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Immunohistologic differential diagnosis of basal cell carcinoma, squamous cell carcinoma, and trichoepithelioma in small cutaneous biopsy specimens.

The distinction between squamoid basal cell carcinoma and basaloid squamous cell carcinoma (or between BCC and trichoepithelioma variants) is usually made readily on the basis of defined histological criteria. However, these differential diagnoses occasionally can pose difficult morphological problems. The stated distinctions are clinically important because the risk of progressive disease is significantly higher with squamous carcinoma of the skin than with basal cell carcinoma (BCC), and a trichoepithelioma misinterpreted as BCC burdens the patient with an inaccurate diagnosis that may result in inappropriate surgery. Recent reports have suggested that reactivity with the monoclonal antibody Ber-EP4 is capable of separating histologically similar basal cell and squamous carcinomas, and that the expression of bcl-2 or CD34 antigen is able to distinguish BCC from trichoepithelioma. However, corroborative studies of these contentions are few in number. In order to investigate the usefulness of the stated immunostains in the above-cited differential diagnoses, the authors analyzed 45 basal cell carcinomas and 22 squamous carcinomas, as well as 36 trichoepitheliomas. The monoclonal antibodies Ber-EP4, My10 (CD34), and anti-bcl-2 were applied to formalin-fixed paraffin sections in all cases, using a standard avidin-biotin-peroxidase complex method. Most BCCs demonstrated strong, diffuse cytoplasmic labeling with Ber-EP4 and anti-bcl-2. In contrast, the squamous carcinomas were uniformly negative for the former marker and only focally reactive for the latter in four examples. 'Peripheral' bcl-2 staining of trichoepitheliomas was noted in 24 of 33 of the immunoreactive tumors, but the remainder were marked diffusely and similarly to most BCCs. Among the latter, immature trichoepitheliomas were diffusely reactive for this marker in 6 of 8 cases. Labeling of epithelium for CD34 failed to discriminate between any of the tumor types under evaluation, whereas staining of peritumoral stroma was characteristic of the majority of trichoepitheliomas and more than one-third of metatypical basal cell carcinomas. These data support the suggestion that Ber-EP4 and bcl-2 are useful in the separation of BCC from squamous carcinomas. Nevertheless, they also serve to caution against reliance upon bcl-2 and CD34 immunostains in attempting to distinguish BCC from trichoepithelioma in histologically enigmatic cases. There is currently no certain method other than conventional microscopy that can be applied successfully to the latter problem.

Antibodies, Monoclonal↗

[Determination of epidermal growth factor (EGF) receptors in basal cell carcinomas, squamous cell carcinomas and melanomas].

We studied the binding of EGF receptors (EGF-R) in 19 basal cell carcinomas, 8 squamous cell carcinomas, and 9 malignant melanomas. Specific binding of EGF-R was detected in 10 of the basal cell carcinomas, and in all the 8 squamous cell carcinomas. None of the malignant melanomas showed EGF-R binding. A comparative study of the receptor status vs. clinical prognostic data, such as grading and clinical course, did not reveal any significant differences, whereas in ovarian carcinomas, the EGF receptor correlated with the prognosis.

Biomarkers, Tumor↗

Trends in basal cell carcinoma, squamous cell carcinoma, and melanoma of the skin from 1973 through 1987.

Major increases have occurred in the incidence of basal cell carcinoma and squamous cell carcinoma of the skin, as well as in cutaneous malignant melanoma during the period 1973 through 1987 in British Columbia. The greatest increases in basal and squamous cell carcinomas are on the head and neck. This indicates that exposure to sunlight is the major causative factor. The greatest increase in melanoma is on the trunk in men and on the lower limbs in women. The dramatic increases in nonmelanoma skin cancers in British Columbia, a relatively low sunlight area, suggest that major prevention programs are needed in areas that are not considered "sunspots."

Adolescent↗

Altered distribution of 1-2B7B antigen in basal cell carcinoma, squamous cell carcinoma and Bowen's disease.

