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Table of Contents
CASE REPORT
Year : 2020  |  Volume : 9  |  Issue : 3  |  Page : 180-183

Metabolically quiescent paraganglioma in a patient with carcinoma cervix: An unusual presentation


1 Department of Nuclear Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
2 Department of Surgical Oncology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
3 Department of Pathology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India

Date of Submission04-Apr-2019
Date of Decision19-Nov-2019
Date of Acceptance28-Feb-2020
Date of Web Publication27-Oct-2020

Correspondence Address:
Ramya Priya Rallapeta
Assistant Professor, Department of Nuclear Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati 517 507, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCSR.JCSR_44_19

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  Abstract 


Paragangliomas (PGLs) are rare tumours arising from sympathetic and parasympathetic paraganglial neural crest cells. Functional PGLs usually present with manifestations of catecholamine excess such as hypertension, flushing and diaphoresis. Non-functional PGLs are diagnosed incidentally during imaging studies and pose a significant diagnostic challenge. Here, we report the case of 42-year-old female patient with carcinoma cervix who presented with a non-fluorodeoxyglucose-avid PGL. This case report highlights the importance of considering PGL in differential diagnosis and the management of retroperitoneal tumours.

Keywords: 18F-fluorodeoxyglucose, positron-emission tomography computerised tomography non-18F-fluorodeoxyglucose-avid, paraganglioma, pheochromocytoma, retroperitoneal tumour


How to cite this article:
Hemalatha D S, Rallapeta RP, Manthri RG, Kalawat TC, Hulikal N, Prayaga A. Metabolically quiescent paraganglioma in a patient with carcinoma cervix: An unusual presentation. J Clin Sci Res 2020;9:180-3

How to cite this URL:
Hemalatha D S, Rallapeta RP, Manthri RG, Kalawat TC, Hulikal N, Prayaga A. Metabolically quiescent paraganglioma in a patient with carcinoma cervix: An unusual presentation. J Clin Sci Res [serial online] 2020 [cited 2020 Nov 30];9:180-3. Available from: https://www.jcsr.co.in/text.asp?2020/9/3/180/298955




  Introduction Top


Pheochromocytoma and paragangliomas (PGLs) are catecholamine-producing tumours of the adrenal medulla and extra-adrenal sympathetic chromaffin tissues, respectively. The combination of nuclear medicine and anatomic imaging is used to delineate the extent of PGLs.[1] Among the various nuclear imaging modalities,18 F-fluorodeoxyglucose positron-emission tomography-computerised tomography (18 F FDG PET-CT) scan has been recognised as one of the effective tools to localise PGL.[1] Previous studies showed that poorly differentiated PGLs and those with succinate dehydrogenase subunit B (SDHB)/Von Hippel–Lindau (VHL) mutations are fluorodeoxyglucose (FDG) avid.[2],[3] Here, we report a case of non-FDG-avid lesion, diagnosed as PGL post-excision, that was coexistent with carcinoma cervix and hence misinterpreted as metastasis from carcinoma cervix.


