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Paraganglioma with a very rare presentation

Case Report

Manika Khare, Manish Kumar Gupta1, Umesh Babu Sharma, K M Garg1

Departments of Pathology and 1Surgery, JNUIMSRC, Jaipur, Rajasthan, India

Address for correspondence:

Dr. Manika Khare, Department of Pathology, JNUIMSRC, Jaipur, Rajasthan, India. E‑mail: drmanika09@gmail.com

ABSTRACT Access this article online

Website: www.ijpmonline.org
Paragangliomas (PGLs) are rare tumors of neural crest origin, with a malignancy PMID: xxxxxxxxx (when available)
rate of approximately 10% and a 5‑year survival rate of <50%. We present a DOI: 10.4103/IJPM.IJPM_334_17
case of malignant PGL arising from the porta hepatis with metastasis to the Quick Response Code:
portal lymph node and bilateral ovaries. PGLs arising from the porta hepatis
are very rare. As per our knowledge, only three cases of hepatic duct PGL have
been reported. It is important to detect it earlier because the treatment modality
and prognosis of benign and malignant PGL differs and defines the prognosis
of the patient.

KEY WORDS: Bilateral ovaries, malignant, paraganglioma

and chromogranin [Figure 1c and d].

INTRODUCTION
Based on the microscopic features and
immunohistochemicalfindings,thediagnosis
Paragangliomas (PGLs) are rare tumors of neural crest origin, with a malignancy rate of
of malignant PGL porta hepatis along with
approximately 10% and a 5‑year survival rate of <50%.[1] Extra‑adrenal tumors are more
metastatic PGL in bilateral adnexa and
likely to be malignant than adrenal tumors. Here, we present a rare case of malignant
portal lymph node was given with grading
PGL arising from the porta hepatis with metastasis to the portal lymph node and bilateral
system for adrenal pheochromocytoma
ovaries.[2] Only three cases are reported arising from hepatic plexus.
and paraganglioma (GAPP) score of
5 (moderately differentiated).
CASE REPORT
DISCUSSION
A 35‑year‑old female  presented with the chief complaints of lower abdominal pain and
generalized weakness associated with weight loss for 3 months. Routine examination
We report here the case of PGL arising
of the patient was done which revealed that the patient was anemic. Her liver profile
from the porta hepatis and metastasizing
showed slightly raised serum glutamic‑pyruvic transaminase (102.8 IU) otherwise in bilateral ovaries. We ruled out that
unremarkable. The patient was the known case of hypertension. Ultrasonography the tumor was retroperitoneal because
abdomen was performed which showed hyperechoic mass in the porta region. Computed it was not attached to any structure and
tomography abdomen showed no adrenal mass. For further evaluation of the patient, was fully mobilized. PGL arising from
magnetic resonance imaging abdomen was done which showed a large heterogeneous the porta hepatis are very rare. As per
mass lesion of size approximately 3.8 cm × 3.5 cm at porta hepatis along with bilateral our knowledge, only single case has been
adnexal mass. Right adnexal mass measured 3.5 cm × 2.1 cm and left adnexal mass reported. However, three cases of hepatic
measured 4.5 cm × 2.8 cm. Multiple enlarged bilateral internal iliac lymph nodes were
also seen. Upper gastrointestinal endoscopy was unremarkable. Surgery of the patient was This is an open access journal, and
planned. A midline incision was given, and a highly vascular porta hepatis mass along articles are distributed under the
terms of the Creative Commons
with adjacent hard lymph node was removed [Figure 1a]. Bilateral salpingectomy was Attribution‑NonCommercial‑ShareAlike 4.0
done for adnexal masses, and specimens were sent for histopathological examination. License, which allows others to remix, tweak,
After surgery patients, blood pressure came within normal limits in 2–3 days. and build upon the work non‑commercially,
as long as appropriate credit is given and
the new creations are licensed under the
Microscopically, the tumor from all the sites showed similar morphology and was identical terms.
highly vascular. The tumor cells were arranged in small islands forming Zellballen For reprints contact: reprints@medknow.com
nests. Individual cells were round to polygonal, with finely granular eosinophilic
to amphophilic cytoplasm and centrally located ovoid nuclei with stippled “salt How to cite this article: Khare M, Gupta MK,
Sharma UB, Garg KM. Paraganglioma with a
and pepper” chromatin and small inconspicuous nucleoli [Figure 1b]. Large areas of very rare presentation. Indian J Pathol Microbiol
necrosis were also noted. The tumor cells were strongly positive for synaptophysin 2018;61:404-6.

