Adenocarcinoma of the cervix involving the fallopian tube mucosa: report of a case
© The Author(s). 2016
Received: 13 May 2016
Accepted: 9 August 2016
Published: 17 August 2016
Fallopian tube involvement by cervical carcinoma has rarely been documented, with literature reports focusing primarily on squamous cell carcinoma.
In this report, we present the case of a 50 year old woman who presented with an abnormal Pap test with atypical squamous and glandular cells. A loop electrosurgical excision procedure (LEEP) was performed and led to the diagnosis of stage IB1 endocervical adenocarcinoma. Subsequent radical hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic lymph node dissection showed a well-differentiated endocervical adenocarcinoma of usual type with superficial spread to the endometrium and right fallopian tube. The patient received no adjuvant therapy and has remained without evidence of disease.
While the advent of more extensive fallopian tube sampling has led to increased discovery and discussion of fallopian tube involvement by metastatic carcinoma, its impact on treatment and prognosis remains to be seen.
Because fallopian tube carcinoma was thought to be a rare occurrence, the fallopian tube had not been emphasized in gynecologic malignances until rather recently. The recognition that serous carcinomas of ovarian type frequently involved the fallopian tube fimbria  has recently led to the concept that, in fact, the fallopian tube epithelium was the origin of most high grade ovarian serous carcinomas. There is now a strong interest in establishing the role of the fallopian tube in gynecologic malignancies and, increasingly, the entire fallopian tube is being submitted for histologic analysis.
In this report, we present a case of a 50 year old woman who was diagnosed with stage IB1 well-differentiated endocervical adenocarcinoma with surface extension to the endometrium and fallopian tube, confirmed by histologic and immunohistochemical analysis. Fallopian tube involvement by cervical adenocarcinoma is a rarely reported entity with as yet unknown effects on patient outcome. The introduction of more extensive adnexal sampling may yield similar cases and encourage further discussion of its significance to treatment and survival.
A 50 year old woman with a normal Pap smear history presented in 2012 with an abnormal Pap smear that showed atypical squamous cells, cannot exclude high grade lesion (ASC-H) and atypical glandular cells. Cervical biopsy and endocervical curettage (ECC) showed atypical glandular/endocervical epithelium. A loop electrosurgical excision procedure (LEEP) was performed, revealing well-differentiated adenocarcinoma of the cervix with mucinous and intestinal features. The tumor measured 12 mm in horizontal spread and invaded 8 mm into the stroma. The deep stromal, endocervical, and ectocervical margins were positive. PET/CT was negative for metastatic disease. Given her apparent stage IB1 disease, the patient was dispositioned to radical hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic lymph node dissection.
Cervical cancer remains the third most common gynecologic malignancy in the United States, occupying 0.8 % of all new cancer cases in the U.S.  Based on 2008–2012 cases and deaths reported in the SEER registry, the number of new cases of cervical cancer was 7.7 per 100,000 women per year . Importantly, the number of new cases of cervical cancer has been declining steadily over the past decade, primarily due to improved Pap smear screening programs. However, this important trend does not extend to all histologic subtypes of cervical cancer. The rate of squamous cell carcinoma has declined steadily with the advent of Pap testing, but the incidence of adenocarcinoma and adenocarcinoma in situ (AIS) appears to be increasing [4, 5]. Particularly, adenocarcinoma appears to be occurring at an increased frequency in younger women [4, 5]. Several factors have been suggested to explain this trend, including the difficulty in diagnosing glandular lesions via Pap smear and other etiologic factors such as nulliparity, obesity, and changes in oral contraceptive use .
