|Year : 2013 | Volume
| Issue : 2 | Page : 328-330
Primary neuroendocrine carcinoma of the vagina with coexistent atypical vaginal adenosis: A rare entity
Anuj Khurana1, Gurudutt Gupta1, Mohit Gupta1, Manpreet Kaur2
1 Department of Pathology, Rajiv Gandhi Cancer Institute and Research Centre, Sector-5 Rohini, Delhi, India
2 Department of Pathology, MVID Hospital, Kingsway Camp, Delhi, India
|Date of Web Publication||13-Jun-2013|
98 SFS Flats Phase-4 Ashok Vihar Delhi-110052
Source of Support: None, Conflict of Interest: None
Primary neuroendocrine carcinoma of the female genital tract is a rare entity with aggressive clinical behavior and a poor prognosis. This kind of malignancy arising in the vagina is extremely rare. We report a case of primary neuroendocrine carcinoma of vagina arising in a setting of atypical vaginal adenosis.
Keywords: Neuroendocrine carcinoma, vagina, vaginal adenosis
|How to cite this article:|
Khurana A, Gupta G, Gupta M, Kaur M. Primary neuroendocrine carcinoma of the vagina with coexistent atypical vaginal adenosis: A rare entity. J Can Res Ther 2013;9:328-30
|How to cite this URL:|
Khurana A, Gupta G, Gupta M, Kaur M. Primary neuroendocrine carcinoma of the vagina with coexistent atypical vaginal adenosis: A rare entity. J Can Res Ther [serial online] 2013 [cited 2019 Sep 16];9:328-30. Available from: http://www.cancerjournal.net/text.asp?2013/9/2/328/113422
| > Introduction|| |
Primary neuroendocrine carcinoma of the female genital tract is a rare entity with the majority of lesions occurring in the cervix.  Primary vaginal small cell carcinomas are rarer, with only 22 cases have been identified in the English literature so far.  Our indexed case was diagnosed having this lesion in association with atypical vaginal adenosis in the background. The atypical adenosis arising in the vagina has been associated with clear cell adenocarcinoma and less commonly, squamous type but the association with a neuroendocrine tumor is exceedingly rare. To our best of knowledge; we believe our patient to be the second such case where a neuroendocrine tumor is seen arising in the background of atypical vaginal adenosis. 
| > Case Report|| |
A 37-year-old female presented with complaint of irregular bleeding per vaginum of three months duration. On per speculum examination, an irregular annular growth was noted in the vagina at the level of junction of upper two-third and lower one-third, extending to sub-urethral region. The cervix was unremarkable with anteverted uterus. Magnetic Resonance Imaging (MRI) of pelvis and upper abdomen showed a diffuse enhancing thickening in relation to mid portion of vagina with apparently free paravaginal planes. [Figure 1]a Uterus revealed a bulky fibroid in the anterior wall extending to the fundal region. Cervix appeared uninvolved. No enlarged pelvic or inguinal lymphnodes were noted. As a part of diagnostic work-up, a Computed Tomography (CT) of the chest was done which showed no lung lesions.
|Figure 1: (a) MRI film showing diffuse thickening of the vaginal wall. (b) Gross photograph showing thickened vaginal wall with nodularity|
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Biopsy from the vaginal lesion showed tightly packed nests of tumor cells having round to oval to spindle morphology with ill-defined cell borders, granular hyperchromatic nuclear chromatin, and absent to inconspicuous nucleoli. The tumor cells exhibited nuclear moulding with marked nuclear anaplasia at places. The mitotic and apoptotic activity was found to be brisk.
On immunohistochemical staining the tumor cells showed cytoplasmic positivity for synaptophysin, CD56 along with dot-like positivity for cytokeratin (CK5 and CK7). The cells were negative for p63, carcino-embryonic antigen (CEA), thyroid transcription factor-1 (TTF-1). Thus a diagnosis of a poorly differentiated neuroendocrine carcinoma was made. In view of unremarkable chest CT, a primary lung lesion was ruled out, and the final diagnosis of Primary Neuroendocrine Carcinoma of vagina was rendered.
Subsequently patient underwent total vaginectomy and pelvic lymphadenectomy. The prosector noted an ill defined, grey-white ulcerated tumor, 4×4×1.5 cms in size with diffuse thickening of the vaginal wall. A nodule was seen in the tumor specimen located near the upper part measuring 2×1.5×1.2 cm, whose cut section revealed a single cyst; 1 cm in diameter [Figure 1]b. Microscopy showed a tumor with similar histologic picture as in the biopsy specimen [Figure 2]. The bulk of this tumor was in the submucosa. In addition, the vaginal epithelium showed extensive adenosis involving all the walls of vagina as well as stroma surrounding the neuroendocrine tumor. [Figure 3]a The glands were lined by single layer of cuboidal to columnar epithelial cells containing abundant cytoplasm and round to oval nuclei with pale chromatin. At places atypical features of nuclear crowding, pseudostratification and hyperchromasia were noted. Transition from benign to atypical adenosis was observed and at places foci of atypical adenosis was merging with the tumor. [Figure 3]b Immunohistochemical staining was repeated on the vaginectomy specimen and the earlier results were confirmed [Figure 4]. A final diagnosis ofneuroendocrine carcinoma of vagina along with co-existent atypical vaginal adenosis was made. All the regional lymphnodes were free of tumor.
