Digital Papillary Adenocarcinoma in Nonacral Skin: Clinicopathologic and Genetic Characterization of 5 Cases.

Digital papillary adenocarcinoma (DPA) is a rare sweat gland neoplasm that has exceptionally been reported outside acral locations. Recently, human papillomavirus 42 was identified as the main oncogenic driver of DPA. Herein, we report 5 tumors arising in extra-acral locations predominantly in the female anogenital skin. Four patients were female and 1 patient was male. The mean age at the diagnosis time was 65 years (range: 55 to 82 y). Tumors were located on the vulva (n=3), perianal area (n=1), and forearm (n=1). Histologically, all tumors were lobular and mainly solid and composed of sheets of cells with rare focal papillae and frequent glandular structures in a "back-to-back" pattern and lined by atypical basophilic cells. Immunohistochemistry showed diffuse positivity for SOX10. Epithelial membrane antigen and carcinoembryonic antigen highlighted the luminal cells and staining for p63 and p40 revealed a consistent and continuous myoepithelial component around glandular structures. Follow-up was available in 3 cases (mean duration: 12 mo [range: 8 to 16 mo]). One patient developed local recurrence and 1 experienced regional lymph node metastases. HPV Capture Next-generation sequencing revealed the presence of the HPV42 genome in all samples. Viral reads distributions were compatible in the 5 cases with an episomal nature of the viral genome, with a recurrent deletion in the E1 and/or E2 open reading frames. In conclusion, this study demonstrates that digital DPA may rarely present in nonacral locations mainly in the female anogenital area, usually with a more solid pattern as compared with those cases presenting on the digits and it is also associated with HPV42.

Sweat Gland Tumors Arising on Acral Sites: A Molecular Survey.

Recurrent oncogenic drivers have been identified in a variety of sweat gland tumors. Recently, integration of human papillomavirus type 42 (HPV42) has been reported in digital papillary adenocarcinoma (DPA). The main objectives of the present study were (i) to provide an overview of the prevalence of previously identified oncogenic drivers in acral sweat gland tumors and (ii) to genetically characterize tumors in which no recurrent genetic alteration has been identified yet. Cases of acral sweat gland tumors were identified from the database of the French network CARADERM. After histologic review, the presence of previously identified genetic alterations was investigated in the entire cohort (n=79) using a combination of immunohistochemistry and targeted DNA and RNA sequencing. Tumor entities with no recurrent genetic alterations were submitted to whole-transcriptome sequencing. CRTC1::MAML2 fusion was identified in cases of hidradenoma and hidradenocarcinoma (n=9/12 and n=9/12). A p.V600E mutation of BRAF was observed in all cases of tubular adenoma (n=4). YAP1:MAML2 and YAP1::NUTM1 fusions were observed in poroid tumors (n=15/25). ETV6::NTRK3 and TRPS1::PLAG1 fusion transcripts were identified in secretory carcinoma (n=1/1) and cutaneous mixed tumors (n=3/4), respectively. The HPV42 genome was detected in most cases of DPA (n=10/11) and in 1 adnexal adenocarcinoma not otherwise specified. Finally, whole-transcriptome analysis revealed BRD3::NUTM1 or NSD3::NUTM1 fusions in 2 cases of NUT adnexal carcinoma and NCOA4::RET and CCDC6::RET fusion transcripts in 2 cystadenoma/hidrocystoma-like tumors. Our study confirms distinctive cytogenetic abnormalities in a wide number of acral adnexal neoplasms and supports the use of molecular analysis as a valuable aid in the diagnosis of these rare and often difficult to diagnose group of neoplasms.

Spiradenoma of the breast: a rare diagnostic pitfall in the evaluation of solid-basaloid breast lesions with a dual cell population.

Breast spiradenoma is extremely rare, with only 4 cases reported previously. We describe an instructive case of breast spiradenoma resembling adenoid cystic carcinoma (AdCC). A 71-year-old woman underwent excisional biopsy of a breast mass after a conclusive diagnosis was unable to be obtained from core needle biopsy showing an AdCC-like pattern. Histopathologically, the lesion demonstrated solid and cribriform foci comprising basaloid cells, luminal cells, and eosinophilic hyaline material, reminiscent of solid-basaloid AdCC, alongside convoluted lumens, stromal edema, lymphocytic infiltration, and c-kit negativity. On molecular analysis, neither MYB fusion genes nor CYLD gene abnormalities were identified. These results were supportive of spiradenoma. Salivary gland- and skin adnexal-type tumors are challenging to diagnose due to morphological overlaps. This case, highlighting histopathological and molecular features, shows that breast spiradenoma can be a diagnostic pitfall among the differential diagnoses of AdCC.

