Gastric-Type Adenocarcinoma of the Uterine Cervix: Role of Magnetic Resonance Imaging for Diagnosis and Management
Gastric-Type Adenocarcinoma of the Uterine Cervix: Role of Magnetic Resonance Imaging for Diagnosis and Management
Drs BY Lee, SC Wong, T Wong, CM Chau, LS Chan, KF Ma.
1) To compare gastric-type adenocarcinoma of the cervix (GAS) with the more common cervical squamous cell carcinoma (SCC) in terms of clinical behaviour, association with human papillomavirus (HPV) and imaging features on pelvic magnetic resonance imaging (MRI). 2) Understand the key imaging features in differentiating benign versus malignant cervical multicystic lesions. 3) Understand the key role of MRI in facilitating targeted biopsy and tumour staging.
Overview Cervical adenocarcinoma is the second most common subtype of cervical cancer (20% of all cervical cancers), and can be categorised into two groups, human papillomavirus (HPV) associated adenocarcinoma and the less common HPV-independent adenocarcinoma. Gastric-type adenocarcinoma (GAS) of the cervix, though being a rare subtype and accounting for less than 3% of all cervical cancer, is yet the most common human papillomavirus (HPV) independent cervical cancer and accounts for about 10% of cervical adenocarcinoma, with well recognised aggressive behavior. With poorer overall survival, higher stage at presentation, frequency of distant metastasis, and resistance to radiotherapy and chemotherapy treatments compared with HPV associated cancer, early recognition of GAS is crucial for timely definitive histological diagnosis and early treatment to maximize patient’s survival. Fertility sparing treatment should not be recommended for HPV-independent adenocarcinoma, including GAS, according to the literature owing to its aggressive tumour behaviour. Due to limited soft tissue contrast resolution of ultrasonography and computed tomography, the visualisation of cervical tumour can be challenging. GAS was found to demonstrate higher prevalence of endophytic growth pattern, preferential involvement of upper cervix or endocervical region with relative sparing of ectocervix, causing difficult tumour visualization on speculum or colposcopy examination and impairing cervical biopsy sampling adequacy. Fortunately, characteristic appearance on pelvic MRI has been recognized in the literature in the past decade. Awareness of this disease entity and its typical imaging features are vital in directing targeted biopsy or adequate tissue sampling (such as by cervical conization procedure) for definitive diagnosis by histology. Cervical tumour and nodal staging can be achieved with pelvic MRI given its excellent soft tissue contrast resolution in accurately depicting tumour disease extent, thereby guiding the choice of management. MRI for Diagnosis On MRI, GAS shows characteristic imaging features (image 1). The classical appearance is an infiltrative mass with ill-defined borders, located at upper endocervix or involving the entire cervix, with intratumoural cysts (which can be of varying sizes) giving rise to mixed solid and cystic appearance. It usually shows restricted diffusion and heterogeneous contrast enhancement. These features show key differences from squamous cell carcinoma (the most common cervical malignancy) and other cervical adenocarcinomas, the majority of which are located at the lower portion of the cervix, and show exophytic growth of a well-formed solid mass with intermediate T2 weighted signal (image 2a-d). While other cervical adenocarcinoma can also have presence of intratumoural cysts or cystic component, including the most common subtype of HPV-associated usual endocervical adenocarcinoma, this is much less commonly seen than in GAS (around 33% in usual endocervical carcinoma, in comparison to up to 80% in GAS). Other factors such as tumour location, growth pattern, and HPV status characteristically can aid in differentiation; P16 immunostaining, being strongly associated with HPV related tumour, is typically negative in GAS. Imaging pattern on MRI is useful in differentiation from benign cystic cervical lesions. Macrocystic lesions confined to the lower portion of the cervix, without solid component, are likely to represent benign glandular lesion or hyperplasia including Nabothian cysts or tunnel cluster (image 2e, 2f). Presence of solid component with mixed solid-cystic pattern, particularly with diffusion restriction, should raise suspicion for malignant tumours, including GAS. MRI in Facilitating Biopsy MRI has an important role in facilitating biopsy. Preoperative tissue diagnosis for cervical tumours are usually obtained by punch biopsy; however, these have limited yield (reported at around 50%) for GAS due to its upper endocervical location and endophytic growth with relative sparing of ectocervix, precluding tumour visualization on speculum examination or colposcopy assessment, easily leading to sampling error. MRI can aid in identifying the tumour site to guide gynecologists in biopsy, and localising solid, cellular areas of tumour to target for biopsy, thus increasing diagnostic yield. In case of strong suspicion of GAS from MRI findings