Malignant Hidradenoma - Anticancer Research

ANTICANCER RESEARCH 26: 2217-2220 (2006)
Malignant Hidradenoma: A Report of Two Cases
and Review of the Literature
Abstract. Introduction: Malignant tumors of the sweat glands
are very rare. Clear cell hidradenoma is a lesion with
histopathological features resembling those of eccrine poroma
and eccrine spiradenoma. The biological behavior of the tumor
is aggressive, with local recurrences reported in more than 50%
of the surgically-treated cases. Materials and Methods: Two
patients are presented, the first with tumor in the right axillary
region, the second with a recurrent tumor of the abdominal
wall. The first patient underwent wide excision with clear
margins and axillary lymph node dissection and the second
patient underwent wide excision of the primary lesion and
bilateral inguinal node dissection due to palpable nodes.
Results: The patients had uneventful postoperative courses. No
additional treatment was administered. However, sixteen
months after surgery, patient 2 developed extensive and massive
recurrence involving almost the whole abdominal wall.
Although he had received several chemotherapeutic agents, the
disease had a relentless course and the patient succumbed two
and a half years following surgery. Conclusion: Malignant
tumors of the sweat glands are very rare neoplasms with no
discrete clinical characteristics. It is necessary to suspect any
lesion which shows evidence of enlargement and to verify its
status by histological evaluation. Additional resection is
generally required, with at least 2-cm clear margins, since
surgery is the only effective treatment.
Malignant tumors of the sweat glands represent rare
oncological entities, characterized by non-specific clinical
presentation and equivocal pathological features. Their
precise diagnosis and histological classification can be very
Correspondence to: Dimitris P. Korkolis, MD, Ph.D., 22 Socratous
St., 1st Floor, Kifissia 14561 Athens, Greece. Tel: +30 210 8083
743, Fax: +30 210 8012 689, Cell: 6937 30 7272, e-mail:
dkorkolis_2000@yahoo.com
Key Words: Sweat gland tumor, malignant hidradenoma, eccrine
poroma, spiradenoma.
I.E. LIAPAKIS 1 , D.P. KORKOLIS 2 , A. KOUTSOUMBI 3 ,
A. FIDA 3 , G. KOKKALIS 1 and P.P. VASSILOPOULOS 2
1 Department of Plastic and Reconstructive Surgery, 2 First Department of Surgical Oncology and
3 Department of Surgical Pathology, Hellenic Anticancer Institute, "Saint Savvas" Hospital, Athens, Greece
0250-7005/2006 $2.00+.40
difficult (1). Clear cell hidradenoma is an extremely rare
tumor with less than 50 cases reported (2, 3).
The cases of two patients, suffering from aggressive
dermal lesions invading the abdominal wall and the axillary
region, are described here. Surgical resection and
histopathological examination ascertained the presence of
malignant clear cell hidradenoma. In addition to these
cases, a review of the literature is also presented.
Case Reports
Patient 1. Patient 1 was a 68-year-old Caucasian male who had
undergone excision of a rapidly growing, ulcerous lesion of the
anterior surface of the abdominal wall in another hospital.
Histology revealed an eccrine spiradenoma of the sweat glands
with squamous differentiation and intense desmoplastic
reaction. The tumor had invaded the dermal lymphatic vessels
and the subcutaneous fat. The margins of resection were free
of disease. During the following six months, the patient
developed multiple satellite nodules and was admitted to our
institution for further diagnosis and treatment. The complete
blood work up, as well as a CT scan of the abdomen and chest,
were normal. Lymphoscintigraphy, however, was positive for
bilateral inguinal nodal disease. Fine-needle aspiration biopsy
of both the skin lesions and enlarged inguinal nodes was
positive for malignancy, suggesting a poorly-differentiated,
metastatic adenocarcinoma. The patient underwent wide local
excision of the abdominal wall nodules with 2-cm margins of
resection, as well as formal bilateral inguinal lymphadenectomy.
From the pathology report the presence of a clear
cell hidradenoma arising from the sweat glands, with multiple
nodal metastases, was ascertained (Figure 1). No adjuvant
treatment was given. The patient died nine months later from
disseminated disease.
Patient 2. The second patient was a 45-year-old Caucasian
male who had undergone excisional biopsy of a whitish
lump, 2 cm in size, arising in the right axillary region. The
histopathological examination was suggestive of a nodular
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Figure 1. Microscopical image of the clear cell hidradenoma arising from
the anterior abdominal wall. A) Elements of tubular and solid neoplastic
configuration arising in the vicinity of a hair follicle. B) Malignant cells
with clear, transparent cytoplasm and round nucleus.
hidradenoma with clear cells and a low grade of malignancy
(Figure 2). The patient was then admitted to the hospital
for a complete wide resection and radical axillary lymphadenectomy.
The pathology report revealed no residual
disease or nodal metastases. Six months after resection, the
patient is doing well with no evidence of recurrence.
