Characterization of a novel human type II epithelial keratin K1b, specifically expressed in eccrine sweat glands

In this study, we show that a novel human type II epithelial keratin, K1b, is exclusively expressed in luminal duct cells of eccrine sweat glands. Taking this luminal K1b expression as a reference, we have used antibodies against a plethora of epithelial keratins to systematically investigate their expression in the secretory globule and the two-layered sweat duct, which was divided into the intraglandular, intradermal, and intraepidermal (acrosyringium) segments, the latter being further subdivided into the sweat duct ridge and upper intraepidermal duct. We show that (i) each of the eccrine sweat gland tissue compartments expresses their own keratin patterns, (ii) the peripheral and luminal duct layers exhibit a sequential keratin expression, with both representing self-renewing cell layers, (iii) the intradermal duct and the sweat duct ridge display hitherto unknown length variations, and (iv) out of all cell layers, the luminal cell layer is the most robust layer and expresses the highest number of keratins, these being concentrated at the apical side of the cells to form the cuticle. We provide evidence that the cellular and intercellular properties of the peripheral and the luminal layers reflect adaptations to different functions.     

Differentiation of eccrine poroma cells to cytokeratin 1 - and 10-expressing cells, the intermediate layer cells of eccrine sweat duct, in the tumor cell nests

It has been shown that an intermediate cell layer exists between a luminal cell layer and a peripheral cell layer in human eccrine sweat ducts by immunohistochemistry using anti-keratin antibodies 34βB4 and DE-K10. These antibodies react to cytokeratin 1 and 10 respectively, and stain the intermediate cells specifically, but not luminal cells nor peripheral cells. Cytokeratin 1 and 10 are considered to appear as a differentiated keratin in the terminal process of epidermal keratinization. We examined 5 cases of eccrine poroma with 34βB4 and DE-K10. Various numbers of the poroid cells reacted to these anti-keratin antibodies in 4 cases. Some positive cells were observed around the cuticular cells in two of them. The present study demonstrated that terminal differentiation in terms of keratinization can occur in eccrine poromas, and that the 34βB4- and DE-K10-positive cells around the cuticular cells differentiate toward the intermediate cells in cytokeratin expression profile and location.     

Immunohistochemical study of angiotensin receptors in normal human sweat glands and eccrine poroma

BACKGROUND: Angiotensin II exerts its actions through its specific receptors. However, expression of these receptors has not been determined in sweat glands. OBJECTIVES: To clarify the expression and localization of the angiotensin receptors in normal human sweat glands and eccrine poroma. METHODS: Expression of angiotensin type 1 (AT1) and type 2 (AT2) receptors in normal human eccrine and apocrine sweat glands and 12 cases of eccrine poroma was studied using immunohistochemistry. RESULTS: In eccrine sweat glands, the acrosyringium and the inner surfaces and luminal cells of the intradermal duct showed positive staining with AT1. In apocrine sweat glands, the intraepithelial duct and luminal cells of the intradermal duct showed positive staining with AT1. In 12 cases of eccrine poroma, some of the tumour cells in the tumour strands and cells surrounding the luminal structures stained positively. There were no positive findings with AT2. CONCLUSIONS: Studying AT1 distribution may be useful in understanding the pathophysiology of sweat glands and sweat gland tumours.     

Comparative cytokeratin analysis of sweat gland ducts and eccrine poromas

Summary Human eccrine sweat gland ducts and benign and malignant eccrine poromas were studied for the expression of various cytokeratins (CK) and vimentin by applying immunoperoxidase and immunofluorescence microscopy to frozen or paraffin-embedded sections, and using two-dimensional gel electrophoresis and immunoblotting. In acrosyringia and dermal eccrine ducts, the luminal cells exhibited intense staining for CKs 1/10/11 and 19. The periluminal cell layers of acrosyringia contained CKs 1/10/11, while CK 5 was absent. In contrast, the basal cell layer of dermal ducts was only positive with the antibody against CK 5, i. e. a pattern resembling that seen in epidermal basal cells. CK 9 was detected only in keratinocytes peripherally surrounding acrosyringia. In benign poromas, gel electrophoresis revealed that CKs 5 and 14 were predominant, with CKs 6, 16 and 17 being minor components. At the immunohistochemical level CKs 1/10/11 and 19 could be further detected with varying frequency in scattered or clustered cells and/or duct-like structures. Occasionally, CK 9-positive cells were observed. Malignant poromas displayed a similar overall gel-electrophoretic pattern. Their immunohistochemical staining patterns were also similar to (albeit rather more variable than) those seen in benign poromas. Our results show that, with respect to their CK expression pattern, the majority of poroma cells resemble the basal cells of both the dermal ducts and the epidermis, while only minor and variable subpopulations acquire features present in ductal/acrosyringial luminal cells that would be indicative of poral differentiation. Thus, the matrix cells of poromas seem to be most closely related to basal cells located at the transition between the glandular epidermal ridge and dermal eccrine duct, being in no way analogous to the cells of the adult acrosyringium above the basal cell level.     

