Hypotheses for the genesis of UV-induced non-melanotic human skin cancer.
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The chemopreventive effects of beta-carotene and 13-cis-retinoic acid (RA) on chemically induced salivary gland tumors were studied in rats. Young male Sprague-Dawley rats were injected in one of the submandibular salivary glands with 1 mg of dimethylbenzanthracene (DMBA) dissolved in olive oil. The contralateral gland was injected with the vehicle alone. Rats were divided into four groups and were fed ad libitum a semisynthetic diet supplemented with 0 or 100 mg beta-carotene/kg diet, or 20 or 100 mg RA/kg diet. Rats were killed at 22 weeks after the DMBA treatment, and tumors were examined histologically. Tumors were generally found to be squamous cell carcinomas or poorly differentiated neoplasms resembling squamous cell carcinomas. The tumor incidence was slightly lower in rats fed the diet supplemented with beta-carotene. RA had no appreciable effect on tumor incidence. A high activity of gamma-glutamyl transpeptidase was histochemically demonstrated in the tumors. There were some mortalities in the beta-carotene and RA supplemented groups, especially in the group fed high levels of RA. This mortality appeared to be related to vitamin K becoming somewhat limited.
A case of a malignant neoplasm with features suggestive of both malignant melanoma and squamous cell carcinoma is reported. The neoplastic cells were positive for both S-100 protein and keratin when stained by the indirect peroxidase-antiperoxidase method. The literature on other instances of bi- or multidirectional differentiation of neoplastic cells is reviewed. The significance of these findings for terminology of neoplasms is discussed.
Most penile neoplasms are squamous cell carcinomas (SCC), but there are subtypes that show morphologic and possibly etiologic differences. Clinicopathologic features of 20 patients with basaloid carcinoma (BC), an unusual variant of squamous cell carcinoma, are presented. Median age was 52 years, and all tumors were located in the glans, three confined to the perimeatal region. Average tumor size was 3.8 cm. Microscopically, nests of small, basophilic cells with numerous mitosis were present. Human papillomavirus DNA sequences (type 16), using the polymerase chain reaction (PCR), were found in 9 of 11 cases. Differential diagnosis included urethral transitional cell, basal cell, small cell neuroendocrine, and metastatic carcinoma. Factors more significantly associated with regional metastasis and mortality were tumor thickness greater than 10 mm and infiltration of the corpus cavernosum. A comparison with typical squamous cell carcinoma showed basaloid carcinoma to have a higher histologic grade, a deeper invasion of penile anatomic levels, and a higher mortality rate. Of 17 patients observed, 10 were dead of disease (average time, 34 months), one was alive with disease 6 months after diagnosis, and 5 were alive and free of disease (average time, 71 months); the remaining patient died of other causes. Basaloid carcinoma is a distinctive morphologic subtype of squamous cell carcinoma frequently associated with the human papilloma virus.
OBJECTIVE: To compare the contribution of endocervical Cytobrush samples to wooden spatula samples in the detection of cervical preneoplastic lesions. STUDY DESIGN: Cytobrush sampling was performed on 56,120 women in conjunction with ectocervical spatula sampling, resulting in two smears per patient. Almost all women with cytologic diagnoses of high grade squamous intraepithelial lesions (CIN 3) or higher were biopsied. RESULTS: For the 221 CIN 3, the contribution of the endocervical sample was clearly more efficient, with diagnosis achieved on 98% of the endocervical samples and on 62% of the ectocervical ones. In the 674 low grade squamous epithelial lesion cases, the endocervical samples were diagnostic in 79% of cases and the ectocervical smears in 64%. Thus, endocervical sampling proved to be superior in the recognition of precancerous lesions. In 93% of the 53 squamous carcinomas, cancer cells were found in both ectocervical and endocervical samples and in 7%, exclusively in endocervical smears. In 76% of the 21 adenocarcinomas, both samples were positive, and in 23% only the endocervical sample contained cancer cells. CONCLUSION: The Cytobrush samples were more efficient in the detection of intraepithelial neoplastic lesions, suggesting that most of them originate in the endocervical epithelium. If the sampling were limited to endocervical brushing, 14% of cervical lesions would not have been detected in the smear. The prominence of preneoplastic cells in the endocervical samples might indicate that the original glandular epithelium is the major site of cervical carcinogenesis.
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AIMS: We describe a previously unrecognized pigmented tumour of the skin and suggest a possible relationship with the follicular bulb. METHODS AND RESULTS: A pigmented epithelial neoplasm clinically simulating a malignant melanoma of the skin was present in a 92-year-old woman, on her left leg. It was composed of three cell types: squamous cells with trichilemmal keratinization, basaloid cells and dendritic melanocytes. The presence of three cell types was confirmed by immunohistochemistry and electron microscopy. CONCLUSIONS: The tumour showed differentiation towards the hair follicular bulb and the descriptive term of follicular baso-squamous melanocytic tumour is suggested.
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The presence of squamous cells in eccrine neoplasms is not well recognized, but is usually considered to denote malignant transformation. The small nests composed of squamoid cells (squamous islands), however, were found in 46% of the eccrine neoplasms we studied. They were divided into three types according to their location, histological structure, and degree of cellular atypia. These types possibly represented intermingling of epidermis or hair follicle, squamous syringo-metaplasia, and malignant transformation. We would like to stress that squamous islands are seen not only in malignant eccrine neoplasms, but also in benign ones, and that their presence should not be interpreted as evidence of malignancy.
