Squamous cell carcinoma of the skin: dual differentiations to rare basosquamous and spindle cell variants

Basosquamous carcinoma (BSC) is defined as a tumor containing the areas of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with a transition zone linking the two. Spindle cell squamous carcinoma (SCSC) may have a variable component of conventional SCC and spindle cells. We present a case of an 89-year-old woman with an eruption on the scalp for several decades. Grossly, the lesion measured 8.5 x 6.0 x 1.8 cm and consisted of a gray-white and focally black tumor. Microscopically, a non-ulcerated upper part of the tumor consisted of large polygonal squamoid cells with occasional keratinization (SCC), trabecular growth of basaloid cells with peripheral palisading (BCC), and an area in which both the components were intermingled. The rest of the tumor was a myxoid area with elongated fusiform spindle cells, which appeared to arise from conventional SCC. Immunohistochemically, the tumor cells in the SCSC (both conventional and spindle cell) area co-expressed CAM5.2, and vimentin. Ber-EP4 was positive in the BCC area with the transition zone of SCC and BCC showing diminished staining. Epithelial membrane antigen was focally positive in the conventional SCC area. To our knowledge, this is the first case report of SCC of the skin that has dual differentiations to BSC and SCSC.     

Differences in sialyl-Tn antigen expression between keratoacanthomas and cutaneous squamous cell carcinomas

Keratoacanthoma and squamous cell carcinoma are common skin tumors, especially in immunosuppressed transplant recipients, but the distinction between these two types of epidermal neoplasia may be difficult. Sialyl-Tn (Sia-GalNAc-O-Ser/Thr) is a cell surface carbohydrate associated with hyperplasia in squamous epithelium, and correlated with poor prognosis in several human adenocarcinomas. Twenty-seven keratoacanthomas and 29 cutaneous squamous cell carcinomas were examined for the expression of sialyl-Tn and of the Ki67 epitope, the latter a marker for cell proliferation. By immunohistochemistry, basaloid tumor cells at the periphery of tumor nests showed some degree of sialyl-Tn expression in 16 keratoacanthomas (59%), while only three squamous cell carcinomas (10%) showed sialyl-Tn-positive basaloid tumor cells (p<0.001). Keratinized, differentiated tumor cells were more often sialyl-Tn-positive in keratoacanthomas (89%) than in squamous cell carcinomas (31%) (p<0.001). A striking sialyl-Tn-positivity in the basal cell layer was found in a border zone directly adjacent to most tumors of both types (88 and 88%). By immunohistochemical examination of parallel sections and by double immunofluorescence, sialyl-Tn antigen expression was primarily seen in cells that did not express Ki67, although some overlap was present. Keratoacanthomas from transplant recipients did not differ in sialyl-Tn expression compared to those from non-immunosuppressed patients. The results indicate that sialyl-Tn expression is not directly related to cell proliferation, but rather to cellular features of post-mitotic cells, and that sialyl-Tn is not associated with a malignant phenotype. Sialyl-Tn may be linked to tumor regression, as seen in keratoacanthomas.     

鳞状细胞癌抗原在几种皮肤病中的检测

目的了解常见皮肤病患者的血清鳞状细胞癌抗原(SCC-Ag,简称SCCA)表达并探讨其在皮肤病诊疗中的意义。方法收集179例患者的临床资料,对42种皮肤科常见疾病患者血清SCCA的测定值进行分析。结果银屑病与红皮病患者的SCCA值高于正常水平者为100%。此外,存在SCCA血清水平增高的疾病还包括天疱疮(12/16)、大疱型类天疱疮(14/23)、湿疹(18/28)、药疹(2/5)、皮肤鳞状细胞癌(2/7)、嗜酸细胞增多性皮病(3/4)等。皮肤表皮受累面积越广、表皮角化、表皮剥脱越严重的疾病SCCA值相对越高。随着病情的好转,患者的SCCA值降低。结论血清SCCA测定值可以作为皮肤病临床诊疗过程中皮损受累程度和治疗效果评价的一项参考指标。     

Defective expression of a desmosome-related keratinocyte membrane antigen in squamous cell carcinoma

