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Year : 2021  |  Volume : 10  |  Issue : 3  |  Page : 215-218

Retroperitoneal nonfunctional extraadrenal paraganglioma: A diagnostic challenge

1 Department of Pathology, Grant Government Medical College and Sir. J.J.Group of Hospitals, Mumbai, Maharashtra, India
2 Department of Basic Sciences, Almaarefa University, Riyadh, Kingdom of Saudi Arabia
3 Department of Pathology, SRL Avinash Phadke Lab, Conwest Jain Hospital, Mumbai, Maharashtra, India
4 Department of Pathology, Bharati Vidyapeeth, Pune, Maharashtra, India

Date of Submission04-Oct-2021
Date of Acceptance05-Nov-2021
Date of Web Publication6-Dec-2021

Correspondence Address:
Wasif Ali Zafar Ali Khan
Department of Basic Sciences, Almaarefa University, Riyadh
Kingdom of Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/sjhs.sjhs_145_21

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Retroperitoneal nonfunctional extraadrenal paragangliomas are uncommon neoplasms arising from the aorticosympathetic chain of paraganglia. Biopsy of these tumors shows diverse cytomorphological features which can pose a significant diagnostic challenge to the histopathologist. We report a case of a 36-year-old male presenting with abdominal pain and a retroperitoneal mass anterior to the left kidney observed on ultrasound and computed tomography (CT) scan. CT-guided needle core biopsy was carried out which revealed varied cytological features suggesting a wide spectrum of differential diagnosis. Knowledge of the histological features along with immunohistochemistry helped us to diagnose this case. Since surgical excision is the preferred treatment of choice, early and accurate diagnosis is of utmost importance.

Keywords: Computed tomography-guided needle core biopsy, extraadrenal paraganglioma, nonfunctional, retroperitoneal

How to cite this article:
Patil P, Khan WA, Sengupta A, Patil K. Retroperitoneal nonfunctional extraadrenal paraganglioma: A diagnostic challenge. Saudi J Health Sci 2021;10:215-8

How to cite this URL:
Patil P, Khan WA, Sengupta A, Patil K. Retroperitoneal nonfunctional extraadrenal paraganglioma: A diagnostic challenge. Saudi J Health Sci [serial online] 2021 [cited 2023 Jun 9];10:215-8. Available from: https://www.saudijhealthsci.org/text.asp?2021/10/3/215/331771

  Introduction Top

Paraganglioma (PG) is an uncommon neoplasm arising from neuroendocrine cells belonging to the “Paraganglion system.” The most common location of these tumors is within the adrenal medulla, where they are called as pheochromocytomas, approximately 70% of extraadrenal PG (EAPs) occur in the head-and-neck region with carotid body tumor being the most common type and remaining of these tumors are seen in the paravertebral region including the retroperitoneal space.[1]

They usually develop in individuals aged 40–50 years but can develop at any age and are observed almost in equal frequency in both sexes.

Fine-needle aspiration particularly the image-guided needle core biopsy combined with immunohistochemistry (IHC) is often used as a diagnostic modality for initial workup.[2] There are only a few studies and case reports highlighting the importance of the diagnostic method, histological features, IHC, and the differential diagnosis in the characterization of EAPs. We present a rare case of retroperitoneal nonfunctional EAP diagnosed on computed tomography (CT)-guided needle core biopsy and the challenges encountered during the diagnosis of the case.

  Case Report Top

A 36-year-old male was admitted to the surgical ward with complaints of persistent lower abdominal pain. Physical examination showed a tender mass on deep palpation. Abdominal ultrasound revealed retroperitoneal soft-tissue mass near the left kidney. CT scan showed a well circumscribed, lobulated isodense retroperitoneal mass of size 65 mm × 49 mm, lying anterior to the left kidney near the aorta, and left renal vein [Figure 1]a. The possibility of soft-tissue tumor was suggested, and CT-guided needle core biopsy was performed.
Figure 1: (a) Computed tomography scan showing retroperitoneal paraganglioma. (b) Hematoxylin and eosin (H and E, ×40) stained section showing a cellular tumor with a prominent vascular framework. (c) Hematoxylin and eosin (H and E, ×100) stained section showing intermediate to large polygonal cells arranged in alveolar patterns. (d and e) Hematoxylin and eosin (H and E, ×100) stained section showing tumor cells arranged in trabecular and cord-like patterns. (f) Hematoxylin and eosin (H and E, ×400) stained section showing tumor cells with ill-defined cytoplasmic borders, granular cytoplasm, nuclear pleomorphism, and hyperchromasia

