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.

Eccrine syringofibroadenoma with co-existent squamous cell carcinoma.

Eccrine syringofibroadenoma (ESFA) is a rare, benign adnexal tumor arising most often on the extremities of elderly individuals. It is typically a slow-growing, flesh- to reddish-colored nodule or plaque. Histologically, the tumor consists of anastomosing cords of cuboidal epithelial cells surrounded by a fibrovascular stroma containing plasma cells. The cords contain scattered ductal structures lined with cuboidal cells resembling eccrine ducts. The co-existence of ESFA with squamous cell carcinoma has been described, eliciting the term eccrine syringofibroadenoma. The differential diagnosis includes poroma, porocarcinoma, fibroepithelioma of Pinkus and clear cell acanthoma. ESFA stain positively with epithelial membrane antigen and carcinoembryonic antigen. Cytokeratin studies have been inconsistent.

Histopathological and immunohistochemical studies of poroid hidradenoma.

Poroid hidradenoma (PH), a less common subtype of poroid neoplasm (PN) than eccrine poroma (EP), has not been immunohistochemically studied before. Six cases of PH (four solitary PH and two PH coexisted with other types of PN) were included in the study. Fifteen cases of EP were also included for comparison. Hematoxylin and eosin, Masson-Zimmerman silver stain, and a variety of immunohistochemical stains were used. Microscopically, PH is not connected to the epidermis. All six PH contained small poroid cells and larger, paler cuticular cells. Some PH showed separate or clusters of sebocytes (2/6), horn cysts (1/6), juxtaposed lymphoid follicles in the stroma (1/6) and foci of keratohyaline granules (2/6), none of which was seen in the 15 EP. Immunohistochemically, the keratin distribution of PH was very similar to that of EP. PH has a very small number of Langerhans cells (significantly lower than the overlying epidermis, P=0.045), and a sparse deposition of melanin. We conclude that except the location, the histopathological and immunochemical differences between PH and EP were small. Sebaceous differentiation in two PH lesions suggested the possibility of an apocrine origin. The deeper parts of eccrine apparatus other than basaloid cells may have been more actively involved in the histogenesis of PH.

Clear cell hidradenoma: a mimic of metastatic clear cell tumors.

Clear cell hidradenoma is a benign skin appendage tumor that may mimic conventional-type renal cell carcinoma. Histologically, clear cell hidradenoma contains small ductular lumens, focal apocrine and squamoid change, and a less prominent vascular pattern than renal cell carcinoma. Furthermore, immunohistochemical studies can aid in distinguishing the 2 tumors. Knowing the cytologic features of primary skin adnexal neoplasms helps distinguish them from cutaneous metastases, which are more commonly referred for fine-needle aspiration biopsy evaluation. Detailed clinical history, physical findings, and ancillary studies are essential for correct diagnosis and categorization of these tumors. We report the rare case of a patient with renal cell carcinoma who underwent excision of an axillary clear cell hidradenoma, which was clinically suggestive of cutaneous metastatic disease.

Hidradenoma papilliferum with mixed histopathologic features of syringocystadenoma papilliferum and anogenital mammary-like glands.

A case of hidradenoma papilliferum with mixed features of syringocystadenoma papilliferum (SCAP) and anogenital mammary-like glands is reported. A single, fresh red-colored nodule developed in the sulcus between the labia majora and minora of a 49-year-old Japanese woman. Histopathologically, the tumor showed epithelial lining with apocrine secretion and slight connective tissues characteristics. Our case was unique because, like SCAP, the tumor was connected to the epidermis and cystic invaginations extended downward into the deep dermis. In addition, beneath the tumor, tubular structures that resembled normal mammary tissue were present in the subcutaneous fatty tissue. In this study, it has been suggested that this tumor might have been developed from these mammary-like glands.

Her-2 expression in cutaneous eccrine and apocrine neoplasms.

