Excision margins for nonmelanotic skin cancer

Scientific evidence for advisable excision margins for nonmelanotic skin carcinoma is poorly documented. Recommended excision margins vary from 2 to 15 mm. A prospective study was performed on 150 skin lesions excised over a 9-month period in an outpatient facility at the authors' institution. Primary nonmelanotic skin lesions were clinically diagnosed as either basal cell carcinoma (nodular, superficial, infiltrating, or sclerosing) or squamous cell carcinoma (well, moderately, or poorly differentiated). Macroscopic surgical excision margins were individually assessed, measured, and excised. Histopathologic analysis was then independently performed to determine the correct diagnosis and to measure the actual microscopic lateral and deep excision margins.Sixty-one percent of lesions were basal cell carcinoma, 25 percent were squamous cell carcinoma, and 15 percent were benign or premalignant. Diagnostic accuracy was 81 percent for basal cell and 59 percent for squamous cell carcinoma. The average diameter of the basal cell carcinoma was 12.1 mm; 47 percent of these lesions had a diameter of less than 10 mm. The average diameter of the squamous cell carcinoma was 16.9 mm; 26 percent of these lesions had a diameter of less than 10 mm. The mean surgical margin was 4.2 mm (3.2 mm adjusted for shrinkage), whereas the mean microscopic lateral margin was 3.4 mm. Overall, complete excision was achieved for 98 percent of basal cell carcinoma and 100 percent of squamous cell carcinoma. The raw data were analyzed to assess the suitability of 1-, 2-, 3-, or 4-mm surgical excision margins. A 4-mm surgical margin would give a microscopic lateral margin beyond one microscopic high-power field (0.5 mm) in 96 percent of cases of basal cell carcinoma and in 97 percent of cases of squamous cell carcinoma.The authors recommend a 4-mm surgical margin as the optimal treatment for skin lesions clinically diagnosed as basal cell or squamous cell carcinoma that are suitable for excision in an outpatient facility. Well-demarcated lesions, such as a nodular basal cell carcinoma, may be excised with a 3-mm margin.     

A prospective study of the accuracy of the surgeon's diagnosis and significance of positive margins in nonmelanoma skin cancers

Even with a precise preoperative diagnosis, complete excision of nonmelanoma skin cancer is not always achieved. The conundrum remains the decision for appropriate secondary treatment. Many surgeons, regardless of the nature of the lesion, consider re-excision to be the only option. In a prior 4-year prospective study that ascertained the accuracy of our clinical diagnosis of skin lesions removed in an office setting, one-fifth were found to be malignant and 98 percent (n = 415) of the lesions were nonmelanoma skin cancer. Unfortunately, 65 (15.7 percent) of the malignant nonmelanoma skin cancer lesions had positive margins. The outcome of our management for these specific lesions was followed prospectively over the 7.5 years of this study to determine whether aggressive surgical intervention was justified in every case.Of 65 patients with lesions, early and complete re-excision of margin-positive nonmelanoma skin cancer was performed for 34 (52.3 percent), with residual tumor found in 11 (32.4 percent), followed by a later recurrence in one (2.9 percent). The remaining 31 patients agreed to semiannual office visits, with one (3.2 percent) recurrence in this group. Thus, the overall rate of recurrence for margin-positive nonmelanoma skin cancer was 3.1 percent, with a mean follow-up of 3.6 years (range, 0 to 7.5 years).There were no recurrences for basal cell carcinoma in either treatment group, suggesting that, at least for "simple" primary lesions without confounding risk factors, there is some validity to a "wait and see" attitude, in which treatment of a potential recurrence would be straightforward. Despite our observed infrequent local recurrences of squamous cell cancers (13.3 percent), the small risk of metastases still suggests the appropriateness of complete surgical eradication for these tumors whenever feasible.     

