Takamitsu Ohnishi

The use of cytokeratins 7 and 20 in the diagnosis of primary and secondary extramammary Paget’s disease

Despite the similarity in clinical appearance, there is a significant difference in the prognosis between primary extramammary Paget’s disease (EPD) and the pagetoid spread of underlying regional internal malignancy (secondary EPD, pagetoid phenomenon). Fifteen cases of primary EPD (11 carcinoma in situ and four invasive carcinoma), seven cases of secondary EPD (five colorectal adenocarcinoma and two urothelial carcinoma), and six cases of anal canal carcinoma were retrieved and analysed immunohistochemically using six kinds of monoclonal anticytokeratin antibodies. No expression of cytokeratins 1, 5, 10, 13 and 14 was observed in any cases examined in this study. All 15 cases of primary EPD had the immunophenotype cytokeratin (CK)7+/CK20–. CK20 expression was diffusely positive in six cases of secondary pagetoid spread (two urothelial carcinoma and four colorectal adenocarcinoma), and focally in one case (a colorectal adenocarcinoma). In anal canal carcinoma, three of six cases showed CK20 diffuse expression and the remaining three cases expressed CK20 focally. CK7 expression was observed in three of six cases of anal canal carcinoma and in two of five cases of secondary EPD associated with colorectal adenocarcinoma. The combination of CK7 and CK20 demonstrates these to be useful markers in distinguishing ‘primary’ EPD from a pagetoid spread of extracutaneous malignancies. Namely, immunophenotypes other than CK7+/CK20– in Paget cells suggest underlying regional internal malignancy.

Immunohistochemical analysis of cytokeratin expression in various trichogenic tumors.

The immunophenotypes, especially expression of cytokeratins, in 13 cases of trichogenic tumors were examined to investigate their histogenesis. Four cases of multiple trichoepithelioma, five cases of classical solitary trichoepithelioma, one case of desmoplastic trichoepithelioma, one case of trichogenic trichoblastoma, one case of trichoblastic fibroma, and one case of giant solitary trichoepithelioma were retrieved. The immunoreactivities of the epithelial nests and the keratinous cysts in these tumors were similar to those of the outer root sheath and the infundibulum of normal hair follicles, respectively. From the comparative studies of the immunophenotypes with those of normal hair follicles, we speculated that all trichogenic tumors differentiate mainly toward the outermost layer of the outer root sheath between the lower part of the permanent portion and the upper part of the transient portion and some parts of them differentiate toward various other parts of the follicles. Although differentiation toward the other follicular structures can vary from case to case, there is no particular staining pattern specific for each kind of trichogenic tumor and no significant differences in immunoreactivity among them. Our observations support a recent notion that all neoplasms of follicular germinative cells should be grouped as a single entity.

Eccrine syringofibroadenoma. Report of a case and immunohistochemical study of keratin expression

We report a 49‐year‐old woman with an eccrine syringofibroadenoma. An asymptomatic nodule appeared on the right heel, and subsequently enlarged gradually. Histological examination revealed anastomosing strands of pale epithelial cells, with occasional duct formation and mucinous fibrovascular stroma. There were two types of strands: thick and thin. Immunohistochemical study, using a panel of monoclonal antikeratin antibodies, revealed that the immunoreactivity differed between the two types of strands. The thick strands showed a staining pattern similar to the uppermost portion of the intradermal duct, and the thin strands showed a pattern similar to the other portion of the duct. This observation suggests that the thick and thin strands differentiate towards the uppermost portion and the remainder of the duct, respectively.

