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E J Wilkinson

Publications and source records attributed to E J Wilkinson.

At least 37 records · Page 2Linked to original sources

Pathology of the vulva and vagina.

Extensive clinical, epidemiologic and pathologic research published in the past year has enhanced our understanding of the pathogenesis and natural history of human papillomavirus induced female genital tract lesions, and refined diagnostic and therapeutic modalities in management of these patients. Current experience with vulvar intraepithelial neoplasia as well as diagnosis and treatment of squamous cell carcinoma of the vagina and vulva are discussed. Advanced imaging techniques and immunohistochemical studies are employed in diagnosis and classification of less common neoplasms. New antibiotics and potent topical steroids are available for treatment of inflammatory vulvovaginitis, particularly in cases of recurrent candidiasis and lichen sclerosus. Persistent or resistant vulvovaginitis may benefit from an interdisciplinary approach to diagnosis and treatment.

Female↗

Quality control considerations for Ki-67 detection and quantitation in paraffin-embedded tissue.

Proliferative activity has prognostic significance in many solid tumors. Immunohistochemical analysis of tumor proliferation may be accomplished with the Ki-67 monoclonal antibody which recognizes a nuclear antigen expressed throughout the cell cycle. This antibody, however, cannot be used with formalin-fixed, paraffin-embedded tissue. Recently, a Ki-67 equivalent murine monoclonal antibody (MIB-a; AMAC, Inc., Westbrook, ME) was generated which can detect tumor proliferative activity in routinely processed tissue with microwave oven heating. Using quantiative image analysis, we assessed the effect of delay in fixation, total time of formalin fixation, and microwave heating time on the immunoreactivity of this antibody. The effect of time to fixation (0, 2, 4, 8, or 24 hours) on MIB-1 immunostaining was determined in various tumor tissues using image analysis. No significant difference in positive nuclear area was observed for tissues in which fixation was delayed for as long as 8 hours relative to controls. A 24-hour fixation delay resulted in a small decrease in positive nuclear area was observed for tissues in which fixation was delayed for as long as 8 hours relative to controls. A 24-hour fixation delay resulted in a small decrease in positive nuclear area relative to controls. The effect of fixation time (4, 24, or 48 hours) and microwave oven heating time on MIB-1 immunostaining was studied in tonsil tissue, and quantitated by image analysis. Good MIB-1 immunostaining was observed for all microwave oven heating times in tissue fixed for 4 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Ploidy results in prostatic carcinoma vary with sampling method and with cytometric technique.

To evaluate the effect of sampling method and cytometric method on DNA ploidy results, a comparison study was performed on 20 whole prostate glands removed at prostatectomy. Fresh sampling was by sampling fine-needle aspiration (FNA). Paraffin sampling was by microdissection and re-embedding of 3 to 13 (average 6) 5-mm foci of microscopically proven tumor. Analysis was by flow cytometry and by image cytometry (microscopically guided). In tumor negative cases, flow and image cytometry of the FNA was diploid in each case, and flow cytometry of paraffin-embedded tissue was diploid in 5/6 cases. In tumor positive cases, non-diploid tumor was detected by image cytometry of the FNA in 70%, by flow cytometry of the FNA in 29%, and by flow cytometry of paraffin-extracted nuclei in 21%. The most effective combination was sampling fine-needle aspiration and image analysis.

Adenocarcinoma↗

Fine needle aspiration of the breast for diagnosis of preinvasive neoplasia.

