Hidekazu Yamamoto mrcs mb bchir (Hons), Department of Urology, Queen Elizabeth Hospital, Birmingham, B15 2TH, UK. Email: email@example.com
Abstract: A rare case of a gastric presentation of a seminoma with burned out primary testicular tumor is described. The patient initially presented with upper gastrointestinal hemorrhage. Endoscopic biopsies were suggestive of seminoma, and testicular ultrasound revealed a focal lesion and testicular microcalcification. Treatment consisted of bilateral orchidectomy, followed by four cycles of etoposide and bleomycin, where a complete response was achieved. Testicular histology was consistent with the ‘burned out’ phenomenon and no tumor cells were found. There are only two previously reported cases of extragonadal seminoma in the stomach.
Germ cell tumors represent the commonest malignancy amongst men aged 15–35 years. Germ cell tumors frequently metastasize via lymphatics to the retroperitoneal lymph nodes, and less commonly to the liver and lungs. Other extragonadal presentations are much rarer. Herein, we report a rare case of seminoma with gastric metastasis which presented initially with upper gastrointestinal hemorrhage, and include a discussion of its subsequent management.
A 39-year-old patient presented to the outpatient clinic with a history of melena, epigastric pain and lethargy. There was no history of alcohol abuse or non-steroidal anti-inflammatory drug (NSAID) use. The patient denied recent weight loss or lethargy, but reported a history of infertility. Past medical history, and physical examination was otherwise unremarkable. Upper gastrointestinal (GI) endoscopy revealed a 3 cm × 3 cm exophytic tumor of the greater curve from which biopsies were taken. Computed tomography (CT) scan showed para-aortic, aortocaval and gastrohepatic lymphadenopathy, and abnormal thickening of gastric mucosa due to tumor (Fig. 1a,b). No pulmonary or hepatic metastases were seen.
Gastric biopsies showed a malignant tumor with an unusual morphology and immunophenotype. Tumor cells were large with well-defined borders and abundant clear cytoplasm, forming nests of varying sizes (Fig. 2a). Cells stained positive for c-KIT (Fig. 2b) but not for placental alkaline phosphatase (PLAP). Immunohistochemistry however, excluded diagnoses of carcinoma, melanoma and lymphoma, as the specimen did not stain for cytokeratin, S-100/HMB45 or any lymphoma markers, respectively. Morphology was neither typical of gastrointestinal tumors, and immunostaining for CD34 and smooth muscle actin were negative. The diagnosis of seminoma was hence favored on the basis of morphology and a strong c-KIT positivity despite PLAP negativity.
The diagnosis of seminoma was further supported by testicular ultrasound findings, which revealed a focal mass measuring 8 mm in diameter within the right testis, as well as bilateral testicular microcalcifications. Both testes were small and atrophic.
Preoperative serum β-human chorionic gonadotropin (β-HCG), α-fetoprotein were both normal, however, lactate dehydrogenase (LDH) was 961 u/L (normal range, 230–460). In addition, testosterone was normal but associated with elevated follicle-stimulating hormone (FSH) and luteinizing hormone (LH), consistent with compensated testicular failure.
Metastatic seminoma was thought to be the most likely diagnosis, and an urgent right orchidectomy followed by chemotherapy was planned. There was a diagnostic doubt regarding the left testis which contained microcalcifications but no focal abnormality on ultrasound. Following a detailed discussion of potential risks, the patient chose to have bilateral orchidectomy with postoperative testosterone replacement therapy.
Macroscopic examination of the pathological specimen revealed bilateral small testes measuring 30 mm × 20 mm × 20 mm in the right and 20 mm × 20 mm × 15 mm in the left. The right testis contained a small white nodule measuring 10 mm in diameter. Histologically, it showed an area of fibrosis with atrophic hyalinized seminiferous tubules (Fig. 3). The left testis showed only atrophy and microcalcification. No intratubular germ cell neoplasia was present in either specimen. Overall findings were suggestive of a ‘burned out’ germ cell tumor of the right testis, with bilateral testicular atrophy.
The patient subsequently underwent postoperative chemotherapy consisting of four cycles of etoposide and cisplatin over a period of 2 months. Interim upper gastrointestinal endoscopy showed reduction in tumor size and, moreover, no active tumor was shown on three subsequent gastric biopsies. CT scans at 1 and 5 months following chemotherapy showed complete radiological remission of the disease, in addition to normal LDH levels. After 2-years follow up, the patient remains well without signs of recurrence (Fig. 1c).
This is a very rare case of a metastatic seminoma to the stomach, presenting as an upper GI hemorrhage. Germ cell tumors characteristically metastasize to retroperitoneal nodes and, less frequently, to lungs, liver, bone or brain. Only two reports, however, exist of seminomatous germ cell metastasis to the stomach.1,2 There are also two reports of non-seminomatous germ cell metastasis to the stomach.3,4 Other gastrointestinal germ cell metastases have been described to the esophagus, duodenum and jejunum5,6 but all are exceedingly rare. These gastrointestinal metastases present commonly as upper GI hemorrhage.
There are several possible routes of metastasis, although we believe an isolated hematogenous event was most likely in this case. Para-aortic lymph nodes above the renal vessels were not enlarged, making direct invasion and retrograde lymphatic spread less likely. It is plausible that gastrohepatic lymphadenopathy occurred from antegrade tumor spread from the stomach.
This phenomenon of ‘burned out’ tumor as in our case is well-documented in the published work, where the primary testicular tumor undergoes complete and spontaneous regression following metastasis.7 Its exact mechanism, however, remains unclear and may represent an autoimmune response.
It is important to distinguish between metastatic germ cell tumor with ‘burned out’ phenomenon and primary extragonadal germ cell tumors.7 In the former situation, the published work agrees that the abnormal testis should be removed prior to chemotherapy. Scrotal ultrasound will identify any structural abnormality within the testis. In our case, testicular ultrasound showed microcalcifications which is associated with a high incidence of germ cell tumor although its true origin is yet to be elucidated.8 If radiological examinations are normal, systematic biopsies from both testes can be used to detect small tumor or carcinoma in situ. Platinum-based chemotherapy should be used to treat the extragonadal component of germ cell tumors, where a seminomatous histology is associated with a better outcome.9