Histogenesis of clear cell hidradenoma: immunohistochemical study of keratin expression

The expression of cytokeratins in 10 cases of clear cell hidradenoma, including 3 cases of solid cystic hidradenoma, were examined using 21 kinds of monoclonal antibodies. We divided them into three histologic patterns: massive nests with a few lumina (M nests), nests with some tubular lumina (L nests), and nests in solid cystic hidradenomas (S nests). All hidradenomas showed similar immunoreactivities to those in the lower dermal ducts or secretory cells of normal eccrine glands. With antibodies against simple epithelial cytokeratins (CKs 7, 8, 18, and 19), however, different immunostaining was noted among the three histologic patterns. Namely, the M nests failed to react to them, although some luminal cells in the L nests revealed a positive staining. Furthermore, a majority of luminal cells in the S nests revealed a positive staining with them. Therefore, we think that the luminal cells in solid cystic hidradenoma mainly differentiate toward the secretory cells, and that the M nests mainly differentiate toward the dermal duct. Those in the L nests are thought to differentiate toward the dermal duct and the secretory cells. The proportion of the differentiation toward luminal cells of dermal ducts to the differentiation toward secretory cells was the main difference among the three nests. In addition, there was no difference in immunophenotypes between clear cells and epidermoid cells in the two kinds of hidradenomas.

Changes in cytokeratin expression in epidermal keratinocytes during wound healing

In order to investigate the re-epithelialization process during wound healing, the hair on the back of guinea pigs was shaved and then excisional wounds were made through the entire thickness of the skin. Histological changes were observed and changes in the expression of different cytokeratin polypeptides were examined using an immunohistochemical technique. Immunohisto chemical study revealed that the proliferating and migrating keratinocytes expressed the same cytokeratins as the basal cells of normal epidermis. In addition, the entire epidermis of fairly remote areas from the edges of the wound where no thickening was observed showed a temporarily abnormal staining pattern. The suprabasal cells in the regenerating epidermis temporarily expressed cytokeratins not only specific for suprabasal cells but also specific for basal cells. The cytokeratins expressed in normal basal keratinocytes were also present in the thickened granular layers. These data indicate that the expression of cytokeratins in the epidermal keratinocytes (even in fairly remote areas from the wound edges) changes during wound healing, that the origin of the migrating keratinocytes from the remaining epidermis seems to be the basal cells in the epidermis, and that the appearance of keratohyalin granules is not related to changes in cytokeratin expression.

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.

Immunohistochemical analysis of keratin expression in clear cell syringoma : A comparative study with conventional syringoma

Immunophenotypes, especially expression of cytokeratins, in 9 cases of clear cell syringoma were examined using antibodies against epithelial membrane antigen (EMA), and 17 kinds of monoclonal anti‐keratin antibodies to investigate its histogenesis. In addition, 7 cases of conventional syringoma were selected for parallel assessment. Conventional syringoma expressed CK1 and CK10, which exists in the acrosyringium and the transitional portion between the acrosyringium and the dermal duct. Based on immunostaining with RCK102 and 35βH11, syringoma was thought to express CK5. Because expression of CK5 was observed in the basal cells of sweat duct ridge (lower acrosyringium) and the outer cells of the dermal duct, but not in the acrosyringium located at upper epidermis, we speculated that syringoma differentiated toward the transitional portion between the acrosyringium and the dermal duct. A comparative study of keratin expression between conventional and clear cell syringoma showed that there was no difference in the immunoreactivities. Based on the above observations, we confirmed that clear cell syringoma is a metabolic variant of conventional syringoma, and differentiates into the transitional portion between the acrosyringium and the dermal duct.

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.

Carcinomatous transformation of eccrine syringofibroadenoma

Background: While squamous cell carcinoma and pseudocarcinomatous hyperplasia have been documented as pre‐existing lesions in cases of reactive eccrine syringofibroadenoma (ESFA), to the best of our knowledge carcinoma occurring in a solitary ESFA has not yet been reported. We present one such case in a 91‐year‐old female who had a dome‐shaped, reddish tumor on the extensor side of the left forearm.

Immunohistochemical analysis of cytokeratin and human milk fat globulin expression in mucinous carcinoma ofthe skin

Background:  Mucinous carcinoma of the skin (MCS) is a rare epithelial tumor which arises primarily in the skin. Metastatic MC from extracutaneous sites, especially breast or colon, mimics MCS and cannot be differentiated from MCS by routine histology alone.