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Khare, et al.: Metastatic paraganglioma
a b
c d
Figure 1: (a) Intraoperative photograph showing enlarged ovaries with
tumor deposits and a tumor at porta hepatis.  (b) Photomicrograph
showing a highly vascular tumor, with tumor cells predominantly
arranged in  Zellballen. (c) Photomicrograph showing neuron‑specific
enolase positivity in tumor cells.  (d) Photomicrograph showing
chromogranin positivity in tumor cells
duct PGL have been reported.[3,4] Two of these cases presented
with obstructive jaundice, whereas the third case did not have
any signs and symptoms related to obstruction. Biliary system
PGLs are predominantly seen in females and are discovered in
the fifth‑to‑sixth decade of life. Although they are usually small
in size, the largest reported tumor was 5 cm in diameter.
So far, no familial association has been reported in any PGL of
the biliary system. Primary hepatobiliary PGLs theoretically
arise from primordia of hepatic plexus, which innervates the
hepatobiliary system, and are formed from sympathetic and
parasympathetic fibers of the left vagus nerve and celiac plexus.[5]
The pathological diagnosis of these tumors is based on careful
gross examination of the specimens, microscopic examination,
and immunohistochemistry. These tumors are positive for the
synaptophysin and chromogranin.
PGLs are classified according to various sites from which they
arise.
According to the 10% rule, only 10% of PGLs are malignant.
Currently, there are no reliable markers for metastatic disease
in PGL. Mitotic activity, vascular invasion, and necrosis are
histological features that are suggestive, but not diagnostic, of
malignant behavior.[6] GAPP score is helpful for predicting the
course of PGL. The only way to diagnose malignancy is the
presence of metastases.
Pheochromocytomas and extra‑adrenal PGLs have unpredictable
behavior and usually show late metastasis. Thus, patients with
PGL have to be followed up for a long time because metastatic
disease or recurrence can appear even after decades free of disease.
The most promising diagnostic/predictive marker for metastatic
PGL so far seems to be the expression of the hypoxia‑inducible
Indian Journal of Pathology and Microbiology ¦ Volume 61 ¦ Issue 3 ¦ July-September 2018
factor‑2α‑regulated SNAIL.[7] Positive staining for primary tumors
correlates well with the presence of distant metastases. However,
these findings have to be carefully evaluated for the different
types of PGL.
Kimura et al. introduced a scoring system to predict the prognosis
of pheochromocytomas and other extra‑adrenal sympathetic
PGLs. This scoring system depends on the tumor pattern
(large, irregular nests, and pseudorosettes), increased cellularity,
vascular invasion, coagulation necrosis, high proliferation index,
and the type of catecholamine secretion. Recently, GAPP scoring
is done for predicting behavior of PGL.[8]
Once the presence of metastases is verified, there is no
reliable cure. Treatment options are as follows: (1) mechanical
removal by excision or ablation, (2) targeted pharmaceutics, or
(3) chemotherapy.[8]
Treatment options include palliative tumor resection to reduce
tumor burden and excess catecholamine‑related symptoms.
Although in benign cases, a laparoscopic approach is preferred,
in metastatic PGL, this is controversial. Laparoscopy is
not advisable when local invasion and/or large tumors are
present or organ resection is required.[9] The most widely used
chemotherapeutic regimen is the cyclophosphamide, vincristine,
and dacarbazine regimen. In addition to tumor removal, treatment
with targeted radiotherapeutics can be beneficial. The most
frequently used radiotherapy is treatment with 131I‑MIBG.
Few newer studies showed that the interleukin ‑13 (IL‑13)
receptor‑α2 is expressed on the tumor cell’s surface in humans
and in a mouse model. The treatment of PGL bearing mice with
IL‑13 coupled to a truncated Pseudomonas exotoxin leads to a
significant decrease in tumor size.[10] Thus, targeting the IL‑13
receptor may be a promising new strategy to treat metastatic and
inoperable PGL.
CONCLUSION
The malignant PGL is very rare. It is important to detect it earlier
because the treatment modality and prognosis of benign and
malignant PGL differs and defines the prognosis of the patient. This
case is a very rare presentation of PGL arising from the porta hepatis
and metastasizing to portal lymph nodes and bilateral ovaries.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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