Metastatic malignancies to the testicle and paratesticular tissue are extremely rare. The most frequent primary cancers are prostate, lung, kidney, gastrointestinal tumors and breast cancers [2]. In particular, very limited cases reported metastasis from pancreatic cancer to the testicle and paratesticular tissue. Kiefer ED first described metastatic epididymal spread from primary pancreatic carcinoma in 1927 as an incidental autopsy finding [3]. To date, less than 30 cases have been reported, including one from China [4], two from South Korea [5–6], ten from Japan [7], six from the USA [8–12] and the other five from European countries [13–17]. The scrotal or inguinal metastasis propensity occurs world-wide, although there is a remarkably high incidence among Japanese men, who account for one harf of published cases. For this literature review, we searched relevant case reports that were available in full-text. Some cases that did not contain detailed information on treatment and prognosis were excluded. Consequently, a total of 15 cases documented in 14 published papers were included in our review (Table 1).
Table 1 Reports of metastatic paratesticular or testicular tumors of pancreatic or duodenum cancer
Case No.
|
Age
(y)
|
Symptoms
|
Duration
|
Site
|
size (cm)
|
Metastatic
Organ
|
Treatment
|
Primary location and histopathology
|
Prognosis after treatment
|
1[4]
|
65
|
Painless scrotal swelling
|
9 months
|
left
|
|
Left testis
Right lung
|
Radical orchiectomy+
Pancreatic mass resection+ right lung tumor biopsy
|
Pancreatic body
adenocarcinoma
|
Alive,9 month
|
2[5]
|
67
|
Painless scrotal swelling
|
3 months
|
left
|
7 × 5
|
Left paratestis
Peritoneum,bone
|
Radical orchiectomy+gemicitabine chemotherapy
|
Pancreatic tail
Mucinous cystadenocarcinoma
|
Died,3 month
|
5[6]
|
69
|
Painful scrotal swelling
|
NA
|
left
|
NA
|
Tunica virginals testis
Liver, peritoneum
Omentum
|
Hydrocelectomy+ gemicitabine chemotherapy
|
Pancreatic tail Adenocarcinoma
|
NA
|
11[7]
|
58
|
Painful scrotal swelling,
|
NA
|
left
|
3-4
|
Epididymis,spermatic cord,Stomach,Left kidney ,spleen
|
Radical orchiectomy+Pancreatic tumor biopsy
|
Pancreatic tail
Adenocarcinoma
|
Died,3
months
|
6[8]
|
42
|
Jaundice,dark urine,pale stool, Painful scrotal swelling, Weight loss
|
3 weeks
|
left
|
NA
|
Omentum, tunica vaginalis testis, porta hepatis.
|
Exploratory laparotomy, left scrotal mass biopsy.
|
Pancreatic tail Adenocarcinoma
|
NA.
|
8[9]
|
53
|
Painful scrotal swelling
|
NA
|
right
|
4
|
Epididymis
Liver
|
Radical orchiectomy+ Pancreatic tumor biopsy
|
Pancreatic head ,body and uncinate process
Adenocarcinoma
|
Died,16 months
|
9[9]
|
36
|
Painless scrotal swelling,
|
18 months
|
right
|
NA
|
right testis,Epididymis
Spermatic cord
|
Radical orchiectomy
|
Ampullary
Adenocarcinoma
|
Died,2
months
|
10[10]
|
58
|
Painful scrotal swelling,
|
1 month
|
left
|
7.0× 4.5×3.5
|
Left testis,
Liver,
|
Radical orchiectomy+ Pancreatic tumor biopsy
|
Pancreatic tail
Adenocarcinoma
|
Alive,6 month
|
12[11]
|
70
|
Painless scrotal swelling,
|
21 months
|
right
|
NA
|
Tunica vaginalis testis
|
Hydrocelectomy Pancreaticoduodenectomy
capecitabine chemoradiation
|
Ampullary Adenocarcinoma
|
Alive,1 month
|
15[12]
|
41
|
painful scrotal swelling
|
4 months
|
right
|
1.7,0.8
|
the spermatic cord
epididymis
|
Radical orchidectomy+ chemotherapy
|
Pancreatic head and body
Adenocarcinoma
|
Died,12 months
|
3[13]
|
36
|
Painful scrotal swelling
|
NA
|
right
|
NA
|
right testis, liver
|
Radical orchiectomy+ chemotherapy
|
Pancreatic tail.Adenocarcinoma
|
Died,3 month
|
4[14]
|
73
|
Painless scrotal swelling,
Weight loss
|
NA
|
left
|
4 × 8
|
Left paratestis
Liver, Lung,
Retroperitoneum,
Left suprarenal gland
|
Radical orchiectomy
|
Pancreatic
Adenocarcinoma
|
Died,2 month
|
7[15]
|
70
|
Painless scrotal swelling,
|
NA
|
right
|
2
|
Epididymis
Spermatic cord,liver
|
Pancreatic tumor biopsy+
orchifunicolectomy+ gemicitabine and abraxane chemotherapy
|
Ductal Pancreatic
Adenocarcinoma
|
NA
|
13[16]
|
77
|
Painless scrotal swelling,
Weight loss, Abdominal pain
|
1 month
|
right
|
3.0× 2.0
|
Right testis
|
Radical orchiectomy+ Pancreatic tumor biopsy
|
Mucinous exocrine pancreatic Adenocarcinoma
|
NA
|
14[17]
|
67
|
Mass in groin, recurrent vomiting
|
3 months
|
right
|
|
the spermatic cord
duodenum
|
Radical orchidectomy
Pancreaticoduodenectomy, splenectomy,chemotherapy
|
Pancreatic body and tail
Adenocarcinoma
|
Alive,4 weeks
|
Our case
|
65
|
Painless scrotal swelling,
|
1 week
|
left
|
2×3
|
Tunica vaginalis testis
Liver, Omentum
Retroperitoneum
|
Radical orchidectomy
|
Pancreatic tail
Adenocarcinoma
|
Died,3
months
|
Abbreviations: NA, not available