Skin lesions of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and Bowen's disease were immunohistochemically examined using the 1-2B7B monoclonal antibody, which recognizes a 120 kDa polypeptide component found in hemidesmosomes of normal human epidermis and hemidesmosome-like adhesion junction of vascular endothelial cells, to disclose altered characteristics of the interface between the tumor cell aggregate and stromal tissues of the epidermal neoplasms. In BCC, 1-2B7B antigen was rarely expressed at the tumor cell aggregate-stromal tissue interface, where poorly developed hemidesmosometonofibril complexes and a normal-looking lamina densa were detectable. In SCC and Bowen's disease, 1-2B7B antigen was expressed not only along the interface of the tumor nest and stromal tissue, but also in the intercellular space of the desmosomes and other adhesion junction structures that lack associating tonofibrils. In the invading front of SCC, 1-2B7B antigen had partly disappeared from the tumor cell aggregate-stromal tissue interface, where neither hemidesmosomes nor lamina densa were noted. The altered distribution of this hemidesmosomal component in the epidermal neoplasms seems to reflect aberrant interaction of neoplasmic cells and surrounding stromal tissue.

Antibodies, Monoclonal↗

Basal cell carcinoma, squamous cell carcinoma and melanoma of the skin: analysis of the Singapore Cancer Registry data 1968-97.

BACKGROUND: There has been an alarming recent increase in skin cancer incidence among fair-skinned populations. Information from Asian populations is less readily available. OBJECTIVES: This study examines time trends and ethnic differences of skin cancers among Asians in Singapore. METHODS: Data from 1968 to 1997 was obtained from the Singapore Cancer Registry, a population-based registry. Age-standardized incidence rates (ASRs) and age-adjusted average annual percentage change, using the Poisson regression model, were calculated. RESULTS: A total of 2650 basal cell carcinomas (BCCs), 1407 squamous cell carcinomas (SCCs) and 281 melanomas were reported. There was an overall increase of skin cancer from 6.0 per 100000 person years (1968-72) to 8.9 per 100000 person years (1993-97). BCC incidence increased 3% annually, melanoma remained constant, and SCC decreased 0.9% annually. BCC ASRs were highest among Chinese, then Malays and Indians. A similar pattern was noted for SCC and melanomas. CONCLUSIONS: The incidence rates of skin cancer increased in Singapore during the period 1968-97. Fairer-skinned Chinese had a higher incidence of skin cancer.

Adult↗

Establishment and characterization of a spindle cell squamous carcinoma cell line.

BACKGROUND: Spindle cell squamous carcinoma (SCSC) is a rare and peculiar biphasic malignant neoplasm that occurs mainly in the upper aerodigestive tract. It consists of sarcomatoid proliferation of pleomorphic spindle-shaped cells and squamous cell carcinoma. METHODS: Here, we established a SCSC cell line from a tumour arisen in gingiva. We characterized the feature of a SCSC cell line by immunohistochemistry. To know the biological feature, we examined the cell growth, invasiveness and epithelial-mesenchymal transition markers of a SCSC cell line in comparison with oral squamous cell carcinoma (OSCC) cell lines. RESULTS: By immunohistochemical analyses, the primary tumour expressed cytokeratin and vimentin, indicating carcinosarcoma-like characters. This tumour also showed overexpression of p53 protein. Cultured SCSC cells resulted in bypass of crisis and maintenance over passage 100. The established SCSC cell line was spindle-shaped and showed identical immunohistochemical characters to those of primary tumour cells. Similar to the primary tumour, the cell line showed p53 overexpression and had p53 mutation at codon 132: AAG (lys)-->AAT (asp). The SCSC cell line grew slower than two other OSCC cell lines (MSCC-1 and HSC-2), whereas SCSC cells had remarkable invasiveness in comparison with these cell lines. Moreover, SCSC cells expressed wnt-5a and vimentin mRNA at high levels, but did not express E-cadherin mRNA. This expression pattern of the markers was similar to that of mesenchymal cells, not of epithelial cells. CONCLUSION: In the present study, we newly established a SCSC cell line with strong invasiveness. This is the first report on the establishment of SCSC cell line. The SCSC cell line can be a useful cell model for the study to know the cytodifferentiation and nature of SCSC.

