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.

Syringomatous carcinoma in a young patient treated with Mohs micrographic surgery.

Syringomatous carcinoma (SC) has typically been observed in middle-aged and older patients. We report a case of SC mimicking an epidermoid cyst in a 23-year-old Asian man. Histopathologic examination results showed a dermal neoplasm consisting of nests of basaloid cells, focal areas of ductal differentiation, moderate dermal fibrosis, and moderate nuclear atypia consistent with a diagnosis of SC. No perineural involvement was noted. Results of 2005. immunohistochemical analysis revealed positivity for high- and low-molecular-weight cytokeratins, as well as for carcinoembryonic antigen (CEA). There was scattered immunoreactivity to S-100 protein. The tumor was completely excised Pennsylvania. using Mohs micrographic surgery (MS). This case demonstrates the importance of differentiating SC from other benign or malignant entities, the value of a prompt diagnosis of SC, and the effective treatment of SC with MMS.

Merkel cells and sclerosing epithelial neoplasms.

Merkel cells are normal constituents of the basal layer of the epidermis and the follicular epithelium. They have been identified in benign neoplasms with follicular germinative differentiation but seem to be absent in basal cell carcinomas (BCCs). Because sclerosing epithelial neoplasms are often sampled by small biopsies, any method that enables distinction among them would be welcome. We used immunohistochemical staining for cytokeratin 20 to assess the presence of Merkel cells in 14 cases of desmoplastic trichoepithelioma (DTE), 12 specimens of syringoma, 11 samples of morpheiform BCC, and 8 specimens of microcystic adnexal carcinoma (MAC). Merkel cells were found in association with all 14 specimens of DTE and in 1 of 11 cases of morpheiform BCC (p < 0.005) but in none of the specimens of syringoma or MAC. Our study supports previous findings that Merkel cells are seen in association with cutaneous neoplasms that are benign and of a follicular germinative origin. Although MAC may differentiate along follicular-sebaceous-apocrine lines, the absence of Merkel cells within it is consistent with its malignancy. The identification of Merkel cells in a sclerosing epithelial neoplasm of the skin points to DTE as the most likely diagnosis.

Cell proliferation in skin tumors with ductal differentiation: patterns and diagnostic applications.

The kinetic features of skin tumors with ductal differentiation (TDD) remain mainly unknown. We selected 88 skin TDD (D-PAS-positive cuticles) classified according to Murphy and Elder's criteria. Tumors studied included 13 poromas, 12 nodular hidradenomas, 10 cylindromas, 6 spiradenomas, 9 syringomas, 9 chondroid syringomas, 7 porocarcinomas, 15 malignant nodular hidradenomas, and 7 not otherwise specified carcinomas. The same tumor areas were evaluated for mitotic figure counting (MFC) and proliferation rate (PR = MIB-1 index), screening 10 consecutive high-power fields (HPFs) in the most cellular areas. Results were recorded by HPF and tumor cellularity, considering both average and standard deviation. Differences were analyzed by Student's t-test and analysis of variance (ANOVA) and considered significant if p<0.05. PR was significantly higher in malignant (23.29 +/- 12.49) than in benign tumors (3.86 +/- 4.44) and in poromanodular hidradenoma (4.99 +/- 3.34) than in spiradenoma-cylindroma-syringoma (1.91 +/- 1.67), but not by malignant tumor type. MFC was significantly higher in malignant (25.52 +/- 4.10) than in benign tumors (1.57 +/- 0.38), showing porocarcinomas the biggest MFC/10 HPF and malignant nodular hidradenomas the highest MFC/1000 cells. PR and MFC are useful malignancy criteria in skin TDD and should be evaluated by tumor cellularity to avoid potential misinterpretations related with tumor heterogeneity.

Sclerosing sweat-duct carcinoma (malignant syringoma) of the upper eyelid: a patient report with immunohistochemical and ultrastructural analysis.

Sclerosing sweat-duct carcinoma or malignant syringoma is a rare eyelid tumor. The authors report the first patient with sclerosing sweat-duct carcinoma involving the upper eyelid and present its immunohistochemical and ultrastructural features. The clinical features and the histopathologic and ultrastructural findings that distinguish this tumor from its benign counterparts are discussed. Sclerosing sweat-duct carcinomas are slow growing but locally invasive neoplasms that have a propensity to recur. Wide and deep surgical excision with frozen section evaluation of margins is recommended.

Eccrine syringofibroadenoma: report of a case and analysis of cytokeratin expression.