Clear Cell Hidradenoma-Basal Cell Carcinoma Collision.

ABSTRACT: A 91-year-old man presented with a tumor on the left temporal area, clinically suspicious of basal cell carcinoma. The histopathologic study showed a central solid-cystic tumor composed by 3 different types of cells (clear or finely granular cells, polygonal cells, and squamoid cells). It had a sclerotic stroma. At the periphery, another tumor composed by smaller interconnected nests was evident. Some nests were separated from the stroma by clefts. The stroma of this second tumor was highly cellular. There was a sharp delimitation between both tumors, with no transitional area. Immunochemistry demonstrated they are different tumor. A diagnosis of clear cell hidradenoma-basal cell carcinoma collision was performed. To the best of our knowledge, this is the first description of this challenging association.

MYB Translocations in Both Myoepithelial and Ductoglandular Epithelial Cells in Adenoid Cystic Carcinoma: A Histopathologic and Genetic Reappraisal in Six Primary Cutaneous Cases.

ABSTRACT: Adenoid cystic carcinoma (ACC) is an infiltrating carcinoma composed of 2 cell types, myoepithelial and ductoglandular epithelial cells. Although approximately 70% of ACC exhibit translocations of the MYB proto-oncogene or MYB proto-oncogene like 1 (MYBL1), expression of MYB is known to be limited in myoepithelial cells. We investigated the histopathologic and genetic characteristics of ACC in 6 primary cutaneous cases. Histopathologically, 3 cases (50%) exhibited well-demarcated nodules composed of large nests, easily misdiagnosed as polymorphous sweat gland carcinoma. Two cases (33%) harbored large cystic structures resembling spiradenoma, hidradenoma, and digital papillary adenocarcinoma. A papillary pattern was focally observed in 2 cases (33%). A melting phenomenon within the myxoid stroma was seen in one case (17%). Fluorescence in situ hybridization (FISH) revealed MYB break-apart in 3 cases (50%). A combined FISH and immunohistochemical method revealed MYB break-apart signals in both p63-positive myoepithelial and p63-negative ductoglandular epithelial cells, suggesting that both cell types constitute elements of the tumor in ACC. Moreover, we established a well-circumscribed variant of ACC and proposed 3 new patterns of cystic, papillary, and melting in addition to the 3 patterns of cribriform, tubular, and solid growth.

Mucinous Syringometaplasia: Surrounding Acanthosis With Hyperkeratosis Tends to Conceal the Change.

A 57-year-old man had a 2-year history of a painful nodule on the right sole. Physical examination revealed an 8 × 8 mm hyperkeratotic plaque with a central fissure. Excisional biopsy disclosed epithelial invagination surrounded by the acanthotic epidermis with parakeratotic hyperkeratosis and focal hypergranulosis. The invaginated epithelium lacked a cornified layer and was composed of a mixture of small basaloid squamous cells and goblet cells showing tubular structures. The patient was diagnosed with mucinous syringometaplasia. Our literature review established that surrounding acanthosis with hyperkeratosis typically tends to conceal mucinous syringometaplastic changes. Because mucinous syringometaplasia often presents as an asymptomatic papule/nodule with no distinct ulcer, fissure, or depressed area, cases may be overlooked.

