Search

Abstract: Mixed tumor of the skin (MTS) is a tumor characterized by folliculosebaceous-apocrine differentiation. Because of the wide range of histological variations, understanding the unique features of MTS can help improve diagnosis. This study describes the histopathological characteristics of MTS, mainly apocrine-type MTS (AMT), using 166 cases of AMT. We found that nodular aggregates of myoepithelial cells, mucinous changes in the stroma, and follicular differentiation were standard characteristic features of MTS. Among the cases studied, 67% showed prominent follicular germinative cells and 40% showed prominent lipomatous metaplasia in the stroma. These cases often pose difficulties for the diagnosis of AMT because of insufficient evidence of sweat glands or myoepithelial cell differentiation. This is the first study to examine how the histological features of AMT change as the tumor extends deeper into the dermis. We found that the proportion of AMT with folliculosebaceous differentiation and large lumina increased as it got deeper into the dermis. Histopathological diagnosis of MTS is vital because the clinical symptoms lack specificity. This study enhances our understanding of the histopathological characteristics of MTS., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: A 77-year-old Japanese man presented to our hospital with subcutaneous tumors of the right upper arm and axilla. A biopsy revealed a cutaneous adnexal tumor, showing apocrine differentiation, and axillary lymph node metastasis. After chemoradiotherapy to shrink the tumors, both lesions were resected. A resected specimen of the arm tumor showed a variegated histology: (1) a classic sebaceoma with an organoid pattern and sebocytes; (2) a sebaceous tumor with cellular atypia; (3) a papillotubular tumor showing a biphasic pattern of pale eosinophilic cells with apocrine differentiation and basaloid cells; and (4) an invasive adenocarcinoma with a micropapillary structure, reminiscent of an invasive micropapillary carcinoma of the breast. The axillary tumor was regressed. To our knowledge, this is the first reported case of an adnexal tumor of the skin with an invasive micropapillary structure arising in a sebaceous tumor., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Apocrine hidrocystomas are benign, cystic neoplastic lesions resulting from the apocrine secretory component of the sweat gland. They most commonly occur on the head and neck, with predilection to the periorbital area. Less frequent sites include the axilla, nipple, external auditory canal, foreskin, conjunctiva, lower lip, and fingers, among others. The authors report a unique case of a nail bed hidrocystoma in a 55-year-old woman, a site not previously described., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Mucinous metaplasia (goblet cell type) is exceptionally rare in the skin. This is the second case of apocrine papillary hidrocystoma with mucinous metaplasia (goblet cell type) and a review of the literature exploring the significance and frequency of mucinous metaplasia with goblet cells in nongenital skin. The patient is an elderly man who presented with a blue-pigmented nodule on the scalp that was clinically suggestive of an atypical nevus. Histologically, the lesion was composed of a simple cyst of cuboidal cells with decapitation secretion and mucinous metaplasia with goblet cells. Papillary formation was identified in the cysts. Most cases of cutaneous mucinous metaplasia have been reported on genital skin, usually after chronic inflammation of the area. This type of mucinous metaplasia is categorized as benign mucinous metaplasia of the genitalia (BMM) and is believed to be unrelated to apocrine glands owing to the different histologic features and absence of apocrine differentiation by immunohistochemistry. Mucinous metaplasia (goblet cell type) has been previously reported in benign adnexal tumors (eccrine acrospiroma/hidroadenoma, mixed tumor, and syringocystadenoma papilliferum) and in malignant tumors (apocrine hidradenocarcinoma and squamous cell carcinoma). To date, mucinous metaplasia has not been identified in the histologically normal apocrine glands., Competing Interests: This manuscript has not been published previously and is not currently under review for publication elsewhere. There are no conflicts of interest to disclose at the time of writing. Please contact us with any questions or concerns, and thank you for your consideration., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Moll gland is a modified tubular-shaped apocrine sweat gland, which is located on the margin of the eyelid. Moll glands are also known as ciliary glands. The function of these glands was not well known for a long time. However, based on the different studies, it was proved that Moll glands are active from birth and have local immunologic function producing immunoglobulin A. We present a case of Moll adenocarcinoma, a type of apocrine carcinoma, arising from the right upper eyelid of a 57-year-old man. Although Moll gland cysts are frequently seen, this type of adnexal malignancy is extremely uncommon. These tumors can have variable presentation and behavior from less invasive forms to highly malignant metastatic recurrent lesions., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Apocrine hamartoma is a rare benign neoplasm. The histology is characterized by an excess of apocrine glands located predominantly in the reticular dermis. Pigmented apocrine hamartoma represents a histopathological variation of apocrine hamartoma containing tubules and linear cysts covered by apocrine cells on the inside with melanin and on the outside with myoepithelial cells. At this time, 4 cases of this pathology have been described. This case report aims to present a case of pigmented apocrine hamartoma of the vulva in a young patient, emphasizing that while occurrence is rare, it must be considered when diagnosing a pigmented lesion of the vulva in young patients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Apocrine chromhidrosis is a rare diagnosis that occurs due to colored sweat being secreted from the apocrine glands, which are located in the axillae, anogenital skin, and areolae and over the skin of the trunk, face, and scalp. We present the case of a 65-year-old woman who presented with a sudden onset of pink sweating affecting mainly her axillae but also her pelvis, causing staining of clothing and bed sheets. There was nil to note on examination and histology with immunostaining demonstrated focally prominent yellow-brown lipofuscin granules in the cytoplasm of the apocrine secretory cells confirming the diagnosis. The disease can have a significant psychosocial impact, and treatment remains challenging. Our case is unique because the red and pink coloring of sweat is less common in cases of apocrine chromhidrosis, which is often in favor of darker colored sweat, and the distribution involved the inguinal canal, which is also less often seen.

