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Biomedical subjects

Edward J Wilkinson

Publications and source records attributed to Edward J Wilkinson.

At least 19 recordsLinked to original sources

Review of terminology of precursors of vulvar squamous cell carcinoma.

The popular term for vulvar squamous cell carcinoma in situ/dysplasia is vulvar intraepithelial neoplasia (VIN). VIN is a histological diagnosis based on loss of squamous epithelial maturation associated with enlarged, hyperchromatic, pleomorphic nuclei and increased, usually atypical mitoses. There are two types of VIN: the usual (not otherwise specified) type, also known as warty-basaloid, and the differentiated type. There are 3 grading systems for warty-basaloid VIN: the traditional 3-grade system of VIN 1-3, a low-grade/high grade Bethesda-like system and the International Society for the Study of Vulvovaginal Disease's proposal for only 1 grade. The ISSVD system eliminates VIN 1 and combines VIN 2 and 3 on the grounds that VIN 1 has not been shown to be a reproducible diagnosis and VIN 2 and 3 are not reliably separated. The evidence supports the ISSVD proposal. Warty basaloid VIN may be sub-typed into warty and basaloid VIN. Sub-typing has clinical relevance but its reproducibility is not proven. Warty-basaloid VIN may regress. Differentiated VIN has been typically diagnosed co-incident with squamous cell carcinoma. With increased frequency of performance of biopsy of hyperplastic lesions, differentiated VIN should be diagnosed more commonly before squamous carcinoma occurs.

Carcinoma in Situ↗

The vulvodynia guideline.

OBJECTIVE: To provide a review of the literature and make known expert opinion regarding the treatment of vulvodynia. MATERIALS AND METHODS: Experts reviewed the existing literature to provide new definitions for vulvar pain and to describe treatments for this condition. RESULTS: Vulvodynia has been redefined by the International Society for the Study of Vulvovaginal Disease as vulvar discomfort in the absence of gross anatomic or neurologic findings. Classification is based further on whether the pain is generalized or localized and whether it is provoked, unprovoked, or both. Treatments described include general vulvar care, topical medications, oral medications, injectables, biofeedback and physical therapy, dietary changes with supplementations, acupuncture, hypnotherapy, and surgery. No one treatment is clearly the best for an individual patient. CONCLUSIONS: Vulvodynia has many possible treatments, but very few controlled trials have been performed to verify efficacy of these treatments. Provided are guidelines based largely on expert opinion to assist the patient and practitioner in dealing with this condition.

Administration, Oral↗

Association between invasive squamous cell carcinoma of the vulva and ABO blood group.

OBJECTIVE: To determine whether the distribution of ABO blood group among women with invasive squamous cell carcinoma (SCC) of the vulva is different from that among a population of women treated for nonneoplastic gynecologic disease. METHODS: A retrospective analysis of pathology reports and blood bank records from January 1996 through September 2003 was performed. The distribution of ABO blood group for 33 women diagnosed with invasive SCC of the vulva was determined. ABO blood group was also recorded for 100 female patients (controls) who underwent a gynecologic procedure for a nonneoplastic process during the period January 2003 through November 2003. The blood group phenotype distribution for the study groups and the controls was compared by an incidence ratio. RESULTS: Statistical analysis gave an incidence ratio for blood group types A and O of 1.55 (p < .20) when the patients with invasive SCC of the vulva were compared with the controls. The p value was not significant. Similarly, the incidence ratio for blood group types B and O equaled 0.386 (p = 1). Again the p value was not significant. In fact, none of the incidence ratios calculated were statistically significant. Although not statistically significant, the incidence ratio for the invasive vulvar SCC group was >1. This may indicate that there is a trend for women with invasive SCC of the vulva to have blood group type A. CONCLUSIONS: Results of this study do not suggest an association between blood group type A, or any other blood group, and vulvar SCC. This study was similar in patient size to another study (33 patients with vulvar SCC vs. 39 patients with vulvar SCC, respectively). The disparity of the results in determining the significance of blood group type A as an associated factor for vulvar SCC in this and the other study may be due to the limited size of the study populations. Additional investigation is needed to further evaluate this issue.

ABO Blood-Group System↗

Human papillomavirus infection and p16(INK4a) protein expression in vulvar intraepithelial neoplasia and invasive squamous cell carcinoma.

