27 Association of anal dysplasia with cervical dysplasia and high-risk HPV subtypes in women

Objectives: High-risk human papillomavirus (hrHPV) infection is a necessary risk factor for cervical and anal dysplasia. Over the last five years, there is increasing evidence that the natural history of hrHPV-induced anal cancer is close to that of cervical cancer. However, evidence-based anal cancer screening recommendations are limited and thus this study aims to characterize the prevalence of cervical dysplasia in women with anal dysplasia. In this study, we aimed to identify the association of anal dysplasia with cervical dysplasia and high-risk HPV subtypes in women. Methods: A retrospective observational study was performed from January 2015 to December 2022 at an academic medical center. Women referred for anal cancer screening with Pap smears and anos-copies were evaluated for lifetime history of cervical dysplasia andfor correlation with hrHPV subtypes during screening. Multivariate logistic regression and chi-square tests were performed. Results: 114 women who underwent anal cancer screening were identified. 78 (68.4%) patients were identified to have anal dysplasia and 16 (20.5%) had high-grade anal dysplasia. Cervical cancer screening data was identified for 109 women, of which 29 (26.6%) had cervical dysplasia, however none had high-grade cervical dysplasia. 50 (43.9%) women were positive for human immunodeficiency virus (HIV). Preliminary analyses show that those with anal dysplasia are more likely to have cervical dysplasia (OR 7.30, p=0.004). Those with cervical dysplasia are more like to have high-risk anal HPV (OR 4.72, p=0.005) and anal dysplasia (OR 7.18, p=0.004). Though those with high-grade anal cytology were not found to have cervical dysplasia, women with HIV were more likely to have cervical dysplasia with high-grade anal cytology (p=0.012). Conclusions: We found that high-risk anal HPV and anal dysplasia were more likely to be found in those with cervical dysplasia. We also found that rates of anal and cervical dysplasia were increased in those with HIV and a history of any malignancy. Since anal dysplasia can be detected and subsequently treated, anal cancer screening should be recommended to women with cervical dysplasia. Further studies are warranted to guide recommendations to screen women with cervical dysplasia for anal dysplasia

Exploring the Potential of Natural Killer Cell-Based Immunotherapy in Targeting High-Grade Serous Ovarian Carcinomas.

High-grade serous ovarian cancers (HGSOCs) likely consist of poorly differentiated stem-like cells (PDSLCs) and differentiated tumor cells. Conventional therapeutics are incapable of completely eradicating PDSLCs, contributing to disease progression and tumor relapse. Primary NK cells are known to effectively lyse PDSLCs, but they exhibit low or minimal cytotoxic potential against well-differentiated tumors. We have introduced and discussed the characteristics of super-charged NK (sNK) cells in this review. sNK cells, in comparison to primary NK cells, exhibit a significantly higher capability for the direct killing of both PDSLCs and well-differentiated tumors. In addition, sNK cells secrete significantly higher levels of cytokines, especially those known to induce the differentiation of tumors. In addition, we propose that a combination of sNK and chemotherapy could be one of the most effective strategies to eliminate the heterogeneous population of ovarian tumors; sNK cells can lyse both PDSLCs and well-differentiated tumors, induce the differentiation of PDSLCs, and could be used in combination with chemotherapy to target both well-differentiated and NK-induced differentiated tumors

A rare case of vulvar extraskeletal myxoid chondrosarcoma: mimics and diagnostic clues

Only 14 cases of extraskeletal myxoid chondrosarcoma (EMC) of the vulva have been documented in the literature. We report a case of a 63-year-old woman with EMC of the vulva confirmed by both EWSR1 and NR4A3 fluorescence in situ hybridization, the latter of which is a more specific probe for this entity. The unusual location of this tumor of prominent myxoid morphology gave rise to a wide differential diagnosis, which necessitated thorough histologic evaluation and confirmatory ancillary testing in the form of immunohistochemistry and cytogenetic studies. This article aims to review extraskeletal myxoid chondrosarcoma of the vulva and various diagnostic clues to help differentiate it from its histologic mimics. This is the fifth case of vulvar EMC in the literature with confirmation of a NR4A3 gene rearrangement

Exploring the Potential of Drug Response Assays for Precision Medicine in Ovarian Cancer

One of the major challenges in the treatment of cancer are differential responses of patients to existing standard of care anti-cancer drugs. These differential responses may, in part, be due to a diverse range of genomic, epigenomic, proteomic, and metabolic alterations among individuals suffering from the same type of cancer. Precision medicine is an emerging approach in cancer therapeutics that takes into account specific molecular alterations, environmental factors as well as lifestyle of individual patients. This approach allows clinicians and researchers to select or predict treatments that would most likely benefit the patient based on their individual tumor characteristics. One class of precision medicine tools are predictive, in vitro drug-response assays designed to test the sensitivity of patient tumor cells to existing or novel therapies. These assays have the potential to rapidly identify the most effective treatments for cancer patients and thus hold great promise in the field of precision medicine. In this review, we have highlighted several drug-response assays developed in ovarian cancer and discussed the current challenges and future prospects of these assays in the clinical management of this disease

Exploring the Potential of Drug Response Assays for Precision Medicine in Ovarian Cancer

