Eccrine ductal and acrosyringeal metaplasia in breast carcinomas: report of eight cases.

Eccrine ductal and acrosyringeal metaplasia was described in 2006 as the presence of tumor structures that resemble the epithelium of the eccrine skin ducts and their opening within the epidermis, the acrosyringeum. Here, we report the clinical, morphological, and phenotypic characteristics of eight breast carcinomas that we collected over the past years showing this metaplasia. Unlike squamous metaplasia, acrosyringeal and eccrine ductal metaplasia are luminated structures comprising cells with eosinophilic cytoplasm that are easily detectable in routine histological slides. These lesions invariably appeared in triple-negative carcinomas, but the cases differed in their clinical, radiological, and histological manifestations. Correct interpretation of these changes may facilitate identification of some metaplastic carcinomas.

Expression of S100A2 and S100P in human eccrine sweat glands and their application in differentiating secretory coil-like from duct-like structures in the 3D reconstituted eccrine sweat spheroids.

Secretory coils and ducts are two components of eccrine sweat glands with different structures and functions. In our previous study, we combined keratins and α-SMA to distinguish between secretory coils and ducts. However, the key deficiency of the method was that none of the antibodies used was specific for ducts. In this study, we first examined the co-localization of K5/K7, α-SMA/K14, K7/S100P and α-SMA/S100A2 by double-immunofluorescence staining to confirm the localization of S100P and S100A2 in native human eccrine sweat glands, and second we identified secretory coil-like and duct-like structures in the 3D reconstituted eccrine sweat gland spheroids by double-immunofluorescence staining for K7/S100P and α-SMA/S100A2. In native human eccrine sweat glands, S100A2 immunoreactivity was confined to the outer layer and S100P to the inner layer of the duct. In 12-week Matrigel plugs containing eccrine sweat gland cells, double-immunofluorescence staining for K7/S100P and α-SMA/S100A2 could easily distinguish duct-like structures from secretory coil-like structures. We conclude that S100A2 and S100P can be used as specific duct markers in eccrine sweat glands, and combined use of S100P or S100A2 with keratins enables easy to distinction between secretory coils and ducts.

Identification of a new sweat gland progenitor population in mice and the role of their niche in tissue development.

Sweat gland cells are responsible for the regulation of body temperature and are critical for wound repair. Furthermore, they have the regenerative potential in response to injury, and show a substantial turnover during both wound healing and homeostasis. However, as a usual research model of sweat gland, mice have not too much glandular cells for experiments. In this study, we identify previously unreported sweat gland progenitor population in mice and characterize them. The progenitor characteristics of sweat gland were confirmed using cellular immunofluorescence assay and quantitative real-time PCR assay. K8 and K18 expression was barely detected in the early stage of skin development (Embryo 17.5d) and increased to a high level at P5d (postnatal 5d), then showed reduction at adult stage (P28d). Further investigation of K8 and K18 positive cells using tissue immunofluorescence revealed the presence of sweat gland progenitors in back epidermis of mice at early stage of sweat gland development and continuous reduction during the developmental process. In vivo transplantation assay with animal models elucidated that sweat gland specific niche in paw pads was critical for the development of sweat gland cells. Although the relationship between new sweat gland progenitors and their niche still needs to be further investigated, the presence of these cells implicates that there is more source ascribed to sweat glands in addition to serving as progenitors in mice.

[Eccrine angiomatous hamartoma: a clinicalopathologic analysis of 4 cases].