An Update on Endocrine Mucin-producing Sweat Gland Carcinoma: Clinicopathologic Study of 63 Cases and Comparative Analysis.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare, low-grade adnexal neoplasm with predilection for the periorbital skin of older women. Histologically and immunophenotypically, EMPSGC is analogous to another neoplasm with neuroendocrine differentiation, solid papillary carcinoma of the breast. Both lesions are spatially associated with neuroendocrine mucinous adenocarcinomas of the skin and breast, respectively. EMPSGC is ostensibly a precursor of neuroendocrine-type mucinous sweat gland adenocarcinoma (MSC), a lesion of uncertain prognosis. Non-neuroendocrine MSC has been deemed locally aggressive with metastatic potential, and previous works speculated that EMPSGC-associated (neuroendocrine-type) MSC had similar recurrence and metastatic potential with implications for patient follow-up. Only 96 cases of EMPSGC have been reported (12 cases in the largest case series). Herein, we present 63 cases diagnosed as "EMPSGC" in comparison with aggregated results from known published EMPSGC cases. We aim to clarify the clinicopathologic features and prognostic significance of the neuroendocrine differentiation of EMPSGC and its associated adenocarcinoma and to determine the nosological relevance of EMPSGC association in the spectrum of MSC histopathogenesis. Results established an overall female predominance (66.7%) and average presenting age of 64 years. EMPSGC lesions were associated with adjacent MSC in 33.3% of cases. The recurrence rate for neuroendocrine-type MSC was ~21%, less than the reported 30% for non-neuroendocrine MSC. There were no cases of metastasis. EMPSGC and neuroendocrine-type MSC are distinct entities with more indolent behavior than previously reported, supporting a favorable prognosis for patients.

Clinicopathologic Characterization of Hidradenoma on Acral Sites: A Diagnostic Pitfall With Digital Papillary Adenocarcinoma.

Hidradenomas are benign sweat gland tumors that typically present as small nodules in adulthood. Their anatomic distribution is wide and rarely includes acral sites. In this setting, reliable separation from digital papillary adenocarcinoma is important, but notoriously difficult. Hematoxylin and eosin-stained sections of 25 hidradenomas on acral skin were retrieved. The clinical presenting features and morphologic findings were recorded, and follow-up was obtained. Immunohistochemistry was performed for AE1/3, CK5/6, EMA, CEA, SMA, S100, p40, and p63. The tumors presented as solitary nodules on the hands (n=17) and feet (n=8) of adults (age range: 20 to 81 y; median: 50 y), with an equal sex distribution. Histologically, the well-circumscribed tumors were lobular, with a solid and cystic growth within dermis. Duct and squamous differentiation and vascularized hyaline stroma were frequent. The majority (n=18) were poroid hidradenomas. Scattered cytologic atypia and mitotic activity (median: 2/10 HPF) were common, and a pseudoinfiltrative growth of strands in a hyaline to sclerotic matrix was noted in 5 tumors. No papillary structures, atypical mitoses, or tumor necrosis were present. Immunohistochemically, all tumors expressed AE1/3, CK5/6, p40, and p63 strongly and diffusely. Luminal differentiation was highlighted by epithelial membrane antigen and carcinoembryonic antigen staining. S100 and SMA staining was absent. Follow-up (1 to 288 mo; median: 61 mo), available for 20 patients, showed no local recurrences and no disease-related mortality. Acral hidradenomas and digital papillary adenocarcinomas share a well-circumscribed dermal growth pattern containing solid, cystic, and tubular areas with mitotic activity and at least focal cytologic atypia. Lack of papillary structures and the diffuse positivity for p40 and p63 in the absence of S100 and SMA expression are helpful features in favor of acral hidradenoma.

Renal Cell Carcinoma Antigen Expression in Primary Cutaneous Endocrine Mucinous Carcinomas: A Case Series of 14 Patients and Review of the Literature.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) and primary cutaneous mucinous carcinoma (PCMC) are both uncommon low-grade cutaneous adnexal tumors with predilection for the eyelids of elderly women. Their clinical appearance is nonspecific, typically presenting as a slowly growing poorly circumscribed papule, nodule, plaque, or swelling. Histological features of EMPSGC include a lobulated dermal neoplasm with bland cytology and an invasive mucinous component in up to half of the cases. PCMC exhibits tumor nests suspended in abundant pools of mucin with focal strands or nests of tumor cells infiltrating the dermis. Because of their rarity and banal cytological features, both entities pose a risk for misdiagnosis with other benign/malignant cutaneous adnexal neoplasms. Histomorphological features can suggest a diagnosis of EMPSGC or PCMC, but immunohistochemistry is necessary for confirmation. A review of the literature showed variable results of antigens present in EMPSGC, and many of the positive markers only show sparse or focal immunoreactivity of tumor cells. As a result, diffusely positive markers play a crucial role in identification of these tumors, particularly with initial superficial biopsies. We present 9 cases of EMPSGC and 5 cases of PCMC with strong and diffuse immunoreactivity to renal cell carcinoma antigen. This novel finding can be useful in the diagnosis of EMPSGC and PCMC in combination with other known positive markers to differentiate them from other cutaneous neoplasms. In addition, it provides further evidence that EMPSGC could be a precursor lesion to PCMC with both existing on a spectrum.