Upper genital tract involvement by cervical carcinoma has received little attention, with limited cases reported in the literature [6, 7]. Ovarian metastasis by cervical cancer is well recognized; the incidence is reportedly higher in adenocarcinoma compared to squamous cell carcinoma . The incidence ranges from 2 to 28.6 % in cervical adenocarcinoma and 0 to 17.4 % for squamous cell carcinoma, depending on disease stage . The suggested variable of tumor size greater than 30 mm affects the incidence of ovarian metastasis in cervical adenocarcinoma, while ovarian metastasis in cervical squamous cell carcinoma appears to depend more on clinical stage . Whether due to changing thoughts about the pathogenesis of ovarian cancer or other factors, increased fallopian tube sampling has led to the interesting discovery of metastatic cancers. Rabban et al.  reported the pattern and topography of 100 non-gynecologic cancers that metastasized to the fallopian tubes. Most tumors were adenocarcinoma, primarily of colon and breast origin. The metastatic tumors primarily favored the fimbriae of the fallopian tube, with patterns of mucosal growth ranging from flat lesions to lesions with varying degrees of exophytic growth and stratification . These metastatic tumors can mimic primary benign and malignant neoplasms of the fallopian tube, creating a potential diagnostic pitfall [10, 11]. In many cases, a high morphologic index of suspicion along with confirmatory ancillary HPV testing helped make the correct diagnosis .
Compared with ovarian metastasis, reports of cervical metastasis to the fallopian tube are extremely rare, with individual case reports primarily of the squamous lesions . Recently, Reyes et al.  analyzed 20 cases of cervical carcinoma with secondary involvement of the uterine corpus and adnexa. Fallopian tube metastasis by endocervical adenocarcinoma was seen in 8 of 10 cases, primarily occurring as microscopic lesions . These microscopic lesions showed mucosal colonization mimicking a primary tubal process. To avoid this potential diagnostic pitfall, the authors emphasized the importance of analyzing distinct morphologic as well as immunohistochemical features to differentiate between endocervical adenocarcinoma and primary tubal malignancies.
Histologic evaluation of these metastatic lesions reveal elongated, hyperchromatic nuclei with focal mucinous areas and typical histologic features of cervical adenocarcinoma, including prominent apical mitoses and numerous apoptotic bodies . Immunohistochemistry and in-situ hybridization (ISH) can provide further clarification of the primary source of malignancy. In particular, endocervical adenocarcinomas are characterized by positive HPV ISH and negative p53 overexpression, while serous tubal intraepithelial carcinomas (STIC) exhibit p53 overexpression or null pattern and negative HPV ISH. WT-1 positive immunostaining would also favor a tubal serous neoplasm . Importantly, immunohistochemistry for p16 is not helpful in this differential, as both high-grade serous tumors and cervical adenocarcinomas are typically strongly and diffusely positive. Fallopian tube involvement by metastatic carcinoma, whether gynecologic or non-gynecologic, has received increased attention with the advent of more extensive fallopian tube sampling. The current paradigm of high-grade serous carcinomas of the ovary potentially arising from the fallopian tube may explain this increased sampling phenomenon [10, 13, 14]. The authors suggest that, due to increased sampling, recognition of metastatic fallopian tube involvement by carcinoma may become more frequent.
In our case, morphologic and immunohistochemical patterns confirmed the spread of primary cervical adenocarcinoma to the endometrium and fallopian tube. The proposed mechanism of upper genital tract involvement by cervical carcinoma is contiguous and transtubal spread . The effect of fallopian tube involvement on prognosis and treatment remains unclear. Certainly, there is concern for possible exposure of the tumor to the peritoneal cavity. FIGO staging of cervical carcinoma remains clinical staging and fallopian tube involvement is not mentioned . The present case suggests that the spread of endocervical adenocarcinoma to the endometrium and adnexa may not necessarily be associated with a worse prognosis in patients with disease that is otherwise localized to the cervix. However, additional follow-up studies are needed. In conclusion, upper genital tract involvement by cervical adenocarcinoma remains a rare event, although more extensive adnexal sampling will likely yield additional examples. The impact of tubal involvement by cervical cancer on patient outcome, if any, remains to be established.
ECC, endocervical curettings; ER, estrogen receptor; ISH, in situ hybridization; LEEP, loop electrosurgical excision procedure; WT-1, Wilms tumor antigen
Availability of data and materials
All available data is enclosed in Case Report.
CDD interpreted the pathology slides, took the photomicrographs and drafted the manuscript. RAA performed the HPV genotyping and participated in writing the manuscript. LLH performed the chart review for the clinical history and follow-up and participated in writing the manuscript. REZ reviewed the pathology slides, participated in the diagnosing the case and oversaw the production of the manuscript. All authors approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Written informed consent for the publication of this case has been obtained from the subject and a copy is available for review by the Editor-in-Chief of this journal.
