J Cutan Pathol 2012: 39: 279–285doi: 10.1111/j.1600-0560.2011.01807.xJohn Wiley & Sons. Printed in Singapore

Copyright © 2011 John Wiley & Sons A/S

Journal ofCutaneous Pathology

Cutaneous myoepithelioma arisingwithin hidradenoma of the scalp

A 62-year-old man presented with a 2-year history of a 2-cm cysticmass involving his occiput. There had been recent enlargement, andthe clinical impression was that of a pilar cyst. Histopathologicalsections showed a partially dermal solid and cystic proliferation. Thetumor contained areas of glandular differentiation with cuboidal tocolumnar cells lining luminal and cystic spaces. A concurrent spindlecell proliferation was seen interspersed between glands and also formedbroad, cellular sheets of cells. The stroma was sclerotic and withoutchondroid or myxoid elements. Immunohistochemistry showed that thespindled cells expressed S100 protein, cytokeratin and smooth musclemyosin. The immunohistochemical profile and the relationship withductal elements supported myoepithelial differentiation. Theproliferation warranted the diagnosis of myoepithelioma arising from ahidradenoma, which to our knowledge has not been previouslydescribed. In addition to discussing this case, we provide a brief reviewof epithelial–myoepithelial neoplasms encountered in the skin.

Keywords: adnexal neoplasms, hidradenoma, histopathology,immunoperoxidase, myoepithelioma

Jakate K, Wong K, Sirbovan J, Hanna W. Cutaneous myoepitheliomaarising within hidradenoma of the scalp.J Cutan Pathol 2012; 39: 279–285. © 2011 John Wiley & Sons A/S.

Kiran Jakate1, Kevin Wong2,Jane Sirbovan3

and Wedad Hanna1,4

1Department of Laboratory Medicine andPathobiology, University of Toronto, Toronto,Ontario, Canada,2Department of General Surgery, TheScarborough Hospital, Toronto, OntarioCanada,3Department of Pathology, The ScarboroughHospital, Toronto, Ontario Canada, and4Department of Anatomical Pathology,Sunnybrook Health Sciences Centre, Toronto,Ontario, Canada

Dr Wedad Hanna,Sunnybrook Health Sciences Centre,2075 Bayview Ave., Room E4 32, Toronto,ON M4N 3M5, CanadaTel.: +416 480 6100 ext. 3565Fax: +416 480 4271e-mail: wedad.hanna@sunnybrook.ca

Accepted for publication August 23, 2011

IntroductionEpithelial–myoepithelial neoplasms are encounteredin the salivary gland, breast and lung and are alsorarely encountered in the skin. These entities crossa spectrum from benign to malignant, and whetherbiphasic or monophasic differentiation is observeddepends on the relative proportion of myoepithelialcells. A benign proliferation of myoepithelial cellsin the absence of duct formation constitutesa myoepithelioma. Cutaneous proliferations ofmyoepithelial cells are most commonly seen inassociation with mixed tumors of the skin. Wereport a case of myoepithelioma arising within ahidradenoma of the scalp. To our knowledge, this isthe first report in the English literature of such a case.

Report of a caseA 62-year-old man presented with a 2-cm cysticmass involving his occiput. He had been aware of the

process for 2 years and it had recently enlarged.While this was associated with some discomfortinitially, the pain later subsided. There was hairloss over the lesion; no ulceration or epidermalabnormalities were noted. The clinical impressionwas that of a pilar cyst. The patient had a historyof hypertension and hypercholesterolemia and wason medications related to both conditions. He wasotherwise healthy. The lesion was excised under localanesthetic. The entire specimen was submitted forpathological examination. Paraffin-embedded tissuesections were cut at 4-μ thickness and were stainedwith hematoxylin and eosin. Based upon microscopicevaluation, a diagnosis of myoepithelioma arisingfrom a hidradenoma was rendered. After diagnosis,the site of occurrence was re-excised, and there hasbeen no evidence of recurrence after 5 months.

