Treatment and outcome of Ganglioneuroma and Ganglioneuroblastoma intermixed

Boris Decarolis, Thorsten Simon, Barbara Krug, Ivo Leuschner, Christian Vokuhl, Peter Kaatsch, Dietrich von Schweinitz, Thomas Klingebiel, Ingo Mueller, Lothar Schweigerer, Frank Berthold, Barbara Hero, Boris Decarolis, Thorsten Simon, Barbara Krug, Ivo Leuschner, Christian Vokuhl, Peter Kaatsch, Dietrich von Schweinitz, Thomas Klingebiel, Ingo Mueller, Lothar Schweigerer, Frank Berthold, Barbara Hero

Abstract

Background: Ganglioneuroma (GN) and ganglioneuroblastoma intermixed (GNBI) are mature variants of neuroblastic tumors (NT). It is still discussed whether incomplete resection of GN/GNBI impairs the outcome of patients.

Methods: Clinical characteristics and outcome of localized GN/GNBI were retrospectively compared to localized neuroblastoma (NB) and ganglioneuroblastoma-nodular (GNBN) registered in the German neuroblastoma trials between 2000 and 2010.

Results: Of 808 consecutive localized NT, 162 (20 %) were classified as GN and 55 (7 %) as GNBI. GN/GNBI patients presented more often with stage 1 disease (68 % vs. 37 %, p < 0.001), less frequently with adrenal tumors (31 % vs. 43 %, p = 0.001) and positive mIBG-uptake (34 % vs. 90 %, p < 0.001), and had less often elevated urine catecholamine metabolites (homovanillic acid 39 % vs. 62 %, p < 0.001, vanillylmandelic acid 27 % vs. 64 %, p < 0.001). Median age at diagnosis increased with grade of differentiation (NB/GNBN: 9; GNBI: 61; GN-maturing: 71; GN-mature: 125 months, p < 0.001). Complete tumor resection was achieved at diagnosis in 70 % of 162 GN and 67 % of 55 GNBI, and after 4 to 32 months of observation in 4 GN (2 %) and 5 GNBI (9 %). Eleven patients received chemotherapy without substantial effect. Fifty-five residual tumors (42 GN, 13 GNBI) are currently under observation (median: 44 months). Five patients (3 GN, 2 GNBI) showed local progression; all had tumor residuals > 2 cm. No progression occurred after subtotal resection. Two patients died of treatment, none of tumor progression.

Conclusions: GN/GNBI account for one quarter of localized NT and differ from immature tumors in their clinical features. Chemotherapy is not effective. Subtotal resection appears to be a sufficient treatment.

Trial registration: ClinicalTrials.gov identifiers - NB97 (NCT00017225; registered June 6, 2001); NB2004 (NCT00410631; registered December 11, 2006).

Keywords: Ganglioneuroblastoma intermixed; Ganglioneuroma; Residual tumor; Subtotal resection; Surgery; Therapy; Treatment.

Figures

Fig. 1
Fig. 1
Grade of differentiation in relation to median age at diagnosis. NB = neuroblastoma, GNBN = ganglioneuroblastoma nodular, GNBI = ganglioneuroblastoma intermixed, GN = ganglioneuroma
Fig. 2
Fig. 2
Extent of initial surgeries and size of residual tumors currently under observation. GNBI = ganglioneuroblastoma intermixed, GN = Ganglioneuroma, n.a. = data not available. a) Surgeries of patients with Ganglioneuroma, b) Surgeries of patients with Ganglioneurblastoma
Fig. 3
Fig. 3
Outcome by histology. NB = neuroblastoma, GNBN = ganglioneuroblastoma nodular, GNBI = ganglioneuroblastoma intermixed, GN = ganglioneuroma. a) Event-free survival (EFS) by histology, b) Overall survival (OS) by histology
Fig. 4
Fig. 4
Outcome of GN/GNBI by tumor residuals. GNBI = ganglioneuroblastoma intermixed, GN = ganglioneuroma. a)EFS for GN/GNBI by tumor residuals, b) OS for GN/GNBI by tumor residuals, p = major residuals vs. no or minor residuals
Fig. 5
Fig. 5
Outcome of ganglioneuroma (GN) by tumor residuals. a) EFS for GN by tumor residuals, b) OS for GN by tumor residuals, p = major residuals vs. no or minor residuals
Fig. 6
Fig. 6
Outcome of ganglioneuroblastoma intermixed (GNBI) by tumor residuals. a) EFS for GNBI by tumor residuals, b) OS for GNBI by tumor residuals, p = major residuals vs. no or minor residuals

