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Use of p63 for distinction of glandular versus squamous lesions in cervicovaginal specimens.

BACKGROUND: Differentiating primary glandular from high-grade squamous intraepithelial lesions (HSIL) that involve endocervical glands is not an uncommon diagnostic problem in liquid-based gynecological cytology. Squamous and atypical glandular cell lesions may show similar cytomorphologic features. The aim of this study was to evaluate the use of p63 as a marker of basal and/or squamous cell derivation in this differential diagnosis. METHODS: Of 59,257 liquid-based cervicovaginal specimens collected over a 3-year period, 149 were diagnosed as atypical glandular cells of uncertain significance (AGUS) or adenocarcinoma and had histological follow-up. Ten cases (8AGUS and 2 adenocarcinomas) were proven to be high-grade dysplasia on cervical biopsies and the remaining cases represented glandular pathology. Slides from discrepant cases were stained with p63 antibody. In addition, the authors stained 25 control cases (10 adenocarcinomas, 10 HSIL, and 5 negative cervicovaginal specimens). RESULTS: In all 10 discrepant cases, the abnormal groups originally interpreted as glandular in origin showed a homogeneous strong nuclear staining for p63 that indicated their squamous origin. Nuclei of isolated HSIL cells and basal cells from atrophic smears were also positive for p63. Benign and malignant glandular cells were uniformly negative. Isolated metaplastic, intermediate, and superficial squamous cells were likewise negative for this antibody. CONCLUSIONS: p63 is a useful immunocytochemical marker for differentiating primary glandular pathology from HSIL in cervicovaginal specimens. It also detects isolated HSIL cells ("litigation cells"). This antibody is not expressed in AGUS, adenocarcinoma, or normal glandular cells. p63 stains basal cells and may be a diagnostic pitfall in atrophic cervicovaginal specimens.

Adenocarcinoma↗

Identification of features of metaplastic cells in sputum for the detection of squamous-cell carcinoma of the lung.

Digitized images of 1,556 squamous metaplastic cells from the sputum of 15 patients with confirmed squamous-cell carcinoma of the lung and 13 subjects without apparent neoplasia were analyzed to determine if features existed within these relatively normal cells that could be used to differentiate between the two populations. Results indicate that such marker features do exist. A cross-validation study using an additional 465 cells confirmed the conclusion that squamous metaplastic cells from patients with squamous-cell carcinoma of the lung do differ from those of subjects without cancer. While such marker features alone are not reliable enough to assist pathologists in the diagnosis of squamous-cell carcinoma of the lung, they might, in sufficient numbers, be used to identify patients for whom follow-up testing would be advised.

Biomarkers, Tumor↗

Prospective validation of the Martinez-Gimeno clinicopathologic scoring system (MGSS) for evaluating risk of cervical lymph node metastases of squamous cell carcinoma of the oral cavity.

BACKGROUND: The prediction of neck metastasis from oral squamous cell carcinoma is an unresolved issue. The Martinez-Gimeno Scoring System (MGSS) is an index designed as a predictive aid that may be implemented after analysis of the tumor resection. METHODS: A double-blind cohort study was designed and carried out in a tertiary hospital. Seventy-nine consecutive patients diagnosed with squamous cell carcinoma of the oral cavity requiring local resection and neck dissections were included. After tumor resection, the MGSS was applied, and patients were then classified into one of four groups on the basis of the MGSS score: group I, 7 to 12 points; group II, 13 to 16 points; group III, 17 to 20 points; and group IV, 21 to 30 points. After this, pathologic analysis of the neck specimen was performed to detect metastasis. The results, histopathologic analysis of the neck specimens, and previously tabulated MGSS scores were then compared, and on the basis of their results an estimation of the predictive validity of MGSS of neck metastases was obtained. A correlational analysis was performed, comparing metastases to a set of predictive factors, including the MGSS score. A logistic binary regression model that used metastases as the dependent variable was adjusted in an attempt to estimate odd ratios for these factors. RESULTS: Twenty-six cases displayed metastases. The metastatic nodes measured from 0.5 to 7 cm and were smaller than 1.5 cm in 46% of the cases. The rates of metastases in the four groups were as follows: group 1, 0%; group II, 21%; group III, 50%; and group IV, 67%. MGSS had a sensitivity of 100% (95% confidence interval [CI], 98% to 100%) for predicting metastases from oral squamous cell carcinoma, a specificity of 55% (95% CI, 44% to 66%), an overall efficiency of 73% (95% CI, 63% to 83%), a positive predictive value of 59% (95% CI, 48% to 70%), and a negative predictive value of 100% (95% CI, 98% to 100%). The correlation between various predictive factors and the presence of metastases showed a value of r = .87 (p = .001) with the MGSS score. No correlation was found between the MGSS score and the size of the metastatic lymph node. In the logistic regression model, the MGSS score displayed an odds ratio of 3.5 (95% CI, 1.9-6.3; p = .00001) for the presence of metastases in patients with squamous cell carcinoma of the oral cavity. CONCLUSION: The MGSS is a useful index for the prediction of neck node metastases that is applied at the start of the analysis of the tumor resection in patients with squamous cell carcinoma of the oral cavity.

