Biomedical subjects
H Gore
Publications and source records attributed to H Gore.
Pap smears: interpreting the new Bethesda terminology.
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Immunoglobulin-containing plasma cells recruited to cervical neoplasia.
OBJECTIVE: To determine the number and isotype of immunoglobulin (Ig)-containing cells that infiltrate various stages of cervical neoplasia from no lesion to invasive cancer. METHODS: By three-color immunofluorescent microscopy, the number and isotype of stromal plasma cells were determined for 91 specimens representing a spectrum of cervical epithelial neoplasia as follows: no lesion (n = 12), koilocytic atypia (n = 13), mild dysplasia (n = 21), high-grade squamous intraepithelial lesions (SIL; n = 22), and invasive carcinoma (n = 23). RESULTS: The Ig-positive cell counts were markedly increased under the low-grade SIL. Specifically, the mean number of IgG-positive plasma cells was significantly increased (P < .003) under the subepithelial stroma of mild dysplasia as compared with no SIL, high-grade SIL, or invasive carcinoma. These immunocyte infiltrates were clustered in the stroma beneath koilocytes, which also demonstrated IgG-positive intracellular staining. CONCLUSION: Low-grade cervical lesions are infiltrated by IgG plasma cells to a greater extent than high-grade or invasive cervical lesions, suggesting that antibody responses are preferentially recruited in early cervical neoplasia, giving credence to the concept that low-grade lesions represent a human papillomavirus infection of the cervix rather than a neoplastic condition.
CD8+ T lymphocytes are recruited to neoplastic cervix.
ToliicIV distinguish normal cervical lymphocyte populations from phenotypes recruited to the cervix in response to cervical neoplasia, lymphocytes were isolated from normal and neoplastic cervix. A portion of the cervical transformation zone was obtained from 19 patients with pathologically confirmed cervical intraepithelial neoplasia and from 20 patients with normal cervices undergoing hysterectomy for benign indications. Mononuclear cells were harvested from cervical tissue using a serial, multienzymatic digestion procedure and enriched by density gradient centrifugation. Isolated cell populations were stained with surface marker-specific monoclonal antibodies and analyzed by fluorescent activated cell sorter to determine the percentage of B cells, total T cells, CD4+ T cells, CD8+ T cells, and natural killer (NK) cells. The distribution of circulating peripheral blood lymphocyte phenotypes was similar for both patients with neoplasia and normal controls. A marked disparity in the proportions of NK cells and T cells was demonstrated among lymphocyte phenotypes infiltrating the cervix. The percentage of CD4+ T cells and NK cells was significantly depressed (P = 0.04, P = 0.03, respectively) in dysplastic tissue as compared to normal cervical tissue. In contrast, the proportion of CD8+ T cells was significantly increased in the dysplastic tissue (P = 0.0001). Analysis of immunocompetent cells in the circulation appears to have little correlation with immunocytes present in the dysplastic epithelium. The depression in the proportion of CD4+ T lymphocytes and NK cells at the cervical squamocolumnar junction reflects a local recruitment of CD8+ T cells to the site of neoplasia in the cervix.
Normal uterine cervix: characterization of isolated lymphocyte phenotypes and immunoglobulin secretion.
PROBLEM: Isolation of viable cervical lymphocyte populations and characterization of their function in healthy tissue is necessary to understand immunity in the genital tract. METHODS: Normal, cervical tissue was digested using a multi-enzymatic digestion procedure. Lymphocytes were characterized using FACS analysis and ELISPOT analysis for immunoglobulin secreting cells. RESULTS: Following the digestion procedure, 0.16 x 10(6) +/- 0.8 cells/g of tissue with a viability of 90-98% were isolated from normal cervical tissue. FACS analysis determined that B lymphocytes were the predominant cell type in normal cervical tissue representing a significantly higher percentage than that found in peripheral blood (P = 0.015). T lymphocytes and NK cells represented a significantly lower percentage than that found in peripheral blood (P = 0.0001 and 0.026, respectively). The largest percentage of immunoglobulin secreting cells isolated were secreting IgG followed by IgA. A limited number of IgM secreting cells were detected. IgA2 secreting cells represented 34.46 +/- 4.6% of the total number of IgA plasma cells. CONCLUSION: These studies represent the first analysis of viable mononuclear cells isolated from normal cervical tissue. The results form a baseline from which it will now be possible to compare changes that occur at the cervical squamocolumnar junction in response to infection or neoplasia.
