Inflammatory angiomyolipoma of the liver: a rare hepatic tumor
Inflammatory angiomyolipoma of the liver: a rare hepatic tumor
Yang Liu 0 1
Jian Wang 0 1
Xu-Yong Lin 0 1
Hong-Tao Xu 0 1
Xue-shan Qiu 0 1
En-Hua Wang 0 1
0 Institute of Pathology and Pathophysiology, China Medical University , Shenyang 110001 , China
1 Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences, China Medical University , Shenyang 110001 , China
Angiomyolipoma (AML) is a rare mesenchymal neoplasm of the tumor, composed of a varying heterogeneous mixture of three tissue components: blood vessels, smooth muscle and adipose cells. Hepatic AML may demonstrate a marked histological diversity. We herein present one case of hepatic AML exhibiting prominent inflammatory cells in the background, which happened in a 61-year-old Chinese female patient, without signs of tuberous sclerosis. Histologically, the striking feature was the infiltration of numerous inflammatory cells in the background, including small lymphocytes, plasma cells, and eosnophils. The tumor cells were spindled and histiocytoid in shape, with slightly eosinophilic cytoplasm, and arranged along the vessels or scattered among the inflammatory background. Sinusoid structure was obviously seen in the tumor. Mature adipocytes and thick-walled blood vessels were focally observed at the boundaries between the tumor and surrounding liver tissues. The tumor cells were positive immunostaining for HMB-45, Melan-A, and smooth muscle actin. The inflammatory AML should be distinguished from other tumors with inflammatory background such as inflammatory myofibroblastic tumor and follicular dendritic cell tumor and deserves wider recognition for its occurrence as a primary hepatic tumor. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/ vs/1828633072762370
Angiomyolipoma; Perivascular epithelioid cell; Inflammatory; Liver
Hepatic angiomyolipoma is a rare, benign, hepatic
mesenchymal neoplasm found in both males and females,
and most commonly in adult females. Angiomyolipoma
occurs most commonly in the kidneys. The liver
represents the second most frequent site of involvement .
Histologically similar to those in the kidney, hepatic
AML consists of a mixture of myoid cells, adipose tissue
and thick-walled vessels. They may have variable
morphologic features and are positive for HMB-45, but
negative for hepatocyte paraffin-1 (Hepar-1) and S100 protein
[1,2]. According to the line of differentiation and
predominance of tissue components, the tumors were
subcategorized into mixed, lipomatous (> = 70% fat),
myomatous (<=10% fat), and angiomatous type. The
most common type is the mixed type which comprises
sheets of epithelioid muscle cells admixed with islands of
adipocytes and abnormal vessels. The lipomatous and
myomatous patterns were regarded as morphologic
variations on a continuous spectrum, depending on the
degree of adipose and myoid differentiation. Myomatous
type was more common in the liver than in the kidney
. Angiomatous AML contained many large
thickwalled vessels and radiologically may be misinterpreted
as intrahepatic arterial aneurysm. According to the
predominant component, growth pattern, cell type, and
other features, the tumors were subcategorized into
trabecular, pelioid and inflammatory variants. Of these,
inflammatory or pelioid pattern usually presents as a focal
finding within the tumor, but very rarely, they become
the predominant pattern , creating great diagnostic
confusion with other tumors such as inflammatory
myofibroblastic tumor (IMT), follicular dendritc cell (FDC)
tumor and other hepatic mesenchymal neoplasms. The
authors herein present such a case of hepatic AML with
a predominantly inflammatory pattern, also known as
A 63-year-old woman was admitted to the First
Affiliated Hospital of China Medical University in June
of 2010 for further examination of the liver tumor which
was detected by ultrasonography in the annual health
check. Physical examination showed no abnormalities.
Hematological and chemical studies, including tumor
markers such as -fetoprotein and carcinoembrionic
antigen, gave normal results. Hepatitis virus markers,
such as hepatitis B surface antibody, hepatitis B surface
antigen and hepatitis C antibody, were all negative.
Conventional ultrasonography revealed well-demarcated
isoechoic tumor with a diameter of 30 mm in the segment
V of the liver. The spleen, pancreas, and kidneys were
without any focal lesions. There are no pathognomonic
clinical signs for tuberous sclerosis. The patient did not
consent to tumor biopsy, and we could not rule out the
possibility of malignancy due to the result of
ultrasonography and CT scan. The patient desired to undergo
tumor resection on her own initiative, and partial
hepatectomy was performed. The patient was alive with no
tumor recurrence or metastasis at 2 years of follow-up.
