Solitary vulvar metastasis from early-stage endometrial cancer: Case report and literature review.

RATIONALE: Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. It is usually diagnosed at early-stage and presents a favorable prognosis. Conversely, advanced or recurrent disease shows poor outcome. Most recurrences occur within 2 years postoperatively, typically in pelvic and para-aortic lymph nodes, vagina, peritoneum, and lungs. Vulvar metastasis (VM) is indeed anecdotal probably because of the different regional lymphatic drainage from corpus uteri. PATIENT CONCERNS: A 3 cm, reddish, bleeding lesion of the posterior commissura/right labia was found in a 74-year-old woman treated with radical hysterectomy, surgical staging, and adjuvant radiotherapy 1 year before for a grade 2 endometrioid type, International Federation of Gynecology and Obstetrics Stage IB. Vulvar biopsy confirmed the EC recurrence. Pelvic magnetic resonance imaging and positron emission tomography excluded other metastases so VM was radically resected. DIAGNOSIS: Postoperative histopathology confirmed the diagnosis of grade 2 EC VM. INTERVENTIONS: A radical excision of VM was performed. OUTCOMES: Patient died from a severe sepsis 27 months after first surgery. LESSONS: Vulvar metastases can show different appearance, occurring as single or diffuse lesions on healthy or injured skin. The surgical approach seems not to influence the metastatic risk, but tumor seeding and vaginal injuries should be avoided. Whether isolated or associated with recurrence in other locations, vulvar metastases imply poor prognosis despite radical treatment. Therefore, any suspected vulvar lesion arisen during EC follow-up should be biopsied and monitored closely, despite that the vulva represents an unusual metastatic site.

Literature Review and Our Experience With Bleomycin-Based Electrochemotherapy for Cutaneous Vulvar Metastases From Endometrial Cancer.

Endometrial carcinoma is the most common gynecological malignancy and the fifth most common malignancy in women. The worldwide incidence is 15.9 new cases per 100,000 women per year, and the incidence in Europe is 22.7 new cases. Minority of cases are diagnosed at an advanced stage of the disease. Cutaneous metastases are very rare with a prevalence of 0.8%. If cutaneous metastases are present, the prognosis is poor with an overall survival of up to 12 months. In this review, we presented clinical data on treatment of gynecological cancers with electrochemotherapy, with focus on treatment of cutaneous vulvar metastases from endometrial cancer. Further, we present our data on the case of a 64-year-old woman with recurrent endometrial adenocarcinoma with vulvar skin metastases. Treatment of endometrial carcinoma metastases is multimodal with surgery, chemotherapy, radiotherapy and hormone treatment. There is still no consensus about the specific treatment of cutaneous metastases from endometrial cancer, in particular in order to release symptoms. Electrochemotherapy may be a treatment option to reduce pain and bleeding and a safe option to treat multiple skin metastases.

Non-human-papillomavirus-related malignancies of the vulva: A clinicopathological study.

BACKGROUND: Malignant tumor of the vulva is the fourth gynecological malignancy in frequency. Close to 70% of all vulvar malignancies are related to high-risk human papillomavirus (HPV) infection. METHODS: A search for non-HPV-related malignant tumors of the vulva was performed in the last 20 years (2000-2020) in the pathology database of a single tertiary institution. We aim to estimate the prevalence of non-HPV-related malignancies in our population, describe clinicopathological features of these tumors and investigate the expression of some potential therapeutic targets. RESULTS: A total of 71 patients were recovered; 26 patients (36%) had the diagnosis of extramammary Paget disease, 17 patients (24%) had basal cell carcinomas, 17 patients (24%) had primary melanomas, 10 patients (14%) had metastatic disease to the vulva and one patient (1%) had a primary dermatofibrosarcoma protuberans. Fifty-four percent of patients with extramammary Paget disease had a secondary malignancy and 12.5% had invasive disease. Programmed death-ligand 1 (PDL-1) was positive in seven out of nine primary melanomas and Her2/neu was overexpressed in six out of seven extramammary Paget disease. CONCLUSION: Non-HPV-related malignancies are important differential diagnoses in patient with vulvar lesions. Additional research is necessary to further understand these complex malignancies and potential new therapeutic targets.

Extensive vitiligo associated to response to c-kit inhibitor in metastatic mucosal melanoma.

Mucosal melanoma is rare and accounts for 1.3-1.4% of all melanomas. Kit mutations are found in approximately 15-20% of mucosal melanomas. Immunotherapy with anti cytotoxic T-lymphocyte associated protein 4 and antiprogrammed cell death protein 1 have reported low clinical efficacy in this melanoma subtype. Studies with Kit inhibitor Imatinib showed response rates ranging from 20 to 30%. We present the case of a patient with a c-kit mutated metastatic melanoma who developed autoimmune vitiligo during treatment with oral tyrosine kinase inhibitor Masitinib.