References

    1. Kaatsch P. Epidemiology of childhood cancer. Cancer Treat Rev. 2010. doi:10.1016/j.ctrv.2010.02.003
    1. Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B. Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee. Cancer. 1999;86(2):349–63. doi: 10.1002/(SICI)1097-0142(19990715)86:2<349::AID-CNCR20>;2-Y.
    1. Mora J, Gerald WL. Origin of neuroblastic tumors: clues for future therapeutics. Expert Rev Mol Diagn. 2004;4(3):293–302. doi: 10.1586/14737159.4.3.293.
    1. McFarland J, Sappington SW. A Ganglioneuroma in the neck of a child. Am J Pathol. 1935;11(3):429–48.
    1. Cushing H, Wolbach SB. The transformation of a malignant paravertebral sympathicoblastoma into a Benign Ganglioneuroma. Am J Pathol. 1927;3(3):203–16.
    1. Sophian L. Mediastinal Ganglioneuroma. Ann Surg. 1935;101(3):827–33. doi: 10.1097/00000658-193503000-00002.
    1. Moschovi M, Arvanitis D, Hadjigeorgi C, Mikraki V, Tzortzatou-Stathopoulou F. Late malignant transformation of dormant ganglioneuroma? Med Pediatr Oncol. 1997;28(5):377–81. doi: 10.1002/(SICI)1096-911X(199705)28:5<377::AID-MPO11>;2-8.
    1. Kulkarni AV, Bilbao JM, Cusimano MD, Muller PJ. Malignant transformation of ganglioneuroma into spinal neuroblastoma in an adult. Case report. J Neurosurg. 1998;88(2):324–7. doi: 10.3171/jns.1998.88.2.0324.
    1. Schulman H, Laufer L, Barki Y, Philip M, Mares AJ, Maor E, et al. Ganglioneuroma: an 'incidentaloma' of childhood. Eur Radiol. 1998;8(4):582–4. doi: 10.1007/s003300050438.
    1. Cronin EM, Coffey JC, Herlihy D, Romics L, Aftab F, Keohane C, et al. Massive retroperitoneal ganglioneuroma presenting with small bowel obstruction 18 years following initial diagnosis. Ir J Med Sci. 2005;174(2):63–6. doi: 10.1007/BF03169133.
    1. Przkora R, Perez-Canto A, Ertel W, Heyde CE. Ganglioneuroma : primary tumor or maturation of a suspected neuroblastoma? Eur Spine J. 2006;15(3):363–5. doi: 10.1007/s00586-005-0964-9.
    1. Ponce-Camacho MA, Diaz de Leon-Medina R, Miranda-Maldonado I, Garza-Guajardo R, Hernandez-Salazar J, Barboza-Quintana O. A 5-year-old girl with a congenital ganglioneuroma diagnosed by fine needle aspiration biopsy: a case report. Cytojournal. 2008;5:5.
    1. Arce Gil J, Arce Terroba Y, Angerri Feu O, Caffaratti Sfulcini J, Garat Barredo JM, Villavicencio MH. Retroperitoneal ganglioneuroma in the infancy. Actas Urol Esp. 2008;32(5):567–70. doi: 10.1016/S0210-4806(08)73886-5.
    1. Rozmus J, Langer M, Murphy JJ, Dix D. Multiple persistent ganglioneuromas likely arising from the spontaneous maturation of metastatic neuroblastoma. J Pediatr Hematol Oncol. 2012;34(2):151–3. doi: 10.1097/MPH.0b013e318221ca82.
    1. Geraci AP, de Csepel J, Shlasko E, Wallace SA. Ganglioneuroblastoma and ganglioneuroma in association with neurofibromatosis type I: report of three cases. J Child Neurol. 1998;13(7):356–8. doi: 10.1177/088307389801300712.
    1. Duhem-Tonnelle V, Vinchon M, Defachelles AS, Cotten A, Dhellemmes P. Mature neuroblastic tumors with spinal cord compression: report of five pediatric cases. Childs Nerv Syst. 2006;22(5):500–5. doi: 10.1007/s00381-005-0009-z.
    1. Geoerger B, Hero B, Harms D, Grebe J, Scheidhauer K, Berthold F. Metabolic activity and clinical features of primary ganglioneuromas. Cancer. 2001;91(10):1905–13. doi: 10.1002/1097-0142(20010515)91:10<1905::AID-CNCR1213>;2-4.
    1. De Bernardi B, Gambini C, Haupt R, Granata C, Rizzo A, Conte M, et al. Retrospective study of childhood ganglioneuroma. J Clin Oncol. 2008;26(10):1710–6. doi: 10.1200/JCO.2006.08.8799.
