Immunohistochemical differentiation of four benign eccrine tumors

Background:  The histogenesis and differentiation of eccrine tumors, including cylindroma, poroma, spiradenoma and syringoma, remains controversial. This controversy may be because of sporadic and incomplete studies of these neoplasms.
Methods:  Ten examples each of normal eccrine structures and of four benign eccrine tumors are analyzed with antibodies to cytokeratin (CK) 7, CD34, CK6, CK10, smooth muscle actin (SMA) and CD10. These markers represent two different immunohistochemical stains for each part of the eccrine structure; CK7 and CD34 stain the secretory coil, CK6 and CK10 stain the straight duct and SMA and CD10 stain the myoepithelial cells. This redundancy in staining is performed on four benign eccrine tumors to better interpret the existing literature.
Results:  We find that CK7 is a sensitive marker for the secretory coil; both cylindromas and spiradenomas express CK7. We also find that CK6 is a marker for the inner ductal cells, while CK10 is a marker for the middle ductal cells; syringomas express both these markers. SMA appears to be a more specific marker for myoepithelial cells surrounding normal eccrine coils, and none of the studied tumors express SMA or CD10.
Conclusions:  Our studies suggest that syringomas are tumors of the eccrine duct, while cylindromas and spiradenomas are tumors of the secretory coil.     

Immunophenotypic aspects of cylindroma and nodular hidradenoma

Background Some adnexal tumours have many controversies about their histogenesis. Objectives To evaluate the eccrine and/or apocrine differentiation phenotype in cases of cylindroma and clear cell hidradenoma with CD15 and p63 antibodies. Methodology Slides and blocks of six cases of cylindroma and seven cases of nodular hidradenoma (clear cells) were analyzed by the technique of immunohistochemistry with CD15 and p63 antibodies. Results In all cases of cylindroma we obtained negative results for CD15 antibody and positive for p63 antibody. In five of seven cases of nodular hidradenoma (clear cell), we could easily observe clear cells between 20% and 50% of tumour cells. In the two other cases, cystic lesions were present and occasional clear cells could be seen. The reaction with CD15 antibody was positive in granular and cytoplasmic pattern in six of seven cases, especially in cells with suggestive clear cytoplasm in lower proportion than this clear cells could be seen in haematoxylin and eosin. The positivity for p63 antibody, nuclear pattern, was observed in six of seven cases, in the major part of tumour cells. In only one case, the positivity was in 20% of cells. Limitation Samples are in small number because these are relatively rare tumours. Conclusions The present study suggests eccrine origin for both tumours: cylindroma and clear cell hidradenoma.     

CD44 expression in normal and inflamed skin

CD44 is the principal cell surface receptor for hyaluronate. In non-inflamed skin, CD44 expression is limited to the cell membrane of eccrine coil cells. The distribution on these cells is assymetric, with intense staining on the dermal side and little staining on the luminal side of the coil cell. In skin containing a pathologic process, either inflammatory or neoplastic, CD44 expression can be widespread on the membranes of keratinocytes and on infiltrating lymphocytes in the vicinity of the process. Diverse roles have been proposed for CD44 and largely involve aspects of cellular adhesion in one setting or another. CD44 may identify a more mobile, proliferating keratinocyte that is responding to local injury. In eccrine coil, the stable presence of CD44 on the non-luminal surface of secretory cells indicates an undefined function for CD44 in the generation of eccrine sweat.     

