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.