Indian Journal of Pathology and Microbiology

CASE REPORT
Year
: 2021  |  Volume : 64  |  Issue : 1  |  Page : 174--176

Mixed endocervical adenocarcinoma and high-grade neuroendocrine carcinoma of the cervix: A case report


Gizem Teoman, Safak Ersoz 
 Department of Pathology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey

Correspondence Address:
Gizem Teoman
Department of Pathology, Karadeniz Technical University Faculty of Medicine, 61030 Trabzon
Turkey

Abstract

Adenocarcinoma admixed with neuroendocrine carcinoma of the uterine cervix is a rare malignancy with a poor prognosis. In the literature, there are few reported cases. Herein, we report a case of a 56-year-old Turkish woman with cervical adenocarcinoma admixed with small cell neuroendocrine carcinoma. Histological examination of endocervical curettage specimens revealed a tumor composed of almost equal areas of small cell neuroendocrine carcinoma and adenocarcinoma. Neuroendocrine differentiation was confirmed by immunohistochemistry for chromogranin-A, synaptophysin, and CD 56. After the adenocarcinoma and small cell neuroendocrine carcinoma association was detected in the curettage material, both cervicovaginal smear and then total abdominal hysterectomy and bilateral salpingo-oophorectomy resection material of the patient were submitted to our pathology department. Histological features of both curettage and resection material were determined by immunohistochemical studies.



How to cite this article:
Teoman G, Ersoz S. Mixed endocervical adenocarcinoma and high-grade neuroendocrine carcinoma of the cervix: A case report.Indian J Pathol Microbiol 2021;64:174-176


How to cite this URL:
Teoman G, Ersoz S. Mixed endocervical adenocarcinoma and high-grade neuroendocrine carcinoma of the cervix: A case report. Indian J Pathol Microbiol [serial online] 2021 [cited 2022 May 26 ];64:174-176
Available from: https://www.ijpmonline.org/text.asp?2021/64/1/174/306491


Full Text



 Introduction



Cervical neuroendocrine carcinomas are categorized into two groups: low-grade (typical and atypical carcinoid tumor) and high-grade (small cell and large cell) neuroendocrine carcinomas.[1] Small cell neuroendocrine carcinoma accounts for 2% of all cervical cancers. Most of them present a pure form, and only 4% of this type of tumors are associated with adenocarcinoma.[2],[3]

Small cell neuroendocrine carcinomas are very aggressive neoplasms and have a poor prognosis. The differential diagnosis is quite important because the aggressive behavior of the tumor urges more aggressive treatment than other cervix carcinomas. Lymph node involvement[4],[5] and distant metastases occur more frequently and earlier compared with other types of cervical cancer. Since aggressive surgery is not adequate for remission, postoperative adjuvant chemotherapy and/or radiotherapy is usually needed to be performed.

Histological studies of small cell neuroendocrine carcinoma with adenocarcinoma in the uterine cervix in biopsy or cytology specimens have been reported in a limited number of cases in the literature.[5],[6],[7],[8] Here, we described an extremely rare case of mixed endocervical adenocarcinoma with high grade neuroendocrine small cell carcinoma, including the histological and immunohistochemical features.

 Case Report



A Fifty six-years-old patient was admitted to our hospital with abnormal postmenopausal vaginal bleeding and abdominal pain. A consent form was taken for necessary diagnostic tests and procedures.. Her diagnostic tests were normal, except magnetic resonance imaging which revealed a cervical mass of 2 cm in diameter. In the patient's history, a positive test for human papillomavirus type 18 was evident 1 year ago. Firstly, endocervical curettage material was accepted to our pathology laboratory and all of the material was examined. Histologically, the tumor comprised of two adjacent components of almost the whole of the area, containing small-sized cells and moderately-sized cells with a villoglandular structure [Figure 1]a. The smaller cells exhibited a scant cytoplasm, and their nuclei were round with nuclear molding. Tumor cells exhibited nuclear hyperchromasia and inconspicuous nucleoli [Figure 1]b. On the contrary, the area with moderately-sized cells exposed villoglandular patterns [Figure 1]c. Immunohistochemical staining with p16 and mCEA (monoclonal carcinoembryonic antigen) revealed that both the endocervical adenocarcinoma and the neuroendocrine carcinoma were positive. We performed immunohistochemical staining of three neuroendocrine markers: chromogranin-A, synaptophysin, and CD 56 [Figure 2]. In neuroendocrine components, these three markers were positive. A punctate pattern of nuclear staining observed with human papilloma virüs in the endocervical adenocarcinoma component by in-situ hybridization assay [Figure 3]. Mitotic figures were numerous in both tumor areas. No evidence for keratinization was observed, and none of these tumor cells expressed p40 and TTF-1.{Figure 1}{Figure 2}{Figure 3}

The patient had smear cytology of the uterine cervix one month after the diagnosis and then total abdominal hysterectomy with bilateral salpingo-oophorectomy procedure was performed. On the smear cytology of the uterine cervix, different atypical cells were observed on the proteinous background. The tumor cells were composed of two distinctly sized cells. The majority of the tumor cells were found to be relatively smaller than adenocarcinoma cells; these smaller cells presented predominantly hyperchromatic crowded clusters with numerous single cells and with a high nuclear/cytoplasmic (N/C) ratio. Nuclei of solid cell clusters were oval, and generally small to moderate in size.

