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Testicular germ cell tumor (GCT) is the most common malignancy
among men aged 15 to 35 years, accounting for 1-2% of all
malignancies.[1] Metastasis from testicular GCTs to the
gastrointestinal (GI) tract is rare.[2,3,4] We report two young males
with a metastatic mixed germ cell tumor, who had massive
gastrointestinal hemorrhage secondary to duodenal invasion
by retroperitoneal lymph node mass.
Case 1
A 25 year old man presented with right testicular swelling for 1
month duration. He underwent right orchidectomy at an outside
center. Histopathological examination revealed a seminoma and
immature teratoma. Subsequently he was referred to our center.
On examination, there was a 5 × 5 cm lump in the right
hypochondrium which was apparently arising from the
retroperitoneum. Chest radiograph showed multiple ill-defined
focal nodules. While being evaluated further, he developed
massive hemoptysis and respiratory failure, for which he
required endotracheal intubation and mechanical ventilation.
Contrast-enhanced computed tomography (CECT) scan of
chest and abdomen confirmed presence of multiple lung
metastases with surrounding hemorrhage and revealed
presence of multiple liver metastases and a pericaval mass
infiltrating the duodenum. His serum alpha-fetoprotein (AFP),
beta-human chorionic gonadotropin (ß-HCG), and lactate
dehydrogenase (LDH) levels were 11.94 ng/mL (reference range
0 to 8), 14546 IU/L (normal less than 5), and 898 U/L (reference
range 100 to 190), respectively.
The patient was diagnosed as a case of testicular mixed
GCT stage IIIC (poor risk) with multiple lung, liver and
retroperitoneal metastases. As the patient was very sick and
on ventilator, he was given single-agent carboplatin 600 mg,
along with packed red blood cell transfusions. Within 48 hours, there was clinical improvement and he was extubated. He was
discharged after 3 days with future plan of continuing
chemotherapy with bleomycin-etoposide-cisplatin (BEP)
regime.
But after ten days, he again presented with history of
malena and microcytic hypochromic anemia; hemoglobin was
4.5 g/dl. Serum ß-HCG had increased to >15,000 mIU/ml. Upper
gastrointestinal tract endoscopy (UGIE) revealed a large
ulcerated friable growth infiltrating the second part of
duodenum with active bleeding from the surface. Argon plasma
coagulation (APC) was applied over the bleeding site to achieve
hemostasis. Endoscopic biopsy revealed choriocarcinoma.
Patient was subsequently taken up for angiography and
selective embolisation of the feeding vessels was done
(Figure 1a & b). There was no further GI bleed and he has
been transfusion-independent since the procedure. Thereafter
he received BEP chemotherapy in reduced doses (cisplatin 40
mg/m2, etoposide 200 mg/m2 and bleomycin 30 IU) to avoid
rapid tumor necrosis. He has tolerated the therapy well and
clinically the abdominal mass has reduced in size. BEP
chemotherapy has been planned for follow up visit.
Case 2
A 21 year old male presented with right testicular swelling of 4
months duration and jaundice for 20 days. On examination,
there was 10 × 10 cm mass in the epigastric region. Serum
bilirubin was 12 mg/dl (conjugated fraction 10 mg/dl). CECT
scan of chest and abdomen revealed multiple pulmonary
metastases, multiple large retroperitoneal lymph nodes
displacing head of pancreas and gastric antrum, and
compression of the common bile duct. He underwent rightsided
high inguinal orchidectomy and histopathological
examination revealed mixed germ cell tumor (embryonal cell
carcinoma and yolk cell tumor).
Post orchidectomy serum AFP, ß-HCG and LDH levels were> 350 ng/mL, 1929 IU/L and 468 IU/L respectively. Final
diagnosis of mixed testicular GCT stage IIIC was made.
Percutaneous transhepatic biliary drainage was performed to
relieve the biliary obstruction Due to hyperbilirubinemia and
poor performance status, he was given low-dose single agent
cisplatin (20 mg per day for 5 days). Because of marginal clinical
response, same treatment was repeated and the patient
discharged while waiting for the serum bilirubin to come down.