Gross examination showed an elastic hard mass with a
diameter of 30 mm. The tumor did not have a capsule,
but it was clearly demarcated from the normal hepatic
parenchyma. The tumor was grayish-white on cut surface.
The neoplasm was demarcated from the surrounding
liver tissues with relative clear boundary, presenting with
a solid cellular growth pattern and abundant vascularity
with frequently dilated vascular channels (Figure. 1A
D). The tumor was characterized by the infiltration of
numerous inflammatory cells in the background,
including small lymphocytes, plasma cells, and eosnophils
(Figure. 1CF). The proportion of tumor area with
inflammatory infiltration was more than 80%. The tumor
cells were spindled and histiocytoid in shape, with
slightly eosinophilic cytoplasm and small central
nucleoli, and arranged along the vessels or scattered among
the inflammatory background (Figure 1EH).
Pleomorphism is absent and mitotic figures are barely seen.
Mature adipocytes and thick-walled blood vessels were
focally observed at the boundaries between the tumor
and surrounding liver tissues. The mature adipocyte
component was less than 5% of the whole tumor and
interrupted by sheets of histiocytoid and spindle myoid
cells (Figure 1I). No necrosis, hemorrhage, or cyst
formation was observed in the tumor. No sclerosing
cholangitis was observed in the intrahepatic bile ducts of the
surrounding liver tissues.
The immunohistochemical study showed that the
histiocytoid cells were faintly positive for AE1/AE3 (Figure 2A
and B), strongly diffuse positive for vimentin (Figure 2C),
HMB-45 (Figure 2D), Melan-A (Figure 2E), focally
positive for smooth muscle actin (SMA) (Figure 2F), and
occassionally positive for CD68 (Figure 2G). They were
strictly negative for CD21 (Figure 2H), S100 (Figure 2I),
ALK (Figure 2J) CD1, Hepar-1, CD35, CD10, CD23,
CD117, DOG-1, synaptophysin and chromogranin A
(data not shown). The lymphocytes among the
epithelioid cells were mainly positive for CD3 (Figure 2K) and
focally positive for CD20 (Figure 2L). Finally, CD31 and
CD34 underlined the rich vascular channels (Figure 2M
and N). Ki67 index was about 5% (Figure 2O).The results
were listed in Table 1.
Hepatic angiomyolipoma, a member of the family of
tumors showing differentiation resembling perivascular
epithelioid cells, was first described by Ishak in 1976 .
Regardless of their location, the tumors in this family
share mature fat, thick-walled poorly organized blood
vessels and spindle-epithelioid myoid cells. Hepatic
AML is a rare mesenchymal tumor of the liver. Tsui
et al.  described many morphologic variations of
hepatic AML which reflect the variable lineage and degree
of differentiation of the myoid cells. The histologic
patterns described in the literature include lipomatous,
myomatous, angiomatous, trabecular, pelioid,
inflammatory and mixed pattern [2,5]. Trabecular variant of AML
was characterized by a rich vascular framework, and the
tumor cells were arranged in clusters and surrounded by
dilated sinusoidal vessels [6,7]. Other unusual
architectural patterns such as pelioid and inflammatory ones
were usually present as focal finding, but sometimes they
may exist as a pure pattern [4,8,9] which makes it
difficult to distinguish with other hepatic tumors.
Although hepatic AML has various types or variants
and mimics various hepatic neoplasms, it can still be
recognized or suspected on morphologic grounds. The
clues to the diagnosis are the 3 characteristic components
(blood vessels, smooth muscle, and fat tissue) and
diagnostic myoid component which may exist in epithelioid,
spindle, and intermediate forms. It has been speculated
that the distinctive epithelioid cells are primitive
mesenchymal cells with an ability to differentiate toward both
myoid and adipose cells. Immunohisochemically, these
cells are strongly positive for HMB-45 and smooth SMA.