Apocrine hidradenomas (AH) once believed to harbor myoepithelial cells are now considered pure epithelial neoplasms. They are categorized separately from adenomyoepitheliomas which consist of apocrine epithelial and myoepithelial components. Reports of myoepithelial tumors arising in AH have suggested a link between the 2. Our goal was to explore whether cases diagnosed on routine microscopy as AH harbored occult myoepithelial elements, which would be disclosed by an immunohistochemical evaluation. Twenty-nine such cases, derived from a teaching collection of one of the authors, formed the basis of the study. Clinical and demographic data were documented, and morphological details of the cases were recorded. A panel of immunohistochemistry (AE1AE3, CK8/18, epithelial membrane antigen, p63, S100 protein, glial fibrillary acid protein, calponin, alpha actin, and others), designed to identify myoepithelial cells, was used. The population consisted of 14 women and 15 men (mean age 55.8; range 26-82 years). The tumors, located on the head/neck (14), limbs (10), and trunk (5), were solid (2) and solid/cystic (27). They exhibited varied (often combined) cytological elements (clear, squamoid, polygonal, and mucinous cells). On immunohistochemistry, aggregates of myoepithelial cells were identified in 5 (17%) cases. Four were calponin+ and AE1AE3+; they occupied ≤30% of tumor volumes and exhibited fusiform cytomorphology. One was S100 protein+ and AE1AE3+; it occupied 70% of tumor volume and exhibited polygonal cytomorphology. The gradation in the volume of myoepithelial elements disclosed by immunohistochemistry in a subset of our cases suggests that AH and adenomyoepitheliomas exist on a biological continuum of adnexal neoplasia. The diagnostic categorization of lesions with dual elements requires further study, but we propose that the term adenomyoepithelioma be restricted to those in which myoepithelial cells constitute ≥25% of tumor volume.

A hybrid cyst is a cutaneous cyst combining different types of keratinization of those seen in the folliculo-sebaceous-apocrine unit. Previous reports found that it may be occasionally associated with Gardner syndrome. This study aimed to clarify the pathologic findings and clinical significance of hybrid cyst based on case series observations. We retrospectively reviewed patients who fulfilled the pathological criteria of hybrid cyst from 2001 to 2015. The patient profiles, clinical presentations, pathological findings, and associated diseases were analyzed by reviewing the medical records and slides. A total of 71 hybrid cysts were confirmed over the study period. There were 12 pathologic variants. The most frequent variant was combined infundibular cyst and tricholemmal cyst (22 in 71 cases, 30%), followed by infundibular cyst and pilomatricoma (14 in 71 cases, 19%). There was no significant association between sex, age, or site and the pathological type of hybrid cyst. Neither extra-intestinal manifestation nor a family history of Gardner syndrome was found in any case. Hybrid cysts could contain a variety of combinations of components from the folliculo-sebaceous-apocrine unit. No clinical significance was found between demographics and the type of hybrid cyst. No association with Gardner syndrome was identified in this case series.

Syringocystadenoma papilliferum (SCAP), apocrine gland cyst (AGC, also called apocrine hidrocystoma or apocrine cystadenoma), and tubular papillary adenoma (TPA) with apocrine differentiation are defined as proliferations of apocrine epithelium with myoepithelial cells. At Sapporo Dermatopathology Institute, we retrieved 308 benign neoplastic lesions diagnosed as SCAP, AGC, or TPA and combinations of these entities. Among the 308 lesions, 202 (66%) exhibited features of only one type, of which 144 (47%) were AGC, 39 (13%) were TPA, and 19 (6%) were SCAP. The other 106 lesions (34%) had features of 2 or more types, including 56 lesions that were AGC + TPA (18%), 2 that were AGC + SCAP (1%), 34 that were TPA + SCAP (11%), and 14 that were AGC + TPA + SCAP (5%). The most frequent site of these lesions was the face (56%), followed by the scalp (13%). Lesions with the features of AGC were more frequently found on the face, especially the periocular region, than at other sites. TPA lesions were more frequent on the face and scalp than at other sites, whereas SCAP lesions were preferentially found on the face, scalp, and trunk. We also retrieved clinicopathological data and other information. We propose a unifying concept for AGC, TPA, and SCAP. Approximately one-third of these lesions are composite entities with the features of 2 or 3 different tumors, and we propose calling such tumors tubulopapillary cystic adenoma with apocrine differentiation.

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.

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.

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.

