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PubMed1999

Secretion of vascular endothelial growth factor in adenocarcinoma and squamous cell carcinoma of the uterine cervix.

OBJECTIVE: To determine whether major differences in vascular endothelial growth factor secretion exist between adenocarcinomas of the uterine cervix compared with squamous cell carcinomas. METHODS: The secretion of vascular endothelial growth factor by eight fresh cervical cancer cell preparations (four adenocarcinomas and four squamous cell carcinomas) and four established squamous cell lines was evaluated using a sensitive enzyme-linked immunosorbent assay in vitro. RESULTS: All cervical tumors secreted significant amounts of vascular endothelial growth factor, and no significant differences between fresh and established squamous cell lines were detectable. In contrast, a highly significant difference in vascular endothelial growth factor secretion was noted between fresh adenocarcinomas (mean = 2712, range between 1700 to 3500 pg/mL/10(5) cells/48 hours) when compared with fresh squamous (mean = 575, range between 200 to 950 pg/mL/10(5) cells/48 hours) or established squamous cervical carcinoma cell lines (mean = 712, range between 400 to 1000 pg/mL/10(5) cells/48 hours) (F-test, P< or =.001). CONCLUSION: These data strongly suggest that major differences in the secretion of vascular endothelial growth factor exist between squamous cell carcinoma and adenocarcinomas of the uterine cervix. Therefore, at least some of the differences in the natural biologic behavior of these two histologic types of cervical cancer, including the propensity for earlier lymphatic and hematogenous metastasis as well as the lower response to radiation treatment, could be related to major differences in the secretion of this powerful angiogenic and immunosuppressive cytokine.

Adenocarcinoma↗

PubMed1996

Human papillomavirus expression in oral mucosa, premalignant conditions, and squamous cell carcinoma: a retrospective review of the literature.

OBJECTIVES: The literature of human papillomavirus detection in normal oral mucosa and oral lesions associated with the dysplastic progression of epithelium was reviewed to help define the role of this virus in the development of oral squamous cell carcinoma. STUDY DESIGN: All available data from published studies were analyzed by chi-square test for association between the human papillomavirus and age, gender, race, DNA type, location, lesional dysplastic progression, method of detection, tissue preservation, and use of tobacco and alcohol. RESULTS: Human papillomavirus was identified with increasing frequency in normal oral mucosa (13.5%), benign leukoplakia (14.8%), intraepithelial neoplasia (18.5%), squamous carcinoma (26.2%), and verrucous carcinoma (27%). It was detected in oral squamous cell carcinoma significantly (p < 0.005) more often (37.1%; 122 of 329) in studies that used a high sensitivity assay (polymerase chain reaction) than studies that used moderate sensitivity assays (25.2%; 84 of 334) (e.g., Southern blot hybridization) and low sensitivity assays (16.9%; 61 of 362) (e.g., immunohistochemistry, in situ hybridization). Human papillomavirus DNA was detected significantly more often (p < 0.001) in frozen oral squamous cell carcinoma (51.6%; 115 of 223) than paraffin-embedded tissue (21.7%; 136 of 628). High-risk human papillomaviruses (2, 16, 18) were detected in 81.4% of OSCCs that contained the virus compared with low-risk human papillomavirus genotypes (6, 11) in 17.9% of oral squamous cell carcinoma that contained the human papillomavirus (p < 0.001). In studies that analyzed the use of chemical cofactors, the use of tobacco and alcohol (87.3%) was associated more often with oral squamous cell carcinoma than the presence of human papillomavirus (51.3%), however, the difference was not significant. CONCLUSION: High-risk human papillomavirus genotypes have a significant association with oral squamous cell carcinoma. However, the presence of this virus in a high proportion of oral normal mucosa makes the virus alone a poor prognosticator of progression to malignancy.

Adult↗

PubMed2003

Epstein-Barr virus (EBV)-related oral squamous cell carcinoma in Okinawa, a subtropical island, in southern Japan--simultaneously infected with human papillomavirus (HPV).