Fibroblasts prepared from different types of malignant tumors stimulate expression of luminal marker keratin 8 in the EM-G3 breast cancer cell line

It is widely recognized that stromal fibroblasts significantly influence biological properties of multiple tumors including breast cancer. However, these epithelial–mesenchymal interactions seem to be essential in tumor biology and it is not fully clear whether this interaction is tumor type-specific or has a more general non-specific character. To elucidate this question, we tested the effect of cancer-associated fibroblasts (CAFs) isolated from different types of tumors (breast cancer skin metastasis, cutaneous basal cell carcinoma and melanoma, squamous cell carcinoma arising from oral cavity mucous membrane) on the EM-G3 breast cancer cell line. The results were compared with control experiments using normal human dermal fibroblasts, 3T3 mouse fibroblasts, and 3T3 fibroblasts influenced by the fibroblasts prepared from the basal cell carcinoma. Our results demonstrated that expression of luminal marker keratin 8 was influenced only by CAFs prepared from any tested tumors. In contrast, all tested types of fibroblasts showed a strong stimulatory effect on the expression of basal/myoepithelial marker keratin 14. The CAFs also elevated the number of cells with positivity for both keratins 8 and 14 that are similar to ductal originated precursor cells. The expression of proliferation marker Ki67 was not influenced by any of the tested fibroblasts. In conclusion, our data indicate that CAFs are able to influence the phenotype of a breast cancer cell line and this effect is based on a tumor type-unspecific mechanism. Finally, a clear functional difference between normal and CAFs was demonstrated.     

TERT Promoter Mutations Are Frequent in Cutaneous Basal Cell Carcinoma and Squamous Cell Carcinoma

Activating mutations in the TERT promoter were recently identified in up to 71% of cutaneous melanoma. Subsequent studies found TERT promoter mutations in a wide array of other major human cancers. TERT promoter mutations lead to increased expression of telomerase, which maintains telomere length and genomic stability, thereby allowing cancer cells to continuously divide, avoiding senescence or apoptosis. TERT promoter mutations in cutaneous melanoma often show UV-signatures. Non-melanoma skin cancer, including basal cell carcinoma and squamous cell carcinoma, are very frequent malignancies in individuals of European descent. We investigated the presence of TERT promoter mutations in 32 basal cell carcinomas and 34 cutaneous squamous cell carcinomas using conventional Sanger sequencing. TERT promoter mutations were identified in 18 (56%) basal cell carcinomas and in 17 (50%) cutaneous squamous cell carcinomas. The recurrent mutations identified in our cohort were identical to those previously described in cutaneous melanoma, and showed a UV-signature (C>T or CC>TT) in line with a causative role for UV exposure in these common cutaneous malignancies. Our study shows that TERT promoter mutations with UV-signatures are frequent in non-melanoma skin cancer, being present in around 50% of basal and squamous cell carcinomas and suggests that increased expression of telomerase plays an important role in the pathogenesis of these tumors.     

Therapy for oral squamous cell carcinoma by tegafur and streptococcal agent OK-432 in combination with radiotherapy: Association of the therapeutic effect with differentiation and apoptosis in the cancer cells

Twenty patients with oral squamous cell carcinoma having mainly stage II or III lesions without distant metastasis, were treated with tegafur and streptococcal agent, OK-432, in combination with radiotherapy. As a consequence, 16 cases among the treated 20 cases showed complete remission by this therapy alone. Especially, we have found that the squamous cell carcinoma arising in non-keratinizing oral epithelium rather than in keratinizing oral epithelium has better response to this therapy. Among the 16 cases with complete remission (CR) by the current therapy, 10 cases were histopathologically diagnosed as well-differentiated squamous cell carcinoma and six cases as moderately differentiated squamous cell carcinoma. When we examined immunohistochemically the expres-sion of various antigens such as proliferating cell nuclear antigen (PCNA), p53 and LeY or the presence of DNA fragmentation by nick-end labelling in the biopsy materials taken at the first visit to our clinic from 20 patients treated with the current therapy, the CR group showed a significantly increased LeY expres-sion level ( p< 0.05) and DNA fragmentation rate ( p< 0.05) as compared with the partial response (PR, n= 3) + no change (NC, n= 1) group. On the other hand, the CR group with respect to PCNA expression level was significantly decreased as compared with the PR + NC group ( p< 0.05). From these findings, it can be considered that the therapy for oral squamous cell carcinoma by UFT and OK-432 in combination with radiotherapy is very effective, which may be associated with differentiation or apoptosis in oral squamous carcinoma cells. In addition, we present the clinical findings and results of immunohistochemical staining for the biopsy materials obtained from four CR cases treated with the current therapeutic method.     

