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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5762_Библиотеки_им_академика_М_И_Перельмана.pdf
178
a
Q. Lu et al.
Zollinger–Ellison Syndrome, neurogenic hypoglycemia,
and carcinoid syndrome, due to the large amount of hormones secreted by the tumor. The symptoms of the latter
are insidious and non-specic, and some patients have
already had liver metastasis at the initial diagnosis [44].
• The incidence of PHNEN is extremely low, and symptoms such as abdominal distension, dull pain, and jaundice usually occur only in the late course of the disease.
• The disease can occur at any age, but mainly in the 40–50
years old, and there is no obvious gender tendency.
• Some studies report that the proportion of female patients
is slightly higher than that of male patients.
• Whether PHNEN or MHNEN, most patients had no history of chronic liver diseases such as hepatitis or cirrhosis. Common serum tumor markers, such as
alpha-fetoprotein (AFP), CEA, and carbohydrate antigen
19-9 (ca19-9), are mostly in the normal range and have
limited diagnostic value.
6.5.5.2 Prognosis
• The 1, 3, 5 years survival rates of resectable PHNEN
patients were reported to be 95.5%, 81.8%, and 67.4%,
respectively [45].
• The 1, 3, 5 years survival rates of 85 MHNEN patients
were reported to be 42.6%, 14.0%, and 7.1%,
respectively.
• The survival rate of HNEN patients may be related to factors as the rst visiting time and the regularity of treatment, and the level of regional economic and medical
development.
6.5.5.3 Treatment
• Surgical treatment in a broad sense includes radical resection, palliative tumor reduction, and liver transplantation.
Despite the high recurrence rate, surgical treatment is the
best way to treat resectable HNEN and it is the only possible way to be cured.
b
c
Fig. 6.19 A case of metastatic hepatic neuroendocrine neoplasm
(MHNEN). B mode ultrasound showed a heterogeneous hypoechoic
lesion in the left hepatic lobe (a). Color ow signals could be detected
around the tumor (b). After injection of contrast agent, the tumor
showed synchronous enhancement in arterial phase (c, d), and wash-out
d
in portal venous and late phases (e, f). Surgical specimen showed central bleeding area (g). Final histopathologic examination proved the
diagnosis of neuroendocrine neoplasm (NEN) (low-power photomicrograph, hematoxylin–eosin staining, original magnication ×10) (h)
6 Rare Malignant Liver Tumors
179
e
g
f
h
Fig. 6.19 (continued)
• For patients with unresectable HNEN, radiofrequency
ablation, cryoablation, microwave therapy, TACE, and
radiation embolization may be considered.
• Since HNEN is typically a high vascularity lesion, with
most of the blood supply coming from the hepatic artery,
the best alternative treatments for diffuse HNEN patients
who do not have the opportunity for surgery are TACE
and radiation embolization.
• Medical treatment includes biotherapy, systemic chemotherapy, targeted therapy, and so on.
6.6 Hepatic Epithelioid
Hemangioendothelioma
Wen-PingWang, Pei-LiFan, and Jia-YingCao
6.6.1 Terminology
Denitions
Hepatic epithelioid hemangioendothelioma (HEHE) is a
rare, vascular origin, low-to-intermediate grade malignant
primary tumor of liver. Both clinical and histological
characteristics of HEHE are between angiosarcoma and
hemangioma. Genetic alteration described that HEHE is
entirely different from neither angiosarcoma or
hemangioma.
6.6.2 Imaging
6.6.2.1 Conventional Ultrasound Findings
• The liver background is mostly normal, with homogeneous isoechogenicity. Only some patients are accompanied by fatty liver background [46, 47].
• The lesions of HEHEs may be unifocal, multifocal, or diffuse. The multifocal lesions are most commonly seen
(80%), which are predominantly located in subcapsular
regions of the liver (Fig.6.21). As the multifocal subtype
progresses, nodules coalesce and may present as the
advanced diffuse subtype at diagnosis. Merger and creeping growth under liver capsule is a characteristic manifestation of HEHE.