  Case Report Top


A 42-year-old female patient was admitted for the evaluation of polymenorrhagia for 5 months. She had complaints of occasional headache. No classical symptoms of PGL such as hypertension, palpitations, facial flushing, nausea, vomiting or blurred vision were present. Initial evaluation for polymenorrhagia showed inflammatory changes in Pap smear, severe dysplasia suggesting squamotransitional carcinoma on cervical biopsy and no evidence of malignancy on endometrial biopsy. Abdominal ultrasonography showed a complex mass in the right side aortocaval region, measuring 5.3 cm × 5.1 cm with few cystic areas. On contrast-enhanced computed tomography of abdomen, a poorly enhancing mass was found in the aortocaval region suggestive of a lymph nodal mass [Figure 1]. With suspicion of carcinoma cervix and possible aortocaval metastatic lymph nodal mass, the patient was referred for18 F-FDG PET-CT which showed non-FDG-avid well-defined soft-tissue density lesion measuring 4.0 cm anteroposterior (AP) × 4.9 cm mediolateral (ML) × 4.2 cm craniocaudal (CC) in the aortocaval region and no metabolically active disease in the pelvis [Figure 2],[Figure 3] and [Figure 4]. Mismatch between clinical and radiological findings was noted, and final diagnosis of cervical intraepithelial neoplasia III with aortocaval mass was made. Further, the patient was planned for hysterectomy and aortocaval mass excision. During intraoperative handling of aortocaval mass, there were fluctuations in blood pressure (maximum being 210/110 mmHg) and tachycardia (pulse 120/min), followed by ventricular bigeminy with ST elevations, raising the suspicion of secretory PGLs. Hence, frozen section was sent, which suggested PGLs, and the total excision of tumour was done. Both frozen section and post-operative histopathological examination from the aortocaval mass revealed a lesion comprising round-to-polygonal cells with vesicular chromatin, moderate-to-abundant granular eosinophilic cytoplasm arranged in sheets and cords and organoid pattern separated by fibrous septae with sustentacular cells-favouring morphology of PGL [Figure 5]. Immunohistochemistry with synaptopysin and chromogranin showed cytoplasmic positivity in tumour cells, which confirmed the morphological diagnosis of PGL. Post-operative total hysterectomy histopathological examination showed round-to-polygonal cells with hyperchromatic nucleus and moderate eosinophilic cytoplasm arranged in nests and islands infiltrating the underlying stroma-favouring diagnosis of non-keratinising squamous cell carcinoma of the cervix [Figure 6]. The patient was discharged in a stable condition after 7 days post-surgery. The patient came for follow-up after 1 month of post-operative period. Twenty-four hours urine normetanephrines and metanephrines values were 148 μg/24 h and 103 μg/24 h, respectively, which was lower than the normal lower limit values.
Figure 1: Axial (a) and coronal (b) contrast-enhanced computerised tomography images showing enlarged lymph nodal mass measuring 5.2 cm × 4.8 cm near pancreatic head in the subhepatic region

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Figure 2: Maximum intensity projection image showing the normal biodistribution of[18]F-fluorodeoxyglucose in the body

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Figure 3: Axial computerised tomography (a) and fused positron-emission tomography/computerised tomography (b) images showing a non-fluorodeoxyglucose-avid aortocaval mass lesion measuring 4.0 (AP) cm × 4.9 (ML) cm × 4.2 (CC) cm

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Figure 4: Axial computerised tomography (a) and fused positron-emission tomography/computerised tomography (b) images showing no metabolically active abnormality in the suspected site in the region of the cervix

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Figure 5:Photomicrograph of the aortocaval mass showing round-to-polygonal cells with vesicular chromatin, moderate-to-abundant granular eosinophilic cytoplasm arranged in sheets and cords and organoid pattern separated by fibrous septae with sustentacular cells-favouring morphology of paraganglioma (Haematoxylin and eosin, ×400)

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Figure 6: Photomicrograph of the post-operative total hysterectomy specimen showing round-to-polygonal cells with hyperchromatic nucleus and moderate eosinophilic cytoplasm arranged in nests and islands infiltrating the underlying stroma-favouring morphology of non-keratinising squamous cell carcinoma of the cervix (Haematoxylin and eosin, ×200)

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  Discussion Top


PGLs are neuroendocrine tumours derived from pluripotent neural crest stem cells and are associated with neurons of the autonomic nervous system occurring anywhere along the paravertebral axis from the base of the skull to the pelvis.[1] PGLs are also known as extra-adrenal pheochromocytomas. Most often, PGLs are benign and progress slowly.[1] The aetiology of sporadic pheochromocytomas and PGL is unknown. However, about 25% of patients have an inherited condition that includes germ line mutations in the SDHB, C, D, complex assembly factor 2 (AF2, also called SDH5) and A, Von Hippel–Lindau disease, hypoxia-inducible factor (HIF) Type 2 A, (RET) in multiple endocrine neoplasia Type 2 (MEN2), fumarate hydratase genes and neurofibromatosis (NF) type 1.[4] Usually, VHL and RET mutations almost always cause pheochromocytomas, and SDHx mutations cause both pheochromocytomas and PGL.

