open access

Vol 69, No 5 (2018)
Case report
Published online: 2018-09-12
Submitted: 2017-08-16
Accepted: 2017-12-28
Get Citation

Clinical case seminar: Familial intracranial germinoma

Mirjana Doknic, Dragan Savic, Emilija Manojlovic-Gacic, Raicevic Savo, Jelena Bokun, Tatjana Milenkovic, Sonja Pavlovic, Misa Vreca, Marina Andjelkovic, Marko Stojanovic, Dragana Miljic, Sandra Pekic, Milan Petakov, Danica Grujicic
DOI: 10.5603/EP.2018.0060
·
Pubmed: 30379323
·
Endokrynologia Polska 2018;69(5):612-618.

open access

Vol 69, No 5 (2018)
Case report
Published online: 2018-09-12
Submitted: 2017-08-16
Accepted: 2017-12-28

Abstract

Background. Intracranial germinomas (ICG) are uncommon brain neoplasms with extremely rare familial occurance. Since ICG invades hypothalamus and/or pituitary, the endocrine dysfunction is one of the common determinants of these tumors. We presented two brothers with the history of ICG. Patient 1 is a 25-year-old male who had been suffering from the weakness of the right half of his body at the age of 18. Cranial MRI revealed mass lesion in the left thalamus. He underwent neurosurgery, tumor was removed completely. Histopathological (HP) and immunohistochemical analyses verified the diagnosis of pure germinoma. He experienced complete remission of the tumor after a radiation therapy. At the age of 22 the diagnosis of isolated growth hormone deficiency (IGHD) was established and GH replacement was initiated. Patient 2 is a 20-year old boy who was presented with diabetes insipidus at the age of 12. MRI detected tumor in the third ventricle and pineal region. After the endoscopic tumor biopsy the HP diagnosis was pure germinoma. He received chemotherapy followed by radiotherapy, and treated with GH during childhood. At the age of 18 GH replacement was reintroduced. A six month follow-up during the next two years in both brothers demonstrated the IGF1 normalization with no MRI signs of tumor recurrence. Conclusion. To the best of our knowledge so far, only six reports have been published related to familial ICG. The presented two brothers are the first report of familial ICG case outside of Japan. They are treated successfully with GH therapy in adult period. < /p > < p >

Abstract

Background. Intracranial germinomas (ICG) are uncommon brain neoplasms with extremely rare familial occurance. Since ICG invades hypothalamus and/or pituitary, the endocrine dysfunction is one of the common determinants of these tumors. We presented two brothers with the history of ICG. Patient 1 is a 25-year-old male who had been suffering from the weakness of the right half of his body at the age of 18. Cranial MRI revealed mass lesion in the left thalamus. He underwent neurosurgery, tumor was removed completely. Histopathological (HP) and immunohistochemical analyses verified the diagnosis of pure germinoma. He experienced complete remission of the tumor after a radiation therapy. At the age of 22 the diagnosis of isolated growth hormone deficiency (IGHD) was established and GH replacement was initiated. Patient 2 is a 20-year old boy who was presented with diabetes insipidus at the age of 12. MRI detected tumor in the third ventricle and pineal region. After the endoscopic tumor biopsy the HP diagnosis was pure germinoma. He received chemotherapy followed by radiotherapy, and treated with GH during childhood. At the age of 18 GH replacement was reintroduced. A six month follow-up during the next two years in both brothers demonstrated the IGF1 normalization with no MRI signs of tumor recurrence. Conclusion. To the best of our knowledge so far, only six reports have been published related to familial ICG. The presented two brothers are the first report of familial ICG case outside of Japan. They are treated successfully with GH therapy in adult period. < /p > < p >
Get Citation

Keywords

intracranial germinoma, familial occurrence, hypopituitarism, GH replacement

About this article
Title

Clinical case seminar: Familial intracranial germinoma

Journal

Endokrynologia Polska

Issue

Vol 69, No 5 (2018)

Pages

612-618

Published online

2018-09-12

DOI

10.5603/EP.2018.0060

Pubmed

30379323

Bibliographic record

Endokrynologia Polska 2018;69(5):612-618.

