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  Table of Contents    
CASE REPORT  
Year : 2018  |  Volume : 61  |  Issue : 3  |  Page : 404-406
Paraganglioma with a very rare presentation


1 Department of Pathology, JNUIMSRC, Jaipur, Rajasthan, India
2 Department of Surgery, JNUIMSRC, Jaipur, Rajasthan, India

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Date of Web Publication13-Jul-2018
 

   Abstract 


Paragangliomas (PGLs) are rare tumors of neural crest origin, with a malignancy rate of approximately 10% and a 5-year survival rate of <50%. We present a case of malignant PGL arising from the porta hepatis with metastasis to the 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.

Keywords: Bilateral ovaries, malignant, paraganglioma

How to cite this article:
Khare M, Gupta MK, Sharma UB, Garg K M. Paraganglioma with a very rare presentation. Indian J Pathol Microbiol 2018;61:404-6

How to cite this URL:
Khare M, Gupta MK, Sharma UB, Garg K M. Paraganglioma with a very rare presentation. Indian J Pathol Microbiol [serial online] 2018 [cited 2019 Dec 11];61:404-6. Available from: http://www.ijpmonline.org/text.asp?2018/61/3/404/236605





   Introduction Top


Paragangliomas (PGLs) are rare tumors of neural crest origin, with a malignancy rate of approximately 10% and a 5-year survival rate of <50%.[1] Extra-adrenal tumors are more likely to be malignant than adrenal tumors. Here, we present a rare case of malignant PGL arising from the porta hepatis with metastasis to the portal lymph node and bilateral ovaries.[2] Only three cases are reported arising from hepatic plexus.


   Case Report Top


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 of the patient was done which revealed that the patient was anemic. Her liver profile showed slightly raised serum glutamic-pyruvic transaminase (102.8 IU) otherwise unremarkable. The patient was the known case of hypertension. Ultrasonography abdomen was performed which showed hyperechoic mass in the porta region. Computed tomography abdomen showed no adrenal mass. For further evaluation of the patient, magnetic resonance imaging abdomen was done which showed a large heterogeneous mass lesion of size approximately 3.8 cm × 3.5 cm at porta hepatis along with bilateral adnexal mass. Right adnexal mass measured 3.5 cm × 2.1 cm and left adnexal mass 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 planned. A midline incision was given, and a highly vascular porta hepatis mass along with adjacent hard lymph node was removed [Figure 1]a. Bilateral salpingectomy was done for adnexal masses, and specimens were sent for histopathological examination. After surgery patients, blood pressure came within normal limits in 2–3 days.
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

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Microscopically, the tumor from all the sites showed similar morphology and was highly vascular. The tumor cells were arranged in small islands forming Zellballen nests. Individual cells were round to polygonal, with finely granular eosinophilic to amphophilic cytoplasm and centrally located ovoid nuclei with stippled “salt and pepper” chromatin and small inconspicuous nucleoli [Figure 1]b. Large areas of necrosis were also noted. The tumor cells were strongly positive for synaptophysin and chromogranin [Figure 1]c and [Figure 1]d. Based on the microscopic features and immunohistochemical findings, the diagnosis of malignant PGL porta hepatis along with metastatic PGL in bilateral adnexa and portal lymph node was given with grading system for adrenal pheochromocytoma and paraganglioma (GAPP) score of 5 (moderately differentiated).


   Discussion Top


We report here the case of PGL arising from the porta hepatis and metastasizing in bilateral ovaries. We ruled out that the tumor was retroperitoneal because it was not attached to any structure and was fully mobilized. PGL arising from the porta hepatis are very rare. As per our knowledge, only single case has been reported. However, three cases of hepatic 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 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 Top


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.



 
   References Top

1.
Higa B, Kapur U. Malignant paraganglioma of the pancreas. Pathology 2012;44:53-5.  Back to cited text no. 1
    
2.
Sclafani LM, Woodruff JM, Brennan MF. Extraadrenal retroperitoneal paragangliomas: Natural history and response to treatment. Surgery 1990;108:1124-9.  Back to cited text no. 2
    
3.
Hitanant S, Sriumpai S, Na-Songkla S, Pichyangkula C, Sindhavananda K, Viranuvatti V, et al. Paraganglioma of the common hepatic duct. Am J Gastroenterol 1984;79:485-8.  Back to cited text no. 3
    
4.
Sarma DP, Rodriguez FH Jr., Hoffmann EO. Paraganglioma of the hepatic duct. South Med J 1980;73:1677-8.  Back to cited text no. 4
    
5.
Miller TA, Weber TR, Appelman HD. Paraganglioma of the gallbladder. Arch Surg 1972;105:637-9.  Back to cited text no. 5
    
6.
Rosai J. Adrenal and other paraganglia. In: Ackerman's Surgical Pathology. 8th ed. St Louis: Mosby; 1996. p. 1115-47.  Back to cited text no. 6
    
7.
Häyry V, Salmenkivi K, Arola J, Heikkilä P, Haglund C, Sariola H, et al. High frequency of SNAIL-expressing cells confirms and predicts metastatic potential of phaeochromocytoma. Endocr Relat Cancer 2009;16:1211-8.  Back to cited text no. 7
    
8.
Kimura N, Takayanagi R, Takizawa N, Itagaki E, Katabami T, Kakoi N, et al. Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma. Endocr Relat Cancer 2014;21:405-14.  Back to cited text no. 8
    
9.
Zografos GN, Vasiliadis G, Farfaras AN, Aggeli C, Digalakis M. Laparoscopic surgery for malignant adrenal tumors. JSLS 2009;13:196-202.  Back to cited text no. 9
    
10.
Lai EW, Joshi BH, Martiniova L, Dogra R, Fujisawa T, Leland P, et al. Overexpression of interleukin-13 receptor-alpha2 in neuroendocrine malignant pheochromocytoma: A novel target for receptor directed anti-cancer therapy. J Clin Endocrinol Metab 2009;94:2952-7.  Back to cited text no. 10
    

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Correspondence Address:
Manika Khare
Department of Pathology, JNUIMSRC, Jaipur, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_334_17

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