Ethics approval and consent to participate
Not applicable for Case Report.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Salvador S, Gilks B, Köbel M, Huntsman D, Rosen B, Miller D. The fallopian tube: primary site of most pelvic high-grade serous carcinomas. Int J Gynecol Cancer. 2009;19:58–64.View ArticlePubMedGoogle Scholar
- Shanesmith R, Allen RA, Moore WE, Kingma DW, Caughron SK, Gillies EM, Dunn ST. Comparison of two line blot assays for defining HPV genotypes in oral and oropharyngeal squamous cells carcinomas. Diagn Microbiol Infect Dis. 2011;70:240–5.View ArticlePubMedGoogle Scholar
- SEER Stat Fact Sheets. Cervix Uteri Cancer. SEER: Surveillance, Epidemiology, and End Results Program [database online]. Bethesda: National Cancer Institute; 1996.Google Scholar
- Wang SS, Sherman ME, Hildesheim A, et al. Cervical adenocarcinoma and squamous cell carcinoma incidence trends among white women and black women in the United States for 1976–2000. Cancer. 2004;100(5):1035–44.View ArticlePubMedGoogle Scholar
- Smith HO, Tiffany MF, Qualls CR, Key CR. The rising incidence of adenocarcinoma relative to squamous cell carcinoma of the uterine cervix in the United States-A 24-year population-based study. Gynecol Oncol. 2000;78:97–105.View ArticlePubMedGoogle Scholar
- Gungor T, Altinkaya SO, Ozat M, et al. Unusual form of superficial spreading squamous cell carcinoma of cervix involving the endometrium, bilateral tubes and ovaries: a case report with literature review. Arch Gynecol Obstet. 2011;283:323–7.View ArticlePubMedGoogle Scholar
- Jaiman S, Surampudi K, Gundabattula SR, Garg D. Bilateral ovarian metastatic squamous cell carcinoma arising from the uterine cervix and eluding the Mullerian mucosa. Diagn Pathol. 2014;9:109.View ArticlePubMedPubMed CentralGoogle Scholar
- Nakanishi T, Wakai K, Ishikawa H, et al. A Comparison of ovarian metastasis between squamous cell carcinoma and adenocarcinoma of the uterine cervix. Gynecol Oncol. 2001;82:504–9.View ArticlePubMedGoogle Scholar
- Reyes C, Murali R, Park KJ. Secondary involvement of the adnexa and uterine corpus by carcinomas of the uterine cervix. A detailed morphologic description. Int J Gynecol Pathol. 2015;34(6):551–63.View ArticlePubMedGoogle Scholar
- Rabban JT, Vohra P, Zaloudek CJ. Nongynecologic metastases to fallopian tube mucosa: a potential mimic of tubal high-grade serous carcinoma and benign tubal mucinous metaplasia or nonmucinous hyperplasia. Am J Surg Pathol. 2015;39(1):35–51.View ArticlePubMedGoogle Scholar
- Ronnett BM, Yemelyanova AV, Vang R, et al. Endocervical adenocarcinomas with ovarian metastases: analysis of 29 cases with emphasis on minimally invasive cervical tumors and the ability of the metastases to simulate primary ovarian neoplasms. Am J Surg Pathol. 2008;32(12):1835–53.View ArticlePubMedGoogle Scholar
- Hashi A, Yuminamochi T, Murata S, et al. Wilms tumor gene immunoreactivity in primary serous carcinomas of the fallopian tube, ovary, endometrium and peritoneum. Int J Gynecologic Pathol. 2003;22(4):374–7.View ArticleGoogle Scholar
- Crum CP. Intercepting pelvic cancer in the distal fallopian tube: Theories and realities. Mol Oncol. 2009;3(2):165–70.View ArticlePubMedPubMed CentralGoogle Scholar
- Singh N, Gilks CB, Wilkinson N, McCluggage WG. Assessment of a new system for primary site assignment in high-grade serous carcinoma of the fallopian tube, ovary, and peritoneum. Histopathology. 2015;67(3):331–7.View ArticlePubMedGoogle Scholar
- Protocol for the Examination of Specimens from Patients with Carcinoma of the Uterine Cervix. College of American Pathologists Cancer Protocol Templates. December 2013. Available at: http://www.cap.org/CANCERPROTOCOLS. Accessed 23 June 2015.