INTRODUCTION:

Neuroendocrine carcinoma of the cervix (NECC) is an uncommon and aggressive tumor type, representing under 2% of all cervical cancer cases. The NECC differentiation can present diagnostic challenges, as its clinical and histopathological features often overlap with other cervical malignancies.

The NECC categorizes into low-grade and high-grade tumours, which are linked to human papillomavirus (HPV) type 18 and, to a lesser degree, with type 16. NECC's most common molecular alterations include Carcinogenic Antigen phosphatidylinositol-3-kinase (PIK3CA), Kirsten rat sarcoma (KRAS), and tumour suppressor gene (TP53) mutations. Immunohistochemical staining with CD56, synaptophysin, and chromogranin serves as a useful aid in the diagnosis.¹

We report the case of a 46-year-old Indian woman with a neuroendocrine tumour of the cervix, diagnosed at an advanced stage and treated with chemotherapy and radiotherapy.

Case Report:

A 46-year-old, single, sexually inactive Indian woman presented with complaints of prolonged menstrual bleeding since January 2024, associated with significant weight loss of 10kg over 5 months and loss of appetite. She had multiple hospital admissions for symptomatic anaemia, requiring blood transfusions in February and July 2024.

During her admission in September 2024, she was noted to be pale but alert. Her vital signs included a pulse rate of 96 beats per minute and a blood pressure of 129/77 mmHg. On speculum examination, an exophytic mass measuring 3x4cm occupying the entire circumference of the cervix and extending into the upper third of the vagina was observed. The bimanual examination revealed bilateral parametrium thickening which was more pronounced on the right side. A per rectal examination revealed an extraluminal mass about 5 cm from the anal verge with mobile smooth anal mucosa and an empty rectum.

A biopsy of the cervical mass was performed. The histopathological examination revealed small, monotonous cells with scant cytoplasm, hyperchromatic nuclei, high mitotic activity and focal extensive necrosis arranged in nests, sheets or trabecular patterns with features of nuclear molding and a "salt and pepper" chromatin pattern with neuroendocrine differentiation [Fig 1]. The tumour has reached the lower part of the vagina and was diagnosed as a Stage IIIIA NECC, based on World Health Organization (2020) Classification.

Fig 1. (A) A neuroendocrine component characterized by small cells with focal necrosis (asterisk), round or ovoid nuclei with finely granular chromatin, evident nucleoli and numerous mitoses (arrows) (magnification, x200). (B) The neuroendocrine component exhibited intense membrane immunoreactivity for synaptophysin (magnification, x200)

Investigations:

1. Transabdominal Ultrasound: The uterus measured 6.5x3.3 cm, with an endometrial thickness of 4.2 mm a massive cervical tumor measuring 9.3x8.2 cm was observed occupying the top part of the vagina The kidneys were normal and the liver was homogeneous.

2. Computed Tomography Thorax, Abdomen, and Pelvis (CT TAP): On 7^th October 2024 a computed tomography scan of the thorax abdomen and pelvis revealed a cervical mass with no discernible fat plane separating it from the uterus, right ovary and rectum. The tumour filled the upper two-thirds of the vagina and no distant metastases were found. The pulmonary artery embolism was also seen.

Management and Treatment:

The diagnosis of neuroendocrine carcinoma required an early intensive treatment strategy involving chemotherapy. The patient and her sister-in-law had an in-depth conversation about the risks and possible complications of chemotherapy, including myelosuppression, nephrotoxicity, and gastrointestinal problems. It was clarified that chemotherapy would be administered every 3–4 weeks over 6 cycles, with at least 3 days of inpatient observation for each cycle because of anticipated side effects

On admission, her haemoglobin level was 6.9g/dl, and she required a transfusion of 2 pints of packed red blood cells. Following transfusion and regular haematinics, her haemoglobin improved to 9.3g/dl.

Due to her history of pulmonary artery embolism, the patient was started on anticoagulation therapy with subcutaneous Clexane for 3 days, followed by oral Rivaroxaban 15mg twice daily for 21 days, then reduced to 20mg once daily for 3 months.

Because of her pulmonary artery embolism, the patient began anticoagulation treatment using subcutaneous Clexane for 3 days, followed by oral Rivaroxaban 15mg twice a day for 21 days, which was then lowered to 20 mg once daily for 3 months.