Egr-1和PTEN在皮肤鳞癌中的表达和临床意义

目的:探讨Egr-1和PTEN在皮肤鳞癌中的表达和临床意义。方法:收集2014年1月到2015年12月100例在我院经病理学诊断为皮肤鳞状细胞癌患者以及100例健康对照的组织样本,采用免疫组化法SP法检测在皮肤鳞癌中Egr-1和PTEN的表达,并分析其与患者肿瘤转移的关系。结果:皮肤鳞状细胞癌组织中Egr-1和PTEN的表达明显高于健康对照组织(P0.05);发生远处转移的皮肤鳞状细胞癌组织中Egr-1水平明显高于未转移者(P0.05)PTEN的表达显著低于未发生远处转移的患者(P0.05)。结论:Egr-1和PTEN在皮肤鳞状细胞癌患者中表达明显增高,并与癌组织远处转移密切相关,二者可能作为皮肤鳞癌诊断和预后评估的参考指标。     

Arsenic and cancer.

Palmar and plantar keratoses developed in seven patients many years after ingeston of trivalent inorganic arsenic. Six had basal cell carcinoma (superficial multicentric type in five), carcinoma "in situ" or squamous cell carcinoma of the skin. Two had systemic carcinoma--one, bilateral breast adenocarcinoma and one, carcinoma of the colon. From these observations and from the findings of a review of the literature, there seems no question that long-term arsenic ingestion can cause palmar and plantar keratoses and skin cancer, particularly basal cell carcinoma of the superficial multicentric type, usually on the torso. It is suspected but not proved to cause other cancers. Although over the last 50 years general exposure to arsenic has greatly decreased, particularly that from insecticides, this element is still found occasionally in drinking water (naturally or as a smelter byproduct), in certain foods and in cigarette smoke.     

Primary squamous cell carcinoma of the breast: A rare case report

BackgroundSquamous cells are normally not found inside the breast. Therefore, a primary squamous cell carcinoma of the breast is an exceptional phenomenon and the management of this type of disease is still debated.AimClinical outcome assessment of a patient with squamous cell carcinoma of the breast.Materials and methodsWe report a case of primary squamous cell carcinoma of the breast (T1cN0M0) in a 51-years-old woman who underwent breast conserving surgery plus adjuvant chemotherapy and radiation therapy (RT).ResultsWith a follow up of 43 months, the patient is alive with no evidence of local or distant recurrence. The patient had Grade 2 acute skin toxicity. No late skin or respiratory toxicity was observed.ConclusionsPure primary squamous cell carcinoma of the breast is a rare and aggressive disease, often treatment-refractory. Our case shows that the addition of RT after breast conserving surgery, allows to achieve a high local control without adding severe toxicity. A multidisciplinary approach seems to be the optimal management for early stages in this rare disease.     

The distribution of immuno-reactive tenascin in the epithelial-mesenchymal junctional areas of benign and malignant squamous epithelia

Tenascin is an extra cellular matrix glycoprotein which is distributed in the mesenchyme surrounding various organs during embryogenesis. It has also been demonstrated in some normal adult tissues and in the matrix of human tumours. The present study has been carried out to analyse the distribution of tenascin in non malignant and malignant skin disorders, in squamous cell carcinomas of the head and neck, in squamous cell carcinoma xenografts and in a squamous cell carcinoma cell line grown on collagen gel. Immunohistochemical localisation of tenascin was performed, using a monoclonal antibody specific for tenascin, by the indirect immunoperoxidase method with silver enhancement. Tenascin was heterogeneously distributed in the extra cellular matrix of squamous cell carcinomas and in squamous cell carcinoma xenografts. It was absent in basal cell carcinoma and in the squamous cell carcinoma cell line grown on collagen gel. The distribution of tenascin in squamous cell carcinoma and basal cell carcinoma is discussed in relation to tumour invasion and differentiation.     