Aged↗

Basal cell carcinomas and squamous cell carcinomas of human skin show distinct patterns of chromosome loss.

Although basal cell carcinomas and squamous cell carcinomas are clinically and pathologically distinct, the molecular basis for these differences is not clear. We have used polymorphic microsatellite markers to determine the pattern and extent of chromosome losses in a series of 44 basal cell carcinomas and 47 squamous cell neoplasms of the skin. Basal cell carcinomas showed a distinctive allelotype with chromosome loss largely confined to a single chromosome arm, 9q (26 of 44 informative tumors). In contrast to the predominance of loss on a single chromosome arm in basal cell carcinomas, squamous cell neoplasms showed more widespread loss with loss of heterozygosity of markers from 35 of 39 chromosome arms in one or more of the tumors studied. The pattern of loss was also different from basal cell carcinomas with frequent loss of heterozygosity of markers from 9p (41%), 13q (46%), 17p (33%), 17q (33%), and 3p (23%) in squamous cell neoplasms. The frequent loss of markers from these chromosome arms relative to other chromosome losses suggests that these arms may contain genes important in the development of cutaneous squamous cell carcinomas.

Basal Cell Carcinoma↗

Metaplastic breast carcinoma histologically mimicking cutaneous spindle cell squamous cell carcinoma.

Squamous cell carcinoma is one of the most common primary cutaneous carcinomas but on rare occasion, metastatic squamous cell carcinoma from a distant site or solid organ can present as a cutaneous lesion. Most metastases occur as dermal nodules or involve the dermal lymphatics, but when they are intimately associated with the epidermis, distinguishing the lesion as primary or metastatic may be extremely difficult and usually requires a clinical history or high index of suspicion. A 71-year-old woman presented with multiple eruptive nodules over her chest, flank, and back. Histologically the lesions appeared to be arising from the surface epithelium and consisted of atypical, predominantly spindle cells, some of which streamed off of the epidermis. Following the initial evaluation, a history of breast carcinoma with subsequent radiation therapy and ultimate mastectomy was obtained, and the original breast biopsy and mastectomy material was reviewed. After performing additional studies, it became clear that the origin of the carcinomas was metastatic from an underlying metaplastic breast carcinoma.

Aged↗

Ultrastructural localization of gap junction protein connexin 43 in normal human skin, basal cell carcinoma, and squamous cell carcinoma.

The expression and localization of connexin 43 (Cx43) were investigated in normal human epidermis, pilosebaceous apparatus, basal cell carcinoma, and squamous cell carcinoma by immunofluorescence as well as by immunoelectron microscopy. In the normal epidermis the immunofluorescence was weak in the basal layer, increased in spinous layer and negative in the horny layer. In the sebaceous gland, peripheral lobular cells showed weak cell membrane dotted pattern. Cell membrane and cytoplasmic fluorescence was strong in the central lobular cells. In the lower hair follicle, the cortex, inner and outer root sheath cells showed cell membrane fluorescence. As cortical cells underwent keratinization, they lost Cx43 epitopes. Basal cell carcinoma and squamous cell carcinoma were poorly stained, and eccrine and apocrine glands were unstained. In immunoelectron microscopy, close membrane appositions of typical gap junctions were often observed in the spinous layers of the epidermis and the immunolabeling for Cx43 was seen along the gap junction structures. Circular and long gap junctions often were found in follicular root sheaths and sebaceous glands. Gold particles labeling Cx43 in these gap junctions were found on the gap junctions or localized in the cytoplasm near the gap junction membranes. Basal cell carcinoma and squamous cell carcinoma had a small number of small gap junctions, and gold particles were not only localized to gap junctions but scattered in the cytoplasm. No gap junctions were labeled in eccrine and apocrine glands. These findings confirmed that 1) long, curved or circular membrane appositions found in hair follicle and sebaceous gland are true gap junctions, 2) immature cells such as epidermal basal cells, peripheral germinative cells of sebaceous gland and basal and squamous cell carcinoma cells do not have fully developed gap junctions, and 3) Cx43 or its precursors are present in the cytoplasm as well as on poorly developed gap junctions in these immature cells. Immunofluorescence findings generally corresponded to ultrastructural distribution and structural maturity of gap junctions.