Apocrine fibroadenoma (AFA) is a common benign entity found in the breast but is rarely seen at other sites. Several studies have documented cases in the anogenital region, but to date, there have been only 4 cases (excluding the current case) of an AFA located in the skin on other parts of the body. The authors present a case of a 66-year-old woman with a 6-year history of a slow growing red nodule on her face. The histopathologic diagnosis was consistent with an AFA. An extensive review of the literature to elucidate a possible pathogenesis of these lesions and relationship to the anogenital counterparts is presented.

Background: Hidradenitis suppurativa (HS) is an inflammatory follicular skin disease. In women and men, the condition starts after puberty, has a peak in the third decade, and is rare after the menopause in women. This age distribution suggests a hormonal influence in the pathogenesis of the disease. We therefore hypothesized that apocrine glands in HS patients have a different expression of androgen receptor (AR) and estrogen receptor (ER) compared with healthy skin., Methods: Axillary, inguinal, and perianal skin biopsies from female and male patients with HS were immunohistochemically stained for AR and ER activities. Expression of both receptors in apocrine glands of HS patients was compared with expression in apocrine glands in normal axillary or inguinal skin of a control group of women., Results: Twenty-two patients with HS were included (16 women), with 10 women in the control group. In the HS group, apocrine glands were present in 11 out of 22 skin biopsies and in the control group in 4 out of 10 biopsies. Expression of ER in the apocrine gland was weak and observed in 2 out of 4 patients in the control group and in none of the HS patients. Expression of the AR was strong and observed in all apocrine glands in both groups., Conclusions: We could not demonstrate a significant difference in the expression of ER and AR in apocrine glands in skin biopsies of patients with HS, compared with healthy skin biopsies. The exact relation between sex hormones and occurrence of HS therefore remains unclear.

: The authors present 2 cases of a subcutaneous biphasic synovial sarcoma with marked apocrine differentiation that potentially may be confused with cutaneous epithelial neoplasms, including malignant apocrine mixed tumor or metaplastic carcinoma with an apocrine glandular component. Microscopically, both neoplasms had a biphasic architecture with the epithelial and spindle cell components. The epithelial component was prominent and consisted of simple glands with round lumina and complex glandular structures with intraluminal bridges forming cribriform areas. The glands were lined by cuboidal to columnar cells with eosinophilic or clear cytoplasm manifesting apical apocrine-like and intraluminal eosinophilic secretions. The spindle cell component was less prominent and was composed of relatively uniform or slightly atypical spindle sells surrounding and merging focally with the glandular structures. Immunohistochemically, the tumor cells in both components were positive for vimentin, AE1/AE3, CK7, and epithelial membrane antigen. Desmin, smooth muscle actin, muscle-specific actin, CD34, and S-100 protein were all negative. SYT-SSX1 gene fusion using fluorescence in situ hybridization and RT-PCR methods was detected in both cases.

Chromhidrosis is a rare idiopathic disorder characterized by colored secretions most typically from the malar cheeks, axilla, or areolar regions. Histologically, chromhidrosis is notable for glandular structures with decapitation secretion indicating ectopic apocrine glands in the dermis, and the presence of lipofuscin pigments under ultraviolet fluorescence and in cytology smears. This case report describes a 26-year-old man who presented with a 2- to 3-year history of black-colored secretions on the bilateral malar cheeks, present on exertion or with squeezing of the cheeks. A 3-mm punch biopsy of the left cheek demonstrated histopathologic findings characteristic of chromhidrosis under hematoxylin and eosin staining and ultraviolet fluorescence. To our best knowledge, this is the second case report in the literature of an adult male being affected by chromhidrosis, and the first of an adult male with black-colored malar cheek secretions in chromhidrosis.

Dermatofibromas (DFs) are common benign fibrohistiocytic lesions, mostly affecting young adults. Many types of DF have been described, depending on architectural, cellular, and stromal peculiarities. Recently, a peculiar type of benign cutaneous tumor showing hemosiderotic DF-like stroma and apocrine glands has been described. We report 2 additional cases of DF without hemosiderotic changes showing entrapped apocrine glandular structures. We speculate about the origin of the glandular component and propose the term adenodermatofibroma for this type of lesions.

Primary signet-ring cell/histiocytoid carcinomas of the eyelid are extremely rare tumors considered to originate from sweat glands. Here, we report the case of a 72-year-old man diagnosed with primary signet-ring cell/histiocytoid carcinoma of the eyelid and present immunohistochemical analyses of the eyelid apocrine gland (Moll gland) and apocrine and eccrine sweat glands of perineum and axilla. Widespread infiltration of tumor cells with signet-ring cell or histiocytoid appearance was observed in his left eyelid, orbit, and periocular lesion. Tumor cells expressed mucins and showed immunoreactivity that was similar to that of the Moll gland: MUC6(+), GlcNAcα1→4Gal→R(-), MUC2(-), MUC5AC(-), GCDFP15(+), CD15(+), S100(-), CK7(+), CK20(-), ER(+), PgR (+), HER2(-), E-cadherin(+), p63(-), PSA(-), and TTF-1(-). The tumor cells differed from those of perineal and axillary apocrine and eccrine sweat glands, which were MUC6(-). The Moll gland was ER(-) and PgR(-), whereas perineal and axillar apocrine sweat glands were ER(+) and PgR(+), and perineal and axillary eccrine sweat glands were ER(+) and PgR(-). The tumor showed characteristics similar to that of the eyelid Moll gland, which is demonstrated to be an apocrine gland with a protein expression distinct from that of other apocrine glands. MUC6 and GCDFP15 expression are useful in identifying the Moll gland immunophenotype and GCDFP15, ER and PgR expression are useful in distinguishing primary eyelid signet-ring/histocytoid carcinoma from gastrointestinal malignancies.

