Mucinous differentiation in adnexal sweat gland tumors

We report an ecerine acrospiroma, on the cheek of a 29-year-old female, in which the presence of abundant mutinous (goblet cell) metaplasia closely mimicked a primary mucoepidermoid carcinoma. To determine the frequency of mutinous differentiation in benign adnexal sweat gland tumors, we evaluated sixty-five cases in hematoxylin and eosin stained sections for the presence of goblet cells and sixty of these for mucicarmine positivity. Goblet cell metaplasia was seen in 3 of 12 acrospiromas, 1 of 8 mixed tumors, and in 1 of 9 cases of syringocystadenoma papil-liferum. All goblet cells were positive for mucicarmine, except in one case of acrospiroma, where goblet cells were not detected on the section stained with mucicarmine. In addition, intracellular mucin, inclusive of goblet cells, was seen in 5 of 12 acrospiromas, 1 of 11 poromas, 5 of 8 mixed tumors, 3 of 13 spiradenomas, 1 of 5 cylindromas, 3 of 9 cases of syringocystadenoma papilliferum and 1 of 3 nipple adenomas. The majority of the tumors had both extracellular mucicarmine positivity (40 of 60) and luminal mucicarmine positivity (39 of 60). We conclude that mutinous differentiation in sweat gland tumors, as defined by the presence of goblet cells and/or intracellular mucicarmine positivity, is common and does not indicate aggressive behavior. Mucinous differentiation in benign sweat gland tumors should not be confused with more aggressive mucoepidermoid carcinomas of salivary gland origin or adenosquamous carcinoma.     

Expression of differentiation antigens in benign sweat gland tumours

Fifty benign sweat gland tumours were studied for the expression of carcinoembryonic antigen (CEA) and apocrine epithelial antigen (AEA), using immunohistochemical methods. CEA was found in thirty-two and AEA in thirty-three neoplasms. Both antigens were located in the epithelium of the luminal structures and in the intraluminar material and CEA was occasionally found also in proliferating cells. Co-expression of CEA and AEA occurred frequently in cases of syringoma, syringocystadenoma papilliferum, hidradenoma papilliferum, eccrine spiradenoma and clear cell hidradenoma. AEA was seen also in tumours showing eccrine differentiation, even though it is not present in normal eccrine sweat ducts.     

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.     

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.     

Secretory immunoglobulin A in sweat gland tumors

The presence of immunoglobulin A (IgA) and secretory component (SC) was investigated in normal human skin and in cutaneous neoplasms including a variety of sweat gland tumors. Immunohistochemistry in normal sweat glands revealed the occurrence of secretory IgA (sIgA) as indicated by reactivity for IgA and SC in serial sections. The majority of 28 cases of sweat gland tumors could be demonstrated to retain their ability to produce IgA and SC. In normal as well as in neoplastic sweat glands heaviest staining for sIgA could be found in the lumina and at the surface of lining epithelia. This is comparable with the presence of sIgA in breast or intestinal neoplasms. In contrast other epidermal cysts or solid tumors were not labelled. In view of recent immunohistochemical studies the demonstration of IgA and SC may be of differentiating value in cutaneous glandular neoplasms.     

Immunohistochemical markers of sweat gland tumors

Using immunoperoxidase methods, normal sweat glands, 44 benign and 4 malignant sweat gland tumors were tested for the presence of carcinoembryonic antigen (CEA), pregnancy-specific-B1-glycoprotein (SP1) and actin (ACT). CEA and SP1 stained the secretory and duct-lining cells of normal eccrine glands. Among benign tumors, 74% were positive for CEA and 44% for SP1. The staining reaction was found mainly in luminal secretions and surrounding cells. Staining by SP1 was reduced, but not suppressed, after absorption with the purified antigen. ACT was found in myoepithelial cells of the secretory tract of normal glands and in basal cells of all cases of hidradenoma papilliferum. Only 3 sweat gland carcinomas reacted for CEA. In a malignant chondroid syringoma, no ACT-positive cells were seen in the myxochondroid stroma. The potential value of CEA, SP1 and ACT in the diagnosis of sweat gland tumors is discussed.     