In this case, the striking feature was the infiltration of
numerous inflammatory cells with scattered histiocytoid
cells among them, so the first diagnosis come to our
mind is FDC tumor instead of inflammatory AML. Its
also hard to totally rule out inflammatory pseudotumor
Figure 1 Histological features of this case. A: The neoplasm was demarcated from the surrounding liver tissues with relative clear boundary.
B: The neoplasm showed a solid cellular growth pattern and dilated vascular channels. C: The cavernous-like vascular areas were composed of
dilated vascular channels lined by monolayer flat endothelial cells, and separated by cellular septa. D: The solid cellular areas contained many
capillaries with the narrow or collapsed lumen. E and F: The tumor was characterized by the infiltration of numerous inflammatory cells in the
background, including small lymphocytes, plasma cells, and eosnophils. G and H: The cellular areas and the septa of cavernous-like vascular areas
were composed of spindled and histiocytoid cells (arrow) with slightly eosinophilic cytoplasm and small central nucleoli. I: Mature adipocytes and
thick-walled blood vessels were focally observed at the boundaries between the tumor and surrounding liver tissues.
(IPT) and IMT on morphologic grounds, so we perform
immunostaining to distinguish between them. To our
surprise, the immunophenotype (CD21-, CD35, S100-,
SMA focal +, ALK-) overthrows the diagnosis of FDC
tumor, IPT and IMT, so we reviewed this case carefully
and found some scattered adipocytes and thick-walled
blood vessels at the boundaries between the tumor and
surrounding liver tissues (As shown in Figure. 1I). This
indicates the diagnosis of AML, so HMB-45 and
MelanA were added to stain and the result (HMB-45+,
MelanA+) demonstrated the diagnosis of AML. We searched
the similar case on PubMed (www.ncbi.nlm.nih.gov) and
found the inflammatory variant of AML may share the
similar feature with our case, so the final diagnosis is
hepatic inflammatory AML.
Inflammatory AML should be distinguished from other
primary or metastatic hepatic tumors especially those
with a prominent inflammatory cell infiltration in the
background, such as IPT, IMT, FDC tumor, lipomatous
tumors, sarcomatoid carcinoma with prominent
lymphocytic infiltration, poorly differentiated hepatocellular cell
carcinoma, gastrointestinal stromal tumors and
metastatic renal cell carcinoma [10-16]. The so-called IPT and
IMT are the first differential diagnosis which should be
distinguished from Inflammatory AML because of the
heavy inflammatory infiltration in the background. The
so-called IPT is composed of inflammatory cells and
some reactive fibroblasts or collagen-rich connective
tissue . While, IMT is thought to be neoplastic and
harbor a clonal cytogenetic aberration that activates the
ALK-receptor tyrosine kinase gene at 2p23. IMT consists
of spindled myofibroblasts which are positive for SMA
and ALK [10,12,14]. The adipose tissue and sinusoidal
vessels are usually absent in IPT or IMT. The
myofibroblastic cells in IMT are predominantly spindled, and
epithelioid myofibroblastic cells are absent or only very
few if present. In addition, immunostaining will be
helpful to distinguish between them because IPT and IMT
are negative for HMB-45. Another important differential
diagnosis of inflammatory AML is FDC tumor, which is
not common in the liver and usually shows a heavy
lymphocytic infiltration in the background. This tumor
can have occasionally inflammatory pseudo-tumor-like
variant which occurs exclusively as primary tumor in the
liver and spleen. However, the nuclei of FDC tumor
usually show vesicular chromatin and distinct nucleoli. The
FDC tumor does not have prominent dilated sinusoidal
and thick-walled blood vessels, and the tumor cells are
Figure 2 Immunohistochemical staining. A: The liver tissues surrounding the tumor were diffusely positive staining for AE1/AE3. B: The
histiocytoid cells were faintly positive staining for AE1/AE3. C-E: The histiocytoid cells were strongly diffuse positive staining for vimentin, HMB-45,
melan-A. F: The histiocytoid cells were focally positive staining for smooth muscle actin, especially the cells around blood vessel. G: Scattered
tumor cells were positive for CD68. H-J: The histiocytoid cells were negative staining for CD21, S100 and ALK. K and L: The lymphocytes among
the histiocytoid cells were mainly positive for CD3 and focally positive for CD20, whereas the histiocytoid cells were negative. M and N: CD31 and
CD34 underlined the rich vascular channels, whereas the histiocytoid cells were negative. O: Ki67 index was about 5%.