OBJECTIVE: Vulvar intraepithelial neoplasia (VIN) is defined histopathologically by distinctive abnormalities of cellular maturation and differentiation. The purpose of this study was to investigate the functional properties of VIN related to expression of p16(INK4a) protein as well as to detection of human papillomavirus (HPV) type 16 by real-time polymerase chain reaction (RT-PCR) analysis. METHODS: A total of 49 vulvar biopsy samples were examined by hematoxylin-eosin staining from benign/reactive lesions, condyloma acuminatum, VIN, and invasive squamous cell carcinoma (SCC). JC8 mouse monoclonal antibodies were used that recognize p16(INK4a) epitope at a dilution of 1:25. The reaction pattern for p16(INK4a) was graded in each sample between 0 and 3+. RT-PCR analysis of formalin-fixed paraffin-embedded sections determined positivity for HPV type 16. RESULTS: p16(INK4a) immunoreactivity was different in VIN 1, VIN 2, VIN 3, and squamous cell carcinoma. Strong expression of p16(INK4a) protein was observed in 92% (22 of 24) of VIN 2 and VIN 3 lesions and 100% (4 of 4) of invasive SCCs. Two (67%) of 3 VIN 2 lesions, 17 (81%) of 21 VIN 3 lesions, and 4 (100%) of 4 SCCs were positive for HPV type 16 by PCR analysis. Two (20%) of 10 VIN 1 lesions were immunoreactive for p16(INK4a), with only 1 lesion positive for HPV type 16. No p16(INK4a) immunoreactivity was observed in any of the benign/reactive and condyloma acuminatum lesions. In addition, none of the benign/reactive or condyloma lesions were positive for HPV type 16 by RT-PCR analysis. CONCLUSIONS: Upregulation of INK4a gene occurs in vulvar carcinogenesis. p16(INK4a) is not a sensitive marker for differentiation of benign vulvar squamous epithelium from condyloma acuminatum or VIN 1 lesions because most VIN 1 lesions are p16(INK4a) negative. Expression of p16(INK4a) may aid in the diagnosis of HPV-related lesions and as such may be of value as a surrogate marker in the diagnosis of vulvar premalignant and malignant lesions.

Adult↗

Uterine-like mass with features of an extrauterine adenomyoma presenting 22 years after total abdominal hysterectomy-bilateral salpingo-oophorectomy: a case report and review of the literature.

Adenomyoma is a benign tumor composed of smooth muscle and benign endometrium. These tumors typically originate within the uterus. An extrauterine adenomyoma is a rare entity. We report a uterine-like mass consistent with an extrauterine adenomyoma presenting 22 years following a total abdominal hysterectomy and bilateral salpingo-oophorectomy. The mass was pear-shaped with uterine-type smooth muscle and a cavity lined by functional endometrial glands and stroma. To our knowledge, only 4 other cases of an extrauterine uterine-like mass are reported in the literature. Three involved the ovary, while one was located adjacent to the broad ligament with normal pelvic organs. Although none of these other uterus-like masses were described as adenomyomas with uterine-like features, the histologic findings are strikingly similar. An understanding of the müllerian system suggests that either an embryologic malformation or a differential multipotentiality existing in the subcoelomic tissues in response to hormonal stimulation results in a supernumerary müllerian structure like a uterus, as observed in this case. The presence of endometrial glands and stroma in the mass confirms that the tissues in this mass are hormonally responsive. It is most likely that this uterine-like mass arose from the tissues of the secondary müllerian system in response to estrogenic stimulation.

Adenomyoma↗

Squamous vulvar intraepithelial neoplasia: 2004 modified terminology, ISSVD Vulvar Oncology Subcommittee.

In the current classification, squamous vulvar intraepithelial neoplasia (VIN) is categorized as VIN 1, 2 and 3 according to the degree of abnormality. There is neither evidence that the VIN 1-3 morphologic spectrum reflects a biologic continuum nor that VIN 1 is a cancer precursor. The VIN 2 and 3 category includes 2 types of lesion, which differ in morphology, biology and clinical features. VIN, usual type (warty, basaloid and mixed), is HPV related in most cases. Invasive squamous carcinomas of warty or basaloid type is associated with VIN, usual type. VIN, differentiated type, is seen particularly in older women with lichen sclerosus and/or squamous cell hyperplasia in some cases. Neither VIN, differentiated type, nor associated keratinizing squamous cell carcinoma is HPV related. The term VIN should apply only to histologically high grade squamous lesions (former terms, VIN 2 and VIN 3 and differentiated VIN 3). The term VIN 1 will no longer be used. Two categories should describe squamous VIN: VIN, usual type (encompassing former VIN 2 and 3 of warty, basaloid and mixed types) and VIN, differentiated type (VIN 3, differentiated type).