Radical hysterectomy in the treatment of patients with bulky early stage carcinoma of the cervix uteri.
This study was done to assess the role of radical hysterectomy in patients with bulky (greater than or equal to 4 centimeters) early stage carcinoma of the cervix uteri. Of 48 patients with bulky carcinoma of the cervix uteri undergoing Type III radical hysterectomy between 1970 and 1987, 46 patients were Stage 1B and two were Stage 2A. Pathologic estimate of the dimensions of the lesion ranged from 4 x 3 to 9 x 11 centimeters. Fourteen patients had evidence of pelvic node metastasis and one patient had evidence of microscopic metastasis to the para-aortic nodes. Twelve patients received adjunctive radiation therapy for findings of nodal metastasis or tumor near or at the surgical margin. There were recurrences in 19 patients, 13 of which were isolated to the pelvic area. Of the patients with isolated pelvic recurrences, five were salvaged with secondary treatment. The overall five year survival rate was 73.6 percent and the ten year survival rate was 60.6 percent. Radical hysterectomy and lymphadenectomy seems to have equal efficacy and morbidity rates when compared with radiation therapy or the combination of extrafascial hysterectomy and radiation therapy in the treatment of patients with bulky early stage carcinoma of the cervix uteri.
Histopathologic predictors of the behavior of surgically treated stage IB squamous cell carcinoma of the cervix. A Gynecologic Oncology Group study.
Disagreement persists about the superiority of Reagan and Ng's method over that of Broders' for the histologic grading of squamous carcinoma of the cervix. Uncertainty about the predictive value and reproducibility of any of the grading methods prompted a comparison of factors previously suggested as indicating the biologic behavior for cervical squamous carcinoma. One hundred ninety-five women, who were enrolled in a Gynecologic Oncology Group treatment protocol of Stage IB squamous carcinoma of the cervix and underwent radical hysterectomy with pelvic and paraaortic node sampling, formed the study population. The tumors were graded first by participating institutional pathologists, with submitted slides subjected to an independent review by two pathologists (R.J.Z. and S.W.). The histologic parameters examined included the presence and amount of keratinization, nuclear pleomorphism, mitotic rate, gestalt grading, pattern of invasion at the stromal interface, and inflammatory cell infiltrate. The depth of invasion and presence or absence of vascular invasion also were assessed. The probability of pelvic lymph node metastasis and the progression-free interval were determined for each parameter. Surprisingly, none of the grading methods was effective in predicting nodal spread or progression-free interval. However, an increasing depth of invasion strongly correlated with nodal spread and a diminished progression-free interval (P less than 0.0001). Vascular invasion was less effective in these predictions (0.05 less than P less than 0.10). Both measurements were reasonable reproducible. It was concluded that histologic grading of surgically treated cervical carcinoma is not useful but that the depth of invasion and vascular invasion are important predictors of behavior that should be reported routinely.
Coexisting intraductal breast carcinoma and metastatic choriocarcinoma presenting as a breast mass.
Identifying choriocarcinoma in breast tissue is a rare phenomenon. This report describes an unusual case of metastatic choriocarcinoma presenting as a breast mass and coexisting with an intraductal breast carcinoma. This is the first documented case of a choriocarcinoma metastatic to the breast that has responded to chemotherapy.
Founders of pediatric pathology: Arthur Tremain Hertig.
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Human papillomavirus screening for women with atypical Papanicolaou smears.