Chondroid syringoma is an uncommon benign neoplasm in the skin. It is composed of epithelial and myoepithelial cells embedded in a matrix with varying amounts of mucoid and cartilaginous material. Chondroid syringoma is classified into 2 types, the apocine type and the eccrine type. Several cases of the eccrine type chondroid syringoma with ossification and calcification have been reported, but the apocrine type chondroid syringoma with calcification has not been reported. In this report, we describe a case of apocrine type chondroid syringoma with calcification.

Background: Hidradenomas are rare benign adnexal neoplasms that encompass a morphological gamut with a range of differentiation. As a consequence, there is a great likelihood of being mistaken for other primary and metastatic tumors. Though conventionally regarded as eccrine, they have been reclassified into eccrine and apocrine types., Objective: This study aims to document the histological spectrum of nodular hidradenomas, with particular reference to categorizing them into eccrine or apocrine tumors., Results: A total of 15 cases with features of nodular hidradenoma with their age ranging from 18 years to 73 years were studied. Most of the cases were solitary, circumscribed, solid and cystic, dermal, symmetrical, lobulated tumors with a sheet-like and papillary architecture. The cells were chiefly eosinophilic with a regular oval grooved nucleus and a small inconspicuous nucleolus. Clear cells were also seen. Squamous differentiation was an important feature, with most showing a infundibular type of keratinization. Sebaceous differentiation is also common. The stroma varied from hyaline to myxoid. Only 1 case showed poroid differentiation., Conclusions: This study describes the assortment of histologic characteristics in hidradenomas. Apocrine hidradenomas are more common, contrary to earlier belief that favored an eccrine origin.

Subungual malignant epithelial tumors with tricholemmal keratinization have rarely been described as "malignant proliferating onycholemmal cyst" and "onycholemmal carcinoma (OC)." We report an additional case of a slow growing OC occurring on the middle finger of a 58-year-old man, which was unusual as it showed sebaceous-apocrine differentiation, in addition to a nail bed carcinoma with tricholemmal microcysts. We therefore consider the descriptive term of microcystic nail bed carcinoma more appropriate than OC. It is recognized that none of the rare cases of OC meet the classical additional criteria proposed by Headington for tricholemmal carcinoma, that is, lobular arrangement, peripheral palisading, thickened basement membrane, and glycogen-positive tumors cells. On the other hand, we suggest that the term follicular microcysts of the nail bed should be retained to describe the true nature of subungual epidermoid inclusions, which show usually a limited differentiation toward the follicular isthmus. Therefore, the previous cases of OC without sebaceous-apocrine differentiation could be best classified as a microcystic nail bed carcinoma arising from the follicular microcysts of the nail bed, with a limited differentiation toward the keratinization of the follicular isthmus.

Apocrine carcinoma (AC) is an extremely rare skin appendage tumor, which is located at lower dermal and subcutaneous tissue. We report a case of an anal AC arising from an apocrine adenoma in the anal region, which is only the second case reported in this region. A 71-year-old male presented to clinic with soreness in the anal region for 6 weeks. An excisional biopsy was performed. Histologically, the lesion was poorly circumscribed, infiltrative, and was composed of small to medium sized glands extending to the surgical margins. There were centrally dilated large glands with duct-like openings into the mucosal surface. The larger central glands contain periodic acid-Schiff-positive eosinophilic acellular secretions. At the periphery, there were smaller glands with significant cytologic atypia and numerous mitoses. A diagnosis of AC was made making it the second case report of this very rare malignancy in this region. Although ACs usually do not have a fatal outcome, there have been case reports of distant metastases and even death from this disease, making histologic distinction of this malignancy from a benign apocrine adenoma important. Wide local excision is typically the treatment of choice, although Mohs micrographic surgery has also been used with similar success.

Apocrine nevus is a rare tumor composed of increased mature apocrine glands and ductal structures within a fibrous stroma, located predominantly in the reticular dermis. They have been reported in association with apocrine carcinoma, extramammary Paget disease, and syringocystadenoma papilliferum; less commonly a pure apocrine nevus is identified, unassociated with another apocrine proliferation. Clinically apocrine nevi may appear as solitary or multiple nodules or plaques on the scalp, presternal skin, though they are seen most commonly in the axillae. We describe 4 cases of pure apocrine nevus, all of which appeared clinically as painless or mildly tender skin-colored axillary masses, 2 of which were bilateral. In each case, the lesions appeared in adulthood, and patients denied knowledge of congenital or childhood presence. Patients denied pruritis, discharge, bleeding, or antecedent trauma. Grossly, the specimens consisted of subcutaneous, multicystic ill-defined nodules. Biopsy showed prominent apocrine glands composed of irregularly columnar luminal cells with eosinophilic cytoplasm arranged in a somewhat organoid pattern filling the reticular dermis and extending into the subcutaneous adipose tissue. The glandular luminal cells displayed decapitation secretion. There was a paucity of pilosebaceous units. In one case, the overlying epidermis was papillomatous. The deepest portion of one specimen had lactational change simulating a lactational adenoma. No atypia was seen in either the glandular structures or the stroma. The adjacent sebaceous and eccrine structures were normal. The histologic features and immunohistochemical profile in relation to other apocrine lesions will be reviewed.