Up to now, many authors have reported on the EBV infection and its carcinogenic importance in undifferentiated nasopharyngeal carcinoma (WHO classification, type III), but the infection of the virus in well differentiated oral squamous cell carcinoma has not been well described. We introduce the EBV-related well differentiated oral squamous cell carcinomas in Okinawa, a subtropical island in the southernmost part of Japan. This study aimed to clarify the pathogenesis of this malignancy in this area by carrying out analysis of the histology and the Epstein-Barr (EBV) and human papillomavirus (HPV) infection. In the Department of Oral Surgery, Ryukyu University Hospital Okinawa, 188 cases of oral malignant tumours were encountered from 1996 to 2000. The histopathological examination and the sequence analysis of LMP-1 carboxy terminal region and EBNA2 region of EBV were carried out, as were the analysis of virus subtypes, A and B, BamHI-F and f, and C and D. Additionally, HPV infection in the squamous cell carcinomas were demonstrated using E6 and E7 region primer sets by PCR method. In Okinawa, 94% (177/188) of the cases were squamous cell carcinomas. A surprisingly large number of EBV (72%) and HPV (78%) infections in the oral squamous cell carcinomas were demonstrated. EBV type B virus infection was found in 36% of EBV-related oral squamous cell carcinoma in Okinawa, but in only 2-5% of the mainland cases. In both regions the incidence of the BamHI- f variant infection was very low. The infected virus in 79 out of 80 (39 Okinawan and 41 mainland) cases was BamHI- F type. In Okinawa, the numbers of C and D variants were almost equal, whereas in the mainland the D variant was rare. Further, a 30 bp deletion in LMP-1 gene was frequently demonstrated in Okinawan and mainland cases of type A virus, but not in type B virus. Lastly, single nucleotide mutations in EBNA2 region of type A virus when compared with B95-8 strain were demonstrated in Okinawan cases. The prognosis for (mostly EBV/HPV infected) squamous cell carcinomas in Okinawa was better than that in the mainland where most cases were negative for EBV and/or HPV.

Adult↗

PubMed1999

Immunohistochemical study of fibroblast growth factor-2 (FGF-2) and fibroblast growth factor receptor (FGF-R) in experimental squamous cell carcinoma of rat submandibular gland.

Fibroblast growth factor-2 (FGF-2) is a member of the heparin-binding growth factor family and has mitogenic activity. Immunohistochemical expression of FGF-2 and its receptor (FGFR) was evaluated in experimentally induced squamous cell carcinoma as well as transforming cells of rat submandibular gland (SMG) induced by 9,10-dimethyl-1,2-benzanthracene (DMBA)/sponge implantation. Proliferating cells detected by proliferating cell nuclear antigen (PCNA) staining during carcinogenesis were also compared with FGF-2 and FGFR stainings. In the normal SMG, FGF-2 and FGFR were present in the excretory, striated and intercalated duct cells. Pillar and transition cells of granular convoluted tubule (GCT) showed FGF-2 staining, PCNA-labeled cells in normal SMG were rarely observed. In 2-3 weeks after carcinogen implantation, the reactions of FGF-2 and FGFR were expressed in epithelial islands, duct-like structures and affected ductal segments. PCNA-positive cells were developed in these epithelial structures. In 4-8 weeks after carcinogen implantation squamous epithelium appeared surrounding DMBA/sponge and gradually transforming with high PCNA labeling in the based cells and strong staining of FGF-2 and FGFR. Squamous cell carcinoma arose within about 12 weeks of the experiment. In squamous cell carcinoma, there was an intense immunohistochemical expression of FGF-2 and FGFR. Basal and parabasal layers of the squamous cell carcinoma showed high PCNA labeling. FGF-2-positive cells were found in the connective tissue stroma and in inflammatory cells around the proliferating duct-like structure. Coexpression of FGF-2 and FGFR was indicated in transforming cells during carcinogenic processes and in experimental squamous cell carcinoma of rat SMG. These findings suggested that FGF may play an important role for squamous metaplasia and carcinogenesis in rat SMG as an autocrine factor and FGF-positive stromal cells may also act to stimulate epithelial proliferation.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2003

Risk factors for adenocarcinoma and squamous cell carcinoma of the cervix in women aged 20-44 years: the UK National Case-Control Study of Cervical Cancer.