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Circulating lymphocytes may home to lymph nodes (LNs) via paracortical postcapillary venules, high-endothelial venules (HEVs) that recognize circulating lymphocytes, enabling them to migrate into nodal cortical/paracortical regions. Our goal was to find any histologic, immunohistochemical, or in vitro evidence to support the hypothesis that squamous cell carcinoma (SCC) may gain access to LNs via an alternative venolymphatic pathway. Slides from 67 neck dissections with SCC were studied. Standard criteria for lymphatic-mediated metastasis were used; criteria for evidence ofvenolymphatic metastasis were tumor nests localized to the paracortical regions, directly contiguous to HEVs but not marginal sinuses. Cases in which LN architecture was obliterated by metastases were excluded. A modified Stamper-Woodruff assay, which assesses HEV binding, incubated cell lines from oral carcinomas and lung adenocarcinomas with fresh frozen LN sections. Double-blinded cell counts were performed by two observers and analyzed by Student's t test. Immunohistochemical examination was undertaken on 19 paraffin-embedded cases with the monoclonal antibody, MoAb CD44v6, to discover whether expression of this adhesion molecule correlated with metastatic pattern. Twenty-nine cases (66%) revealed evidence only for the LN route of metastasis; 4 cases (9%) were classified as venolymphatic metastasis; 11 cases (25%) showed evidence for both pathways. The Stamper-Woodruff assay confirmed that SCC cells preferentially bound to HEV within cervical LN sections more than did adenocarcinoma cells (P = .02). Strong staining to MoAb CD44v6 was seen in 18 (95%) of 19 SCCs with a membranous pattern. Occasionally, CD44v6 highlighted tumor emboli adjacent to HEVs, but no overall correlation could be made between CD44v6 expression and pattern of spread. Tumor metastasis via lymphatic channels is the predominant mode of metastatic spread, but the venolymphatic route is a plausible alternative pathway. The preferential attachment of SCC cells to HEVs supports this theory.
Transforming growth factor beta1 (TGF-beta1) regulates both cell growth and cellular plasticity and is therefore important in the molecular control of both the developmental and neoplastic processes. It has been suggested that TGF-beta1 may be a positive or negative regulator of tumorigenesis. Stimulation of tumorigenesis could be due to its action as an immunosuppressor or as an inducer of angiogenesis, or by its direct action on the cell in promoting cellular plasticity. In the current study, we provide evidence that TGF-beta1 can act directly on keratinocytes in vivo to induce the reversible epithelial-mesenchymal conversion of a malignant metastatic keratinocyte cell line. Two squamous clones from the cell line were shown to undergo a reversible conversion to a fibroblastoid phenotype after culture in 1 ng/ml TGF-beta1. The morphological conversion became apparent at 24 h post-TGF-beta treatment and was complete after another 24 h. The conversion was characterized by a rapid delocalization of E-cadherin within 6-12 h posttreatment, followed by down-regulation of E-cadherin levels by 72 h. These squamous clones spontaneously converted to a fibroblastoid phenotype after s.c. injection in nude mice. Importantly, four of four clones that had been stably transfected with a dominant negative TGF-beta type II receptor were unable to undergo this mesenchymal switch in vivo, despite the fact that all clones stably transfected with neomyocin resistance alone retained their spindle characteristics in vivo. This demonstrates that the epithelial-mesenchymal conversion event is mediated directly via the TGF-beta signaling pathway of the tumor cell per se, and that it is sufficient to significantly enhance tumorigenicity and the malignant and invasive characteristics of the tumor in vivo.
BACKGROUND: Several lines of evidence support the epidermal growth factor receptor (EGFR) as a molecular target for therapy in head and neck squamous cell carcinomas (HNSCC). Determination of tumor EGFR levels by conventional immunohistochemistry has not always predicted antitumor efficacy. Quantitative assays may provide more accurate assessment of the level of EGFR receptor in the tumor, which may thus provide more reliable prognostic and predictive information. We studied the prognostic value of quantitative assessment of EGFR in oropharyngeal squamous cell cancers treated with radiotherapy. EXPERIMENTAL DESIGN: We studied EGFR protein expression on a tissue microarray composed of 95 oropharyngeal cancer cases using an in situ molecular-based method of quantitative assessment of protein expression (AQUA) and correlated those with clinical and pathologic data. Automated, quantitative analysis uses cytokeratin to define pixels as cancer (tumor mask) within the array spot and measures intensity of EGFR expression using a Cy5-conjugated antibody within the mask. A continuous index score is generated, which is directly proportional to the number of molecules per unit area, and cases were defined as high expressing if they were above the median expression level. RESULTS: The mean follow-up time for survivors was 44.9 months, and for the entire cohort was 34.8 months. Patients with high tumor EGFR expression levels had a local recurrence rate of 58% compared with 17% for patients with low EGFR tumor expression (P < 0.01). Similarly, patients with high nuclear EGFR expression had a local recurrence rate of 54% compared with 21% for patients with low EGFR nuclear expression (P < 0.05). Additionally, patients with high tumor and nuclear EGFR levels had inferior disease-free survival compared with low expressors (19% versus 43% and 19% versus 45%, respectively. P < 0.05 for each). In multivariate analysis adjusting for well-characterized prognostic variables, high tumor and nuclear EGFR expression levels retained their prognostic significance. CONCLUSION: The AQUA system provides a continuous measurement of EGFR on paraffin-embedded tissue and was able to reveal the association between EGFR expression and outcome expected from the biological role of EGFR. In the future, EGFR AQUA score may be useful in predicting response to EGFR-targeted therapies.
The authors have presented a very rare case of multiple primary neoplasms of parotid gland: adenolymphoma and squamous cell carcinoma. Primary multiple neoplasms and multifocal neoplasms are a very complex problem and therefore have been a topic of many articles. The authors describe mechanism of origin, frequency of occurrence, possibilities of diagnostics. The main reason of these neoplasms origin are simultaneously exposure of the tissue to damaging factors and special tissue sensitivity.
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