Keywords

intracranial germinoma
familial occurrence
hypopituitarism
GH replacement

Authors

Mirjana Doknic
Dragan Savic
Emilija Manojlovic-Gacic
Raicevic Savo
Jelena Bokun
Tatjana Milenkovic
Sonja Pavlovic
Misa Vreca
Marina Andjelkovic
Marko Stojanovic
Dragana Miljic
Sandra Pekic
Milan Petakov
Danica Grujicic

References (35)
  1. Kyritsis AP. Management of primary intracranial germ cell tumors. J Neurooncol. 2010; 96(2): 143–149.
  2. Okamoto K, Ito J, Ishikawa K, et al. Atrophy of the basal ganglia as the initial diagnostic sign of germinoma in the basal ganglia. Neuroradiology. 2002; 44(5): 389–394.
  3. Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007; 114(2): 97–109.
  4. Aoyama I, Kondo A, Ogawa H, et al. Germinoma in siblings: case reports. Surg Neurol. 1994; 41(4): 313–317.
  5. Kido G, Takeuchi T, Tsukiyama T, et al. [Tumor of the pineal region in three brothers]. No Shinkei Geka. 1984; 12(8): 975–980.
  6. Wakai S, Segawa H, Kitahara S, et al. Teratoma in the pineal region in two brothers. Case reports. J Neurosurg. 1980; 53(2): 239–243.
  7. Nakasu S, Handa J, Hazama F, et al. Suprasellar yolk-sac tumor in two sisters. Surg Neurol. 1983; 20(2): 147–151.
  8. Nitta N, Fukami T, Nozaki K. Germinoma in two brothers: case report. Neurol Med Chir (Tokyo). 2013; 53(10): 703–706.
  9. Shimizu K, Mineharu Y, Imamura H, et al. Intracranial germinomas in a father and his son. Childs Nerv Syst. 2014; 30(12): 2143–2146.
  10. Gabeau-Lacet D, Grant E, Stemmer-Rachamimov A, et al. Sellar abnormalities in female first-degree relatives. Clin Neurol Neurosurg. 2008; 110(2): 202–206.
  11. Grahovac G, Alden T, Nitin W. Mixed pineal mature teratoma and germinoma in two brothers of the fraternal triplets. Childs Nerv Syst. 2017; 33(5): 859–863.
  12. Horvath A, Korde L, Greene MH, et al. Functional phosphodiesterase 11A mutations may modify the risk of familial and bilateral testicular germ cell tumors. Cancer Res. 2009; 69(13): 5301–5306.
  13. Kamakura Y, Hasegawa M, Minamoto T, et al. C-kit gene mutation: common and widely distributed in intracranial germinomas. J Neurosurg. 2006; 104(3 Suppl): 173–180.
  14. Fukushima S, Otsuka A, Suzuki T, et al. Intracranial Germ Cell Tumor Genome Analysis Consortium (iGCT Consortium). Mutually exclusive mutations of KIT and RAS are associated with KIT mRNA expression and chromosomal instability in primary intracranial pure germinomas. Acta Neuropathol. 2014; 127(6): 911–925.
  15. Ichimura K, Fukushima S, Totoki Y, et al. Intracranial Germ Cell Tumor Genome Analysis Consortium. Recurrent neomorphic mutations of MTOR in central nervous system and testicular germ cell tumors may be targeted for therapy. Acta Neuropathol. 2016; 131(6): 889–901.
  16. Karapetis CS, Khambata-Ford S, Jonker DJ, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008; 359(17): 1757–1765.
  17. Do H, Krypuy M, Mitchell PL, et al. High resolution melting analysis for rapid and sensitive EGFR and KRAS mutation detection in formalin fixed paraffin embedded biopsies. BMC Cancer. 2008; 8: 142.
  18. Yang X, Qian J, Sun A, et al. RAS mutation analysis in a large cohort of Chinese patients with acute myeloid leukemia. Clin Biochem. 2013; 46(7-8): 579–583.
