Acta Neurochir DOI 10.1007/s00701-013-1678-0
LETTER TO THE EDITOR - SPINE
Recurrent multiple spinal paragangliomas as a manifestation of a metastatic composite paraganglioma-ganglioneuroblastoma Jens Gempt & Sachin S. Baldawa & Gregor Weirich & Claire Delbridge & Maja Hempel & Peter Lohse & Bernhard Meyer & Florian Ringel
Received: 7 January 2013 / Accepted: 24 February 2013 # Springer-Verlag Wien 2013
Dear editor, We describe the occurrence of multiple recurrent, aggressive spinal paragangliomas as the initial manifestation of a metastatic composite paraganglioma-ganglioneuroblastoma in a 51-year-old patient. The patient developed progressive weakness and hypesthesia of both lower extremities. MRI demonstrated two intraspinal extradural lesions (Fig. 1a). A T4 and T6 hemilaminectomy was performed, and both intraspinal tumors were resected. During the postoperative period, the patient’s neurological deficit significantly improved. Histology revealed a paraganglioma (Fig. 1b, c). Six months later, the patient presented with low back pain, and radicular and progressive ataxia. MRI scan revealed J. Gempt (*) : S. S. Baldawa : B. Meyer : F. Ringel Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München, Germany e-mail:
[email protected] S. S. Baldawa Department of Neurosurgery, Lokmanya Tilak Muncipal Medical College, Dr. Babasaheb Ambedkar Road, Sion (West), Mumbai 400022, India G. Weirich : C. Delbridge Abteilung für Neuropathologie des Instituts für Allgemeine Pathologie und Pathologische Anatomie, Technische Universität München, Ismaninger Str. 22, 81675 München, Germany M. Hempel Institute of Human Genetics, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München, Germany P. Lohse Institut für Klinische Chemie-Großhadern, Ludwig-Maximilians-Universität München, Marchioninistr. 15, 81377 München, Germany
multiple intraspinal extradural lesions. Hemilaminectomy was performed at the T6-T9 and L2-L3 level, and tumor debulking was carried out. Histological examination was consistent with a paraganglioma. Due to the clinical course, a staging CT was performed. It revealed a large tumor of the left adrenal gland, and extensive spinal and pelvic tumor dissemination (Fig. 1d). Biopsies from the adrenal tumor and from the bone marrow revealed a composite paraganglioma-ganglioneuroblastoma (Fig. 1e). The patient received cisplatin, doxorubicin, etoposide, and endoxane chemotherapy for 9 months after resection of the left adrenal gland, kidney, spleen, and left colonic flexure. Two years after the initial diagnosis, the patient died of pneumonia after progression of the bone marrow infiltration and subsequently compromised immune status. Paragangliomas are tumors that originate from extraadrenal chromaffin cells or paraganglia lying adjacent to the sympathetic ganglia [5, 9] and occur most often in the head and neck and rarely in the retroperitoneum [6, 9]. Though benign and malignant paragangliomas may have a similar microscopic appearance, aggressive paragangliomas are histologically characterized by necrosis and vascular invasion [5]. However, prognosis is predicted best by the clinical behavior of paragangliomas in the form of recurrence or metastasis. Neuroblastomas are the more aggressive tumors and the most common extracranial tumor in childhood, and they are derived from primitive neural crest cells [4]. Ganglioneuroblastomas are transitional tumors containing elements of malignant neuroblasts and benign ganglion cells. All neurogenic tumors except ganglioneuroblastomas and neuroblastomas are common in adults. Surgical resection of the primary tumor followed by radiotherapy is recommended. Composite tumors of the adrenal medulla or paraganglia are uncommon, and their biologic behavior, treatment, and the outcome has not been well elucidated because of their relative rarity [4, 5, 9]. These tumors have two histologically different
Acta Neurochir
predisposition syndrome [Hippel-Lindau (VHL) syndrome, multiple endocrine neoplasia (MEN) type 2, and neurofibromatosis type 1], and testing of the VHL gene was declined by the patient [4, 8]. In summary, we present a case of an aggressive composite paraganglioma-ganglioneuroblastoma. Recurrent multiple spinal paragangliomas can be the initial clinical manifestation of a metastatic malignant composite paraganglioma-ganglioneuroblastoma. In patients with recurrent paragangliomas, metastasis from a composite paraganglioma tumor should be considered. Conflicts of interest None.
