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 Table of Contents  
Year : 2018  |  Volume : 30  |  Issue : 3  |  Page : 310-314

An interesting case of malignant paraganglioma of the mandible with calvarial metastasis

1 Department of Oral Medicine and Radiology, Subharti Dental College and Hospital, Meerut, Uttar Pradesh, India
2 Department of Oral Medicine and Radiology, Career Postgraduate Institute of Dental Sciences, Lucknow, Uttar Pradesh, India
3 Department of Oral Medicine and Radiology, Purvanchal Institute of Dental Sciences, GIDA, Gorakhpur, Uttar Pradesh, India

Date of Submission17-Apr-2018
Date of Acceptance02-Jul-2018
Date of Web Publication18-Oct-2018

Correspondence Address:
Dr. Ravi Prakash Sasankoti Mohan
Department of Oral Medicine and Radiology, Subharti Dental College and Hospital, Meerut, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jiaomr.jiaomr_61_18

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Paraganglioma is a rare neuroendocrine tumor arising from the neuroectodermally derived paraganglionic cells scattered throughout the body. Other neuroendocrine tumors include carcinoids, islet cell tumors, medullary carcinoma of thyroid, melanoma, mastocytoma, merkel's cell tumor of the skin, neurocytomas, oat cell carcinoma, pinealoma, and pituitary adenoma. Very few cases have been reported intraorally. Only few cases of neuroendocrine tumor of mandible have been reported till date. This is an interesting case of malignant paraganglioma of the mandible in a 30-year-old male patient with metastasis to the calvarium.

Keywords: Calvarium, gangliocytic, malignant, mandible, neuroendocrine tumor, paraganglioma

How to cite this article:
Sasankoti Mohan RP, Agarwal N, Gupta S, Sidhu VK. An interesting case of malignant paraganglioma of the mandible with calvarial metastasis. J Indian Acad Oral Med Radiol 2018;30:310-4

How to cite this URL:
Sasankoti Mohan RP, Agarwal N, Gupta S, Sidhu VK. An interesting case of malignant paraganglioma of the mandible with calvarial metastasis. J Indian Acad Oral Med Radiol [serial online] 2018 [cited 2022 Nov 26];30:310-4. Available from: http://www.jiaomr.in/text.asp?2018/30/3/310/243659

   Introduction Top

The term “paraganglioma” is a generic one applied to the tumors arising from paraganglia regardless of location. These are rare neuroendocrine neoplasms that arise from the extra-adrenal paraganglionic tissue derived from the neural crest. These can occur in individuals at any age, although most arise in fourth and fifth decade of life without sex predilection.[1],[2] The most common paragangliomas within the head and neck are carotid body, jugulotympanic, vagal, and laryngeal paragangliomas. Very few cases have been reported intraorally till date on tongue, palate, tonsils, mandible, mucobuccal fold, and buccal mucosa.[3]

Majority of these paragangliomas are nonfunctional and benign; however, they may secrete catecholamines or have malignant potential.[4] The incidence of malignant paraganglioma varies from 2% to 36%.[1] Because of their rarity, little information is available regarding the natural history of these tumors and patient outcome after resection.[5]

The present case in a 30-year-old male patient presented as a diagnostic challenge due to the uncommon occurrence and presentation of this rare entity at this site.

   Case Report Top

A 30-year-old male reported to the department of Oral Medicine and Radiology with a chief complaint of slow growing swelling of the left lower jaw since 2 months with intermittent pain. He noticed another swelling on the same side of the face, and a growth intraorally 20 days back. There was a loss of one tooth 8 days back. Past medical history was non contributory. All the vital signs were in normal limits. Extraoral examination revealed two diffuse: tender and soft to firm swellings in the left parasymphysis and ramus region [Figure 1]a and [Figure 1]b. The regional lymph nodes were not palpable. Intraorally, a large 2 × 1.5 cm magenta red color sessile mass was present in the left premolar and first molar region. The surface presented with some vascular markings and indentations of opposing teeth [Figure 2]. It bled profusely on probing. It was soft to firm on palpation without any pulsations or bruit. Left first premolar was missing, and teeth in vicinity of the growth were grade 2 mobile. Provisional diagnosis considered was osteosarcoma of mandible. Differential diagnosis considered was metastatic tumor.
Figure 1: (a and b) Extraoral profile photographs showing two swellings on left side of the face, one near parasymphysis region and the other in left ramus region