  19. Wang L, Yamaguchi S, Burstein MD, et al. Novel somatic and germline mutations in intracranial germ cell tumours. Nature. 2014; 511(7508): 241–245.
  20. Tanabe M, Mizushima M, Anno Y, et al. Intracranial germinoma with Down's syndrome: a case report and review of the literature. Surg Neurol. 1997; 47(1): 28–31.
  21. Nakata Y, Yagishita A, Arai N. Two patients with intraspinal germinoma associated with Klinefelter syndrome: case report and review of the literature. AJNR Am J Neuroradiol. 2006; 27(6): 1204–1210.
  22. Fukushima S, Yamashita S, Kobayashi H, et al. Intracranial Germ Cell Tumor Genome Analysis Consortium (The iGCTConsortium). Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas. Acta Neuropathol. 2017; 133(3): 445–462.
  23. Smith AA, Weng E, Handler M, et al. Intracranial germ cell tumors: a single institution experience and review of the literature. J Neurooncol. 2004; 68(2): 153–159.
  24. Foote M, Millar BA, Sahgal A, et al. Clinical outcomes of adult patients with primary intracranial germinomas treated with low-dose craniospinal radiotherapy and local boost. J Neurooncol. 2010; 100(3): 459–463.
  25. Sa ki N, Tamaki K, Murai H, et al. Long-term outcome of endocrine function in patients with neurohypophyseal germinomas. Endocr J. 2000; 47(1): 83–89.
  26. Aida T, Abe H, Fujieda K, et al. Endocrine functions in children with suprasellar germinoma. Neurol Med Chir (Tokyo). 1993; 33(3): 152–157.
  27. Uchino Y, Saeki N, Iwadate Y, et al. Recurrence of sellar and suprasellar tumors in children treated with hGH. Endocr J. 2000; 47(SupplMarch): S33–S36.
  28. Kortmann RD. Current concepts and future strategies in the management of intracranial germinoma. Expert Rev Anticancer Ther. 2014; 14(1): 105–119.
  29. Fuller BG, Kapp DS, Cox R. Radiation therapy of pineal region tumors: 25 new cases and a review of 208 previously reported cases. Int J Radiat Oncol Biol Phys. 1994; 28(1): 229–245.
  30. Janjetovic S, Bokemeyer C, Fiedler W, et al. Late recurrence of a pineal germinoma 14 years after radiation and chemotherapy: a case report and review of the literature. Onkologie. 2013; 36(6): 371–373.
  31. Kiltie AE, Collins CD, Gattamaneni HR, et al. Relapse of intracranial germinoma 23 years postirradiation in a patient given growth hormone replacement. Med Pediatr Oncol. 1997; 29(1): 41–44.
  32. Allen DB, Backeljauw P, Bidlingmaier M, et al. GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults. Eur J Endocrinol. 2016; 174(2): P1–P9.
  33. Chung TT, Drake WM, Plowman PN, et al. No clear evidence for an association between GH replacement and relapse of intracranial germ cell tumours: single centre and KIMS experience. Eur J Endocrinol. 2010; 163(2): 357–358.
  34. Yuen KCJ, Heaney AP, Popovic V. Considering GH replacement for GH-deficient adults with a previous history of cancer: a conundrum for the clinician. Endocrine. 2016; 52(2): 194–205.
  35. Brignardello E, Felicetti F, Castiglione A, et al. GH replacement therapy and second neoplasms in adult survivors of childhood cancer: a retrospective study from a single institution. J Endocrinol Invest. 2015; 38(2): 171–176.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Via MedicaWydawcą serwisu jest  "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl