Rapid Progression of Mixed Adenocarcinoma with Large-cell Neuroendocrine Carcinoma of the Cervix

Abstract

Background: Large cell neuroendocrine carcinoma (LCNEC) is very rare and represents about 12.5% of neuroendocrine cervical tumors. These highly aggressive tumors may present as small lesions, but most are deeply invasive. They exhibit the usual features of neuroendocrine carcinoma, and high mitotic indices and necrosis are common. Following this, mixed adenocarcinoma with large cell neuroendocrine carcinoma (MALCNEC) is even very rare. Aims: The case report raises awareness regarding diagnostic challenges associated with this rare and aggressive tumor. Case presentation: A 37-year-old woman presented with a 2-month history of post-coital bleeding with abnormal vaginal discharge. Initial examination revealed a grossly normal cervix, but cervical screening indicated atypical squamous cells-cannot exclude high-grade squamous intra-epithelial lesion (ASC-H). Colposcopic assessment showed a small hyperemic area with thin aceto-white uptake, which was biopsied and later confirmed to be adenocarcinoma with clear cell differentiation. The management was delayed due to an active upper respiratory tract infection. During re-evaluation 2 weeks later, the previously grossly normal cervix had transformed into barrel- shaped cervix containing a hard mass, indicating rapid disease progression. It was clinically staged as FIGO stage 1B3 and the patient subsequently underwent radical hysterectomy. Final histopathology revealed a mixed tumor comprising both adenocarcinoma and large-cell neuroendocrine carcinoma with metastatic involvement of pelvic lymph nodes. The patient is then undergone adjuvant radiotherapy and recently completed chemotherapy with cisplatin and etoposide. Discussion: Mixed neuroendocrine and non-neuroendocrine carcinomas of the cervix are exceedingly rare and tend to behave aggressively. They often present at advanced stages with metastases and carry a poor prognosis. Despite the initial presentation without an obvious cervical lesion and extra-pelvic spread, this case demonstrated rapid tumor progression, underscoring the tumor’s aggressive nature. Conclusion: Diagnostic challenges associated with this pathology are well illustrated in this case. Heightened awareness may allow early recognition and prompt intervention in managing these aggressive tumors. This rarity poses significant challenges in accurate diagnosis and in developing more effective, optimal treatment strategies. To address these challenges, further research and increased collaboration among clinicians, radiologists, pathologists, and oncologists are essential.