Metástase de Mieloma Múltiplo em Parênquima Cerebral.
5. Participant: Erasto Gaertner Hospital Neurosurgeon 6 Participant: Medical School student.
SUMÁRIO
O mieloma múltiplo em sistema nervoso central (SNC) é uma condição extremamente rara, sendo descrita em pouco mais de 100 casos na literatura. Neste artigo, os autores descrevem o caso de uma paciente do sexo feminino de 55 anos, submetida a transplante autólogo de medula óssea, e, mais tarde, à biopsia de tecido cerebral com confirmação imunohistoquímica, revelando tecido cerebral infiltrado por grande quantidade de plasmócitos, compatível com a história clínica de mieloma múltiplo. A paciente foi então submetida a radioterapia adjuvante em SNC, permanecendo em acompanhamento ambulatorial com a oncologia clínica e utilizando pamidronato dissódico mensal. Mesmo sendo uma afecção incurável, a radioterapia mostrou-se importante para o controle local.
Palavras-chave: mieloma múltiplo; plasmócitos; radiotera-
pia; sistema nervoso central.
ABSTRACT
Multiple myeloma in the central nervous system (CNS) is an extremely rare condition, described in over 100 cases in the literature. In this article, the authors report the case of a 55-year-old female patient, subjected to an autologous bone marrow transplant, and, furthermore, to a brain tissue biopsy with immunohistochemistry confirmation, revealing infiltra- tion by a great amount of plasma cells, compatible with the clinical history of multiple myeloma. The patient was then subjected to CNS adjuvant radiotherapy, with constant ob- servation by clinical oncology and monthly pamidronate di- sodium prescription. Despite being an incurable pathology, radiation therapy showed important local control.
Keywords: multiple myeloma; plasma cells; radiation thera-
py; central nervous system.
I
ntroduCtIonMultiple myeloma is a progressive and incurable neoplasia of the B cells, characterized by the unregulated and clonal proliferation of the bone marrow plasma cells, which produce and secrete monoclonal immunoglobulin (Ig) or its fragments , called protein M8. Extramedullary involvement such as liver,
skin, perineum, endocrine glandules, lymph nodes, digestive tract, nasopharynx, larynx, or superior respiratory tract is seen in less than 5% of patients7. Central nervous system involvement
is not common, being observed in 1% of multiple myeloma cases, as dural myeloma or intraparenchymal infiltration, or yet with diffuse leptomeningeal involvement1,5,6. The male/
female rate is 1.4 / 1.010, being more common over 65 years of
age . Nieuwenhuizen et al mention 109 cases of CNS multiple myeloma reported in the literature7.
C
Aser
eportA fifty-five years-old female patient was evaluated at Erasto Gaertner Hospital (HEG) in December 2009 with a history of multiple myeloma and thoracic tomography (CT) in June 2009 indicating fracture in the T10 thoracic spine, with signs of spi- nal cord compression. At admission she mentioned that, for six months, she had been having pain in a left arm, for 30 days with paresthesias in both legs and for one week with weakness of inferior limbs . In December 2009, she was started on VAD scheme (vincristine, doxorubicin, dexamethasone) chemothe- rapy for 5 days. Soon after, she was evaluated by radiotherapy, orthopedics and neurology services at HEG. In February 2010 she was subjected to an spinal arthrodesis and fixation of ver- tebrae T7-L1. Biopsy material revealed bone marrow infiltra- tion of plasmacytic cells, compatible with multiple myeloma.
In May 2010 she underwent new chemotherapy with a VAD regimen for 5 days. In July , bone marrow cells were collected for autologous transplantation (TAMO) , which was done a month later. In October she was hospitalized for sudden headache: CT showed multiple lesions compatible to myelo- ma. She was also subjected to brain magnetic resonance (MRI) , which showed a cortico-subcortical left paramedian solid no- dular occipital lesion, measuring approximately 25 x 20 mm, and multiple ill-defined spots in the supratentorial white matter with asymmetrical distribution. The patient was subjected to
craniotomy with tumor resection with the following histolo- gical diagnosis: extensively necrotic brain tissue with a great amount of plasma cells, compatible with myeloma. Imunohis- tochemical study is presented as follows (Table 1).
Table 1 - Imunohistochemical Pannel Marker Result
CD 138 Positive In The Plasma Cells CD 20 Negative
CD 3 Positive In The T Lymphocytes KI 67 Positive In 20% Of The Plasma Cell Core
Pathology reported that the brain tissue in question was in- filtrated by a great amount of plasma cells, compatible with the clinical history of multiple myeloma. CNS adjuvant ra- diotherapy 2D with a total dosage of 37,5Gy (15 fractions of 250cGy) was then performed. She is currently under follow- up as an outpatient.
d
IsCussIonMultiple myeloma (MM) is a progressive and incurable neopla- sia of the B cells, representing 10% of hematological tumors and only 1% of all the malignant neoplasia4,9 . CNS involve-
ment is not common, being observed in less than 1% of cases of patients with MM1,5,6. Other extra involvement sites such as
liver, skin, perineum, endocrinal glandules, lymph nodes, di- gestive tract, nasopharynx, larynx, or superior respiratory tract is observed in less than 5% of the patients7.