Intercellular junctions of keratinocytes are essential for coordination of the epithelial tissue function. Neoplastic transformation is often accompanied by changes in the glycolipid and glycoprotein composition of the cell membranes, although no evident structural modifications can be observed. We have investigated one aspect of the keratinocyte cell-cell contact in squamous cell carcinoma using KM48 monoclonal antibody as a differentiation-related marker for desmosomes. Quantitative analysis of the immunogold labelling revealed that the tumor cells lose the KM48 antigen during their neoplastic transformation. The process could also be observed, although to a lesser degree, in clinically and ultrastructurally normal marginal epidermis. The desmosome frequency in the tumor tissue also decreased, but not as radically as did the KM48 expression. Decreased expression of the desmosome-related membrane antigen suggests qualitative and perhaps functional modifications of the junction in squamous cell carcinoma.     

皮肤鳞状细胞癌和基底细胞癌癌细胞表达CD54抗原的免疫电镜研究

为探讨皮肤鳞状细胞癌（鳞癌）和基底细胞癌（基癌）癌细胞上是否低水平表达CD54抗原,应用低温聚合、包埋后染色的胶体金免疫电镜技术,对3例鳞癌和3例基癌CD54免疫组化色阴性的癌细胞进行了研究。在3例鳞癌和3例基癌中,各2例癌细胞表面及突起处观察到CD54胶体金颗粒的存在;其中1例鳞癌张力微丝－桥粒复合体处还可见CD54胶体金颗粒分CD54抗原。该结果可解释皮肤鳞癌和基癌临床上可发生转移,但发生率较低的机理,值得进一步研究。     

Cell-mediated immunity in patients with basal and squamous cell skin cancer

T and B lymphocyte levels were normal in fifty patients with basal and squamous cell skin cancer. Patients with basal cell carcinomas and small squamous cell carcinomas reacted normally to intradermal antigens and to dinitrochlorobenzene (DNCB). However, patients with large (greater than 3 cm) squamous cell carcinomas appeared to have defective systemic cell-mediated immunity because only 33% of them reacted to at least one intradermal antigen, and only 67% could be sensitized to DNCB. Presently, it is unknown whether this defect is related to the occurrence or behavior of squamous cell carcinoma.     

Pseudovascular squamous cell carcinoma

The adenoid form of squamous cell carcinoma is a neoplasm that is characterized by the fact that it presents a pseudoglandular pattern in the histological study. The biological phenomenon that explains this histological pattern is acantholysis; when the latter is massive, the tumor may even mimic a vascular proliferation, and is known as pseudovascular squamous cell carcinoma. This tumor has the clinical characteristics of a squamous cell carcinoma, but histologically, it may mimic an angiosarcoma. Most cases of pseudovascular squamous cell carcinoma of the skin have a poor prognosis.     

Studies of cellular mediated immunity in malignant melanoma patients by leukocyte adherence inhibition test

Summary Sixteen malignant melanoma patients with different levels of tumor progression, two patients with melanoma in situ (Clark 1) two bronchogenic carcinoma patients and nine healthy controls were tested by means of the leukocyte adherence inhibition (LAI) test to assess the function of their cellular mediated immunity. Blood leukocytes were incubated with allogeneic melanoma-associated antigen obtained from potassium chloride extract of tumor cells.Fifteen malignant melanoma patients with clinical stage I–III (Clark level 2–5) showed positive LAI-reaction when leukocytes were tested with melanoma associated antigen. Leukocyte adherence inhibition was neither monitored in healthy controls, in patients with melanoma in situ, nor in those two patients with squamous and oat cell type bronchogenic carcinoma. Extracts prepared from normal skin showed no inhibitive effect on leukocyte adherence in malignant melanoma patients and controls.A decreased percentage of LAI was observed in malignant melanoma patients with disseminated disease due to an increased spontaneous leukocyte adherence in these patients. This increase in spontaneous leukocyte adherence was probably caused by non-specific activation of adherent cells (macrophages) as a result of the prolonged therapy and/or the progressive tumor levels in these patients.This work was supported by the Agnes-and Georg-Blumenthal-Stiftung 26/7/4     

Alterations of mitogenic responses of mononuclear cells by arsenic in arsenical skin cancers.