We report results on risk factors for invasive squamous cell and adenocarcinomas of the cervix in women aged 20-44 years from the UK National Case-Control Study of Cervical Cancer, including 180 women with adenocarcinoma, 391 women with squamous cell carcinoma and 923 population controls. The risk of both squamous cell and adenocarcinoma was strongly related to the lifetime number of sexual partners, and, independently, to age at first intercourse. The risk of both types of cervical cancer increased with increasing duration of use of oral contraceptives, and this effect was most marked in current and recent users of oral contraceptives. The risk of squamous cell carcinoma was associated with high parity and the risk of both squamous cell and adenocarcinoma increased with early age at first birth. Long duration smoking (20 or more years) was associated with a two-fold increase in the risk of squamous cell carcinoma, but smoking was not associated with the risk of adenocarcinoma. Further studies are needed to confirm the suggestion from this and other studies of differences in risk related to smoking between squamous cell and adenocarcinomas of the cervix.

Adenocarcinoma↗

PubMed1997

bcl-2 and p53 immunophenotypes in pre-invasive, early and advanced oesophageal squamous cancer.

AIMS: An inverse correlation between bcl-2 and p53 expression has been reported in several types of epithelial tumour. The role of bcl-2 and p53 in the development of oesophageal squamous carcinoma has yet to be established. The expression of bcl-2 and p53 proteins has been evaluated in the multistage oesophageal tumorigenesis, which progresses from normal mucosa to dysplasia (squamous intraepithelial lesion, SIL), to invasive early and advanced oesophageal squamous cancer. METHODS AND RESULTS: Sixty-four cases of squamous oesophageal cancer, coexisting with SIL in 18 cases, were immunohistochemically analysed for any overexpression of bcl-2 and p53 proteins. Any association of bcl-2 and p53 protein expression with patient survival was also analysed. We observed bcl-2 expression that decreased significantly during the progression of oesophageal carcinogenesis. A decreasing frequency in the expression of bcl-2 in advanced oesophageal squamous cancer coincided with frequent p53 overexpression. bcl-2 expression was correlated with patient survival by univariate analysis. The association disappeared after adjusting for tumour stage, p53 overexpression showed no association with patient survival by either univariate or multivariate analysis. CONCLUSIONS: The down-regulation of bcl-2 and upregulation of p53 in advanced oesophageal squamous cancer suggest that bcl-2 and p53 proteins may interact in the progression of oesophageal squamous cancer.

Adult↗

PubMed2001

Extremely high Langerhans cell infiltration contributes to the favourable prognosis of HPV-infected squamous cell carcinoma and adenocarcinoma of the lung.

AIMS: The infiltration of Langerhans cells in adenocarcinomas and squamous cell carcinomas of the lung was examined in relation to prognostic implications and human papillomavirus (HPV) infection. METHODS AND RESULTS: Samples from 62 adenocarcinoma and 59 squamous cell carcinoma patients in 1995-97, the prognosis of which had been followed up, were used. The Langerhans cells were demonstrated immunohistochemically using anti S100a and CD1 antibodies. Human papillomavirus (HPV) infection was examined by polymerase chain reaction (PCR) and nonisotopic in-situ hybridization (NISH) methods. Statistical analysis was carried out using the Kaplan-Meier method (Wilcoxon analysis) and multiple regression analysis. HPV infection was demonstrated in 12 cases (19.4%) of adenocarcinoma. The HPV-infected adenocarcinomas had abundant faintly eosinophilic cytoplasm, and were immunohistochemically positive for the surfactant apoprotein A. In the 59 cases of squamous cell carcinomas 19 were of the well differentiated form, and 29 and 11 were moderately and poorly differentiated cases, respectively. HPV was detected in 29 cases (49.2%) (13 well and 16 moderately differentiated cases). In all HPV-infected adenocarcinoma and squamous cell carcinoma cases, extremely large numbers of Langerhans cells (more than 100 per high-power field) were demonstrated in the tumour nests. In contrast, in the non-HPV-infected adenocarcinomas and squamous cell carcinomas, only a few (less than about 10 per high-power field) Langerhans cells were observed. The squamous cell carcinoma cases with high Langerhans cell infiltration, which were also infected with HPV, showed a significantly good prognosis (P = 0.007). The adenocarcinoma cases with high Langerhans cell infiltration tended to have a better prognosis than the cases with low Langerhans cell infiltration, but the difference was not statistically significant. The low number of highly infiltrated cases was insufficient for an adequate statistical analysis. Furthermore, there was no significant correlation between either Langerhans cell infiltration and smoking, or HPV infection and smoking, in either squamous cell carcinoma or adenocarcinoma cases. CONCLUSIONS: It was considered that the extremely high Langerhans cell infiltration in the tumours was caused by HPV infection. The extremely large number of Langerhans cells in the tumours contributes to the favourable prognosis for HPV-infected lung cancer.

