Case presentation:
A 19-year-old boy with no chronic medical illness presented with
abdominal pain, weight loss, and bleeding per rectum for the last two
months. His abdominal pain was vague, colicky in nature, and associated
with reduced appetite and food aversion.He also developed altered bowel
habits mainly diarrhea and occasionally blood mixed in stools. No
extraintestinal symptoms were reported. No family history of
inflammatory bowel disease or any malignancy was present. No history of
any prior surgery. He smoked cigarettes occasionally for less than 1
month. The clinical exam was remarkable for mild right upper quadrant
tenderness. No palpable lymph nodes. The digital rectal exam was
negative for fresh blood or melena. The scrotal exam was normal. Initial
labs revealed mild anemia and slightly elevated transaminases (Table 1).
US abdomen revealed an enlarged liver measuring 19.7 cm in length.
Multiple heterogeneous hyperechoic lesions were noted in the liver, the
largest measuring 9.9 x 9.7 in the right lobe and 10 x 8.3 in the left
lobe. The main portal vein measured 15 mm in diameter. There was a
filling defect in the intrahepatic main portal vein extending into the
main right and left branches, suggestive of thrombosis. A few periportal
lymph nodes were noted, the largest measuring 17 x 14 mm. Mild ascites.
Based on the initial ultrasound malignancy was suspected and an MRI of
the abdomen was performed which showed nlarged liver with multiple focal
lesions 11 cm in maximal dimension, involving all segments with the
largest two at the left lobe and the subdiaphragmatic part of the right
lobe. Tumor thrombus of the left and right portal branches as well as
some of the segmental branches. The lesions had more radiological
features of multi-centric primary malignant liver neoplasm particularly
hepatocellular carcinoma than metastases. Dilated intrahepatic bile
ducts particularly at the left lobe were seen. Enlarged lymph nodes at
the retrocaval, porta hepatis, upper paraaortic, and mesenteric regions
23 mm in maximal short axis, impressive of metastatic lymph nodes
(Figures 1a-1b). Alpha-fetoprotein (AFP) was requested and came very
high (Table 1).
The patient was discussed in the tumor board although the radiologic
impression was multifocal hepatocellular carcinoma plan was to biopsy
the lesion and perform a colonoscopy and pan CT scan to rule out other
primary lesions. Colonoscopy was performed as well to rule out primary
colonic malignancy given a history of bleeding per rectum.
Contrast enhanced CT scan revealed multiple large necrotic liver masses
in all segments, showing heterogenous enhancement, largest at segment
VII, measuring 13.0 x 9.6 cm. large filling defect was seen at the
distal part of the portal vein, likely representing tumor thrombus. A
heterogenous soft tissue mass seen at the sigmoid mesentery infiltrating
the sigmoid colon wall. Multiple enhancing peritoneal nodules were seen
at the abdomen and pelvis, largest in the pelvic region measuring 3.8 x
2.8 cm suggesting peritoneal metastasis. Multiple enlarged lymph nodes
at mesenteric, retrocaval, and paraaortic regions. Other structures were
unremarkable. Moderate free fluid is seen in the abdomen and pelvis. No
lung or bony lesions were seen. (See Figure 2).
Colonoscopic examination revealed a circumferential ulcerative and
infiltrative mass lesion of around 6-7 cm, extending from 19-26 cm from
the anal verge (Figure 3). The rest of the colonic mucosa appeared
normal, and biopsies were taken, suspicion of the primary colonic tumor
was raised. Gastroscopy was also performed to rule out the GI origin of
the tumor and was normal. An ultrasound-guided liver biopsy was
performed from one of the larger liver lesions.
The liver biopsy consisted of multiple fragments of tumor tissue,
composed of predominantly clear cells arranged in reticular, solid, and
focal hepatoid and microcystic growth patterns. In places, the tumor
cells exhibited marked nuclear pleomorphism with a high
nuclear-cytoplasmic ratio. Mitotic figures were easily identifiable.
Frequent hyaline globules were noted, and foci of necrosis were also
seen(Figure 4-5).
A wide panel of immunostains was performed, which revealed that the
tumor was positive for Cytokeratin AE1/AE3, Glypican 3, CDX2 (strong
patchy positivity), and SALL4(Figure 6-7). The hyaline globules stained
weakly for AFP, but the tumor cells were AFP negative. Immunostains for
arginase, Hep par 1, CD30, Oct3/4, and S100 were negative.
The tumor morphology, along with a combination of positive staining for
cytokeratin, Glypican 3, SALL4, CDX2, and high serum AFP levels were
highly suggestive of a yolk sac tumor. In addition, in this biopsy, no
other germ cell tumor morphology was noted. The appearances in the
separately sent sigmoid colon biopsy showed similar tumor morphology and
were likely representing metastasis of the sigmoid colon.
After the diagnosis was confirmed and revealed to the family discussion
was made regarding starting chemotherapy. Given the high tumor burden,
there was a high risk of tumor lysis syndrome as well as the dose was
adjusted for liver and renal parameters. The patient was started on
Bleomycin, Etoposide 50 % dose reduction, Cisplatin 25 % dose
reduction, and dexamethasone 5 mg IV. For tumor lysis syndrome
Rasburicase IV pre-treatment, with allopurinol was started. After the
first cycle patient became severely ill with respiratory distress and
was admitted to ICU requiring non-invasive ventilation. After his
condition stabilized, he received a second cycle of chemotherapy on day
5 of the first cycle. After the second cycle, his clinical condition
deteriorated with episodes of vomiting resulting in aspiration
pneumonia, and the patient was intubated and started on mechanical
ventilation. The patient was neutropenic and was started on
broad-spectrum antibiotics including Meropenem IV, and Vancomycin IV. On
day 6 of the first cycle, the patient had a cardiac arrest and could not
be revived.