Coexpression of cytokeratin and vimentin intermediate filaments in benign and malignant sweat gland tumors

The coexpression of cytokeratin and vimentin intermediate filaments has been immunohistochemically evaluated in 124 benign and malignant sweat gland tumors of various types in comparison to normal sweat glands. In addition, all neoplasms have been stained by an antibody to alpha-smooth muscle actin. Epithelial cells reacted with the pan-cytokeratin antibody lu-5. In normal sweat glands, vimentin immunoreactivity was restricted to myoepithelial cells and to some cells of the coiled duct. In benign sweat gland tumors (n=88), coexpression of vimentin and alpha-smooth muscle actin was frequently found in basal cells of neoplasms considered to differentiate towards the secretory coil of the eccrine or apocrine gland. These included eccrine spiradenoma, apocrine cystadenoma, hidradenoma papilliferum, syringocystadenoma papilliferum, and cylindroma. Thus, in these tumors, vimentin-reactive cells corresponded to myoepithelial cells. Vimentin-positive cells were also found in 14 of 36 sweat gland carcinomas, including 1 case of sclerosing sweat duct carcinoma, 1 case of porocarcinoma, 4 cases of eccrine adenocarcinoma, 1 case of mucinous eccrine carcinoma, and 5 cases of apocrine adenocarcinoma. Co-expression of vimentin and alpha-smooth muscle actin was observed in some cells of eccrine and apocrine adenocarcino-mas. Therefore, in these neoplasms, some vimentin-positive cells appear to represent myoepithelial cells. In contrast, vimentin-positive cells in all other malignant tumors did not express alpha-smooth muscle actin. Our results indicate that coexpression of cytokeratin and vimentin may be frequently found in a variety of benign and malignant sweat gland tumors. In the majority of these neoplasms, vimentin-positive cells correspond to myoepithelial cells. Because vimentin is not specific for myoepithelial cells, additional stains for alpha-smooth muscle actin should be performed to prove the myoepithelial nature of vimentin-positive cells.     

Myoepithelial differentiation in benign sweat gland tumors

One hundred and two cases of benign sweat gland tumors of the skin were studied for the presence of myoepithelial cells specifically identified by a monoclonal antibody to alpha-smooth muscle actin on paraffin-embedded tissues. The monoclonal antibody gave a positive result in 12 of 12 cases of cylindroma, 14 of 16 cases of spiradenoma, 2 of 2 cases of apocrine tubular adenoma (papillary eccrine adenoma), 5 of 5 cases of apocrine hidrocystoma, 5 of 5 cases of hidradenoma papilliferum, and in 10 of 10 cases of syringocystadenoma papilliferum. Rare myoepithelial cells were detected in only 1 of 10 cases of mixed tumor, apocrine type. There was no immunoreactivity for alpha-smooth muscle actin in eccrine hidrocystoma (2 cases), mixed tumor of eccrine type (2 cases), syringoma (7 cases), hidroacanthoma simplex (1 case), eccrine poroma (14 cases), clear cell hidradenoma (15 cases), and in 1 case of eccrine syringofibroadenoma. Our data support the concept that myoepithelial cells are seen in most sweat gland tumors considered to differentiate toward the secretory coil of the normal sweat gland. In contrast, myoepithelial cells are absent in tumors showing differentiation toward the excretory (ductal) component of the gland.     

Cylindroma and eccrine spiradenoma coexistent in the same lesion

Two patients complained of having a tender nodule. One patient had the nodule on the scalp and the other on the face. Each nodule contained a cylindroma and an adjacent eccrine spiradenoma. While eccrine spiradenoma is of eccrine derivation, the origin of cylindroma is controversial because of variable histochemical and enzyme histochemical findings. The presence of cylindroma and eccrine spiradenoma in one clinical nodule contributes circumstantial evidence for the similar derivation of both tumors.     

CD44 expression in alopecia areata and androgenetic alopecia

CD44 is a widely distributed cell surface protein thought to be involved in multiple steps of normal immune cell function, including T-cell activation, and in cellular adhesion where it mediates cell attachment to hyaluronate. In normal skin, CD44 is found by immunohistochemical means to be primarily in eccrine coil cells. In this study, we have looked at the expression of CD44 in normal scalp and in two different hair disorders, androgenetic alopecia and alopecia areata. In normal scalp and androgenetic alopecia, CD44 was found in its normal distribution in eccrine coil cells. In scalp of 30 patients with alopecia areata, there was no expression of this glycoprotein. Patients were also assessed pre and post treatment for their alopecia areata, and even though they had no significant hair regrowth, 2 patients regained expression of CD44, indicating a variable expression of this protein in the alopecia areata disease process. The absence of CD44 expression in alopecia areata-affected scalp may give further information regarding the pathogenesis of this disease.     