    1. Cohn SL, Pearson AD, London WB, Monclair T, Ambros PF, Brodeur GM, et al. The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol. 2009;27(2):289–97. doi: 10.1200/JCO.2008.16.6785.
    1. Okamatsu C, London WB, Naranjo A, Hogarty MD, Gastier-Foster JM, Look AT, et al. Clinicopathological characteristics of ganglioneuroma and ganglioneuroblastoma: a report from the CCG and COG. Pediatr Blood Cancer. 2009;53(4):563–9. doi: 10.1002/pbc.22106.
    1. Brodeur GM, Pritchard J, Berthold F, Carlsen NL, Castel V, Castelberry RP, et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol. 1993;11(8):1466–77.
    1. Spitz R, Hero B, Ernestus K, Berthold F. FISH analyses for alterations in chromosomes 1, 2, 3, and 11 define high-risk groups in neuroblastoma. Med Pediatr Oncol. 2003;41(1):30–5. doi: 10.1002/mpo.10313.
    1. Berthold F, Boos J, Burdach S, Erttmann R, Henze G, Hermann J, et al. Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial. Lancet Oncol. 2005;6(9):649–58. doi: 10.1016/S1470-2045(05)70291-6.
    1. Hero B, Simon T, Spitz R, Ernestus K, Gnekow AK, Scheel-Walter HG, et al. Localized infant neuroblastomas often show spontaneous regression: results of the prospective trials NB95-S and NB97. J Clin Oncol. 2008;26(9):1504–10. doi: 10.1200/JCO.2007.12.3349.
    1. Simon T, Spitz R, Faldum A, Hero B, Berthold F. New definition of low-risk neuroblastoma using stage, age, and 1p and MYCN status. J Pediatr Hematol Oncol. 2004;26(12):791–6.
    1. Kaplan EL, Meier P. Nonparametric Estimation from Incomplete Observations. J Am Stat Assoc. 1958;53(282):457–81. doi: 10.1080/01621459.1958.10501452.
    1. Coldman AJ, Elwood JM. Examining survival data. Can Med Assoc J. 1979;121(8):1065–8.
    1. Kaatsch P, Spix J. German Childhood Cancer Registry - Report 2013/2014 (1980-2013). Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI) at the University Medical Center of the Johannes Gutenberg University Mainz; 2014. .
    1. Joshi VV, Cantor AB, Altshuler G, Larkin EW, Neill JS, Shuster JJ, et al. Recommendations for modification of terminology of neuroblastic tumors and prognostic significance of Shimada classification. A clinicopathologic study of 213 cases from the Pediatric Oncology Group. Cancer. 1992;69(8):2183–96. doi: 10.1002/1097-0142(19920415)69:8<2183::AID-CNCR2820690828>;2-C.
    1. Haas D, Ablin AR, Miller C, Zoger S, Matthay KK. Complete pathologic maturation and regression of stage IVS neuroblastoma without treatment. Cancer. 1988;62(4):818–25. doi: 10.1002/1097-0142(19880815)62:4<818::AID-CNCR2820620430>;2-K.
    1. Garvin JH, Jr, Lack EE, Berenberg W, Frantz CN. Ganglioneuroma presenting with differentiated skeletal metastases. Report of a case. Cancer. 1984;54(2):357–60. doi: 10.1002/1097-0142(19840715)54:2<357::AID-CNCR2820540230>;2-4.
    1. Eyre-Brook AL, Hewer TF. Spontaneous disappearance of neuroblastoma with maturation to ganglioneuroma. J Bone Joint Surg Br. 1962;44-B(4):886–90.
    1. Hayes FA, Green AA, Rao BN. Clinical manifestations of ganglioneuroma. Cancer. 1989;63(6):1211–4. doi: 10.1002/1097-0142(19890315)63:6<1211::AID-CNCR2820630628>;2-1.
    1. Nishihira H, Toyoda Y, Tanaka Y, Ijiri R, Aida N, Takeuchi M, et al. Natural course of neuroblastoma detected by mass screening: s 5-year prospective study at a single institution. J Clin Oncol. 2000;18(16):3012–7.

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