Cutaneous eccrine and apocrine glands have many histologic and immunologic similarities to ducts and acini of the breast. Thus, differentiating a primary cutaneous process from a metastatic breast carcinoma can be nearly impossible. In all, 10-34% of breast carcinomas overexpress HER-2 protein, a membrane-associated protein that functions in cell differentiation, adhesion and motility. As expression of this gene in cutaneous neoplasms has not been well characterized, we sought to determine HER-2 expression in a sample of benign and malignant cutaneous eccrine and apocrine neoplasms and to determine if there is value in using this protein expression in differentiating primary cutaneous from metastatic breast lesions. Totally, 85 primary cutaneous neoplasms and 11 cutaneous metastases from HER-2-positive breast carcinomas were retrieved from archived material at our institute. All cases were evaluated for HER-2 protein expression using the Dako Hercept Test kit. Membranous HER-2 staining was noted in three of the 85 cutaneous adnexal neoplasms: one hidrocystoma and two nodular hidradenomas. Seven of the 11 cutaneous metastases from HER-2-positive breast carcinomas maintained moderate-to-strong HER-2 expression. In conclusion, while 10-34% of breast carcinomas overexpress the HER-2 protein, only 3.5% of cutaneous apocrine and eccrine neoplasms in this study stained with the HER-2 antibody. These HER-2-positive cutaneous neoplasms typically do not pose a diagnostic dilemma in the setting of differentiation from breast metastasis. Additionally, although histologically these breast and cutaneous lesions may have morphologic similarities, the relative lack of HER-2 overexpression suggests that they are different nosologically. Finally, this study suggests that HER-2 protein expression can be a useful tool in differentiating a primary cutaneous appendageal neoplasm from HER-2 expressing metastatic breast carcinoma.

Hidrosadenoma of the anal canal: a case report with review of the literature.

Hidrosadenoma of the anal canal is an extremely rare tumour. Only nine cases with similar histologic structure have been described in the literature, most representing tumours resected from the anal or rectal mucosa. We present a case of anal hidrosadenoma with immunohistochemical staining features identifying it as a true sweat gland tumour.

Tubular apocrine adenoma in association with syringocystadenoma papilliferum.

Tubular apocrine adenoma is a very rare sweat gland tumor. In this report, a case of tubular apocrine adenoma in association with syringocystadenoma papilliferum on the scalp is presented. The stroma of the tubular apocrine adenoma consisted of numerous, young fibroblasts with mitotic activity. It was difficult to distinguish stromal cells and epithelial cells from each other in some areas. The characteristics and differences in histopathologic and immunohistochemical findings in these tumors are described.

Mixed tubulopapillary hidradenoma and syringocystadenoma papilliferum occurring as a verrucous tumor.

Tubulopapillary hidradenoma (TPH)1 is a term proposed to describe morphological dermal ductal tumors with both eccrine and apocrine differentiation. The term TPH encompasses a spectrum of lesions that includes tubular apocrine adenoma (TAA) and papillary eccrine adenoma (PEA):2 PEA and TAA can be indistinguishable both clinically and histologically. We described a case of TPH with both prominent eccrine and apocrine differentiation combined with syringocystadenoma papilliferum (SCAP) over the distal extremity. This rarely encountered dermatopathological phenomenon is the sixth reported case from the literature in which PEA or TAA and SCAP were present in the same lesion.3-7 Furthermore, the tumor had a warty surface, which is histologically consistent with a typical viral verruca. Although PCR and DNA probe hybridization for human papilloma virus (HPV) types 2, 6/11, 16 and 18 failed to reveal positive results, the location and clinicopathologic correlation convinced us that superimposed HPV could not be excluded.

Malignant mixed tumor ex eccrine spiradenoma: an unusual pattern of malignant dedifferentiation.

Eccrine spiradenoma (ES) is a benign tumor of the skin adnexal origin. It is often seen in the head and neck region of young adults and may be present for years. While there have been numerous case reports of malignant degeneration within ES, they have been mostly carcinomatous dedifferentiation and rarely carcinosarcomas. A malignant mixed tumor is a neoplasm with a malignant epithelial component and areas of chondroid and myxoid differentiation within the malignant epithelial proliferation. While the epithelial component is malignant, the mesenchymal component is felt to represent a benign, metaplastic response of the stroma. While the malignant mixed tumor has a benign counterpart, the benign mixed tumor, the former is usually not seen in continuity with the latter. We describe a case of ES with malignant degeneration and demonstrate the transformation from benign to malignant. The histology and immunohistochemistry of the neoplasm supports a malignant mixed tumor, an extremely unusual neoplasm to see in association with ES or any benign adnexal neoplasm.

An unusual melanocytic lesion associated with eccrine duct fibroadenomatosis and syringoid features.