Carcinoma, Squamous Cell↗

Primary adenocarcinoma of the vagina with mucinous-enteric differentiation: a report of two cases with associated vaginal adenosis without history of diethylstilbestrol exposure.

Primary adenocarcinoma of the vagina is rare, and mucinous-enteric differentiation is exceptional. A few sporadic cases of primary vaginal adenocarcinoma with mucinous-enteric differentiation have been reported. Reports of the clinical histories, pathologic findings, and immunohistochemical studies of two cases of primary vaginal adenocarcinomas in a 67-year-old and in a 45-year-old woman are presented. Knowledge of the differentiation of Mullerian epithelium and immunohistochemistry studies are helpful to better characterize these tumors.

Journal Article↗

2001 consensus guidelines for the management of women with cervical intraepithelial neoplasia.

OBJECTIVE: The study was undertaken to provide consensus guidelines for the management of women with histologically confirmed cervical intraepithelial neoplasia (CIN) that can act as a precursor to invasive cervical cancer and represents one of the most common significant gynecologic diseases of women of reproductive age. PARTICIPANTS: An independent panel of 121 experts in various aspects of the diagnosis and management of cervical cancer precursors, including representatives from 29 participating professional organizations, federal agencies, national and international health organizations, and others were invited by the American Society for Colposcopy and Cervical Pathology (ASCCP). CONSENSUS PROCESS: Guidelines for the management of women with CIN were developed through a multistep process. Draft management guidelines were developed by working groups who performed formal literature reviews and obtained input from the professional community at large by way of an interactive internet-based bulletin board. At the ASCCP Consensus Conference, September 6 through 8, 2001, in Bethesda, Md, all guidelines were discussed, revised, and adopted by formal vote. CONCLUSION: Evidence-based guidelines have been developed for the management of women with biopsy-confirmed CIN.

Biopsy↗

Vulvar paget disease: one century after first reported.

OBJECTIVES.: To provide a critical assessment of the published literature on vulvar Paget disease and to allow individualized approaches to affected patients. MATERIALS AND METHODS.: A computerized search for studies published in the literature up to June 2002 was carried out using Ovid(c) and Medline databases. We excluded single case reports, letters to editors, and abstracts. RESULTS.: Historical and epidemiological aspects of vulvar Paget disease are summarized. Clinical and histopathological data support a recent proposal to classify vulvar Paget disease into two categories, primary and secondary, with significant clinical and prognostic implications. The treatment for primary vulvar Paget disease is wide and deep surgical excision. Inguinofemoral lymphadenectomy is added in the management of invasive neoplasms. In the presence of secondary Paget disease, therapy must be directed toward treatment of associated carcinoma. CONCLUSIONS.: The subclassification of vulvar Paget disease is essential for correct clinical management and treatment. Immunohistochemistry may assist in this important distinction.

Journal Article↗

2001 Consensus guidelines for the management of women with cervical intraepithelial neoplasia.

OBJECTIVE: To provide consensus guidelines for the management of women with histologically confirmed cervical intraepithelial neoplasia (CIN), which can act as a precursor to invasive cervical cancer and represents one of the most common significant gynecologic diseases of women of reproductive age. PARTICIPANTS: An independent panel of 121 experts in various aspects of the diagnosis and management of cervical cancer precursors, including representatives from 29 participating professional organizations, federal agencies, national and international health organizations, and others invited by the American Society for Colposcopy and Cervical Pathology (ASCCP). CONSENSUS PROCESS: Guidelines for the management of women with CIN were developed through a multistep process. Working groups, who performed formal literature reviews and obtained input from the professional community at large by way of an interactive Internet-based bulletin board, developed draft management guidelines. At the ASCCP Consensus Conference, September 6-8, 2001, in Bethesda, Maryland, all guidelines were discussed, revised, and adopted by formal vote. CONCLUSIONS: Evidence-based guidelines have been developed for the management of women with biopsy-confirmed CIN.