Emergence of KRAS p.G13D mutation and acquired resistance to cetuximab in colorectal cancer with vulvar metastasis: A case report.

RATIONALE: Vulvar metastasis of colorectal cancer (CRC) and acquired resistance to cetuximab is a very rare phenomenon. To our knowledge, few cases have been reported in the English literatures. PATIENT CONCERNS: A 55-year-old woman was diagnosed as adenocarcinoma of the rectum and the primary tumor was detected to be Kirsten-RAS (KRAS) wild type. DIAGNOSES: The patient was diagnosed with rectal adenocarcinoma by colonoscopy. Positron emission tomography/computed tomography (PET-CT) revealed multiple lymph node and bone metastases. INTERVENTIONS: The patient received a first-line course of palliative chemotherapy with FOLFOX combined with cetuximab. OUTCOMES: After an initial response, acquired resistance to cetuximab occurred and vulvar metastasis was established by a second biopsy. Further molecular analysis showed that the KRAS mutation was detected in plasma samples and tumor tissues. LESSONS: Vulvar metastasis from CRC is relatively rare and indicates a poor prognosis. Routine physical examinations of cutaneous and subcutaneous may facilitate early detection of metastases and timely intervention of medical technology. Moreover, combining serial tumor biopsy, liquid biopsy, and radiologic imaging could help to define mechanisms of drug resistance and to guide selection of therapeutic strategies.

Recurrent genetic alterations and biomarker expression in primary and metastatic squamous cell carcinomas of the vulva.

Using a comprehensive next-generation sequencing pipeline (143 genes), Oncomine Comprehensive v.2, we analyzed genetic alterations on a set of vulvar squamous cell carcinomas (SCCs) with emphasis on the primary and metastatic samples from the same patient, to identify amenable therapeutic targets. Clinicopathologic features were reported and genomic DNA was extracted from 42 paraffin-embedded tumor tissues of 32 cases. PD-L1 expression was evaluated in 20 tumor tissues (10 cases with paired primary and metastatic tumors). Fifteen (88%) of 17 successfully analyzed HPV-unrelated SCCs harbored TP53 mutations. 2 different TP53 mutations had been detected in the same tumor in 4 of 15 cases. Other recurrent genetic alterations in this group of tumors included CDKN2a mutations (41%), HRAS mutations (12%), NOTCH1 mutations (12%) and BIRC3 (11q22.1-22.2) amplification (12%). Six HPV-related tumors harbored PIK3CA, BAP1, PTEN, KDR, CTNNB1, and BRCA2 mutations, of which, one case also contained TP53 mutation. Six cases showed identical mutations in paired primary site and distant metastatic location and four cases displayed different mutational profiles. PD-L1 expression was seen in 6 of 10 primary tumors and all 6 paired cases showed discordant PD-L1 expression in the primary and metastatic sites. Our results further confirmed the genetic alterations that are amenable to targeted therapy, offering the potential for individualized management strategies for the treatment of these aggressive tumors with different etiology. Discordant PD-L1 expression in the primary and metastatic vulvar SCCs highlights the importance of evaluation of PD-L1 expression in different locations to avoid false negative information provided for immunotherapy.

A new entity in the pathological spectrum of vulvar neoplasms: The first report of a primary endometrioid adenocarcinoma.

We report the first evidence of primary endometrioid adenocarcinoma arising in the vulva, expanding the morphological spectrum of the glandular neoplasms in this anatomic region.

18F-FDG PET/CT in a Case of Metastatic Breast Cancer to the Vulva.

A 56-year-old woman, previously treated for breast cancer, presented to gynecologists with a lump of the left labium major of the vulva. The FDG pattern resembled as a cIV stage vulvar cancer, whereas biopsy indicated metastases from breast cancer. Metastatic disease to the vulva is particularly uncommon, representing 5% to 8% of all vulvar cancer lesions. However, gynecological uptakes, including vulvar site, have to be kept in mind as a possible site of metastatic lesions from breast cancer.

Recurrence of endometrial carcinoma presenting as vulvar lesions.

Vulvar metastasis is an unusual presentation of recurrent endometrial cancer and should be part of the differential diagnosis of vulvar lesion.

Asymptomatic Isolated Vulvar Metastasis in Old Treated Case of Carcinoma Rectum-Diagnosis and Treatment Response Evaluation by 18F-FDG PET/CT Scan.

We report a clinically asymptomatic, old treated case of carcinoma rectum, presenting with raised serum carcinoembryonic antigen level, referred for F-FDG PET/CT scan for restaging. Whole-body PET/CT scan revealed an isolated FDG-avid lesion in the left labia majora region, which on histopathology was found to be metastasis from carcinoma rectum. Subsequent F-FDG PET/CT done after 4 cycles of chemotherapy revealed favorable response to therapy. F-FDG PET/CT facilitates the detection of unusual site of metastasis and its subsequent response evaluation in the index case.