[Clinicopathologic characterization of malignant mixed tumor of the skin accompanied by eccrine porocarcinoma].

Objective: To investigate the clinicopathologic features, immunophenotype, pathological diagnosis and treatment of malignant mixed tumor (MMT). Methods: Clinical and pathological features including immunohistochemical phenotypes were analyzed in a case of MMT accompanied with eccrine porocarcinoma (EP) involving both hands, diagnosed definitely in January 2018 along with review of relevant literature. Results: A 64-year-old man presented with multiple rash on both hands for 4 years. Three lesions of 0.5 to 2.2 cm were removed for pathological evaluation. The pathological changes on little finger of left and right hands were MMT with EP, whereas that removed from the right ring finger was EP. MMT showed infiltrative growth with vascular wall invasion and consisted of epithelial (glandular or tube differentiation) and mesenchymal components (mucinous and/or cartilage stroma). The endothelial cells showed moderate to severe cytological atypia, nuclear pleomorphism and increased mitotic activity. The glandular component had histological characteristics of syringocarcinoma with moderately atypical chondrocytes but without myoepithelium. EP was composed of basal cells with visible vacuoles in cytoplasm and the presence of tubular and squamous differentiation, along with obvious atypia. Immunohistochemically cavosurface epithelium of glandular differentiation of MMT showed positivity for CK7, EMA and CD117. Myoepithelium showed S-100, CK5/6 and p63 positivity and stromal cells were positive for S-100. Differential diagnoses included metaplastic carcinoma, malignant myoepithelioma and atypical mixed tumor of skin. Conclusions: MMT with EP is extremely rare.The diagnosis of MMT depends on the morphologic features. Immunohistochemical staining is helpful for differential diagnosis. Surgical excision with safety margins is the treatment of choice. Complementary radiotherapy and/or chemotherapy is still controversial. The clinical course of MMT is deemed unpredictable and long-term follow-up is necessary.

Expression of growth hormone-releasing hormone receptors in apocrine adnexal tumours and apocrine glands of the skin.

Encouraged by our previous finding of growth hormone-releasing hormone receptor (GHRH-R) expression in metaplastic and neoplastic apocrine breast epithelium, we examined a small series of skin adnexal tumours with various degrees of apocrine (oxyphilic) differentiation, as well as normal axillary and anogenital apocrine sweat glands, for the expression of GHRH-R. Sections of formalin-fixed paraffin-embedded tissue blocks were immunostained for gross cystic disease fluid protein-15 (GCDFP-15) and androgen receptor (AR), to prove apocrine differentiation and correlate it with areas of GHRH-R expression. All but one of 19 tumours with apocrine epithelium and all five benign apocrine glands stained with both anti-GHRH-R antibodies used, each labelling a different domain of the receptor. Non-apocrine areas of the tumours and four eccrine tumours without oxyphilic features did not stain, but most sebaceous glands and some eccrine glands were labelled. Our data suggest that anti-GHRH-R antibodies highlight apocrine differentiation at extramammary sites also. Although GHRH-R seems to have a sensitivity comparable to classic apocrine markers such as AR and GCDFP-15, it seems to be inferior in specificity. The GHRH-R labelling of apocrine glands and neoplastic epithelium might also interfere with the emerging anti-GHRH targeted treatment of some malignancies acting on these receptors.

Cutaneous Apocrine Carcinoma With an In Situ Component and Histiocytoid and Signet-Ring Cells.

We present a case of cutaneous apocrine carcinoma arising in the axilla of a 71-year-old man. The tumor had a significant component of histiocytoid and signet-ring cells as well as in situ carcinoma within the apocrine glands. The cells expressed GATA3, gross cystic disease fluid protein 15, androgen receptor, and E-cadherin. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 were negative. Clinical correlation was required to rule out a metastasis from the breast or the gastrointestinal tract. Although most cutaneous apocrine carcinomas do not behave aggressively, our patient developed bone metastases and eventually died of his disease. It is debated whether histiocytoid and signet-ring cell cutaneous carcinomas should be classified as apocrine neoplasm. The presence of in situ carcinoma associated with this kind of tumor has been reported only once in the literature. This characteristic and the immunohistochemical profile are in favor of apocrine differentiation.