Pathologically, the gross specimen consisted of agray–white nodule measuring 2 cm in maximumdimension. The cut surface was solid, tan and

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Fig. 1. A panoramic scan of all tumor pieces is apparent (hematoxylinand eosin).

friable in some areas. Microscopic sections showedfragments of a solid and cystic mass, whichappeared dermal-based, although epidermis wasnot seen (Fig. 1). The tumor contained areas ofglandular differentiation (Fig. 2A–C) with cuboidalto columnar secretory cells lining luminal andcystic spaces. Some glands showed overt apocrinedifferentiation (Fig. 2C). There were also nodularaggregates of poroid cells punctuated by ducts. Clearcells were not identified. The glandular luminaranged from large and irregular to tubular. Abasal layer of cells was seen lining many of theglands. The stroma was focally sclerotic (Fig. 3A–C)and the overall appearance was consistent with ahidradenoma.

A second component consisted of a spindle cellproliferation that was focally interspersed among theglandular elements and also formed broad, cellularaggregates arranged in short fascicles (Fig. 4A–D).The spindled cells had eosinophilic cytoplasm andovoid nuclei. Mitoses were infrequent (1/10 high-power fields), and there was no necrosis, substantialcellular atypicality or atypical mitotic figures. Ductswere inconspicuous in the diffusely spindled areas.Chondroid or myxoid stroma or mesenchymalelements were not seen.

Immunohistochemical staining showed that thespindled cells expressed S100 protein, high and lowmolecular weight cytokeratins, and smooth muscle

Table 1. Source, dilution and antigen retrieval for antibodies labelingmyoepithelial cells

Antibodies Clone Source DilutionAntigenretrieval

S100 4C4.9 Ventana, Tucson,AZ, USA

Pre-diluted None

CK5/6 D5 &16B4 Ventana Pre-diluted HIER∗

SMM SMMS-1 Ventana Pre-diluted HIER∗

LMWK CAM5.2 BD Biosciences,Franklin Lakes,NJ, USA

1 : 25 Protease

HIER, Heat-induced epitope retrieval; CK5/6, cytokeratin 5/6; SMM,smooth muscle myosin; LMWK, low molecular weight cytokeratin.∗HIER using ethylenediaminetetraacetic acid buffer, pH 8.0 at 95◦Cfor 64 min.

myosin (Fig. 5A–C). Sources, dilutions and antigenretrieval methods for these antibodies are providedin Table 1. Epithelial membrane antigen (EMA)stained the glands with accentuation of the lumina,as would be expected with glandular differentiation.The spindled cells lacked expression of Melan-A, c-kit and CD34. The proliferative index measured byKi-67 was less than 2%. The immunophenotype andthe relationship of spindled elements with the ductalelements suggested myoepithelial differentiation.The observed features warranted the diagnosis ofmyoepithelioma arising within a hidradenoma.

DiscussionMyoepithelial cells have variable morphology andmay be spindled, epithelioid and plasmacytoidin configuration. Cytoplasm can be eosinophilicor clear. Immunohistochemical staining patternsof myoepithelium reflect their dual myoid andepithelioid phenotype. Over 95% of myoepithelialcells will exhibit some cytokeratin positivity and mostwill also show S100 protein expression.1 Smoothmuscle markers such as actin, myosin and calponinmay also be expressed, while desmin staining isnegative. Other possible positive stains include EMA,glial fibrillary acidic protein and vimentin.2

In the skin, myoepithelial cells line the ductsof eccrine and apocrine glands. They are not anuncommon finding in glandular neoplasms suchas hidrocystoma, tubular adenoma, hidradenomapapilliferum and syringocystadenoma papilliferum.Myoepithelial cells do not obviously populatehidradenomas, which are benign glandular adnexalneoplasms of apocrine or eccrine lineage. Thearchitectural pattern of hidradenoma is mostoften nodular, and varying ductal or glandulararrangements can be seen.1

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Cutaneous myoepithelioma arising within hidradenoma of the scalp

A B

C

Fig. 2. The glandular hidradenoma component is illustrated at increasing magnification (panels A–C). Overt apocrine differentiation isapparent at high magnification (panel C).

