CD99 and cytokeratin-20 in small-cell and basaloid tumors of the skin.

Although it is classically a deep soft-tissue tumor of childhood, primitive neuroectodermal tumor (PNET) can occur at any age and may occasionally involve cutaneous sites. Merkel cell carcinoma (MCC) and basaloid neoplasms of cutaneous adnexa are the principal diagnostic alternatives to that tumor. The common expression of CD99 in PNET and cytokeratin-20 (CK20) in MCC suggests that these markers may be of value in this diagnostic setting, but they have not been rigorously examined in other small-cell and basaloid lesions of the skin. Accordingly, we evaluated CD99 and CK20 reactivity in formalin-fixed, paraffin-embedded sections of 30 MCC, five cutaneous metastases of pulmonary small-cell neuroendocrine carcinomas, 10 primary cutaneous adnexal carcinomas with basaloid features, 18 benign basaloid adnexal neoplasms of the skin (nine spiradenomas and nine cylindromas), and two cutaneous PNETs, using a standard immunohistologic technique and microwave-mediated epitope retrieval. Of the 30 MCC, 12 showed crisp membrane staining for CD99. Among the remaining tumors, only the two PNETs were positive for that marker. Although the majority of MCCs did not label for CD99, the pattern of reactivity in positive cases was indistinguishable from that observed in PNETs. Eighteen of 27 MCCs that were stained for CK20 were reactive for that protein, in contrast to metastatic small cell carcinomas, cutaneous PNETs, and appendageal skin tumors, which were uniformly negative for this marker. However, a subset of nine tumors, which were most consistent with MCC on clinical grounds, was CD99 positive and CK20 negative. Hence, reliance on CD99 alone as a diagnostic marker for PNET in this context cannot be recommended. Rather, careful assessment of the clinical presentation, together with extended immunophenotyping that includes other lineage markers and, when possible, cytogenetic analysis for characteristic chromosomal aberrations, remains the best means of separating MCC from PNET. Finally, the lack of CD99 reactivity in basaloid adnexal neoplasms of the skin suggests a utility in their differential diagnosis from cutaneous tumors with neuroendocrine or neuroectodermal differentiation.

CD44 distribution in sweat gland tumors suggests it has different functional roles in the various cell types.

CD44 is a polymorphic group of membrane glycoproteins with multiple functions that include cell adhesion. Since on normal sweat glands CD44 is expressed only in eccrine coil secretory cells, it has been considered as a possible marker of this type of differentiation. We have immunohistochemically investigated the distribution of CD44 in paraffin-embedded samples of 41 benign and malignant sweat gland tumors by using a monoclonal antibody directed against the standard isoform of CD44. CD44 was strongly expressed in epithelial cells at the peripheral row of syringomas and in cuticular areas of eccrine poromas. Apocrine tumors such as apocrine hidrocystoma, syringocystadenoma papilliferum, or hidradenoma papilliferum showed intense CD44 positivity in the portion of cells in contact with the neighboring stroma and focally on the luminal side of cells with apocrine secretion. Cylindromas and spiradenomas presented focal CD44 positivity, virtually limited to clear cells. Malignant neoplasms exhibited irregular CD44 staining, which was more intense in the less differentiated zones and tumors. Our results indicate that CD44 is not a useful marker for a specific form of sweat gland differentiation. Nevertheless, its characteristic patterns of distribution might reflect the variety of functional roles assumed by the different CD44 isoforms in each epithelial cell.

Ber-EP4 immunoreactivity in normal skin and cutaneous neoplasms.

Ber-EP4 is an antibody raised against a cell membrane glycoprotein of, as yet, unknown function. In the skin, the ability to distinguish basal cell carcinoma from squamous cell carcinoma has been emphasized. Immunoreactivity in apocrine and eccrine secretory coil epithelium, Merkel cell carcinoma, and cutaneous mixed tumor has been reported. Having observed more widespread staining than previously reported, we sought to characterize further Ber-EP4 immunoreactivity by examining 76 formalin-fixed and paraffin-embedded proliferative epithelial skin lesions, 2 sections of fetal skin with developing adnexa, and frozen sections of skin from Mohs surgery procedures, using hematoxylin and eosin and Ber-EP4 immunostaining. In paraffin-embedded skin, matrical and outer sheath epithelium of vellus anagen follicles, inferior segment epithelium of vellus telogen follicles, and secretory coils of sweat glands stain with Ber-EP4, but anagen terminal follicle epithelium and eccrine and apocrine sweat ducts are negative. On frozen section, additional staining of eccrine ducts and cells in the outer sheath and matrix of the inferior segment of terminal follicles is noted. Basaloid epithelium of trichoepitheliomas, follicular induction over dermatofibromas, mammary Paget's disease, and selected other neoplasms showing eccrine or apocrine differentiation stain with Ber-EP4. These data indicate that in addition to basal cell carcinoma, Ber-EP4 staining may be seen in a variety of proliferative epidermal and adnexal lesions.