180
a
e
Q. Lu et al.
b
c
d
f
Fig. 6.20 A case of metastatic hepatic neuroendocrine neoplasm
(MHNEN). The lesion was isoechoic with an unclear margin on B
mode ultrasound (white arrow) (a). Color ow signals could be detected
around the lesion (b). The lesion showed rim-like hyperenhancement
and showed centripetal ll-in in the arterial phase (c, d). It showed rapid
wash-out at 30s after injection of contrast agent (e). The lesion was
hypoenhanced in the portal venous and late phases (f)
a
6 Rare Malignant Liver Tumors
181
• Most HEHEs have an inclination to affect two adjacent
lobes of liver (70%). If HEHE appears solitary, the right
lobe may have a greater chance to be affected (Fig.6.21).
• HEHE usually appears consistently hypoechoic with illdened margin. A hypoechoic halo may be visualized,
especially around those bigger lesions (Fig.6.22).
• Calcication is seldom seen in HEHE lesion (20%).
Bleeding and necrotic liquefaction areas are also rarely
seen [46, 47].
• Color ow signals can be observed around most lesions,
and the blood ow resistance index is about 0.6–0.7.
Branched vessels may be detected in some lesions [46].
6.6.2.2 Contrast Enhanced Ultrasound Findings
• Due to the lack of sufcient case support, HEHE is still
controversial in the imaging diagnosis of CEUS.
• The imaging appearances of HEHE can be highly variable on CEUS due to the highly heterogenous characteris-
tics of HEHE and the difference of vascular architecture
within different regions of HEHE lesions.
• HEHE usually present peripheral rim-like or heterogeneous hyperenhancement in arterial phase and hypoenhancement in portal venous and late phases. Central
unenhanced areas may be observed in some lesions [46–
48] (Fig.6.23).
• Some lesions of HEHE may manifest heterogeneous
isoenhancement or hypoenhancement in arterial phase
and hypoenhancement in portal venous and late phases
(Figs.6.21 and 6.22).
• Wash-out of HEHE is faster than that of metastatic liver
cancer. Most lesions even show wash-out in the late arterial phase or early portal venous phase.
• More lesions that are inapparent on conventional ultrasound can be detected in portal venous and late phases on
CEUS, and the margins of the lesions will be much
clearer.
b
c
d
Fig. 6.21 Multiple hepatic epithelioid hemangioendotheliomas in a
31-year-old male. B mode ultrasound showed hypoechoic lesions
merged with each other, and the lesions were prone to creeping growth
near the liver capsule (arrows) (a). Color Doppler imaging showed
peripheral color ow signals (b). In the arterial phase (23s after injection of SonoVue), the lesions showed heterogeneous isoenhancement
(arrows) (c, d, e, f). In the portal venous and late phases, the lesions
wash-out quickly and became hypoenhancement (g, h). On MRI, the
lesions showed hypointense on T1-weighted image (WI) (arrows) (i).
The lesions showed hyperintense with clear borders and irregular shape
on T2WI, and the portal vein branch was cut off in the peripheral zone
of the lesion, showing a “lollipop” sign (arrowhead) (j). On contrast
enhanced MRI, the lesions showed mild and heterogeneous enhancement with “vascular signs” in the arterial phase (arrow) (k). The lesions
showed progressive enhancement with “vascular signs” (arrow) in portal venous phase (l). “Lollipop” sign could also be detected (arrowhead)
(k, l). On gross specimen, the lesion was grayish-white and yellowish
with a clear boundary with surrounding liver parenchyma (m)
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Q. Lu et al.
e
g
f
h
Fig. 6.21 (continued)
6 Rare Malignant Liver Tumors
183
i
j
k
lm
Fig. 6.21 (continued)
184
a
Q. Lu et al.
6.6.2.3 CT Findings
• Most of the lesions are multiple low-density nodules, with
uniform or uneven density. They mostly grow near the
liver capsule and can merge with each other. The liver
capsule adjacent to the lesion can show signs of contraction, that is, “capsular contraction signs.” It is formed by
collapse after hyaline degeneration and necrosis in the
central brosis area, plus to the pulling of tumor cell
brous tissue hyperplasia [49–52].
