Immunohistochemical analysis of cytokeratin expression in eccrine spiradenoma: similarities to the transitional portions between secretory segments and coiled ducts of eccrine glands

Despite light and electron microscopic and histochemical studies, there is no consensus on the cellular differentiation of eccrine spiradenoma. In the present study, eight specimens of eccrine spiradenoma were analysed by immunohistochemical techniques, using a panel of monoclonal antibodies against cytokeratins. Two types of epithelial cells were identified in tumour nodules: large, pale epithelial cells in the centre, and small, dark epithelial cells situated at the periphery. These nodules frequently contained tubular structures lined by cuboidal, columnar or, less commonly, flattened epithelial cells. Cytokeratin expression in eccrine spiradenoma was compared with expression in normal eccrine glands. Immunohistochemistry revealed that large, pale epithelial cells expressed immunophenotypes similar to those of luminal cells in the transitional portions between the secretory portions and the coiled ducts. The small, dark cells expressed immunophenotypes similar to those of basal cells in the transitional portions. Tubular structures observed in eccrine spiradenoma showed staining patterns similar to those of the luminal cells in the transitional portions. Eccrine spiradenoma may, therefore, differentiate towards the transitional portions between the secretory portions and colled ducts of eccrine glands. Some of the large, pale epithelial cells in eccrine spiradenoma differentiate towards tubular structures, forming a lumen lined by a cuticle.     

Papillary eccrine adenoma

A 28-year-old man came to us with a solitary skin colored, mildly tender nodule of 6 months duration on the dorsum of the right hand. On histological examination, multiple dilated ducts without apparent continuity with the surface were found in the dermis. These dilated ducts had branching tubules with eosinophilic amorphous material filling most of the lumina. The peripheral cells of the tubules resembled myoepithelial cells, whereas the luminal border cells were cuboidal or low columnar. Papillary projections arising from the inner cells were seen extending into the lumen. These features were diagnostic of a rare tumor, papillary eccrine adenoma.     

Histogenesis of clear cell hidradenoma: immunohistochemical study of keratin expression

The expression of cytokeratins in 10 cases of clear cell hidradenoma, including 3 cases of solid cystic hidradenoma, were examined using 21 kinds of monoclonal antibodies. We divided them into three histologic patterns: massive nests with a few lumina (M nests), nests with some tubular lumina (L nests), and nests in solid cystic hidradenomas (S nests). All hidradenomas showed similar immunoreactivities to those in the lower dermal ducts or secretory cells of normal eccrine glands. With antibodies against simple epithelial cytokeratins (CKs 7, 8, 18, and 19), however, different immunostaining was noted among the three histologic patterns. Namely, the M nests failed to react to them, although some luminal cells in the L nests revealed a positive staining. Furthermore, a majority of luminal cells in the S nests revealed a positive staining with them. Therefore, we think that the luminal cells in solid cystic hidradenoma mainly differentiate toward the secretory cells, and that the M nests mainly differentiate toward the dermal duct. Those in the L nests are thought to differentiate toward the dermal duct and the secretory cells. The proportion of the differentiation toward luminal cells of dermal ducts to the differentiation toward secretory cells was the main difference among the three nests. In addition, there was no difference in immunophenotypes between clear cells and epidermoid cells in the two kinds of hidradenomas.     

Papillary eccrine adenoma—a light-microscopic and immunohistochemical study

We report a case of papillary eccrine adenoma. This benign cutaneous tumour had a diagnostic microscopic appearance that consisted of multiple dilated ducts lined by two or more layers of cells. The inner layer often formed intraluminal papillary projections of variable complexity. The lumina were filled by eosinophilic amorphous material. Immunoperoxidase studies showed carcino-embryonic antigen in the luminal border of the ducts, but S-100 protein was absent for tumoral ducts. We discuss the eccrine and apocrine differentiation of this neoplasm on the basis of the immunoperoxidase results. The differential diagnosis includes other cutaneous neoplasms with intraductal papillary proliferation.     

Papillary eccrine adenoma: an electron microscopic study

A case of papillary eccrine adenoma was studied by electron microscopy. Dilated ducts that contained granular eosinophilic material, often associated with intraluminal papillary projections were observed. The ductlike structures were composed of basal and luminal cells. Within the luminal cells there were intracytoplasmic cavities, but neither secretory granules nor glandular structure were observed. On the basis of our observations, papillary eccrine adenoma appears to differentiate toward ductal structures of the eccrine sweat apparatus.     

Eccrine hidrocystoma: two cases of Robinson and Smith types.