DNA image cytometry in malignant and benign sweat gland tumours

The histopathological differentiation between well‐differentiated carcinomas and atypical adenomas of sweat gland origin may be difficult, even if immunohistochemical methods are used. Therefore, additional techniques may be helpful. We previously demonstrated that DNA image cytometry (ICM‐DNA) can be useful in distinguishing between malignant and benign clear cell hidradenoma. In the present study, a larger series of sweat gland tumours, with a clear‐cut diagnosis as malignant or benign on histopathological criteria, was examined by ICM‐DNA. Enzymatic cell separation specimens were prepared from paraffin‐embedded tissues of 18 sweat gland carcinomas (14 porocarcinomas, one classic eccrine adenocarcinoma, two microcystic adnexal carcinomas and one mostly ductal apocrine carcinoma) and 47 benign sweat gland tumours (three syringocystadenomas, five spiradenomas, 14 cylindromas, three syringomas, seven nodular hidradenomas, 10 cutaneous mixed tumours, four poromas and one apocrine hidrocystoma). Specimens were examined by ICM‐DNA according to the current recommendations of the European Society for Analytical Cellular Pathology with the AutoCyte QUIC‐DNA workstation using mesenchymal cells as an internal reference. DNA aneuploidy was detected by the stemline interpretation according to Böcking and/or at least three 5[c]‐exceeding events. DNA aneuploidy was detected in 16 of 18 (89%) of the sweat gland carcinomas, but in none of the 47 adenomas. These results suggest that the detection of DNA aneuploidy in sweat gland tumours using ICM‐DNA is a clear and specific indicator of prospective malignancy.     

Immunohistochemical study of lysozyme in various benign sweat apparatus tumors

We investigated the existence of lysozyme in various sweat apparatus tumors by adopting the avidin-biotin-peroxidase complex method. Positive reactions for lysozyme were found in four cases of apocrine cystadenoma, hidradenoma papilliferum, and an apocrine sweat apparatus benign tumor resembling "apocrine spiradenoma", all of which derive from apocrine sweat apparatus. On the other hand, in ten cases of syringoma, eccrine hidrocystoma, clear cell hidradenoma, eccrine spiradenoma, and eccrine poroma, which derive from eccrine sweat apparatus, no positive stainings for lysozyme were obtained. In four out of five cases of mixed tumor of the skin, the apocrine type exhibited positive results. Two cases of syringocystadenoma papilliferum were negative for lysozyme. The investigation of lysozyme in various sweat apparatus tumors is useful in determining the direction of differentiation in these tumors.     

Bowen''s disease with invasive carcinoma showing sweat gland differentiation

A 75-year-old Japanese woman presented an erythematous macular lesion on the flexor aspect of her left wrist. A reddish nodule, 4 mm in diameter, was observed at the medial portion of the macule. The macular lesion was histologically confirmed to be a typical Bowen's disease. The nodular lesion was composed of intradermal solid nests of bowenoid neoplastic cells, and in some areas of the dermal component, prominent gland-like structures were observed. Immunohistochemically, most neoplastic cells of the intradermal solid nests were positive with S-100 protein, and the cells lining the gland-like structures along with amorphous material within the lumens were positive with carcinoembryonic antigen. Judging from these findings, this case was diagnosed as Bowen's disease with invasive carcinoma, whose dermal component showed sweat gland differentiation not only morphologically but also immunohistochemically.     

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.     

Multiple tumors of follicular infundibulum with sweat duct differentiation

A 67-year-old man is reported with multiple tumors of follicular infundibulum containing ducts. Approximately 30 hypopigmented, scaling macules and minimally elevated papules were present on the face. Skin biopsy specimens from 5 representative lesions revealed similar findings. There was a proliferation of ramifying strands of pale-staining keratinocytes in the upper dermis showing connections with follicular infundibula of vellus follicles and epidermis. There was evidence of hair follicle differentiation with small follicular bulbs, papillary mesenchymal bodies, keratocysts, and occasional hair shafts in the tumor. These findings are characteristic of prior reports of TFI. Ducts were also present within the epithelial cords. Carcinoembryonic antigen, gross cystic disease fluid protein-15, epithelial membrane antigen, and S-100 protein were identified within the tumor. We theorize that the ductal elements within these TFI reflect the multipotential differentiating capacity of portions of infundibular epithelium.
Horn TD, Vennos EM, Bernstein BD, Cooper PH. Multiple tumors of follicular infundibulum with sweat duct differentiation.     

Immunohistochemistry of gross cystic disease fluid protein (GCDFP-15) in 65 benign sweat gland tumors of the skin

Sixty-five cases of benign sweat gland tumors of the skin were studied for the expression and localization of gross cystic disease fluid protein-15 (GCDFP-15) by immunoperoxidase methods. There was positive staining of tumors of probable apocrine differentiation in 10 of 11 cases of apocrine hidrocystoma and five of five cases of hidradenoma papilliferum. There was no immunoreactivity for GCDFP-15 for tumors of probable eccrine differentiation, including five cases of eccrine hidrocystoma, five cases of eccrine poroma, five cases of eccrine spiradenoma, 10 cases of clear cell hidradenoma, and nine cases of syringoma. There was variable positive staining of tumors of more uncertain histogenesis, including eight of eight cases of syringocystadenoma papilliferum, one of four cases of cylindroma, and two of two cases of chondroid syringoma (mixed tumor). The above data support a functional differentiation of the expression of GCDFP-15 by eccrine compared to apocrine glandular epithelium with benign tumor development.     