Discussion
The recognition of hidradenoma as a distinct entity was first
reported in 1941 by Mayer, whereas the term “clear cell
hidradenoma” was proposed in 1954 by Keasby and Hadley
(4). The malignant form of hidradenoma is extremely rare,
with less than 50 cases ever reported in the literature. All
these cases were characterized by a significant rate of
locoregional recurrence. Some patients developed distant
metastatic spread as well (3, 5). The disease is usually
expressed as a small intradermal mass which remains
inactive for a long period of time before increasing in size.
Its aggressive behavior is more apparent after each local
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ANTICANCER RESEARCH 26: 2217-2220 (2006)
Figure 2. Histological features of the axillary hidradenoma. A) Malignant
cells with eosinophilic cytoplasm and nuclear atypia. B) Intradermal
development of malignancy and separation from the epidermis with a
fibrous sheath.
relapse with faster growth and invasion of the surrounding
tissues. In most cases, no epidermal participation is
encountered. Hidradenoma usually affects middle-aged
women, although its malignant form shows no age or gender
predilection (6-8).
Malignant hidradenoma is usually found in the scalp, face
or anterior surface of the trunk. Regional lymphadenopathy,
with or without serous discharge, may develop years after
initial treatment. Wong et al. (5) described three patients
suffering from clear cell hidradenoma who developed
metastatic disease in the regional lymphatic basins 8-22
years after initial surgical extirpation.
Histologically, clear cell hidradenoma seems to originate
from the ductal epithelium of the sweat glands, whereas
histogenetically it appears to represent a transitional
tumor, sharing features of eccrine poroma and eccrine
spiradenoma (6).

Currently, there is no clear distinction between eccrine
and apocrine glands, or between their malignant
counterparts. The characterization of a sweat gland tumor,
however, as of eccrine or apocrine origin, still remains
useful (9, 10). In general, clear cell hidradenoma is
considered to have an eccrine background, although quite
recently Gianotti and Alessi (11) supported an apocrine
histology based on their own series of five consecutive cases.
Clear cell hidradenoma consists of two main cell
subpopulations. The first one is composed of round or
polygonic cells with round nuclei and clear cytoplasm, which
is the result of abundant glycogen storage. The second
subpopulation consists of multifaceted cells comprised of
oval nuclei and basophilic cytoplasm evenly arranged at the
periphery of the first cellular line (12). Clear cells may be
also seen in other, more frequent malignancies of the head
and neck, such as squamous and basaloid tumors, as well as
in metastatic deposits of renal cell carcinoma (6).
The recognition of the eccrine origin of a malignant
hidradenoma may be accomplished through specific
immunohistochemical techniques, a positive PAS stain, as
well as with the presence of lobules with epidermal
differentiation (5, 13-15).
Clear cell hidradenoma may contain keratinocytes
forming keratin congregates (13). In addition, some cystic
configurations noted on the specimen most probably
represent empty spaces between degenerated cells rather
than ductal formations of the tumor itself (6).
Malignant clear cell hidradenoma usually develops de novo
and invades the dermis and subcutaneous tissue. Surprisingly,
it might share significant histopathological features with its
benign form. The mitotic index may not be representative or
may affect only a small cellular subpopulation. Thereafter,
the diagnosis of malignancy through standard pathological
examination may prove extremely difficult (16).
In our small series, it was interesting to note that, in
contrast to the final diagnosis, previous pathology reports had
ascertained the presence of an eccrine spiradenoma. The
latter is a benign tumor of the sweat glands with similar
clinical presentation and equivocal enzyme reactions, which
pose tremendous diagnostic dilemmas (12). Because of the
rarity of these oncological entities, as well as their
histopathological similarity, it is almost impossible to define
whether a malignant clear cell hidradenoma had been
developed from a benign eccrine spiradenoma or was the
correct diagnosis from the beginning.
The most recent reports support the fact that malignant
clear cell hidradenoma should be considered as a distinct
entity rather than the result of a malignant transformation of
its benign type, underlining the importance of a precise initial
diagnosis (7, 17). Rosen et al. (19) presented a case of a clear
cell hidradenoma of the eyelid complicated by multiple
recurrences and invasion of nearby structures. Histologically,
Liapakis et al: Malignant Hidradenoma
no atypia or increased nuclear mitoses were found. The
precise identification of a benign or malignant hidradenoma,
based on pathological examination, was not possible. Similar
findings were noted in other case reports of clear cell
hidradenoma (20-25).
Surgical excision remains the therapeutic modality of
choice. Wong et al. (5) supported wide surgical resection
with a least 2 cm of clear margins for both primary disease
and local recurrences. Elective regional lymphadenectomy
after lymphoscintigraphy should also be performed. The
role of sentinel lymph node biopsy in the treatment of
malignant hidradenoma is controversial. Locoregional
recurrence even after wide surgical excision has been
reported in more than 50% of cases, although overall and
disease-free survival rates are hard to determine as the
result of the very limited number of reported cases (18).
Adjuvant chemotherapy and radiotherapy have no impact
in local control or survival (26).
In conclusion, malignant clear cell hidradenoma is a rare
oncological entity, with no particular clinical or
histopathological features. It should be included in the
differential diagnosis of dermal lesions with an aggressive
behavior and multiple recurrences, despite aggressive
surgical treatment.
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Received February 16, 2006
Accepted March 31, 2006