Edward J. Wilkinson

Histological typing of female genital tract tumours

Histological Classification of Tumours of the Female Genital Tract Definitions and Explantory Notes Uterine Corpus Gestational Trophoblastic Disease Uterine Cervic Vagina Vulva Illustrations Subject Index

The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology.

Abstract The terminology for human papillomavirus (HPV)–associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) Project was cosponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology and included 5 working groups; 3 work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation of the LAST recommendations. After an open comment period, the draft recommendations were presented at a consensus conference attended by LAST work group members, advisors, and representatives from 35 stakeholder organizations including professional societies and government agencies. Recommendations were finalized and voted on at the consensus meeting. The final, approved recommendations standardize biologically relevant histopathologic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive squamous carcinomas across all lower anogenital tract sites and detail the appropriate use of specific biomarkers to clarify histologic interpretations and enhance diagnostic accuracy. A plan for disseminating and monitoring recommendation implementation in the practicing community was also developed. The implemented recommendations will facilitate communication between pathologists and their clinical colleagues and improve accuracy of histologic diagnosis with the ultimate goal of providing optimal patient care.

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.

The Lower Anogenital Squamous Terminology Standardization project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology.

The terminology for human papillomavirus (HPV)-associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) project was co-sponsored by the College of American Pathologists (CAP) and the American Society for Colposcopy and Cervical Pathology (ASCCP) and included 5 working groups; three work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation of the LAST recommendations. After an open comment period, the draft recommendations were presented at a consensus conference attended by LAST work group members, advisors and representatives from 35 stakeholder organizations including professional societies and government agencies. Recommendations were finalized and voted upon at the consensus meeting. The final approved recommendations standardize biologically-relevant histopathologic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive squamous carcinomas across all lower anogenital tract sites and detail appropriate use of specific biomarkers to clarify histologic interpretations and enhance diagnostic accuracy. A plan for disseminating and monitoring recommendation implementation in the practicing community was also developed. The implemented recommendations will facilitate communication between pathologists and their clinical colleagues and improve accuracy of histologic diagnosis with the ultimate goal of providing optimal patient care.

US Assessment of HPV Types in Cancers: Implications for Current and 9-Valent HPV Vaccines

BACKGROUND This study sought to determine the prevaccine type-specific prevalence of human papillomavirus (HPV)-associated cancers in the United States to evaluate the potential impact of the HPV types in the current and newly approved 9-valent HPV vaccines. METHODS The Centers for Disease Control and Prevention partnered with seven US population-based cancer registries to obtain archival tissue for cancers diagnosed from 1993 to 2005. HPV testing was performed on 2670 case patients that were fairly representative of all participating cancer registry cases by age and sex. Demographic and clinical data were evaluated by anatomic site and HPV status. Current US cancer registry data and the detection of HPV types were used to estimate the number of cancers potentially preventable through vaccination. RESULTS HPV DNA was detected in 90.6% of cervical, 91.1% of anal, 75.0% of vaginal, 70.1% of oropharyngeal, 68.8% of vulvar, 63.3% of penile, 32.0% of oral cavity, and 20.9% of laryngeal cancers, as well as in 98.8% of cervical cancer in situ (CCIS). A vaccine targeting HPV 16/18 potentially prevents the majority of invasive cervical (66.2%), anal (79.4%), oropharyngeal (60.2%), and vaginal (55.1%) cancers, as well as many penile (47.9%), vulvar (48.6%) cancers: 24 858 cases annually. The 9-valent vaccine also targeting HPV 31/33/45/52/58 may prevent an additional 4.2% to 18.3% of cancers: 3944 cases annually. For most cancers, younger age at diagnosis was associated with higher HPV 16/18 prevalence. With the exception of oropharyngeal cancers and CCIS, HPV 16/18 prevalence was similar across racial/ethnic groups. CONCLUSIONS In the United States, current vaccines will reduce most HPV-associated cancers; a smaller additional reduction would be contributed by the new 9-valent vaccine.

Microinvasive carcinoma of the vulva.

Thirty cases of microinvasive squamous cell carcinoma of the vulva were seen from 1972 to 1978 inclusive. They comprised 37.7% of 77 cases of squamous carcinoma of the vulva seen during this period of time. The results of analysis of multiple factors, including tumor depth and pattern of invasion, nuclear and histologic grade, volume, inflammatory response, presence of vascular invasion, and depth of invasion as compared to the depth of adjacent skin appendages and rete ridges are presented. Two patients were found to have inginual lymph node metastasis: in one of these patients the tumor was deeper than the adjacent deepest skin appendages while in the second patient skin appendages were not adjacent to the tumor. These tumors measured 2.25 and 1.8 mm in depth, respectively. In both patients the tumor was of high nuclear grade and had a diffuse pattern of infiltration. No nodal metastases were found in patients whose tumors did not invade deeper than 1.5 mm or deeper than the adjacent deepest skin appendage. Tumors measuring 1.5 mm in depth had tumor volumes under 1,000 mm3. The only death from tumor that occurred in this series occurred in a woman who had a second primary tumor of the vulva following a local excision for her microinvasive carcinoma. The definition and measurements of microinvasive carcinoma of the vulva are discussed and an improved method of measurement is proposed.

The histopathology of vulvar vestibulitis syndrome.

Forty-one cases of vulvar vestibulitis syndrome are presented. All cases were studied to provide a histopathological description of this condition in terms of location, intensity, and characterization of the inflammatory response. Alterations of the normal histology of minor vestibular glands forming vestibular clefts are described. The association of this condition with other disease processes, and special studies done to elucidate an etiology, are discussed.

Unrecognized invasive carcinoma in vulvar intraepithelial neoplasia (VIN).

Sixty-nine patients having had pretreatment biopsy diagnosis of vulvar intraepithelial neoplasia were treated with surgical excision of all visible lesions. Complete surgical specimens were submitted for pathological study in an attempt to identify occult invasive vulvar carcinoma. Unsuspected invasion was noted in 13 patients (18.8%). Superficial invasion (less than 1 mm) was seen in 8 patients, 4 had greater than 1 mm of invasion, and one verrucous carcinoma was identified. Patients of advancing age with disease that had a raised and irregular surface pattern were more likely to have lesions with occult invasion. Treatment that utilizes ablative techniques cannot be recommended based on the use of preoperative representative biopsies.

Review of Terminology of Precursors of Vulvar Squamous Cell Carcinoma

Abstract: 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 Diseases 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.

Alpha-fetoprotein and endodermal sinus tumor of the ovary

A patient with endodermal sinus tumor of the ovary was studied with serial alpha-fetoprotein (AFP) serum determinations. Serum AFP levels were found to correlate with the size of palpable tumor. The origin of AFP in patients with endodermal sinus tumor of the ovary is explored and the 9 previously reported patients with these findings are reviewed. AFP determination may serve as an indication of endodermal sinus tumor of the ovary as well as a monitor of therapeutic progress.