Adenocarcinoma↗

PubMed2001

Spindle cell squamous carcinoma of the oesophagus: an analysis of 17 cases, with new immunohistochemical evidence for a clonal origin.

AIMS: To study the morphological and immunohistochemical characteristics of spindle cell squamous carcinoma of the oesophagus, in order better to understand the histogenesis of this tumour. METHODS AND RESULTS: In this study we analysed the morphological and immunohistochemical characteristics of 17 cases of spindle cell squamous carcinoma of the oesophagus. Most tumours were polypoid, but tumours with an ulcerated and infiltrative pattern were also observed. Histologically, most tumours were of superficial type, with a characteristic morphological aspect consisting of two types of tumour cells, i.e. differentiated squamous cells, and spindle cells with transition zones between the two components. On immunohistochemistry, the squamous cells were positive for cytokeratin and the spindle cells showed variable expression of cytokeratin, vimentin and smooth muscle actin. p53 protein was over-expressed in 10 cases, both tumour cell types showing strong nuclear positivity. In most tumours, E-cadherin was expressed in the squamous cells and absent in the spindle cells. CONCLUSIONS: The similar pattern of p53 protein expression in the two tumour cell types of spindle cell squamous carcinoma of the oesophagus suggests their common origin. The change in adhesion molecule expression with loss of E-cadherin expression may be associated with the acquisition of spindle cell morphology by the squamous tumour cells.

Actins↗

PubMed2000

Extension of squamous epithelium into the proximal stomach: a newly recognized mucosal abnormality.

BACKGROUND AND STUDY AIMS: The presence of squamous epithelium in the stomach has been rarely noted in the past with only sporadic case reports of squamous cell carcinoma of the stomach and a variety of other pathological processes. We report the documentation, over a period of 9 months, of squamous epithelium extending beyond the esophagogastric junction and into the proximal stomach in 16 patients who underwent upper endoscopy. PATIENTS AND METHODS: This newly recognized mucosal abnormality was systematically identified by both antegrade and retrograde views of the esophagogastric junction during routine upper endoscopy. Other associated mucosal abnormalities were also evaluated (Barrett's esophagus, erosive esophagitis, etc.). Biopsies were obtained from the distal esophagus, cardia, antrum and the squamous extension. Additionally, all patients underwent a detailed interview. RESULTS: Of the patients, 14 were Caucasian and two Hispanic; all were males, with a mean age 61.2+/-4.2. Indications for upper endoscopy included dysphagia, Barrett's esophagus surveillance, failure of antireflux treatment and anemia. Heartburn was reported by 12 patients (75%). None of the patients reported a history of corrosive injury, foreign body ingestion or surgery. A total of 12 patients had a solitary tongue of squamous cell extension, three had two tongues and in addition, two had squamous islands. Hiatal hernia was present in all patients, Barrett's esophagus in six (37.5 %), and esophageal stricture in four. CONCLUSION: Squamous cell extension into the proximal stomach is a newly recognized mucosal abnormality with presently unknown clinical significance. This mucosal abnormality may represent an esophageal mucosal response to proximal gastric injury.

Aged↗

PubMed2000

Clinical presentation of actinic keratoses and squamous cell carcinoma.

BACKGROUND: Actinic keratosis is a skin lesion that can progress to squamous cell carcinoma but cannot always be clinically distinguished from a squamous cell carcinoma. OBJECTIVE: The purpose of this article is to describe the clinical presentation of actinic keratoses and squamous cell carcinoma. METHODS: The author's clinical experience and a review of the literature were used to describe actinic keratoses and squamous cell carcinoma. RESULTS: There is a continuum and a progression from actinic keratoses to squamous cell carcinoma so that there is no way to reliably distinguish between the two diagnoses. CONCLUSION: Because it can be impossible to distinguish between an actinic keratosis and squamous cell carcinoma, treatment of actinic keratoses should be aggressive to stop the progression to squamous cell carcinoma.

Carcinoma, Squamous Cell↗

PubMed2000

Cell activation via CD44 occurs in advanced stages of squamous cell carcinogenesis.