Multiple eccrine spiradenoma: case report and review

Benign eccrine spiradenoma is an adnexal tumor that occurs as either a solitary lesion or as multiple nodules. A case of multiple eccrine spiradenoma occurring on the scalp and mimicking multiple cylindroma is described and discussed. In addition, 9 previously reported cases of multiple eccrine spiradenoma are reviewed.     

Malignant transformation of eccrine tumors

Malignant transformation occurred in pre-existing sweat gland tumors in 7 patients. Three lesions showed an histologic pattern of eccrine spiradenoma, 2 eccrine poroma, one cylindroma and one papillary eccrine adenoma. Malignant transformation was histologically characterized by the presence of solid tumor areas populated with large cells having irregularly shaped nuclei and mitotic figures. There were multiple foci of squamous metaplasia, areas of loss of basement membrane and invasion of the surrounding connective tissue.     

Immunohistochemistry of GCDFP-24 and zinc alpha2 glycoprotein in benign sweat gland tumors

The immunohistochemical localization of two other proteins that are present in breast gross cystic disease fluid, GCDFP-24 and zinc alpha 2 glycoprotein (Zn2GP), were studied in normal skin and in 41 benign sweat gland tumors. GCDFP-24 was localized to apocrine glands. There was no staining of eccrine glands or ducts. There was positive staining in the following sweat gland tumors: apocrine hidrocystoma (four of five), hidradenoma papilliferum (two of four), syringocystadenoma papilliferum (six of seven), mixed tumor (one of one), and glandular elements of cylindroma (one of four). No staining for GCDFP-24 occurred among the following SGT: eccrine hidrocystoma (two cases), eccrine poroma (three cases), syringoma (eight cases), eccrine spiradenoma (two cases), or clear cell hidradenoma (five cases). Zn2GP was localized to both apocrine glands and eccrine glands. Positive staining was seen in the following SGT: apocrine hidrocystoma (five of five), hidradenoma papilliferum (two of four), syringocystadenoma papilliferum (four of seven), mixed tumor (one of one), cylindroma (one of four), eccrine spiradenoma (two of two), and clear cell hidradenoma (one of five). No staining for Zn2GP was seen in the following SGT: eccrine hidrocystoma (two cases), eccrine poroma (three cases), or syringoma (eight cases). GCDFP-24 appears to be a discriminant of apocrine differentiation and function. Zn2GP was expressed predominantly in tumors of apocrine differentiation. However, it was also expressed in some tumors of eccrine differentiation.     

The expression of CD23 in cutaneous non-lymphoid neoplasms

BACKGROUND: Cluster designation 23 (CD23) is generally used as a lymphoid marker. Its utility in cutaneous epithelial tumors has never been studied. In our routine practice, we observed that CD23 reacted strongly with eccrine and apocrine secretory coils. METHODS: Immunohistochemical staining of CD23 was performed in a total of 131 cases of apocrine, eccrine, follicular and other cutaneous non-lymphoid tumors. RESULTS: CD23 expression was detected in all benign apocrine tumors and in half of benign eccrine tumors, particularly those derived from secretory coils. CD23 staining was seen in 42% (8/19) of microcystic adnexal carcinoma (MAC), while no staining was observed in tumor cells of desmoplastic trichoepithelioma, morpheaform basal cell carcinoma and syringoma. All mammary and extramammary Paget's disease were labeled with CD23. In comparison, pagetoid Bowen's disease, melanoma in situ and sebaceous carcinoma exhibited negative staining. In addition, CD23 reacted diffusely with cutaneous mucinous eccrine carcinoma in a manner similar to breast or colonic adenocarcinoma. CONCLUSION: CD23 appears to be a reliable immunohistochemical marker of the eccrine/apocrine secretory coil and helpful in identifying sweat gland tumors of such origin. It is of ancillary value in differentiating MAC from its mimicker. CD23 is a useful addition to the diagnostic immunohistochemical panels for Paget's disease.     