Eccrine syringofibroadenoma (ESFA) is a rare disorder which shows differentiation toward the eccrine sweat apparatus. There is a controversy concerning the pathogenesis and precise differentiation of this tumor. We report a case of ESFA and its differentiation pattern by an analysis of cytokeratin expression. Using paraffin-embedded materials, histopathological and immunohistochemical studies were performed. Staining patterns of the luminal, peripheral, and inner cells of the tumor strands closely matched or mimicked those of the luminal, outer and intermediate cells of the normal eccrine dermal duct, respectively. The case of ESFA reported revealed a pattern of differentiation suggestive of an eccrine duct origin.

Epithelial markers and differentiation in adnexal neoplasms of the skin: an immunohistochemical study including individual cytokeratins.

Applying immunohistochemical procedures for the detection of eight different cytokeratin (CK) polypeptides and other differentiation markers, we compared the staining patterns of normal cutaneous structures with those of benign adnexal tumors (n = 65). Syringomas exhibited a marker pattern highly reminiscent of that seen in normal dermal eccrine ducts (EMA in peripheral cells, CK 10 in intermediate cells, and CK 6, CK 19, and CEA in luminal cells). Nodular hidradenomas exhibited complex patterns suggesting relationship between tumor cells, including clear cells, and normal secretory coil cells (CK 7, CK 8, CK 19, and EMA); however, dermal-duct and epidermoid differentiation were also detectable. In both cylindromas and spiradenomas, zonal staining patterns were apparent: modified myoepithelial cells were positive for smooth-muscle-type actin, while the luminal cells mainly expressed ductal markers (CK 6 and CK 19) and, less prominently, secretory-coil markers including CK 7. Eccrine poromas exhibited a widespread reaction for CK 5/6 and EMA, analogous to peripheral dermal duct cells, but focal maturation toward inner-ductal and secretory-coil cells was also demonstrable. The staining pattern observed in trichoepitheliomas resembled that of the outer but not the inner root sheath. In conclusion, the detailed marker profiles obtained in the present study have broadened our understanding of the differentiation and nature of these highly singular tumor types.

Progesterone receptor positivity supports hormonal control of syringomas.

Syringomas may be at least partially under estrogen and/or progesterone influence, as they are more common in women and are known to proliferate at puberty. During pregnancy and the premenstrual period an increase in tumor size has also been described. We examined nine syringomas using immunohistochemical markers for estrogen (ER) and progesterone (PR) receptors. Scattered tumor cells displaying nuclear and cytoplasmic staining for ER were noted in one of the nine cases. Intense nuclear and cytoplasmic staining for PR was noted in most (> 80%) of the neoplastic cells in 8/9 syringoma cases. Current immunohistochemical evidence supports the theory that syringomas are under hormonal control.

Filaggrin immunoreactive composite keratohyalin granules specific to acrosyringia and related tumours.

The luminal cell layer of acrosyringia contains heterogeneous globular keratohyalin granules, some of which contain basophilic and eosinophilic components. Using immunoelectron microscopy we found that the majority of the granules, which are basophilic, are strongly reactive to an anti-filaggrin antibody, while the minority, which are eosinophilic, are not. Similar heterogeneous keratohyalin granules were observed in syringomas and in an eccrine syringofibroadenoma. Since such granules are not normally observed in other human cutaneous epithelia, it is suggested that these composite keratohyalin granules with partial filaggrin immunoreactivity might serve as a useful marker for acrosyringial differentiation in both normal and pathological material.

Sweat gland adenomas: immunohistochemical study with emphasis on myoepithelial differentiation.

Thirty-one dermal appendage tumors of sweat gland differentiation including 7 spiradenomas (SPA), 8 cylindromas (CYL), 8 acrospiromas (ACS), and 8 chondroid syringomas (CS) were analyzed using antibodies to epithelial membrane antigen (EMA), cytokeratin (AE1, AE3, CAM 5.2, 34BE12), S-100 protein, actin (ACT), and desmin (DES) to characterize the immunocytochemical profile of benign sweat gland tumors. Cytokeratin expression was variable; AE1, 34BE12, AE3, and CAM 5.2 were present in 31, 24, 23, and 22 tumors respectively; 29 tumors contained EMA. Seventeen tumors, (6 SPA, 8 CYL, 2 ACS, 1 CS) stained with antibody to alpha smooth muscle actin, and 26 (7 SPA, 7 CYL, 4 ACS, 8 CS) expressed S-100 protein. Although some prior studies had reported actin filaments on electron microscopy in both spiradenoma and cylindroma, these tumors have previously been considered to be negative for myoepithelial differentiation. All spiradenomas and cylindromas we studied demonstrated actin and/or S-100 protein positivity in basal epithelial cells, consistent with myoepithelial differentiation. The organization of actin and S-100 protein positivity displayed by the spiradenomas and cylindromas we studied suggests that the tumors are differentiated towards the secretory portion of the eccrine sweat gland.