Squamous cell carcinoma (SCC) derives from dysplastic or metaplastic stratified epithelia. The process of squamous cell carcinogenesis has been investigated for the potential role of the adhesion molecule CD44, whose standard form (CD44s) and isoforms generated by alternative splicing of variant exons are known to display altered expression during tumorigenesis in other systems. We have utilized an in vitro correlate of squamous cell carcinogenesis, in which progression stages from normal squamous epithelium to dysplastic lesions and to SCC are represented by primary cultures of normal keratinocytes, by human papilloma virus-immortalized keratinocytes (UP) and by HPVimmortalized/v-Ha-ras transfected tumorigenic keratinocytes (UPR). We investigated expression of CD44 and of variant isoforms, from mRNA to intracellular and surface protein levels, and found no relationship between expression of CD44 and stages of squamous cell carcinogenesis. However, when the function of CD44 was analyzed as Ca(2+) mobilization ability upon monoclonal antibody binding and crosslinking, signal transduction via CD44 was found only for the neoplastic stage (UPR cells). Ca(2+) mobilization was completely independent of density of surface CD44. We have performed similar analyses in an in vitro model of SCC in which four squamous tumor cell lines and UPR cells were sorted according to increasing resistance to external cytotoxic stimuli, i.e. starving conditions, treatment with the retinoid N-(4-hydroxyphenyl)retinamide and cytolytic activity of effector lymphokine-activated killer cells. No relationship between expression of CD44 and level of cell resistance against external cell death-inducing stimuli was found, while CD44-mediated Ca(2+) mobilization ability was restricted to the highly resistant tumor cell lines. Our results indicate that the role(s) of CD44 in squamous cell proliferative disorders can be evinced from the functional features of the molecule, rather than from its phenotypic repertoire.

Apoptosis↗

PubMed2000

Comparison of genetic changes in schistosome-related transitional and squamous bladder cancers using comparative genomic hybridization.

The development of bladder tumors has been associated with a number of causative agents, including schistosomiasis. Schistosome-related cancers show different clinical and pathological features compared with non-schistosome-related bladder cancers, occurring in younger patients, and being predominantly of squamous cell type. This study addresses the difference between squamous and transitional tumor types in the presence of schistosome infection as a measure of the relationship between tumor genotype and phenotype. We have used comparative genomic hybridization to analyze primary muscleinvasive schistosome-related bladder tumors in 54 patients. Twenty-six of these tumors were squamous cell carcinomas; the remaining 28 were of transitional cell type. On average, transitional cell tumors showed 1.8 times the number of chromosomal aberrations as squamous cell tumors (14.4 versus 8.2, P: < 0.001). For both groups combined, the most prevalent genetic alterations were losses of 8p and 18q, and gains of 8q. Transitional cell cancers also showed frequent losses involving 5q, 9p, 10q, 11p and 11q, and gains at 1q and 17q. Loss of 11p was significantly more frequent in TCC than in SCC tumors (50 versus 4%, P: = 0.01). Squamous cell cancers showed more frequent losses of 17p and 18p than transitional tumors, which was clearly significant given the overall reduced frequency of changes in squamous cancers (P: = 0.001 and P: = 0.03, respectively). These data show that different histologic subgroups of bladder tumors are characterized by distinct patterns of chromosomal alterations. The genetic changes found in the transitional cell group are similar to those reported in non-schistosome-related transitional cell tumors, but differ from tumors exhibiting squamous differentiation.

Animals↗

PubMed1994

Induction of squamous differentiation by interferon beta in a human non-small-cell lung cancer cell line.

BACKGROUND: More than 95% of lung cancers occur in the bronchi, appearing as adenocarcinoma, squamous carcinoma, large-cell and small-cell carcinoma, or mixed types. Generally, the least aggressive form is squamous cell lung cancer, suggesting the possibility that promotion of squamous cell differentiation may have therapeutic potential for non-small-cell lung cancer, a disease having no effective systemic therapy. Interferons are a group of glycoproteins with known antiproliferative effects, including the ability to induce differentiation in certain cases. PURPOSE: These studies were conducted to determine whether interferon beta induces squamous cell differentiation in non-small-cell lung cancer in vitro. METHODS: NCI-H596 adenosquamous cells were grown to confluence to maximize their differentiation potential. Growth and parameters for squamous differentiation (cross-linked envelope competence, transglutaminase activity, and relative involucrin expression) were then measured when the cells were exposed to various concentrations of interferon beta. RESULTS: Interferon beta inhibited growth of the NCI-H596 cell line and stimulated envelope competence, involucrin expression, and type 2 transglutaminase activity. Alterations in transglutaminase activity and involucrin expression preceded induction of envelope competence and growth suppression. CONCLUSIONS: Interferon beta suppresses the growth and stimulates markers of squamous differentiation in NCI-H596. While the mechanism(s) for such effects are unknown, the sequence of effects suggests a causal relationship between differentiation induction and subsequent growth suppression. IMPLICATIONS: Interferon beta may have clinical usefulness in squamous differentiation strategies for the treatment of non-small-cell lung cancer. More must be learned about the mechanisms whereby interferons and other biologic agents induce differentiation, and clinical trials will be needed to determine whether in vitro results are pertinent in vivo.