negative for HMB-45 but positive for CD21 and CD35
Primary or metastatic lipomatous tumor of the liver is
extremely rare and may occasionally show an
inflammatory background , but thick-walled blood vessels and
the perivascular arrangement of epithelioid cells are
seldom seen in these tumors. In addition, melanin marker
(HMB-45) and muscle marker (SMA) will be helpful to
diagnosis . Sarcomatoid carcinoma always
demonstrates obvious cytological atypia and does not have the
thick-walled vessels and adipose tissue. In difficult cases,
stains for CK and EMA as well as HMB-45 should be
able to distinguish this tumor from inflammatory AML.
Occasionally, inflammatory AML might be mistaken for
hepatocellular carcinoma when a trabecular pattern is
focally present or the epithelioid cells show clear cytoplasm
[7,18]. However, hepatocellular carcinoma mostly occurs
in a background of cirrhosis and usually lacks mature
adipose tissue. Hepar-1, HMB-45 and SMA will be
helpful to distinguish between them. In addition, other
spindled cell tumors such as epithelioid leiomyosarcoma
and inflammatory malignant fibrous histiocytoma may
Table 1 Panel of Immunohistochemical Stains
occasionally occur in the liver with an inflammatory
background and histologically mimic inflammatory
AML. However, the prominent nuclear atypia, frequent
mitotic figures, and negativity for HMB-45 would be
helpful to diagnosis. Metastatic gastrointestinal stromal
tumors may show cytoplasmic clearing but typically do
not have the adipose tissue and inflammatory
background. The sinusoidal vascular structure is also absent
in gastrointestinal stromal tumor. Finally, poorly
differentiated cholangiocarcinoma or other metastatic
carcinoma such as renal cell carcinoma may have a prominent
inflammatory background occasionally. In the differential
diagnosis with these tumors, a panel of antibodies
including HMB-45, Hepar-1, AFP, CK18, and CK19 would be
helpful for the correct diagnosis.
The treatment of hepatic AML is hepatectomy for
large tumors and conservative follow-up for small ones.
Most hepatic AMLs behave in a benign fashion,
although malignant hepatic AML has been reported in the
literature [19,20]. This phenomenon may attribute to the
malignant transformation which has been reported in
many tumors with different histological types [21-23].
Based on the criteria described by Nguyen , the
differences between benign and malignant hepatic AML
were summarized in Table 2. In this case, coagulative
necrosis was not found, and the tumor was 30 mm in
diameter. Moreover, the patient was alive with no tumor
recurrence or metastasis at 2 years of follow-up. All these
features support the diagnosis of benign hepatic AML.
Since CD117 was negative in this case, careful follow-up
of patients is recommended in this case. Inflammatory
AMLs do not show any difference in prognosis from the
classical AMLs. This variant of AML should be
recognized and avoid misdiagnosing as other malignant or
intermediate tumors such as hepatic FDC tumor and
IMT, which require an active treatment regimen.
In this case, the tumor was nearly mistaken for IMT or
FDC tumor which indicates its hard to distinguish
between them in the practical work. The 3 characteristic
components (myoid cells, adipose tissue and
thickwalled vessels) maybe indicates a diagnosis of
hemangioblastoma, but dont exclude the probability when
one or two components were hardly seen, especially in
the pelioid and inflammatory variant of AML.
Therefore, AML must be included in the differential
diagnosis of hepatic tumors with histiocytoid appearance and
inflammatory background to not underestimate this
tumor in this location and so to better evaluate its real
frequency and not establish wrongly a diagnosis of
malignancy to this benign tumor. Using combination of
immunohistochemistry may be helpful to some rare
Written informed consent was obtained from the patient
for publication of this case report and accompanying
images. A copy of the written consent is available for
review by the Editor-in Chief of this Journal.
YL analyzed the data and wrote the manuscript as a major contributor. JW,
XL and HX helped to perform the immunochemical staining. XQ and EW
helped to revise the discussion section of this manuscript. All authors have
read and approved the final manuscript.
1. Petrolla AA , Xin W : Hepatic angiomyolipoma . Arch Pathol Lab Med 2008 , 132 ( 10 ): 1679 - 1682 .
2. Tsui WM , et al: Hepatic angiomyolipoma: a clinicopathologic study of 30 cases and delineation of unusual morphologic variants . Am J Surg Pathol 1999 , 23 ( 1 ): 34 - 48 .