One of the major challenges in the treatment of cancer are differential responses of patients to existing standard of care anti-cancer drugs. These differential responses may, in part, be due to a diverse range of genomic, epigenomic, proteomic, and metabolic alterations among individuals suffering from the same type of cancer. Precision medicine is an emerging approach in cancer therapeutics that takes into account specific molecular alterations, environmental factors as well as lifestyle of individual patients. This approach allows clinicians and researchers to select or predict treatments that would most likely benefit the patient based on their individual tumor characteristics. One class of precision medicine tools are predictive, in vitro drug-response assays designed to test the sensitivity of patient tumor cells to existing or novel therapies. These assays have the potential to rapidly identify the most effective treatments for cancer patients and thus hold great promise in the field of precision medicine. In this review, we have highlighted several drug-response assays developed in ovarian cancer and discussed the current challenges and future prospects of these assays in the clinical management of this disease

Management of Clitoral Melanoma Presenting as an Exophytic Clitoral Mass: A Case Report and Review of the Literature

Primary mucosal melanomas of the female genital tract account for one percent or less of all cases of melanoma with even fewer originating in the clitoris. Given the rarity of diagnosis of clitoral melanoma, there is a paucity of data guiding management. There is no supporting evidence that radical vulvectomy (with or without inguinal lymphadenopathy) is associated with improved disease-free or overall survival compared to partial vulvectomy or wide local excision. Additionally, there is no data to evaluate the role of sentinel lymph node biopsy or extensive lymphadenectomy in clitoral melanoma, however previous evidence demonstrates the utility of regional lymph node sampling in predicting survival in women with female genital tract mucosal melanoma. Adjuvant therapy considerations are often extrapolated from their use in treating cutaneous melanomas, including immune checkpoint inhibitors and other immunotherapy agents. Adjuvant radiation therapy has limited utility except in cases of bulky, unresectable disease, or when inguinal lymph nodes are positive for metastasis. The 52 year-old patient presented in this review was diagnosed with locally invasive advanced stage clitoral melanoma presenting as an exophytic clitoral mass. She underwent diagnostic primary tumor resection, which demonstrated ulcerative melanoma with spindle cell features extending to a Breslow depth of at least 28 mm. She subsequently underwent secondary wide local excision with groin sentinel lymph node biopsy, and adjuvant treatment with pembrolizumab. This article also emphasizes the importance of a multidisciplinary team involving gynecologic oncology, medical oncology, radiology, and pathology for management of this rare type of primary mucosal melanoma of the female genital tract

Management of Clitoral Melanoma Presenting as an Exophytic Clitoral Mass: A Case Report and Review of the Literature

Primary mucosal melanomas of the female genital tract account for one percent or less of all cases of melanoma with even fewer originating in the clitoris. Given the rarity of diagnosis of clitoral melanoma, there is a paucity of data guiding management. There is no supporting evidence that radical vulvectomy (with or without inguinal lymphadenopathy) is associated with improved disease-free or overall survival compared to partial vulvectomy or wide local excision. Additionally, there is no data to evaluate the role of sentinel lymph node biopsy or extensive lymphadenectomy in clitoral melanoma, however previous evidence demonstrates the utility of regional lymph node sampling in predicting survival in women with female genital tract mucosal melanoma. Adjuvant therapy considerations are often extrapolated from their use in treating cutaneous melanomas, including immune checkpoint inhibitors and other immunotherapy agents. Adjuvant radiation therapy has limited utility except in cases of bulky, unresectable disease, or when inguinal lymph nodes are positive for metastasis. The 52 year-old patient presented in this review was diagnosed with locally invasive advanced stage clitoral melanoma presenting as an exophytic clitoral mass. She underwent diagnostic primary tumor resection, which demonstrated ulcerative melanoma with spindle cell features extending to a Breslow depth of at least 28 mm. She subsequently underwent secondary wide local excision with groin sentinel lymph node biopsy, and adjuvant treatment with pembrolizumab. This article also emphasizes the importance of a multidisciplinary team involving gynecologic oncology, medical oncology, radiology, and pathology for management of this rare type of primary mucosal melanoma of the female genital tract

Management of Clitoral Melanoma Presenting as an Exophytic Clitoral Mass: A Case Report and Review of the Literature

Primary mucosal melanomas of the female genital tract account for one percent or less of all cases of melanoma with even fewer originating in the clitoris. Given the rarity of diagnosis of clitoral melanoma, there is a paucity of data guiding management. There is no supporting evidence that radical vulvectomy (with or without inguinal lymphadenopathy) is associated with improved disease-free or overall survival compared to partial vulvectomy or wide local excision. Additionally, there is no data to evaluate the role of sentinel lymph node biopsy or extensive lymphadenectomy in clitoral melanoma, however previous evidence demonstrates the utility of regional lymph node sampling in predicting survival in women with female genital tract mucosal melanoma. Adjuvant therapy considerations are often extrapolated from their use in treating cutaneous melanomas, including immune checkpoint inhibitors and other immunotherapy agents. Adjuvant radiation therapy has limited utility except in cases of bulky, unresectable disease, or when inguinal lymph nodes are positive for metastasis. The 52 year-old patient presented in this review was diagnosed with locally invasive advanced stage clitoral melanoma presenting as an exophytic clitoral mass. She underwent diagnostic primary tumor resection, which demonstrated ulcerative melanoma with spindle cell features extending to a Breslow depth of at least 28 mm. She subsequently underwent secondary wide local excision with groin sentinel lymph node biopsy, and adjuvant treatment with pembrolizumab. This article also emphasizes the importance of a multidisciplinary team involving gynecologic oncology, medical oncology, radiology, and pathology for management of this rare type of primary mucosal melanoma of the female genital tract