Monoclonal antibody analysis of keratin expression in carcinomas of sweat glands

Characteristics of keratins of five carcinomas of sweat gland origin were immunohistochemically investigated with several antikeratin monoclonal antibodies with differing specificities. Specimens were obtained from two cases of mucinous carcinoma of the skin, two cases of classic type of eccrine adenocarcinoma, and a case of eccrine porocarcinoma. The tumor cells of mucinous carcinoma expressed only simple epithelial keratins. In a case of eccrine adenocarcinoma, simple epithelial keratin 19 was diffusely expressed. The expression of the other simple epithelial keratins was confined to the luminal cells, whereas the remaining tumor cells further expressed stratified epithelial keratins. Eccrine porocarcinoma and a second case of eccrine adenocarcinoma did not express simple epithelial keratins, although stratified epithelial keratins were diffusely expressed. These data suggest that carcinomas of sweat glands express various combinations of simple and stratified epithelial keratins. Development of additional data along these lines may help to further define their classification.     

Eccrine syringofibroadenoma (Mascaro): an ultrastructural study

To confirm the eccrine acrosyringeal differentiation of eccrine syringofibroadenoma (ESFA) and to elucidate the histogenesis of its angiofibrotic stroma, a case of ESFA from a 45-year-old man was examined by light and electron microscopy. Histologically, the parenchyma featured anastomosing, slender epithelial cords containing small cuboidal cells and occasional duct-like structures. The stroma had increased numbers of mast cells, increased capillaries with swollen endothelial cells, and prominent fibrosis. Ultrastructurally, the following findings were characteristic of ESFA: a) abundant glycogen particles in epithelial cells, b) numerous intracytoplasmic and extracellular spaces lined with microvilli, c) intraepithelial duct formation, consisting of microvilli, vesicles, rod-shaped dense bodies, multivesicular dense bodies, and peripheral network of tonofilaments, and d) large numbers of mast cells, closely associated with fibroblasts, surrounding increased numbers of capillaries containing swollen endothelial cells. These ultrastructural features support the acrosyringeal differentiation of ESFA. We hypothesize that mast cell hyperplasia and degranulation may play an important role in the formation of the angiofibrotic stroma.     

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.     

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.     

Solitary eccrine syringofibroadenoma with prominent plasma cell infiltration

Eccrine syringofibroadenoma (ESFA) is a rare, benign, adnexal neoplasm thought to be eccrine ductal differentiation displaying variable clinical findings and characteristic histological features. It usually occurs as a solitary nodule on the extremities of an elderly person. Histological findings typically show a proliferation of anastomosing strands, cords, and columns of monomorphous epithelial cells that harbor eccrine duct formations embedded in a fibrovascular stroma. Acrosyringial nevus, though usually regarded as an identical lesion, is sometimes regarded as a different entity showing prominent plasma cell infiltration. We report two cases of solitary ESFA with prominent plasma cell infiltration. Clinicopathological features of both cases suggest that acrosyringeal nevus and ESFA may be of the same disease entity. Prominent plasma cell infiltration may be just one of the common histological features of ESFA.     

Eccrine Syringofibroadenoma Associated with Bowen's Disease: A Case Report and Review of the Literature

Eccrine syringofibroadenoma (ESFA) is a rare, benign adnexal neoplasm which usually manifests as a solitary nodule on the extremities of elderly patients. Few case reports have described an association between ESFA and carcinomas including squamous cell carcinoma, porocarcinoma, and basal cell carcinoma. A 66-year-old male presented with a pruritic, erythematous brownish solitary plaque with crusted and verrucous surface on the extensor side of the right thigh. The lesion developed 6 to 7 years ago, and had been growing slowly. Biopsy revealed anastomosing epithelial strands which were composed of 2 areas: the upper area consisting of dysplastic cells with prominent nucleoli and abundant mitoses, and the lower area consisting of oval and round cells, and occasionally small luminal ducts. Dysplastic cells comprised almost the entire epidermis but did not invade into the dermis. Benign syringofibroadenomatous lesion surrounded the dysplastic cells in the lowermost portion of the epidermis. Although it is still unclear whether ESFA undergoes malignant transformation or it is a reactive change to carcinoma, complete excision should be performed to prevent malignant transformation with unknown risk.     

Reactive eccrine syringofibroadenomatosis secondary to primary cutaneous amyloidosis: a novel association

We report the unprecedented case of reactive eccrine syringofibroadenoma (ESFA) secondary to primary cutaneous amyloidosis. A 62‐year‐old woman of Asian ethnicity presented with a pruritic rash on the back of long‐standing duration. Physical examination revealed diffuse hyperpigmentation localized to the interscapular region; there were a multitude of hyperpigmented macules merged in a rippled pattern intermixed with scattered papules and cobblestone‐like areas. A punch biopsy from a papule was taken. Histopathological examination revealed a network of epithelial strands and cords hanging from the epidermis and harboring foci of ductal differentiation. Eosinophilic collections of amorphous material were found between the epithelial strands, obscuring the superficial dermis. The microscopic picture was consistent with primary cutaneous amyloidosis associated with reactive ESFA. Results of histochemical and immunohistochemical staining confirmed the diagnosis. We speculate that pathogenetic mechanisms intrinsic to primary cutaneous amyloidosis, in addition to unknown genetic factors, resulted in clinical changes of lichen amyloidosus associated with an abnormal hyperplastic epithelial response with histopathological features of ESFA rather than the common epidermal change of acanthosis and hyperkeratosis.     