Primary testicular tumors are usually diagnosed between the second and fourth decades, while secondary testicular tumors peak in the fifth and sixth decades.The mean age of incidence was 59 years (range: 36 to 77 years), and the peak incidence was in the 5th through 7th decades, with the similarity of the review reported by Tanaka H [7]. As the presentation of pancreatic cancer is often insidious, with nonspecific symptoms such as nausea and anorexia, which delay diagnosis until other more ominous symptoms such as weight loss, abdominal pain, or gastrointestinal symptoms develop. Our review showed that most testicular metastasis cases present as a palpable, painless or painful, slowly enlarging mass in the scrotum, which were easily neglected or misdiagnosed as primary testis leision. There were only three cases who present with weight loss or other digestive system discomfort [8, 14, 16]. One patient was referred because of acutely developed severe pain of right testis [13], who was likely diagnosed as orchitis. Kim YW and colleagues reported a metastatic testicular tumor from pancreas, who presented only with hydrocele as initial symptom [6]. In the present case, the scrotal mass was the first clinical manifestation of the underlying malignancy.The average duration of onset was ranged from one week to 21 months. Hirano D and colleagues found that the bilateral testis were equally involved in metastatic tumors of the spermatic cord originating from 8 stomach cases, 8 colon cases, 2 liver cases, and 2 kidney cases in his review[18]. Tanaka H and colleagues reveled right testis was easily involved in metastatic tumors of the epididymis and the spermatic cord from pancreatic carcinoma, with the ratio 9 to 1[7]. However, in our literature review, we found that the same occurrence in both sides in cases of scrotal or inguinal metastasis from pancrcatic carcinoma.The average metastatic tumor size of in the identified 15 cases was 3.6 cm in a diameter(range:1.6 to 6.5 cm). The tumor size ranged from 2.0 cm to 8.0 cm. Large tumor was reported in two cases [5, 10]. In addition, we discovered a significant feature that 8 cases of carcinomas originating from pancreatic tail were susceptible to metastasize to testis or paratestis compared with tumors from pancreatic head or ampulla.
The mechanisms of metastasis to the scrotal and inguinal tissues from primary malignant neoplasms have not been precisely elucidated. But it has been widely recognized that main routes include arterial embolization, transperitoneal seeding through tunica vaginalis. In our review, the metastatic tumors extending to the testis were found in five (31%) of the identified 16 cases [4, 9, 10, 13, 16], of which one cases invaded the epididymis[9]. Meanwhile, the tumors extending to the paratestis were reported in 11 cases[5, 6, 7, 8, 11, 12, 14, 15, 17], of which 4 cases involved the tunica vaginalis rather than testis[6, 8, 11], six cases invaded the spermatic cord and /or epididymis[5, 7, 1214, 15, 17]. Our case is unique since there were almost no symptoms of the primary tumor, only with paratesticular nodules, which proved to be metastasis and the first sign of pancreatic carcinoma. As there was obvious evidence of retroperitoneal involvement showed in CT scan, the suspected route of tumor spread in this case is either lymphatic or direct transperitoneal seeding from peritoneal carcinomatosis. Due to only one-week duration of onset, the right testicle was clear.
Clinically, no specific features that differentiate primary from secondary testicular or paratesticular tumors are available, as both may present with painful or painless mass, or an indurated testis. Serum tumor markers such as AFP and β-hCG are not helpful in distinguishing primary from secondary testicular tumors. However, one third of patients with pancreatic exocrine adenocarcinoma were found elevated β-hCG levels. Taylor H described a case of pancreatic adenocarcinoma presenting as a testicular tumor featured raised 10-fold hCG levels due to extragonadal secretion [16]. Immunohistochemistry is currently considered as the most sensitive and specific way of determining the origin of the tumor. CA19-9, CDX-2, cytokeratin are reliable markers. Another new markers, such as homeobox protein NANOG, SOX2, and Oct-3/4 have been applied in diagnosis [19–20]. In our case, pancreatic origin was suspected because of extremely elevated tumor markers CA 19 − 9 and positive CT results.
Most cases as well as our case underwent radical orchiectomy, while hydrocelectomy with preservation of the testis was found in two cases [6, 11]. One patient with omentum involvement was managed by scrotal mass biopsy [8]. About half of the cases received chemotherapy including gemicitabine or capecitabine. But the outcome was unsatisfactory with high mortality. In our literature review, two thirds of the patients died in their recorded follow-up period. The shortest survival duration recorded was only 2 months. Compared to other pancreatic origin, ampullary tumors have a higher rate of resectability and a more favorable prognosis. Our review shows that one metastatic ampullary adenocarcinoma patient who underwent pancreaticoduodenectomy had better outcome compared to another case who did not receive primary tumor resection.