Adult↗

Histologic differentiation and chemosensitivity of human head and neck squamous cell carcinomas.

The chemosensitivities of 42 human head and neck squamous cell carcinomas were examined using the in vitro succinate dehydrogenase inhibition (SDI) test. The tumor tissues obtained at surgery or biopsy were exposed to five different antitumor drugs: adriamycin (ADM), cisplatin (CDDP), carboquone (CQ), 5-fluorouracil (5-FU), and 1-hexylcarbamoyl-5-fluorouracil (HCFU). The results were analyzed according to the histopathologic degree of differentiation of well, moderately, and poorly differentiated squamous cell carcinoma. The average decrease in succinate dehydrogenase activity was 43.2 +/- 24.9 for ADM, 29.0 +/- 14.2 for CDDP, 32.9 +/- 17.6 for CQ, 64.2 +/- 20.6 for 5-FU, and 26.8 +/- 16.9 for HCFU. There was a statistically significant difference in the decrease of succinate dehydrogenase activity between well and poorly differentiated squamous cell carcinomas. These data suggest that, for patients with a poorly differentiated squamous cell carcinoma, the response to anti-cancer drugs may be more satisfactory than in those with a well-differentiated squamous cell carcinoma.

Antineoplastic Agents↗

Quantitation and localization of cellular retinol-binding protein in squamous-cell carcinomas of the cervix uteri and of the oral cavity.

The concentration of cellular retinol-binding protein (CRBP) was determined by radioimmunoassay in biopsies of normal mucosa and squamous-cell carcinomas of cervix uteri from 30 women. The tumour tissues contained significantly higher concentrations of CRBP (median = 120 micrograms/g protein) than normal mucosa (median = 32 micrograms/g protein). The distribution of CRBP in normal mucosa and squamous-cell carcinomas from cervix uteri and from oral cavity was evaluated by immunohistochemical techniques. In tissue sections of normal epithelium from the cervix uteri and the oral cavity, the maturing keratinocytes in the prickle-cell layers were moderately or strongly stained when antiserum against CRBP was used, while the proliferating cells in the basal-cell layer were stained only lightly if at all. Squamous-cell carcinomas of the cervix uteri and the oral cavity presented much the same picture. The observed difference in CRBP concentration between squamous-cell carcinomas and normal squamous-cell mucosa may therefore be more quantitative than qualitative.

Adult↗

Squamous cell differentiation markers in normal, premalignant, and malignant epithelium: effects of retinoids.

Vitamin A and some of its analogs (retinoids) maintain normal differentiation of epithelial tissues by preventing aberrant squamous differentiation of cells in nonkeratinizing epithelia. They can also reverse squamous metaplasia, which develops in vivo during vitamin A deficiency. These effects are the result of the ability of retinoids to suppress the expression of genes associated with squamous differentiation (e.g., transglutaminase type I, loricrin, involucrin, filaggrin, and keratin K1). In addition, retinoids reverse keratinizing premalignant lesions in the oral cavity, and inhibit the growth and squamous differentiation of head and neck squamous cell carcinomas (HNSCCs) in vitro. Nuclear retinoic acid receptors, which function as DNA-binding, trans-acting, transcription-modulating factors, are considered to be the proximate mediators of the effects of retinoids on gene expression and may mediate the re-regulation of aberrant differentiation and growth of premalignant and some malignant cells, thereby suppressing the development of head and neck cancer.