• On contrast enhanced CT, most lesions are mild peripheral enhancement or heterogeneous enhancement, and the
peripheral region of the lesions continues to be enhanced
in portal and delay period. Some lesions may show nonenhancement in three phases.
• After the enhancement, some lesions can see the blood
vessel passing inside, which called “vascular sign.” Some
lesions in the portal phase show the “target sign,” which is
related to nonenhancement in the central brosis area but
the surrounding regions of the tumor are enhanced.
• Lollipop-sign: a new cross-sectional sign of HEHE on
contrast-enhanced CT imaging, being a well-dened
peripherally enhanced (or non-enhanced) lesion with an
avascular core on contrast enhanced images (the candy in
the lollipop) and a histologically occluded vein (the stick).
6.6.2.4 MRI Findings
• Most of the lesions are multiple with clear borders and
some lesions are irregular in shape. Mostly located near
the liver capsule can be merged with each other, and “capsular contraction sign” can also be observed on MRI.The
lesions show hypointensity, hyperintensity, and hyperintensity on TIWI, T2WI, and DWI, respectively. Some of
the hyperintensity lesions on T2WI showed a higher signal in the center but lower signal in the surrounding,
which called “halo” sign [49, 50, 52, 53].
• There are various enhancement imaging methods. Most
lesions have mild-to-moderate peripheral enhancement
in arterial phase and show persistent enhancement in
the portal and the delay phases. A small number of
lesions show inapparent enhancement in arterial phase
but show progressive enhancement in portal and delay
phases.
b
c
d
Fig. 6.22 Features of hepatic epithelioid hemangioendotheliomas. The
lesions were hypoechoic with hypoechoic halo on B mode ultrasound
(arrows) (a). Color ow signals could be detected around the lesion (b).
After injection of SonoVue, the lesions showed heterogeneous rim
hyperenhancement in the arterial phase (arrows) (c, d, e, f). In the portal
venous phase, the lesions wash-out quickly and showed punched
hypoenhancement (j)
6 Rare Malignant Liver Tumors
185
e
f
g
Fig. 6.22 (continued)
• Similar to enhanced CT, enhanced MRI can also present
“vascular signs,” “target signs,” and “lollipop sign”
(Fig.6.21).
6.6.2.5 PET/CT Findings
Most lesions showed light-to-moderate FDG uptake, and a
few showed similar to the surrounding liver parenchyma.
The average SUV
shown that the size of the lesion is not related to the SUV
was 3.6±1.1 (1.7–6.6). Studies have
MAX
MAX
value [53].
6.6.2.6 Best Imaging Protocol Advices
• HEHE is usually detected by imaging, usually by abdominal ultrasound or CT/MRI scan.
• The ultrasound should be considered as the rst choice
because of its safety, availability, and low cost. In addition, as HEHE is of vascular origin, CEUS may potentially play an important role in arriving at an early and
accurate diagnosis.
• The performance of contrast-enhanced imaging techniques is important. Patterns of contrast enhancement
between CEUS, CT, and MRI are highly similar. This
conrms mainly the consistency of dynamic perfusion
imaging in a specic lesion.
• To make a denite diagnosis, a liver biopsy should be
performed.
6.6.3 Dierential Diagnosis
6.6.3.1 Hepatocellular Carcinoma
Previous literatures reported that the typical HCC enhancement
is generally overall enhancement in the arterial phase and often
faster than the surrounding liver parenchyma. It shows hyperenhancement when it reaches the peak, and decline in the portal
and late phases. The enhancement level of HCC is much higher
than that of HEHE at the peak enhancement. When the HCC
lesion is larger, hemorrhage and necrosis are prone to appear as
heterogeneous enhancement in arterial phase, while HEHE
lesions have less bleeding and necrosis. Although the inner area
of the ring-enhanced lesion is not enhanced, the shape of the
non-enhanced area is still regular due to the susceptibility to
brosis within the tumor. HEHE often begins to decline at the
late stage of the artery, and its decline rate is signicantly faster
than that of HCC. In addition, patients with HCC are often
accompanied by splenomegaly, cirrhosis, and chronic liver disease. Clinically, HBsAg is mostly positive and AFP is often
signicantly increased in HCC but usually normal in HEHE.