A case of cystic dermal duct tumor corresponding to poroid hidradenoma.

A case of dermal duct tumor on the back of a 61-year-old male, representing a cystic lesion, is reported. Such cystic dermal duct tumors seem to be considered poroid hidradenomas according to the recently suggested classification of poromas. Poroid hidradenoma is rarely mentioned in the literature, and no description of its clinical features has yet been published. Carcinoembryonic antigen (CEA) immunostaining was positive in the tumor cells adjacent to the cystic space. We suppose that these CEA-positive cells were associated with cyst formation in our case.

Distribution of epithelial membrane antigen in eccrine poroma.

Using immunohistochemical methods, we investigated the distribution of epithelial membrane antigen (EMA) on the normal eccrine gland, eccrine poroma and hidroacanthoma simplex. Granular membrane-associated reaction of EMA was detected on the outer cells of both the intraepidermal and the upper portion of intradermal eccrine ducts, as well as on the luminal surfaces and intercellular canaliculi of eccrine glands. Clear immunolabeling was also present in the tumor cells of eccrine poroma and hidroacanthoma simplex. Thus, it is suggested that the constituent cells of these tumors originate from the outer cells of the intraepidermal and/or the upper portion of the intradermal eccrine ducts. There was no immunolabeling for EMA on the tumor cells of seborrheic keratosis and basal cell carcinoma. Immunohistochemical staining for EMA is a useful tool for the diagnosis of skin appendage tumors.

Chondroid syringoma associated with hidrocystoma-like changes. Possible differentiation into eccrine gland. A histologic, immunohistochemical and electron microscopic study.

A case of chondroid syringoma associated with hidrocystoma-like changes was investigated by histology, immunohistochemistry and electron microscopy. Chondroid syringoma was histologically compatible with apocrine mixed tumor, and hidrocystoma-like changes did not fulfill diagnostic criteria of either eccrine hidrocystoma or apocrine hidrocystoma. However, epithelial cellular elements composing both chondroid syringoma and hidrocystoma-like changes suggested, immunohistochemically and electron microscopically, differentiation into eccrine gland. The lesions of both had an apparent transition of ductal structures of chondroid syringoma into hidrocystoma-like changes. Therefore, chondroid syringoma and hidrocystoma-like changes in this case may be organized as a peculiar type of cutaneous appendage tumor differentiating toward eccrine gland.

Siringofibroadenoma encrino de mascaro / Syringofibroadenoma of mascaro

Se estudió un tumor glandular localizado en la piel de la mama izquierda en una paciente de 74 años cuya histología permite establecer el diagnóstico de siringofibroadenoma, descripto en 1963 por Mascaró. El Antígeno Cárcino-Embrionario es positivo en las luces canaliculares intracordonales de la lesión (AU)

Siringofibroadenoma encrino de mascaro / Syringofibroadenoma of mascaro

Se estudió un tumor glandular localizado en la piel de la mama izquierda en una paciente de 74 años cuya histología permite establecer el diagnóstico de siringofibroadenoma, descripto en 1963 por Mascaró. El Antígeno Cárcino-Embrionario es positivo en las luces canaliculares intracordonales de la lesión

Immunohistochemical staining patterns of sweat glands and their neoplasms using two monoclonal antibodies to keratins.

The staining patterns of normal sweat glands and sweat gland-derived neoplasms using 2 monoclonal antibodies to keratins (Dako-CK1, Cam 5.2) has been assessed. Based on findings in normal glands, the differentiation of these benign neoplasms is considered, with positive evidence for apocrine and eccrine differentiation, and in the latter, differentiation to ductal or secretory type epithelia. This easily applied technique (indirect immunoperoxidase) is suitable for use in routinely processed tissue and employs 2 commercially available monoclonal antibodies. The findings may be of assistance in general surgical reporting of problematic cases.

Three cases of eccrine porocarcinoma.

