Sabato 27 ottobre 2012 - Pacini Editore

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thors 2 3 report the benign nature of these lesions with either a diagnosis
of nodular regenerative hyperplasia (NRH) or focal nodular
hyperplasia (FNH) being made. We report on a case of multiple
hypervascular liver nodules in a 20 year old post BMT woman.
Materials and methods. A 14-year-old female was diagnosed
with acute lymphoblastic leukemia, at the Giannina Gaslini Pediatric
Hospital in Genova, in 2005. She presented with generalized
lymphadenopathy, splenomegaly and mild thrombocytopenia.
Her treatment consisted of chemotherapy with Ifosfamide, Cyclophosphamide,
Methotrexate, Daunorubicin, Doxorubicin, Vincristine,
Vindesine, Etoposide, ARA C, L-ase, 6-mercaptopurine,
6-Thioguanine, Steroid and allogenic transplant of hemopoietic
staminal cells by volunteer donor, preceded by total body irradiation
(1200 cGy) and Etoposide. Immunosuppressive therapy with
Cyclosporine was stopped after 10 months from transplant. There
was no evidence of disease recurrence for 5 years after chemotherapy.
During follow-up the patient developed hypergonadotropic
hypogonadism, cataract and bile-stones. Liver function tests were
within normal range and serology was negative for hepatitis C
and B virus. At 3 years from the end of chemotherapy on routine
ultrasonography (USG), two hepatic nodules were identified
respectively in segment 4 and 5. The first measured 3 cm in
maximum diameter, and was hypovascular at Colour Doppler
while the second measured 1 cm. Contrast-enhanced CT showed
multiple hepatic intraparenchymal nodules characterized by rapid
uptake and rapid wash out of contrast. Review of the most recent
USG and abdominal CT examinations performed 1 year earlier
showed no underlying hepatic abnormality. Six months later,
upper abdominal magnetic resonance imaging (MRI) confirmed
the lesions seen at USG and CT which appeared slightly enlarged
(4 cm in maximum diameter) and hyperintense compared to the
surrounding liver parenchyma in T1 and T2-weighted image. One
year later USG was performed during follow up which showed
lesions to be substantially larger (maximum diameter 6 cm) and,
at Color Doppler, a vascular peripheral ring with some branches
with centripetal trend were seen. Abdominal MRI was therefore
performed and it showed a total of 7 lesions in many segments
ranging from 1 cm to 5.7 cm in diameter. Signal characteristics
were in keeping with solid nodular hepatocellular lesions. The
substantial increase in size over time prompted USG-guided
percutaneous liver biopsy at the IRCCS San Martino Hospital,
Genova in 2012, when the patient was 20.
Two liver biopsy cores measuring 23 and 3 mm obtained from the
5.7 cm lesion were received at the Histopathology section, DISC,
University of Genova, IRCCS San Martino Hospital. Sections
were stained with haematoxylin and eosin, Masson’s Trichrome,
Gordon and Sweet’s Reticulin stain as well as immunohistochemical
reactions against cytokeratin 7, CD34, smooth muscle actin
(SMA) and beta catenin.
Results. Histological examination showed hepatic parenchyma
composed of hepatocyte plates measuring 1-2 hepatocytes thick
without atypia and without mitotic activity. Portal tracts with bile
ducts (Fig. 1a) were documented in all fragments and in some
minimal ductular reaction was present. No significant fibrosis
was observed. No abnormal vessels were identified. The reticulin
histochemical staining was preserved and showed aspects suggestive
for nodular regenerative hyperplasia.
As far as vascularization, focal areas of capillarization (identified
with anti-CD34 antibodies) (Fig. 1b), and above all scattered individual
arterioles (identified with anti-SMA antibodies) (Fig. 1c)
were observed. These findings are consistent with the radiological
assessment of hypervascularity.
These findings are therefore in keeping with the diagnosis of a benign
regenerative lesion such as nodular regenerative hyperplasia.
No malignancy was seen.
Conclusions. An increased incidence of nodular regenerative lesions
has been reported in the literature in both adult and pediatric
oncologic patients post chemotherapy and radiotherapy 3-6 . Most
CONGRESSO aNNualE di aNatOmia patOlOGiCa SiapEC – iap • fiRENzE, 25-27 OttOBRE 2012
patients are asymptomatic and may only show mild abnormalities
in their liver function tests. When a confident diagnosis of benign
nodules can be made using imaging, conservative management
is recommended and these cases can be followed up with serial
US 2 7 . However when imaging fails to characterize these entities
definitely or the lesions increase in size or become symptomatic,
liver biopsy is recommended to make the diagnosis 2 8 . Hypervascularization
in benign hepatic regenerative lesions, such as FNH
or NRH of the liver, is mostly interpreted as a compensatory response
to vascular injury and hepatic circulatory disturbances 9 10 .
Various references in the literature report that anti-cancer therapies
may determine the onset of these hepatic lesions precisely
through therapy-induced vascular injury 2 .
Most of these regenerative nodules have been described in the
Literature from a clinical/radiological point of view. No histological
case series however has up till now completely described the
pathologic characteristics of such lesions. Most nodules are described
as being either FNH or NRH even though few have been
biopsied; considering that nodules are not routinely biopsied, no
exact knowledge is available about the true histological aspects of
these regenerative lesions in this specific post-malignancy group.
We report a case of a 20 year old woman who had undergone a
BMT in adolescence and was being followed up for multiple hypervascular
liver lesions, the largest of which was biopsied.
In particular we confirm the benign regenerative nature of the
lesion. Furthermore we describe the presence of single arterioles
within the parenchyma which may explain the hypervascularity
seen at imaging. Indeed, partial capillarization seen with anti-
CD34 antibodies is also secondary to hypervascularization.
These findings have never been described in post chemotherapy
regenerative nodules to our knowledge. This probably depends
greatly on the absence of descriptive histological case series as
most patients are radiologically followed up. This may prove to be
a distinctive feature of these lesions and identify them as a specific
subgroup within the spectrum of hepatic regenerative lesions.
Future collection and evaluation of biopsies from post-treatment
pediatric livers may be interesting to validate our findings or at
least accurately describe the histopathologic features.
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