Primary Clear Cell Adenocarcinoma of the Vulva: A Case Study With Mutation Analysis and Literature Review

Abstract

Primary vulvar clear cell carcinoma (CCC) is extremely rare. In this article, we report a primary vulvar CCC along with immunohistochemical and gene mutation analyses results and literature review to discuss the clinicopathological features and tumorigenesis of this rare tumor. A 70-year-old (gravida 2 para 2) Japanese woman complained of bleeding from a vulvar mass at a past episiotomy site. A 1.8 × 1.8 × 0.5 cm exophytic sessile mass was present on the vestibular area inside the left labium minora. Radical local excision of the tumor and resection of the inguinal lymph nodes on both sides were performed. Histopathology revealed a vulvar CCC with immunohistochemical positivity for PAX8, HNF-1β, ER, and CA125, and negativity for p16, CD10, GATA3, PTEN, and PAX2, suggesting its Müllerian origin. No lymph node metastasis was observed. The tumor was a 5-mm exophytic growth without deep stromal invasion; thus, it was difficult to measure the invasion depth assuming a squamous cell carcinoma. To investigate pathogenic/oncogenic mutations in 50 cancer-related genes, we used the AmpliSeq Cancer Hotspot Panel. However, no pathogenic/oncogenic mutations were detected. Literature review revealed that most cases of vulvar CCC are associated with vulvar endometriosis. In particular, cases with clinically evident endometriosis at the episiotomy scar should be carefully observed. Evidence-based pathological stages of vulvar adenocarcinoma including CCC remain to be established owing to its rarity, with nationwide or global accumulation of cases required in future.

Diagnosis and Treatment of Vulvo-Perineal Endometriosis: A Systematic Review

“…It is difficult to distinguish benign from malignant perineal endometriosis based on symptoms and clinical examination and a biopsy or surgical excision will always be necessary to confirm the diagnosis of malignant transformation (13). Histological observations are dominated by endometrioid carcinoma and sarcoma (107), but can also present as dermatosarcoma, clear cell carcinoma and serous papillary cystadenocarcinoma (87,106,(108)(109)(110)(111)(112)(113)(114)(115)(116). As malignant transformation appears uncertain, unpredictable and may be very delayed, long-term follow-up is recommended.…”

Malignancies Associated with Extraovarian Endometriosis: A Literature Review

“…A total of 158 reports were identified, including 19 case series and 147 case reports. Out of the identified 258 cases, 45 cases were excluded as follows: detail was not described about each cases (15 cases in 1 case series) [24]; benign diseases (11 cases: 8 cases including 2 case series, mesothelial tumor [25][26][27][28][29]; 1 case, abscess [30]; 1 case, adenofibroma [31]; 1 case, endosalpingiosis was suspected by histological image [32]); no history or coexistence of endometriosis (7 cases) [33][34][35][36][37][38][39]; histological types that were not associated with endometriosis (3 cases) [40][41][42]; coexisting intestinal cancer (2 cases) [43,44]; dissemination of ovarian tumor (2 cases) [45,46]; tumor derived from adenomyosis (2 cases) [47]; primary peritoneal borderline tumor (1 case) [48]; malignancy from endosalpingiosis (1 case) [42]; review from other papers (1 case) [49].…”

Primary clear cell carcinoma of the vulva: A case report

“…In five cases, the CCC arose within a prior episiotomy site. These case reports theorize that the extra-gonadal endometriotic precursor lesions are caused by iatrogenic seeding of endometrial tissue to the vulva at time of episiotomy during vaginal delivery ( Kojima et al, 2019 , Buppasiri et al, 2018 ).…”

“…Primary clear cell carcinoma (CCC) of the vulva is an extremely rare malignancy. Only fourteen cases of vulvar CCC have been reported in the literature ( Sampson, 1925 , Kojima et al, 2019 , Buppasiri et al, 2018 , Bolis and Macciò, 2000 , Mesko et al, 1988 , Lim et al, 2002 , Chatzistamatiou et al, 2015 , Herghelegiu et al, 2018 , Sachdeva et al, 2021 ). Due to its rarity, there is no consensus on standardized therapy, nor well-defined prognostic indicators for this cancer.…”