Fine needle aspiration (FNA) of the breast is a well-tolerated procedure used to evaluate palpable breast masses, has a reported mean specificity of 99%, and a reported sensitivity of 70-99%. The false positive rate varies from 0-0.4% in most larger series, with a reported false negative rate ranging from 0.7-22%; however, higher false negative rates have been reported in tumors under 2 cm in diameter. The FNA technique uses a fine, 20 gauge or less, needle and is not associated with a significant risk of tumor growing out the needle tract. FNA cytology is not effectively used if a breast mass cannot be palpated or distinguished from fibrous tissue within the breast. The procedure can be applied to nonpalpable masses detected by mammography by employing stereotactic techniques. The cytologic samples obtained from FNA can be used to distinguish atypical ductal hyperplasia from in situ or invasive ductal carcinoma; however, cytologic criteria to effectively distinguish ductal carcinoma in situ (DCIS) from invasive adenocarcinoma are not definitive in many cases, and are dependent on variables related to the type of intraductal tumor, the size and character of the cell groups, and the presence of single or disaggregated tumor cells. Employing current cytologic criteria, lobular carcinoma in situ (LCIS) may be distinguished from invasive lobular carcinoma in some cases; however, the individual LCIS cells are not morphologically distinct from lobular carcinoma cells. Atypical lobular hyperplasia has cellular features essentially the same as those seen in LCIS. Needle biopsy (NB) employs larger needles of 14-16 gauge.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy, Needle↗

Tissue section image analysis of breast neoplasms. Evidence of false aneuploidy.

Two methods have emerged for measuring the DNA content of paraffin-embedded tissue using image cytometry: (1) analysis of thin sections, and (2) analysis of nuclei extracted from thick sections. These methods were evaluated using 31 breast tumors for which paraffin-embedded material was available. Cases selected represented 11 diploid, 11 tetraploid, and 9 aneuploid tumors. Results generated using image cytometry methods were compared with those obtained using flow cytometry. For thin sections, the tissue correction feature of the CAS 200 Image Cytometer was used to estimate the DNA content of whole nuclei from measurements made on sectioned nuclei. DNA histograms were generated from tissue sections cut at the same microtome setting (5 microns) before and after software corrections of 4.5 microns, 5.0 microns, 5.5 microns, 6.0 microns. 6.5 microns, 7.0 microns, and 7.5 microns. A comparison of flow cytometry and thin-section image analysis in the absence of tissue correction showed 90% concordance for diploid, 27% concordance for tetraploid, and 77% concordance for aneuploid tumors. The ploidy estimated on thin sections by at least one of the correction values was discordant in 72% of diploid, 91% of tetraploid, and 78% of aneuploid tumors. For cell nuclei extracted from paraffin, excellent agreement was found between flow and image cytometry (r = 0.933). It was concluded that in most cases, cell nuclei extracted from paraffin are preferable to tissue sections for ploidy analysis of breast tumors using image cytometry.

Aneuploidy↗

Vulvar vestibulitis is rarely associated with human papillomavirus infection types 6, 11, 16, or 18.

Vulvar vestibular biopsy specimens from 31 women with clinical and pathologic findings of vulvar vestibulitis were studied using polymerase chain reaction (PCR) for the identification of human papilloma virus (HPV). The PCR technique specifically probed for HPV types 6, 11, 16, and 18. Of the 31 subjects, three were found to have HPV within the biopsy specimens; two had HPV type 11 and one had HPV 16. Five of the 31 cases had histopathologic features of koilocytosis consistent with HPV effect; three of these five were found to have HPV. The findings support the hypothesis that HPV types 6, 11, 16, and 18 are rarely associated with vulvar vestibulitis. The frequencies identified were similar to those seen with control patients. True koilocytosis is the most useful pathologic feature distinguishing HPV-related cases; it is rarely identified in typical vulvar vestibulitis. Nonspecific changes in the vestibular epithelium associated with glycogen effect should not be interpreted as koilocytosis.

Adult↗

Comparison of two antibodies for evaluation of estrogen receptors in paraffin-embedded tumors.