We have studied the endemic occurrence of chronic arsenism in a limited area on the southwest coast of Taiwan. The effects of arsenic on the mitogenic responses of mononuclear cells (MNC) derived from patients with arsenical skin cancers in that area were evaluated. The subjects enrolled in this study included patients with 1) Bowen's disease, 2) arsenical skin cancers (basal cell carcinoma and squamous cell carcinoma), 3) non-arsenical skin cancers (basal cell carcinoma and squamous cell carcinoma), 4) nasopharyngeal cancer and 5) healthy controls from endemic and non-endemic areas. Phytohemagglutinin (PHA) stimulated [3H]thymidine incorporation in MNC in all groups except the arsenical skin cancer group. However, when a low concentration of As2O3 (2.5 x 10(-7) M) was added to PHA-stimulated MNC, a tremendous amplification of the uptake of [3H]thymidine was noticed in patients with arsenical skin cancer. In this study, this phenomenon did not occur in cancers not related to arsenic. This result shows that arsenical carcinomas are hyperreactive to its specific etiology--arsenic. Arsenic seems to play a role as a co-stimulant of PHA similar to interleukin-1.     

Immunohistochemical localization of ornithine decarboxylase in human skin

The localization of ornithine decarboxylase (ODC) in human skin and cultured keratinocytes was studied with an immuno-histochemical method. ODC was found in the epidermis, hair follicles, sweat glands and errector muscles. Irritation induced by stripping or UV-B irradiation did not change the staining pattern in the epidermis. In psoriasis, the staining was most marked at the tip of the epidermal rete ridges. In basal cell carcinoma, there was a homogeneous labelling of the tumor cells and, in squamous cell carcinoma, the labelling was strong but less homogeneous. Melanoma and dermal naevus also positively stained for ODC. Cultured human keratinocytes also showed ODC positive immunofluorescence. This technique detects the ODC antigen present rather than levels of ODC activity.     

基底细胞癌和鳞状细胞癌中转化生长因子βⅠ型和Ⅱ型受体表达

目的探讨转化生长因子β(TGFβ)受体在基底细胞癌和鳞状细胞癌中表达水平的变化及其意义。方法采用实时定量PCR和SP免疫组化技术分别检测基底细胞癌、鳞状细胞癌及正常人对照皮肤中Ⅰ型和Ⅱ型TGFβ受体(TGFβRⅠ,TGFβRⅡ)mRNA和蛋白的表达。结果对18例基底细胞癌、24例鳞状细胞癌患者的皮损及正常人对照皮肤的研究显示,基底细胞癌和鳞状细胞癌皮损TGFβRⅠ和TGFβRⅡ的mRNA表达水平均显著低于正常人对照皮肤。免疫组化试验结果显示;TGFβRⅠ染色强度在基底细胞癌组、鳞状细胞癌组较正常人对照皮肤组显著降低(P<0.001);TGFβRⅡ在二组表皮肿瘤与正常人对照皮肤组问表达差异也有统计学意义(P<0.01)。结论基底细胞癌和鳞状细胞癌中TGFβ受体表达下调可能有助于这些上皮细胞起源的表皮肿瘤的形成。     

Parotideal lymph node metastasis in squamous cell carcinoma of the skin

BACKGROUND: Metastatic involvement of the parotideal lymph nodes from cutaneous squamous cell carcinoma is rare in occurrence, but has a high prognostic value. The aim of the present study was to define a patient group with a high risk for development of regional metastasis and to determine the follow-up course and therapy of metastasis in these patients. MATERIAL AND METHODS: Nineteen patients treated with malignancies of the parotid gland over a time period of four years were analyzed prospectively. RESULTS: In 6 out of 19 patients the parotideal tumor proved to be a lymph node metastasis of previously treated poorly differentiated squamous cell carcinoma of the skin. The diameter of the primary tumor was at least 1.5 cm in 5 out of 6 cases. The time interval between detection of metastatic involvement of the parotid gland and diagnosis of a preexisting skin cancer was approximately 7 months. Metastastic infiltration of cervical lymph nodes could be shown in 4 patients. In one patient pulmonary metastases were detected. CONCLUSION: On the basis of data from the literature and the results presented here, patients who are at high risk for regional metastasis were defined. Clinical examination of the parotid gland and cervical lymph nodes should be performed frequently in these patients at least for 18 months after primary tumor diagnosis. Parotideal lymph node metastases of a squamous cell carcinoma of the head skin should have similar treatment to primary squamous cell carcinoma of the parotid gland provided that a curative option exists.     