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Figure 2: Intraoral photograph showing growth in lower left premolar molar region

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A survey orthopantomogram revealed osteolytic lesion with diffuse and irregular margins in the left body and ramus of mandible [Figure 3]. The osteolytic lesion in the left body of mandible revealed thick, multiple wispy septa interweaving each other in some areas. The inferior border was presented with sclerosis. The roots of involved teeth had external root resorption. Thin curved septas were seen internally in the osteolytic lesion in left ramus of mandible. A mandibular lateral cross-sectional occlusal radiograph of the left quadrant revealed the effacement of the buccal cortex with cortical reaction resembling sunray appearance [Figure 4]. Lateral skull radiograph demonstrated multiple lytic lesions on the calvarium with irregular margins giving the appearance of craters on moon [Figure 5]. Three-dimensional computed tomogram of the skull confirmed the destructive lytic lesions to be confined to the mandible and calvarium [Figure 6]. Clinico radiographic diagnosis was thought to be multiple myeloma. Differential diagnosis considered was metastatic tumor.
Figure 3: Panoramic view shows two distinct osteolytic lesions with irregular margins and wispy septa in left parasymphysis and ramus of mandible. Sclerosis is also seen at inferior border

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Figure 4: Left lateral topographic occlusal radiograph shows sunray appearance with thin expanded buccal cortical plate from lower left first premolar to second molar

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Figure 5: Left lateral skull radiograph shows multiple osteolytic lesions with irregular margin

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Figure 6: (a and b) Three dimensional computed tomogram of the skull shows multiple osteolytic lesions on calvarium giving an appearance of craters on moon

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Urine analysis for Bence Jones protein and serum protein electrophoresis failed to detect any monoclonal spike (M protein) in gamma zone. Hemogram, random blood sugar, erythrocyte sedimentation rate, serum C-reactive protein, beta 2 microglobulin, albumin, and calcium and phosphorus levels were all within normal limits. Only serum alkaline phosphatase level was slightly raised (205.6 IU/L).

Incisional biopsy was then done, which revealed features that suggested a “Zell-Ballen” appearance, which was diagnostic of paraganglioma [Figure 7]a. Immunohistochemistry of the specimen further confirmed it as gangliocytic paraganglioma being strongly positive for chromogranin A and synaptophysin [Figure 7]b and [Figure 7]c; and negative for glial fibrillary acid protein (GFAP) [Figure 7]d and cytokeratin.
Figure 7: Photomicrographs of (a) H and E stained (×100) biopsy specimen with characteristic “Zell-Ballen” appearance of paraganglioma. (b) Immunohistochemical staining (×200) using chromogranin A: strongly positive. (c) Immunohistochemical s t a i n i n g (×2 0 0) u s i n g s y n a p t o p h y s i n : s t r o n g l y positive. (d) Immunohistochemical staining (×100) using glial fibrillary acid protein: Negative suggesting malignant nature of paraganglioma

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To find out the primary site of this tumor, following investigations were done that included whole body ultrasound scanning, endoscopy, radiographs of chest and pelvis, and liver and thyroid function test. All were normal. Serum vanillyl mandelic acid and catecholamine levels were also in normal limits. [18F]-Fluorodeoxyglucose-Positron emission tomography ((18)F-FDG PET) was planned; but before this could be done, he died within 7 days of his reporting to the department. This case represents a malignant gangliocytic paraganglioma of the mandible which probably has metastasized to the calvarium.

   Discussion Top

Paraganglioma and pheochromocytoma are embryologically related tumors, sharing neural crest origin. Paragangliomas are usually diagnosed in patients older than 40–50 years, whereas hereditary forms are diagnosed in younger patients usually associated with multiple endocrine neoplasia syndrome type 2, neurofibromatosis type 1, tuberous sclerosis, and Von Hippel Lindau syndrome; and mutation in subunits of succinic dehydrogenase enzyme enzyme and Carney's triad.[1],[5] The present case was of a 30-year-old male patient with histological appearance of gangliocytic paraganglioma. Gangliocytic paraganglioma typically occurs nearly exclusively in the second portion of the duodenum, particularly in the periampullary region. The pathognomonic feature of this neoplasm is the identification of three distinct cellular elements: spindle cells, epithelial cells, and ganglion cells. These tumors are considered benign, yet occasionally metastasize to regional lymph nodes as well as to distant organs.[6]