A case of subungual reactive eccrine syringofibroadenoma

Eccrine syringofibroadenoma (ESFA) is a rare eccrine tumor. We report the case of a 70-year-old woman who had presented a pincer nail deformity on the toes for 55 years and a left painless subungual tumor for 2 years. Histologic examination revealed branching anastomosing strands of epithelial cells with ductal structures in a fibrovascular stroma. The luminal cells showed positive staining for carcinoembryonic antigen, as in acrosyringeal cells and cells of dermal ducts. To our knowledge, our case is the first with a subungual location. In the context of chronic trauma due to a pincer nail, it may be classified in the reactive subtype recently described.     

Clear cell syringoid carcinoma: an ultrastructural and immunohistochemical study

Syringoid carcinoma (syringoid "eccrine" carcinoma or eccrine epithelioma) is a rare cutaneous tumor with some controversy regarding its correct definition. It may also be difficult to differentiate from its benign counterpart (syringoma), other adnexal carcinomas, and cutaneous metastasis from adenocarcinomas. We present a case of a syringoid carcinoma of the clear cell variant complemented with an immunohistochemical and ultrastructural study, the latter revealing cytoplasmic accumulation of glycogen and presence of intercellular and intracellular lumina in clear tumor cells, as well as diverse hallmarks of malignancy (i.e., perineural invasion, tumor necrosis, and deep invasion). Clear tumor cells showed cytoplasmic and membranous immunoreactivity to epithelial membrane antigen, carcinoembryonic antigen, keratins, and S-100. Our ultrastructural and immunohistochemical results support the ductal differentiation of the glycogen-filled clear cell tumor population.     

A Case of Reactive Eccrine Syringofibroadenoma

Eccrine syringofibroadenoma is a rare adnexal tumor of eccrine ductal differentiation with variable clinical features. It manifests as either a solitary or multiple papules and nodules arranged in a symmetrical or linear pattern. The anatomical distribution is wide and includes the face, trunk, extremities, and rarely the nails. Histopathological findings show anastomosing cords and strands of uniform cuboidal cells surrounded by fibrovascular stroma. Herein, we report a case of reactive eccrine syringofibroadenoma which developed on the foot of a 37-year-old woman, after self-paring of tissue and subsequent infection and ulceration.     

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.     

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.     

Papillary eccrine adenoma: immunohistochemical studies of keratin expression

Despite various studies, there are serious disagreements about the cellular differentiation of papillary eccrine adenoma. In the present study, 2 specimens of papillary eccrine adenoma were analyzed by immunohistochemical techniques, using a panel of monoclonal antibodies against keratins, to elucidate its differentiation. Histopathologically, the tumor was composed of multiple tubular structures lined by two or more layers of epithelial cells. The luminal cells of the tubules were flattened or cuboidal. The former were noted in large dilated tubules. The latter were usually observed in small-to-moderate-sized tubules, and formed intra-luminal papillary projections in some tubules. Immunohistochemically, there were two kinds of cuboidal cells in the luminal layers of the tubules. Most of the large dilated tubules and some of the small-to-moderate-sized tubules expressed immunophenotypes similar to those of the eccrine dermal duct. The other tubular structures, including the small tubules resembling those of syringoma, expressed immunophenotypes similar to those of the transitional portions between the dermal ducts and the secretory segments of eccrine glands. From the above comparative studies, papillary eccrine adenoma is considered to differentiate towards the dermal duct and the transitional portions between the dermal ducts and the secretory segments of eccrine glands.     

A reactive acrosyringeal proliferation in a patient with ectodermal dysplasia: eccrine syringofibroadenoma-like lesion

A 33-year-old man with ectodermal dysplasia (ED) has suffered from keratotic, exudative, erythematous plaques on the genital area, thighs, and soles since age 17. Verrucous soft nodules in a cobblestone arrangement developed on the erythematous plaque on his left thigh when he was 31 years old. Histologic examination of the verrucous nodules demonstrated that they were composed of anastomosing thin cords of uniform, cuboidal, epithelial cells and a fibrovascular stroma. The changes are indicative of eccrine syringofibroadenoma of Mascaro (ESFA), which has been reported as a neoplasm, a hamartoma, or a nevus. With etretinate treatment, the verrucous nodules completely disappeared within two months. Similar, but much flatter, verrucous lesions recurred and disappeared twice during the subsequent two years period. These verrucous lesions were likely induced by irritation from urine, stool, and/or mechanical friction. This case of ESFA in a patient with ED clearly showed a reactive process which was successfully managed with oral etretinate.     