Apoptosis↗

PubMed1978

Squamous cells in the human thyroid gland.

Squamous epithelium in the thyroid, which may be basaloid, epidermoid, or truly squamous, may be derived from several sources. In the normal thyroid, usually rests of one type or another are responsible for these cell nests. Thus, thymic or ultimobranchial remanants may be found in the lateral lobes of normal thyroid glands. Maldevelopment or excessive descent of thyro-glossal duct remnants may be responsible for squamous epithelial cysts noted in the central portions of the thymus, especially in the isthmus. In diseased thyroids, the most likely derivation of squamous or epidermoid epithelium is through metaplasia of follicular epithelial cells. Thus, in adenomatous goiter and various types of thyroiditis as well as follicular derived neoplasms, such a derivation is most likely. In tumors containing malignant squamous epithelium (adenoacanthoma, adenosquamous carcinoma, or pure squamous carcinoma) there is a range of such lesions, and since many of them appear to be derived from follicular epithelium, it is most likely that squamous metaplasia which has undergone malignant transformation has occurred in these neoplasms.

Adult↗

PubMed1992

Pseudovascular adenoid squamous cell carcinoma of the skin. A neoplasm that may be mistaken for angiosarcoma.

The adenoid variant of squamous cell carcinoma has been well-documented in several anatomic sites, including the skin. This tumor is characterized by acantholytic arrays of neoplastic keratinocytes that form pseudoglandular profiles. Although it is typically confused with adenocarcinomas, adenoid squamous cell carcinoma also may be mistaken for malignant vascular proliferations. This report concerns six acantholytic cutaneous squamous cell carcinomas that closely simulated angiosarcomas on conventional histologic examination. They arose in sun-exposed skin areas in middle-aged or elderly patients (mean age, 60 years), five of whom were men. In contrast to the typical clinical appearance of angiosarcoma, pseudovascular adenoid squamous cell carcinoma presented itself as a discrete cutaneous ulcer or crusted tanpink nodule. Microscopically, this lesion was characterized by interanastomosing cordlike arrays of polygonal or flattened tumor cells, with internal pseudolumina that contained detached tumor cells. A connection between the dermal neoplasm and the epidermis was apparent in three cases, but it was focal. Erythrocytes were seen in pseudovascular spaces in five tumors. Immunohistochemically, all examples of pseudovascular adenoid squamous carcinoma were reactive with antibodies to cytokeratin and epithelial membrane antigen (EMA). In addition, three expressed vimentin, two exhibited blood group antigen-positivity, and two bound Ulex europaeus I agglutinin. None of them was immunoreactive for Factor VIII-related antigen, and two of three studied for CD34-reactivity were likewise negative. A control group of six cutaneous angiosarcomas was uniformly nonreactive for cytokeratin and EMA, but they showed positivity for vimentin, Ulex binding, and CD34 positivity in all instances. Pseudovascular adenoid squamous cell carcinoma may be distinguished effectively from angiosarcoma of the skin by attention to its clinical features and by appropriate immunohistochemical studies. These two tumors differ in biologic behavior; three patients with pseudovascular adenoid squamous cell carcinoma died of their tumors, whereas all angiosarcomas in this series proved fatal.

Adenocarcinoma↗

PubMed1993

Basaloid and warty carcinomas of the vulva. Distinctive types of squamous cell carcinoma frequently associated with human papillomaviruses.