The common clinical syndromes including PGLs and/or pheochromocytomas as their endocrine components are MEN2, NF, VHL syndrome, Carney–Stratakis syndrome, Carney triad and hereditary PGL syndrome.[5] PGLs and/or pheochromocytomas are known to be associated with pituitary adenoma, medullary carcinoma thyroid, pancreatic tumours,[6] renal cell carcinoma,[7] gastric and pulmonary tumours,[8] rarely with papillary carcinoma of thyroid.[9] To the best of our knowledge, synchronous PGL with carcinoma cervix has uncommonly been documented in literature. Our case report documents unusual presentation of carcinoma cervix with aortocaval PGL.

Various tracers used for imaging PGLs are131 I or123 I-radiolabelled metaiodobenzylguanidine (mIBG),18 F-fluorodopamine (18 F-FDA) and18 F-fluoro-L-dopa (18 F-FDOPA),18 F-FDG,111 Indium octreotide,68 Gallium (68 Ga) 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-octreotate (68 Ga-DOTATATE) and11 C-hydroxyephedrine. Functional imaging using131 Ior123 I mIBG and more recently,18 F-FDA and18 F-fluorodopa positron-emission tomography (PET) have been used in the detection of metastatic PCCs and PGLs with substantial sensitivity and specificity.[10] mIBG is a norepinephrine analogue, traditionally used for the diagnosis of extra-adrenal tumours to rule out multicentricity and metastasis.[1],[11] However, among all these presently available tracers,18 F-FDG is the most accessible tracer and plays an increasingly vital role in PGL imaging.18 F-FDG uptake tends to be related to dedifferentiation and aggressiveness of the tumour. Hence, imaging with18 F-FDG provides information regarding metabolic activity and biologic aggressiveness of these tumours.

The18 F-FDOPA is considered to be first-choice radiopharmaceutical preferred in the evaluation pheochromocytoma, extra-adrenal abdominal and thoracic sympathetic PGL.[12] The68 Ga-DOTA peptides are the preferred radiopharmaceuticals in the evaluation of parasympathetic PGL and metastatic pheochromocytoma or PGL.[12]18 F-FDG is the second-choice radiopharmaceutical in extra-adrenal abdominal, thoracic sympathetic PGL and metastatic pheochromocytoma or PGL that are SDHx mutated.[12] In our case, the aortocaval mass is a parasympathetic PGL, hence non-avid on18 F-FDG PET CT scan.

In our patient with retroperitoneal extra-renal mass in the aortocaval region,18 F FDG PET-CT was used to differentiate PGLs from neurogenic tumours, lymph nodal disease or mesenchymal tumours. Usually,131 Ior123 I mIBG is superior in abdominal PGLs but suboptimal in cases of small lesions or those with special phenotypic assets.[13]18 F FDG PET-CT is sensitive in detecting sympathetic extra-adrenal PGLs, probably as a result of higher prevalence of SDHB mutation.[2],[3] The18 F-FDG avidity is due to Warburg effect (aerobic glycolysis).[14] Usually, PGLs with SDH and VHL gene mutation are FDG avid, due to SDH/VHL genes inactivation-induced hypoxic response even in the presence of oxygen called as pseudohypoxic state. Hypoxia-induced factors (HIFs) accumulation or HIF hydroxylation impairment through increased production of reactive oxygen species results in increased glucose uptake that is visualised in18 F-FDG PET CT scan.18 F FDG avidity is also seen in poorly differentiated tumours.[14] Hence, non-avidity in18 F FDG PET-CT scan indicates well-differentiated tumour or absence of SDH/VHL mutation. Surgery after adequate pre-operative preparation remains the treatment of choice.[11] In our case, as the tumour was suspected intraoperatively and diagnosed post-operatively, no prior preparation was done.

