Daniel Tritz, OSU Center for Health Sciences, OMS IV
Yoon Cho, D.O., Oklahoma State University Center for Health Sciences, Department of Radiology
Brooke White, D.O., Oklahoma State University Center for Health Sciences, Department of Radiology
Donald von Borstel, D.O. Oklahoma State University Center for Health Sciences, Department of Radiology
Mucinous minimal deviation endocervical adenocarcinoma, also known as adenoma malignum, is a rare subtype of mucinous adenocarcinoma of the cervix; adenoma malignum is about 1-3% of endocervical adenocarcinoma. It shows no ethnic predilection and can present in a wide age range with average age being between the 5th and 6th decades of life. It can be associated with Peutz-Jeghers syndrome. Patients often present with watery or mucinous vaginal discharge and/or irregular uterine bleeding. The cervix may be firm on physical exam. Endocervical biopsies can be misleading due to the benign pathologic appearance or may be normal, which may lead to misdiagnosis. The main treatment for this condition is surgical resection.
This case study illustrates the atypical clinical presentation, diagnostic evaluation, and therapeutic intervention of a patient with the rare diagnosis of endocervical minimal deviation adenocarcinoma.
A 53-year-old female presented with rectal pain on sitting and pelvic discomfort for 2-months prior to her initial evaluation by her primary care physician. She was then referred to a gastroenterologist for colonoscopy. She denied any other gastrointestinal symptoms, nausea, vomiting, blood in her stool, or change in bowel movements at that time. The colonoscopy identified a mass that was 7 cm from the anal verge. Multiple biopsies were performed that identified the mass as adenocarcinoma extending to all margins.
A follow-up computed tomography (CT) scan abdomen and pelvis revealed an additional 6.4cm lesion in the lower uterine segment with poor visualization of the rectal mass (Figure 1). She then received a PET/CT scan which identified hypermetabolic activity in the rectum and the lower uterine segment. The patient had a rectal ultrasound with a magnetic resonance image (MRI) of the abdomen and pelvis for further cancer staging.
Figure 1. A
Figure 1. B
Figure 1. C
Figure 1A. On a coned down T2-weighted fat saturated axial sequence of the pelvis, the cervix demonstrates numerous hyperintense cystic lesions within an enlarged cervix (solid white arrow). There is also a hypointense mass seen at the sigmoid colon (solid yellow arrow). B. On coronal STIR sequence of the pelvis, the cystic lesions demonstrates hyperintense signals with enlargement of the cervix. The cysts are seen extending deep into the cervical stroma with an associated solid component. C. Coronal T2-weighted fast relaxation fast spin echo sequence (FRFSE) sequence demonstrates mixed solid and cystic cervical lesion (solid white arrow).
Figure 3. Numerous mucin-producing architecturally abnormal glands (black arrows) lined by cuboidal to columnar cells with minimal cytologic atypia with basally located nuclei.
It is estimated that almost 300,000 women in the US were living with cervical cancer in 2016 1. Squamous cell carcinoma is responsible for about 80% of cervical cancer with adenocarcinoma representing the other 20%2. Minimal deviation adenocarcinoma, or adenoma malignum, is a subtype of cervical cancer which is caused by proliferation of well-differentiated gastric mucinous cells3. Common presenting symptoms for this rare type of cancer include profuse mucoid vaginal discharge and irregular or post-coital vaginal bleeding4,5. In comparison, our patient denied any significant symptoms and only complained of vague rectal and vaginal discomfort with sitting.
Since squamous cell carcinoma is a more common type of cervical cancer, there has been a higher rate of success at preventing squamous cell carcinoma, which has a near 100% link to human papilloma virus (HPV), with preventative medical options such as HPV vaccines 6. Unfortunately, adenoma malignum, or minimal deviation adenocarcinoma, is not related to HPV and shows association with other systemic conditions such as Peutz-jegher syndrome and Lynch syndrome. The incidence of this condition has not decreased at the same rate compared to squamous cell carcinoma7,8,9.