Causes of treatment failure and death in carcinoma of the lung

Studies of patterns of failure and causes of death have been undertaken based upon the WHO histopathologic classification. In a randomized trial of thoracic irradiation +/- chemotherapy (hydroxyurea and CCNU), patterns of failure did not seem to differ by cell type; the largest group was "death without progression." A subsequent clinical trial of thoracic irradiation +/- cranial irradiation permitted a more detailed evaluation. Patients with squamous cell carcinoma had a higher rate of local failure than distant metastasis. Those with small cell carcinoma had a lower local failure rate and a high rate of distant spread. Patients with adenocarcinoma and large cell carcinoma had the lowest local failure rate, but had a high rate of distant metastasis. In 300 consecutive patients with autopsies, 75 percent with squamous carcinoma died of complications of the thoracic tumor and only one-quarter had extrathoracic dissemination; 30 percent with small cell carcinoma died of local tumor complications and 70 percent had carcinomatosis; 40 percent of patients with adenocarcinoma and large cell carcinoma died of intrathoracic complications, and 55 percent had distant metastases. Half the patients with small cell carcinoma, large cell carcinoma, and adenocarcinoma had brain metastases at autopsy. Future clinical trials should emphasize better control of the most common sites of failure.     

Expression patterns of α2,3-Sialyltransferase I and α2,6-Sialyltransferase I in human cutaneous epithelial lesions

Skin tumors have become one of the most common cancers in the world and their carcinogenesis is frequently associated with altered glycosylation patterns. The aberrant sialylation, a type of glycosylation, can mediate pathophysiological key events during various stages of tumor progression, including invasion and metastasis. Sialyltransferases play a key role in a variety of biological processes, including cell-cell communication, cell-matrix interaction, adhesion, and protein targeting. In this study, it was evaluated the expression of ST3Gal I and ST6Gal I in cutaneous epithelial lesions that include actinic keratosis (n=15), keratoacanthoma (n=9), squamous cell carcinoma (n=22) and basal cell carcinoma (n=28) in order to evaluate if sialyltransferases expression is different in premalignant and in malignant tumors. The expression of ST3Gal I was observed in actinic keratosis (53%), keratoacanthoma (78%), squamous cell carcinoma (73%) and basal cell carcinoma (32%) with statistic differences between basal cell carcinoma and keratoacanthoma (P=0.0239) and basal cell carcinoma and squamous cell carcinoma (P=0.0096); for ST6Gal I, cytoplasmic expression was noted in actinic keratosis (40%), heterogeneous and cytoplasmic expression was noted in keratoacanthoma (67%), squamous cell carcinoma (41%) and basal cell carcinoma (7%) with statistic differences between basal cell carcinoma and squamous cell carcinoma (P=0.0061) and basal cell carcinoma and keratoacanthoma (P=0.0008). In summary, our results showed that the high expression of ST3Gal I and ST6Gal I, in skin tumors, is associated with tumors with greater potential for invasion and metastasis, as in the case of squamous cell carcinoma, and this may be related to their behavior.Key words: sialic acid, α2,3-sialyltransferases, α2,6-sialyltransferases, basal cell carcinoma, squamous cell carcinoma, actinic keratosis, keratoacanthoma     

Establishment and characterization of an osteopontin-null cutaneous squamous cell carcinoma cell line