186
a
e
Q. Lu et al.
b
c
d
f
g
h
Fig. 6.23 A case of typical multiple lesions of hepatic epithelioid
hemangioendothelioma (HEHE). Multiple hypoechoic lesions could be
detected in the right lobe of liver on B mode ultrasound (a, b, c, d).
After injection of SonoVue, the lesion showed typical rim-like hyperen-
hancement during arterial phase, central unenhanced area could also be
observed (e, f, g, h, i). In portal venous phase, the lesions showed wash-
out quickly and punched hypoenhancement (g)
ij
6 Rare Malignant Liver Tumors
Fig. 6.23 (continued)
187
6.6.3.2 Cholangiocarcinoma
ICC often shows dendritic enhancement from the periphery
to the center. ICC is often accompanied by bile duct stones,
bile duct dilatation, and other signs like hilar lymph node
metastasis. While HEHE dendritic enhancement performance is more confused, generally no hilar lymph node
metastasis. The number of HEHE lesions on ultrasound is
often more than that of ICC, and can be accompanied by
multiple lesions of other organs. HEHE often occurs in
young patients, and mostly CA199 is normal.
6.6.3.3 Metastatic Liver Cancer
Patients often have a history of primary disease. Liver metastases often show arterial phase hyperenhancement followed
by wash-out in the portal venous/late phase, and the peaking
intensity of liver metastases is often higher than that of
HEHE.Both liver metastases and HEHE decline faster, and
it is difcult to distinguish between the portal phase and the
delayed phase, but if HEHE shows typical enhancement
characteristics like low or equal enhancement and slow-in or
same-in with the liver parenchyma in arterial phase, and the
creeping growth of the lesion can help identify. Patients with
metastatic liver cancer have more severe clinical manifestations and are older than HEHE. Tumor markers may be
abnormal in liver metastases and HEHE is basically normal.
6.6.4 Pathology
ber-rich oligocellular area or a sclerosis area, and the outer
periphery of the tumor is a cell-rich area. The central area
may undergo hyaline degeneration or brosis, and the tumor
cell atrophy decreases. As the tumor progresses, the interstitial area gradually expands and the tumor occurs extensive
brosis within the organization. Microscopically, three types
of cells can be seen in HEHEs, intermediate, dendritic, and
epithelioid cells. Epithelioid cells are present in all lesions,
are of endothelial origin, and may present with vacuoles causing it to resemble signet cell morphology. Dendritic cells are
stellate in shape and have multiple processes. The intermediate cells share features of both cell types [54, 55].
Dietze divides HEHE into three main histological types:
(1) peripheral type: tumor cells are mainly distributed in the
periphery, scattered between normal hepatocyte cords; (2)
cell type: tumor cells are mixed with atrophic liver cells, at
the same time, there is a small amount of brous interstitium;
(3) sar type: sparsely distributed tumor cells scattered in the
dense brous matrix. The pathological distribution of tumor
stromal is closely related to the imaging performance of
HEHE [54, 55].
Due to the endothelial origin feature of HEHEs, these
tumors usually express the FLI-1 protein, which has been
shown to be sensitive in identifying vascular tumors. The
nal diagnosis of HEHE requires pathological immunohistochemistry to express at least one of CD31, CD34, FVII-RAg,
and Vimentin.
The World Health Organization denes HEHE as a malig-
6.6.5 Clinical Issues
nant tumor with lesions due to nodular tumors growing in
size and coalescing together.
Histologically, tumor cells consist of epithelial-like cells
or neurite-like cells, both of which can exhibit characteristic
intracytoplasmic vascular differentiation, that is, intraluminal
luminal formation, similar to signet ring cell-like, with erythrocytes in the cavity. The intramucosal vacuole mucus and
PAS staining were negative. The central area of the tumor is a
Presentation
There are no specic clinical manifestations for
HEHE.Patients with HEHE usually presenting with general
symptoms, such as right upper quadrant pain or weight loss.
Most patients are found during physical examination. Some
patients may present with liver failure, Budd-Chiari syndrome, or portal hypertension, while others may be asymptomatic. HEHE occurs in adult women 30–40 years old, and