Tumors In The Liver - Diagnostic Problems
Case 12 -
Linda D. Ferrell, M.D.
Wendy L. Frankel, M.D.
23 year old woman presented with 40 lb unintentional
weight loss, abdominal fullness, and non-specific abdominal pain. Abdominal CT demonstrated a hepatic
neoplasm, and at surgery, a greater than 10 cm hemorrhagic and necrotic mass was found.
Case 12 - Figure 1 - Proliferation of spindled and stellate cells, low power
Case 12 - Figure 2 - Spindled and stellate cells with ill-defined cell borders and rare multinucleated giant cell, high power
Case 12 - Figure 3 - Epithelioid cells, low power
Case 12 - Figure 4 - Epithelioid atypical cells containing hyaline globules (arrow) within the cytoplasm and stroma, PAS stain with diastase, high power
Pathologic findings: Proliferation of spindled and stellate cells, low
power. Spindled and stellate cells with ill-defined cell borders and rare multinucleated giant cell,
high power.Epithelioid atypical cells containing hyaline globules within the cytoplasm and stroma, PAS
stain with diastase, high power.
Diagnosis- Embryonal Sarcoma
Undifferentiated (Embryonal) sarcoma
Clinical Features. Embryonal sarcoma is a rare tumor that typically occurs in
children between the ages of 6 and 10, with some occurring in a slightly older age group (under the age
of 20). The presenting features are often that of a mass or of abdominal pain. Complete surgical
excision generally offers the best outcome.
Gross findings. Embryonal sarcomas are usually large, soft tumors, with a variably
cystic and solid areas and a white, shiny or gelatinous or mucoid surface. Additional areas of necrosis
and hemorrhage are often present.
Microscopic findings. These tumors contain a mixture of spindled and stellate
cells embedded in a myxoid stroma. The tumor cells have a granular to bubbly, light pink cytoplasm, and
many contain cytoplasmic globules of various sizes which are PAS-digest-positive. These globules may
also be noted in the stroma. Other cellular features include the presence of other large atypical tumor
cells with hyperchromatic nuclei as well as multinucleated tumor cells. The surrounding stroma is
usually myxoid but some dense collagen deposits can be present. Mitotic figures are usually numerous.
Hematopoeisis is often noted and entrapped hepatocytes and/or ductules can be present at the tumor's
Special studies. The tumor cells of the lesion have been shown to
immunohistochemically stain for vimentin, alpha-1 antitrypsin, alpha-1 antichymotrypsin.
Clinical features. Mesenchymal hamartoma (MH) is a benign tumor which occurs
primarily in young children, predominantly presenting at less than 2 years of age. It is the third most
common tumor of the liver in this age group (following hepatoblastoma and infantile
hemangioendothelioma). The patient often presents with such clinical symptoms as a palpable liver mass,
abdominal enlargement, or respiratory distress due to compression by the tumor. No risk for malignant
transformation has been noted.
Gross findings. The tumor can be solid or cystic, with the solid areas of this
tumor typically a tan color. When cysts are present, they contain a translucent fluid or a gelatinous
material. These cysts may form due to the degeneration of the loose
mesenchymal tissue of the tumor, and it is thought that the tumor probably enlarges by continued
accumulation of fluid into these cysts.
Microscopic features. MH has epithelial and stromal
components. The former consistent of relatively normal-appearing hepatocytes and bile ducts, both which
are surrounded by varying amounts of myxoid to fibrous stroma. The hepatocytes are cytologically
unremarkable and are arranged for the most part either in small clusters or in larger groups with
retention of the cell plate architecture as in the normal liver. The bile duct structures are typically
arranged in a branching pattern, and often are associated with an acute inflammatory infiltrate in the
duct walls or adjacent to it. The cystic spaces, when present, may be lined by flattened to cuboidal
epithelial cells, which are surrounded by a loose to dense fibrous tissue. Cysts may also lack any
lining cells. The stroma generally contains increased numbers of small vascular structures (but the
cysts are not lined by endothelial cells), spindle cells, and inflammatory cells. No normal portal zones
are present. Extramedullary hematopoiesis is often noted.
