Vaginal intraepithelial neoplasia (VaIN 2/3): comparing clinical outcomes of treatment with intravaginal estrogen.

OBJECTIVE: To determine the outcomes of women treated for vaginal intraepithelial neoplasia grade 2/3 (VaIN 2/3) with intravaginal estrogen. MATERIAL AND METHODS: A retrospective chart review was performed of 106 patients with VaIN 2/3 evaluated at a single institution between 2000 and 2008. Medical records were reviewed for demographic information, risk factors, HPV status, treatment type, pathologic diagnosis, and outcome information. Patients with VaIN 1 and invasive disease at the time of initial presentation were excluded. In addition, patients who were lost to follow-up or who developed other genital tract malignancies during the study period were excluded from the final analysis. RESULTS: After exclusions, 83 patient records were included in the statistical analysis. The mean age at diagnosis was 54.3 years. Of these patients, 88.0% were postmenopausal and 88.0% had undergone previous hysterectomy. Moreover, 63.9% of the patients reported previous treatment for preinvasive disease (cervical, vaginal, or vulvar dysplasia). Of all the patients, 44.6% reported prior and/or current tobacco use and 48.2% tested positive for high-risk HPV types. Treatment modalities included intravaginal estrogen, CO(2) laser ablation, topical 5-fluorouracil, wide local excision, loop electrosurgical excision procedure, and vaginectomy. Some patients underwent more than 1 treatment modality. Of those patients treated with intravaginal estrogen alone (n = 40), 90.0% had regression or cure of high grade disease. Of those patients treated with intravaginal estrogen and 1 or more other treatment modalities (n = 32), 81.3% experienced regression or cure. In contrast, 71.4% of patients undergoing treatment without intravaginal estrogen experienced regression or cure of high-grade disease. Conditions of 2 patients progressed to invasive vaginal carcinoma during the study period. The mean length of follow-up for all patients was 47.6 months. CONCLUSIONS: This cohort of women with VaIN 2/3 further delineates the demographic and clinical risk factors associated with VaIN 2/3. High rates of regression and cure were found in patients treated with intravaginal estrogen, whether alone or in combination with other treatment modalities. Treatment of VaIN 2/3 with intravaginal estrogen therapy offers an alternative to standard therapies with a success rate that is comparable to that previously reported with other more potentially morbid therapies.

Risk of residual disease and invasive carcinoma in women treated for adenocarcinoma in situ of the cervix.

OBJECTIVE: Cervical adenocarcinoma in situ (AIS) is increasing in incidence among reproductive-age women. Cervical conization is an alternative to hysterectomy that allows future fertility, however reports regarding the risk of residual AIS and underlying adenocarcinoma are conflicting. The purpose of this study was to determine the outcomes of a large cohort of women treated for AIS. METHODS: The medical records of 180 women with cervical AIS evaluated at the University of Texas MD Anderson Cancer Center and its outlying clinics between 1983 and 2011 were reviewed for demographic information, treatment history, pathologic findings and outcomes. RESULTS: The mean age at diagnosis was 33.8years (range 17.6-76.1years). 172 of the 180 women had at least one cone biopsy performed, with 110 (64.0%) undergoing a cold knife cone (CKC), and 62 (36.0%) undergoing a loop electrosurgical excision procedure (LEEP) as their initial method of treatment. Positive margins were noted in 35.0% of patients undergoing CKC compared with 55.6% undergoing LEEP (p=0.017). 71 patients ultimately underwent hysterectomy with residual disease noted in 10 patients (14.1%), 8 patients (11.3%) with residual AIS and 2 patients (2.8%) with invasive carcinoma. Of the 101 patients who did not undergo hysterectomy, 2 patients (2.0%) developed recurrent AIS at a median of 27.5months (range 18-37months) from the last cone, and none developed invasive carcinoma. CONCLUSION: Patients undergoing conservative management for AIS with cervical conization alone should be monitored closely and counseled regarding the potential risks of residual and recurrent disease, even when negative cone margins are obtained.