Cytokeratin expression of apocrine and eccrine poromas with special reference to its expression in cuticular cells

BACKGROUND: There are no immunohistochemical studies on cytokeratin (CK) expression in large series of cases of apocrine poroma. In addition, detailed immunohistochemical analysis of cuticular cells, a specific type of constituent cells of poromas, has not been reported. METHODS: Using the avidin-biotin method, we compared immunostaining patterns of eleven different anti-CK antibodies in 12 cases of apocrine and 21 cases of eccrine poromas, and normal adult skin. RESULTS: Poroid cells were exclusively positive for CK1/5/10/14, CK5/8 and CK14, which were expressed in the outer cells of normal dermal sweat ducts. Poroid cells were heterogeneously stained with anti-CK7, CK8/18, CK 10/11 and CK19 antibodies, which reacted in the inner cells of dermal ducts and in the secretory cells of sweat glands. The cuticular cells showed constant expression of CK1/5/ 10/14 and CK10/11, and various expression patterns of CK5/8, CK6, CK7, CK14, CK8/18, CK17, and CK19. CONCLUSIONS: Based on the keratin immunohistochemistry, the neoplastic cells in eccrine and apocrine poromas are considered to be closely related to the cells of dermal sweat ducts. Also the cuticular cells are considered to occupy an intermediate spectrum between the inner and outer cells of the dermal ducts. Although it is difficult to differentiate apocrine poroma from eccrine poroma by keratin expression patterns alone, the data obtained here can be helpful in differentiation of apocrine poroma from other hair follicle-related neoplasms.     

Immunohistochemical detection of calmodulin. A contribution to the histogenetic classification of eccrine poroma and clear cell acanthoma

In previous immunohistochemical studies calmodulin (CaM) was detected in the sweat duct. In further investigations we searched for CaM-reactivity in eccrine poromas and clear cell acanthomas. CaM was only detectable in whorl-like areas, so confirming the concept of a ductal origin of this tumor. CaM-reactivity was failing in both, intraepidermal and malignant eccrine poroma. Acanthomas with clear cell pattern failed to give uniform results, suggesting a heterogenous origin of clear cells in the tumours investigated.     

Poromatosis in pregnancy: a case of 8 eruptive poromas in the third trimester

The poroid family of neoplasms includes hidroacanthoma simplex, eccrine poroma, dermal duct tumor, and poroid hidradenoma. These benign adnexal neoplasms are derived from the eccrine or apocrine sweat ducts or glands. Poroid neoplasms, including poromas, have been reported during pregnancy and have been hypothesized to be hormonally influenced. Poromatosis, the occurrence of multiple poromas, rarely has been reported in association with hidrotic ectodermal dysplasia, prior radiation therapy, and non-Hodgkin lymphoma occurring after chemotherapy. We report a case of eruptive poromatosis in pregnancy with 8 poromas occurring in the third trimester, further supporting the hypothesis of a hormonal association in the etiology of this neoplasm.     

