Symptoms of cervical or vaginal metastasis from colorectal cancer, such as vaginal bleeding, lumps, and abnormal secretions [2, 3], can mimic primary cervical or vaginal cancer. This similarity can make diagnosis challenging, as clinicians might overlook the possibility of metastasis due to its rarity. In this case, the postoperative pathology showed adenocarcinoma. This finding is significant because cervical and vaginal cancers are predominantly squamous cell carcinoma; adenocarcinoma accounts for only 0.42–11.7% of cervical cancers [4] and 8% of vaginal cancers [5]. Furthermore, most vaginal cancers are metastatic, often originating from adjacent organs like the cervix or other sites. Primary vaginal cancer itself is uncommon, representing only 1–2% of female reproductive system malignancies and 10% of all vaginal cancers [6]. Thus, the possibility of metastasis was a key consideration in this patient. Immunohistochemistry is crucial for determining the origin of metastatic colon cancer. CK7-, CK20+, and CDX2 + expression patterns are valuable for distinguishing primary colon cancer from breast, ovarian, or lung cancers. Typically, primary colon cancer is CK7-/CK20+, while breast, ovarian, or lung cancers are often CK7+/CK20-. This is because CK7 is usually absent in the colon but present in tissues like the lung, breast, ovary, and vagina, whereas CK20 is almost exclusively found in gastrointestinal and urinary epithelium. CDX2 expression serves as an auxiliary marker for colorectal adenocarcinoma, especially when CK7 and CK20 results are ambiguous [7, 8]. This patient’s immunohistochemical results (CK7-, CK20+, CDX2+) were consistent with a colonic origin.
The diagnostic process focused on distinguishing metastasis from a new primary tumor. Preoperative pathological assessment of the cervical mucosa and cervical canal yielded no evidence of malignancy; the cervical lesion was localized to the cervical stroma rather than the mucosal layer. Preoperative colonoscopy revealed unremarkable intestinal mucosa, confirming no recurrence of the ascending colon cancer diagnosed three years earlier. However, external compressive changes were detected in the rectum, 8 centimeters from the anus. Postoperative pathology demonstrated that the rectal lesion extended from the muscularis propria through to the serosa. While tumors originating in the muscularis propria are typically of mesenchymal origin, both the preoperative evaluation of the vaginal lesion and postoperative pathological analysis identified the lesion as an adenocarcinoma—an epithelial-derived malignancy. In conjunction with the patient’s immunohistochemical findings and history of ascending colon cancer, these observations strongly support the conclusion that the cervical and vaginal lesions are metastatic from the ascending colon cancer.
In addition, patients with Lynch syndrome have a significantly increased risk of multiple malignant tumors, including colorectal cancer, gastric cancer, endometrial cancer, ovarian cancer, and pancreatic cancer. Their clinical manifestations are complex and diverse, and sometimes it is difficult to distinguish them from sporadic tumors [9]. When patients have malignant tumors other than colorectal cancer or multiple Lynch syndrome-related tumors, the possibility of Lynch syndrome should be considered. The patient discovered malignant lesions in the cervix and vagina following colon cancer surgery. However, the pathological results of the two surgeries showed positive mismatch repair defect (MMR) gene-related proteins, ruling out Lynch syndrome. We can assist in differential diagnosis based on the patient’s immunohistochemical results and combined with the patient’s medical history data.
The most common metastatic sites of colorectal cancer are the liver, lung, peritoneum, and lymph nodes. In contrast, cervical metastasis and vaginal metastasis are less common. The most common extragenital organs that metastasize to the cervix and vagina are the gastrointestinal tract, breast, pancreas, and kidney [10,11,12]. Literature reports of colorectal cancer metastasizing to the cervix and vagina typically describe single-organ metastasis or vaginal involvement secondary to cervical metastasis [2, 3, 13] (Table 1). This case is distinct because the patient had both cervical and vaginal metastases that were discontinuous. Several metastatic pathways could explain the cervical and vaginal lesions. First, colon cancer cells might have exfoliated from the serosa and implanted in the cervix via the pouch of Douglas. The patient’s cervical lesion was mainly in the posterior lip mesenchyme, growing eccentrically and infiltrating the anterior rectal wall. Post-surgery, a nodule was faintly visible in the retroflection of the pouch of Douglas peritoneum. While cervical tumor cells can spread retrogradely through vaginal mucosal lymphatics to form distant vaginal nodules, this patient had no lymph node metastasis, and intravascular cancer emboli were seen after the second surgery. This suggests the isolated vaginal lesion more likely resulted from hematogenous dissemination from the cervical lesion.