A study was undertaken to evaluate the utility of human papillomavirus (HPV) DNA screening and colposcopy in the management of women whose Papanicolaou smears demonstrated atypia less than dysplasia. Fifty patients whose initial Papanicolaou smears were interpreted as showing atypia less than dysplasia were evaluated for the presence of HPV 16 DNA in exfoliated cervicovaginal cells and for histologic findings on biopsy. Those 50 patients were compared to two groups of patients: one consisting of 124 patients with biopsy-documented cervical intraepithelial neoplasia (CIN) and another of 112 patients with normal Papanicolaou smears. The presence of HPV 16 DNA was confirmed with Southern analysis in 46% of patients with atypical Papanicolaou smears, 46% with confirmed CIN and 11.6% with normal Papanicolaou smears. The 50 patients with atypical smears underwent colposcopically directed cervical biopsies, revealing the following results: 14 (28%) had normal histology, 29 (58%) had koilocytosis without dysplasia, and 7 (14%) had CIN. HPV 16 DNA was present in exfoliated cervicovaginal cells from a large percentage of patients from each category (50% of patients with normal histology, 41.2% with koilocytosis and 57% with CIN). HPV 16 DNA screening did not predict which patients with atypical smears had underlying CIN. Colposcopically directed biopsy remains the evaluation method of choice.
Secretory immune system of the female reproductive tract. II. Local immune system in normal and infected fallopian tube.
The existence of a secretory immune system in the female genital tract has been demonstrated by the predominance of immunoglobulin (Ig)A-producing plasma cells in human fallopian tube, uterine cervix, and vagina. Epithelium lining fallopian tubes expresses a receptor for IgA, secretory component (SC), and thus resembles other secretory tissues such as intestine, mammary, lacrimal, and salivary glands. The present study extends the characterization of the local immune system in the fallopian tube and assesses its response to infection. We examined normal and infected fallopian tubes from surgical specimens, obtained at tubal ligation and abdominal hysterectomy, for the presence of Ig-producing cells, T cells, and natural killer cells. All tubular segments contained a predominance of IgA plasma cells in the subepithelial lamina propria. The epithelial cells were strongly positive for SC. Luminal contents stained positively for IgA, SC, and J chain, suggesting that this material contained secretory IgA. Submucosal plasma cells of IgM and IgG classes were less frequent than IgA. T cells were present in numbers approximately twofold greater than plasma cells in normal fallopian tubes. T-suppressor (CD8+) cells, which may function in the induction of immune tolerance, were present in the intraepithelial spaces. Infected segments of fallopian tubes demonstrated six- to tenfold increased numbers of plasma cells of all classes. These data suggest that a local immune system is functioning in the human fallopian tube and may provide a first line of defense against tubal infection and the prevention of tubal factor infertility.
Hormonal contraception and trophoblastic sequelae after hydatidiform mole (a Gynecologic Oncology Group Study)
A prospective randomized study was undertaken to determine whether the administration of oral contraceptives after the evacuation of a hydatidiform mole affects the human chorionic gonadotropin serum level in a way that leads to an increased frequency in the diagnosis of postmolar trophoblastic disease. Between 1981 and 1988, 266 patients were randomly assigned to either oral contraceptives or barrier contraception after evacuation of a hydatidiform mole. Patients were followed up until serum levels of human chorionic gonadotropin were normal or until specific criteria for the diagnosis of postmolar trophoblastic disease were met. Twenty-three percent of patients receiving oral contraceptives had postmolar trophoblastic disease, whereas those using a barrier method had a rate of 33%. The median time to spontaneous regression in the oral contraceptives group was 9 weeks, whereas the median time to regression in the barrier group was 10 weeks. Twice as many patients in the barrier group became pregnant in the immediate follow-up period. We conclude that oral contraceptives are the preferred method of contraception after evacuation of a hydatidiform mole.
Analysis of prognostic features in adenocarcinoma of the cervix.
Uncertainties regarding the clinical behavior and management of women with primary adenocarcinoma of the cervix persist. A series of 162 patients was evaluated with emphasis on histopathology, clinical features, treatment, and survival. Sixty-seven patients underwent radical hysterectomy alone, 65 patients underwent radiation therapy alone, while the remainder were treated with combined surgery and radiotherapy. When compared to a matched series of squamous cell carcinoma patients, no statistical differences in survival could be demonstrated. Clinical stage (P less than 0.001) and lesion size (P less than 0.001) were the most important prognostic factors for the entire series. Patients with adenocarcinoma of varied histologic patterns were compared to patients with adenosquamous lesions and no statistical difference in survival could be demonstrated. Multivariate analysis of those women with Stage I adenocarcinoma of the cervix identified risk groups based on tumor grade, lesion size, and patient age. Patients in the low risk group had a 5-year survival of 89.5% while patients in the intermediate and high risk groups had 5-year survival rates of 68.4 and 37.3%, respectively. In patients with Stage I well-differentiated lesions survival was excellent, independent of lesion size.
