Small Round Cell Tumor/Primary Neuroendocrine Tumor Vagina
Corresponding Author: Romman Fatima, Department of Internal Medicine, Olive Hospitals, Hyderabad, Telangana, India, Phone: +91 9381305172, e-mail: firstname.lastname@example.org
How to cite this article: Fatima R, Srikanth J, Fatima A. Small Round Cell Tumor/Primary Neuroendocrine Tumor Vagina. J Obstet Gynaecol Pract POGS 2023;1(2):58–60.
Source of support: Nil
Conflict of interest: None
Received on: 30 July 2023; Accepted on: 30 August 2023; Published on: 22 November 2023
Background: Primary neuroendocrine tumors are neural crest cells in origin composed of solid sheets of undifferentiated small round cells that stain for CD99, S100 protein, neuron-specific enolase, and vimentin. Neuroendocrine tumors are also referred to as amine precursor uptake and decarboxylation (APUD) tumors because these cells often show amine precursors like levodopa and 5-hydroxytryptophan uptake and their subsequent decarboxylation to produce amines such as serotonin and catecholamines. Neuroendocrine tumors can be classified according to their anatomical (Novel Treatment of Small-Cell Neuroendocrine of the Vagina, n.d.) and by their levels of differentiation. They are graded histologically into GX-indeterminate; G1 – having a mitotic count below 2; G2 – mitotic count between 2 and 20; and G3 – mitotic count greater than 20. The Ki67 index can also be used for grading the tumors where grade 1 corresponds to 3%, grade 2 corresponds to between 3 and 20%, and grade 3 corresponds to above 20%.
Since these tumors secrete metabolites, that can be used as biomarkers; new markers are extensively studied besides those mentioned above like truncated heat shock protein 70, high levels of CDX2 a homeobox gene end product that plays a vital role in intestinal differentiation, and protein 55 which belongs to the chromogranin family. Several other methods are available to diagnose small tumors that are missed on CT scans, such as octreoscan, somatostatin receptor scintigraphy indium-111 scan, and even more accurate gallium-68-DOTATOC (Primary Small Cell Neuroendocrine Carcinoma of Vagina: A Rare Case Report, n.d.) scan.
These tumors have an incidence of about 2.5–5 per 1,000 cases; one such case of genitourinary neuroendocrine tumor is described in this article.
Keywords: Case report, Gynecological cancer, Menopause, Vaginal.
A 56-year-old gravida 0, para 5, live 5 (G0P5L5) female presented to the hospital with chief complaints of postcoital spotting and discharge per vaginam which was not associated with pruritis, weight loss, nausea, vomiting, and low appetite. She was a known type 2 diabetic and had hypertension. Her surgical history was significant for total abdominal hysterectomy 18 years back, for dysfunctional uterine bleeding (age of menarche, 14 years; attained menopause, 18 years back; status, postsurgery).1,2
On speculum examination as shown in Figure 1, a 3 cm × 2 cm friable mass was located on the lateral wall of the vagina that did not bleed on touch, was polypoidal, and had a 1 cm stalk. The remainder of the vagina appeared healthy, bilateral parametria free and no inguinal lymph nodes were palpable. A surgical biopsy from the lesion along with immunohistochemistry followed by whole-body positron emission tomography–computed tomography (PET–CT) was performed.
The lesion biopsy, as depicted in Figure 2, showed a soft tissue section lined by stratified squamous epithelium with infiltrative cells arranged in clusters and sheets. The cells were small round and uniform with a hyperchromatic nucleus and scant cytoplasm. Mild stromal lymphocytic infiltration without any perineural or lymphovascular invasion conclusive of primitive neuroectodermal tumor or small round cell tumor of the vagina. The tumor was characterized further using immunohistochemical markers such as a pan-cytokeratin (PANCK), marker of the epithelial or ectodermal component (dot positive); synaptophysin weakly diffuse positive; CD99 negative; KI67 index of 70–80% (high); and P16 immunostain positive suggestive of neuroendocrine origin.
Positron emission tomography–computed tomography revealed an intensely fluorodeoxy glucose (FDG) avid heterogeneous enhancing nodular soft tissue lesion in the lower vagina measuring 1.9 cm × 2.1 cm × 2 cm in size with a hypermetabolic small volume left axillary lymph node and diffuse hypermetabolic activity in the stomach, as shown in Figure 3, which was suggestive of a primary vaginal malignancy. A fine needle aspiration cytology (FNAC) was performed on the axillary lymph node to look for possible metastasis of primary, reports revealed inflammatory hyperplasia. This was followed by deep blind endoscopic and colonoscopy biopsies that revealed insignificant for second primaries.
Viral markers for HIV, hepatitis B, and hepatitis C were sent along with polymerase chain reaction (PCR) for human papillomavirus (HPV) 16/18/31. Investigations revealed a negative viral screen. The patient was treated by wide local excision with a 1 cm margin of the nodule followed by further evaluation to ascertain clear margins which eliminated the role of lymph node dissection. The patient was given three cycles of concurrent chemoradiotherapy with 60 mg/m2 of cisplatin, 100 mg/m2 of etoposide, and 70Gy external beam radiation along with brachytherapy. Reassessment on follow-up after 3 months revealed a good response to the regimen and a maintenance regimen of 75 mg/m2 cisplatin and 120 mg/m2 etoposide was initiated. The patient was to return for continuing further cycles of chemotherapy and was discharged in stable condition.
Primary vaginal small round cell tumors are rare malignancies that make up about 1–2% of all gynecological malignancies. Their median age of incidence is around 58 (Kessler, n.d.) years from all the cases ever reported and ranges typically between 32 and 81 years overall.3 These malignancies can be asymptomatic but can also present with postcoital bleeding, vaginal mass, discharge, dyspareunia, and rarely may secrete paraneoplastic substances like adrenocorticotropic hormone that can result in Cushing’s disease. These have a propensity to occur in the cervix followed by ovaries, endometrium, vagina, and vulva in order of descending frequencies. Their close differential diagnosis includes melanoma, endometrial sarcomas, primitive neuroectodermal tumors, and rhabdomyosarcomas. Several markers have been studied to distinguish these tumors along with immunohistochemical stains example perinuclear dot staining for CAM-5, paranuclear staining for CK20, and expression of CDX2. There has been a strong association of these cancers with HPV strains but the definite role is still unclear. These malignancies exhibit aggressive behavior and have a median survival of around 11–12 months after diagnosis with a poor survival rate. About half of the cases present with advanced stage and 90% of them have tumor size of greater than 3 cm. Therefore, multimodal therapy is initiated when identified in the early stage as they have demonstrated a greater survival benefit. The commonly administered chemotherapy regimens include cisplatin, doxorubicin, vincristine, cyclophosphamide, and etoposide in addition to radical surgical excision of the lesion, node dissection, and regional radiotherapy. The above-mentioned case did not bear any underlying risk factors and was a classic example of the sporadic origin of the tumor with an absence of metastasis to the rest of the body. Recent advances in treatment include peptide receptor radionuclide therapy with lutetium 177, yttrium-90, and indium 111 which are highly targeted therapies that have minimal adverse effects and are useful for low-grade tumors, and AdVince therapy or oncolytic adenovirus therapy is in phase 1 trial of studies and is yet to be approved but can be a source of new targeted therapy for neuroendocrine tumor.
3. Prasad CJ, Ray JA, Kessler S. Primary small cell carcinoma of the vagina arising in a background of atypical adenosis. Cancer 1992;70(10):2484–2487. DOI: 10.1002/1097-0142(19921115)70:10<2484:aid-cncr2820701015>3.0.co;2-o.
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