Eccrine poroma. A clinico-pathologic and immunohistologic study with special reference to tumor cell differentiation]

In this study 15 eccrine poromas were analysed clinically, histologically and immunohistologically. They were all solitary lesions, showing a predilection for the head and neck. In none of the tumours was diagnosis possible on the basis of clinical examination. Histomorphologically, eccrine poromas were characterized by aggregations of neoplastic cells continuous with the epidermis. The neoplasms consisted of two cell types, poroid and cuticular. Poroid cells predominated, while cuticular cells were only found in small foci, sometimes showing tubular differentiation. Immunohistologically, most of the tumour cells showed a cytokeratin pattern (CK1, 5, 10, 11+, CK1-19+) favouring differentiation toward the abluminal cell of the dermal eccrine duct rather than toward the abluminal cell of the intraepidermal segment of the eccrine duct. Only a small proportion of cells revealed the immunohistological features of the abluminal cell of the intraepidermal duct (CK1+, CK1, 5, 10, 11+, CK1-19+). In addition, cuticular cells showed differentiation toward the luminal cell of the eccrine duct (CK19+, CK1, 5, 10, 11+, CK1-19+). Simple-type cytokeratins such as CK7 and CK18 were not expressed. In conclusion, our findings favour the hypothesis that ascribes the origin of eccrine poroma to a pluripotential stem cell of the transitional zone between the dermal and the intraepidermal segments of the eccrine duct.     

Eccrine Poroma on the Postauricular Area: A Rare Presentation

An eccrine poroma is a benign neoplasm that originates from the intraepidermal ductal portion of the eccrine sweat duct. Although eccrine poromas are most commonly found on the sole or side of the foot, eccrine poromas have been observed on other areas of the skin, such as the scalp, neck, and chest. We report an interesting case of an eccrine poroma, which presented as a 1×1 cm protruding dome-shaped, skin-colored-to-black nodule on the right postauricular area. The patient denied a previous history of trauma to this area. The histopathologic diagnosis was consistent with an eccrine poroma. There has been no local recurrence 5 months after complete excision.     

Clear-cell porocarcinoma in situ: a cytologic variant of porocarcinoma in situ.

Poromas are benign neoplasms composed of poroid and cuticular cells. Four histopathologic variants of poromas are accepted, according to the architectural features of the neoplasm: hidroacanthoma simplex or intraepidermal poroma; eccrine poroma, which is a poroma connected to the epidermis that extends to superficial dermis; dermal duct tumor, which develops when the neoplasm is composed of small, solid aggregations of poroid and cuticular cells confined to the dermis with little or no connection with the epidermis; and poroid hidradenoma, which is a solid-cystic, dermal poroma. The malignant counterpart of hidroacanthoma simplex is named malignant hidroacanthoma simplex or porocarcinoma in situ. This report describes an example of clear-cell malignant hidroacanthoma simplex, a cytologic variant of porocarcinoma in situ, which, to our knowledge, has not been previously reported. In contrast with other clear-cell neoplasms, a relation with diabetes mellitus could not be clearly established in this case.     

Distribution of epithelial membrane antigen in eccrine poroma.

Using immunohistochemical methods, we investigated the distribution of epithelial membrane antigen (EMA) on the normal eccrine gland, eccrine poroma and hidroacanthoma simplex. Granular membrane-associated reaction of EMA was detected on the outer cells of both the intraepidermal and the upper portion of intradermal eccrine ducts, as well as on the luminal surfaces and intercellular canaliculi of eccrine glands. Clear immunolabeling was also present in the tumor cells of eccrine poroma and hidroacanthoma simplex. Thus, it is suggested that the constituent cells of these tumors originate from the outer cells of the intraepidermal and/or the upper portion of the intradermal eccrine ducts. There was no immunolabeling for EMA on the tumor cells of seborrheic keratosis and basal cell carcinoma. Immunohistochemical staining for EMA is a useful tool for the diagnosis of skin appendage tumors.     

A single lesion showing features of pigmented eccrine poroma and poroid hidradenoma

Poroid hidradenoma (PH) is a variant of poroma. This entity was defined by Abenoza and Ackerman in 1990. This neoplasm shows architectural characteristics of hidradenoma (tumor cells confined entirely within the dermis in both solid and cystic components) and cytologic characteristics of poroid neoplasm (poroid and cuticular cells, the latter showing ductal differentiation). We herein document a case of single poroid lesion with the features of both eccrine poroma and PH. The patient was a 55-year-old woman with a pigmented nodular lesion on her upper back for 7 years. The histopathologic features of the lesion were consistent with those of eccrine poroma and PH. Unlike most eccrine poromas, this case was pigmented, clinically and microscopically.     