OBJECTIVE: To investigate the clinical and histopathologic features, diagnosis and differential diagnosis of eccrine angiomatous hamartoma(EAH). METHODS: Four cases of eccrine angiomatous hamartoma were studied by light microscopy and immunohistochemical staining along with review of the literature. RESULTS: There were 3 male and 1 female patients at diagnosis in age of 4 months, 3.5 years, 5.5 years and 14.0 years, respectively. Tumor sites included the left little finger (1 case), right index finger (1 case), lower back (1 case) and knee (1 case). Clinically, most cases presented as a solitary, flesh or reddish papule, plaque or nodule with size of 0.4-6.0 cm in diameter. The skin lesions in 3 cases enlarged commensurate with the growth of the patients, and local hyperhidrosis in one case. Histologically, EAH was characterized by proliferation of well-differentiated eccrine secretory and ductal elements closely associated with thin-walled angiomatous channels in the middle or deep dermis and subcutaneous tissue. By immunohistochemistry, the vascular components were positive for CD31, CD34 and factor Ⅷ related antigen while the eccrine glands were positive for S-100 protein, CEA, EMA, CAM5.2 and GCDFP15. Local surgical resection was performed in 4 cases and follow-up data (0.5 to 4.5 years) showed no recurrence. CONCLUSION: EAH is a rare, benign cutaneous hamartoma. Combination of clinical manifestations, histological changes and immunohistochemical findings is useful for the diagnosis and differential diagnosis.

Preferential expression of OVOL1 in inner root sheath of hair, sebaceous gland, eccrine duct and their neoplasms in human skin.

OVOL1 is an important transcription factor for epidermal keratinization, which suppresses proliferation and switches on the differentiation of keratinocytes. A recent genome-wide association study has revealed that OVOL1 is one of the genes associated with susceptibility to atopic dermatitis. Although it is known to be expressed in murine skin and hair follicles, no investigations have focused on its localization in human skin. In the present study, we thus immunolocalized the expression of OVOL1 in normal and diseased human skin. In normal human skin, OVOL1 was preferentially expressed in the suprabasal layer of the epidermis, inner root sheath of hair, mature sebocytes and the ductal portion of the eccrine glands. Compared to this, no remarkable change in the expression of OVOL1 was observed among inflammatory skin diseases. The expression of OVOL1 was evident in eccrine poroma and hidradenoma. Moreover, it was overexpressed in Bowen's disease and sebaceous adenoma, in sharp contrast to its downregulation in their more malignant counterparts, squamous cell carcinoma and sebaceous carcinoma. OVOL1 may play an important role in human skin morphogenesis and tumorigenesis.

Cutaneous ciliated cyst of the scalp: a case report of a cutaneous ciliated eccrine cyst and a brief review of the literature.

Cutaneous ciliated cysts (CCC) are rare benign cysts known to occur in the lower extremities of females of reproductive age. Currently, there are 2 theories that attempt to explain the histogenesis of this rare entity. The theory of Mullerian heterotopia provides a plausible histogenetic explanation for the vast majority of CCC. A proposed alternative theory is the ciliated metaplasia of eccrine glands. We believe that previously reported cases of CCC include 2 distinct entities. We report, herein, the first case reported in the literature of a cutaneous ciliated eccrine cyst occurring on the scalp.

Eccrine angiomatous hamartoma is a lymphatic proliferation.

BACKGROUND: Eccrine angiomatous hamartoma (EAH) is recognized as a vascular hamartoma composed of abnormal proliferation of blood vessels and eccrine glands. OBJECTIVE: We sought to investigate the immunohistochemical results of D2-40 and Prox1 in EAH in order to gain further insight into its histogenesis. MATERIALS AND METHODS: We collected 21 cases of EAH diagnosed in a dermatology department. Immunohistochemical staining of D2-40 and Prox1 was performed on all cases. RESULTS: Prox1 was universally positive in the endothelial cells of proliferated vessels in all cases. D2-40 was universally positive in the endothelial cells of proliferated vessels in 3 cases, focally positive in 18 cases. CONCLUSION: EAH is a lymphatic proliferation and therefore we suggest the name of eccrine lymphangiomatous hamartoma.

Immunohistochemical sweat gland profiles.

BACKGROUND: Human sweat glands are heterogeneous in their structures and functions. Accordingly, eccrine, apocrine, and apoeccrine glands are distinguished. AIMS: Some immunohistochemical markers are expected to distinguish the sweat gland types in their secretory and excretory parts. METHODS: This study used two sets of antibodies. The first panel was composed of antibodies directed to well-defined sweat gland structures. The molecular targets included the low-molecular-weight cytokeratins CAM 5.2, the S100-B protein, the epithelial membrane antigen (EMA), the carcinoembryonic antigen (CEA), and the lectin Ulex europaeus agglutinin-1 (UEA-1). A second exploratory panel of antibodies targeted syndecan-1 (CD138), NKI-C3 (CD63), and CD68. They were used to disclose some undescribed antigen expressions in human sweat glands. RESULTS: The first set of antibodies confirmed previous findings. The immunoreactivities of the three sweat gland types were similar in the excretory ducts. By contrast, they were distinguished in the deeper coiled secretory portions of the glands. CONCLUSION: Clues supporting their distinction and probably their functional activity were obtained by immunohistochemistry using the S100-B protein, CEA and CD63 antibodies. The immunoreactivity to the S100-B protein, CEA and CD63 possibly help identifying apoeccrine sweat glands or a peculiar functional activity of eccrine sweat glands.

Immunohistochemical study of calretinin in normal skin and cutaneous adnexal proliferations.

Calretinin is a calcium-binding protein member of the EF-hand family. The presence of calretinin has been demonstrated in certain stages of the cellular cycle in a wide variety of normal and neoplastic tissues. The main aims of our study were (1) to investigate what structures of the normal skin and cutaneous adnexal proliferations express immunoreactivity for calretinin and (2) to determine the value of immunohistochemical expression for calretinin as a marker for follicular, sebaceous, apocrine, and eccrine differentiation in cutaneous adnexal proliferations. We studied 139 biopsy specimens, including 10 cases of normal skin of different locations and 129 benign and malignant cutaneous adnexal proliferations. In normal skin, we found that calretinin is expressed in the innermost cell layer of the outer root sheath in anagen hair follicle, in both the duct and sebolemma of the sebaceous gland, in the secretory portion of eccrine glands, and in mast cells of the stroma. In cutaneous adnexal proliferations, we found strong immunoreactivity for calretinin in tricholemmal cysts, tricholemmomas/inverted follicular keratoses, tumors of follicular infundibulum, and in some basal cell carcinomas. Focal positivity was also seen in trichoadenomas, trichoblastomas/trichoepitheliomas, pilomatricomas, proliferating tricholemmal tumors, pilar sheath acanthomas, trichofolliculomas, follicular hybrid cysts, cutaneous mixed tumors, steatocystomas, sebaceous hyperplasias, and sebaceomas. These results demonstrate that immunohistochemical study for calretinin may be helpful to identify the innermost cell layer of the outer root sheath in anagen hair follicle and the cutaneous adnexal proliferations showing differentiation toward this structure. Calretinin immunoreactivity supports eccrine differentiation in some sweat gland neoplasms, and it is also useful in identifying neoplasms with ductal sebaceous differentiation.

Expression of stem-cell markers (cytokeratin 15 and nestin) in primary adnexal neoplasms-clues to etiopathogenesis.

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.

Squamoid eccrine ductal carcinoma: a case report and review of the literature.

Eccrine ductal carcinoma is a rare adnexal tumor. Squamoid eccrine ductal carcinoma (SEDC) represents an exceptionally rare variant with only 6 cases reported to date. This neoplasm is deeply infiltrative and may provide a diagnostic challenge in superficial shave biopsies of skin. We present a case of SEDC in an immunocompromised patient, who, after an initial shave biopsy for diagnostic purposes, underwent a complete excision of his tumor by Mohs micrographic surgery. A combined histologic and immunohistochemical approach is necessary to identify and confirm the unique characteristics of SEDC. Because this cancer is very rare and little is known about its biologic behavior, optimal diagnostic and treatment guidelines need to be developed.

New concepts on the histogenesis of eccrine neoplasia from keratin expression in the normal eccrine gland, syringoma and poroma.

