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Abstract
We report the case of a woman in her 70s with a stage IVA small cell neuroendocrine carcinoma of the vagina. The patient started chemotherapy with cisplatin and etoposide followed by concurrent chemoradiotherapy and adjuvant chemotherapy. Pelvic MRI after completion of treatment did not show residual disease. Three years and 8 months after definitive treatment, the patient remains on regular follow-up without evidence of disease.
- Gynecological cancer
- Chemotherapy
- Radiotherapy
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Background
Small cell neuroendocrine carcinoma (SCNC) is a highly proliferative disease. It commonly arises in the lung and only 2.5%–5% are extrapulmonary.1–3 Primary SCNC of the female genital tract constitutes less than 2% of all gynaecological cancers.4–6 It has been reported in the cervix, endometrium, ovary, vagina and vulva. SCNC of the vagina is a very rare entity with a dismal prognosis.2 The mean age at diagnosis is 59 years,6 and the most common symptom is postmenopausal bleeding.7 Due to its rarity and lack of data, there are no established treatment guidelines. We report a case of SCNC of the vagina, its treatment and follow-up.
Case presentation
We report the case of a woman in her 70s, gravida 4, para 1, stillbirth 1 and abortus 3, with Eastern Cooperative Oncology Group performance status of 0, with a medical history of hypertension, transient ischaemic attack, peripheral vertigo and bilateral oophorectomy and hysterectomy 25 years earlier, for unknown reasons. No family history of cancer was found.
The patient presented with pruritus and vaginal bleeding for 1 month, with no pain or abnormal smell. On gynaecological examination, a haemorrhagic lesion was observed in the anterior wall of the vagina and a biopsy was performed. Pathology identified small cells with dispersed chromatin nuclei and visible nucleolus, scarce cytoplasm with undefined limits in a lobulated growth, extensive necrosis and high mitotic index (60 mitoses per 10 high-power fields), with atypical mitoses. On immunohistochemistry examination, tumour cells were positive for AE1/AE3, CD56 and synaptophysin, and negative for chromogranin, CD10, CD45, CD99, vimentin, desmin and actin. Ki67 index was >90% (figure 1). Therefore, the histology was consistent with SCNC.
Histology showed a high-grade carcinoma with positive neuroendocrine markers, abundant mitotic figures and a proliferative index of >90%, consistent with SCNC. SCNC, small cell neuroendocrine carcinoma.
Rectal examination showed no involvement of the parametrium. A pelvic MRI revealed a 60 mm lesion with external bladder invasion and regional lymph nodes involvement (figure 2). Cystoscopy revealed no extramural transgression. A positron emission tomography scan showed a lesion in the vagina, enlarged bilateral external iliac lymph nodes and no evidence of metastatic disease. Therefore, the final diagnosis was a stage cT4N1M0–IVA SCNC of the vagina.
Pelvic MRI with a 60 mm lesion (T2 sagittal), external bladder invasion (T2 sagittal) and regional lymph node involvement (T2 axial).
Tumour board discussion proposed concurrent chemotherapy and radiotherapy. The patient underwent two cycles of intravenous cisplatin 80 mg/m2 on D1 and etoposide 100 mg/m2 on D1–D3, followed by concurrent chemotherapy (two cycles of 3 weekly cisplatin and etoposide) in addition to radiation therapy with 28 external beam fractions to the tumour and lymph nodes of 1.8 Gy each and a boost of 8 fractions of 2 Gy each on the tumour. After concurrent chemoradiotherapy, the patient received two more cycles of cisplatin and etoposide.
Despite acute grade 1 asthenia and grade 1 peripheral sensory neuropathy, the treatment was well tolerated, and the patient became asymptomatic from the presenting symptoms. No dose reduction or interruption was necessary.
Outcome and follow-up
Pelvic MRI performed 6 weeks after completion of treatment did not show residual disease. She was kept on regular follow-up, with gynaecological examination every 4–6 months and pelvic MRI and chest and abdominal CT scans every 6 months. Three years and 8 months after definitive chemoradiotherapy, the patient has no evidence of disease, remaining asymptomatic with good quality of life.
Discussion
SCNC of the vagina was first reported by Scully et al in 1989.8 It is a very rare and aggressive disease with no standard treatment and the majority of the patients die within a year of diagnosis.3 Since female genital tract and lung SCNC have similar pathological features,4 treatment of non-metastatic disease often includes a combination of etoposide/platinum-based chemotherapy and radiotherapy.3 Due to its rarity, there is no consensus about the optimal therapy of SCNC of the vagina. There are other described therapeutic options according to staging, such as radiation therapy of the lung and prophylactic cranial irradiation, which may cause cognitive impairment and compromise quality of life.9
A summary of the literature regarding SCNC of the vagina is shown in table 1. Forty-nine patients with primary SCNC of the vagina have been reported in 38 English-language articles to date, with a mean age at diagnosis of 54 years. The most common symptom at presentation was bleeding (23 patients). Of the described patients, 12 were International Federation of Gynecology and Obstetrics (FIGO) stage I, 12 FIGO stage II, 12 FIGO stage III and 11 FIGO stage IV. Twenty-four patients died, 15 of them (63%) within 1 year of diagnosis.
Summary of SCNC of the vagina case reports in literature
Cisplatin–etoposide was the most common chemotherapy regimen, used in 21 cases (42%), in the adjuvant setting, with concurrent radiotherapy or in metastatic setting. Due to the heterogeneity of the reported cases, the rarity of the disease and the absence of prospective studies, it is difficult to conclude which should be the preferred treatment.
Our patient was treated with cisplatin–etoposide chemotherapy followed by concurrent chemoradiotherapy with an external beam radiotherapy boost. Surgery was not an option as this was a locally advanced disease with bladder invasion (FIGO stage IVA), whose cases are associated with less favourable outcomes with surgery as primary treatment modality. A radiotherapy boost was given after taking into consideration tumour size, bladder invasion and constraints in the availability of interstitial brachytherapy. Despite the locally advanced disease, she remains free of relapse after 44 months.
Learning points
Small cell carcinoma of the vagina is a rare disease with a dismal prognosis.
There is no established standard treatment of small cell neuroendocrine carcinoma of the vagina.
Locally advanced small cell carcinoma of the vagina can be treated with cisplatin and etoposide concurrent chemoradiotherapy.
Ethics statements
Patient consent for publication
References
Footnotes
Contributors All authors contributed extensively to the case. LL-C contributed to planning, conduct, reporting, conception and design, and acquisition of data. JG contributed to patient management, initial planning and conduction, manuscript writing and extensive review. PS and MC-N contributed to manuscript writing and review. Radiology department contributed to image selection. Pathology department contributed to histological images selection and description.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.