3. Nonomura A , Minato H , Kurumaya H : Angiomyolipoma predominantly composed of smooth muscle cells: problems in histological diagnosis . Histopathology 1998 , 33 ( 1 ): 20 - 27 .
4. Kojima M , et al: Hepatic angiomyolipoma resembling an inflammatory pseudotumor of the liver . A case report. Pathol Res Pract 2004 , 200 ( 10 ): 713 - 716 .
5. Shi H , et al: Inflammatory angiomyolipomas of the liver: a clinicopathologic and immunohistochemical analysis of 5 cases . Ann Diagn Pathol 2010 , 14 ( 4 ): 240 - 246 .
6. Tsui WM , et al: Hepatic angiomyolipomas with a deceptive trabecular pattern and HMB-45 reactivity . Histopathology 1992 , 21 ( 6 ): 569 - 573 .
7. Szekely E , et al: Trabecular angiomyolipoma mimicking hepatic cell carcinoma . Pathol Oncol Res 2000 , 6 ( 3 ): 224 - 226 .
8. Nonomura A , et al: Angiomyolipoma mimicking true lipoma of the liver: report of two cases . Pathol Int 1996 , 46 ( 3 ): 221 - 227 .
9. Shintaku M : Hepatic angiomyolipoma with 'oncocyte-like' features . Histopathology 1998 , 33 ( 6 ): 581 - 583 .
10. Chen ST , Lee JC : An inflammatory myofibroblastic tumor in liver with ALK and RANBP2 gene rearrangement: combination of distinct morphologic, immunohistochemical, and genetic features . Hum Pathol 2008 , 39 ( 12 ): 1854 - 1858 .
11. Granados R , et al: Cytopathology of a primary follicular dendritic cell sarcoma of the liver of the inflammatory pseudotumor-like type . Diagn Cytopathol 2008 , 36 ( 1 ): 42 - 46 .
12. Schnelldorfer T , et al: Inflammatory myofibroblastic tumor of the liver . J Hepatobiliary Pancreat Surg 2007 , 14 ( 4 ): 421 - 423 .
13. Zen Y , et al: Pathological classification of hepatic inflammatory pseudotumor with respect to IgG4-related disease . Mod Pathol 2007 , 20 ( 8 ): 884 - 894 .
14. Solomon GJ , Kinkhabwala MM , Akhtar M : Inflammatory myofibroblastic tumor of the liver . Arch Pathol Lab Med 2006 , 130 ( 10 ): 1548 - 1551 .
15. Bai LY , et al: Follicular dendritic cell tumor of the liver associated with Epstein-Barr virus . Jpn J Clin Oncol 2006 , 36 ( 4 ): 249 - 253 .
16. Brittig F , et al: Follicular dendritic reticulum cell tumor mimicking inflammatory pseudotumor of the spleen . Pathol Oncol Res 2004 , 10 ( 1 ): 57 - 60 .
17. Nakamura N , et al: A hepatic lipoma mimicking angiomyolipoma of the liver: report of a case . Surg Today 2009 , 39 ( 9 ): 825 - 828 .
18. Chen P , Yuan T , Liu H : Hepatic angiomyolipoma mimicking hepatic clear cell carcinoma . J Int Med Res 2009 , 37 ( 1 ): 257 - 263 .
19. Nguyen TT , et al: Malignant hepatic angiomyolipoma: report of a case and review of literature . Am J Surg Pathol 2008 , 32 ( 5 ): 793 - 798 .
20. Nonomura A , et al: Invasive growth of hepatic angiomyolipoma; a hitherto unreported ominous histological feature . Histopathology 2006 , 48 ( 7 ): 831 - 835 .
21. Peng L , et al: Skull base metastases from a malignant solitary fibrous tumor of the liver . A case report and literature review. Diagn Pathol 2011 , 6 : 127 .
22. Dettmer M , et al: Giant ectopic liver, hepatocellular carcinoma and pachydermia-a rare genetic syndrome? Diagn Pathol 2011 , 6 : 75 .
23. Babarovic E , et al: High grade angiosarcoma arising in fibroadenoma . Diagn Pathol 2011 , 6 : 125 .