By Ouellette, James R; Harboe-Schmidt, Jens Erik; Luthringer, Daniel; Brackert, Sandra; Silberman, Allan W
Metastatic lesions to the testicle are uncommon. The authors report a testicular mass as the initial manifestation of distant metastasis from colorectal cancer. This case describes a 51-year- old white man who presented with an enlarged right testicle 9 months after undergoing a right hemicolectomy for a stage IIIC colon adenocarcinoma. The diagnostic and management strategy is discussed. In addition, the literature is reviewed to characterize this uncommon entity further. Although rare, testicular metastasis must be considered in patients with previously resected colorectal carcinoma.
METASTASIS TO THE testicle from nonlymphomatous cancer usually occurs in conjunction with diffuse metastatic disease.1-5 The most common primary is prostatic carcinoma.1,2 The prevalence of testicular metastasis from colon cancer has been reported to approximate 8 per cent of all testicular metastatic lesions.1,6 All testicular masses require evaluation and usually represent primary disease. However, metastatic testicular lesions may become more commonly diagnosed with advancing technology and imaging capabilities.
A 51-year-old white man initially presented to the emergency room with marked swelling of his left lower extremity. A duplex scan revealed deep venous thrombosis involving his entire left lower extremity. Tests for pulmonary embolus were negative. Further workup revealed anemia with an elevated carcinoembryonic antigen (CEA) level of 202 ng/ml. A computerized axial tomographic scan showed a lesion in the ascending colon. In preparation for both colonoscopy and operation, the patient had placement of an inferior vena cava filter followed by open right hemicolectomy. The pathology revealed a 7-cm mucinous adenocarcinoma with 31 of 36 positive nodes (T4N2MO; stage IIIC). Postoperatively, the patient received FOLFOX (5fluorouracil, oxaliplatin, leucovorin) chemotherapy in addition to bevacizumab (Avastin). The initial pathology also confirmed loss of immunoreactivity of the DNA mismatch repair gene hMLH-1, but not hMSH-2 or hMSH-6, suggesting microsatellite instability and a familial cause of the cancer.7, 8 Of note is that both parents and a sister had colon cancer at a young age (
The patient’s CEA level returned to normal after the operation and chemotherapy. After completion of chemotherapy, the patient was followed with physical examinations, serial CEA levels, and imaging studies. Three months after the completion of chemotherapy, the patient’s CEA level rose to 17 ng/mL. A positron emission tomographic (PET)/CT scan at that time showed increased fluorodeoxyglucose uptake in a 6-mm lymph node in the right iliac chain. On physical examination, the patient had an enlarged, tender right testicle that had developed during the prior 2 months. The PET scan confirmed increased fluorodeoxyglucose uptake with the corresponding testicular mass on CT (Fig. 1). The patient’s CEA level continued to rise to 75 ng/mL with no other evidence of metastatic disease. Alphafetoprotein and human chorionic gonadotropin measurements were normal.
The patient was taken to surgery and a radical right orchiectomy with right iliac lymph node dissection was done through an extended right inguinal approach. Pathologic examination confirmed adenocarcinoma consistent with the colon primary in both the testicle and a single iliac lymph node (Figs. 2 and 3).
Testicular metastasis from any cancer is rare, especially as an isolated entity. In reviews by Meacham and others,1, 2, 6 the most common primary tumors were prostate (29-34.6%) followed by lung (1517.3%), melanoma (8.2-11%), and kidney (9%). Colorectal metastases accounted for less than 8 per cent of all testicular metastatic lesions.4
FIG. 1. CT scan showing solid right testicular mass consistent with physical exam findings.
FIG. 2. Bisected fixed testicular specimen.
