Primary Vaginal Small-Cell Carcinoma Treated with Concurrent Chemoradiotherapy and Interstitial Irradiation: A Case Report and Review of the Literature

Introduction

Vaginal cancer is a rare malignant disease that accounts for ∼1% of gynecologic cancers. Histologic types include, in decreasing order of frequency, squamous-cell carcinoma, adenocarcinoma, melanoma, sarcoma, and lymphoma. Primary vaginal small-cell (VSC) neuroendocrine carcinoma is extremely rare and is associated with a poor prognosis. Treatment of VSC differs by institute, and optimal treatment strategies remain unclear. Herein, this article reports a case of VSC treated successfully by concurrent chemoradiation therapy (CCRT) with interstitial irradiation.

Case

A 54-year-old woman who had a surgical history of hysterectomy, due to a myoma she had at age 37, visited a nearby hospital due to abnormal vaginal bleeding, where she underwent loop electrosurgical excision procedure (LEEP) coagulation for hemostasis. Two months after the LEEP coagulation, she visited the Juntendo University Faculty of Medicine, Tokyo, Japan, due to recurrence of her vaginal bleeding. On examination, a 1.5-cm mass was observed and removed for biopsy. Hematoxylin and eosin (H&E) stained sections showed the tumor was composed of packed, small round cells with scanty cytoplasm and indistinct cell borders; the cells were arranged in small nests or formed cords (Fig. 1A and B). Immunohistochemical analysis results were negative for chromogranin A, synaptophysin, and thyroid transcription factor-1; strongly diffusely positive for CD56 and cytokeratin 7 (CK7); and weakly positive for p16 (Fig. 1C–E). The tumor was diagnosed as a small-cell carcinoma based on this histology.

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FIG. 1.

Pathologic findings. (A and B) Histologic sections showing infiltrating tumor cells under the epithelium, with nest and cord formation (hematoxylin and eosin stain). Magnification: (A) × 100; (B) × 400). (C, D, and E) Immunohistochemical analysis of tumor cells (magnification: × 400). Cells were strongly diffusely positive for CD56 (C) and CK7 (D), and weakly positive for p16 (E).

Magnetic resonance imaging showed a 1.5-cm mass at the vaginal stump (Fig. 2A). Positron emission tomography showed fluorodeoxyglucose accumulation in the same area (SUV_max 21.9) and in the left external iliac lymph nodes (SUV_max 2.4) (Fig. 2B and C). The tumor markers carcinoembryonic antigen, cancer antigen–125, squamous-cell carcinoma antigen, and neuron-specific enolase were negative. The tumor was determined to be stage III (cT1N1M0), and CCRT with interstitial irradiation was selected for treatment. Extended-field radiation therapy (RT) and brachytherapy were delivered with chemotherapy (40 mg/m² of cisplatin [CDDP] every week for 5 cycles).

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FIG. 2.

Tumor appearance. (A) Magnetic resonance imaging showed a 1.5-cm mass at the vaginal stump. (B and C) Positron emission tomography showed (B) fluorodeoxyglucose accumulation at the tumor (SUV_max 21.9) and (C) left external iliac lymph nodes (SUV_max 2.4).

Results

The patient did not show any evidence of recurrence 12 months after the CCRT.

Discussion

CCRT with interstitial irradiation was effective in the current patient, who had advanced-stage VCS. Primary VCS is extremely rare, with only 24 cases reported in the English literature (Table 1).^1–16 Of these 24 patients, 5 (20.8%) showed no evidence of disease (NED), although only 1 of these 5 patients experienced long-term survival. Furthermore, only 3 (60%) of 5 patients with stage I disease showed NED. These results indicate that VCS is associated with an extremely poor prognosis.

Of the 24 cases of VGS cited in the literature, 6 underwent CCRT, 4 of which showed complete responses; furthermore, 2 cases had NED. In 4 cases, chemotherapy consisted of combination cisplatin and etoposide; 1 patient received cisplatin alone; and 1 patient received combination carboplatin and etoposide. Of the 6 patients who received CCRT, 4 received combination external RT and brachytherapy, 2 of whom had NED. Of the 2 cases who received surgery alone, all died due to disease, suggesting that poor tumor control is achieved by surgery alone, so combination treatment with surgery, chemotherapy, and/or RT is recommended. All 5 patients who lived for >12 months received combination RT and chemotherapy. In the present case, CCRT was selected; it consisted of weekly CDDP, external RT, and interstitial brachytherapy, to enhance local tumor reduction.

Kanayama et al. reported that, for primary vaginal cancer, external-beam RT with brachytherapy (interstitial or intracavitary) should be used as definitive RT regardless of International Federation of Gynecology and Obstetrics stage. ¹⁷ With respect to RT for treating vaginal cancer, the American Brachytherapy Society consensus guidelines include recommendations for interstitial brachytherapy in patients with vaginal cancer. ¹⁸ These guidelines recommend that patients with bulky disease (∼ > 0.5 cm thick) should be considered for treatment with interstitial brachytherapy. The criteria for interstitial brachytherapy for vaginal cancer are established by each institution due to the technical difficulty of this treatment. In the present case, during CCRT, the swollen pelvic lymph node disappeared due to external RT and the vaginal tumor disappeared due to interstitial brachytherapy.

Conclusions

Although the current patient has not shown any evidence of recurrence 12 months after CCRT, it is necessary to be aware that the length of follow-up does not predict long-term survival, according to the literature review presented here. To the current authors' knowledge, this is the first report about the efficacy of CCRT using interstitial brachytherapy for primary VSC: CCRT (daily CDDP plus external RT) and interstitial irradiation were effective for this patient who had advanced-stage VSC.