A MEDLINE search of the articles with keywords “gangliocytic paraganglioma: mandible” or “gangliocytic paraganglioma: oral cavity” did not yield any result. Subsequently, terms “paraganglioma: mandible” or “neuroendocrine tumors: mandible” was conducted. There have been three reported cases of neuroendocrine tumors in the mandible [Table 1].[2],[7],[8] The present case as per the literature search is the first reported case of malignant paraganglioma of the mandible with metastasis to the calvarium. Because of the failure to conduct (18) F-FDG-PET due to unfortunate death of our patient, we could not confirm whether this paraganglioma had arisen from mandible and metastasized to the calvarium, or it had arisen from the duodenum and metastasized both to mandible and calvarium.
Table 1: Previously reported cases of paraganglioma involving jaw bones in literature

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The classic manifestation of nonfunctional paragangliomas is an insidiously enlarging palpable mass or pain related to local growth of a tumor mass.[1] The clinical features in all the three neuroendocrine tumors of mandible reported[2],[7],[8] were enlarging soft tissue mass as was seen in the present case and all were non functional. The unusual occurrence of this neoplasm in mandible may be a reflection of the migratory and differential properties of neural crest cells during embryogenesis. Abnormalities in these processes may produce ectopic nests of cells capable of neoplastic transformation.[4]

The radiographic appearance in all the cases was a destructive lesion in the body of the mandible with honey comb pattern in two cases, and osteoblastic tumor with sunburst pattern in one case.[2],[7],[8] In the present case, however, multiple osteolytic lesions were seen with irregular margin with a characteristic sunray appearance on occlusal radiograph. The differential diagnosis of such lesion must include osteosarcoma, chondrosarcoma, multiple myeloma, hemangiopericytoma, lymphoma, and metastatic disease.[2],[7] Other neuroendocrine tumors such as carcinoids, islet cell tumor, medullary carcinoma of thyroid, mastocytoma, melanoma, neurocytoma, oat cell carcinoma, pinealoma, pituitary adenoma, melanotic neuroecodermal tumor of infancy, small-cell carcinomas, and Merkel cell carcinoma should also be added as differential diagnosis.[2],[4],[7]

The most important radiographic differential diagnosis in the present case was multiple myeloma as jaw lesions if present are more common in mandible with predilection for angle, ramus, and molar teeth. It is characterized by presence of multiple typical punched out, regular, circular, or ovoid radiolucency in the skull instead of crater on moon-like appearance with irregular margins as seen in our patient.[9] Second important differential diagnosis was metastatic jaw tumor as metastases to the mandible occur four times more frequently than maxilla. This could be the first indication of an occult malignancy arising from breast, lung, kidney, thyroid, prostate, GI tract, retinoblastoma and other miscellaneous sites. Radiographically, it is mostly similar to that of the primary tumor. On occasion, mixed lesion of osteolytic and osteoblastic areas may be encountered. Histopathology may help identify the primary disease.[9] Since in our case, histopathology was gangliocytic paraganglioma, there still remains a high probability of primary tumor arising from duodenum.

Histologically, paragangliomas are usually easy to diagnose, with well-defined characteristics. These lesions are clearly delimited and highly vascular and are composed of cell balls (Zellballen] separated by thin fibrous septa as was seen in the present case. These cell balls are composed of two types of cells: chief cells and sustentacular cells. With immunohistochemical techniques, the chief cells are positive for neuroendocrine markers (neuron specific enolase, chromogranin A, synaptophysin, and serotonin), while sustentacular cells are positive for S-100 protein.[1] The tumor has multiple synthetic activities, and inspite of its heterogeneity, chromogranin A and synaptophysin are the most common neuropeptide synthesized as they are associated with the presence of neuroendocrine storage granules.[5] In the present case, these two markers were strongly positive, whereas GFAP and cytokeratin were negative suggesting malignant paraganglioma. GFAP positivity of type 2 cells and presence of abundance of S-100 positive subtentacular cells are suggestive of benign paraganglioma.[5],[10]

