A mixture of neuroendocrine carcinoma and adenocarcinoma in the cervix is a tumor that has characteristics of neuroendocrine differentiation and cervical adenocarcinoma, this disease is very rare. Neuroendocrine tumors in the cervix can arise from neuroendocrine granule cells that are normally present in the cervix or from the cervical reserve/stem cells. There are 4 classifications of this type of tumor, namely typical carcinoid tumors, atypical carcinoid tumors, small cell carcinomas, and large cell carcinomas.1 Small cell carcinoma types are more common than other types, which is around 2% to 5% of all cervical cancers.2 Some studies state that only 4% of small cell carcinomas are coexistent with adenocarcinoma.3 This type of tumor has a poor prognosis and so far no standard treatment has been obtained for this type of tumor.4
A 35-years-old woman presented with chief complaint of bleeding outside of menstruation. This bleeding persisted as from the last year accompanied by discomfort in the lower abdomen. Patients also experience vaginal discharge accompanied by blood since the last 6 months. Patient had history of using 6-month oral contraception.
The physical examination showed an exophytic mass of 4 cm diameter in the portio of cervix. Ultrasound shows enlarged portio with a mass of 4.2 cm × 2.9cm. Temporary diagnosis of this patient is cervical Ca stage II and recommended for biopsy of the cervix. Microscopic biopsy results showed invasive epithelial malignant tumor into the connective tissue formed mostly solid structures, sheets, papillaries, and few form glands and cribiform structures (Figure 1).
Relatively large tumor cells which shows invasively proliferate with organoid nesting pattern and central necrosis. Immunohistochemical staining of the biopsy tissue was done by staining Chromogranin, synaptophycin, CD 56, NCAM, P40, p63 and Ki 67 to detect neuroendocrine carcinoma (Figure 2) In biopsy tissue, P63 immunohistochemical staining was negative result and chromogranin, synaptophycin, CD 56, NCAM were positive result. In biopsy tissue, P40 immunohistochemical staining was positive result and so did CK 19, CEA, and CK 7 staining to detect positive for confirming adenocarcinomas. Patient treated with concurrent chemoradiotherapy but outcome not so well. Furthermore, that patient received palliative chemotherapy for residual mass along with symptomatic management.
I report a very rare case, a mixture of neuroendocrine carcinoma and adenocarcinoma of the cervix. Patient had clinical manifestations of bleeding outside the menstrual cycle accompanied by vaginal discharge and discomfort in the hip. This is consistent with the theory that states that tumors with small and large cell neuroendocrine carcinoma components have manifestation of vaginal bleeding, cervical mass, and/or abnormal cervical cytology. In biopsy tissue, P63 immunohistochemical staining was performed to detect squamous cell carcinoma with negative results. This was done to eliminate the diagnosis of squamous cell carcinoma. Usually, more frequent cases founded were squamous cell carcinoma or a mixture of squamous cell carcinoma with adenocarcinoma (adenosquamos carcinoma). Furthermore chromogranin, synaptophycin, CD 56, NSE, and P40 immunohistochemical staining were performed to detect neuroendocrine with positive results and so did CK 19, CEA, and CK 7 staining to detect positive adenocarcinomas. This shows that this tissue is indeed a mixed case between neuroendocrine carcinoma and adenocarcinoma in cervix. In biopsy tissue, a mixture of neuroendocrine carcinoma and adenocarcinoma is suspected, immunohistochemical staining should also be done to detect adeno-squamous carcinoma. So that patient could get appropriate management and prognosis.
This case is a mixture of neuroendocrine carcinoma and adenocarcinoma in cervix due to the positive markers supporting the carcinoma.