Aggressive Digital Papillary Adenocarcinoma With Multiple Organ Metastases: A Case Report and Review of the Literature.

Aggressive digital papillary adenocarcinoma (ADPA) is a rare sweat gland neoplasm with a high recurrence rate and metastatic potential. In this study, the authors describe a case that originally appeared to benign spiradenoma, but took an ominous course eventually resulting in the diagnosis of ADPA. A 73-year-old woman developed a gradually growing nodule on the second toe of her left foot, which she had first noticed 4 years previously. An excisional biopsy was performed followed by histological examination. The authors initially considered the tumor to be a benign spiradenoma and did not perform reexcision. However, she experienced local recurrence 24 months later, and multiple pulmonary metastasis 31 months later. On histological examination, both the primary and locally recurrent tumors were found to be composed of discrete and well-circumscribed solid nodules, lacking cystic space. All tumors (the primary tumor, locally recurrent tumor, and lung metastases) presented with a pattern of fused back-to-back tubular structures and myoepithelial differentiation confirmed by immunohistochemical examination. On the basis of these findings, the authors finally diagnosed ADPA with multiple pulmonary metastases. The patient underwent chemotherapy, but died of disease 49 months later. This case highlights the importance of high clinical suspicion of ADPA when digital lesions present.

High Relative Expression of Pannexin 3 (PANX3) in an Axillary Sweat Gland Carcinoma With Osteosarcomatous Transformation.

Primary cutaneous sweat gland carcinomas (SGCs) are rare tumors that commonly involve axillae, have a high local recurrence rate, and rarely show sarcomatoid transformation. A 68-year-old man presented with rapid enlargement of a previously stable, asymptomatic pea-sized nodule in the left axilla. Initial excision (with positive surgical margins) at another institution showed characteristic histologic features of a high-grade osteosarcoma and molecular analysis using a 92-gene real-time quantitative reverse transcription-polymerase chain reaction assay confirmed a diagnosis of osteosarcoma with 96% certainty. Notably, the molecular assay demonstrated consistently high relative expression of pannexin 3 (PANX3), a gene involved in normal osteoblast differentiation which, when highly expressed, strongly predicts osteosarcoma per the assay's algorithm. However, on further histologic review, the tumor also contained focal cystic areas, nests, and ducts composed of malignant epithelial cells reminiscent of SGC; these areas directly transitioned into the osteosarcomatous component and were strongly positive for pancytokeratin, CK7, and p63. Within 2 weeks, the lesion recurred and grew rapidly, prompting complete resection, histologic sections of which showed high-grade osteosarcoma without residual epithelial elements. This is the fifth report, to our knowledge, of osteosarcomatous transformation in a SGC, and the only report to date including molecular data. This case demonstrates that osteosarcoma arising from a SGC has a similar molecular profile to de novo primary osteosarcoma of bone. It also emphasizes the importance of histopathologic findings as the established diagnostic gold standard and the need to interpret molecular results within the clinical context.

Cutaneous Adenomyoepithelioma: Report of a Case and Review of the Literature.

Adenomyoepithelioma (AME) is a biphasic neoplasm of epithelial and myoepithelial cells. It is most commonly found in the breast, although rare cases have been reported from the lung, salivary glands, and skin. There are 5 well-documented cases of cutaneous AME in the literature. We report a new case of cutaneous AME. Our case was commingled with apocrine hidrocystoma. This is the first report of cutaneous AME in a male patient and the first to describe SOX10 immunostaining in cutaneous AME. We review the literature on cutaneous AME and note the greater than chance colocalization with other adnexal tumors. We speculate that AME may represent localized overgrowth of myoepithelial cells within a pre-existent sweat gland tumor. Histopathologists should be aware of the potential of SOX10-positive myoepithelial neoplasms to mimic nodular melanocytic proliferations.

Syringocystadenocarcinoma Papilliferum In Situ-Like Changes in Extramammary Paget Disease: A Report of 11 Cases.