Malignant transformation of eccrine spiradenoma

Two patients are described in whom malignant transformation occurred within an eccrine spiradenoma. Their findings were compared with those of six similar patients from the literature, and a characteristic clinicopathologic picture was evident. The typical history was one of rapid enlargement of a cutaneous nodule of long standing. The neoplasms were composed, at least in part, of large, markedly atypical basaloid cells with numerous mitotic figures. Adjacent benign spiradenoma was observed microscopically in each case, and some of the carcinomas retained architectural features reminiscent of spiradenoma. One patient died of disseminated tumor, but follow-up was short or lacking in several cases. Malignant transformation of eccrine spiradenoma shares many clinical and pathologic features with malignant transformation of dermal cylindroma.     

Papillomavirus antigen in the epidermoid cyst of the sole. Immunohistochemical and ultrastructural study

An epidermoid cyst of the sole was studied immunohistochemically and ultrastructurally. Papillomavirus particles were present in the horny layer and in the upper layers of the epidermis of the cyst and within the acrosyringeal epithelium overlying the cyst. Thickened basal lamina-like structures similar to those found in the eccrine sweat duct tumors such as in cylindroma and eccrine spiroadenoma existed at the epidermal-dermal junction of the cyst wall. Carcinoembryonic antigen was immunohistochemically demonstrated in the center of the epidermoid cyst and the DAB reaction products took the shape of a circle resembling that of the sweat ducts in the horny layer.     

Papillomavirus antigen in the epidermoid cyst of the sole

An epidermoid cyst of the sole was studied immunohistochemically and ultrastructurally. Papillomavirus particles were present in the horny layer and in the upper layers of the epidermis of the cyst and within the acrosyringeal epithelium overlying the cyst. Thickened basal lamina-like structures similar to those found in the eccrine sweat duct tumors such as in cylindroma and eccrine spiroadenoma existed at the epidermal-dermal junction of the cyst wall. Carcinoembryonic antigen was immunohistochemically demonstrated in the center of the epidermoid cyst and the DAB reaction products took the shape of a circle resembling that of the sweat ducts in the horny layer.     

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.     

Pedigree of multiple benign adnexal tumours of Brooke-Spiegler type

A pedigree of autosomal dominant expression of multiple benign adnexal tumours is presented. Seven cases spanning three generations are discussed. The clinical manifestations of these tumours are quite variable, including multiple papules concentrated on the face, scalp nodules and a large turban tumour. One member of the family had a linear papular eruption involving one half of his body. Histopathology of all lesions demonstrated benign adnexal characteristics, including well-characterized eccrine spiradenomas, trichoepitheliomas and an eccrine cylindroma. The cutaneous tumours occurring in these patients have continued to develop during their lifetimes. The authors propose that this pedigree has phenotypic characteristics consistent with Brooke-Spiegler syndrome.     

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.     

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.     

Immunohistochemical detection of carcinoembryonic antigen and protein S-100 in sweat gland tumors

Carcinoembryonic antigen (CEA) and S 100 protein (S 100) have been demonstrated in formalin-fixed paraffin sections of eccrine and apocrine sweat glands, and tumors of the sweat glands, as well as, for comparison, in a variety of tumors deriving from epidermal and follicular structures using the peroxidase-antiperoxidase technique. CEA is detectable, as a membrane antigen, in the normal coil of eccrine sweat glands and in the cytoplasm of luminal cells in eccrine and apocrine sweat ducts up to the horny layer. Nearly all tumors of the sweat glands contain variable amounts of CEA. S 100 is localized in the cytoplasm of eccrine coils and secreted with the sweat. Apparently it is only found in tumors derived from the eccrine and apocrine sweat gland coils. Immunohistochemical demonstration of CEA and S 100 thus facilitates the diagnosis of tumors of the sweat glands and their differentiation from epidermal and follicular tumors.