References
Fig. 1 a Preoperative MRI revealed the solid tumor at the level of T4 and T6 to be an extradural, intraspinal tumor mass (indicated by white arrows) with little Gd enhancement on T1 images. b Histopathological image of tumor tissue of the first tumor resection at T4 and T6: hematoxylin and eosin stain and synaptophysin immunostain. Fibrovascular septa divide cells into the typical ‘Zellballen’-alveolar pattern. The cells show small rounded nuclei with a finely dispersed chromatin and a cytoplasmatic reaction to synaptophysin immunostaining. d CT reveals a huge left-sided adrenal tumor. e Hematoxylin and eosin stain of the ganglioneuroblastoma component showing immature ganglion cells and small round blue cells divided by a fine fibrillary network
components, a neuroendocrine component (paraganglioma or pheochromocytoma) mixed with a neuronal component (ganglioneuroma, neuroblastoma, ganglioneuroblastoma, or peripheral nerve sheath tumors) [1, 4, 5, 7, 9]. In our patient, the epidural lesions were either the result of the continuation of the retroperitoneal tumor along the neural foramina or part of disseminated metastasis. The multiple recurrent spinal metastases were histologically proven paragangliomas. The widespread bony metastases, in contrast, most likely originated from both the neuronal and neuroendocrine components as evidenced by histology. In the absence of metastasis, curative resection should be attempted; however, prolonged follow-up is essential in these patients because of the inherent risk of late metastasis [7]. Germline mutations in SDH (succinate dehydrogenase) subunit B, C, and D genes are associated with paragangliomas [2, 3]. Our patient tested negative for mutations or deletions in SDHB, SDHC, and SDHD. There were no additional symptoms for a tumor
1. Armstrong R, Greenhalgh KL, Rattenberry E, Judd B, Shukla R, Losty PD, Maher ER (2009) Succinate dehydrogenase subunit B (SDHB) gene deletion associated with a composite paraganglioma/ neuroblastoma. J Med Genet 46:215–216 2. Brouwers FM, Eisenhofer G, Tao JJ, Kant JA, Adams KT, Linehan WM, Pacak K (2006) High frequency of SDHB germline mutations in patients with malignant catecholamine-producing paragangliomas: implications for genetic testing. J Clin Endocrinol Metab 91:4505– 4509 3. Burnichon N, Rohmer V, Amar L, Herman P, Leboulleux S, Darrouzet V, Niccoli P, Gaillard D, Chabrier G, Chabolle F, Coupier I, Thieblot P, Lecomte P, Bertherat J, Wion-Barbot N, Murat A, Venisse A, Plouin PF, Jeunemaitre X, Gimenez-Roqueplo AP (2009) The succinate dehydrogenase genetic testing in a large prospective series of patients with paragangliomas. J Clin Endocrinol Metab 94:2817–2827 4. Candanedo-Gonzalez FA, Alvarado-Cabrero I, Gamboa-Dominguez A, Cerbulo-Vazquez A, Lopez-Romero R, Bornstein-Quevedo L, Salcedo-Vargas M (2001) Sporadic type composite pheochromocytoma with neuroblastoma: clinicomorphologic, DNA content and ret gene analysis. Endocr Pathol 12:343–350 5. Fritzsche FR, Bode PK, Koch S, Frauenfelder T (2010) Radiological and pathological findings of a metastatic composite paraganglioma with neuroblastoma in a man: a case report. J Med Case Rep 4:374 6. Hirasaki S, Kanzaki H, Okuda M, Suzuki S, Fukuhara T, Hanaoka T (2009) Composite paraganglioma-ganglioneuroma in the retroperitoneum. World J Surg Oncol 7:81 7. Inzani F, Rindi G, Tamborrino E, Cobelli R, Bordi C (2009) Extraadrenal composite paraganglioma with ganglioneuroma component presenting as a pancreatic mass. Endocr Pathol 20:191–195 8. Reichardt P, Apel TW, Domula M, Trobs RB, Krause I, Bierbach U, Neumann HP, Kiess W (2002) Recurrent polytopic chromaffin paragangliomas in a 9-year-old boy resulting from a novel germline mutation in the von Hippel-Lindau gene. J Pediatr Hematol Oncol 24:145–148 9. Shankar GM, Chen L, Kim AH, Ross GL, Folkerth RD, Friedlander RM (2010) Composite ganglioneuroma-paraganglioma of the filum terminale. J Neurosurg Spine 12:709–713