Among epithelial–myoepithelial tumors that canbe encountered in the skin (Table 2) mixed tumors(chondroid syringomas) are the most common.Similar to its salivary gland counterpart, pleomorphicadenoma, cutaneous mixed tumor is composed ofvarying proportions of epithelial and myoepithelialcomponents set within chondroid, myxoid orfibrous stroma. Squamous, adipocytic and bonydifferentiation can also be observed. The overallmitotic index tends to be low (<2/10 high poweredfield). Infiltrative growth, cellular pleomorphism or

necrosis should raise suspicion of the possibility ofmalignant mixed tumor.1

Tumors comprised entirely of myoepithelial cellsand lacking glandular differentiation are termedmyoepitheliomas. They are rare in the skin andoften present as a painless nodule of variableduration.3 Our case was somewhat unusual asits clinical presentation was as a cystic lesion.Histopathologically, most reported cases are wellcircumscribed and confined to the dermis. Myxoidchange in the stroma is common; the presence of

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A B

C

Fig. 3. The glandular hidradenoma component was surrounded by stroma that was focally sclerotic (panels A–C).

mature adipocytes has also been reported.2– 4 Themitotic index can vary (ranging from 0 to 6 per10 high-power fields). In a study of eight cutaneouscases, three recurred locally within 2 years of surgicalexcision. One showed lymph nodal metastasis after5 years.3 Overt features of malignancy raise thepossibility of myoepithelial carcinoma, although thisentity is exceedingly rare in the skin.5

Mixed tumors may harbor focal secondarymyoepithelial cell proliferations. Because of this

and their shared myxoid stroma, mixed tumorsand myoepitheliomas are thought to representsimilar entities along the same continuum.2 Neitherchondroid nor myxoid stroma was identified in ourcase; therefore interpretation as a mixed tumorwith myoepithelioma-like areas was not appropriate.However, the stroma of our case was focally sclerotic,as is characteristic of hidradenoma. By convention,myoepitheliomas are free of glandular differentiation.Although our tumor had clear epithelial areas,

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Cutaneous myoepithelioma arising within hidradenoma of the scalp

A B

C D

Fig. 4. Sheets of spindled myoepithelial cells were contiguous to the glandular elements in a distinct nodule (panels A–D). At high magnification,no cellular atypicality or necrosis is appreciable (panels C–D).

the solid, sheet-like foci of myoepithelial cellswithin our lesion compelled us to recognizemyoepithelioma as a distinct component of theproliferation.

Adenomyoepitheliomas consist of myoepithelialcell proliferations around well-formed, roundedepithelium-lined spaces. Adenomyoepitheliomasare found most frequently in the breast, andmalignant transformation has been described.Rare cutaneous examples have been reported6,7

but experience with the risk of recurrence ormalignancy in the skin is limited.5 Interestingly, sixtumors with combined adenomyoepithelioma and

spiradenoma-like features have been documented.6,7

In one such case, nests of myoepithelial cells weredescribed but constituted a minor component ofthe lesion.6 Although in our case myoepithelial cellswere focally observed interspersed among glandularlumina, these glands showed variable sizes andshapes. Adenomyoepitheliomas are generally solidlesions.

In conclusion, epithelial–myoepithelial and glan-dular adnexal neoplasms of the skin are bothprone to variations in appearance that canmake interpretation and classification a challenge.

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A B

C

Fig. 5. Immunoperoxidase staining showed diffuse expression of S100 protein (panel A), patchy expression of smooth muscle myosin (panelB), and intense expression of low molecular weight keratin (panel C).

Table 2. Epithelial–myoepithelial tumors encountered in the skin

Tumors Differentiation Pathologic features

Myoepithelioma Monophasic Well circumscribed, cytologically bland myoepithelialproliferation without admixed glandular elements

Adenomyoepithelioma Biphasic Myoepithelial cells arrayed around well-formedepithelial-lined spaces

Mixed tumor Biphasic Well circumscribed, epithelial and myoepithelial proliferationwith chondroid, myxoid or fibrous stroma

Malignant mixed tumor Biphasic Infiltrative, with variable atypicality in epithelial andmesenchymal components; zones of necrosis may be seen

Myoepithelial carcinoma Monophasic Infiltrative, with nuclear atypicality and increased mitoticindex (>3–4/10 high-power field); tumor necrosis may beseen

We present a case in which these two tumortypes converge in a combination not previouslydescribed. We suggest a diagnosis of myoepitheliomaarising within a hidradenoma based upon thepresence of two distinct morphologies, namely

classic hidradenoma-like areas in conjunction withsheets of myoepithelial cells without ducts, andalso based upon exclusion of other adnexal orepithelial–myoepithelial tumors from the differentialdiagnosis.

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