with discrepancy with cervical punch biopsy, further adequate histological sampling from conization should be pursued to achieve a definitive diagnosis. MRI in Staging and Follow-Up MRI also plays an integral role in staging and follow-up for GAS and other cervical cancers. In 2018, the International Federation of Gynaecology and Obstetrics (FIGO) 2018 criteria formally included MRI as an adjunct to clinical examination (pelvic examination, colposcopy, and cystoscopy) for tumour staging. Pelvic MRI has been recommended as mandatory for initial pelvic tumour extent and staging to guide treatment options by the European Society of Gynecological Oncology (ESGO), European Society for Radiotherapy and Oncology (ESTRO), and European Society of Pathology (ESP) guidelines for cervical cancer management in 2023. Superior soft-tissue resolution of MRI compared to other imaging modalities such as computed tomography (CT) or ultrasound allow detailed assessment of local staging criteria, which includes assessment of tumour size, depth of stromal invasion, and extent of involvement to parametrium [FIGO IIB], lower one-third of vagina [IIIA], pelvic sidewall [IIIB] or pelvic and para-aortic lymph nodes [IIIC], or adjacent pelvic or distant organs [IV]. Large field-of-view sequences aid identification of paraaortic nodal or distant metastases, though sensitivity for distant nodal or organ metastases is below that of fluorodeoxyglucose positron-emission (FDG-PET) CT. MRI performed for local staging should be performed at 1.5 Tesla field strength or greater. Sequences should include multiplanar fast spin-echo T2-weighted sequences for assessment of parametrial and pelvic sidewall involvement; and post-gadolinium contrast-enhanced sequences for peritoneal nodal, and bone metastases. If no further CT or PET-CT imaging is planned, a large field-of-view image (scan range from renal hilum to pelvic floor) should be attained for assessment of hydronephrosis secondary to ureteric involvement at pelvic sidewall, and for nodal metastases. Diffusion-weighted imaging (DWI) improves detection of small tumours, and accuracy of local staging, usually using a maximum b-value of 800-1000 sec/mm2. Axial or double oblique axial imaging planes are critical to accurate local staging. The position of the uterine cervix is highly variable, and may be angled anteriorly or posteriorly, or to the left or the right of the midline. An axial oblique image obtained perpendicular to the sagittal plane of the cervix will account for tilting in the sagittal plane, but may not show a true axial image of the cervix if there is significant leftward or rightward tilting, and will be subject to partial volume artefact. A ‘double oblique’ axial accounts for both the sagittal and the coronal tilt of the cervix to give images along the true axis of the cervix, allowing better demonstration of crucial anatomy such as the cervical stromal ring and therefore more accurate assessment of tumour invasion, as that would have an impact on the decision for surgery or chemoradiation management (image 3). MRI also plays a key role in follow-up imaging for local recurrence, due to the ability to differentiate between post-irradiation fibrosis and local tumour recurrence based on enhancement and diffusion characteristics. It is useful during reporting to compare with pre-operative or treatment naive MRI study for the appearance of the original tumour. Recurrent tumour will show signal intensity similar to the original tumour in pre-treatment MRI (image 4). It will also demonstrate restricted diffusion and early gadolinium enhancement, in contrast to post-irradiation fibrosis which does not restrict diffusion and enhances late, or not at all.
1a) Sagittal T2-weighted, 1b) axial T2-weighted, and 1c) sagittal T1-weighted gadolinium-enhanced MRI of pathology-proven GAS in a 43-year-old lady with adenomyosis and endometriosis. She initially presented with hemorrhagic and chronic pelvic pain. Pelvic examination revealed poorly felt anterior cervical rim with firmness and bulging in small posterior cervical rim with occasional contact bleeding. Two repeated cervical biopsies showed no evidence of malignancy. She was referred for MRI pelvis examination. MRI shows an infiltrative tumour mass with ill-defined margins involving the entire cervix, with multiple tiny intratumoral cysts demonstrated on T2-weighted images (1a and 1b, white arrows). Post-contrast T1-weighted images show mildly heterogeneous hypoenhancement of the tumour (1c, black arrow). Evidence of thickened posterior junctional zone consistent with posterior uterine adenomyoma (white asterisk), and adhesion bands from posterior uterine body with tethering of the rectum due to endometriosis (white arrow). She underwent hysterectomy with a final diagnosis of GAS confirmed on surgical specimen. Adjuvant chemoradiotherapy was given in view of tumour involvement of resection margin. However, tumour recurrence was detected at 9 months after completion of chemoirradiation. Disease progression developed despite multiple lines of chemotherapy and she eventually passed away at 3 years after first diagnosis.