The main differential diagnosis for adenoma malignum would be a conglomerate of nabothian cysts or endocervical glandular hyperplasia. Sonographic imaging findings of adenoma malignum consists of cystic lesions seen in the lower uterine segment with enlarged cervix. MRI shows multiple irregular T2 hyperintense cystic lesions with enhancing stroma on post-contrast image. Takatsu et. al. described the finding as "Cosmos pattern" as the irregular cystic lesions often seen in floret-like pattern10. The lesions may demonstrate restrictions on diffusion weighted sequence (DWI)3,11. Nabothian cysts can be seen deep within the cervical stroma which can make the diagnosis difficult. The cervix can be enlarged in both etiologies although the main distinguishing factor would be the enhancing solid component of adenoma malignum which would not be present with nabothian cysts. Nabothian cysts also are typically smaller and demonstrate well-defined margins which would help differentiate them12. An additional entity in the differential diagnosis is endocervical glandular hyperplasia which is thickening of the endocervical mucosa with resultant cyst formation in the endocervix. Endocervical hyperplasia is typically hyperintense on T1- and T2-sequences. A differentiating feature of hyperplasia is the lack of an enhancing solid component that is commonly seen with adenoma malignum. Ultrasound may be the initial imaging to use in patients that have an unconfirmed genitourinary malignancy, but MRI is more specific and better for staging as there is a higher resolution for soft tissues13. Bourgioti et. al. quantified the ability of MRI to accurately stage cervical cancer compared to clinical assessment and found that MRI was superior in comparison to clinical assessment alone, and even better results when MRI and clinical assessment were combined14.
The European Society for Medical Oncology suggests different treatment approaches depending on the staging and metastatic status of cervical cancer, but does not differentiate between adenocarcinomas and squamous cell histology15. Treatment of earlier stage disease requires local surgery with recommended neoadjuvant chemotherapy to reduce tumor size, eradicate micrometastatic disease, and increase tumor vascularization to reduce the number of hypoxic cells. In advanced or metastatic cases, such as ours, current treatment recommendations are more extensive including surgery (radical hysterectomy with bilateral salpingo-oophorectomy with possible lymph node dissection), three-drug chemotherapy, and potential radiation for better outcomes15,16. Unfortunately, adenocarcinoma of the cervix is less responsive to chemoradiotherapy than squamous cell carcinoma and often results in decreased overall survival at 10-year follow-up17.
Poor prognosis for adenoma malignum commonly occurs from delays in diagnosis due to benign symptoms and benign appearing endocervical biopsy causing late presentation3. Cervical adenocarcinoma, as a whole, has a poor response to radiation and chemotherapy with treatment being less successful than squamous cell. Poor response to radiation is surprising given that adenocarcinomas of the cervix are most often well-differentiated and stage I or II when first diagnosed18. Adenoma malignum has few studies looking at the poor prognosis separate from other cervical adenocarcinomas, and is thus discussed in general terms applicable to both3.The most common recommendation for the prevention of all forms of cervical cancer is HPV vaccination19. Since HPV has been associated with the majority of cervical cancer, the current recommendation by CDC for HPV vaccination is to initiate routine vaccination at age of 11-12 years or to vaccinate females aged 13-26 years if they have not adequately vaccinated previously20.
Screening for cervical cancer, including pap smears and HPV serology, has improved the detection of asymptomatic early cellular metaplasia. Our patient had no documentation of being diagnosed with HPV or being vaccinated for it. Unfortunately, as mentioned above, adenoma malignum has not been closely associated with patients infected with HPV21,22. Screening tools to aid in the diagnosis of adenoma malignum are the HIK1083-latex agglutination test or MUC6 that identifies gastrin mucus present in cervical discharge23-25. With all of the screening techniques, any positive or unspecified results warrant radiographic follow-up with ultrasound and biopsy sampling followed by MRI.
Our case describes a rare case of mucinous minimal deviation endocervical adenocarcinoma, also known as adenoma malignum, with concurrent occurrence of an independent colonic adenocarcinoma. Our patient was further complicated by having an atypical clinical presentation with no substantial genitourinary or gastric symptoms, which may have led to a delay in diagnosis. Imaging work up with ultrasound and staging by MRI played an integral role in diagnosis of our patient and allowed for expedited surgical management before further complications or distant metastasis could occur.
Statement of funding sources:
No funding was obtained for the writing of this manuscript.
Conflicts of interest disclosures:
None of the authors have conflicts of interest or relevant financial relationships to disclose.
Key Words: Adenocarcinoma, Uterine mass, Adenoma malignum
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