Osteopontin (OPN) is a secreted glycoprotein implicated to function in cancer development and metastasis. Although elevated expression of OPN are observed in cancer cells of various types, in some cases, only the cells in the stromal region surrounding the tumor express OPN, suggesting distinct functional roles for this protein derived from host cells and from cancer cells. To provide a model for addressing the functions and mechanisms of host-derived OPN in cancer progression and metastasis, a cutaneous squamous cell carcinoma cell line (ONSC) that lacks the OPN gene, Spp1, was established. This line of cells was derived from a squamous cell carcinoma that developed in a female, OPN-null mouse subjected to two-stage skin carcinogenesis. Morphologically, ONSC cells resemble epithelial cells, and they express the epithelial markers, K1, K14, and p63, as confirmed by immunohistochemical analyses. Genomic analyses indicate the presence of mutated H-Ras and p53 genes. ONSC cells form colonies in soft agar and, subcutaneously injected into athymic nude mice, develop into squamous cell carcinomas that metastasize to the lungs. Lacking OPN expression, these squamous cell carcinoma cells provide a model to address the function of host OPN in the context of cancer progression and metastasis.     

Incidence of non-melanocytic skin cancer treated in Australia

In 1985, as part of a national random household omnibus survey by a market research company, 30 976 Australians (mostly of European origin) were asked whether they had ever been treated by a doctor for skin cancer. The treating doctor or hospital was then approached for confirmation of the diagnosis of all those people who claimed to have been so treated within the past 12 months. Demographic data were also collected, permitting analysis by age, sex, country of birth, current residence, and skin reaction to strong sunlight.Melanomas accounted for less than 5% of the tumours treated. The world standardised incidence of melanoma was 19/100 000 population. The standardised incidence of treated non-melanocytic skin cancer in Australia was estimated to be 823/100 000. The standardised rates for basal cell carcinoma and squamous cell carcinoma were 657 and 166/100 000 respectively, yielding a standardised rate ratio of about 4:1. Standardised rates based on medically confirmed cases only were 555, 443, and 112/100 000 for all non-melanocytic skin cancers, basal cell carcinomas, and squamous cell carcinomas respectively.Significant differences and trends in incidence were noted with respect to age and sex. Rates in men were higher than those in women but significantly so only after the age of 60. People born in Australia had a rate of 936/100 000 compared with 402/100 000 in British migrants. Rates for non-melanocytic skin cancer showed a gradient with respect to latitude within Australia. The rate in people residing north of 29°S was 1242/100 000 compared with a rate of 489/100 000 in those living south of 37°S. A person''s skin reaction to strong sunlight was a good indicator of the risk of skin cancer, tanning ability being inversely related to its incidence. The rate in those who always burnt and never tanned when exposed to strong sunlight was 1764/100 000 compared with a rate of 616/100 000 in those who always tanned and never burnt.These findings have important implications for public education programmes in relation to exposure to sunlight in Australia.     

Epidermal malignant tumors: pathogenesis, influence of UV light and apoptosis

Basal cell carcinoma and squamous cell carcinoma, collectively termed non-melanoma skin cancers are the most common malignant tumors in humans. Basal cell carcinoma grows slowly and metastatic spread is very rare. Squamous cell carcinoma is characterized by infiltrative, destructive growth and metastasis. Long-term exposure of skin to UV light has a great impact on development of these epidermal malignancies. UV light induces cascade of events like well known DNA damage of keratinocytes as well as still completely undetermined influence on apoptotic process through expression of proapoptotic and antiapoptotic molecules. The major role in development of skin cancer is given to proapoptotic p53 molecule or tumor suppressor gene which mutation due to UV exposure leads to resistance of DNA-damaged cell to apoptosis. Other proapoptotic molecules such as Fas ligand (FasL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) are strongly expressed in basal cell carcinoma and squamous cell carcinoma that could be explained by the ability of tumor to escape the attack of immune system.     