Hidradenoma papilliferum of the anogenital region was previously believed to originate from apocrine glands but has recently been accepted as originating from anogenital mammary-like glands. We describe a case of hidradenoma papilliferum with mixed features of syringocystadenoma papilliferum and mammary-like glands from the left labia majora of a 25-year-old woman. Histopathologically, the lesion showed an epithelial lining with apocrine secretion, and like syringocystadenoma papilliferum, the lesion extended from the epithelium as invaginations into the dermis. Adjacent to this lesion were ductal and glandular structures resembling normal mammary tissue. This review of the literature highlights the heterogeneity and complexity of lesions arising from anogenital mammary-like glands, and this case serves as further documentation of the association between anogenital mammary-like glands and hidradenoma papilliferum.

Apocrine mixed tumor of the skin is a benign adnexal neoplasm usually posing no diagnostic problem for a histopathologist. The purpose of our investigation is to present a small series of 4 benign cutaneous apocrine mixed tumors of the skin that contained small foci of intravascular tumor deposits, a feature not previously described, to the best of our knowledge. The 4 lesions were identified retrospectively after a review of 312 apocrine mixed tumors and 51 eccrine mixed tumors in the collective files of the authors. In all cases, this feature was originally overlooked. The patients were 3 men and 1 woman, ranging in age at diagnosis from 29 to 66 years. Locations included nose (2), forehead (1), and the fifth toe (1). Histopathologically, all 4 neoplasms demonstrated typical features of a benign apocrine mixed tumor; 2 cases were classified as hyaline cell-rich tumors. In all cases, there were either blood or lymphatic vessels containing small intraluminal collections of neoplastic cells, which had the appearances of hyaline cells and immunohistochemically expressed cytokeratins and were partly immunoreactive for S-100 protein and calponin, thus indicating the myoepithelial phenotype. The intravascular location of the neoplastic cells was confirmed by CD31 staining. The nature of the vessels (lymphatics vs. blood vessels) was supported by staining for alpha smooth muscle actin, which stained pericytes in blood vessels. Lymphatic vessels were also stained for D2-40. No eccrine mixed tumor manifested intravascular tumor deposits. Follow-up of the patients revealed no recurrences or metastasis (range: 2-21 years). It is concluded that occurrence of intravascular involvement in benign apocrine mixed tumor of the skin is rare (approximately 1%-2%). This feature is discrete and is easy to overlook. At present, its significance is not completely clear. Until proved otherwise in future, we suggest to consider intravascular deposits in cutaneous apocrine mixed tumors as an innocuous phenomenon.

Sebaceoma is a benign sebaceous neoplasm, which has been reported to show characteristic growth patterns, such as, ripple, labyrinthine/sinusoidal, and carcinoid-like patterns. Another recent finding regarding in sebaceoma is the observation of apocrine differentiation within the sebaceoma lesion. This report describes a case of carcinoid (a partial ripple and labyrinthine) pattern sebaceoma with apocrine differentiation with a literature review and immunohistochemical studies. The various characteristic growth patterns in sebaceoma were suggested to simply be variations of the same growth pattern arranged in cords, namely, a unified term "ripple/carcinoid pattern." The primitive sebaceous germinative cells in sebaceoma may still have the ability to undergo apocrine differentiation. Most of the reports so far on sebaceoma with apocrine differentiation, including the present case, describe a ripple/carcinoid pattern, thus suggesting that ripple/carcinoid pattern sebaceoma is composed of more primitive sebaceous germinative cells than conventional sebaceoma.

Background: The overlap in histopathologic features and immunoprofile of eccrine and apocrine neoplasms confounds basic issues relating to lineage of these entities., Methods: We evaluated expression of follicular stem-cell markers, cytokeratin (CK) 15 and nestin, in 78 benign and 23 malignant adnexal neoplasms., Results: CK15 and nestin expression were noted in 39 of 78 (50%) and 36 of 78 (46%) cases in the benign group, respectively (8 cutaneous mixed tumor, 10 hidradenoma papilliferum, 9 apocrine cystadenoma, 11 cylindroma and/or spiradenoma, and 9 poroma/dermal duct tumor). CK15 and nestin expression were noted in 11 of 23 (48%) and 7 of 23 (30%) cases in the malignant group, respectively (6 microcystic adnexal carcinoma, 7 porocarcinoma, and 9 eccrine carcinoma). Except 1, both markers were negative in 4 syringocystadenoma papilliferum, 10 hidradenoma, 1 syringofibroadenoma, 10 syringoma, 1 eccrine adenoma, 8 poroma/dermal duct tumor, 5 eccrine hidrocystoma, and 1 apocrine carcinoma., Conclusions: Given that follicular germinative cells give rise to the folliculosebaceous apocrine unit, expression of CK15 and nestin in the majority of cutaneous mixed tumor, hidradenoma papilliferum, apocrine cystadenoma, and cylindroma/spiradenoma is suggestive of an apocrine origin/differentiation of these neoplasms. Reinforcing this and a novel finding of our study is the preferential expression of nestin in myoepithelial cells of these lesions.