Immunohistochemistry of the blood group A,B,H isoantigens and Oxford Ca antigen as prognostic markers for stage IB squamous cell carcinoma of the cervix.
Currently, there is lack of a histologic classification of squamous cell carcinoma of the cervix that correlates significantly with patient survival. This study investigated the survival predictive value of two immunohistochemical markers, the blood group A,B,H isoantigens and the Oxford Ca antigen, on conventional histologic sections of tumor tissues from 85 surgically treated patients with Stage IB squamous cell cervical cancer. The results indicated that the two antigens are two distinct markers, neither of which correlates with tumor grade. The expression of the A,B,H isoantigens is significantly related to patient survival after adjustment for the depth of stromal invasion of the tumor, whereas the Oxford Ca antigen has no survival predictive value.
Pseudomonas keratitis and folliculitis from whirlpool exposure.
A local outbreak of pseudomonal folliculitis from whirlpool exposure occurred in 12 persons. A corneal ulcer developed in one patient within 48 hours of using the whirlpool. Treatment with fortified gentamicin resolved the corneal infiltrate and vision returned to normal. A second patient, who had not showered immediately after leaving the whirlpool, was left with areas of skin hyperpigmentation and scarring despite treatment with ultraviolet rays and tetracycline. Although the skin rash may be self-limited, the potential for visual loss from pseudomonal keratitis emphasizes the need for proper disinfection of swimming and whirlpool water.
Lymph node metastasis in cancer of the cervix: a preliminary report.
Accurate assessment of lymph node metastasis in cervical cancer is imperative to treatment plan. A histologic sampling method is suggested in which surgically excised lymph nodes are dissected at multiple levels before paraffin embedding. This approach proves to be a more sensitive procedure than the current bisection method in detecting metastasis.
Study of superficially invasive carcinoma of the cervix.
A detailed histologic study has been completed on 125 patients with squamous cell carcinoma of the cervix invading to a depth no greater than 5 mm. Depth of invasion was 3 mm or less in 73% and 3.1 to 5 mm in 27%. The median width was 4.8 mm (range 0.08 to 20 mm). Most of the lesions were multifocal (82%); the number of invasive foci correlated well with increasing width and depth of invasion. Lymphvascular space invasion was found in seven patients, none of whom had lymph node metastases, although in one a single focus of carcinoma was present in the parametrium. Therapy consisted of radical hysterectomy and pelvic lymphadenectomy in 55% of the women, including 43 patients with lesions invading less than 3 mm. There was tumor metastatic to lymph nodes in only one of 69 patients with dissected nodes (1.4%). The mean follow-up time was 5.0 years; there was one recurrence (cervical intraepithelial neoplasia only). This study and a survey of the recent literature imply that tumor pattern, width, and confluence can be ignored in lesions invading to 5 mm, and that the most important factor to consider in therapy planning is depth of invasion. The following guidelines are proposed. In lesions without lymphvascular space invasion, those invading the stroma to no more than 3 mm may be treated with a total abdominal or vaginal hysterectomy. In lesions invading between 3 and 5 mm, a total abdominal hysterectomy and a pelvic lymphadenectomy seem adequate therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of endocervical curettage in colposcopy.
Two-thousand three-hundred and four patients with abnormal cervical cytology were evaluated by colposcopy, cervical biopsy, and endocervical curettage. The endocervical curettage was more accurate than the cervical biopsy in 1.2% of patients with satisfactory colposcopic examinations, 15.7% of patients with unsatisfactory examinations, and 30.5% of patients with no lesions observed. The endocervical curettage contained neoplastic epithelium in all 15 of the patients with invasive cancer and in seven patients it was the only diagnostic parameter that indicated invasion. The information from the endocervical curettage, when correlated with the cervical cytology, colposcopic findings, and cervical biopsy, eliminated the need to do a diagnostic conization in 76% of patients with unsatisfactory examinations and 79% of patients with no lesion identified. It is recommended that the endocervical curettage be a part of every colposcopic examination.