The total abdominal hysterectomy and bilateral salpingo-oophorectomy material was macroscopically 10 × 8 × 4 cm in size and a 2 × 2 × 1.5 cm solid tumor lesion, involving all cervical quadrants. The histological appearance of the resection material was different from endocervical curettage material. Most of the material has a conventional endocervical adenocarcinoma pattern. In a very small area of endocervical adenocarcinoma with villoglandular pattern and small cell, neuroendocrine carcinoma was observed. Therefore, we believe that the small cell neuroendocrine carcinoma component we had previously detected was luminally growing into the endocervical canal. Therefore, we described the small cell neuroendocrine carcinoma component in the curettage material but in the total abdominal hysterectomy and bilateral salpingo-oophorectomy material, the neuroendocrine component was scarce. No abnormal keratinization was observed in any of the specimens.

 Discussion



In this report, we present a rare case of adenocarcinoma admixed with small cell neuroendocrine carcinoma. According to the current WHO (World Health Organization) classification, tumors that show neuroendocrine differentiation in association with variants of cervical adenocarcinoma are defined as “adenocarcinoma admixed with neuroendocrine carcinoma” in which the prognosis is similar to that of cervical small cell neuroendocrine carcinoma.[7] Small cell neuroendocrine carcinoma of the cervix are uncommon and constitute approximately 2% of cervical neoplasia cases. These tumors are extremely aggressive and are characterized by early nodal and distant metastases.[5] The histological findings of this rare malignancy have been reported only in a few cases in the literature.[5],[6],[7],[8]

During histological examination with curettage material, small cell neuroendocrine carcinoma diagnoses may be intervened with the other malignancies, for example, non-keratinized squamous cell carcinoma; because it contains a neuroendocrine component in a limited number of nested patterns.[2] In squamous cell carcinoma, the nuclei are hyperchromatic with coarsely granular and irregularly distributed chromatin. Nuclear molding is usually absent in squamous cell carcinoma. Especially nuclear molding should be considered the typical morphological features of small cell neuroendocrine carcinoma.[6]

In addition to the cytological examination, human papillomavirus typing techniques may also be useful in the evaluation of patients who were diagnosed with cervical cancer. Human papillomavirus type 18 is more frequently associated with adenocarcinoma and neuroendocrine carcinoma than squamous cell carcinoma.[9] Besides, punctate nuclear positivity of human papillomavirus by in-situ hybridization in the endocervical adenocarcinoma component of these tumors is one of the most important findings in the diagnosis. Therefore, both cytological examination and human papillomavirus genotyping contribute to the diagnosis.

 Conclusion



Adenocarcinoma admixed with neuroendocrine carcinoma of the uterine cervix is a rare malignancy with a poor prognosis and there are a limited number of cases in the literature. Prognosis is mostly related to the behavior of the neuroendocrine component. The association between neuroendocrine malignancies and human papillomavirus subtypes are clinically important for diagnosis. More extensive data are needed to provide for definitive treatment protocols and clinical approaches for this type of tumor but the rarity of this entity is the limiting factor.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Kurman RJ, Carcangiu ML, Herrington CS, Young RH. IRAC WHO Classification of Tumours of Female Reproductive Organs. 4th ed. Lyon: IRAC Press; 2014.
2Toki T, Katayama Y, Motoyama T. Small-cell neuroendocrine carcinoma of the uterine cervix associated with micro-invasive squamous cell carcinoma and adenocarcinoma in situ. Pathol Int 1996;46:520-5.
3Ramalingam P, Malpica A, Deavers MT. Mixed endocervical adenocarcinoma and high-grade neuroendocrine carcinoma of the cervix with ovarian metastasis of the former component: A report of 2 cases. Int J Gynecol Pathol 2012;31:490-6.
4Viswanathan AN, Deavers MT, Jhingran A, Ramirez PT, Levenback C, Eifel PJ. Small cell neuroendocrine carcinoma of the cervix: Outcome and patterns of recurrence. Gynecol Oncol 2004;93:27-33.
5Eichhorn JH, Young RH. Neuroendocrine tumors of the genital tract. Am J Clin Pathol 2001;115:94-112.
6Shimojo N, Hirokawa Y, Kanayama K, Yoneda M, Hashizume R, Hayashi A, et al. Cytological features of adenocarcinoma admixed with small cell neuroendocrine carcinoma of the uterine cervix. Cytojournal 2017;14:12.
7Alphandery C, Dagrada G, Frattini M, Perrone F, Pilotti S. Neuroendocrinwe small cell carcinoma of the cervix associated with endocervical adenocarcinoma. Acta Cytol 2007;51:589-93.
8Hye Rim Park, MD, Yong Woo Lee, MD, Young Euy Park, MD. Composite tumor of adenocarcinoma and small cell neuroendocrinwe carcinoma of the uterine cervix. Kor J. Cytopath 1990;1:111-20.
9Serrano B, Alemany L, Tous S, Bruni L, Clifford GM, Weiss T, et al. Potential impact of a nine-valent vaccine in human papillomavirus related cervical disease. Infect Agent Cancer 2012;7:38.