He presented after three weeks with malena and anaemia.
UGIE showed large friable growth with multiple clots in second
part of duodenum. Argon plasma coagulation was used over
bleeding points and packed red blood cells were transfused. In
spite of above, the patient had an episode of massive upper GI
bleeding with hemorrhagic shock. He was resuscitated with
intravenous fluids, blood and plasma transfusions. Gel-foam
embolisation of feeding vessel was planned but no feeding
vessel could be identified on digital subtraction angiography.
After recovery he was treated with first cycle of BEP regimen,
following which the epigastric mass reduced by 50% and there
was no further GI bleed. Further plan for this patient includes BEP chemotherapy
Discussion
Testicular GCTs are often metastatic to distant sites including
retroperitoneal lymph nodes, lungs and liver. Clinically apparent
gastrointestinal involvement from metastatic testicular cancer
occurs in less than 5% of cases and is more commonly
associated with non seminomatous germ cell tumours (NSGCT)
than with seminomas.[2,3,4,5,6,7,8,9] However in a post-mortem study
gastrointestinal metastases were found in 27% of cases.[5]
Patients with intestinal metastases can present with perforation,
obstruction and bleeding at diagnosis or during treatment. The
sites of GI involvement include duodenum, jejunum, ileum,
stomach, oesophagus, colon, and pancreas, with duodenum
being the most common site.[4,5,6]
The close anatomical proximity between retroperitoneal
nodes and duodenum may explain the high frequency of
duodenal involvement.[9] In both patients who presented here,
GI bleed was due to local invasion of duodenum by
retroperitoneal lymph node mass. Onset was after the diagnosis
of metastatic testicular GCT and while on chemotherapy for
the same. Chemotherapy induced tumor necrosis might have
potentiated bleeding in both cases.
Compared with other GCTs, choriocarcinoma frequently
spreads hematogenously rather than through the lymphatic
system.[1] It is the most aggressive GCT and has the tendency
to outgrow its blood supply resulting in ulceration, necrosis,
bleeding and perforation. In the first case, the primary tumor
revealed seminoma and immature teratoma, whereas duodenal
mass showed choriocarcinoma. A markedly high serum ß-HCG
at baseline suggested that choriocarcinoma was a significant
component of the tumor from the outset. As the primary tumor
did not show any foci of choriocarcinoma, possibly a transformation in histology of the tumor to choriocarcinoma
occurred at the metastatic site, which resulted in increased
susceptibility to necrosis and bleed.
The outcome of the patients of metastatic GCT with GI
involvement has been shown to be quite poor, and in one
series, 4/5 patients died from unresponsive or progressive
disease.[6] Management of such patients mostly requires
multimodality approach, including endoscopic techniques,
chemotherapy and angio-embolisation.
Obstructive jaundice has rarely been reported as a
complication of metastatic GCT. Unsuspected testicular
seminoma, metastatic to retroperitoneal lymph node has been
reported to cause obstructive jaundice and mimic primary
pancreatic cancer in an elderly male.[10] In analogy to obstructive
jaundice caused by other solid-organ malignancies,
management involves biliary drainage procedures and
chemotherapy in reduced doses. As cisplatin and carboplatin
are excreted through liver, they may be used safely in these
patients. But in a chemo responsive tumor like GCT, whether
chemotherapy alone can result in relief of the obstruction is
not clear. In present patient we used biliary drainage and single
age cisplatin initially, followed by BEP chemotherapy after
normalising of serum bilirubin.
These two cases serve to illustrate several points: 1) GI
haemorrhage in a young male may represent an underlying
metastatic GCT; 2) endoscopic techniques and selective
angiographic embolisation play an important role in controlling
intestinal bleeding in such patients; and 3) there is increased
risk of recurrent GI hemorrhage during the initial phase of
therapy, likely due to chemotherapy induced tumor necrosis.
The importance of a multidisciplinary management for these
patients, encompassing the fields of medical oncology, urology,
gastroenterology and interventional radiology, is also
highlighted.
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