2a) Sagittal T2-weighted and 2b) axial T2-weighted MRI of pathology-proven squamous cell carcinoma of cervix. A solid mass with T2-intermediate signal seen involving the entire cervix (white arrowheads), with exophytic component protruding to the anterior vaginal fornix (white asterisk). There is invasion and thickening of the upper vaginal vault (white arrows). Obstructive effect by cervical tumour causes hydrometra (white triangle). An incidentally noted simple cystic left adnexal lesion (black asterisk). 2c) Sagittal T2-weighted and 2d) axial T2-weighted MRI of invasive stratified mucin-producing carcinoma (an HPV-associated subtype of cervical adenocarcinoma) in a 40 year old female. A 8cm large solid and cystic mass at the lower cervix, with exophytic protrusion to the vaginal vault (black arrows). Presence of high T2-signal mucinous component is seen at its posterior aspect (black triangle), though lacking the characteristic appearance of multiple intratumoural cysts seen in GAS. 2e) Sagittal T2-weighted and 2f) axial T2-weighted MRI of a cervical tunnel cluster, seen as a macrocystic endocervical lesion at the lower cervix (black arrowheads). The absence of any solid component differentiates this lesion from malignant tumour or GAS.
The utility of oblique imaging planes for local staging in a patient with gastric-type adenocarcinoma of the cervix (the same patient as shown in Image 1). 3a) Sagittal T2-weighted MRI shows significant angulation of the cervix in the sagittal plane. Oblique axial (red line) and oblique coronal (white line) planes along the true axes of the cervix allow accurate delineation of cervical zonal anatomy for assessment of presence and depth of stromal invasion and parametrial invasion. 3b) Oblique axial plane, showing clear delineation of the T2 hypointense cervical stroma. Suspected disruption of the hypointense cervical stromal ring at 5 o’clock position (white arrow), suggesting invasion through the cervical stroma into parametrium. Paracervical involvement was confirmed on pathological examination. 3c) Axial T2-weighted MRI showing the oblique coronal plane of the cervix. Mild blurring of the T2 hypointense cervical stromal layer again seen (white arrow), suspicious for stromal disruption and parametrial invasion, which was confirmed on pathology. Double-oblique images were not required for this patient as there was no significant left- or right-ward tilting of the cervix in the coronal plane (not shown).
Recurrence of GAS on follow-up after total abdominal hysterectomy and bilateral salpingectomy. 4a) Sagittal T2-weighted and 4b) axial T2-weighted images revealed a mass at the vaginal vault showing characteristic intratumoral cysts (white arrows), consistent with GAS recurrence. 4c) Axial FDG-PET CT demonstrated FDG avidity of the recurrent GAS (white asterisk). 4d) Axial pre-contrast T1-weighted images show an isointense mass (white arrowheads), which demonstrates contrast enhancement on post-gadolinium contrast-enhanced T1 weighted image (4e; black arrowheads).
Gastric-type adenocarcinoma of the uterine cervix is an aggressive, human papillomavirus-independent subtype carrying poor prognosis, with greater propensity for metastases, and resistance to chemotherapy and radiotherapy. Distinctive MRI features of intratumoral cysts, upper endocervical location with endophytic growth, and heterogeneous enhancement which can aid in identification of GAS and differentiation from cervical squamous cell carcinoma and other benign cervical multicystic lesions. Targeted and adequate biopsy on suspicious solid areas identified on MRI is crucial for early definitive histological diagnosis. High soft-tissue resolution of MRI and the use of dedicated double-oblique imaging planes allows accurate local tumour staging. Diffusion-weighted imaging and enhancement pattern make MRI indispensable in differentiating between post-irradiation fibrosis and recurrent tumour on post-treatment follow-up.