In a previous study, we described an elevated prevalence of human papillomavirus (HPV) in two specific types of squamous cell carcinoma of the vulva designated basaloid carcinoma (BC) and warty carcinoma (WC) compared with the conventional type of keratinizing squamous cell carcinoma (KSC). To determine whether there were other differences in their clinical presentation or behavior, we examined 100 cases of squamous cell carcinoma of the vulva classified as BC (28 cases), WC (seven cases), and KSC (65 cases). We included only cases in which tissue adjacent to the tumor was present so that the presence of intraepithelial lesions (squamous hyperplasia, lichen sclerosus, and vulvar intraepithelial neoplasia [VIN]) could be correlated with the different types of invasive carcinomas. Microscopically, BC was characterized by a relatively uniform population of small, ovoid cells with a high nuclear-cytoplasmic ratio resembling VIN 3. Although WC was similar to typical squamous cell carcinoma, it contained many squamous cells that displayed marked nuclear pleomorphism, enlargement, atypia, and multinucleation in conjunction with cytoplasmic cavitation resembling koilocytotic atypia in intraepithelial lesions. The majority of the women with BC and WC were less than 60 years of age, and the proportion of black women was higher as compared with the women with KSC, the majority of whom were white and over 65 years of age. On crude comparison, women with BC appeared to have a survival advantage compared with women with KSC; however, through multivariate modelling, when all possible confounding variables were taken into account, there was little residual impression of a survival advantage of women with BC compared with those having KSC. Substantial differences were found among the three types of carcinoma with regard to the prevalence of adjacent intraepithelial lesions. Squamous hyperplasia was found adjacent to KSC in 54 (83%) of the 65 cases, whereas 27 (77%) of 35 cases of BC and WC had adjacent basaloid or warty VIN. These findings suggest that VIN is a precursor of BC and WC. In view of the high frequency of HPV-DNA detected in VIN and in BC and WC, the findings support the view that HPV has a role in the development of these tumors. In addition, a difference was found in the distribution of associated cervical and vaginal tumors with the three types of vulvar carcinomas.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

PubMed1991

Vulvar granular cell tumors with pseudocarcinomatous hyperplasia: a comparative analysis with well-differentiated squamous carcinoma.

The clinical and pathological findings in 10 cases of vulvar granular cell tumor are reviewed. Nine patients presented with solitary, grossly circumscribed, subcutaneous or submucosal nodules and one with synchronous bilateral labial nodules; two exhibited surface epithelial ulceration. Striking pseudocarcinomatous hyperplasia of the overlying squamous epithelium was noted in five of the 10 cases, leading to a misdiagnosis of invasive squamous carcinoma on superficial biopsy in one case. In contrast to previously published data, it was found that pseudocarcinomatous hyperplasia contained numerous mitotic figures, squamous pearls, mildly atypical nuclei, focally prominent nucleoli, and focal single cell infiltration; follicular infundibula were not preferentially involved. Excluding the presence of the underlying granular cell tumor, these features rendered the hyperplastic proliferation nearly indistinguishable from infiltrative squamous carcinoma. Marked squamous cell atypia, although not always present in biopsies of well-differentiated squamous carcinoma, was the only distinguishing histologic feature not found in pseudocarcinomatous hyperplasia. Although vulvar granular cell tumor is an unusual neoplasm, it should be considered in the differential diagnosis of an apparently infiltrative squamous lesion of the vulva when the base of the lesion is not present in the biopsy specimen. This is particularly true of tumors with a nodular, radially symmetric gross appearance.

Adult↗

PubMed1993

Histopathologic classification of cervical carcinomas and recognition of mucin-secreting squamous carcinomas.

Recently, cervical mucin-secreting squamous carcinomas have been reported to be more common in younger women than in older women, leading some to conclude that any histologic classification of cervical carcinoma should include a specific category of this tumor type. One hundred and ninety-six invasive cervical carcinomas were classified using two histologic classification systems--the World Health Organization (WHO) and a system that recognized mucin-secreting squamous carcinomas (Fox). Analyses were performed to determine whether there was an association between age and glandular tumor types in either system. In the WHO System, 72% were classified as squamous carcinoma, 22% adenocarcinoma, and 6% adenosquamous. In the Fox System, 54% were squamous carcinoma, 22% adenocarcinoma, 4% adenosquamous, and 20% squamous carcinoma with mucin secretion. Specimen type did not significantly affect the classification of a carcinoma. No association was established between age and a diagnosis of adeno- and adenosquamous carcinomas in the WHO System, or age and adeno-, adenosquamous, and mucin-secreting squamous carcinomas in the Fox System. We conclude that use of the WHO Classification System does not obscure significant epidemiologic trends that are evident in a classification system that identifies mucin-secreting squamous carcinomas.

Adenocarcinoma↗