RCAS1 antigen is highly expressed in extramammary Paget's disease and in advanced stage squamous cell carcinoma of the skin

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1), which is a type II membrane protein expressed on cervical carcinoma cells, induces apoptosis in RCAS1 receptor expressing cells. RCAS1 is thus presumed to protect tumor cells from immune surveillance by infiltrating RCAS1 receptor-positive immunocytes (Sonoda et al. Int J Oncol 1995; 6: 1899-1904; Nakashima et al. Nature Med 1999; 5: 938-942). We performed immunohistochemical analysis of RCAS1 expression in various skin tumors. RCAS1 was not detected in normal human epidermis. One of 21 seborrheic keratosis (4.8%), one of 12 actinic keratosis (8.3%), two of 16 keratoacanthomas (12.5%), and two of 14 basal cell carcinomas (14.2%) expressed RCAS1. RCAS1 was not detected in Bowen's disease (0/17). RCAS1 was positive in 45 of 61 (73.8%) squamous cell carcinomas. Interestingly, the expression of RCAS1 was mostly correlated with clinical stages of squamous cell carcinoma. It was found that 46.1% of stage I, 61.1% of stage II, 85.7% of stage III, and 83.3% of stage IV squamous cell carcinomas were RCAS1-positive. In addition, RCAS1 was found to be highly expressed in extramammary Paget's disease. Fifty nine of 63 extramammary Paget's disease samples (93.7%) were positive for RCAS1. Fifty eight (92%) showed co-expression of RCAS1 and carcinoembryonic antigen (CEA). While two of 24 cases of melanoma (8.3%) expressed RCAS1 antigen, none of 20 cases of nevus pigmentosus showed positive staining. These results indicate that RCAS1 is a highly sensitive marker for extramammary Paget's disease. RCAS1 is also expressed in various skin tumors including squamous cell carcinoma, where positive correlation with clinical staging was documented.     

CD163~+肿瘤相关巨噬细胞在常见上皮性皮肤肿瘤中的分布

目的:检测CD163+肿瘤相关巨噬细胞在皮肤鳞状细胞癌、基底细胞癌、鲍温病、日光性角化病中的分布。方法:采用免疫组织化学法(Max Vision法)检测CD163标记的肿瘤相关巨噬细胞在正常皮肤、鳞状细胞癌、基底细胞癌、鲍温病、日光性角化病中的分布。结果:每高倍镜视野下正常皮肤、鲍温病、日光性角化病真皮浅层中CD163+巨噬细胞个数为(9.5000±1.71594)、(43.9200±9.98716)和(49.4000±8.73830)个;基底细胞癌肿瘤间质中为(42.1724 1±11.73234),鳞状细胞癌的肿瘤间质中及肿瘤实质内为(65.8421±14.05649)。结论:CD163+肿瘤相关巨噬细胞可能与皮肤上皮性肿瘤的发生、发展相关。     

Immunohistochemical Detection of Ki-67 in Epithelial Skin Tumors in Formalin-fixed Paraffin-embedded Tissue Sections Using a New Monoclonal Antibody (MIB-1)

The expression of the Ki-67 antigen was investigated in 44 epithelial skin tumors using an immunohistochemical technique on formalin-fixed, paraffin-embedded tissue sections. Microwave oven heating was employed for retrieval of the antigen in these tissue sections. The staining patterns varied among the epithelial skin tumors. The assessment of immunohistochemical staining was based upon the growth fraction (GF), defined as the number of Ki-67 positive cells divided by the total number of tumor cells counted and expressed as a percentage. GF was 9.7 ± 3.1% in seborrheic keratosis, 19.5 ± 2.9% in keratoacanthoma, 23.1 ± 4.9% in basal cell carcinoma, 18.5 ± 6.3% in actinic keratosis, 37.1 ± 6.0% in Bowen's disease, and 32.9 ± 10.5% in squamous cell carcinoma. There was a significant difference in GF between the keratoacanthoma and squamous cell carcinoma (p<0.01). Actinic keratosis showed a relatively low GF, whereas Bowen's disease showed a high one. Furthermore, the GF tended to increase with tumor cell differentiation in squamous cell carcinoma: 23.7% (±5.0) in well-differentiated, 35.0% (±6.2) in moderately-differentiated, and 47.6% (±4.5) in poorly-differentiated squamous cell carcinomas. Immunohistochemistry with MIB-1 may give useful additional information in the differential diagnosis of KA and SCC.     