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Microscopic examination of the biopsy revealed a cellular tumor with a prominent vascular framework containing many dilated and congested blood vessels [Figure 1]b. The intermediate to large polygonal cells were arranged in alveolar, trabecular, and cord-like patterns [Figure 1]c, [Figure 1]d, [Figure 1]e. Tumor cells exhibited ill-defined cytoplasmic borders with amphophilic granular cytoplasm and ovoid nuclei with vesicular chromatin. Nuclear pleomorphism and hyperchromasia cannot be overemphasized [Figure 1]f. However, mitotic activity was not evident. Considering the varied cytological features, we suspected adrenal cortical adenoma, renal cell carcinoma, metastatic adenocarcinoma, vascular tumor, PG, sarcoma, and metastatic melanoma. Subsequently, IHC was performed to confirm and rule out the abovementioned differential diagnosis. Tumor cells showed strong and diffuse positivity for chromogranin A and synaptophysin [Figure 2]a and [Figure 2]b. Cytokeratin, CD31, and vimentin were negative [Figure 2]c, [Figure 2]d, [Figure 2]e. S100 showed focal positivity. MIB-1 index was 1% [Figure 2]f. Taking into consideration, the CT scan findings, cytological features, and immunohistochemical reactivity, we made a diagnosis of retroperitoneal nonfunctional EAP.
Figure 2: (a and b) Photomicrograph (Immunostain, ×100) reveals strong chromogranin and synaptophysin positive tumor cells. (c-e) Photomicrograph (Immunostain, cytokeratin, CD31, and vimentin, ×100) showing the absence of immunoreactivity. (f) Photomicrograph (Immunostain, Ki67, ×100) reveals 1% proliferative activity

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  Discussion Top

PGs may be functional and produce excess of catecholamines leading to headache, palpitations, sweating, and hypertension.[3] Nonfunctional tumors comprise 10%–15% of these tumors. The majority of them grow slowly and are often locally invasive with a high frequency of local recurrence after excision.[4] They usually present with abdominal pain, palpable mass, or in some cases with symptoms related to distant metastasis. In the absence of typical clinical manifestations, diagnosis of retroperitoneal nonfunctional PGs is often delayed.

Previously, PGs were classified as benign and malignant, but as per the recent WHO criteria, the term benign has been abolished and all PGs should be considered to have metastatic potential.[5] There is no histologic feature that reliably predicts clinical behavior; hence, histology cannot be used to diagnose malignancy and the definitive diagnosis rests on the presence of distant metastasis.[1] Metastasis is observed in almost 20%–42% of EAPs and the common metastatic sites are lymph nodes, bone, liver, and lung. These patients have a poor prognosis with the 5-year survival rate of 36%.[4]

Tissue sampling is essential to confirm the diagnosis and devise a proper treatment strategy, particularly in an area such as the retroperitoneal space where several pathologic processes are known to occur and can pose diagnostic difficulty.[6] Nowadays, image-guided needle biopsy has become a well-established method for the diagnosis of malignancy in adults.[7]

EAP shows a varied gamut of cytomorphologic features.[2],[8],[9] A study by Handa et al.[2] showed clusters and singly scattered round to polygonal cells with moderate-to-abundant cytoplasm with fine pink granularity and pleomorphic nuclei. Additional features such as acinar formation, nuclear grooves, inclusions, membrane irregularity, budding, and nucleoli were also noted. Varma et al.[9] have reported nuclear budding in the majority of cytologically diagnosed cases of PG. A study by Fite and Maleki[8] showed cells arranged in clusters, acini, or syncytial patterns. The cells were usually plasmacytoid or spindled with abundant cytoplasm. The nuclei showed nuclear anisonucleosis, pleomorphism, binucleation and/or multinucleation, and nuclear knobbing.

