We had an experience with the case of urethral metastasis from a sigmoid colon cancer in male. In this case, urethral tumor was considered to have metastasized from colon cancer pathologically by both morphological examination with hematoxylin and eosin staining and immunohistochemical examination. As to the immunohistochemical analysis, the expression of CK20, CK7, and CDX2 was useful for identifying the primary site of metastatic adenocarcinoma. T. Tot summarized the results of 29 studies about for CK20/CK7 phenotype, and stated that colorectal carcinomas showed the CK20+/CK7- phenotype in 78% of the cases and were concluded to be usually CK20+ and CK7- . Therefore, the CK20+/CK7- phenotype indicates metastatic adenocarcinoma, most often from the colorectum. In regard to CDX2, Barbareschi et al. showed that CDX2 immunostained all colorectal adenocarcinomas metastatic to the lung, although it was completely absent in all primary lung neoplasm and in all other adenocarcinoma metastatic to the lung . However, CDX2 is not entirely specific for colorectal cancer, because Weling RW et al. reported that the expression of CDX2 was found ovarian mucinous carcinoma, adenocarcinoma of the urinary bladder, and prostatic adenocarcinoma . The present case exactly showed the phenotype of CK20+/CK7-/CDX2+, suggesting that the urethral tumor was derived from primary tumor of sigmoid colon.
Colorectal cancer with urethral metastasis is generally considered a systemic disease, and the prognosis is generally poor according to the previous case report . Moreover, patients with metachronous metastases were considered to have a worse prognosis than those with synchronous metastases . The clinicopathological features of these 9 patients with urethral metastasis from colorectal cancer are shown in Table 1. The average size of urethral tumor was 2.3 cm. Moreover, the average duration of the detection of metachronous urethral metastasis postoperatively was 2.7 years. In comparison, the urethral metastasis in the present case was detected as a mass with relatively small size and at a long postoperative interval, which might be the reason of the better outcome in current cases. The cases with synchronous reccurence were three, and all cases were female. Among them, two cases (67%) were alive without symptoms of recurrence for 6 and 30 months, respectively. In contrast, the patients with metachronous were 6, and all cases were male including our case. Only two cases (33%) were alive without symptoms of recurrence for 20 and 84 months, respectively. In the present case, both urethral and solitary lung metastasis were detected after curative surgery for sigmoid colon cancer. Additional therapy whether surgical resection or systemic chemotherapy was considered. Recently, neoadjuvant therapy using FOLFOX (with approved biological agent) chemotherapy was recommended as a nonsurgical management of patients with no obstructing metastatic (stage IV) colorectal cancer, and demonstrated excellent result with few complications . This suggests nonsurgical chemotherapy using FOLFOX plus biological antibodies might have beneficial effect on patients with urethral metastasis from colorectal cancer. Therefore, 6-cycle FOLFOX4 was administered to the patient after informed consent about additional therapy, and these metastases were disappeared with no recurrence of disease. This aggressive chemotherapy might help to improve the disease free survival and patient’s overall quality of life.
Possible mechanisms for metastatic spread to the penis have been described as direct arterial extension, secondary and tertiary embolism, instrumental spread, paradoxical embolism, retrograde lymphatic spread and direct extension . Of these, the latter three mechanisms are considered to be most likely, when the primary tumor arises from the rectosigmoid colon. Batson OV described that the communication between pelvic and vertebral veins would easily account for retrograde venous spread during Valsalva maneuvers when proximal venous channels are blocked with tumor . Selikowitz SM et al. also described that blockage of proximal lymphatics might allow retrograde lymphatic spread to occur via connections between inferior hemorrhoidal and pudendal lymphatics, and direct extension was possible from the ischiorectal fossa, through the junction of Collees fascia with the triangular ligament, to the superficial perineal pouch. Nevertheless, the number of the cases with urethral metastasis was few. Moreover, only 3 cases (33%) out of nine cases that were reported previously had lymph node metastasis (stage C of Dukes’ classification) or distant metastasis (stage D of Dukes’ classification). The accumulation of these cases is necessary for exact clarification of the mechanism for metastasis to the urethra.
In patients with colorectal cancer, postoperative follow-up, including tumor markers (carcinoembryonic antigen, carbohydrate antigen 19–9, and serum p53 antibody), chest X-ray, liver ultrasound, computed tomography, and colonofiberscopy is routinely performed. Urethral metastasis from colorectal cancer is a very rare occurrence. Therefore, the examination of the urinary system as a part of the routine postoperative follow-up protocol would not be justified. However, in the presence of urinary symptoms, the possibility of the urethral metastasis should be considered.
Written informed consent was obtained from the patient for publicatin of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.