BACKGROUND: Peripheral and luminal layers of eccrine sweat gland ducts are self-renewing structures. Proliferation is restricted to the lowermost luminal layer, but randomly scattered in the peripheral layer. Each layer exhibits differential expression of keratins K5/K14 and K6/K16. Keratin K1 occurs only in peripheral cells and the novel keratin K77 is specific for luminal cells. OBJECTIVES: To investigate the expression of luminal (K77), peripheral (K1) and further discriminatory keratins in two eccrine sweat gland tumours: syringoma, thought to show differentiation towards luminal cells of intraepidermal sweat ducts and eccrine poroma, considered to arise from poroid cells, i.e. peripheral duct cells; and keratinocytes of the lower acrosyringium/sweat duct ridge differentiating towards cells of intradermal/intraepidermal duct segments. METHODS: Paraffin-embedded sections were examined by immunohistochemistry using several keratin, smooth muscle actin and Ki-67 antibodies. RESULTS: We confirmed the ductal nature of syringomas. Despite drastic morphological alterations in both layers, their keratin patterns remained almost undisturbed compared with normal ducts. In eccrine poroma epidermal keratins K5/K14 were ubiquitously expressed in all poroid cells. Cell islands deviating morphologically from poroid cells contained epidermal keratins K1/K10. K77 expression was limited to luminal cells of intact duct structures within the tumours. CONCLUSIONS: Syringomas are benign tumours of luminal cells of the lowermost intraglandular sweat duct. Poroid precursor cells of poromas do not comprise peripheral duct cells nor do poromas differentiate towards peripheral or luminal duct cells. Instead, poroid cells consist only of keratinocytes of the lowermost acrosyringium and the sweat duct ridge and poromas tend to differentiate towards the cells of the upper acrosyringium.

Ductal eccrine carcinoma with squamous differentiation: apropos a case.

Sweat gland carcinomas are rare. Given this, they can pose a diagnostic challenge especially in shave biopsy specimens. We present a case of ductal eccrine carcinoma with extensive squamoid differentiation that was repeatedly misdiagnosed by multiple dermatopathologists as squamous cell carcinoma in the initial few biopsies. As the distinction between these two neoplasms is crucial to patient management, we highlight the histologic features of this uncommon entity to highlight the potential diagnostic pitfalls.

Immunohistochemical differentiation and localization analysis of sweat glands in the adult human axilla.

BACKGROUND: The classic concept of axillary glands differentiates between eccrine glands, producing abundant clear, nonodorous sweat; and apocrine glands, excreting small amounts of turbid, odorous milky sweat. A third type of sweat glands, the "apoeccrine" glands, were recently identified. To define the different types of sweat glands and their location and number, the authors carried out a prospective histologic study on adult human axillary skin, including various immunohistochemical markers. METHODS: Forty-three consecutive Caucasian, subjectively normhidrotic patients, who underwent a surgical procedure in the axilla unrelated to the axillary glands, were included in the study. For verification of normhidrosis, the gravimetric test was carried out by measuring the amount of sweat secretion per minute. Then, a 1 x 1-cm measuring piece of skin and subcutaneous tissue was excised in the apex of the axilla, divided into three samples--altogether, 129 samples--and processed for histologic examination. RESULTS: In the dermis, the authors found only very few eccrine (average, 0.3 gland/cm in only 12 percent of all patients) and apocrine glands (average, 0.1 gland/cm in only 4.7 percent of patients), and no apoeccrine glands in any patient. In the subcutaneous tissue, the mean number of glands per centimeter squared was 10 for the eccrine glands, nine for the apocrine glands, and six for the apoeccrine glands. CONCLUSIONS: In the authors' Caucasian subjects, all or most of the sweat glands were found in the subcutaneous tissue near the border to the dermis and not in the dermis. For extremely hyperfunctioning sweat glands, the authors recommend less radical surgical methods, with the preservation of skin, based on the knowledge that most glands are localized in the subcutaneous tissue.

Giant vascular eccrine spiradenoma: report of a case with immunohistochemical study.

We report a rare case of giant vascular eccrine spiradenoma (GVES) which developed in 56-yr-old Korean woman. It is a rare variant of eccrine spiradenoma (ES), which might be mistaken for angiomatous lesions in view of its florid vascularity and hemorrhagic features. Histogenesis of GVES is not clearly elucidated although it is known that ES presumably originates in the eccrine glands. To clarify the histogenesis of GVES, immunohistochemical stainings using various monoclonal antibodies were also performed. The tumor was composed of three types of cells, namely pale epithelial cells, small basal cells, and myoepithelial cells. Therefore, we conclude that GVES originated from eccrine gland and mainly differentiates toward secretory portion of secretory coil.