The diverse differential diagnosis includes epithelial tumors such as adrenal cortical tumor, renal cell carcinoma, and metastatic adenocarcinoma. In adrenal cortical adenoma, the cells are comparatively less pleomorphic with small lipid droplets in the cytoplasm. In renal cell carcinoma, the cells borders are distinct with cytoplasmic vacuolization. In some cases, EAP may mimic hepatocellular carcinoma, metastatic melanoma, neurogenic tumors, and sarcomas.[2],[6]

Ancillary techniques such as IHC are necessary to arrive at a definite diagnosis and to rule out other close differential diagnosis.

Histologically, EAP is composed of polygonal to spindle-shaped chromaffin cells or chief cells, clustered with the sustentacular cells into small nests or alveoli characteristically called as “zellballen” and surrounded by a rich vascular network, a feature accentuated by the reticulin stain. The cytoplasm has a finely granular appearance. The nuclei are usually round to ovoid, with a stippled “salt and pepper” chromatin that is characteristic of neuroendocrine tumors. Neuroendocrine markers (e.g., chromogranin A, synaptophysin, neuron-specific enolase, S100, and CD56) are almost always positive in EAPs. If chromogranin A is negative, the diagnosis of EAP should be doubted.[5]

As evident in our case, diffuse positivity for neuroendocrine markers together with a negative cytokeratin reaction helped us to rule out other neuroendocrine tumors of the pancreas and gastrointestinal tract, adrenal cortical tumors, renal cell carcinoma, and urothelial carcinoma of the bladder. The absence of S100 positivity excluded metastatic melanoma. In view of the highly vascular nature of the EAP, CD31, and vimentin negativity eliminated angiosarcoma and other mesenchymal tumors, respectively. The Ki-67 proliferative index (MIB-1) is usually low in EAPs.

Regarding the management, complete surgical resection is considered the gold standard and offers the only chance of cure. Therefore, an accurate preoperative diagnosis is essential for the implementation of proper treatment strategy as early as possible.

To summarize, the diagnosis of retroperitoneal EAP was difficult on cytological features observed on CT-guided needle core biopsy. Although rare, they should be considered as one of the differential diagnosis while dealing with tumors arising in the retroperitoneum. Classic “zellballen” pattern may not be evident on the biopsy; hence, histological examination and IHC is essential to either confirm or rule out the differential diagnosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that their name and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Kumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis of Disease. 10th ed. Philadelphia, PA: Elsevier; 2020.  Back to cited text no. 1
Handa U, Kundu R, Mohan H. Cytomorphologic spectrum in aspirates of extra-adrenal paraganglioma. J Cytol 2014;31:79-82.  Back to cited text no. 2
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Lenders JW, Eisenhofer G, Mannelli M, Pacak K. Phaeochromocytoma. Lancet 2005;366:665-75.  Back to cited text no. 3
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. 4
Lloyd RV, Osamura RY, Kloppel G, Rosai J, editors. WHO Classification of Tumours of Endocrine Organs. 4th ed. Lyon: IARC; 2017.  Back to cited text no. 5
Gupta RK, Cheung YK, Wakefield L, Wakefield SJ, Johnson P. Fine-needle aspiration cytology of malignant retroperitoneal paraganglioma. Diagn Cytopathol 1998;18:287-90.  Back to cited text no. 6
Zikan M, Fischerova D, Pinkavova I, Dundr P, Cibula D. Ultrasound-guided tru-cut biopsy of abdominal and pelvic tumors in gynecology. Ultrasound Obstet Gynecol 2010;36:767-72.  Back to cited text no. 7
Fite JJ, Maleki Z. Paraganglioma: Cytomorphologic features, radiologic and clinical findings in 12 cases. Diagn Cytopathol 2018;46:473-81.  Back to cited text no. 8
Varma K, Jain S, Mandal S. Cytomorphologic spectrum in paraganglioma. Acta Cytol 2008;52:549-56.  Back to cited text no. 9


  [Figure 1], [Figure 2]


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