Two cases of eccrine hidrocystoma, one of which is a "classic" Robinson type and the other a Smith type, were reported. The walls of both cysts consisted mainly of two layers of flat or low cuboidal epithelial cells with eosinophilic cytoplasm. Immunostaining for S-100 protein was negative in the cells of the cyst wall of the Robinson type and only weakly positive in the inner luminal layer of the Smith type. Electron microscopically, the Smith type showed double-layered cuboidal lining and cell membrane interdigitations as junctions of neighboring cells without any characteristics of the secretory segment of sweat glands, indicating substantial similarity to those of the intradermal portion of the eccrine sweat duct.     

Immunohistochemical localization by monoclonal antibody of human epidermal growth factor in mixed tumours of the skin

Immunohistochemical distribution of human epidermal growth factor (hEGF) was described in 17 cases of mixed tumour of the skin with monoclonal antibody. In normal sweat glands, epithelial cells in the secretory portion and in the transitional area between secretory portion and duct showed prominent staining for hEGF. In the salivary pleomorphic adenoma type of mixed tumour of the skin, luminal tumour cells of tubular and duct-like structures gave a very characteristic hEGF staining reaction. The tumour cells showing strong staining for hEGF were scattered throughout the solid foci in this type of mixed tumour. Tubular epithelial cells in the clear cell adenoma type also displayed a positive hEGF reaction. And apocrine mixed tumours strong staining for hEGF occurred on the apical side of tubular and ductal tumour cells. In view of the immunohistochemical staining patterns for hEGF, the histologic origin of mixed tumours of the skin is suggested to be cells in the secretory portion and those in the transitional portion between secretory portion and duct of the sweat gland.     

Mammary and extramammary Paget's disease: expression of Ca 15-3, Ka-93, Ca 19-9 and CD44 in Paget cells and adjacent normal skin

The histogenesis of mammary Paget's disease (MPD) and extramammary Paget's disease (EMPD) cells remains controversial. The purpose of this study was to investigate MPD and EMPD immunohistochemically with antibodies to some tumour markers (Ca 15-3, KA-93 and Ca 19-9), and a cell surface receptor for hyaluronate (CD44), as these have been shown to be expressed in normal eccrine or apocrine glands and/or the epidermis, as well as some tumours. Surgically excised, formalin-fixed, paraffin-embedded tissues, or frozen tissues, from seven mammary, five vulvar, two scrolal and two axillary lesions were studied. Paget cells stained strongly with antibodies to Ca 15-3 and KA-93, but did not stain with those to Ca 19-9 and CD44. Staining with the antibody to Ca 15-3 was also observed in the ductal and secretory portions of the eccrine and apocrine glands, and in the sebaceous gland cells. Staining with the antibody to KA-93 was also seen in the apocrine secretory coils, lactiferous duct, epidermal dendritic cells, and cells in the dermal inflammatory infiltrate. Staining with the antibody to Ca 19-9 was observed only in the eccrine duct, and that to CD44 was seen in eccrine secretory cells and epidermal keratinocytes. These findings suggest that the origin of Paget cells may be the secretory cells of apocrine sweat glands (in EMPD) or the luminal lactiferous ducts (in MPD). We found that the antibodies to Ca 15-3 and CD44 were useful in differentiating Paget cells from surrounding keratinocytes, by showing positive and negative immunoreactivity, respectively.     

Papillary eccrine adenoma: Immunohistochemicai study and literature review

A case of papillary eccrine adenoma on the right forearm of a 78-year-old Japanese woman is reported. The tumor was 1.3 cm in diameter, occupying the whole thickness of the dermis. Histologically, the tumor was composed of dilated tubules of various sizes with intraluminal papillary projections, and was surrounded by a fibrous stroma. An immunohistochemical study revealed that the proliferating tubules were composed of a single outermost layer of α-smooth muscle actin-and keratin 14-positive myoepithelial cells, and keratin 8-positive inner cells. This antigen expression pattern was comparable to that of the normal eccrine secretory coil, which indicates that the tumor differentiated toward the secretory coil of an eccrine sweat gland.     

Immunohistochemical studies of normal sweat glands, sweat gland tumors and extramammary Paget's diseases. II. Immunohistochemical studies of sweat gland tumors and extramammary Paget's diseases

Localizations of 18 antigens were analyzed in 41 cases with benign sweat gland tumors (13 with eccrine acrospiroma, 4 with eccrine spiradenoma, 2 with hidroacanthoma simplex, 9 with chondroid syringoma, 4 with syringocystadenoma papilliferum, 1 with tubular apocrine adenoma, 1 with papillary eccrine adenoma, 1 with apocrine cystadenoma, 1 with cylindroma, 5 with syringoma), 14 with malignant sweat gland tumors (7 with eccrine porocarcinoma, 3 with eccrine duct carcinoma, 3 with apocrine gland carcinoma, 1 with mucinous carcinoma) and 13 with extramammary Paget's disease. The results I obtained were compared with those in the normal sweat glands for determination of a differentiation of each tumor.     

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.     

