Small Cell Carcinoma of Vagina(SmCC) is one of the distinctive and uncommon aggressive tumour.It comprises 1-2 percent of all gynaecological malignancies [1]. Survival rate of patients treated in early stages is 2 years [2]. SmCC is a high grade neuroendocrine tumour that emerges from the neuroendocrine cells or as a result of dedifferentiation of an aggressive non-neuroendocrine tumour . It commonly arises from the lungs and only 5 % are extrapulmonary. Only 44 cases have been reported in the entire world of primary small cell carcinoma of vagina.

There is a sequeale of investigations which needs to be done before definitive diagnosis of Primary SmCC of Vagina is made .This includes PAP smear ,MRI Pelvis , Tumor markers ,Vaginal Biopsy and  a definitive histopathology report and a Whole body PET-CT to rule out any distant dissemination before a definitive diagnosis of SmCC Vagina is made .These tumours are clinically aggressive and with rapid recurrences and distant metastasis and thus a regular follow up of the patient is essential in managing the same .As the rarity of the tumour and very less cases reported till date it is required to report such cases so that a definitive protocol in managing this tumour is ascertained and different management options to be explored per -se to improve the overall survival rate of the patient.

Case Report

A 48yr old P3L3 presented to the Kamla Nehru Hospital IGMC Shimla OPD with complaints of discharge per vaginum over two months. She is menopausal over last 2 years. She is non-hypertensive, non-smoker, non-diabetic and is no family history of any cancers .She was moderately built with her BMI -24.The discharge is mixed vaginal discharge ,non-foul smelling and non- purulent with   associated   complaint of vaginal itching present. On per-speculum examination there was evidence of a whitish lesion of size 2*3cm on the posterior vaginal wall that bleeds on touch. PAP smear report of the patient was inflammatory (Figure 1-2).

Figure 1: Colposcopic View

Figure 2: Histopathology Report-Small Round Blue Cells with High Grade Dysplasia

Investigations

The vaginal biopsy was taken from the posterior vaginal wall at the site of the lesion confirmed it to be Small Cell Carcinoma of Vagina . There was evidence of fragments lined by round to oval cells with high grade dysplasia with neutrophilic exocytosis, high N:C ratio ,round-oval hyperchromatic nuclei .Atypical hemorrhagic areas were also seen in the film .MRI Pelvis showed predominantly an exophytic mass of size 1.7*4.4*2.5cm in relation to the posterior fornix cranial extent up till the uterocervical junction and caudal uptill the external os with the involvement of inner parametrium. PET-CT of the patient ruled out distant dissemination. The diagnosis of Stage 2 Vaginal Small Cell Carcinoma was made. The immunohistochemistry of the patient was Synaptophysin and Chromogranin A positive and Ki-67 of the patient (80-90 percent) which further confirmed the diagnosis.

MANAGEMENT

Due the ongoing research in various treatment options-in this case as the diagnosis of STAGE-2 VAGINAL SMALLCELL CARCINOMA was made, the patient was started on Concurrent EBRT(External Beam Radiotherapy) with 50 grays and weekly Cisplatin and Etoposide on Days 1-3 every 3 weeks .Currently the patient is undergoing CTRT (Chemotherapy-Radiotherapy)4th week. It is recommended to have 3 monthly Whole Body CT for follow up of the patient as this tumour has very high recurrence rate.

Primary vaginal cancer is a rare cancer accounting for 2-3 % of all genital malignancies Most vaginal cancers are metastatic cancers (84%).Histologically most(80%) vaginal cancers are squamous cell carcinomas.

The small cell carcinomas account for 1- 2% of all malignancies diagnosed in the female genital tract. Its most common primary site is lungs (95%).The most common site involvement of the female genital tract is the cervix, followed by the ovary, endometrium, vagina ,and finally the vulva [3]. The primary site in our patient was the vagina, since the imaging showed no primary disease in most common sites such as the lungs [4].  Albores Saavedra et al. documented the first small cell neuroendocrine carcinoma of the lower female genital tract in 1972, as a carcinoid tumor of the uterine cervix [1]. The first small cell carcinoma with vaginal primary was diagnosed in 1984 by Scully et al. The primary small cell carcinoma of vagina manifests with vaginal bleeding or metastatic symptoms or by leucorrhea or mixed vaginal discharge as in our patient.

The rarity of Small Cell Carcinoma is responsible for the uncertainty of the best therapy and it is basedon the treatment for small cell carcinoma of the lung [5]. Cases of Small Cell Carcinoma restricted to the lungs have better responses with chemoradiotherapy compared to chemotherapy alone, both in complete remission and in survival.

Local therapy alone in small cell carcinoma of the vagina is associated with poor survival, requiring a combination of therapies, as with small cell carcinoma in other primary sites. Initial treatment is chemotherapy associated with radiotherapy or surgical resection associated with adjuvant chemotherapy and radiotherapy. Initial response is excellent, however, distant recurrence is common [6]. So a mandatory 3 monthly Whole Body CT is essential to rule out any distant metastasis.

Small Cell Carcinoma of the vagina is a rare disease with poor prognosis. The effectiveness of combined chemotherapy and radiotherapy is therefore required. The  follow up of this disease is thus required and a 3 monthly Whole Body CT is thus required for follow up due to its high recurrence rate .As only 44 cases have been reported in the entire world ,and Standard therapy has not been established for the disease ,necessitating further accumulation of cases and discussions.

1. Albores-Saavedra, J. et al. “Primary carcinoid of the uterine cervix.” Patologia, vol. 10, 1972, pp. 185–193.

2. Weberpals, J. et al. “A rare case of ectopic adrenocorticotropic hormone syndrome in small cell carcinoma of the vagina: a case report.” Journal of Lower Genital Tract Disease, vol. 12, 2008, pp. 140–145.

3. Hayashi, M. et al. “Primary small cell neuroendocrine carcinoma of the vagina.” Oncology, vol. 58, 2000, pp. 300–304.

4. Cohen, J.G. et al. “The management of small-cell carcinomas of the gynecologic tract.” Current Opinion in Oncology, vol. 24, no. 5, 2012, pp. 572–579.

5. Jeremic, B. et al. “Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited small-cell lung cancer: a randomized study.” Journal of Clinical Oncology, vol. 15, no. 3, 1997, pp. 893–900.

6. Mirhashemi, R. et al. “Vaginal small cell carcinoma mimicking a Bartholin’s gland abscess: a case report.” Gynecologic Oncology, vol. 68, no. 3, 1998, pp. 297–300.