Distribution of cytokeratin polypeptides in syringomas. An immunohistochemical study on paraffin-embedded material.

The distribution of cytokeratin (CK) polypeptides expressed in syringomas (12 cases) was compared with that in normal eccrine sweat ducts using immunohistochemical techniques on paraffin-embedded tissue. Intradermal and intraepidermal segments of the eccrine duct showed reactivity with an antibody to CK1/5/10/11 in all cell layers, whereas CK19 expression was restricted to the luminal cell layer. CK14 was expressed in all cells of the eccrine duct except for the peripheral cells of the intraepidermal duct. Expression of CK5/6 was seen in the basal cells of the dermal duct and of the lower intraepidermal duct (sweat duct ridge) exclusively. Reactivity with an antibody to CK1 was found in the intermediate cells of the uppermost part of the eccrine dermal duct. In addition, this antibody gave a strong staining of the peripheral cells of the intraepidermal duct, leaving basal cells of the sweat duct ridge and luminal cells unstained. In syringoma, CK distribution was essentially comparable with that found in the uppermost part of the dermal duct and in the sweat duct ridge. Namely, ductal luminal cells expressed CK1/5/10/11, CK19, and variably CK14. Intermediate cells of ductal structures and solid nests were homogeneously stained by antibodies to CK1 and CK1/5/10/11, whereas CK14 was expressed heterogeneously. The basal or outermost layer of ductal structures and solid nests was reactive with antibodies to CK1/5/10/11, CK5/6, and CK14. With regard to CK expression, the results indicate that syringoma represents a tumor differentiating toward both the uppermost part of the dermal duct and the lower intraepidermal duct (sweat duct ridge) of the eccrine sweat gland.     

Eccrine Poroma: One Tumor, Many Faces

Pinkus initially described eccrine poroma as a benign neoplasm of the acrosyringium. The tumor, often consisting of broad anastamosing bands, arises from the epidermis and extends downward into the dermis. However, it may be completely intraepidermal ("hidroacanthoma simplex"), and, at times, appear to be completely dermal ("dermal duct tumor"). The characteristic tumor cell is squamoid, but smaller than the epidermal squamous cell. The cell has a cuboidal appearance with a uniform basophilic nucleus, and intercellular bridges. One can usually observe a sharp line of demarcation between the adjacent epidermis and the tumor cells. The histological sections presented are offered as evidence of the eclectic nature of eccrine poroma. The examples to be discussed include: the intraepidermal variant, the intraepidermal variant with "microcysts, the intraepidermal variant with "macrocysts" the epidermal/classic variant, the dermal variant, the pigmented variant, the irritated variant, the chondroid variant, the syringomatous variant and the focally malignant variant. Each example has the classic features of eccrine poroma and an outstanding individual characteristic. But, all are eccrine poromas. These specimens are from the Medical College of Virginia/Francis H. McMullan collection, representing fifty years of practice, teaching and service.     

Ultracytochemical study on eccrine acrsyringium of human embryos

Summary Ultracytochemical demonstration of acid phosphatase (ACPase) activity during the developing of intraepidermal eccrine sweat duct (eccrine acrosyringium) of human embryos was performed in order to elucidate the functional relationship between multivesicular dense bodies and intracellular cavities formed within the inner cells of eccrine sweat apparatus anlagen and to clarify the ultracytochemical characteristics of the multivesicular dense bodies. ACPase activity was characteristically detected in the unit membrane structures of small pinched-off vesicles within cavities and of immature microvilli lining these cavities as well as in those of multivesicular dense bodies. These findings give strong support to the theory that the multivesicular dense bodies are lysosomes and through their action the autolytic formation of intraepidermal eccrine sweat duct is carried out.     

Poromatosis: the occurrence of multiple eccrine poromas

Eccrine poromas are rare, benign adnexal tumors derived from the intraepidermal portion of sweat ducts. Historically they were thought to arise from eccrine ducts although today it is thought that they may also have an apocrine origin. They usually appear as solitary, slow-growing, skin-colored papules on acral surfaces. Here we present the unusual situation of a patient with multiple poromas only three of which are located near the distal extremities.     