The intimate association of nevomelanocytic nevi with eccrine ducts commonly seen in congenital nevi was emphasized by Mishima, who described as eccrine-centered nevi those lesions characterized by nevomelanocytic cells predominantly proliferating around and within the eccrine sweat duct walls. However, there were no changes in the overlying epidermis, dermis, or eccrine acrosyringeal or dermal duct proliferation in these lesions. We present the case of a 16-year-old boy with a 1-year-history of a 0.6-cm diameter single tan papule on the right heel, clinically thought to be a Spitz nevus. Histopathologic examination revealed a compound nevomelanocytic nevus associated with epidermal hyperplasia, thin anastomosing cords of acrosyringeal epithelium extending within the dermis, and eccrine ductal proliferation in a syringoma-like pattern associated with a dense fibrous stroma. Features that distinguish our case from eccrine-centered nevus are that the latter lacks epidermal and eccrine duct hyperplasia and a dense fibrous stroma. The location of the lesion on the heel in our case suggests the possibility that the pathologic changes observed could result from repetitive trauma.

Carcinomas of sweat glands: report of 60 cases.

CONTEXT: Several aspects of sweat gland carcinomas (incidence, classification, diagnosis, and behavior) have not been definitively clarified and need to be studied further. OBJECTIVE: The clinicopathologic findings of a large series of sweat gland carcinomas, collected during a period of 15 years, are presented. METHODS: Sixty sweat gland carcinomas (41 porocarcinomas, 3 syringomatous carcinomas, 8 ductal carcinomas, 5 adenoid cystic carcinomas, and 3 mucinous carcinomas) were analyzed histologically and immunohistochemically. RESULTS: Porocarcinomas were composed of eosinophilic and clear atypical cells arranged in solid-cystic lobular masses. These tumors were divided into 2 subgroups: horizontal porocarcinomas, showing a prominent intraepidermal component, and nodular porocarcinomas, which demonstrated predominant nodular growth. Syringomatous carcinomas presented keratinizing and nonkeratinizing cysts, dilated tubules (sometimes with a "tadpole" appearance), small neoplastic ducts, solid islands, and cellular cords. Ductal carcinomas were characterized by a prominent formation of tubules, solid islands, and cellular cords. Adenoid cystic carcinomas presented a characteristic pattern, showing basaloid monomorphous cells with moderately atypical nuclei, arranged in cribriform or solid islands and in tubular structures. Mucinous carcinomas were composed of moderately atypical cells with eosinophilic vacuolated cytoplasm, forming solid and cystic islands floating in large mucin pools. Immunohistochemically, cytokeratin was found in neoplastic cells in all cases, carcinoembryonic antigen was detected in 73% of cases, and actin-positive (myoepithelial) cells were not found. CONCLUSIONS: Although numerous studies have been published in recent years, the histologic features, histogenesis, and classification of sweat gland carcinomas still remain controversial and need to be clarified by further studies.

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.

Immunohistochemical analysis of cytokeratin expression in reactive eccrine syringofibroadenoma-like lesion: a comparative study with eccrine syringofibroadenoma.

In addition to solitary eccrine syringofibroadenoma (ESFA), there is another type of ESFA which is associated with underlying dermatoses (reactive ESFA-like lesion). Five lesions in 4 patients of reactive ESFA-like lesion were analyzed by an immunohistochemical method using 13 kinds of anti-cytokeratin (CK) antibodies. Two cases of solitary ESFA were also studied by the same procedure for comparison. Suprabasal staining pattern of AE1 and MNF116, which stain CKs 6, 16 and 17, markers of hyperproliferative state, was observed diffusely in 5 lesions of reactive ESFA-like lesions except for focal negative staining in one case, and was observed focally in one case of solitary ESFA. Furthermore, differentiation-specific cytokeratin expression was reduced in 3 of 5 lesions of reactive ESFA-like lesions. Both ESFA and reactive ESFA showed basically similar immunoreactivity suggesting differentiation toward the dermal duct. The above slight difference in immunoreactivity between both lesions may be explained due to inflammatory infiltrates associated with underlying dermatoses.

p53 expression in two cases of spiradenocarcinomas.

p53 protein is a nuclear 53-kDa phosphoprotein that acts as a suppressor protein. There are several studies on the expression of p53 in skin tumors, but few deal with adnexal malignant tumors because of their rarity. We performed immunohistochemistry for the detection of p53 and Ki-67 in two cases of malignant spiradenomas and six cases of spiradenomas retrieved from our files. In our cases, p53 was expressed only in the malignant areas of the lesions, whereas the benign areas of the spiradenocarcinomas and all the spiradenomas were negative (nuclear positivity <10%). These results seem to support the idea that p53 is implicated in the malignant transformation of adnexal tumors.