Verruciform xanthoma in an adolescent: a case report.

BACKGROUND: Verruciform xanthoma is a benign mucocutaneous, verrucous, papillary lesion characterized by large foam cells in the parakeratotic layer, lipid-laden macrophages (xanthoma cells), epidermal hyperplasia, and hyperkeratosis. Verruciform xanthoma is thought to be a reactive rather than a neoplastic process secondary to epithelial damage and the presence of foamy histiocytes. The human papillomavirus has not been proven to be a causative factor. Differential diagnoses include verrucous carcinoma, condyloma acuminatum, seborrheic keratosis, verruca simplex, and vulvar intraepithelial neoplasia. CASE: We describe the clinical and pathologic findings of a 16-year-old girl with verruciform xanthoma of the vulva, the third such reported case in an adolescent girl. COMMENT: It is important to recognize this rare entity because it can mimic many other conditions, and the usual treatment modalities for wartlike growths on the vulva (i.e., imiquimod, podophyllin, and trichloroacetic acid) are not effective. Wide local excision seems to be the only effective and curative treatment modality for verruciform xanthoma, as has been reported in the literature and is such with our case.

Progress in chemoprevention drug development: the promise of molecular biomarkers for prevention of intraepithelial neoplasia and cancer--a plan to move forward.

This article reviews progress in chemopreventive drug development, especially data and concepts that are new since the 2002 AACR report on treatment and prevention of intraepithelial neoplasia. Molecular biomarker expressions involved in mechanisms of carcinogenesis and genetic progression models of intraepithelial neoplasia are discussed and analyzed for how they can inform mechanism-based, molecularly targeted drug development as well as risk stratification, cohort selection, and end-point selection for clinical trials. We outline the concept of augmenting the risk, mechanistic, and disease data from histopathologic intraepithelial neoplasia assessments with molecular biomarker data. Updates of work in 10 clinical target organ sites include new data on molecular progression, significant completed trials, new agents of interest, and promising directions for future clinical studies. This overview concludes with strategies for accelerating chemopreventive drug development, such as integrating the best science into chemopreventive strategies and regulatory policy, providing incentives for industry to accelerate preventive drugs, fostering multisector cooperation in sharing clinical samples and data, and creating public-private partnerships to foster new regulatory policies and public education.

Abnormal Uterine Bleeding as the Presenting Symptom of Hematologic Cancer.

OBJECTIVE: To estimate the percentage of women with a hematologic cancer who present with abnormal uterine bleeding (AUB). METHODS: We performed a retrospective analysis of the records of women with hematologic malignancies treated at our institution from January 2002 through January 2016. Women with AUB as the chief presenting symptom were identified. RESULTS: Of the 10,682 women with hematologic malignancies, 38 had AUB as their chief presenting symptom. These women were young (median age 34 years), premenopausal, and otherwise healthy. The top four additional presenting symptoms were fatigue, dyspnea or shortness of breath, bruising or petechiae, and fever, with means (95% confidence interval) of 58% (41-74%), 42% (26-59%), 42% (26-59%), and 24% (11-40%), respectively. The complete blood count on initial presentation with AUB revealed that 33 (87%) women had anemia (mean hemoglobin level 8.6 g/dL) and 34 (89%) had thrombocytopenia (mean platelet count 81,000/microliter). Twelve (32%) women had neutropenia, eight (21%) women had normal white blood cell counts, and 18 (47%) women had leukocytosis. Thirty-three women (87%) were diagnosed with acute leukemia, one with myelodysplastic syndrome (3%) and four (11%) with chronic leukemia. CONCLUSION: We estimate the incidence of AUB as the chief presenting symptom is 3.6 cases per 1,000 women with hematologic cancer. These young, otherwise healthy women who present with acute, new-onset heavy menstrual bleeding in conjunction with thrombocytopenia or pancytopenia should be referred to hematology for evaluation of possible hematologic malignancy.