In conclusion, SDH and VHL mutation-associated PGLs and poorly differentiated PGLs are usually noted to be18 F-FDG avid. This case report highlights the significance of considering extra-adrenal PGLs, as one of the differential diagnoses in the management of retroperitoneal tumours, in spite of its rarity and non-18 F-FDG avidity.

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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Taïeb D, Sebag F, Barlier A, Tessonnier L, Palazzo FF, Morange I, et al. 18F-FDG avidity of pheochromocytomas and paragangliomas: A new molecular imaging signature? J Nucl Med 2009;50:711-7.  Back to cited text no. 1
    
2.
Timmers HJ, Kozupa A, Chen CC, Carrasquillo JA, Ling A, Eisenhofer G, et al. Superiority of fluorodeoxyglucose positron emission tomography to other functional imaging techniques in the evaluation of metastatic SDHB-associated pheochromocytoma and paraganglioma. J Clin Oncol 2007;25:2262-9.  Back to cited text no. 2
    
3.
Zelinka T, Timmers HJ, Kozupa A, Chen CC, Carrasquillo JA, Reynolds JC, et al. Role of positron emission tomography and bone scintigraphy in the evaluation of bone involvement in metastatic pheochromocytoma and paraganglioma: Specific implications for succinate dehydrogenase enzyme subunit B gene mutations. Endocr Relat Cancer 2008;15:311-23.  Back to cited text no. 3
    
4.
Lefebvre M, Foulkes WD. Pheochromocytoma and paraganglioma syndromes: Genetics and management update. Curr Oncol 2014;21:e8-e17.  Back to cited text no. 4
    
5.
LeBlanc M, Tabrizi M, Kapsner P, Hanson JA. Synchronous adrenocortical neoplasms, paragangliomas, and pheochromocytomas: Syndromic considerations regarding an unusual constellation of endocrine tumors. Hum Pathol 2014;45:2502-6.  Back to cited text no. 5
    
6.
Almeida MQ, Stratakis CA. Solid tumors associated with multiple endocrine neoplasias. Cancer Genet Cytogenet 2010;203:30-6.  Back to cited text no. 6
    
7.
Petr EJ, Else T. Pheochromocytoma and Paraganglioma in Neurofibromatosis type 1: Frequent surgeries and cardiovascular crises indicate the need for screening. Clin Diabetes Endocrinol 2018;4:15.  Back to cited text no. 7
    
8.
Alrashdi I, Bano G, Maher ER, Hodgson SV. Carney triad versus Carney Stratakis syndrome: Two cases which illustrate the difficulty in distinguishing between these conditions in individual patients. Fam Cancer 2010;9:443-7.  Back to cited text no. 8
    
9.
Sisson JC, Giordano TJ, Avram AM. Three endocrine neoplasms: An unusual combination of pheochromocytoma, pituitary adenoma, and papillary thyroid carcinoma. Thyroid 2012;22:430-6.  Back to cited text no. 9
    
10.
Chrisoulidou A, Kaltsas G, Ilias I, Grossman AB. The diagnosis and management of malignant phaeochromocytoma and paraganglioma. Endocr Relat Cancer 2007;14:569-85.  Back to cited text no. 10
    
11.
Goldfarb DA, Novick AC, Bravo EL, Straffon RA, Montie JE, Kay R. Experience with extra-adrenal pheochromocytoma. J Urol 1989;142:931-6.  Back to cited text no. 11
    
12.
Castinetti F, Kroiss A, Kumar R, Pacak K, Taieb D. 15 Years of paraganglioma: Imaging and imaging-based treatment of pheochromocytoma and paraganglioma. Endocr Relat Cancer 2015;22:T135-45.  Back to cited text no. 12
    
13.
van der Harst E, de Herder WW, Bruining HA, Bonjer HJ, de Krijger RR, Lamberts SW, et al.123 I-metaiodobenzylguanidine and111 In-octreotide uptake in benign and malignant pheochromocytomas. J Clin Endocrinol Metab 2001;86:685-93.  Back to cited text no. 13
    
14.
Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J Gen Physiol 1927;8:519-30.  Back to cited text no. 14
    


    Figures

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



 

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