Head and neck paragangliomas are usually benign in contrast to the present sporadic malignant paraganglioma as evident by the metastases in calvarium. For the diagnosis of malignancy in paraganglioma, the only absolute criterion is metastases to the sites where chromaffin tissue is not usually found. Thus, the term “malignancy,” which is usually spreading of a primary tumor by tissue and/or vascular invasion and/or metastazising, does not necessarily apply to paraganglioma.[5],[10],[11]

Large size tumors (>5 cm), PASS score >6, and Ki-67 labeling index >3% are the most robust indices of metastasis in parangangliomas. Germline succinate dehydrogenase complex, subunit B (SDHB) mutation and plasma and urinary methoxytyramine are also important in prediction of metastasis. Conventional imaging is used for tumor localization, whereas(18) F-FDG-PET for staging of metastatic pheochromocytoma/paragangliomas especially those related to SDHB gene mutations.[11],[12]

   Conclusion Top

Inspite of its rarity, neuroendocrine tumors may arise in the mandible. Although this case is not confirmed as primary or secondary paraganglioma of the mandible, but still this case is important because it is a histologically proven case of paraganglioma. It is the first reported case with the unique presentation of paraganglioma metastasis to the calvarium. Scattered reports of metastatic or primary neuroendocrine tumors of the mandible suggest that they usually appear as osteolytic or mixed lesions with irregular margin, honeycombed, sunburst, or moth eaten appearance. Paragangliomas must also be considered in the differential diagnosis of vascular lesions in the oral cavity and also in differential diagnosis of multiple myeloma although multiple myeloma presents with classical punched out osteolytic lesions in the skull and jaw bone in contrast to the irregular destructive margins and crater on moon like appearance on skull.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names 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

Lee KY, Oh YW, Noh HJ, Lee YJ, Yong HS, Kang EY, et al. Extraadrenal paragangliomas of the body: Imaging features. AJR Am J Roentgenol 2006;187:492-504.  Back to cited text no. 1
Peters E, Richards A, Hille J, Phillips J. Malignant neuroendocrine tumor presenting in the mandible. Head Neck 1991;13:234-8.  Back to cited text no. 2
Yoshida H, Onizawa K, Hirohata H. Neuroendocrine carcinoma of the tongue: Report of a case. J Oral Maxillofac Surg 1995;53:823-7.  Back to cited text no. 3
Coles CP, Alexander DI, Gross M, Holness RO, Covert AA, Murray SK, et al. Intraosseous paraganglioma of the sacrum: A case report. Can J Surg 2000;43:137-9.  Back to cited text no. 4
Feng N, Zhang WY, Wu XT. Clinicopathological analysis of paraganglioma with literature review. World J Gastroenterol 2009;15:3003-8.  Back to cited text no. 5
Wong A, Miller AR, Metter J, Thomas CR Jr. Locally advanced duodenal gangliocytic paraganglioma treated with adjuvant radiation therapy: Case report and review of the literature. World J Surg Oncol 2005;3:15.  Back to cited text no. 6
Coleman H, Kennedy M, Altini M, Crooks J, Tsakiris P. Neuroendocrine (carcinoid) tumor of the mandible: A case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;81:74-8.  Back to cited text no. 7
Sugawara C, Takahashi A, Kawano F, Kudoh T, Yamada A, Ishimaru N, et al. Neuroendocrine tumor in the mandible: A case report with imaging and histopathologic findings. Oral Surg Oral Med Oral Pathol Oral Radiol 2015;119:e41-8.  Back to cited text no. 8
Weber AL, Bui C, Kaneda T. Malignant tumors of the mandible and maxilla. Neuroimaging Clin N Am 2003;13:509-24.  Back to cited text no. 9
Achilles E, Padberg BC, Holl K, Klöppel G, Schröder S. Immunocytochemistry of paragangliomas--value of staining for S-100 protein and glial fibrillary acid protein in diagnosis and prognosis. Histopathology 1991;18:453-8.  Back to cited text no. 10
Fliedner SM, Lehnert H, Pacak K. Metastatic paraganglioma. Semin Oncol 2010;37:627-37.  Back to cited text no. 11
Angelousi A, Kassi E, Zografos G, Kaltsas G. Metastatic pheochromocytoma and paraganglioma. Eur J Clin Invest 2015;45:986-97.  Back to cited text no. 12


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]

  [Table 1]


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