A vulvar mass as the first presentation in colorectal carcinoma: An unusual site of metastasis masquerading a primary cancer.

OBJECTIVE: To demonstrate a case with a vulvar metastasis masquerading a primary vulvar malignancy. The clinical and histological features, mechanism, and impact to the prognosis are discussed. CASE REPORT: A 58-year-old woman presented to gynecologist for abnormal vaginal discharge. A vulvar nodule was noticed during physical examination. Biopsy showed adenocarcinoma (ADC) and she was referred for further survey under the impression of Bartholin duct ADC. Later she was further found to also have a colorectal tumor with liver metastasis and subsequently received surgery under the suspicion of a double primary cancer involving the colon and vulva. The pathology revealed colorectal ADC with both hepatic and vulvar metastasis. CONCLUSION: Secondary tumor in female genital tract is unusual and vulvar metastasis is the rarest kind. The clinical manifestation may be perplexing especially if a patient is presented with a nonspecific gynecological symptom such as abnormal vaginal discharge without any past history.

Vulvar Recurrences After Intensity-modulated Radiation Therapy for Squamous Cell Carcinoma of the Anus.

OBJECTIVES: The objective is to determine localregional control (LRC), distant metastasis free survival, disease-free survival, overall survival (OS), and toxicity for patients with squamous cell carcinoma of the anus treated with definitive chemotherapy and intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: We conducted a retrospective review of patients treated using IMRT for squamous cell carcinoma of the anus at our institution since 2005. Patients with local recurrences were identified and reviewed. The Kaplan-Meier curves were used for LRC and OS. RESULTS: From 2005 to 2014, 52 patients were treated with IMRT-based chemoradiation for squamous cell carcinoma of the anus. Median dose to the primary tumor was 54 Gy. LRC, distant metastasis free survival, OS, and disease-free survival were 92.3%, 88.5%, 86.5%, and 84.6%, respectively, with a median follow-up of 20 months. Two local failures occurred at the anal primary site and 2 in the vulva. Despite subsequent palliative radiotherapy and chemotherapy, neither patient with a vulvar recurrence achieved disease control. CONCLUSIONS: In a cohort of patients treated with IMRT-based chemoradiation, 2 vulvar recurrences were identified within the avoided external genitalia despite limited recurrence rates within the cohort overall. This experience suggests that for patients with a locally advanced primary tumor and bulky bilateral inguinal or pelvic disease, the in-transit vulvar dermal lymphatics may be at risk for subclinical involvement and subsequent recurrence. If substantiated by a similar pattern of recurrence at other institutions, the external genitalia may need to be reclassified from an avoidance structure to a clinical treatment volume in patients with locally advanced anal cancer.

Infiltrating Mammary Duct Adenocarcinoma in the Right Labia Majora Along the Milk-Line.

Introduction Breast tissue rarely arises from the vulva and malignancy might develop in it. Case Thirty-eight-year-old woman presented with a suspicious ulcer in the right labia majora discovered accidently and removed by wide local excision. Histopathology revealed infiltrating mammary duct adenocarcinoma along the milk line. Immunohistochemistry was positive for estrogen and progesterone receptors and equivocal overexpression for HER2 protein with a score of 2+. Metastatic work-up was clear. Inguinal lymph nodes were enlarged and lymphadenectomy done which showed positive lymph nodes on the right side and none on the left. She is receiving adjuvant therapy. Conclusion Mammary duct carcinoma along the nipple line is rare but should be considered when dealing with suspicious vulvar lesions.

Gastrointestinal adenocarcinoma metastasizing to the vulva: a case report.

BACKGROUND: Metastatic vulval adenocarcinoma is a rare occurrence with only a few cases reported to date. They can arise from the breast, gastrointestinal system, or endometrium. CASE PRESENTATION: We present the case of a 55-year-old Black African woman who presented with vulval itching which progressed to warty lesions. Histology revealed a vulval adenocarcinoma which immunohistochemistry suggested was of gastrointestinal origin. Colonoscopy later confirmed an anorectal tumor as the primary site. Despite extensive chest metastases she looked surprisingly well and had no pulmonary symptoms. The major source of symptomatic distress was the itchy extensive warty lesions on her vulva. She has since had a vulvectomy which gave her significant symptomatic relief. CONCLUSIONS: This case was interesting as vulval adenocarcinoma is a rare histological diagnosis found in less than 10% of vulval cancers. Primary vulval adenocarcinoma is rare with most of these cancers being secondary metastases from a distant site. Her symptoms were predominantly vulval with no chest symptoms even though she had extensive pulmonary metastases. She has been clinically well except for the itching suggesting an indolent course.