Estrogen receptor (ER) content in breast cancer specimens is correlated with a prolonged disease free survival and increased likelihood of response to hormone therapy. Relatively few anti-ER antibodies are currently available for use in formalin-fixed, paraffin-embedded tissue. Recently, a new anti-ER monoclonal antibody (ERID5; AMAC, Westbrook, Maine) was generated which requires antigen retrieval by microwave oven heating for detection in routinely processed tissue. The specific aim of this study was to compare the ERID5 antibody with the commercially available rat monoclonal (ER-ICA; Abbott, Chicago, IL) which requires proteolytic enzyme digestion for detection in paraffin-embedded tissue. Sections from 20 cases of primary breast carcinoma previously assayed by dextran-coated charcoal (DCC) analysis were examined. Quantitation of ER antibody staining was performed without knowledge of the DCC values. Specimens containing > or = 20% specifically stained malignant cells were considered ER positive. The sensitivity and specificity of visual ER-ICA immunostaining were 57% and 83%, respectively. The sensitivity and specificity of visual ERID5 immunostaining were 93% and 50%, respectively. The predictive value of positive staining was 89% for the ER-ICA antibody and 81% for the ERID5 antibody. The predictive value of negative staining was 45% for the ER-ICA antibody and 75% for the ERID5 antibody. Previous studies have demonstrated a linear correlation between DCC values and the positive nuclear area (PNA) generated by image analysis for ER-ICA immunostaining. In the present study, a similar correlation between DCC value and ERID5 percentage PNA was observed (R = 0.670; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A method for detecting variability arising from errors in sample processing of paraffin-embedded tissue for DNA content analysis.

We present a method for controlling variability that may arise from inconsistencies in sample preparation for DNA content analysis of paraffin-embedded tissue. Human tonsil tissue obtained from routine surgical specimens was embedded in paraffin according to standard protocols. Fifty-micrometer sections were cut from the block and analyzed each day for 20 days to establish control ranges. One tonsil tissue section was processed in parallel with each run of clinical specimens. In this context, a run was defined as the simultaneous processing of 50-microns tissue sections for extraction of cell nuclei (dewaxing and rehydrating). If the tonsil G0/G1 peak coefficient of variation (CV) exceeded 2 SDs of the established mean, and optimum instrument performance and staining were verified, all samples prepared with the tonsil control were reprocessed. Instrument performance and staining were assessed by using the appropriate external controls. By using this rejection rule (12s), the frequency of sample reprocessing in our laboratory was approximately 6%. When the run was repeated and the tonsil control CV was within acceptable range, the G0/G1 peak CV of the corresponding clinical specimens improved 25% of the time. Because most investigators are willing to accept higher CVs for paraffin-embedded tissue than for fresh tissue, it is desirable to have a control to detect decreased peak resolution, resulting from errors in sample processing.

Cell Nucleus↗

Quantitative morphologic assessment of nuclei extracted from paraffin for DNA flow cytometry.

We present a method for quality control of flow cytometric DNA content studies using nuclei extracted from paraffin-embedded tissue. This method is based on a quantitative morphologic assessment of extracted nuclei. Cell nuclei prepared from 22 paraffin-embedded tumors known to contain discrete diploid and aneuploid stemlines were deposited onto poly-L-lysine-coated glass slides. Nuclei were stained with Diff-quic and examined by light microscopy. Two hundred nuclei were counted and classified based on morphologic appearance into tumor and nontumor groups. Classification criteria included differences in nuclear size, nuclear chromatin structure, the degree of nuclear chromatin condensation, and the presence of nucleoli. Excellent agreement was found between two independent observers (R = 0.989) on the classification of nuclei. The relative number of tumor nuclei on the morphologic preparation was compared with the relative number of aneuploid cells in the DNA histogram. Good agreement was observed (R = 0.975) in all but three cases in which the relative number of tumor nuclei was underrepresented by the percentage of aneuploid nuclei in the DNA histogram. In each case, further analysis by image cytometry demonstrated a diploid and aneuploid component of the tumor cell population. This quantitative method of morphologic examination of the preparation ultimately analyzed by flow cytometry offers several distinct advantages, including: (a) identification of peaks in the DNA histogram, (b) assessment for selective loss of cell nuclei in the extraction process, and (c) identification of biologic heterogeneity in tumor populations.

Cell Nucleus↗

Cervical neoplasia. Its association with human papillomavirus infection.

