|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 26, No 27 (September 20), 2008: pp. 4507-4509 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2008.17.0787
Intracranial Granulocytic Sarcoma After Chemotherapy for Pineal Germinoma and Testicular CancerDivision of Neurology, Azienda Ospedaliera-Universitaria di Verona, Verona, Italy
Division of Medical Oncology, Central Hospital, Bolzano, Italy
Division of Neurology, Azienda Ospedaliera-Universitaria di Verona, Verona, Italy
Division of Pathology, Azienda Ospedaliera-Universitaria di Verona, Verona, Italy
Institute of Pathology, San Raffaele Hospital, Milan, Italy
Division of Medical Oncology, Central Hospital, Bolzano, Italy A 29-year-old male patient was diagnosed with a seminoma of the pineal gland, leptomeningeal metastasis at the level of the first thoracic vertebra, and synchronously stage I embryonal carcinoma of the right testicle in 1998. He underwent an inguinal orchiectomy and four courses of chemotherapy according to PEB regimen (bleomycin 30 mg intravenously on days 2, 8 and 15; etoposide100 mg/m2 and cisplatin 20 mg/m2 intravenously on days 1 through 5). A magnetic resonance imaging (MRI) after two cycles showed a complete remission of the pineal gland germinoma and the epidural metastasis. Considering the excellent response of germ cell tumors to chemotherapy and the risk of long-term toxicity of radiation therapy in a young patient (intellectual dysfunction, growth retardation, endocrine dysfunction, and hearing loss), the conventional radiotherapy for pineal germinoma was omitted.1 In May 2006, the patient was referred to our institute for a neurologic evaluation due to behavioral disturbances, confusion, generalized asthenia, and headache accompanied with fever. He appeared obtunded and disoriented in time and space; no focal neurologic deficits were detected. Laboratory findings such as tumor markers (alpha-fetoprotein and human chorionic gonadotropin), lactate dehydrogenase concentration, inflammation indexes, and complete blood count were within the normal ranges. The CSF examination documented a mild hyperproteinorrachia (0.78 g/L) and the absence of neoplastic cells. A computed tomography scan of the brain did not show any alteration. Blood smears demonstrated nomal cells without evidence of leukemia. A brain MRI with gadolinium demonstrated an enhancing iperintense lesion in the right caudate nucleus, contiguous to the third ventriculus and to the antero-medial thalamus profile, with a subepedimal diffusion (Fig 1A). MRI of the spine did not show lesions. Total body computed tomography scan was normal. After wide spectrum antibiotic therapy plus steroids, both clinical conditions and neuroradiologic images improved (Fig 1B). During the next weeks, the patient developed periodic hypersomnia attacks associated with bulimia, irritability, sexual disinhibition, and other behavioral disturbances (Kleine Levin Syndrome). A new brain MRI with gadolinium demonstrated a progression of the lesion extending to controlateral hemisphere (Fig 1C). Clinical conditions of the patient rapidly worsened with left hemiplegia, comatous status, fever, and then death. The autopsy showed a necrohemorrhagic mass involving right thalamus, caudate nucleus and internal capsula extending to corpus callosum, and septum pellucidum and contra lateral basal ganglia; vasculitis signs were associated. A histopathologic examination of the mass revealed that tumor was composed of a cell necrosis and a diffuse proliferation of immature granulocytic elements (Figs 2A and 2B). Immunohistochemical staining demonstrated that tumor cells were positive for myeloperoxidase (Figs 3A and 3B). The histologic conclusion confirmed a diagnosis of extramedullar myeloid tumor of the brain.