Journal Article↗

2001 Consensus Guidelines for the management of women with cervical cytological abnormalities.

OBJECTIVE: To provide evidence-based consensus guidelines for the management of women with cervical cytological abnormalities and cervical cancer precursors. PARTICIPANTS: A panel of 121 experts in the diagnosis and management of cervical cancer precursors, including representatives from 29 professional organizations, federal agencies, and national and international health organizations, were invited to participate in a consensus conference sponsored by the American Society for Colposcopy and Cervical Pathology (ASCCP). EVIDENCE AND CONSENSUS PROCESS: Guidelines for the management of women with cervical cytological abnormalities were developed through a multistep process. Starting 6 months before the conference, working groups developed draft management guidelines based on formal literature reviews of English-language articles published in 1988-2001, as well as input from the professional community at large, obtained using interactive Internet-based bulletin boards. On September 6-8, 2001, the ASCCP Consensus Conference was held in Bethesda, Md. Guidelines with supporting evidence were presented and underwent discussion, revision, and voting. CONCLUSIONS: Management of women with atypical squamous cells (ASC) depends on whether the Papanicolaou test is subcategorized as of undetermined significance (ASC-US) or as cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H). Women with ASC-US should be managed using a program of 2 repeat cytology tests, immediate colposcopy, or DNA testing for high-risk types of human papillomavirus (HPV). Testing for HPV DNA is the preferred approach when liquid-based cytology is used for screening. In most instances, women with ASC-H, low-grade squamous intraepithelial lesion, HSIL, and atypical glandular cells should be referred for immediate colposcopic evaluation.

Adolescent↗

Uroplakin-III to distinguish primary vulvar Paget disease from Paget disease secondary to urothelial carcinoma.

Paget disease of the vulva can be mimicked by several disease entities histopathologically, but most of these entities can be clinically distinguished from vulvar Paget disease. However, vulvar Paget disease is in itself a heterogeneous group of epithelial neoplasms that can be similar both clinically and histopathologically. The subtypes of vulvar Paget disease include primary Paget disease arising from a pluripotent stem cell within the epithelium of the vulva, and secondary Paget disease of the vulva. Secondary vulvar Paget disease results from spread of an internal malignancy, most commonly from an anorectal adenocarcinoma or urothelial carcinoma of the bladder or urethra, to the vulvar epithelium. We have recently proposed that these lesions be classified as primary (of cutaneous origin) or secondary (of extracutaneous origin). These subtypes can present similarly as eczematoid skin lesions and may appear similar on routine hematoxylin and eosin-stained slides. Immunohistochemical studies can help differentiate between them. Our current study includes 17 patients with a pathologic diagnosis of vulvar Paget disease. We performed a panel of immunohistochemical stains, including cytokeratin (CK) 7 and 20, carcinoembryonic antigen (CEA), gross cystic disease fluid protein-15 (GCDFP-15), and uroplakin-III (UP-III). Of these 17 patients, 14 (80%) had primary intraepithelial cutaneous Paget disease, 13 without invasion and 1 with associated invasion. Three patients had urothelial carcinoma with spread to the vulva, manifesting as secondary vulvar Paget disease. Immunohistochemically, primary vulvar Paget disease is immunoreactive for CK 7 and GCDFP-15, but uncommonly for CK 20. Vulvar Paget disease secondary to anorectal carcinoma demonstrates CK 20 immunoreactivity but is usually nonreactive for CK 7 and consistently nonimmunoreactive for GCDFP-15. Vulvar Paget disease secondary to urothelial carcinoma is immunoreactive for CK 7 and CK 20 but nonimmunoreactive for GCDFP-15. In addition, we propose the use of a new, commercially available antibody, UP-III, which is specific for urothelium and, in our experience, is immunoreactive in secondary vulvar Paget disease of urothelial origin. The distinction between these 3 types of Paget and Paget-like lesions is essential in that the specific diagnosis has a significant influence on current treatment. The difference in surgical approach to the subtypes of vulvar Paget disease justifies classifying them into distinct lesions, which may be aided by the use of immunohistochemistry, including UP-III.

Biomarkers, Tumor↗