Almost 70 human papillomavirus (HPV) types have been identified. An estimated one-third are anogenital associated. Their presence in the genital tract is associated with cancer, and certain particular types have a high correlation with cervical intraepithelial neoplasia (CIN) and carcinoma. Although a spectrum of histopathologic features within the epithelium characterize changes caused by HPV infection, only DNA analysis accurately detects and determines the type of infection. The variety of molecular methods for detection of HPV DNA primarily reveal whether or not a lesion is in fact associated with HPV infection. For minor grade cervical squamous lesions or equivocal Pap smear results, HPV detection and typing can help identify patients at increased risk for cervical carcinoma. Cervical colposcopy and biopsy are indicated for definitive diagnosis.

Female↗

Normal histology and nomenclature of the vulva, and malignant neoplasms, including VIN.

In this article, vulvar anatomy and histology are reviewed, and nonneoplastic and neoplastic epithelial disorders are presented. Included are lichen sclerosus, squamous cell hyperplasia, vulvar intraepithelial neoplasia, vulvar Paget's disease, and squamous cell carcinoma. Current terminology, tumor measurements, and staging for vulvar carcinoma are reviewed.

Carcinoma, Squamous Cell↗

Postpartum vaginal atrophy.

Postpartum vaginal atrophy has been briefly noted without adequate clinical description. We present a study of 215 puerperas at a scheduled 4-week postpartum visit, investigating colorpHast vaginal pH, vestibular cotton swab testing, vaginal wall tenderness, and both fixed and wet mount cytologic studies. Thirty-seven patients with vaginal atrophy (17.2%) had a mean pH of 6.55 with a mean maturation index of 49.2% parabasal, 46.5% intermediate, and 4.3% superficial cells. Eighty patients (37.2%) served as control subjects, with a mean maturation index of 0.3% parabasal, 73.6% intermediate, and 26.1% superficial cells, and a mean vaginal pH of 4.68. Ninety-eight patients (45.6%) were excluded for multiple confounding conditions, the most common of which was bacterial vaginosis in 37 (17.2%). This study demonstrates the existence of postpartum vaginal atrophy, notes lactation as an apparent causal factor, and establishes a statistically significant (p less than 0.0001) relationship between vaginal pH and maturation index. Further studies are needed to confirm therapeutic efficacy of estrogens.

Atrophy↗

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↗

Pathology of the vagina.

This review summarizes key articles published in 1990 relevant to abnormalities of the vagina. The subjects covered include vaginal squamous neoplasia, including epidemiologic characteristics, vaginal intraepithelial neoplasia, superficially invasive carcinoma of the vagina, and the expression of epidermal growth factor and HER-2neu in normal and neoplastic epithelium. Clear cell adenocarcinoma is discussed, and recent epidemiologic factors distinguishing vaginal from cervical clear cell adenocarcinoma, as they are related to in utero diethylstilbestrol exposure, are presented. Small cell neuroendocrine carcinoma of the Bartholin's gland, presenting as a vaginal mass, is documented in a reviewed case report. A series of primary malignant melanomas of the vagina are presented and clinical and pathologic features, as well as survival data and factors influencing survival are presented. Three studies on vaginal fibroepithelial polyps, clinical and pathologic evaluations, as well as differential diagnosis and concepts of origin, are reviewed. These findings provide new insights into the understanding of the properties of the subepithelial stroma of the lower female genital tract and its capacity to change in pregnancy and the postpartum state.

Adenocarcinoma↗

Techniques and results of aspiration cytology for diagnosis of benign and malignant diseases of the breast.

The use of fine needle aspiration to obtain cellular material for pathologic examination was introduced in 1930 but fell out of favor for several years. In today's medical environment, fine needle aspiration is proving to be more efficacious and cost effective than conventional breast biopsy. The authors detail the technique, its complications, the reliability of the results and ways to improve it, and the suitability of the material for hormone receptor assays, detection of tumor-related problems, and ultrastructural study as well as for standard cytologic diagnosis.

Biopsy, Needle↗