Serum AFP was grossly elevated at 900 ng/ml. 

In addition, a non-contrast CT scan showed diffuse nodularity of the liver.  

• Cohesive clusters of polygonal cells forming acini and sometimes vague trabecular structures
• Enlarged eccentric or central nuclei
• Macronucleoli
• Abundant granular cytoplasm
• Clean background

Without the clinical history, the initial morphologic differential diagnoses of an acini-forming neoplasm are wide ranging and would include:

1. Adenocarcinoma of the thoracic, abdominal or pelvic visceral sites (i.e. prostatic acinar adenocarcinoma, acinar cell carcinoma of the pancreas)
2. Acini/follicle forming carcinomas of the head and neck including acinic cell carcinoma of salivary gland tissue, follicular thyroid carcinoma.
3. Anaplastic meningioma should also be considered owing to the site of the tumour but it should be excluded based on imaging findings

Thus, in such an instance, it is helpful to look at clinical investigations, in order to narrow down the differential diagnosis. Important clues to the diagnosis include the grossly elevated AFP and the abnormal finding on liver imaging.

Taking into account the raised AFP and imaging findings, the revised DDx list includes: 

⁃ Metastatic hepatocellular carcinoma
⁃ Germ cell tumour i.e. yolk sac / embryonal carcinoma
⁃ Metastatic prostatic acinar adenocarcinoma
⁃ Metastatic adenocarcinoma of other visceral sites

The cell block showed limited amounts of tumour and the following stains were performed:

Hep Par 1 showed very focal reactivity. Glypican 3 was negative, arguing against the diagnosis of a germ cell tumour (e.g. yolk sac tumour). The possibility of metastatic Hepatocellular carcinoma was considered but the results were not definitive on the cell block.

The mass subsequently resected and the histology is as follows:

Metastatic hepatocellular carcinoma

The difficulty in this case lies in the dominant acinar architecture, presence of vague trabecular structures (noted in retrospect, and more apparent in the cell block than the smears) and absence of endothelial wrapping around the clusters. No bile pigment was identified as well, and this was noted in the cytology report.

Cytomorphologic hallmarks of hepatocellular carcinoma are the presence of trabecular architecture, endothelial wrapping around cell groups and intracytoplasmic bile pigment. Interestingly, the histology sample showed an overwhelming classic sinusoidal-trabecular architecture while the pseudoacinar pattern was only focally noted; the latter being the predominant pattern in the cytology sample.

These sampling issues highlight the importance of rigorous attention to clinical investigations, in particular, where the cytomorphologic features are not fully classical or specific.