Although considered incurable, MM treatment has advanced with the introduction of drugs like thalidomide, lenadomide and bortezomib3. New parameters of prognosis have been pro-
posed with the combination of β2 microglobulin and serum albumin, resulting in a system of simple and reliable staging called International Staging System2,8,9, described in table 2.
J Bras Neurocirurg 22 (3): 124-127, 2011
Francisco AF, Pizzatto RF, Smaniotto GH, Morais RL, Morais AL, Brito RN - Multiple Mieloma Metastases In Brain Parenchyma.
Table 2 - International Staging System for multiple myeloma
Stage Durie-Salmon systema International Staging System
I All of the following:
• Hemoglobin level > 10 mg/dL • Serum calcium level normal or 12 mg/dL
• On x-ray, normal bone structure (scale 0) or solitary bone plas- macytoma only
• Low M-component production rates: Immunoglobulin (Ig) - G value < 5 g/dL IgA value < 3 g/dL
Bence-Jones protein level < 4 g/24 h
Serum β2-microglobulin level < 3.5 mg/L Serum albumin level > 3.5 g/d
II Fitting neither stage I nor stage III Not stage I or IIIb III One or more of the following:
• Hemoglobin level < 8.5 mg/dL • Serum calcium level > 12 mg/dL • Advanced lytic bone lesions (scale 3) • High M-component production rates: IgG value > 7 g/dL
IgA value > 5 g/dL
Bence-Jones protein level > 12 g/24h
Serum β2-microglobulin level > 5.5 mg/L
aSubclassification: A = relatively normal renal function (serum creatinine (Scr) value < 2.0 mg/dL);
B = abnormal renal function (Scr > 2.0 mg/dL)
bFor stage II, there are two categories: serum β2 - microglobulin level < 3.5 mg/L, but serum albumin level < 3.5 mg/dL; or serum β2 - microglobulin level of 3.5
to < 5.5 mg/L, irrespective of the serum albumin level. Ig = immunoglobulin
Adapted from Durie BG, Salmon SE: Cancer 36:842-854, 1975; and Greipp PR, San Miguel J, Durie BG, at al: J Clin Oncol 23:3412-3420, 2005.
f
InAlC
onsIderAtIonsDue to the little information about the ideal treatment, the team preferred to use adjuvance with radiotherapy, considering the necessity of local control, aiming to impede or minimize the chance of CNS recurrence . During the treatment, the patient didn´t complain about any adverse reaction to radiotherapy, evolving in a satisfactory way and is currently being followed- up at the HEG Clinical Oncology, under monthly pamidro- nate disodium.
Consent
The Hospital Research Ethics Committee approved this pro- ject.
r
eferenCes1. Angtuaco EJ, Fassas ABT, Walker R, Sethi R, Barlogie B. Mul- tiple Myeloma: Clinical Review and Diagnostic Imaging. Ra- diology. 2004 Apr; 231(1):11-23
2. Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, et al. International staging system for multiple my- eloma. J Clin Oncol. 2005;23(15):3412-20.
3. Hideshima T, Anderson KC. Molecular mechanisms of novel therapeutic approaches for multiple myeloma. Nat Rev Can-
cer. 2002 Dec;2(12):927-37.
4. Hussein MA, Juturi JV, Lieberman I. Multiple myeloma: pres- ent and future. Curr Opin Oncol. 2002;14(1):31-5.
5. Méndez CE, Hwang BJ, Destian S, Mazumder A, Jagannath S, Vesole DH. Intracranial multifocal dural involvement in multiple myeloma: case report and review of the literature.
6. Naqi R, Azeemuddin M, Ahsan H. Central nervous system involvement in multiple myeloma. J Pak Med Assoc. 2010 Sep;(60): 771-3
7. Nieuwenhuizen L, Biesma DH. Central nervous system myelomatosis: review of the literature. Eur J Haematol. 2007;80(1):1-9. Epub 2007 Oct 23.
8. Silva ROP, Brandão KMA, Pinto PVM, Faria RMD, Clementino NCD, Silva CMF, et al . Mieloma múltiplo: características clínicas e laboratoriais ao diagnóstico e estudo prognóstico.
Rev Bras Hematol Hemoter. 2009;31(2):63-8
9. Rajkumar SV, Kyle RA. Plasma cell disorders. In: Goldman L,
Ausiello D, editors. Cecil Textbook of Medicine 23ed. Philadel- phia: Saunders; 2007. p1426-37.
10. Sorenson SM, Gentili A, Masih S. Multiple Myeloma. (Online) 2011 (Cited 2008 October 17). Available from URL: http:// emedicine.medscape.com/article/391742-overview.
C
orrespondIngA
uthor HOSPITAL ERASTO GAERTNER / LPCC RADIOTHERAPY SERVICECURITIBA / PR
Correspondent author: Allison de Freitas Francisco e-mail: allisonfrancisco@hotmail.com
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