The patient was started on a chemotherapy regimen of Etoposide and Cisplatin for 6 cycles. Full blood counts, liver function tests, renal profiles, and electrolyte investigations were monitored after each chemotherapy cycle. The six cycles of chemotherapy were completed on 20th December 2024. The follow-up CT TAP on 23^rd December 2024 showed no signs of disease progression [Fig 2].

Fig. 2 (A) CT TAP before treatment.

Fig. 2 (B) CT TAP after treatment.

Follow-up and Future Plans:

The patient will proceed to radiotherapy after the completion of chemotherapy. A cystoscopy will be arranged before initiating radiotherapy to further evaluate her condition. Ongoing monitoring will include regular follow-up appointments to assess for any potential side effects from the treatment and to evaluate for any signs of disease recurrence.

DISCUSSION:

NECC is a rare and highly aggressive malignancy that accounts for 0.9 – 1.5% of all cervical malignancies.¹ This form of cancer is often late diagnosed due to its nonspecific symptoms of prolonged vaginal bleeding, weight loss and anaemia. These symptoms are common to several other conditions, thus leading to delayed diagnosis and treatment. In this case, the patient presented prolonged menstrual bleeding, significant weight loss, and anaemia, which are non-specific typical symptoms and delayed early recognition of the malignancy.

Given the rarity and aggressive nature of neuroendocrine carcinoma, it is crucial to provide early and aggressive treatment, which may significantly affect patient outcomes. The treatment for this malignancy typically involves a combination of surgery, chemotherapy and radiotherapy. However, in this patient, due to the advanced stage at diagnosis, surgery was not considered a viable option. Chemotherapy remains the cornerstone of treatment with Etoposide and Cisplatin being the most used regimens for this disease (Verma et al.,2023; Tangella & Yadlapalli, 2023).^2,3 In this case, the patient was also treated with Etoposide and Cisplatin for six cycles, which is consistent with current treatment protocols for neuroendocrine carcinoma of the cervix (Zhang et al., 2023).⁵

Furthermore, the patient’s treatment was complicated by the presence of pulmonary artery embolism which is a known risk in cancer patients undergoing chemotherapy. The patient was placed on anticoagulation therapy with Clexane and Rivaroxaban which is critical in managing thromboembolic events. Early recognition and management of such complications are essential in maintaining patient stability and preventing further adverse outcomes during chemotherapy (D'Adda et al., 2021).⁴

NECC is known to have a poor prognosis due to their aggressive behaviour and tendency to present at later stages. As highlighted by Suresh & Ferriss (2023)⁶, chemotherapy, often combined with radiotherapy, is the standard approach to treating these tumours. Immunotherapy has turned out has a backbone in the treatment of cervical cancer, particularly after the approval of pembrolizumab (anti-PD1) in combination with chemotherapy as first-line treatment in metastatic and recurrent PD-L1-positive cervical cancers (Walsh and Tan, 2021)⁷. However, despite aggressive multimodal treatment, the prognosis remains guarded. To increase survival rates, early detection and timely treatment beginning are essential.

This instance emphasizes how crucial a multidisciplinary approach is to the treatment of aggressive and uncommon tumors like NECC. Early diagnosis, suitable chemotherapy regimens, and supportive treatment (such as anticoagulation for thromboembolic events) might enhance the patient's quality of life and perhaps prolong longevity, even though the prognosis is still poor.

CONCLUSION:

This case emphasized the importance of early recognition by regular Pap smear test, HPV screening test and cervical biopsy in abnormal Pap smear and HPV test results with multidisciplinary management of NECC. Despite its rarity, aggressive treatment with chemotherapy and radiotherapy can offer significant benefits for patients with this condition. Continued follow-up is essential to monitor for recurrence and manage potential treatment-related complications.

CONSENT:

Written informed consent was obtained from the patient to publish this case report.

DECLARATION OF COMPETING INTEREST:

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

REFERENCES:

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Received on 11.01.2025 Revised on 21.03.2025

Accepted on 24.05.2025 Published on 12.06.2025

Available online from June 14, 2025

Research J. Pharmacy and Technology. 2025;18(6):2697-2699.

DOI: 10.52711/0974-360X.2025.00387

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