|Figure 2: Microphotograph showing tight nests and scattered tumor cells exhibiting nuclear pleomorphism. Salt and pepper type chromatin of the nuclei can be seen.(H and E, × 400)|
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|Figure 3: (a) Microscopy showing vaginal adenosis lying beneath stratified squamous epithelium. (Hematoxylin and Eosin ×200) (b) Microphotograph showing vaginal adenosis merging with the neuroendocrine tumor.(H and E, × 200)|
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|Figure 4: Synaptophysinimmunostain diffusely staining the cytoplasm of the tumor cells. (DAB, × 400)|
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Post operatively the patient received 6 cycles of etopside (140 mg) and cisplatin (50 mg) based chemotherapy (CT). The serial serum levels of Neuron specific enolase and chromogranin showed a gradual decline over the 6 cycles of CT.
Thereafter she received external beam radiotherapy (RT) to the pelvis to a dose of 45 gray in 25 fractions.After the completion of the CT and RT, patient is well and symptom-free of the disease since last 1 year.
| > Discussion|| |
Primary neuroendocrine carcinoma of the female genital tract is rare, constituting less than 2% of all gynecologic malignancies.  It has beenreported in the cervix, endometrium, ovary, vagina, and vulva, in decreasing frequency.  Primary vaginal small cell carcinoma, first reported by Scully et al., is very rare. 
Patients with small cell carcinoma of female genital tract may be asymptomatic but usually present with localized pain, vaginal bleeding, abdominal bloating or a mass. They may also present with symptoms of metastatic disease to the liver, bone, lung or regional lymph node.  Median survival of the patients is 11 months ranging from 4 months to 24 months. 
Vaginal adenosis is defined as the presence of glandular epithelium in the vagina and is thought to be the result of persistence of embryonic mullerian epithelium islets in postembryonic life; the presence of atypicality of the nuclei in this epithelium defines it as atypical adenosis.  Vaginal adenosis may arise in up to 90% of the women who have been prenatally exposed to diethylstilboestrol (DES) however mostly it is considered an insignificant coincidental finding.  Its association with in-utero exposure of DES and a subsequent high risk of clear-cell vaginal adenocarcinoma is well known.  Since the withdrawal of DES, vaginal adenosis is rarely encountered.  The mother of our patient was not available, though the patient on detailed questioning told that her mother had bad obstetric history and conceived seven years post marriage. Hence we presume that DES could have been administered to the mother of the patient, though there is no conclusive evidence.
The indexed case is unusual for many reasons. The rare tumor was a pure primary vaginal neuroendocrine carcinoma, which was associated with infrequently encountered vaginal adenosis. The vaginectomy specimen, although extensively sampled, did not show any other component to the lesion, namely squamous carcinoma or adenocarcinoma. Thus, this lesion does not appear to represent a multidirectional or bidirectional differentiation of some primitive precursor. Hence, we propose that the vaginal adenosis was the cell of origin for the neuroendocrine carcinoma.
These tumors are aggressive with propensity to early dissemination. In view of such behaviour, though no consensus is there, a multimodality therapy even in the early stage of the disease is recommended.
| > Acknowledgement|| |
Dr Jatin S.Gandhi, Department of Pathology, Rajiv Gandhi Cancer Institute And Research Centre, Sector-5 Rohini, Delhi - 110 085.
| > References|| |
|1.||Prasad CJ, Ray JA, Kessler S. Primary small cell carcinoma of the vagina arising in a background of atypical adenosis. Cancer 1992;70:2484-7. |
|2.||Bing Z, Levine L, Lucci JA, Hatch SS, Eltorky MA. Primary small cell neuroendocrine carcinoma of the vagina: Aclinicopathologic study. Arch Pathol Lab Med 2004;128:857-62. |
|3.||Crowder S, Tuller E. Small cell carcinoma of the female genital tract. SeminOncol 2007;34:57-63. |
|4.||Scully RE, Aguirre P, DeLellis RA. Argyrophilia, serotonin, and peptide hormones in the female genital tract and its tumors. Int J GynecolPathol 1984;3:51-70. |
|5.||Anderson ES, Paavonen J, Murnaghan M, Ostor AG, Hanselaar AG, Bergeron C, et al. Tumors of vagina. World Health Organization Classification of Tumors. Pathology and Genetics of Tumors of the Breast and Female Genital Organs. Lyon: IARC Press; 2003. p. 299. |
|6.||Cebesoy FB, Kutlar I, Aydin A. Vaginal adenosis successfully treated with simple unipolar cauterization. J Natl Med Assoc 2007;99:166-7. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]