Syringoid eccrine carcinoma: report of a case with immunohistochemical analysis of cytokeratin expression

Syringoid eccrine carcinoma is an extremely rare cutaneous malignant tumor, thought to be derived from eccrine sweat apparatus. We report a case of syringoid eccrine carcinoma occurring on the scalp of a 66-year-old woman and analyzed its cytokeratin expression immunohistochemically to clarify its histogenesis. The tumor consisted mainly of numerous small cords and nests extending from the reticular dermis to the subcutaneous tissue, which formed luminal or tubular structures mimicking the nests of syringoma. Immunohistochemical analysis revealed that most tumor cells expressed simple epithelial cytokeratins (CKs 7, 8, 18, 19) suggesting their sweat secretory differentiation, and that a small number of tumor cells showed an expression of stratified epithelial cytokeratins (CKs 5, 14) suggesting their ductal differentiation. We believe that the syringoid eccrine carcinoma of our case may differentiate mainly toward the sweat secretory cells rather than toward the dermal ductal cells.     

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.     

Papillary eccrine adenoma

A 28-year-old man came to us with a solitary skin colored, mildly tender nodule of 6 months duration on the dorsum of the right hand. On histological examination, multiple dilated ducts without apparent continuity with the surface were found in the dermis. These dilated ducts had branching tubules with eosinophilic amorphous material filling most of the lumina. The peripheral cells of the tubules resembled myoepithelial cells, whereas the luminal border cells were cuboidal or low columnar. Papillary projections arising from the inner cells were seen extending into the lumen. These features were diagnostic of a rare tumor, papillary eccrine adenoma.     

Acrosyringeal adenomatosis (eccrine syringofibroadenoma of Mascaro). A case report and review of the literature.

The case of a 63-year-old man with acrosyringeal adenomatosis (eccrine syringofibroadenoma of Mascaro) is reported. Asymptomatic papular lesions had appeared on the dorsum of both of his feet 30 years earlier, then extended gradually and symmetrically to his hands, arms, legs, trunk, and auriculae. Although his hair, teeth, and nails were normal, he had glaucoma, chronic sinusitis, chronic otitis media, chronic pancreatitis, and gastrointestinal polyposis. No similar symptoms were found in the family history. Histopathologically, proliferations of pale epithelial cells extended from acrosyringia into the dermis, forming interconnected epithelial cords, within some of which were ductal structures. A syringoma and syringoma-like structures were closely associated with these lesions. Enzyme-histochemical, immunohistochemical, and ultrastructural studies supported the concept that this case represents a benign tumor derived from the acrosyringium, which is different from eccrine poroma. Acrosyringeal adenomatosis seems to be a more appropriate name for such a lesion than does eccrine syringofibroadenoma (Mascaro).     

Immunohistochemical analysis of cytokeratin expression in eccrine spiradenoma: similarities to the transitional portions between secretory segments and coiled ducts of eccrine glands

Despite light and electron microscopic and histochemical studies, there is no consensus on the cellular differentiation of eccrine spiradenoma. In the present study, eight specimens of eccrine spiradenoma were analysed by immunohistochemical techniques, using a panel of monoclonal antibodies against cytokeratins. Two types of epithelial cells were identified in tumour nodules: large, pale epithelial cells in the centre, and small, dark epithelial cells situated at the periphery. These nodules frequently contained tubular structures lined by cuboidal, columnar or, less commonly, flattened epithelial cells. Cytokeratin expression in eccrine spiradenoma was compared with expression in normal eccrine glands. Immunohistochemistry revealed that large, pale epithelial cells expressed immunophenotypes similar to those of luminal cells in the transitional portions between the secretory portions and the coiled ducts. The small, dark cells expressed immunophenotypes similar to those of basal cells in the transitional portions. Tubular structures observed in eccrine spiradenoma showed staining patterns similar to those of the luminal cells in the transitional portions. Eccrine spiradenoma may, therefore, differentiate towards the transitional portions between the secretory portions and colled ducts of eccrine glands. Some of the large, pale epithelial cells in eccrine spiradenoma differentiate towards tubular structures, forming a lumen lined by a cuticle.     

Eccrine syringofibroadenoma in a patient with a burn scar ulcer

A 72-year-old woman with a burn scar on the calves of both legs developed an ulcer on her right heel, surrounded by multiple verrucous nodules and plaques. She had experienced similar verrucous lesions on both legs in the burn scar areas. Although the clinical diagnosis was Marjolin's ulcer, histologically the ulcer region showed thick fibrous tissue without any atypical epithelial cells. The verrucous lesions were consistent with the diagnosis of eccrine syringofibroadenoma (ESFA). Moreover, an ESFA-like growth pattern was seen in the elevated margin of the ulcer. Our findings suggest that these lesions developed as a result of reactive eccrine duct hyperplasia followed by skin tissue remodelling.