) in the
epithelium lining these glands.
tissue.1–5 This origin of HP explains its resemblance to mammary intraductal papilloma. Hormonal influences and a role
for the human papillomavirus (HPV) in the etiology of disease have been suggested, but HPV is detected only in
a minority of cases, suggesting that HPV has an unlikely
causal role.10,21
In our study, in almost one-third of cases, we noticed
the presence of AGMLG remnants adjacent to the lesion,
strongly suggesting a histopathogenetic association of HP
with AGMLG. The epithelium lining these glands appeared
normal (56%) or manifested alterations compatible with
columnar cell change (38%) or columnar cell hyperplasia
(18%) as defined in breast pathology. Sometimes normal
epithelium and columnar cell change/hyperplasia coexisted.
We and others have shown that HP is characterized by
great cytoarchitectural variability, sometimes within the same
tumor.7,9,10,12,20 In this study, some tumors were essentially
solid and composed of papillary and tubular areas, whereas
others were predominantly cystic lesions. Both locations
within a large cystic duct and massive necrosis are seen sometimes in breast intraductal papilloma.14,22 In addition, we
observed a range of other morphological features analogous
to those occurring in benign breast disease. These included
sclerosing adenosis-like changes, atypical and usual ductal
604
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FIGURE 13. HP associated with EMPD. Note the intraepidermal carcinoma cells above the HP.
hyperplasia and solid and streaming growth patterns. These
features may impart unusual appearances and should not be
misinterpreted as malignant. The recognition of myoepithelial
cells in areas of solid growth aid in the distinction from
invasive carcinoma.10
Some HP have a connection to the epidermis or
follicular infundibulum, often accompanied by a subepidermal
plasma cell infiltrate, thus occasioning a resemblance to
syringocystadenoma papilliferum.23–25 In fact, some reported
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Hidradenoma Papilliferum
cases of syringocystadenoma papilliferum in the anogenital
area likely represent this occurrence.
The most common type of metaplasia of the epithelium was oxyphilic. The exact nature of this change remains
unknown.10 It can occur due to a plethora of nonribosomal
cytoplasmic organelles.26 The term “apocrine metaplasia” is
used for such changes in breast pathology, but we prefer
oxyphilic as HP manifests apocrine differentiation, so the
term apocrine metaplasia would be an oxymoron. Besides
occurring in intraductal papilloma, oxyphilic metaplasia is
most frequently observed in the epithelium of simple cysts
and hyperplastic ducts, in sclerosing adenosis, fibroadenomas, and other benign epithelial proliferations, both in orthotopic breast and in lesions of AGMLG.10,14 Sometimes
these cells show moderate cellular and nuclear pleomorphism consistent with apocrine adenosis. It is important
not to confuse this change, especially in areas of solid
growth, with adenocarcinoma.7
Squamous metaplasia was a rare finding in our and
other studies.9 This change also can be seen in breast intraductal papilloma.22,27 The presence of an extensive squamous component in a mammary lesion should raise the
suspicion of malignancy.14 The rarest cell types, as found
by others,12 were mucinous and clear cells, the latter being
a degenerative phenomenon.12,28 Clear epithelial cells can
be found in breast lesions and sometime are termed lamprocytes.10 Rarely, clear cells can imitate sebocytes as in
a case of intraductal papilloma.27 Clear cell change involving myoepithelial cells proved to be a more frequent feature
(17% of cases).
The presence of foamy macrophages in HP was not
an uncommon finding, occurring within the lumina of the
tubules (23%) and in the stroma (7%). Such cells, with
a centrally located nucleus and a markedly vacuolated
cytoplasm,
morphologically
resembled
sebaceous
cells.29,30 With respect to the breast, Damiani et al31 reported similar stromal and intraluminal foamy cells in 50
benign breast lesions. HP also can be a part of complex
neoplastic lesions involving AGMLG. Two cases with
mixed histopathological features of fibroadenoma and
HP and pseudoangiomatous stromal hyperplasia have been
reported.32,33
HP can rarely be seen in association with different
benign and malignant diseases, including Bartholin gland
abscess,34 melanoma,35 and squamous cell carcinoma.36 An
extremely rare occurrence is concomitant presentation of
EMPD and HP, previously reported twice.35,37 In our study
2 cases showed a combination of HP and EMPD. In 1 case,
HP was present beneath the intraepidermal areas affected
by the EMPD, whereas in the second case, HP and EMPD
were present in different blocks. The differential diagnosis
for the latter instance is Toker cell hyperplasia. Clear cells
of Toker (intraepithelial cells found in normal nipples and
in association with AGMLG of the vulva as a normal constituent of genital skin) have been hypothesized to be a precursor of both mammary and EMPD some cases.5–8,38
Toker cell hyperplasia has been described both in breast
and in extramammary locations. However, there are no
strict criteria for distinguishing Toker cell hyperplasia
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Am J Dermatopathol Volume 38, Number 8, August 2016
Konstantinova et al
and incipient EMPD.39,40 In our cases, the diagnosis of
EMPD did not pose a problem, as there were large carcinoma cells having abundant pale cytoplasm infiltrating the
epidermis along the affected areas.
The clinical data of patients from our study in terms of
the age, location, clinical presentation, duration of the disease,
and size of the lesion corroborate the previously published
data9,12,20,28 HP affects almost always white women.9,12,20,28,41
Only a single case of anogenital (perianal) HP has been
described in a male.42 All but 1 HP in our series were solitary
and small. Only 1 woman presented with 4 lesions involving
both labia majora. Multiple HP have been described but are
rare. Woodworth et al20 reported 3 patients who had
multiple vulvar HP, 1 patient having 3 lesions, and 2 patients each having 2 lesions. Meeker et al 9 also reported 2
patients each having 2 tumors. Also rare are reports of
lesions exceeding 2 cm.43,44
HP is a benign lesion with good prognosis. The mitotic
index in these lesions can be often high (up to 13/10 highpower field), but it does not predict a more aggressive
outcome.11 In most of the cases, only surgical removal is
required to cure the patient.41 Because of the recognized
benignity of the lesions, no follow-up was obtained.
In conclusion, we present the largest series of HP,
detailing a wide spectrum of morphological changes that may
occur in these lesions and adjacent AGMLG, analogous to
those occurring in breast and benign breast conditions. Some
changes may impart unusual histological appearances and
thus represent a diagnostic pitfall; however, keeping in mind,
analogies with breast pathology will aid in the correct
interpretation of the alterations.
1. van der Putte SC. Anogenital “sweat” glands. Histology and pathology of
a gland that may mimic mammary glands. Am J Dermatopathol. 1991;
13:557–567.
2. Van der Putte SC. Ultrastructure of the human anogenital “sweat” gland.
Anat Rec. 1993;235:583–590.
3. van der Putte SC. Mammary–like glands of the vulva and their disorders.
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