Granulocytic sarcoma (GS), also called chloroma or myeloblastoma, is a rare solid extramedullary tumor composed of poorly differentiated cells of the myeloid series such as leukemic myeloblasts and/or myeloid precursor.2 The greenish tint exhibited by these tumors is attributed to myeloperoxidase present in myeloid cells.3 GS generally occurs concomitantly with myelodisplastic syndromes, myeloproliferative disorders, and myeloid leukemias,4,5 or as a complication of acute myeloid leukemia (AML), and may be the first sign of relapse after bone marrow transplantation.5-8 Rarely GS antedates the onset of systemic leukemia.3 A few cases of GS with no associated hematologic disorder have been described.3,9 The most frequently involved sites are subcutaneous tissue (4%), orbit (24%), paranasal sinus (11%), lymph node (11%), and bone and periosteum (5%).10 Intracranial involvement of the CNS by GS not associated with acute myeloid leukemia or myelodysplastic syndrome is rare.11 and it is not commonly described as a long-term complication in patients treated with chemotherapy for previous neoplasms. Prognosis of GS is poor, with generally short survival. In our opinion, the present case of pineal germinoma and synchronously embryonal carcinoma of the right testicle's favorable response to chemotherapy deserves attention for the subsequent development of a neoplasm usually associated with hematologic disease. Germ cell tumors are the most common solid tumors in young men aged between 20 and 35 years. While there is a high cure rate with chemotherapy in patients with this disease, some long-term complications from chemotherapy have been recognized, including secondary leukemia and therapy-related solid tumors. Most therapy-related leukemias following chemotherapy for germ cell cancer occur as acute myeloid leukemia (t-AML). Either cisplatin, an alkylating agent, or etoposide, a topoisomerase II inhibitor, may act synergistically in the induction of therapy-related leukemias, and the risk appears to be correlated with the total dose given.12 Leukemias following alchylating agent–containing regimens most often occur after an average interval of 5 to 7 years, and they are preceded by a preleukemic period of myelodysplasia, frequently progressing to M1 or M2 AML. The risk of induction leukemia after cisplatin increases with higher doses and a prolonged duration of therapy.13 Topoisomerase II inhibitor–related secondary leukemia is generally diagnosed 2 to 3 years following treatment and most commonly exhibits M4 or M5 phenotype. Most studies report a cumulative incidence of t-AML below 0.6% after 5 years of follow-up after cumulative etoposide doses of up to 2 g/mq,14-16 which corresponds to the maximal cumulative dose applied with first-line standard-dose chemotherapy such as four cycles of PEB. To our knowledge, this is the first case of extramedullary myeloid tumor presented as a long-term complication in a patient who didn't display hematologic disorder and was previously treated with combination PEB regimen. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
REFERENCES
1. Hupperets PS, Defesche HF, De Bruijckere LM, et al: The role of chemotherapy in intracranial germinoma: A case report. Ann Oncol 10:723-726, 1999 2. Byrd JC, Edenfield WJ, Shields DJ, et al: Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: A critical review. J Clin Oncol 13:1800-1816, 1995 3. Neiman RS, Barcos M, Berard C, et al: Granulocytic sarcoma: A clinicopathologic study of 61 biopsied cases. Cancer 48:1426-1437, 1981[CrossRef][Medline] 4. Krishnan K, Ross CW, Adams PT, et al: Neural cell-adhesion molecule (CD 56)-positive, t(8;21) acute myeloid leukemia (AML, M-2) and granulocytic sarcoma. Ann Hematol 69:321-323, 1994[CrossRef][Medline] 5. da Silva MA, Moriarty A, Schultz S, et al: Extramedullary disease in myelodysplastic syndromes. Am J Med 85:589-590, 1988[Medline] 6. Millot F, Facon T, Kerckaert JP, et al: Unusual recurrence of chronic myelogenous leukemia following bone marrow transplantation. Bone Marrow Transplant 7:393-395, 1991[Medline] 7. Orlandi E, Morra E, Lazzarino M, et al: Multiple granulocytic sarcoma during complete hematologic remission of acute nonlymphoid leukemia. Acta Hematologica 81:41-43, 1989 8. Thalhammer F, Gisslinger H, Chott A, et al: Granulocytic sarcoma of the prostate as the first manifestation of a late relapse of acute myelogenous leukemia. Ann Hematol 68:97-99, 1994[CrossRef][Medline] 9. Nickels J, Koivuniemi A, Heiskanen O: Granulocytic sarcoma (chloroma) of the cerebellum and meninges: A case report. Acta Neurochir (Wien) 46:297-301, 1979[CrossRef][Medline] 10. Smidt MH, de Bruin HG, van't Veer MB, et al: Intracranial granulocytic sarcoma (chloroma) may mimic a subdural hematoma. J Neurol 252:498-499, 2005[CrossRef][Medline] 11. Yoon DH, Cho KJ, Suh YL, et al: Intracranial granucolocytic sarcoma (chloroma) in a nonleukemic patient. J Korean Med Sci 2:173-178, 1987[Medline] 12. Kollmannsberger C, Kuzcyk M, Mayer F, et al: Late toxicity following curative treatment of testicular cancer. Semin Surg Oncol 17:275-281, 1999[CrossRef][Medline] 13. Travis LB, Holowaty EJ, Bergfeldt K, et al: Risk of leukemia after platinum-based chemotherapy for ovarian cancer. N Engl J Med 340:351-357, 1999 14. Bokemeyer C, Schmoll HJ: Secondary neoplasms following treatment of malignant germ cell tumors. J Clin Oncol 11:1703-1709, 1993 15. Pedersen-Bjergaard J, Daugaard G, Hansen SW: Increased risk of myelodysplasia and leukaemia after etoposide, cisplatin, and bleomycin for germ-cell tumours. Lancet 338:359-363, 1991[CrossRef][Medline] 16. Nichols CR, Breeden ES, Loehrer PJ: Secondary leukemia associated with a conventional dose of etoposide: Review of serial germ cell tumor protocols. J Natl Cancer Inst 85:36-40, 1993
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