Animals↗

Clinical benefit of chemosensitivity test for patients with regional lymph node-positive esophageal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: Patients who have undergone resection for lymph node-positive esophageal squamous cell carcinoma are at high risk of recurrence and early death. The role of the postoperative adjuvant chemotherapy in this population needs to be determined. The present study was designed to determine whether the chemosensitivity test in fresh human esophageal squamous cell carcinoma, using highly purified tumor cells, correlates with the clinical response. METHODS: A retrospective review of all patients with resected squamous cell carcinoma of the thoracic esophagus between 1993 and 2000 was performed. We determined the chemosensitivity for cisplatin (CDDP), 5-fluorouracil (5-FU), mitomycin C, and adriamycin in vitro in fresh human esophageal squamous cell carcinoma using the MTT assay. Regional lymph node-positive (N1) patients who received sequential postoperative chemotherapy were compared with lymph node positive patients who underwent surgery alone. RESULTS: A total of 50 patients were reviewed, and chemosensitivity tests were successfully performed in 46 patients: 20 patients received surgery alone (S group), and 26 patients received surgery plus postoperative chemotherapy (SC group) according to results of MTT assay using highly purified tumor cells. When the SC group was divided into an SC-low group (inhibition rate of CDDP + 5-FU was below 85%, n = 15) and an SC-high group (over 85%, n = 11), the SC-high group showed more significant survival prolongation than the S group or the SC-low group (P < 0.01). CONCLUSIONS: Our results suggest that the results of the conventional MTT assay may be useful in evaluating the optimum adjuvant chemotherapy for patients with regional lymph node positive (pN1) esophageal squamous cell carcinoma.

Aged↗

Squamous cell carcinoma of the thyroid: a report of two cases.

Two patients with squamous cell carcinoma, which accounts for 1.1% of all primary thyroid carcinomas, are described. Squamous metaplasia is the most likely etiology, but an occasional carcinoma may be derived from remnants of embryonic origin. Although squamous metaplasia has been documented in several conditions involving the thyroid, no evidence exists that this predisposes to squamous cell carcinoma. Metastases and direct extension of squamous cell carcinoma in the thyroid gland are much more frequent than primary involvement and are always part of a generalized carcinomatosis. A primary lesion must always be sought; however, diagnosis may not be possible until an initially occult tumor becomes evident or even until autopsy. Because this lesion typically runs a fulminant course, radical surgical resection at the earliest opportunity offers the best hope for cure. The lesions are usually radioresistant, and chemotherapy has not been shown to alter the course of this disease.

Aged↗

Squamous cell carcinoma of the thyroid gland -- transition from adenocarcinoma.

Eight autopsy cases of thyroid carcinoma, in which adenocarcinoma and squamous cell carcinoma coexisted, and presented. In these adenosquamous cell carcinoma, pathological findings suggest direct transition from papillary adenocarcinoma to squamous cell carcinoma, rather than transformation to squamous cell carcinoma via squamous metaplasia. We believe that squamous cell carcinoma arises from adenocarcinoma of the thyroid in most cases.

Adenocarcinoma, Papillary↗

Antigen specificity of squamous cancers of the head and neck based on tumor site using the slide leukocyte adherence inhibition assay.

Patients with a diagnosis of squamous cancer of the upper aerodigestive (UAD) system were tested with extracts of squamous cancer arising from several regions of the UAD tract and compared to various control populations, using the slide leukocyte adherence inhibition (LAI) assay. Seven tumor extracts were tested. Twenty-five of 77 tests (32%) were positive in unselected UAD squamous cancer patients. However, matching patients with tumor extract by the site of origin within the UAD tract, 19 of 22 tests (86%) were positive when the site of origin was identical for leukocyte donor and extract. Two of four patients tested with an extract prepared from a different site with in the same region of the UAD system were positive; whereas only 4 of 51 tests (8%) were positive in patients tested with an extract from a cancer arising from a different region within the UAD tract (P less than 0.001). One of 33 tests using patients with either not cancer (11 tests), squamous cancer of other regions (15), or adenocarcinoma (7) reacted to the extracts of UAD tract cancers. We conclude that patients with squamous cancer of the UAD tract can recognize distinct tumor-associated antigens that are site-specific and are non-cross-reactive using the LAI technique.