Clinical features. The infantile hemangioendothelioima (IHE) is the second most
common tumor in children under three years of age, second only to hepatoblastoma, and almost all the
reported cases have occurred in infants less than six months old. The tumor is almost twice as common in
girls than in boys. The tumors are often multifocal within the liver and about 10% of the patients also
have hemangiomas present in other organs. The tumors may also be associated with other congenital
anomalies, such as bilateral renal agenesis, Beckwith-Wiedemann syndrome, hemihypertrophy, and
meningomyelocele. The clinical presentation may be an abdominal mass or distention (with hepatomegaly),
jaundice, diarrhea, constipation, vomiting, congestive heart failure, or failure to thrive. Other less
common findings can include thrombocytopenia due to sequestration of platelets within the tumor(s) or
rupture with hemoperitoneum. These tumors are generally benign histologically, but because of their
multifocality and/or large size, the patients have a high mortality rate due to cardiac or hepatic
failure. The tumors can regress, but therapy such as resection, embolization, hepatic arterial
ligation, or chemo/radiation is often necessary for patient survival. Angiosarcoma may rarely arise in
Gross findings. IHE is often a poorly circumscribed lesion, and can be solid and
cystic, with variable hemorrhagic foci. These foci typically alternate with the fibrotic (solid)
zones. The tumors are multifocal.
Microscopic findings. Two histologic subtypes have been described for this lesion,
although practically speaking, distinguishing the two can be difficult. Type 1 is defined by a mixture
of large numbers of small vascular channels and fewer, large, irregularly shaped spaces with a cavernous
appearance, with both types of vascular channels lined by a single layer of endothelial cells. The
vascular spaces are separated by a poorly-developed stroma with only scattered collagen or reticulin
fibers. Small bile ducts and well as hepatocytes can be seen in the stroma as well, often near the
periphery of the tumor. Focal necrosis, hemorrhage, fibrosis, and calcification are often present. Type
2 lesions contains endothelial cells with more atypical cytologic features, with mitotic activity and
hyperchromasia, and arranged in a more complex budding or branching pattern [Craig, 1989 #396] than noted
in type 1 lesions.
Special studies. The endothelial cells of the tumor
will stain with CD34, CD31, and Factor VIII. The stromal cells underlying the basement membrane of the
capillary structures are alpha-smooth muscle actin and HHF35 positive, desmin negative, a profile
consistent with pericytes.
- Abbassi V, Hoy G, Weintraub B: HCG production by hepatoblastoma causing isosexual precocious puberty. Pediatric Research 13:375-381, 1979.
- Altmann H: Epthelial and mixed hepatoblastoma in the adult. Pathology, Research and Practice 188:16-26, 1992.
- Anthony P: Tumours and tumour-like lesions of the liver and biliary tract. In MacSween R, Anthony P, Scheuer P, et al (eds): Pathology of the Liver 3rd ed. Edinburgh, Churchill Livingstone, 1994, pp 635-711
- Conran R, Hitchcock C, Waclawiw M, et al: Hepatoblastoma: The prognostic significance of histologic type. Pediatric Pathology 12:167-183, 1992.
- Haas J, Muczynski K, Krailo M, et al: Histopathology and prognosis in childhood hepatoblastoma and hepatocarcinoma. Cancer 64:1082-1095, 1989.
- Haggitt R, Reid B: Hereditary gastrointestinal polyposis syndromes. American Journal of Surgical Pathology 10:871-887, 1986.
- Lack E, Schloo B, Azumi N, et al: Undifferentiated (embryonal) sarcoma of the liver: Clinical and pathologic study of 16 cases with emphasis on immunohistochemical features. American Journal of Surgical Pathology 15:1-16, 1991.
- Ruck P, Harms D, Kaiserling E: Neuroendocrine differentiation in hepatoblastoma: An immunohistochemical investigation. American Journal of Surgical Pathology 14:847-855, 1990.
- Ruck P, Kaiserling E: Melanin-containing hepatoblastoma with endocrine differentiation: An immunohistochemical and ultrastructural study. Cancer 72:361-368, 1993.
- Saxena R, Leake J, Shafford E, et al: Chemotherapy effects on hepatoblastoma: A histological study. American Journal of Surgical Pathology 17:1266-1271, 1993.
- Stocker J: Hepatoblastoma. Seminars in Diagnostic Pathology 11:136-143, 1994.
- Stocker J, Ishak K: Undifferentiated (embryonal) sarcoma of the liver: Report of 31 cases. Cancer 42:336-348, 1978.
- Weinberg A, Finegold M: Primary hepatic tumors of childhood. Human Pathology 14:512-537, 1983.