Case 3 -
Raouf E. Nakhleh
Mayo Clinic Jacksonville
Click on each slide thumbnail image for an enlarged view
A 60yo Caucasian male with end-stage liver disease secondary to alcohol use undergoes liver
transplantation. At the time of transplant, the patient had refractory ascites requiring a TIPS
procedure a year prior. The native liver weight was 1210gm and was diffusely nodular. Near the hilum a
prominent 1.2cm tan nodule was present and is seen on the slides.
Case 3 - Figure 10 - High power view of spindle cells
Case 3 - Figure 11 - Immunohistochemical stain for HMB-45 shows diffuse positivity within the nodule.
Case 3 - Figure 12 - HMB 45. A granular cytoplasmic staining pattern is present in a majority of the lesional cells.
Case 3 - Figure 13 - Immunohistochemical stain for actin shows patchy staining within the nodule.
Case 3 - Figure 14 - Actin. Epithelioid and spindle cells within the nodule are immunoreactive for actin.
Histopathologic features and differential diagnosis
A tumor is noted in a background of cirrhosis. The tumor is well demarcated but not encapsulated.
Within the tumor nodule there is an entrapped portal tract. The tumor nodule is very cellular with
variable morphology. The tumor demonstrates a solid growth pattern. The majority of cells are
epithelioid with slightly pleomorphic nuclei and occasional nucleoli without mitosis. The cytoplasm of
these cells is eosinophilic with peripheral clearing. More cellular areas within the tumor have a
hepatoid look with more crowded nuclei and less cytoplasm. Focally, the cells are spindled with
cytoplasmic clearing. Occasional thick-walled vessels are seen, but a sinusoidal pattern is not
present. A very small amount of fat is noted within the tumor. Immunostains performed are as follows;
HMB-45 (+) diffusely, actin (+) in spindled areas and vessels.
Hepatic angiomyolipoma (AML) is a rare mesenchymal tumor. Clinically, AML occurs predominantly in
women with a ratio of 5:1 and is usually discovered in adults with a median age of about 45yrs. 10% of
cases occur in the setting of tuberous sclerosis, but these cases usually also have coexisting renal AML.
Tumor size can vary widely from less than 1cm to over 25cm. Small tumors typically present as incidental
findings. Larger tumors present with symptoms related to a space-occupying lesion such as abdominal pain
or fullness. Acute rupture has been reported. Multiple tumors in the liver and multi-organ involvement
have been described. Radiographically, AML is said to have characteristic imaging features because of
the presence of fatty tissue, yet the diagnosis is only correctly suggested in a minority of cases.
While there are reports of malignant transformation in renal AML, there has only been one report of
malignant degeneration in a liver AML.
Most AML's are well circumscribed but not encapsulated. They usually occur in non-cirrhotic livers.
AML's have three key components, tortuous vessels, fat and myoid cells. Liver AML's demonstrate solid
growth with a variable amount of fat and myoid elements. Hematopoietic cells may also be seen in some
cases. Myoid cells may be epithelioid, spindled or intermediate. Epithelioid cells have a central
cytoplasmic granular eosinophilic material with peripheral clearing giving a spider web appearance. The
nuclei are round to oval with moderate pleomorphism and a distinct nucleolus. Spindled myoid cell
typically have pale or clear cytoplasm and are arranged in fascicles. The fat component is typically
mature, however, lipoblast like cells may be found. A hallmark of this lesion is the existence of
tortuous, thick walled vessels that are usually lacking in elastic lamina and are often rimed by
epithelioid myoid cells. A number of variant patterns have been described including trabecular, pelioid,
inflammatory, oncocytic, and pleomorphic.
The diagnosis of AML may be confirmed by immunohistochemistry. Tumor myoid cells are reactive to
HMB-45. No other liver tumor consistently stains for HMB-45, however, aberrant HMB-45 expression has
been reported in rare hepatocellular carcinomas. Other melanoma markers including HMSA5, MART-1, HMB-50,
and CD63 may also be seen in AML's. Desmin, and actin stain variably and usually in the spindle myoid
cells. S-100 stains the fat cells but may also be seen in myoid cells.
The primary differential diagnosis is with hepatocellular carcinoma, and epithelioid leiomyosarcoma.
AML with predominant epithelioid myoid cells can be confused with hepatocellular carcinoma. The main
distinguishing features are related to the architectural features of the tumor. Hepatocellular
carcinoma(HCC) should have a growth pattern that resembles normal liver architecture. This includes a
trabecular pattern of hepatocytes with associated sinusoids lined by endothelial cells. Unfortunately a
trabecular sinusoidal pattern has been described in AML's and therefore other features should be used to
distinguish AML's from hepatocellular carcinoma, such as the presence of myoid or fat cells. As
mentioned above the demonstration of HMB-45 or other melanoma markers is ideal for this diagnosis. AML's
are negative for cytokeratin. Keratin AE1/AE3 stains only 20% of hepatocellular carcinoma, but low
molecular weight keratin CAM5.2 stains 90-95% of HCC's. Differentiating AML's from leiomyosarcoma also
hinges on the demonstration of HMB-45 staining since both tumors express muscle markers. Since AML is
primarily a lesion of adulthood and hepatoblastoma is a tumor of childhood, differentiating these tumors
from each other is usually not an issue, but would follow the same logic as above for hepatocellular
carcinoma. Hepatoblastoma however, more consistently stains with keratin AE1/AE3.
Some authors believe that AML' s represent a hamartomatous process, but recent studies have
demonstrated evidence suggesting a clonal proliferation that favors a neoplastic process. The
histogenesis of AML is unclear. Some authors believe that various cell types are derived form precursor
cells present in the prerivascular space. Perivascular epithelioid cells (PEC) are thought to be more
primitive cells that differentiate to become spindled myoid cells or fat cells. These PEC cells have no
normal corollary and are thought to be the precursor of a group of lesions that can be found in many
different organs and are closely related to tuberous sclerosis including AML's, clear cell sugar tumors
of the lung and elsewhere, lymphangiomyoma, lymphangiomyomatosis, renal capsuloma and clear cell
myomelanocytic tumor. AML's composed of a large number of epithelioid cells have been termed PEComa
(perivascular epithelioid cell tumor).
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