Sudoriferous acrosyringeal acantholytic disease

Three selected cases of transient acantholytic dermatosis were studied because of their definitive correlation with sweating due to fever and/or bed-ridden situations. Biopsy specimens were serially sectioned and acantholysis was found in the acrosyringium or traced to connect to the acrosyringium in all biopsy specimens. Carcinoembryonic antigen (CEA) and eccrine gland-specific monoclonal antibody, IKH-4, were positive in acantholytic cells. Electron microscopy revealed electron dense material filling the lumen of intraepidermal eccrine ducts. This material leaked into lateral intercellular spaces of the luminal cells, passing tight junctions. Marked edema and numerous lysosomes were reminiscent of those found when eccrine acrosyringium is formed in the embryo; this suggested that an occluded and damaged eccrine intraepidermal duct was being rebuilt via lysosomal digestion.     

Immunohistochemical identification of interleukin 1α and β in human eccrine sweat-gland apparatus

Bouin-fixed paraffin sections or acetone-fixed cryostat sections were labelled with the avidin-biotin complex (ABC) or peroxidase-antiperoxidase (PAP) method using three monoclonal antibodies (MAbs) and two polyclonal antisera to human recombinant interleukin I beta (IL-I beta) and three polyclonal antisera to human recombinant interleukin I alpha (IL-I alpha). In the secretory coil both IL-alpha and beta were detected in the clear, but not in the dark cells. Both luminal and basal cells of the coiled and straight ducts expressed IL-I alpha and beta, the IL-I labelling being more intense in the luminal cells. IL-I was not usually detected in the initial portion of the intraepidermal eccrine sweat duct, whereas intense labelling was seen in the upper part including through the stratum corneum. In skin biopsies of the palm, taken after exercise, there was only faint IL-I labelling of the secretory cells, whereas the luminal cells of the dermal ducts showed intense labelling for both IL-I alpha and beta. In the acrosyringium, exercise did not alter the pattern for IL-I alpha and beta, except that in the palm, some of the antibodies to IL-I beta produced a more intense immunolabelling of the acrosyringeal cells. This study identifies a distinct and similar distribution of the two forms of IL-I throughout the eccrine sweat-gland apparatus and indicates that part of the IL-I epidermal pool originates from the sweat.     

Immunohistochemically detectable duct-like structures in benign and malignant eccrine poromas: CEA and involucrin immunostaining

The duct-like structures present in 7 cases of benign and malignant eccrine poroma were examined by immunohistochemical staining for carcinoembryonic antigen (CEA), involucrin, and S-100 protein. The demonstration of CEA and involucrin was helpful in the recognition of these structures. The overt immunopositivity precedes morphological evidence for duct formation. On the basis of the CEA immunostaining, the duct-like structures were divided into 4 types: 1) mature acrosyringeal structure, 2) cystic luminal structure lined by elongated cells, 3) immature acrosyringeal structure, and 4) vacuole- or dot-like potential lumen in a single cell. Involucrine was observed in the lining cells of 1) and 2). None of the 4 types showed positive reactivity for S-100 protein, suggesting the irrelevance of these structures to the secretory element of sweat gland. The polymorphism of the ductal formation tended to be more remarkably observed in malignant eccrine poromas than in the cases of benign eccrine poroma and poroepithelioma tested.     

Poroma: a review of eccrine,apocrine, and malignant forms

Poroma is a benign adnexal neoplasm of the terminal sweat gland duct. Although poromas have traditionally been thought to originate from the eccrine sweat gland, there have been cases of apocrine etiology as well. Eccrine and apocrine poromas typically present as erythematous or flesh‐colored nodules on the palms and soles. As these features overlap with a multitude of differential diagnoses, it is imperative to have a firm understanding of the characteristics that make the diagnosis of poroma. In addition, the malignant counterpart to the poroma, the eccrine porocarcinoma, manifests in a similar nonspecific fashion. Case studies and literature reviews have contributed immensely to our present knowledge of poroma and porocarcinoma. Given the rarity of these neoplasms, however, there remains a relative paucity of information on atypical presentations and rates of malignant transformation. In this article, the epidemiology, clinical presentation, diagnosis, and management of poroma and porocarcinoma will be reviewed. This systematic approach may serve as a guide in navigating the diagnostic dilemma of these rare cutaneous lesions.