Vascular eccrine giant spiradenoma--a case report with histology and immunohistology of a rare variant of benign sweat gland tumors

Giant vascular eccrine spiradenoma (GVES) is a rare variant of benign tumors of the sweat glands, which differs from common eccrine spiradenoma in both its size and vascularity. Clinically as well as macroscopically, this intradermal or subcutaneous encapsulated tumor might be mistaken for an angiomatous lesion or thrombosis. Histological examination reveals clearly delimited "cords" showing two types of cells, prominent blood-filled cavities and extensive hemorrhages. According to immunohistochemical findings, the epithelial cells contain cytokeratin, protein S-100 and carcino-embryonal antigen (CEA). Like the endothelial cells of vessels, some of the luminal epithelial cells also bind Ulex europaeus lectin; however, they do not show factor VIII-associated antigen.     

Immunohistochemical demonstration of ferritin in sweat gland and sweat gland neoplasms

Using a rabbit anti-human liver ferritin antibody, we examined the binding patterns of this reagent in normal skin and observed a unique binding pattern limited to the outermost layer of the eccrine duct. Examination of a variety of sweat gland neoplasms revealed 2 distinct patterns. One was the binding of this antibody to the outermost layer of cells in the epithelial cords of syringoma, producing a characteristic ring when seen in cross-section. This pattern of binding did not occur in other neoplasms known to be related to the eccrine duct such as dermal duct tumor and eccrine poroma. Only sparse sporadic binding occurred in other eccrine and apocrine neoplasms. A second characteristic binding pattern, not related to that noted in syringoma and diffuse in pattern, was seen in acrospiroma and in a number of adnexal carcinomas. Diffuse ferritin expression has been described in malignant neoplasms in tissues other than skin. Diffuse ferritin staining of certain sweat gland neoplasms may be an indication of biologic activity and potential aggressivity of these neoplasms.     

Myoepithelial differentiation in basal cell carcinoma

Five cases of basal cell carcinomas (BCC) of the skin are described showing morphologic and immunohistochemical features of myoepithelial differentiation. Histologically, they were characterized by a dermal proliferation of tumor cells connected with the epidermis by areas showing the features of conventional BCC, with the deeper portions of the lesion showing a population of oval to spindle cells with eccentric nuclei and homogeneous, ground-glass, or hyaline eosinophilic cytoplasm characteristic of the so-called hyaline cell of myoepithelial tumors of salivary glands. Additionally, scattered cells showing a signet ring configuration were present, and in two cases, focal areas displaying chondromyxoid elements were also seen that appeared to merge imperceptibly with the surrounding spindle cell population. By immunohistochemistry, the tumor cells in the spindle cell component showed strong, diffuse positivity for CAM 5.2 and muscle specific actin, and variable expression of keratin AE1/AE3, vimentin, glial fibrillary acidic protein, and S-100 protein, these findings being consistent with the immunostaining pattern of myoepithelial cells and their neoplasms. A brief review of the literature on the topic is presented, along with a discussion of the possible pathogenesis of this process.     

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.     

Eccrine sweat gland development and sweat secretion

Eccrine sweat glands help to maintain homoeostasis, primarily by stabilizing body temperature. Derived from embryonic ectoderm, millions of eccrine glands are distributed across human skin and secrete litres of sweat per day. Their easy accessibility has facilitated the start of analyses of their development and function. Mouse genetic models find sweat gland development regulated sequentially by Wnt, Eda and Shh pathways, although precise subpathways and additional regulators require further elucidation. Mature glands have two secretory cell types, clear and dark cells, whose comparative development and functional interactions remain largely unknown. Clear cells have long been known as the major secretory cells, but recent studies suggest that dark cells are also indispensable for sweat secretion. Dark cell‐specific Foxa1 expression was shown to regulate a Ca²⁺‐dependent Best2 anion channel that is the candidate driver for the required ion currents. Overall, it was shown that cholinergic impulses trigger sweat secretion in mature glands through second messengers – for example InsP3 and Ca²⁺ – and downstream ion channels/transporters in the framework of a Na⁺‐K⁺‐Cl^? cotransporter model. Notably, the microenvironment surrounding secretory cells, including acid–base balance, was implicated to be important for proper sweat secretion, which requires further clarification. Furthermore, multiple ion channels have been shown to be expressed in clear and dark cells, but the degree to which various ion channels function redundantly or indispensably also remains to be determined.