Malignant hepatic epithelioid angiomyolipoma with recurrence in the lung 7 years after hepatectomy: a case report and literature review
Fukuda et al. Surgical Case Reports
Malignant hepatic epithelioid angiomyolipoma with recurrence in the lung 7 years after hepatectomy: a case report and literature review
Yasunari Fukuda 0 1
Hideyasu Omiya 0
Koji Takami 0
Kiyoshi Mori 3
Yoshinori Kodama 3
Masayuki Mano 3
Yoriko Nomura 2
Jun Akiba 7
Hirohisa Yano 7
Osamu Nakashima 6
Mitsumasa Ogawara 5
Eiji Mita 4
Shoji Nakamori 0
Mitsugu Sekimoto 0
0 Department of Surgery, National Hospital Organization Osaka National Hospital , Osaka , Japan
1 Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita, 565-5111 Osaka , Japan
2 Department of Gastroenterological Surgery, Kurume University School of Medicine , Kurume , Japan
3 Department of Pathology, National Hospital Organization Osaka National Hospital , Osaka , Japan
4 Department of Gastroenterology and Hepatology, National Hospital Organization Osaka National Hospital , Osaka , Japan
5 Department of Respiratory Medicine, National Hospital Organization Osaka National Hospital , Osaka , Japan
6 Department of Clinical Laboratory Medicine, Kurume University Hospital , Kurume , Japan
7 Department of Pathology, Kurume University School of Medicine , Kurume , Japan
Angiomyolipoma (AML) arising in the liver is rare and usually benign, but it occasionally has malignant potential. A 58-year-old man with a liver tumor identified by a previous doctor with features suggestive of hepatocellular carcinoma on computed tomography (CT) underwent anterior segmentectomy of the liver in 2006. Microscopically, the tumor was composed of exclusively epithelioid cells that were scatteredly positive for human melanoma black 45 on immunohistochemistry. Accordingly, primary hepatic epithelioid AML (eAML) was diagnosed. The patient was subsequently referred to our hospital for follow-up after hepatectomy. He had event-free survival for nearly 7 years. In 2013, two well-defined round nodules were detected in the right lung field by chest CT, and partial pneumonectomy was performed for diagnosis and treatment. Histological examination of the resected lung tissue showed that it was morphologically and immunohistochemically identical to his primary hepatic eAML, leading to the diagnosis of pulmonary metastasis. This paper demonstrates a rare case of malignant hepatic eAML with late recurrence in the lung after hepatectomy.
Hepatic angiomyolipoma; Perivascular epithelioid cell; Malignant potential
Angiomyolipoma (AML) is a relatively rare
mesenchymal tumor. Histologically, it is composed of blood
vessels, adipose tissue, and smooth muscle. AML is
most commonly observed in the kidney, followed by
the liver. The tumor is thought to originate from
pluripotent perivascular epithelioid cells (PECs),
although its normal tissue counterpart remains unclear
]. PEC is immunopositive for melanocytic and
myogenic markers . In addition, a group of tumors
formed by PEC proliferation has been recognized as
PEComas, firstly described by Bonetti and colleagues
in 1992 [
] and currently recognized by the World
Health Organization [
]. AML is considered a
member of the PEComa family [
]. AML can be
histologically classified according to the ratio of the three
heterogeneous components, from the classic triphasic
type to a monotypic type [
]. Among the monotypic
types of AML, epithelioid AML (eAML) is
predominantly composed of epithelioid cells and does not
contain blood vessels or adipose tissue. Although in
general AML has good biological behavior, it can have
malignant potential with distant metastasis,
recurrence, and associated mortality [
]. We describe a
case of malignant hepatic eAML that recurred in the
lung nearly 7 years after hepatectomy for the initial
tumor and review the characteristics of malignant
hepatic AML with recurrence.
A 58-year-old man was incidentally found to have a
liver tumor measuring 20 mm by abdominal
ultrasonography during a routine company health examination
in 2004. The tumor grew in size over the next 2 years,
and closer inspections were conducted by a previous
physician in 2006. Enhanced computed tomography
(CT) of the abdomen showed a 70-mm mass with
hemorrhagic and necrotic changes in the right lobe of
the liver (segment 5), with early arterial phase
staining and late phase washout, which seemed to be
consistent with hepatocellular carcinoma (HCC) (Fig. 1).
Anterior segmentectomy of the liver was performed.
Macroscopically, non-encapsulated tumor had
irregular borders. Sectioning of resected specimen revealed
a white to yellow, friable, hemorrhagic mass
measuring 63 × 50 mm (Fig. 2). Microscopically, hematoxylin
and eosin staining showed atypical epithelioid cells
containing abundant clear to eosinophilic granular
cytoplasm arranged in nests and sheets. The cells
were unevenly distributed and had pleomorphic nuclei
of varying sizes. Blood vessels were inconspicuous
and mature adipose tissue was not detected. Both bile
ducts and portal tracts were involved in the tumor.
Immunohistochemically, the tumor cells were negative
for hepatocyte paraffin 1 (HepPar 1) and alpha
fetoprotein. In contrast, the tumor cells were scatteredly
positive for melanocytic markers including human
melanoma black 45 (HMB-45) and Melan A, but
negative for smooth muscle antigen (SMA) and S100
protein, together with negative for c-kit and
moderately high Ki-67 labeling index (12.9 %) (Fig. 3).
