S. Ansai

A histochemical and immunohistochemical study of extra-ocular sebaceous carcinoma

A histochemical and immunohistochemical study of five cases of extra‐ocular sebaceous carcinoma was performed using formalin‐fixed and paraffin‐embedded tissue specimens. Histochemically, the clear cells of sebaceous carcinomas were negative with periodic acid‐Schiff and alcian blue staining. Immunohistochemically, the tumour cells of sebaceous carcinomas showed positive reactions for epithelial membrane antigen, human milk fat globules subclass 1, human milk fat globules subclass 2 and Leu M1, but did not express carcinoembryonic antigen, breast carcinoma associated antigen, S‐100 protein, gross cystic disease fluid protein‐15 or Dako M1. These histochemical and immunohistochemical findings were compared with those of other skin cancers which must be distinguished histopathologically from sebaceous carcinoma. We conclude that sebaceous carcinoma can be distinguished from eccrine porocarcinoma, malignant clear cell hidradenoma, extramammary Pagets disease, malignant trichilemmoma, squamous cell carcinoma and basal cell carcinoma by histochemical and immunohistochemical techniques using formalin‐fixed and paraffin‐embedded tissue specimens.

An immunohistochemical study of E-cadherin expression in human squamous cell carcinoma of the skin: relationship between decreased expression of E-cadherin in the primary lesion and regional lymph node metastasis.

E‐cadherin is a Ca2+‐dependent, intercellular adhesion molecule that is specifically expressed in epithelial tissues and is essential for maintaining intercellular connections. It has been reported that E‐cadherin expression of tumor cells is often decreased in some types of metastasizing carcinomas as compared with those without metastasis.

A case of tubular apocrine adenoma with syringocystadenoma papilliferum.

We report a new case of a Japanese man who developed a tubular apocrine adenoma in association with syringocystadenoma papilliferum. The differences in the histopathological and immunohistochemical findings in these 2 tumors are described. This is the first immunohistochemical study of tubular apocrine adenoma.

A case of ductal sweat gland carcinoma connected to syringocystadenoma papilliferum arising in nevus sebaceus

We report a case of a tumor arising in the preauricular region in a 50‐year‐old woman. The histopathological findings revealed it to be a ductal sweat gland carcinoma connected to a syringocystadenoma papilliferum (SCAP) arising in a nevus sebaceus. Mucinous stroma, considered to be deposition of hyaluronic acid, was also observed in the ductal carcinoma portion. The immunohistochemical and ultrastructural findings in the ductal carcinoma were compared with those in the SCAP. The proliferating cell nuclear antigen labeling index of the cells in the ductal carcinoma was higher than that of those in the SCAP. Both the ductal sweat gland carcinoma and SCAP showed findings compatible with the ductal segment of a sweat gland.

An Immunohistochemical Study of Sebaceous Carcinoma with Anti‐Keratin Monoclonal Antibodies: Comparison with Other Skin Cancers

Formalin‐fixed and paraffin‐embedded tissue specimens of six cases of extraocular sebaceous carcinoma were studied immunohistochemically with eight anti‐keratin monoclonal antibodies, 34βB4, 35βH11, Ks13.1, Ks19.1, PKK1, LP34, KL1 and AE1. The staining patterns of sebaceous carcinoma were compared with those of normal sebaceous glands and other skin cancers which should be distinguished from sebaceous carcinoma histopathologically. The other skin cancers compared were eccrine porocarcinoma, malignant clear cell hidradenoma, extramammary Pagets disease with underlying adenocarcinoma, malignant trichilemmoma, and squamous cell carcinoma. Most cases of sebaceous carcinoma were stained with 35βH11, Ks19.1, LP34, KL1 and AE1, while normal sebaceous glands were positive only with 35βH11, LP34, KL1 and AE1. By immunostaining, sebaceous carcinoma was distinguishable from extramammary Pagets disease with underlying adenocarcinoma, squamous cell carcinoma, malignant trichilemmoma, and eccrine porocarcinoma, but was not clearly distinguishable from malignant clear cell hidradenoma. These findings demonstrate that sebaceous carcinoma shows positive reactions with antibodies to simple epithelial keratin, probably as a result of neoplastic transformation, and that immunohistochemical examination using anti‐keratin monoclonal antibodies is useful in distinguishing sebaceous carcinoma from several other skin cancers.

