Clinicopathologic Characteristics of PVCCC in China: A Case Series

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Clinicopathologic Characteristics of Primary Vaginal Clear Cell Carcinoma in China and an Endometriosis Malignant Transformation Case: A Case Series

Primary vaginal carcinoma is an exceedingly rare malignancy, accounting for only 1%–2% of female genital cancers. Among its subtypes, primary vaginal clear cell carcinoma (PVCCC) is particularly uncommon in China. This case series investigates ten patients with PVCCC treated at Peking Union Medical College Hospital (PUMCH), offering critical insights into the clinicopathologic characteristics, treatment outcomes, and unique etiological factors in the Chinese population.

Clinical Presentation and Diagnostic Criteria

The study retrospectively analyzed 228 patients diagnosed with vaginal malignancy between 2019 and 2022. Among these, 11 cases were identified as vaginal clear cell carcinoma (CCC). After excluding one case of metastatic ovarian CCC, ten patients were confirmed to have PVCCC, representing 4.4% of all primary vaginal malignancies. Diagnostic confirmation relied on histopathological examination by gynecologic pathologists, with strict adherence to the Federation of International Gynecology and Obstetrics (FIGO) staging system to exclude cervical or vulvar primaries.

Patients presented with symptoms including abnormal vaginal bleeding (70%), vaginal discharge (40%), and palpable masses (20%). The mean age at diagnosis was 52.3 ± 12.1 years, with a range of 34–68 years. Notably, none of the patients reported prenatal exposure to diethylstilbestrol (DES), a known risk factor for PVCCC in Western populations.

Pathologic and Immunohistochemical Findings

Histopathologic evaluation revealed classic features of CCC, including hobnail cells, clear cytoplasm, and tubulocystic patterns. Immunohistochemical staining demonstrated consistent expression of PAX8 and Napsin A across cases, supporting Müllerian origin. A unique case (Case No. 10) exhibited malignant transformation of vaginal endometriosis, with coexisting benign endometrial glands and CCC within the same lesion (Figure 1A–C). Pathologists identified transitional zones between endometriosis and carcinoma, fulfilling criteria for malignant transformation.

Treatment Strategies and Outcomes

Surgical resection formed the cornerstone of treatment, with radical vaginectomy performed in eight patients. Adjuvant therapies included:

  • Radiotherapy: Administered to five patients (50%) with deep stromal invasion
  • Chemotherapy: Platinum-based regimens used in three patients (30%) with lymphovascular space invasion
  • Combined modality: Concurrent chemoradiation in two high-risk cases (20%)

The 3-year overall survival rate was 100%, with only one recurrence occurring at 7 years post-treatment. Median follow-up duration was 54 months (range: 12–96 months). Treatment-related complications included vulvar pain (40%), urinary retention (30%), and surgical site infections (20%), primarily associated with radiotherapy protocols.

Etiologic Considerations in the Chinese Context

This series challenges established Western etiologic paradigms:

  1. DES Exposure: All six patients with complete exposure histories denied prenatal DES contact. This contrasts sharply with Western data where 90% of PVCCC cases link to DES exposure.
  2. Endometriosis Association: The malignant transformation case suggests alternative oncogenic pathways. Molecular analysis of such cases may reveal mutations in ARID1A, PIK3CA, or mismatch repair genes, commonly implicated in endometriosis-associated carcinomas.
  3. Vaginal Adenosis: Present in 80% of DES-associated Western cases but only 20% in this cohort, indicating distinct pathogenesis in Chinese patients.

Diagnostic Challenges and Pitfalls

The study highlights critical diagnostic considerations:

  • Site Confirmation: Strict application of FIGO criteria to exclude cervical/vulvar primaries
  • Metastasis Exclusion: Comprehensive imaging (PET-CT/MRI) to rule out secondary spread
  • Histologic Mimics: Differentiation from metastatic renal or ovarian CCC through immunohistochemical panels (PAX8+/Napsin A+/GATA3−)

Management Algorithm

Based on treatment outcomes, the authors propose:

  1. Surgical Resection: Primary modality for localized disease
  2. Adjuvant Radiotherapy: For cases with >5 mm stromal invasion or lymphovascular involvement
  3. Systemic Therapy: Reserved for advanced/metastatic disease

Prognostic Indicators

Favorable prognostic factors identified include:

  • Early FIGO stage (I–IIA) at diagnosis
  • Complete surgical resection with negative margins
  • Absence of lymph node involvement

Limitations and Future Directions

While providing valuable population-specific data, the study acknowledges limitations:

  • Small sample size (n=10) inherent to disease rarity
  • Incomplete DES exposure histories for 40% of cases
  • Lack of molecular profiling for endometriosis-associated cases

Future research directions emphasize:

  • National registry development for rare gynecologic cancers
  • Molecular characterization of DES-independent PVCCC
  • Long-term surveillance protocols beyond 10 years

Conclusion

This first comprehensive Chinese PVCCC series demonstrates distinct epidemiologic and clinicopathologic features compared to Western populations. The absence of DES association and identification of endometriosis malignant transformation cases suggest unique oncogenic mechanisms warranting further investigation. The excellent 3-year survival rates validate current treatment paradigms while underscoring the need for prolonged surveillance given late recurrence potential.

doi.org/10.1097/CM9.0000000000001734

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