The authors report 11 cases of extramammary Paget disease (EMPD), all of which also demonstrated a combination of histological changes highly reminiscent of syringocystadenocarcinoma papilliferum in situ. In addition to the classical features of EMPD, characterized by the intraepidermal spread of individually dispersed neoplastic cells with ample cytoplasm, many of which contained mucin, there were areas of acanthosis with the substitution of spinous layer keratinocytes by neoplastic cells, whereas the native basal cell layer was intact. In addition to acanthosis (and sometimes papillomatosis), the dermal papillae showed a prominent infiltrate of plasma cells, completing the resemblance to syringocystadenocarcinoma papilliferum in situ; this similarity was further enhanced in 2 cases, which showed conspicuous gland formation. One additional case showed multifocal dermal proliferations compatible with eccrine syringofibroadenoma (syringofibroadenomatous hyperplasia). The changes described herein seem to be relatively rare in EMPD, and they can represent a diagnostic pitfall, as evidenced by 2 cases that were originally misinterpreted as syringocystadenocarcinoma papilliferum in situ. Clinically, these microscopic changes sometimes corresponded to nodular lesions, which were specifically noted to have a papillated erosive surface.

"Apocrine Hidrocystoma and Cystadenoma"-like Tumor of the Digits or Toes: A Potential Diagnostic Pitfall of Digital Papillary Adenocarcinoma.

Digital papillary carcinoma (DPC) is a rare, underreported, and often misdiagnosed malignant tumor of the sweat glands. It is often located on the digits and toes and most commonly occurs in male individuals in their fifties to seventies. Because of lack of pain, slow growth, and an inconspicuous appearance, clinical diagnosis is often missed or delayed. In contrast, apocrine hidrocystoma (AH) is a cystic adenoma that arises from the apocrine secretory coil, and it is extremely rare for AHs to develop on the digits. We report 7 cases of DPC, including clinical course, histopathologic and immunohistochemical findings, and therapeutic approach in which the initial histopathologic diagnosis in all cases was AH or cystadenoma. However, complete excision of the neoplasms led to a final diagnosis of DPC. After an adequate treatment, no recurrence or metastasis was found in any of the cases described. All the cases studied showed similar histopathologic and immunohistochemical findings. The initial incisional biopsy showed large unilocular or multilocular cystic spaces situated within the dermis, lined by a double layer of epithelial cells with tiny papillary structures. No cellular atypia, necrosis, or pleomorphism was observed. However, complete excision revealed neoplastic lesions involving the dermis and/or subcutis, with an infiltrative pattern and papillary projections into luminal spaces. Immunoperoxidase studies showed positivity for CK7, S-100 protein, CEA, p63, smooth muscle actin, and calponin. DPC is a rare but life-threatening malignancy, therefore it is important to be able to identify such a lesion both clinically and histopathologically, treat it, and monitor the patient for the tumor's potential recurrence and metastasis. Pathologists and dermatopathologists should be aware that a histopathologic diagnosis of AH or cystadenoma on the fingers and toes should be established with caution, because probably those lesions represent the superficial and cystic component of an underlying DPC, and a wider excision should be performed.

A Comparative Study of Immunohistochemical Myoepithelial Cell Markers in Cutaneous Benign Cystic Apocrine Lesions.

The use of immunohistochemical markers for myoepithelial cells (MEC) is a useful tool in the distinction of benign from malignant epithelial neoplasms. Although their use in breast tumors is well recognized, little is known concerning its application in comparable cutaneous lesions. Using benign cutaneous cystic apocrine lesions as a study model, the aim of this study was to compare 5 immunohistochemical markers [calponin, p63, smooth muscle actin (SMA), cytokeratin 14, and CD10] in their effectiveness to highlight MEC. Cases of apocrine hidrocystoma and cystadenoma (n = 44) were reviewed with a particular emphasis on proliferative features and apocrine change. The MEC staining pattern and the intensity and distribution scores in proliferative (n = 29) and nonproliferative (n = 15) lesions were assessed, and the differences between the 2 groups were statistically analyzed using Fisher exact test. Calponin and SMA stained MEC in the most consistent manner. Being a nuclear stain, p63 was easy to interpret but typically showed discontinuous staining. Cytokeratin 14 not only effectively highlighted MEC but also stained some luminal epithelial cells in an unpredictable manner. Because of prominent background dermal fibroblast staining, CD10 was often difficult to interpret. Only SMA and p63 showed a statistically significant difference in MEC staining intensity scores between the proliferative and nonproliferative groups. Our results show that immunohistological staining for MEC in benign cystic apocrine lesions of the skin is variable. The authors recommend that a panel of markers that includes calponin and p63 be used and highlight the need for awareness of specific caveats associated with individual markers.