Treatment of metastatic colorectal cancer has improved in recent years as a result of improved systemic therapy and the use of excisional or ablative techniques for isolated or localized metastatic disease.9-13 In this case, the initial postoperative metastatic evaluation (PET/CT) demonstrated no evidence of distant metastatic disease despite multiple positive nodes. The patient was given a regimen of FOLFOX plus the angiogenesis inhibitor bevacizumab (Avastin).14, 15 It was not until chemotherapy was completed that his symptomatology began and the CEA level began to increase. This prompted another search for metastatic disease. The only finding of note on the follow-up PET/CT was a 6-mm right iliac lymph node suggesting increased activity. However, on physical examination, a right testicular mass was noted. This prompted rereview of both the PET and CT scans, which confirmed uptake in the testicular lesion.
FIG. 3. Microscopic examination showing poorly differentiated carcinoma with signet ring cells similar to colonie primary.
Several modes of spread have been proposed to account for testicular metastases. These include arterial embolization, retrograde lymphatic spread, direct spread along the vas deferens to the epididymis and testis, and transperitoneal spread from a patent tunica vaginalis.4 Pathologic evaluation of our specimen showed diffuse replacement of the testicle with highgrade mucinous adenocarcinoma, with tumor present in angiolymphatic spaces. In addition, the iliac node metastasis also showed evidence of vascular space invasion, suggesting a hematogenous route of spread in this case. There have been less than 25 reported cases of colorectal metastases to the testicle. All cases have been associated with widespread metastatic disease.1, 2, 4, 5, 16 In many of the case reports, the primary lesion was unresectable at the time of diagnosis because of bulky disease or diffuse peritoneal involvement. This is the first reported case of an isolated metastasis that was amenable to surgical extirpation. Radical inguinal orchiectomy is the treatment of choice for testicular masses, both primary and metastatic.1-6 We also performed a limited right iliac lymph node dissection that confirmed the presence of metastatic nodal disease, as suggested by the PET/CT scan.
This case also raises the question of whether the secondary lymph node metastasis was from the primary tumor or the testicular lesion. The right iliac location and the isolated lymph node involvement tend to favor metastasis from the testicular lesion. Other authors have noted that metastatic lesions can metastasize to lymph nodes.17- 19 Mesenteric nodal involvement is often seen in melanoma metastatic to the small bowel.17 In addition, axillary lymph node metastases from gallbladder cancer previously metastatic to a laparoscopic port site have recently been described.18 More commonly, there are numerous reports of colorectal metastases to portal lymph nodes in patients with hepatic lesions.19-21 The possibility that the iliac node was a secondary metastasis rather than an indicator of widespread distant disease led us to remove the iliac nodal disease in conjunction with the orchiectomy.
Although this patient knew of his family history of colon cancer, he was unaware of the possibility of a familial colon cancer syndrome such as hereditary nonpolyposis colon cancer. Recent reports of hereditary nonpolyposis colon cancer patients with microsatellite instability have suggested a less aggressive course for these tumors.7,8 This is clearly not the case here. This patient presented with bulky disease and multiple lymph node metastases. In addition, he quickly developed metastatic disease after completion of chemotherapy. Although resected, a testicular metastasis portends a poor prognosis.
Testicular metastatic disease is uncommon, particularly from colorectal cancer. Most patients with metastatic disease to the testicle present with advanced or unresectable disease, which portends an overall poor prognosis. Careful follow-up and newer technologies, such as PET/CT scans, permit earlier diagnosis of metastases in unusual locations. Surgical treatment may be beneficial in the rare case of an isolated metastasis. Effective systemic therapy will be necessary to achieve long-term survival.
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JAMES R. OUELLETTE, D.O.,*[double dagger] JENS ERIK HARBOE- SCHMIDT, PH.D.,* DANIEL LUTHRINGER, M.D.,[dagger] SANDRA BRACKERT, B.S.N.,* ALLAN W. SILBERMAN, M.D., PH.D., F.A.C.S.*
From * Cedars Sinai Medical Center Department of Surgery, Division of Surgical Oncology, [dagger] Department
of Pathology, Los Angeles, California and [double dagger] Wright State University Department of Surgery, Division of
Surgical Oncology, Dayton, Ohio
Address correspondence and reprint requests to Allan W. Silberman, M.D., Ph.D., Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048.
Copyright The Southeastern Surgical Congress Jan 2007
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