Primary Yolk Sac Tumor of the Liver: A Rare Cause of Bile Duct Obstruction

Primary yolk sac tumor (YST) of the liver is an extremely rare extragonadal germ cell tumor. Here, we present a case of a young man who developed primary YST of the liver which metastasized to periductal lymph nodes causing bile duct obstruction. A 32-year-old male was referred from an outside hospital for evaluation of painless jaundice. Initial investigation showed common bile duct compression from periductal lymph nodes. Inital biopsy results were concerning for adenocarcinoma. The patient was ultimately diganosed with primary YST of the liver. He was then started on a curative-intent chemotherapy regimen of bleomycin, etoposide, and cisplatin. This case highlights the importance of keeping the primary YST of the liver on the differential diagnosis as initial staining patterns are similar to adenocarcinoma which has a very different management.


Introduction
Bile duct obstruction presents clinically with jaundice and elevated liver enzymes.Bile duct obstruction can be due to either luminal pathology such as biliary stones or strictures or extrinsic compression due to tumor or enlarged lymph nodes.
Extragonadal germ cell tumor (GCT) is a tumor that is histologically of gonadal origin despite being located outside of the gonads.Te common extragonadal GCT sites are midline structures including the mediastinum, retroperitoneum, and the sacral region [1].Primary yolk sac tumor (YST) of the liver is an extremely rare extragonadal GCT.In this case report, we highlight a case of primary YST of the liver in a young man, some peculiar features, and important learning points that can be drawn from this case.

Case Report
A 32-year-old male was referred from an outside facility for evaluation of painless jaundice.He had multiple prior hospitalizations with evidence of a distal bile duct stricture on computed tomography (CT).Endoscopic ultrasound (EUS) was performed, showing enlarged periportal and periductal lymph nodes in addition to a dilated common bile duct (CBD) secondary to the distal common bile duct (CBD) stricture.EUS-guided fne-needle biopsy (FNB) was obtained from the largest periductal lymph node.An endoscopic retrograde cholangiopancreatography (ERCP) was then performed with the placement of a plastic biliary stent to decompress the biliary tree and relieve the CBD obstruction secondary to lymphadenopathy.His serum bilirubin levels normalized 1 week later.
FNB results took several rounds of staining before coming to a fnal diagnosis.Initial staining results were signifcant for a positive cytokeratin 7 (Figure 1(a)) and a negative cytokeratin 17 and cytokeratin 20.Te second round of staining was positive for alpha fetoprotein (AFP) (Figure 1(b)) and glypican-3 (Figure 1(c)).Te fnal round of staining was positive for sal-like protein 4 (SALL4) (Figure 1(d)) and negative for hepatocyte parafn-1 (Hep-Par-1) and arginase-1 (Arg-1).Tis confrmed the presence of a YST.Serum AFP was found to be elevated at >1,000 ng/ mL, and serum cancer antigen 19-9 was elevated at 67.1 U/ mL.A scrotal ultrasound was then performed but revealed no primary testicular mass, testicular atrophy, or scars, which confrmed the diagnosis of a primary YST of the liver.
Te patient was then referred to oncology where a positron emission tomography (PET) scan was performed and showed no potential secondary sites of malignancy.He started a curative-intent chemotherapy regimen of bleomycin, etoposide, and cisplatin for a total of 4 cycles.Tis course was complicated by a single episode of neutropenic fever at the end of cycle 1 which led to a one-day delay in starting cycle 2. Te patient ultimately required bonemarrow transplantation.He underwent ERCP 2 months after transplantation, during which the biliary stent was removed and a repeat cholangiogram confrmed resolution of the distal bile duct stricture.He is in remission as of 1 year of transplantation.

Discussion
Primary YST of the liver is a very rare extragonadal YST with only approximately 20 cases reported, the frst being in 1975 by Hart et al. [2,3].Of note, only fve of these cases were adult males [3].Te reported mortality rate is >50% [4].Tis is attributed to the highly malignant nature of YSTs.Primary YST of the liver has been associated with young females and a high AFP according to Wong et al. [5].Schiller-Duval body is pathognomonic of a YST and if identifed can be a useful fnding to diferentiate from other malignancies.
Tere are three existing hypotheses for the pathogenesis of primary YSTof the liver [3].Te frst is aberrant migration of primordial germs which, instead of migrating towards the gonads, migrated towards a diferent location during embryogenesis [3].Te second hypothesis is reverse migration of the transformed germs cells where cells reach the gonads but then continue to migrate to a secondary location [3].Te third hypothesis is abnormal diferentiation of somatic cells, where there were no issues with embryogenesis, but instead, the somatic cells underwent similar diferentiation as germ cells in the gonads [3].
Tis case was unique in that the patient only became symptomatic once the tumor spread to periductal lymph nodes causing extrinsic compression of the CBD.In addition, abdominal CT and PET scan failed to fnd a primary mass in the liver or the testes; as a result, there was no appreciable tumor to surgically remove.Since YST is a highly malignant tumor, our hypothesis is that this primary liver tumor quickly metastasized to the periductal and periportal lymph nodes causing him to be symptomatic much earlier in his disease course.Important to note is that a routine testicular biopsy is not recommended if the scrotal ultrasound shows no testicular mass [6].As a result, we did not elect to perform a testicular biopsy.Tis was further supported by the fact that there was no lumbar or para-aortic lymphadenopathy appreciated upon further investigation which could have suggested metastases of a primary testicular malignancy.
An important learning point from this case is that the FNB results took several rounds of staining before coming to the diagnosis of YST.Te initial rounds of staining were suggestive of either YST, adenocarcinoma, or some rare variants of hepatocellular carcinoma.It was not until the fnal round of staining, showing a positive SALL4, negative HepPar-1, and negative Arg-1 which confrmed YST.Given the similar initial staining patterns between YST, adenocarcinoma, and certain variants of hepatocellular carcinoma, it is important to consider YST in the diferential diagnosis.Tis is primarily because the management of  Case Reports in Gastrointestinal Medicine adenocarcinoma frequently requires surgery whereas primary YST of the liver can be managed with only chemotherapy as illustrated by Whelan et al. [7].Of note, most cases of primary YST of the liver do end up requiring surgery; however, only after the tumor burden was decreased with chemotherapy.
In conclusion, although a rare diagnosis, primary YST of the liver should be considered in the diferential diagnosis of young patients with CBD obstruction secondary to extrinsic compression from periductal lymph nodes.