A complex poroma-like adnexal adenoma

Hidroacanthoma simplex, eccrine poroma, and dermal duct tumor are benign adenomas that develop from excretory ducts of eccrine glands and all three are variants of eccrine acrospiroma. To date, counterparts in apocrine or sebaceous glands have not been reported, but in this study we describe an adnexal, poroma-like adenoma that showed apocrine and sebaceous differentiations. Apocrine structures have the same embryonic origin as does the pilosebaceous system; both are derived from the primary epithelial germ. We suggest that the lesion we describe is truly a sebaceous and apocrine poroma. It must be distinguished from an infundibular adenoma whose pattern reproduces that of follicular poroma.     

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.     

Eccrine tubular adenoma--a histopathological, histochemical, and ultrastructural study

A case of eccrine tubular adenoma on the dorsum of the right foot is presented. Histopathologically, in the central nodule of the tumor, the whole dermis was involved and the tumor islands were connected to the epidermis; in the rest of the lesion, tumor islands were observed in the upper dermis. The tumor islands were composed of cystic or alveolar structures and cell masses possessing multiple lumina. Tubules were surrounded by two or more layers of epithelium forming papillations projecting into the lumen. There were only a few basaloid islands and no sclerotic strands. The tumor cells were well differentiated. Acid mucopolysaccharides were seen in the stroma. Histochemically, phosphorylase and acid phosphatase reacted moderately. Succinic dehydrogenase gave a weak reaction and β-glucuronidase was negative in tumor cells. Ultrastructurally, intracellular ducts with numerous microvilli, periluminal filamentous zones, and many multivesicular dense bodies surrounded by a limiting membrane were observed. Keratohyalin granules were absent. Based on these findings, the tumor reported here was considered to be an adenoma differentiating toward the eccrine duct. Some aspects resembled tubular apocrine adenoma, syringoma and basal cell tumor with eccrine differentiation, but they were most similar to papillary eccrine adenoma.     

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.     

Intra-epidermal and intra-dermal sebocrine adenoma with cystic degeneration and hemorrhage

BACKGROUND: The ducts of eccrine glands may give rise to intra-epidermal, confluent epithelial and intra-dermal adenomas known as hidroacanthoma simplex, eccrine poroma, and dermal duct tumor, respectively. An apocrine and sebaceous counterpart of the eccrine poroma has been described by several authors as adnexal, poroma-like adenoma with apocrine and sebaceous differentiation or sebocrine adenoma. METHODS: Using clinical history and routine histologic techniques, we describe a new lesion with features similar to sebocrine adenoma but representing the intra-epidermal and intra-dermal counterparts with cystic degeneration and hemorrhage. Briefly, an 84-year-old female presented with a 6 mm dark tan papule on the neck that clinically appeared as an unusual macular seborrheic keratosis with underlying hemorrhage. RESULTS: Histopathological examination showed a benign dermal cystic appendage tumor with pale polygonal cells, occasional non-keratinizing ducts, sebaceous differentiation and central hemorrhage with fibrin deposits. Serial sections did not reveal any epidermal connection. However, epithelioid cells with large nuclei in an intra-epidermal pagetoid pattern were focally seen. CONCLUSION: These findings represent a new cystic, hemorrhagic variant of sebocrine adenoma.     

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.     

Ultrastructure of eccrine cystadenoma. A case report

A case of eccrine cystadenoma was studied by electron microscopy. The tumor showed two types of cells, luminal and basal cells. The cells lacked the characteristics of the secretory segment of the sweat glands. The features of the luminal cells are similar to those of the intradermal portion of the eccrine sweat duct. In some areas, the lesion showed features characteristic of apocrine gland structure. Nuclear bodies were very frequent. The ultrastructural findings of eccrine cystadenoma support an origin from the ductal portion of eccrine sweat glands.     

Papillary eccrine adenoma. Immunohistochemical and ultrastructural analyses

A case of papillary eccrine adenoma was analysed with immunohistochemical and ultrastructural methods regarding their direction of differentiation. It was found that the majority of the structures show either eccrine ductal or glandular differentiation. There were some segments, particularly in those exhibiting papillary growth, where cells similar to eccrine secretory (clear) cells or cells with characteristics of both ductal basal cells and glandular myoepithelial cells were present.     

Porokeratotic eccrine ostial and dermal duct naevus with dermatomal trunk involvement: literature review and report on the efficacy of laser treatment

Porokeratotic eccrine ostial and dermal duct naevus (PEODDN) is a rare, benign hamartomatous malformation involving the eccrine sweat duct. The existence of filiform keratinous plugs that represent cornoid lamellae overlying dilated infundibula of eccrine ducts is a distinctive feature and the presence of associated abnormal dermal ducts is frequent. We report a patient with PEODDN who exhibited lesions on the left side of her chest. Cases of PEODDN reported in the literature are reviewed. Our experience in treating this patient with ultrapulsed carbon dioxide laser is also presented.