Genetic analysis of cutaneous squamous cell carcinomas arising from different areas

Although cutaneous squamous cell carcinomas (SCC) occur most frequently in sun‐exposed areas of the skin, they can also arise in non‐sun‐exposed areas. Some risk factors for cutaneous SCC, such as ultraviolet (UV) light, are well known. However, the major factor for carcinogenesis may depend on the site of the tumor as well as the ethnicity of the patient. In this study we examined 41 Japanese cutaneous SCC cases, focusing on the area of appearance and the presence of genetic alteration, with 27 cases from sun‐exposed areas, 10 from non‐sun‐exposed areas (excluding genital areas), and four from burn scars from sun‐exposed areas. Squamous cell carcinomas arising in sun‐exposed areas showed less frequent p53 gene mutations compared to SCC arising in non‐sun‐exposed areas. Ultraviolet light‐specific mutations were found in only two cases of SCC from sun‐exposed areas. Human papilloma virus (HPV) DNA was detected in two cases (7.4%) of the sun‐exposed areas and none of the non‐sun‐exposed or scar areas. The frequency of loss of heterozygosity on D5S178 in non‐sun‐exposed SCC was significantly higher than in sun‐exposed SCC. Furthermore, the incidence of fractional allelic loss (FAL) was significantly higher in non‐sun‐exposed SCC than in sun‐exposed SCC. Our findings suggest that sun‐exposed SCC in Japan may be relatively less involved with p53 mutation, and that non‐sun‐exposed SCC acquire more genetic alterations than sun‐exposed SCC.

An immunohistochemical study of BCA-225 in various skin cancers

We performed an immunohistochemical study of BCA‐225, which is a glycoprotein secreted by the T47D breast carcinoma cell line and recognized by monoclonal antibody BRST‐1 (clone name: CU‐18), in normal skin and various skin cancers. In normal skin, BCA‐225 was positive only in the secretory portion of both eccrine and apocrine glands and in mature cells of the sebaceous gland. We observed 10 cases of squamous cell carcinoma of the skin, 10 cases of basal cell carcinoma without sebaceous differentiation, 3 cases of basal cell carcinoma with sebaceous differentiation, 6 cases of malignant trichilemmoma, 8 cases of eccrine porocarcinoma, 3 cases of ductal carcinoma, 1 case of malignant clear cell hidradenoma, 1 case of apocrine adenocarcinoma, 6 cases of extra‐ocular sebaceous carcinoma, 5 cases of extramammary Pagets disease with underlying adenocarcinoma, and 11 cases of extramammary Pagets disease without underlying adenocarcinoma. Most of the cases of sweat gland carcinoma, basal cell carcinoma with sebaceous differentiation, sebaceous carcinoma, and extramammary Pagets disease were positive for BCA‐225, while none of the cases of squamous cell carcinoma, basal cell carcinoma without sebaceous differentiation, or malignant trichilemoma were positive. Based on these findings, we believe that BCA‐225 is useful in distinguishing tumors with sweat gland and sebaceous differentiation and extramammary Pagets disease from tumors without such differentiation.

Keratin specificity analyses of eight anti-keratin monoclonal antibodies, and their immunostaining patterns in normal skin using formalin-fixed and paraffin-embedded tissue specimens

Keratin specificity analyses of eight anti-keratin antibodies (34ΒB4 (K1), 35ΒH11 (K8), Ks 13.1 (K13), Ks 19.1 (K19), PKK1, LP34 (CK1), KL1 and AE1) using keratin protein derived from normal thigh epidermis, normal parotid gland and a human squamous cell carcinoma cell line (HSC-5) were performed, and compared with those described in the data sheets. The reactivities of LP34, KL1 and PKK1 were markedly different from those mentioned in the data sheets. The immunostaining pattern of these antibodies in normal skin using formalin-fixed and paraffin-embedded tissue specimens was also examined. The staining patterns of suprabasal keratinocytes (K1, K13, CK1 and KL1 positive), basal cells of the epidermis (PKK1 and AE1 positive), inner cells of the ducts (K8, K13, CK1, KL1 and AE1 positive) and secretory cells of sweat glands (K8, K19, PKK1, KL1 and AE1 positive), mature cells (K8 and KL1 positive) and peripheral cells (CK1, KL1 and AE1 positive) of sebaceous glands and outer root sheaths (PKK1, CK1, KL1 and AE1 positive) were specific. Thus, we conclude that the differentiation of epidermis and skin appendages is possible by immunostaining with these eight anti-keratin antibodies using formalin-fixed and paraffin-embedded tissue specimens with proper protease pretreatment.

Malignant transformation of benign hidroacanthoma simplex

A case of malignant hidroacanthoma simplex of the anterior aspect of the right ankle in a 75-year-old man is reported. A specimen obtained in 1987 showed the features of benign hidroacanthoma simplex, whereas that taken in 1991 revealed malignant transformation. We performed immunohistochemical studies on these two specimens, and they suggest this tumor derives from the outer cells of intraepidermal ducts. The proliferating cell nuclear antigen labelling index and argyrophil nucleolar organizer regions of these two specimens were also compared and correlated with malignant transformation.

A patient with rhabdomyosarcoma and clear cell sarcoma of the skin

We describe a patient with rhabdomyosarcoma of the posterior cervical region and clear cell sarcoma on the occipital scalp. These two tumors later metastasized to distant skin. We differentiated these tumors by histopathologic, histochemical, immunohistochemical, and ultrastructural findings. Cells of the posterior cervical tumor showed differentiation toward striated muscle, whereas those of the occipital tumor showed findings compatible with melanocytic differentiation.