Fox-Fordyce disease is a condition with protean histopathological alterations whose pathogenesis remains a mystery. Although recent studies have addressed histological changes specific of this disease, including perifollicular xanthomatosis, no attention has been given to apocrine acini dilation as an adjunct histopathological finding to the diagnosis. Moreover, although previous efforts were done to demonstrate that perifollicular foamy histiocytes harbor apocrine secretion content, this concept has not been proved to date. In this study, we report 2 cases harboring prominent dilation of apocrine coils with mucinous content. Such mucinous content showed mucin profile identical to the dermal mucin deposits in both cases. Of note, perifollicular foamy histiocytes demonstrated cytoplasmic mucin, supporting the suggestion that these cells phagocytose apocrine secretion. Although not specific, apocrine coil dilation is another histopathological feature of Fox-Fordyce disease and it may be used as a low-power magnification clue for the correct diagnosis. We also propose that the so-called perifollicular xanthomatosis may be composed of muciphages or mixed cell (muciphages/xanthomatous) population, an issue that should be further investigated in future studies.

Apocrine differentiation is a rare event in sebaceoma, and only 3 cases have been reported. We report a case of sebaceoma with extensive apocrine differentiation on the scalp in a 73-year-old Japanese woman. The resected tumor was located entirely within the dermis and subcutis as a well-circumscribed, lobulated, solid, and partially cystic mass, measuring 35 mm at the largest diameter. Histopathologically, it was composed of uniform basaloid cells with clusters of sebocytes, squamous islands of ductal structures, and apocrine cells with apparent decapitation secretion. Nuclear atypia of all types of cells was inconspicuous, and mitotic figures were infrequent. We considered the lesion to be a sebaceoma with apocrine differentiation.

Presented here are three cutaneous sebaceous tumors (one carcinoma and two sebaceomas), each demonstrating a focal glandular pattern representing apocrine differentiation. The patients, two males and one female, each clinically presented with a small solitary nodule or tumor on the scalp. None of the patients had features of Muir-Torre syndrome. Surgical removal of the lesions was performed in all cases. None of the patients developed recurrence or metastasis after surgery (follow-up ranged from 18 to 24 months). The glandular areas represented a minor but significant component of the lesions and appeared as glands of various complexity, mostly as simple round or elongated tubular structures lined by a row of cuboidal to columnar cells with eosinophilic cytoplasm and round nuclei, with or without a distinct nucleolus. Decapitation secretion was evident but not prominent. In both sebaceomas, at least a portion of the glands had a peripheral small-cell layer that appeared similar to the basal/myoepithelial cells of normal eccrine and apocrine ducts. In some glands, the basal/myoepithelial cells seemed to have undergone hyperplasia, resulting in two or more rows of cells that even formed small islands, with an overall appearance reminiscent of basal cell hyperplasia in the prostate, arising in the basal layer of the prostatic glands. The descriptive terms seboapocrine carcinoma or seboapocrine sebaceoma are proposed for such lesions. These tumors may be viewed as rare histopathological variants of sebaceous carcinoma and sebaceoma, with a second type of differentiation along the lines of the folliculosebaceous-apocrine unit.

We herein report an unusual case of apocrine carcinoma on the forehead. The lesion was formed by the anastomosis of numerous tubular structures with widespread decapitation secretion, thus demonstrating apocrine differentiation. However, we observed some unusual histopathologic features that differed from those found in typical examples of apocrine ductal carcinoma, namely: 1) a relatively well-circumscribed lesion in the dermis, and 2) nodular or solid aggregations composed of basaloid cells. We believe the present case is an apocrine ductal carcinoma, although it has a nodular appearance and basaloid cells. Otherwise, it could be a hitherto undescribed variant of apocrine carcinoma. This apocrine carcinoma on the forehead may have originated from either pluripotential cells or from apocrine glands at an unusual site.

Apocrine fibroadenoma (AFA), considered a counterpart of fibroadenoma of breast, is a rare cutaneous apocrine neoplasm occurring almost exclusively in women. We describe a 75-year-old man who presented with a red dome-shaped papule near the nasal bridge. The tumor was composed of numerous tubular, cystic, and partially branching lumina and struts of epithelial cells oriented perpendicular to the skin surface, with which it connected through infundibula. The epithelial strands were embedded in fibrocollagenous stroma. These histopathological features are consistent with AFA. The cytokeratin profiles of our case were similar to those of apocrine or eccrine neoplasms. Progesterone and estrogen receptors (PR/ER) were not expressed. The stroma cells were stained strongly positive for vimentin, but nonreactive for alpha-smooth muscle actin, S-100 protein, or glial fibrillary acidic protein. To the best of our knowledge, this is the first report of facial AFA in man. Different from a more common anogenital AFA, this neoplasm might represent a second type of AFA with unique histopathologic and immunopathological features.