Comparative proteomics approach to screening of potential diagnostic and therapeutic targets for oral squamous cell carcinoma

This work demonstrates that a comprehensive strategy of proteomics identification combined with further validation and detailed functional analysis should be adopted in the field of cancer biomarker discovery. A comparative proteomics approach was utilized to identify differentially expressed proteins in 10 oral squamous carcinoma samples paired with their corresponding normal tissues. A total of 52 significantly and consistently altered proteins were identified with eight of these being reported for the first time in oral squamous carcinoma. Of the eight newly implicated proteins, RACK1 was chosen for detailed analysis. RACK1 was demonstrated to be up-regulated in cancer at both the mRNA and protein levels. Immunohistochemical examination showed that the enhanced expression of RACK1 was correlated with the severity of the epithelial dysplasia as well as clinical stage, lymph node involvement, and recurrence, which are known indicators of a relatively poor prognosis in oral squamous carcinoma patients. RNA interference specifically targeted to silence RACK1 could initiate apoptosis of oral squamous carcinoma cells. Taken together, the results indicate that RACK1 is up-regulated in oral squamous carcinoma, not only being closely related to cell proliferation and apoptosis but also linked to clinical invasiveness and metastasis in carcinogenesis. The observations suggest that RACK1 may be a potential biomarker for early diagnosis, prognosis, and monitoring in the therapy of oral squamous carcinoma. Further this comprehensive strategy could be used for identifying other differentially expressed proteins that have potential to be candidate biomarkers of oral squamous carcinoma.     

Ubiquitin-specific protease 14 regulates cell proliferation and apoptosis in oral squamous cell carcinoma

Ubiquitin-specific protease 14, a deubiquitinating enzyme, has been implicated in the tumorigenesis and progression of several cancers, but its role in oral squamous cell carcinoma remains to be elucidated. The aim of this study was to explore the expression pattern and roles of Ubiquitin-specific protease 14 in the occurrence and development of oral squamous cell carcinoma. Interestingly, Ubiquitin-specific protease 14 was overexpressed in oral cancer tissues and cell lines at both mRNA and protein levels. b-AP15, a specific inhibitor of Ubiquitin-specific protease 14, significantly inhibited the growth of cancer cells and increased cell apoptosis in a dose-dependent manner. Moreover, knockdown of Ubiquitin-specific protease 14 by shRNA significantly inhibited the proliferation and migration of cancer cells in vitro. Finally, using a xenograft mouse model of oral squamous cell carcinoma, knockdown of Ubiquitin-specific protease 14 markedly inhibited tumor growth and triggered the cancer cell apoptosis in vivo, supporting previous results. In conclusion, for the first time we have demonstrated the expression pattern of Ubiquitin-specific protease 14 in oral squamous cell carcinoma and verified a relationship with tumor growth and metastasis. These results may highlight new therapeutic strategies for tumor treatment, application of Ubiquitin-specific protease 14 selective inhibitor, such as b-AP15, or knockdown by shRNA. Collectively, Ubiquitin-specific protease 14 could be a potential therapeutic target for oral squamous cell carcinoma patients.     

Morphological and molecular aspects of cancerogenesis in the lung

Morphology and some molecular aspects of hyperplastic (bronchial basal cell hyperplasia and alveolar cell hyperplasia), metaplastic (squamous metaplasia), preneoplastic and early neoplastic (dysplasia in squamous metaplasia, cancer in situ and atypical alveolar cell hyperplasia) changes were studied in 180 lungs resected due to non-small cell lung cancer: 106 cases (58.9%) of squamous cell carcinoma, 42 (23.3%) of adenocarcinoma and 32 (17.8%) of large cell carcinoma. P53 protein and PCNA expressions were detected immunohistochemically (using formalin-fixed, paraffin-embedded sections). DNA extracted from the microdissected P53-positive cells was analysed for point mutations in the P53 gene. No P53 immunostaining was observed in normal mucosa, hyperplasia of basal cells, squamous metaplasia without and with minor and moderate dysplasia of bronchial mucosa as well as alveolar cell hyperplasia. Overexpression of P53 protein occurred in 3 out of 12 (25%) cases of severe bronchial dysplasia, 5 out of 11 (45.5%) cases of intraepithelial carcinoma and 6 out of 45 (13.3%) cases of alveolar cell hyperplasia. Using direct sequencing, mutations in the P53 gene were detected in 11 out of 14 (87%) P53-immunopositive samples, including all severe dysplasias, all carcinomas in situ and 3 of 6 alveolar cell hyperplasias. A significant association was observed between PCNA expression and preinvasive as well as invasive lesions. The data clearly show that lung resected due to primary cancer ought to be treated as "field cancerization" in which one can find early morphologic events of multi-step cancerogenesis. P53 protein alterations and P53 gene mutations can occur before invasion and its frequency depends on the degree of dysplasia.     