We report three cases of eccrine poroma, present for many years, in which features were seen suggesting transformation from a benign to a malignant tumour. These changes ranged from in situ Bowenoid dysplasia to frankly invasive squamous carcinoma. The most helpful diagnostic feature in distinguishing the origin of the tumours was the presence of strong cytoplasmic staining for carcinoembryonic antigen (CEA) in cells surrounding, and giving rise to, neoplastic ducts and clefts. Dermatopathologists examining eccrine poromata should examine the lesions carefully for any evidence of malignant change.

Presence and distribution of carcinoembryonic antigen and lectin-binding sites in benign apocrine sweat gland tumours.

The presence and distribution of carcinoembryonic antigen (CEA) and lectin-binding sites in benign apocrine sweat gland tumours was investigated using immunoperoxidase and immunofluorescent techniques respectively. CEA was present in apocrine hidrocystoma, hidradenoma papilliferum, and syringocystadenoma papilliferum. The distribution pattern of CEA was indistinguishable in each of the three types of tumour. The distribution of lectin-binding sites was similar in all cases of a given type of neoplasm, and the staining patterns were similar but not identical in hidradenoma papilliferum and syringocystadenoma papilliferum. However, the distribution of lectin-binding sites in apocrine hidrocystoma was different. These results could be useful in elucidating the nature of the cells of origin of benign apocrine sweat gland tumours and providing a basis for their classification.

Syringocystadenoma papilliferum. A plasmacytotropic tumor.

Seven cases of syringocystadenoma papilliferum were studied by immunohistochemical methods for the presence of IgG, IgA, IgM, and secretory component in tumor epithelial cells and IgG, IgA, and IgM in plasma cells underlying the tumor epithelium. Six of seven cases showed IgA positivity within epithelial cells, one case showed faint intraepithelial IgG staining, and none stained for IgM. Four of five cases were positive for secretory component. The plasma cells were predominantly of the IgG and IgA class. These findings suggest that the association of plasma cells with this tumor is a consequence of epithelial attraction via a mechanism similar to that utilized by glands of the normal secretory immune system.

[Contribution of monoclonal antibody D 47 in the study of sweat gland pathology]. / Apport de l'anticorps monoclonal D 47 dans l'étude de la pathologie sudorale.

D 47 is a monoclonal antibody (IgG2) reacting with a surface antigen of cortical thymocytes. On normal human skin, D 47 was found to react with a cytoplasmic antigen of the cells of the secretory portion of eccrine sweat glands (ESG). No reactivity with D 47 is detected on the excretory part of ESG, on apocrine glands and all other cutaneous structures. In this work we studied through an indirect immunofluorescence method on frozen skin sections the reactivity pattern of D 47 on a group of epithelial skin tumours of certain or alleged glandular differentiation. These consisted of: eccrine spiradenoma (ES, 1 case); chondroid syringoma (CS, 1 case); syringomas of the eyelid (1 case); clear-cell hidradenocarcinoma (1 case); eccrine porocarcinoma (1 case); naevus sebaceus of Jadassohn (2 cases, one of which associated to a syringocystadenoma papilliferum); clear-cell acanthoma (1 case); extramammary Paget's disease (3 cases); basal-cell epithelioma (2 cases). D 47 yielded in a strong labelling of a significant proportion of cells in the cases of ES and CS, while on the remaining tumours, apart from normal ESG occasionally present in the peritumoral connective tissue, no reactivity was seen. From this study it becomes clear that D 47 represents an immunohistologic marker of eccrine-secretory differentiation and that it can be applied in the investigation of the differentiation and of the differential diagnosis of sweat-gland neoplasms.

Epithelial markers in primary skin cancer: an immunoperoxidase study of the distribution of epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA) in 65 primary skin carcinomas.

Sixty-five primary malignant skin tumours have been stained for carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA) using rabbit polyclonal affinity-purified antibodies and an indirect immunoperoxidase technique. The tumours consisted of 15 invasive squamous carcinomas, 23 basal cell carcinomas, 16 malignant eccrine poromas (porocarcinomas), and 11 sebaceous carcinomas. The basal cell carcinomas were negative for CEA and EMA except where there was keratotic or sebaceous differentiation. All the sebaceous and squamous carcinomas and 15/16 porocarcinomas contained EMA. 12/15 squamous carcinomas were positive for CEA. The malignant poromas were negative for CEA except on the ulcerated surface of two. In tumours classified as sebaceous carcinomas there was positive staining for CEA in some cells, cyst contents and/or keratotic foci. These findings have implications for the use of immunoperoxidase localization of epithelial markers in the differential diagnosis of primary and metastatic skin cancer.