Alternatively, both lesions might have arisen from hematogenous dissemination, possibly with the vagina being the initial metastatic site, followed by spread to the cervix. Mazur et al. found the ovaries and vagina to be the most common metastatic sites in the female genital tract, irrespective of the primary tumor’s location [10]. The cervix, being small, highly fibrous, and with limited blood flow, and with pelvic lymphatic vessels mostly distant from it, is generally less favorable for metastatic tumor growth [14]. In contrast, the vagina’s abundant blood vessels and lymph nodes make it more conducive to such growth. The patient’s vaginal lesion was on the anterior wall of the lower vagina, an area supplied by arteries from the internal iliac artery, including the vaginal artery and the cervicovaginal branch of the uterine artery. Some reports suggest venous channels, particularly the vertebral vein system, are the most probable route for colon cancer metastasis to the vagina [15]. This valveless system, described by Batson, runs parallel to and interconnects with the portal, pulmonary, and caval systems, offering a bypass for blood flow. Its widespread connections and lack of valves can permit reversed blood flow, especially with increased intra-abdominal or pelvic pressure, shunting blood and tumor cells to distant organs, potentially bypassing liver or lung filtration [16, 17]. Batson’s experiments showed significant communication between the pelvic venous plexus (also valveless with many anastomoses) and vertebral veins [16]. Therefore, the cervical lesion in this case might have resulted from hematogenous metastasis from the vaginal lesion. Other hypotheses, such as lymphatic metastasis or tumor cell implantation via the fallopian tubes/uterus to the vagina [2, 11], are less consistent with this case’s colon lymph node routing.
Understanding colorectal cancer’s metastatic pathways to the cervix and vagina has critical clinical implications. It mandates thorough gynecological workups, including imaging, for survivors presenting with new pelvic symptoms. This knowledge directly shapes surgical strategies regarding margins and resections, particularly when routes like peritoneal seeding or local vascular spread are considered. Hematogenous spread, potentially via the vertebral venous system, implies a higher risk of widespread disease, impacting prognosis and necessitating comprehensive staging and vigilant follow-up. Recognizing these pathways is also vital for differential diagnosis from primary or other metastatic gynecological tumors. Ultimately, considering these complex routes improves anticipation, diagnosis, and comprehensive treatment planning for these rare metastatic presentations.
When cervical or vaginal metastases from colorectal cancer are detected, the patient’s prognosis is often poor, as it usually signals that widespread dissemination is imminent or may have occurred. Raider [15] reported three patients with widely disseminated vaginal metastases died within 10–39 months of lesion discovery. Therefore, if such metastases are diagnosed, determining if the disease has spread elsewhere is crucial. Even with only cervical or vaginal metastases initially, regular follow-up is needed as this may be the start of widespread dissemination. No standard treatment plan exists for these rare metastases. After a multidisciplinary discussion, the patient’s cervical and vaginal lesions could be classified as oligometastases from colorectal cancer, and surgical resection might be an appropriate treatment option. No lymph node metastases were detected on preoperative imaging and intraoperative exploration, therefore lymph node dissection was not considered and only tumour cytoreduction was performed with the aim of complete resection of local metastases in order to achieve a disease-free state and minimise trauma. According to previous reports, 3–14% of colorectal cancer patients may experience ovarian metastasis (50–70% of cases are bilateral metastases, and 6–25% are occult metastases) [18]. If the ovaries are not removed, the risk of ovarian metachronous lesions is 1.3–2.4% [19]. When the ovaries or uterus may be directly invaded in patients with colorectal cancer, therapeutic surgery will involve total resection [20]; thus, bilateral adnexectomy is performed to reduce subsequent ovarian metastasis risk. The patient’s vaginal lesion was isolated from the cervical lesion, which compressed and infiltrated the anterior rectal wall, necessitating partial vaginal and rectal resection with intestinal anastomosis. For postoperative internal medicine treatment, future genetic testing could help develop a suitable systemic plan (chemotherapy + targeted or immune therapy) for better patient survival, assuming good compliance.