Antigens, Neoplasm↗

Squamous metaplasia with Hashimoto's thyroiditis presenting as a thyroid nodule.

A 59-year-old Japanese female presented a well-limited and movable thyroid nodule. Histologically, the nodule consisted of clusters of squamous cells surrounded by dense connective tissue in Hashimoto's thyroiditis. The squamous cells were well arranged and showed no mitotic figures. We therefore interpreted this nodule as being squamous metaplasia with Hashimoto's thyroiditis rather than squamous carcinoma of the thyroid. There are no previous reports in the literature of nodular formation of squamous metaplasia in the thyroid.

Carcinoma, Squamous Cell↗

Squamous cell carcinoma with cyst of the thyroid.

Two cases of primary squamous cell carcinoma associated with a thyroid cyst in the thyroid are described. The majority of squamous cell carcinomas reported so far have had some degree of co-existing adenocarcinoma, while the cases presented in this report had no glandular component at all. The histogenesis of squamous cell carcinoma is not clear, but at present, it is believed that most cases arise from the follicular epithelium. In our cases, in spite of an intensive examination of serially sectioned specimens, no areas of adenocarcinoma, squamous metaplasia from the follicular epithelium, or congenital squamous remnants could be found.

Aged↗

Immunohistochemical localization of basement membrane type IV collagen in invasive and metastatic squamous carcinomas of the head and neck.

The immunohistochemical localization of basement membrane type IV collagen was investigated with a mouse monoclonal antibody in major surgical resections from 25 patients with invasive squamous carcinomas of the head and neck. Irrespective of site, size or stage of the disease, the 16 primary invasive tumours were almost completely surrounded by a layer of type IV collagen. Focal abnormalities were regularly present, consisting of thickening and aggregation of type IV collagen together with attenuation and segmental loss. Similar changes were seen in metastatic squamous carcinomas in 36 cervical lymph nodes. It is suggested that the probable formation of a normal basement membrane protein by these squamous carcinomas indicates the preservation of a normal function of differentiating squamous epithelia. The results indicate that a major basement membrane component, type IV collagen, continues to co-exist with invasive and metastatic squamous carcinomas.

Adult↗

Recombinant human erythropoietin for the treatment of chronic anemia in multiple myeloma and squamous cell carcinoma.

Recombinant human erythropoietin (rHuEPO) improves chronic anemia of cancer, but the proportion of patients who respond favorably to the treatment varies depending on the type of neoplasia. Preliminary data of the two malignancies with the highest response rates, namely, multiple myeloma and squamous cell carcinoma, are reported. Twenty patients with multiple myeloma and 14 with squamous cell carcinoma, who had presented with hemoglobin levels < 11 g/dl, were treated with rHuEPO, 150 U/kg, three times/week. Response, defined as an increase of at least 2 g/dl hemoglobin within 12 weeks, was achieved by 15 myeloma patients (75%) and 11 patients with squamous cell carcinoma (79%). Tolerance of the treatment was excellent. The WHO performance status and quality of life improved in responders. The remarkably low levels of endogenous EPO in our patients with squamous cell carcinoma, most of whom had been treated with cisplatin-or carboplatin-containing regimens, suggest that anemia in these cases had been at least partly chemotherapy induced. In myeloma patients, the blunted EPO response to the anemic condition may have been partly caused by subclinical tubular insufficiency induced by toxic paraproteins. Future studies should aim to elucidate factors which are responsible for the inability of some patients to respond to rHuEPO treatment, even though in multiple myeloma and squamous cell carcinoma these non-responders are a small minority.

Anemia↗

Combined use of intraoperative lymphatic mapping and lymphoscintigraphy in the management of squamous cell cancer of the vulva.

BACKGROUND: The standard care of the patient with squamous cell cancer of the vulva is radical vulvectomy along with inguinal-femoral node dissection. We explored the feasibility of sentinel lymphadenectomy in patients with squamous cell cancer of the vulva. METHODS: Patients with biopsy proven squamous cell cancer of the vulva were studied with preoperative lymphoscintigraphy, intraoperative lymphatic mapping with isosulfan blue combined with intraoperative lymphoscintigraphy utilizing a hand-held gamma counter. RESULTS: Five patients with invasive squamous cell cancer were studied. Sentinel nodes were identified in six lymphatic basins. One lymphatic basins had two sentinel nodes. Six of seven sentinel nodes were blue and all retained radioactivity at a ratio of at least 3:1 above the background levels in the regional node basin. One patient was found to have metastatic tumor which was confined to a sentinel lymph node. There was minimal morbidity associated with the procedure. CONCLUSIONS: Lymphatic mapping is feasible in patients with squamous cell cancer of the vulva. These initial results suggests further study is warranted.