Skin cancer--primary and secondary prevention (information campaigns and screening)--with a focus on children & sunbeds

Solar and artificial (sunbed) UV-exposure is the main risk factor for the development of epithelial skin cancer (basal cell carcinoma, BCC, and squamous cell carcinoma, SCC) as well for malignant melanoma (MM). UV exposure in childhood and adolescence is especially important. Therefore, adequate methods of primary prevention have continuously to be used and to be developed further to target these age-groups in order to reduce the risks of intensive UV-exposure. Primary prevention can effectively be combined with secondary prevention (early detection, screening) to reduce the burden of skin cancer and to decrease incidence, morbidity and mortality.     

Skin cancer after X-ray treatment for scalp ringworm

Some 2,224 children given X-ray therapy for tinea capitis (ringworm of the scalp) have been followed for up to 50 years to determine cancer incidence, along with a control group of 1,380 tinea capitis patients given only topical medications. The study found a relative risk (RR) of 3.6 (95% confidence interval, 2.3-5.9) for basal cell skin cancer (BCC) of the head and neck among irradiated Caucasians (124 irradiated cases and 21 control cases), in response to a scalp dose of about 4.8 Gy. No melanomas of the head and neck have been seen, and only a few squamous cell carcinomas. About 40% of irradiated cases have had multiple BCCs, for a total of 328 BCCs. Although 25% of both the irradiated and control groups are African-American, only 3 skin cancers have been seen among them, all in the irradiated group, indicating the importance of susceptibility to UV radiation as a cofactor. Light complexion, severe sunburning and North European ancestry were predictive of BCC risk in the irradiated group, but chronic sun exposure was not. Children irradiated at young ages had the highest BCC risk. The RR for BCC risk is approximately constant with time since exposure, suggesting that risk will probably last for a lifetime.     

Cytologic and DNA cytometric diagnosis and therapy monitoring of squamous cell carcinoma in situ and malignant melanoma of the cornea and conjunctiva

OBJECTIVE: To investigate the diagnostic accuracy of exfoliative cytology of the cornea and conjunctiva and DNA image cytometry for quality control and monitoring of therapy for malignant neoplasms. STUDY DESIGN: Conjunctival or corneal smears from six cases clinically suspicious for malignant melanomas and eight suspicious for carcinomas in situ were investigated. Smears from 18 cases clinically nonsuspicious for neoplastic diseases served as negative controls. Repeated smears were obtained during and after local mitomycin C (MMC) therapy. RESULTS: In none of 18 nonsuspicious cases, cytology revealed abnormal cells. DNA cytometry showed nonaneuploidy in all of these. All smears from patients with histologically proven malignant melanomas (MM) and squamous cell carcinomas in situ revealed abnormal cells. Image cytometry demonstrated DNA aneuploidy in 66.6% of patients with MM and 80% with carcinoma. Sensitivity of cytology thus was 100% for both MM and carcinoma; specificity also was 100%. DNA measurements after MMC therapy revealed euploid polyploidization of nonneoplastic squamous cells. DNA cytometry provided an objective identification of tumor cell regression. CONCLUSION: Cytologic examination of corneal and conjunctival smears is a noninvasive tool with high diagnostic accuracy for detection of epithelial neoplasms. DNA image cytometry can serve for quality control and for objective monitoring of the effect of local chemotherapy.