Adult↗

Mixed Merkel cell carcinoma and squamous cell carcinoma of the skin.

Four mixed Merkel cell and squamous cell carcinomas of the skin are described. The patients ranged in age from 74 to 90 years and demonstrated or had a history of previous ultraviolet or infrared damage to the skin, manifested by basal cell carcinoma, squamous cell carcinoma, actinic keratoses, solar elastosis, and erythema ab igne. Light microscopic examination of all 4 cases revealed invasive neoplasms consisting of 2 distinct but admixed cell types. The predominant cell type was consistent with Merkel cell carcinoma and was characterized by scant cytoplasm, a small dark polygonal nucleus with granular chromatin, a high mitotic rate, and cytokeratin 20 positivity. In each case, the Merkel cell component merged with a cytokeratin 20 negative squamous component characterized by abundant eosinophilic cytoplasm, intercellular bridges, and keratinization with focal squamous pearl formation. Immunohistochemical staining patterns were consistent with the usual pattern for that cell type; transitional cells were not demonstrated. The intimate admixture of the 2 antigenically different neoplastic cell types, and common etiologic role of ultraviolet and possibly infrared damage, lend support to the theory that some Merkel cell carcinomas and squamous cell carcinomas may arise from a pluripotent epidermal stem cell.

Aged↗

Intralesional interferon alpha-2b in the treatment of basal cell carcinoma and squamous cell carcinoma: revisited.

BACKGROUND: Intralesional interferon (IFN) alpha-2b has been shown to be a safe and effective mode of treatment for basal cell carcinoma and squamous cell carcinoma. Multiple studies published in the 1980s through the early 1990s have demonstrated the efficacy of intralesional interferon in the treatment of these malignancies. Unfortunately, this modality appears to be underused. OBJECTIVE: This article serves to remind dermatologists that in addition to cryotherapy, electrodesiccation, and surgical excision, intralesional IFN-alpha is an important part of the armamentarium in the treatment of nonmelanoma skin cancers. METHODS: In addition to a review of the literature, we present eight cases in seven patients successfully treated with intralesional IFN for basal cell carcinoma and squamous cell carcinoma. CONCLUSIONS: Its nonsurgical approach and excellent cosmetic results make IFNalpha-2b an attractive option for patients and an important alternative when other treatment modalities are impractical or contraindicated.

Aged↗

Cutaneous melanin density of Caucasians measured by spectrophotometry and risk of malignant melanoma, basal cell carcinoma, and squamous cell carcinoma of the skin.

Recent advances have enabled quite accurate estimation by spectrophotometry of the density of cutaneous melanin. The relation between skin cancers and this objective measure of skin phenotype is examined here. For this purpose, a population-based case-control study of subjects aged 20-59 years of northern European ancestry was conducted in Tasmania, Australia. Cases (n = 244) of cutaneous malignant melanoma during 1998-1999, and a sample of cases of basal cell carcinoma (n = 220) and squamous cell carcinoma (n = 195) of the skin were identified from cancer registrations. Controls (n = 483) were selected from a comprehensive population listing. Melanin at the upper inner arm was estimated from skin reflectance of light of 400 and 420 nm wavelengths. For melanoma, basal cell carcinoma, and squamous cell carcinoma, respectively, the odds ratios comparing the least with the highest of four melanin categories were 6.2 (95% confidence interval (CI): 2.3, 16.6), 6.3 (95% CI: 2.6, 15.1), and 4.2 (95% CI: 1.7, 10.8) for men and 1.9 (95% CI: 1.0, 3.7), 1.4 (95% CI: 0.7, 3.0), and 0.7 (95% CI: 0.3, 1.7) for women. The gender differences were not due to disparities in site of occurrence or (for melanoma) in thickness of the lesion. The authors conclude that, particularly for men, cutaneous melanin density at the upper inner arm is a strong predictor of risk of skin cancer.