Adenolipoma is a rare microscopic variant of cutaneous lipoma composed of large lobules of mature adipocytic tissue admixed with eccrine ducts and glands. We report a new case of cutaneous adenolipoma, and the first showing an apocrine cystic glandular component. This lesion may not be a specific entity, and could represent entrapment of epithelial structures within a lipoma.

Two cases of an unusual cutaneous lesion characterized by a dermal nodule with apocrine gland cysts surrounded by a hemosiderotic dermatofibroma-like proliferating stroma are reported. The first case was a 52-year-old female who presented with a nodule on the back of several years of evolution and with the clinical diagnosis of lipoma; the second case was a 41-year-old male who presented with a forehead nodule of several years of evolution with a clinical diagnosis of epidermal cyst. Histologically, an ill-delimited non-encapsulated nodule composed of cystic spaces and solid areas was found. The cystic spaces consisted of ductal structures and a bilayered epithelial covering with apocrine differentiation; the surrounding area showed a stroma composed of a mixture of both fibrocytes and macrophages and abundant hemosiderin granules; foci of recent hemorrhages and a more dense fibrous stroma at the periphery with typical storiform areas were also visible. Both cases have shown a benign course without local recurrence in follow up until this report date.

Trichoblastoma is a rare, benign tumor that differentiates toward the hair germ, the embryonic precursor of a hair follicle. Several cases of trichoblastoma showed multiple differentiation toward more than one type of adnexal structure. We report a case of a trichoblastoma, which had developed on the scalp as a solitary 1-cm nodule 3 years ago. A histologic examination indicated that the specimen had features of multiple differentiation. In particular, there were occasional foci of decapitation secretion, as well as cells with web-like and bubbly cytoplasm suggesting seboblasts, and a sebaceous duct-like structure. In addition, there were occasional germinative cells in the palisade, and scattered hair papilla-like structures showing follicular differentiation. An immunohistochemical study showed that the neoplasm, or areas in it, stained positive for low molecular cytokeratin, high molecular cytokeratin, EMA, S-100, and GCDFP-15. This is an unusual case of a trichoblastoma with apocrine and sebaceous differentiation.

Basal cell carcinoma (BCC) has many histologic variants. These variants may show differentiation toward benign and malignant tumors of cutaneous appendages, especially hair follicles. Herein we describe a lesion that was clinically thought to be a BCC, but a superficial biopsy showed histologic features suggestive of an apocrine hidrocystoma. Because of some cytologic atypia, complete excision was recommended. The excision specimen revealed a cystic BCC. The importance of examining the entire neoplasm before reaching a final pathologic diagnosis is emphasized.

We investigated the pathway of differentiation in a case of mucinous carcinoma of the skin (MCS) arising on the right temple of a 70-year-old man. Histopathologic findings of the tumor showed evidence of apocrine-type differentiation such as distinctive decapitation secretion. Additionally, by employing a panel of antibodies, the immunohistochemical staining pattern of tumor cells was shown to be compatible with that of apocrine glands. Although the differentiation of this neoplasm remains controversial, the findings in our case suggest apocrine differentiation.

We reviewed the pathologic findings on a family with multiple hereditary trichoepitheliomas. Although the majority of the lesions were trichoepitheliomas, basal cell carcinomas, spiradenomas, and spiradenomas with cylindromatous foci (spiradenocylindroma) were present, representing a spectrum of lesions exhibiting folliculosebaceous (trichoepithelioma, basal cell carcinoma) and apocrine (spiradenoma, spiradenocylindroma) differentiation. Multiple familial trichoepitheliomas may be a syndrome whereby tumors develop from undifferentiated germinative cells of the folliculosebaceous-apocrine unit. Published findings regarding the genetics of this syndrome and solitary trichoepitheliomas are reviewed; although the molecular basis for the tumors has yet to be determined, current data suggest that a tumor suppressor gene may be involved.

Extramammary Paget disease of the axilla with underlying apocrine carcinoma has been reported only in six cases until now. This report deals with a seventh case characterized by the unique finding of comedo-like features evocative of large cell ductal breast carcinoma within an otherwise typical in situ apocrine carcinoma. This is characterized by spiral-shaped foci of epithelial proliferation with decapitation secretion and central masses of necrotic debris. A possible connection between the solid neoplasm and the overlying Paget disease is illustrated by a few apocrine-follicular units colonized by both the Paget cells and the structured adenocarcinoma. Here, although they display the same immunohistologic pattern of glandular differentiation, the two populations seem to be cytologically different and do not show signs of gradual transition to one another. Thus, they give the impression of parallel but distinct processes, which is consistent with the hypothesis of proliferative induction of a preexisting intraepidermal scattered population from the underlying adnexal carcinoma. The observed resemblance between apocrine carcinoma and comedo carcinoma of the breast, with its ontogenetic and phylogenetic implications, links not only the two neoplasms and the corresponding glands of origin but also mammary and extramammary Paget disease. This reinforces the unifying conception of Paget disease.