CD-10 immunostaining differentiates superficial basal cell carcinoma from cutaneous squamous cell carcinoma

Basal cell carcinoma and squamous cell carcinoma are common entities in clinical practice. Their distinction can be difficult clinically as well as histologically. CD10 or common acute lymphoblastic leukemia antigen (CALLA) is a metallomembrane endopeptidase expressed on a variety of normal and neoplastic cells. We sought to determine if the CD10 immunostain could have diagnostic utility in distinguishing between early superficial basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). CD10 was strongly expressed in 14 out of 14 superficial BCCs and failed to express in 2 out of 2 deeply infiltrative BCCs. CD10 was negative in the tumor cells in 13 out of 13 superficially invasive SCCs and SCC in situ. CD10 expressed weakly in the surrounding stromal cells of 2 out of 13 SCCs. These findings support the utility of CD10 as a marker for early BCC, especially when SCC cannot be excluded clinically or by conventional stains. Furthermore, these results implicate CD10 in the pathogenesis of BCC.     

Immunohistochemical localization of proliferating cell nuclear antigen/cyclin in human skin

Summary Expression of proliferating cell nuclear antigen/cyclin (PCNA/cyclin) in skin tissue specimens and cultured keratinocytes was studied using a monospecific antibody, obtained from a patient with systemic lupus erythematosus, and a monoclonal antibody. Indirect immunofluorescent staining revealed that cultured keratinocytes obtained from human foreskins expressed PCNA/cyclin as variable nuclear patterns in 15–30% of the cells. In normal human skin tissue specimens, PCNA/cyclin was demonstrated in only a few basal cells. Interestingly, PCNA/cyclin was expressed strongly in almost all the cells of the lowest layer of the epidermis adjacent to squamous cell carcinomas, whereas the tumor aggregates themselves had no positive staining. In contrast, no such characteristic staining was demonstrated in specimens of basal cell carcinoma. The staining pattern of PCNA/cyclin was different from that of Ki-67 in the skin tissue specimens. Our results suggest that PCNA/cyclin could be a useful marker of cell proliferation.     

外阴白斑和外阴鳞癌中基底膜蛋白的研究

目的：研究层黏连蛋白(LN)和IV型胶原在外阴白斑和外阴鳞癌中的表达。方法：采用SABC免疫组化法，对59例外阴白斑和9例外阴鳞癌标本进行基底膜蛋白染色。结果：正常皮肤组织、外阴白斑(增生型、硬化萎缩型和混合型)LN和IV型胶原基底膜染色密度高，呈连续线状。LN和IV型胶原的染色密度和基底膜的连续性与外阴白斑的异常增生度及鳞癌的分化程度(由高分化到低分化)呈负相关。结论：基底膜蛋白的表达和分布与外阴白斑分型有关，外阴鳞癌和不典型增生组织中表达阳性率明显低于外阴白斑各型，基底膜蛋白有可能作为早期诊断癌前病变的一种生物学指标。     

T cell subsets and soluble immune response suppressor (SIRS) factor in skin squamous cell carcinoma

T cell subsets (theophylline-sensitive T lymphocytes and T gamma lymphocytes), and the activity of soluble immune response suppressor (SIRS) factor have been investigated in a total of 53 patients with squamous cell carcinoma (SCC) of the skin. Eight of these had metastatic regional lymph nodes. The results showed decreased values for theophylline-sensitive T lymphocytes and elevated values for T gamma cells. Suppressor function evaluated by means of SIRS factor was normal in 36 patients with non-metastatic skin SCC and decreased in 8 with metastatic skin cancer.