Accordingly, primary hepatic eAML was diagnosed at
After hepatectomy, the patient was referred to our
hospital and followed every 6 months on an
outpatient basis. No hepatic recurrence was observed
over nearly 7 years. In 2013, a chest X-ray showed a
well-defined nodule in the right lung field (Fig. 4a).
Chest CT showed two round nodules in segments 1
and 3 of the right lung, measuring 10 and 4 mm,
respectively (Fig. 4b, c). Fluorodeoxyglucose-positron
emission tomography did not show any uptake. Since
the diagnosis could not be confirmed by inspection
through bronchoscopy, partial pneumonectomy was
performed for diagnostic and therapeutic purposes.
Macroscopically, the two resected specimens included
solid white masses. Microscopically, the neoplastic
cells were morphologically similar to those of the
primary hepatic tumor. There was no evidence of
vascular invasion. Immunohistochemically, the tumor cells
were diffusely positive for HMB-45 and negative for
SMA and S-100 protein. In addition, the tumor cells
were negative for c-kit and the Ki-67 labeling index
was 9.0 % (Fig. 5). Therefore, a diagnosis of lung
metastases from hepatic eAML was made. Loss of
tuberous sclerosis complex (TSC) genes, TSC1 and TSC2,
was not detected. The patient has remained
recurrence-free on a closer follow-up schedule for
2 years after pneumonectomy.
Since it was first described by Ishak [
] in 1976,
hepatic AML is now a well-recognized tumor. The
number of reports on hepatic AML, including
malignant cases, has continued to increase worldwide. In
recent years, the clinicopathological characteristics of
malignant hepatic AML have been intensively
investigated despite many challenges. Tumor size has been
reported as a simple and clear predictor of malignant
]. Although the cutoff value varies in
the literature, Ding and colleagues  identified that
tumors greater than 60 mm in diameter might have
malignant potential and this was true of our case
(63 mm). In terms of histology, cytologic atypia,
pleomorphism, necrosis, and high mitotic rate were reported
as predictors of malignant potential [
10, 11, 13, 17
presence of cytologic atypia and necrosis are
frequently observed in malignant cases, including ours.
However, Nonomura and colleagues  demonstrated
that atypia and pleomorphism are occasionally found
in epithelioid cells and does not always indicate
malignant hepatic AML. In addition, the monotypic
epithelioid variant of AML arising from the kidney had
been regarded as having malignant potential [
whereas data on those of hepatic origin are scarce.
Recently, the number of reports on malignant
classical AML in the liver has also been increasing
10, 12, 13, 15
]. Accumulation of cases is necessary to
clarify the histological differences between malignant
and benign AML.
Immunohistochemically, there was a difference in
the degree of staining for HMB-45 between primary
and metastatic lesion. Considering intratumoral
heterogeneity has been observed in various malignancies
], this difference may suggest malignant potential
in our case. Moreover, a previous investigation
showed that lack of c-kit expression is suggestive of
malignant hepatic AML, [
] in contrast to c-kit
immunopositivity in benign lesions [
]. Indeed, in
four cases where c-kit expression was evaluated, all
were negative or weakly positive. Although further
investigation of the intensity of c-kit staining in
malignant cases is required, it is potentially a predictive
There is a paucity of detailed data on the metastasis
or recurrence pattern of malignant hepatic AML. As
summarized in Table 1, the most frequently observed
site of recurrence is the liver (nine cases), followed by
the lung (three cases), pancreas (two cases), and other
organs, indicating a hematogenous pattern of
metastasis for malignant hepatic AML. Furthermore, our case
showed that the lung could be the first site of
recurrence for malignant hepatic AML. Thus, prudent
evaluation of the lung fields by chest X-ray or chest
CT in addition to following the residual liver should
Four patients died due to disease recurrence,
indicating an unfavorable prognosis after recurrence
]. In a case described by Dalle and
colleagues , the tumor was observed for 5 years
before it was resected, and multiple metastases appeared
in the residual liver just 5 months after resection.
Moreover, median recurrence-free survival of the ten
patients with recurrence was 36 months (range, 5–
108 months); three patients relapsed more than
5 years after initial resection. Prompt surgical
treatment and careful follow-up for a long period is
crucial to increasing the survival of patients with
malignant disease. In addition, our case suggests that
early detection and re-resection of the site of
recurrence could improve the prognosis of patients with
In conclusion, we reported a case of malignant
hepatic AML with late recurrence in the lung and
examined the characteristics of recurrence in patients with
malignant hepatic AML. The prognosis of patients
with malignant hepatic AML is poor. In this respect,
we regard hepatic AML as a borderline malignant
tumor, and aggressive therapeutic intervention is
recommended since surgical resection is indisputably the
most reliable curative treatment.
Written informed consent was obtained from the
patient for publication of this case report and any
accompanying images. A copy of the written consent is
available for review by the Editor-in-Chief of this
AML: angiomyolipoma; CT: computed tomography; eAML: epithelioid AML;
HCC: hepatocellular carcinoma; HepPar 1: hepatocyte paraffin 1;
HMB45: human melanoma black 45; PEC: perivascular epithelioid cell;
SMA: smooth muscle antigen; TSC: tuberous sclerosis complex.
The authors declare that they have no competing interests.
YF drafted the manuscript. YF, HO, and KT were the patient’s attending
physicians and performed the resection of the pulmonary lesions. MO and
EM followed the patient in the outpatient clinic. SN and MS were the
supervising surgical oncologists. YN, JA, HY, and ON participated in the
pathological examination of the primary hepatic eAML, and KM, YK, and MM
participated in the pathological examination of the pulmonary lesions. All
authors read and approved the final manuscript.
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