Adult↗

Interferon therapy for basal cell carcinoma and squamous cell carcinoma.

Totally 161 basal cell and squamous cell carcinoma (BCC, SCC) patients were treated with human natural leucocytic interferon (HNLI) and recombinant IFN alpha 2c. After HNLI treatment, 61 out of 86 BCC patients and 29 out of 45 SCC patients were cured according to histopathologic and clinical findings. In 13 BCC and 13 SCC patients, the cancer lesion was reduced 25%-90%. After recombinant IFN alpha 2c treatment, 14 of 20 BCC patients and 4 of 10 SCC patients were cured according to histopathologic and clinical findings. In 6 BCC patients and 5 SCC patients the cancer lesion was reduced 25% to 90%. Both types of interferons are effective in the treatment of BCC and SCC patients. Local application of interferon stimulates immune reaction at the site of the tumor. There is a marked difference between the spontaneous macrophage activity and that induced by interferon. The interferon activated macrophages are significantly larger, the number of lysosomes and the density of macrophages is increased. In difficult locations intralesional therapy can be considered to avoid disfigurement of the patients with or without surgery.

Adult↗

[Squamous cell carcinoma].

Squamous cell carcinoma of the skin is common skin malignancy arising from malignant proliferation of the keratinocytes of the epidermis. Chronic exposure to ultraviolet radiation in sunlight is the most important risk factor for squamous cell carcinoma. Early diagnosis and appropriate treatment provide the best opportunity to cure cutaneous squamous cell carcinomas. Although it is locally invasive, squamous cell carcinomas usually remain localized and can be cured by a variety of techniques. Surgical excision is the most broadly used treatment for high-risk squamous cell carcinoma. It is well-tolerated, extremely effective, and the completeness of the procedure can be evaluated through histologic assessment of the specimen's margins. About 10 percent of squamous cell carcinomas in Japan spread to regional lymph nodes or more distant sites with a relatively poor outcome. Five-year cure rates are reported to be 85 to 80 percent for Japanese patients with squamous cell carcinomas, respectively. Recommendations for surgical margins vary depending upon the risk of local recurrence, especially; squamous cell carcinomas with perineural extension also need more extensive procedures. Patients with clinically enlarged lymph nodes may require radiographic imaging, fine needle aspiration, or lymph node biopsy. Depending upon the results of these tests, regional lymph node dissection may be done. Recently the sentinel lymph node biopsy technique is being evaluated for its ability to detect microscopic involvement in patients with high-risk patients who have no clinical evidence of lymph node metastasis. The occurrence of regional lymph node metastases places the patient at increased risk for the subsequent development of distant metastases. Distant metastases are associated with a markedly increased risk of disease-related mortality. Systemic chemotherapy has been to limited benefit in patients with disseminated squamous cell carcinoma patients. In Japanese patients with distant metastases, the five-year survival rate is about 10 percent. The ability of current chemotherapy protocols to increase the cure ratio in squamous cell carcinoma is still controversial.

Antineoplastic Agents↗

Actinic keratoses, basal cell carcinoma, and squamous cell carcinoma: uncommon treatments.

This contribution will discuss the treatment of actinic keratoses, basal cell carcinomas, and squamous cell carcinoma using methods that are not routinely established but have been used for a long period. The purpose of this article is simply to expand the reader's knowledge of what has been or could be used to treat such lesions. This article should not be interpreted as advocating the use of the methods discussed because there are obviously efficient well-established treatments for these lesions.

Administration, Topical↗