Trichoblastoma is a benign neoplasm with primitive hair follicle differentiation. The tumor is characterized by nests and cords of epithelial cells in an organized relation to stroma. The epithelial cells differentiate toward follicular germ and follicular sheath. More divergent differentiation in the form of sebaceous elements in trichoblastoma has infrequently been reported in the literature. We report a trichoblastic neoplasm showing typical features of trichoblastoma as well as areas of apocrine differentiation. The neoplasm, which was present for several months, was removed from the chin of a 31-year-old woman. Histologic examination showed a neoplasm composed of basaloid nests with occasional papillary mesenchymal bodies as well as ducts and glands exhibiting apocrine differentiation. Trichoblastoma with apocrine features is rarely reported in the literature.

A 54-year-old male had a dome-shaped and skin-colored nodule on his nose. Histopathologically, we diagnosed this neoplasm as a low-grade sebaceous carcinoma rather than a sebaceoma based on the scanning magnification and cytology. This low-grade sebaceous carcinoma was associated with glandular structures. We regarded the glandular structures as those of apocrine glandular differentiation based on 1) the histopathologic features of the glandular structures formed by columnar luminal cells with evidence of decapitation secretion; 2) the expression of cytokeratin (CK) 19, CK8, CK8/18, and CK7 in the luminal cells; 3) the positive reaction of carcinoembryonic antigen and epithelial membrane antigen on the luminal surface and in the cytoplasm of the luminal cells; and 4) the common embryologic origin of the folliculosebaceous-apocrine unit. We found CK15 expression in undifferentiated cells within the mantles of normal hair follicles, suggesting that sebaceous stem cells might exist in mantles as follicular stem cells exist in bulge areas. Pluripotent stem cells in the folliculosebaceous-apocrine unit can give rise to follicular stem cells, sebaceous stem cells, and apocrine stem cells. Our patient's neoplasm showed apocrine glandular differentiation and partial immunohistochemical positivity for CK15 in the neoplastic aggregations. We believe this neoplasm originated from pluripotent stem cells destined to become sebaceous stem cells or from sebaceous stem cells, which also have the ability to differentiate within apocrine glands.

Nevus sebaceus of Jadassohn is a hamartoma that combines epidermal, follicular, sebaceous, and apocrine gland abnormalities. Classically, several types of cutaneous neoplasms have been associated with this hamartoma, with basal cell carcinoma being the most frequently described malignancy. We studied a series of 155 examples of nevus sebaceus of Jadassohn with clinicopathologic correlation. Several histopathologic changes related to the age of the patients were found. In our series, we could not identify any cases of authentic basal cell carcinoma. In contrast, several examples of primitive follicular induction and of trichoblastomas were seen. Other cutaneous hamartomas, hyperplasias, and neoplasms found in our series of nevus sebaceus of Jadassohn included syringocystadenoma papilliferum, sebomatricoma, apocrine gland cyst, poroma, different histopathologic variants of warts (classic warts, tricholemmoma, and desmoplastic tricholemmoma), primitive follicular induction, and ductal induction. In our series, no examples of malignant neoplasms were identified. On the basis of these findings, the classically recommended treatment for this hamartoma, which consists of early excision to prevent the development of malignancy, seems to be inappropriate.

Traditionally, poromas have been classified as eccrine neoplasms, but several recent reports of poroid tumors with sebaceous, follicular, and apocrine differentiation have challenged this idea. In support of alternative differentiation, a case of an "apocrine" poroma is reported in a 19-year-old man with the nevoid basal cell carcinoma syndrome. A papule on the right cheek, thought clinically to be a basal cell carcinoma, was excised. Anastomosing lobules of small uniform basaloid (poroid) cells formed small ductular structures lined by eosinophilic cuticles and extended into the superficial reticular dermis. The neoplasm originated from follicular infundibula and was surrounded by a myxoid stroma. Focally, primitive hair bulb and papillae differentiation was present, and some of the ducts were lined by cells suggesting decapitation secretion. The histologic pattern and the common embryologic origin of the folliculosebaceous-apocrine unit support apocrine differentiation of this tumor. The association with the nevoid basal carcinoma syndrome appears to be unique. This case, in addition, demonstrates overlapping features with the infundibulocystic type of basal cell carcinoma commonly seen in the basal cell nevus syndrome.

A 74-year-old Japanese man developed a reddish, indurated plaque composed of multiple nodules on his right axilla. Histopathologic examination showed a solid tumor that extended from the upper dermis into the subcutis, with both inter- and intracellular lumen formation, cellular arrangement in single files, a fibrotic reaction around the tumor cells, and the presence of mucinous material in the cytoplasm. There was both nuclear and cytoplasmic pleomorphism. Both lysozyme and GCDFP-15 were identified in the tumor cells. Electron microscopic examination showed periluminal condensation of the cytoplasm. Because thorough clinical and laboratory examinations were unremarkable, we regarded this to be a case of primary adenocarcinoma with signet ring cells of the axilla. The neoplasm might have differentiated toward the apocrine sweat glands or the mammary glands. Radiation therapy was effective to some degree. This seems to be the first reported case in which adenocarcinoma with signet ring cells of the skin affected a site other than the eyelids.