Carcinoma, Squamous Cell↗

Synchronous ovarian and cervical squamous intraepithelial neoplasia: an analysis of HPV status.

In contrast to the strong association between human papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN), the relationship between HPV and squamous epithelial lesions of the ovary is less clear. We report a case of synchronous ovarian and cervical squamous intraepithelial neoplasia. To investigate the possible association between HPV and squamous intraepithelial neoplasia/carcinoma in situ (CIS) of the ovary, DNA was extracted from paraffin-embedded tissues including normal cervix, CIN, CIS from both ovaries, and an area of ovarian endometriosis. All samples were positive for HPV 16 E6 except for one of the two samples from the normal cervical squamous epithelium. These results support the hypothesis that HPV may be involved in the development of ovarian squamous intraepithelial neoplasia.

Carcinoma, Squamous Cell↗

Use of hormone replacement therapy and adenocarcinomas and squamous cell carcinomas of the uterine cervix.

INTRODUCTION: Exogenous hormones may influence the development of cervical adenocarcinomas. Incidence rates of adenocarcinomas and use of noncontraceptive hormones have increased since the 1970s, but few studies have investigated this potential relationship. METHODS: We conducted a multicenter case-control study of 124 women with adenocarcinomas, 139 women with squamous cell carcinomas matched on age, diagnosis date, clinic, and stage of disease (in situ or invasive) to adenocarcinoma cases, and 307 healthy community controls who were also matched on age, ethnicity, and residence to adenocarcinoma cases. Participants completed in-person interviews regarding exogenous hormone use before diagnosis and other risk factors and volunteered cervical samples for human papillomavirus (HPV) testing via a PCR-based method. Odds ratios (ORs) with 95% confidence intervals (CIs) estimated relative risks. RESULTS: Only 13 adenocarcinoma cases (10.5%), 7 squamous carcinoma cases (5%), and 20 controls (6.5%) had used noncontraceptive hormones for menopausal symptoms, irregular periods, or disease prevention; most use was short-term, former use. Ever-use was associated with adenocarcinomas (OR = 2.1, 95% CI 0.95-4.6) but not squamous carcinomas (OR = 0.85, 95% CI 0.34-2.1). No trends were seen with duration of use or ages at first use, but unopposed estrogens were positively associated with adenocarcinomas (OR = 2.7). Unopposed estrogens remained associated with adenocarcinomas (OR = 2.0) when analyses were restricted to the HPV-positive controls. Menopausal status was not associated with adenocarcinomas or squamous carcinomas and did not modify the other associations. CONCLUSION: Although small numbers warrant tentative conclusions, exogenous estrogens, especially unopposed estrogens, were positively associated with adenocarcinomas. Noncontraceptive hormones were negatively but weakly associated with squamous carcinomas.

Adenocarcinoma↗

Primary squamous cell carcinoma of the breast in a pregnant woman: report of a case.

Although reports on primary squamous cell carcinoma of the breast have been increasing in number, the morbidity rate of the disease is comparatively low. Its onset in pregnant women, especially, is quite rare. We herein report a case of primary squamous cell carcinoma of the breast in a pregnant woman. A 33-year-old woman was admitted with a lump in the right breast and an abnormal bloody nipple discharge. The breast mass was 5.6 x 5.4 cm in size, and both ultrasonogram and CT scanning showed that it consisted of a cystic tumor for the most part. A large amount of bloody cystic fluid was aspirated by fine-needle aspiration; squamous cell carcinoma of the breast was suspected by a cytological study on the fluid. Twelve days after an induced abortion was performed, a modified radical mastectomy was carried out. Histological findings of the resected specimen demonstrated that the tumor was squamous cell carcinoma which had been well differentiated with partial keratinization and cancer pearls. Noninvasive ductal carcinoma was also observed in a very small region of the specimen, which indicated that the tumor was probably originally adenocarcinoma which later transformed into squamous cell carcinoma.

Adult↗