Gastric cancer is the fifth most common cancer among women and the fourth leading cause of cancer-related death worldwide. The most prevalent subtype of gastric cancer is adenocarcinoma, which is subdivided into the intestinal-type and diffuse-type according to the Lauren classification. Additional subtypes include signet ring cell carcinoma, adeno-squamous carcinoma and squamous cell carcinoma, among others. Metastatic gastric cancer commonly involves the liver (48%), peritoneum (32%), lung (15%) and bone (12%). Metastatic gastric cancer presenting in the uterine cervix is a rare occurrence.
In general, metastasis to the female genital tract from extrapelvic malignancies is highly unusual. Regardless of the location of the primary cancer, metastasis commonly affects the ovaries and vagina. The cervix is less affected compared to the uterine corpus.[9, 10] Moreover, less than 1% of all cervical malignancies originate from non-gynaecological metastatic primaries. These metastatic primary cancers originate from the breast (42.9%), colon (17.5%), stomach (11.1%), pancreas (11.1%), gallbladder (4.8%), cutaneous melanoma (3.2%) urinary bladder (3.2%) and thyroid (1.6%). In 1999, an examination of 40 cases of primary extragenital malignancies with metastasis to the cervix found that the most common source of primary malignancy was that of breast cancer and gastric cancer.
Non-gynaecological cancers may metastasize to the cervix according to three mechanisms: haematogenous spread, retrograde lymphatic spread and transperitoneal seeding.[10, 11] Wallach and Edberg proposed several reasons for the rare presentation of metastatic cancer in the cervix. These include – the small size of the target area, limited blood and lymphatic supply of the cervix and unfavourable conditions for growth of a tumour in the fibromuscular stroma. Similar to the Krukenberg tumour of the ovary, it is postulated that lymphatic dissemination is responsible for metastasis from a gastric primary cancer to the cervix.
In the case presented, histopathology showed aggregates of metastatic cells in the lymphovascular spaces of the cervix which correlates with current literature regarding
mechanisms of metastasis to the cervix. The lymphatic vessels of the cervix drain in a circumferential pattern.[3, 10] Metastasis by this route may only occur if tumour emboli obstruct distant lymphatic channels. Of significance, conditions are unfavorable for metastatic growth in the postmenopausal cervix due to the high density of fibrous tissue and decreased blood supply.[3, 12] Therefore, patients suffering from metastatic cancer to the cervix are typically young and premenopausal.[11, 13]
The presentation of primary cervical cancer and metastatic cancer of the cervix is the same. Patients commonly report abnormal vaginal bleeding, post-coital bleeding, intermenstrual bleeding and malodorous vaginal discharge. Advanced disease manifests with bowel or urinary symptoms and with pelvic or lower back pain. In the case of metastasis to the cervix, symptoms of a primary cancer may or may not be present. Early cervical disease is usually asymptomatic and detected on routine screening by an abnormal cervical smear. Rarely, abnormal glandular cells are seen on cervical smears which may be suggestive of ectopic tumour cells.[10, 11, 17]
Likewise, the pelvic examination findings in patients with metastasis to the cervix often resembles that of primary cervical cancer.(14) Such findings include a friable bleeding cervical lesion or mass with possible invasion into the upper vagina. The cervix may be enlarged and stony hard.[11, 14] Imachi reported that in 50% of patients, the cervix was found to be normal on pelvic examination. This highlights the fact that cytologic and histological assessments of the cervix are necessary for the diagnosis of metastatic adenocarcinoma to the cervix.
In the work-up for a primary cancer, immunohistochemistry (IHC) provides guidance on the identification of carcinomas of unknown primary site, tumour classification, behaviour, and prognosis. An initial immunohistochemistry profile performed on suspicious tissue samples cover a broad spectrum of cytokeratins such CK7 and CK20 followed by organ specific markers like PAX8, CDX-2 and GATA3.(19) Both intestinal and diffuse-type gastric adenocarcinoma show variable expression for CK7 and CK20.[18, 20] Specifically, CDX-2 is identified in over 70% of diffuse-type gastric adenocarcinoma. Findings in our patient correlate with current literature as both cervical and gastric immunohistochemistry showed positivity for CK7 and CDX-2
The prognosis in patients with gastric metastasis to the cervix is poor and a hysterectomy does not improve the outcome. The management involves chemotherapy to maximize quality of life and prolong survival. Although there are no established treatment protocols for patients diagnosed with gastric cancer metastasis to the cervix, platinum-based compounds combined with fluoropyrimidine may be used.[5, 9] According to Yamamoto et al. the median survival from time of discovery of cervical metastasis is four months.
In conclusion, this case highlights a rare manifestation of metastatic gastric adenocarcinoma in a 47-year-old woman. The histopathological findings of atypical cells in the lymphovascular spaces of the cervix following surgery for a benign indication, led to the discovery of a primary gastric cancer. For the unsuspecting gynaecologist, isolated cervical metastasis should be considered as part of the differential diagnosis when atypical cells are identified in the cervix. Furthermore, immunohistochemistry has a vital role in identifying the primary tumour site. Until treatment protocols are established, chemotherapy using fluoropyrimidine and platinum-based compounds may maximize quality of life in these patients.