Case of the Month: Gastrointestinal and Liver Pathology

February 2016 Case of the Month authored by Gastrointestinal and Liver Pathology Fellow Michael Feely, D.O.

Clinical History

A 27-year-old female presented to the emergency room with intractable abdominal pain she had already experienced for several days. A computerized axial tomography (CT) scan revealed a 14 cm liver lesion in the right lobe. The lesion appeared fluid-filled and had characteristics suggestive of a hemangioma. At the time of resection, an intraoperative ultrasound was performed, which suggested the lesion was, in fact, solid. A right trisegmentectomy was performed.

Pathologic Findings

A 15 cm mass was present in the right lobe of the liver (Figure 1).

Figure 1: Gross representation of the liver mass

The tan-white mass had a gelatinous cut surface. This lesion had a tendency to bulge from the cut surface and contained focal areas of central hemorrhage. The mass was lobulated at its periphery, with some lobules of lesion extending into the surrounding liver parenchyma. No other discrete lesions were identified.

Histologically, the tumor was composed of haphazard arrangements to sheets of spindle, oval and stellate cells embedded in a myxoid stroma. In some areas, tumor cells exhibited marked pleomorphism with frequent giant cell forms (Figure 2).

Figure 2: Histologic features of the liver mass (H&E stain, 100X)

Intracytoplasmic and extracellular, eosinophilic globules were present which were found to be PAS-D positive (Figure 3).

Figure 3: Eosinophilic globules highlighted by PAS-D stain (100X)


Due to the undifferentiated nature of this tumor, a panel of antibodies was used to characterize it; the panel included:
•    Cytokeratin (AE1/AE3)
•    Hepatocellular marker (HepPar1)
•    Skeletal muscle markers (desmin and myogenin)
•    Gastrointestinal stromal markers (cKit and DOG-1)
•    Glypican-3

Immunohistochemical studies revealed tumor cell expression of glypican-3 (Figure 4) with focal reactivity for AE1/AE3 and desmin. DOG-1. cKit, myogenin and HepPar1 were non-reactive.

Figure 4: Immunohistochemical study for glypican-3 (100X)

 



Diagnosis

(Hover the cursor over the link above to read the diagnosis for this case.)
 




Discussion

Undifferentiated (embryonal) sarcoma (UES) is a rare pediatric liver neoplasm of uncertain etiology. Although these lesions tend to present during the sixth through tenth year of life, a number of cases have been reported outside of that classic age range, particularly in young adults. The presenting symptoms are frequently nonspecific, and these rare tumors are often encountered incidentally on imaging studies performed for other reasons. Characteristically, radiographic studies may reveal what appears to be a fluid-filled mass on CT or magnetic resonance imaging (MRI), while ultrasound will show the mass to be solid.

Grossly, UES range in size from 10 - 30 cm and often appear lobulated, as in this case. The cut surfaces are typically tan-white, with areas of necrosis and hemorrhage. Areas of variable macroscopic appearance and interface of the tumor with the adjacent liver parenchyma should be sampled for histology.

Microscopically, these tumors are composed of spindled-to-stellate cells, with scattered, bizarre, multinucleated cells; the cellularity can vary significantly.

Characteristic intracytoplasmic and extracellular globules are almost invariably present as in this case, and extramedullary hematopoiesis may be encountered. Entrapped hepatocytes and bile ducts can be seen at the periphery of the tumor.

Immunohistochemical studies are non-specific, but negativity for hepatocellular, gastrointestinal stromal and skeletal muscle markers help rule-out hepatocellular carcinoma, gastrointestinal stromal tumor and rhabdomyosarcoma, which are major differential diagnoses for UES in this young adult population. Recent studies have shown some tumor cell expression of glypican-3, as can be seen in this case, particularly in the large multinucleated tumor cells.

The exact pathogenesis of UES has yet to be established; however, several cases of composite UES-mesenchymal hamartomas have been reported in literature, suggesting a common link among these two pediatric neoplasms. Although the prognosis for UES is historically poor, the advent of newer chemotherapeutic agents, which are utilized following complete resection, has shown some promising outcomes.

References

  1. Lenze F, Birkfellner T, Lenz P, Hussein K, Länger F, Kreipe H, Domschke W. Undifferentiated embryonal sarcoma of the liver in adults. Cancer. 2008. May 15;112(10):2274-82.
  2. Crider M, Hoggard E, Carlos Manivel J. Undifferentiated (Embryonal) Sarcoma of the Liver. RadioGraphics. 2009. 29(6):1665-1668.
  3. Levy M, Trivedi A, Zhang J, Miles L, Mattis AN, Kim GE, Lassman C, Anders RA, Misdraji J, Yerian LM, Xu H, Dhall D, Wang HL. Expression of glypican-3 in undifferentiated embryonal sarcoma and mesenchymal hamartoma of the liver. Hum Pathol. 2012. May;43(5):695-701.
  4. Kiani B, Ferrell LD, Qualman S, Frankel WL. Immunohistochemical analysis of embryonal sarcoma of the liver. Appl Immunohistochem Mol Morphol. 2006. Jun;14(2):193-7.
  5. Lauwers GY, Grant LD, Donnelly WH, Meloni AM, Foss RM, Sanberg AA, Langham MR Jr. Hepatic undifferentiated (embryonal) sarcoma arising in a mesenchymal hamartoma. Am J Surg Pathol. 1997. Oct;21(10):1248-54.
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