Journal of Clinical Neuroscience xxx (2011) xxx–xxx
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Case Report
Cervical extramedullary lymphomatoid granulomatosis Nicola Montano a,⇑, Corrado Lucantoni a, Luigi Maria Larocca b, Fabio Papacci a, Mario Meglio a a b
Institute of Neurosurgery, Catholic University, 8 Largo Agostino Gemelli, Rome 00168, Italy Institute of Pathology, Catholic University, Rome, Italy
a r t i c l e
i n f o
Article history: Received 26 June 2010 Accepted 31 August 2010 Available online xxxx Keywords: Lymphomatoid granulomatosis MRI Spinal cord
a b s t r a c t Lymphomatoid granulomatosis (LYG) is a rare multisystem disease involving most frequently the lung, kidney and skin. LYG is characterized by an infiltration of atypical lymphocytoid and plasmocytoid cells, with granulomatous inflammation in an angiocentric and angiodestructive pattern. There have been only a few reports of spinal involvement of LYG. To our knowledge, we report the first patient with cervical extramedullary LYG undergoing surgical removal of a lesion causing spinal cord compression, and review the pertinent literature. The patient underwent C5-partial T1 laminectomy with partial removal of the lesion and decompression of the spinal cord. A diagnosis of a grade III LYG was made and chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) was administered. The patient was in good neurological condition at the 6-month follow-up but died 5 months later because of systemic progression of the disease. Although prognosis of LYG remains poor, surgery can be considered to improve pain relief and neurological morbidity of spinal LYG. Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction Lymphomatoid granulomatosis (LYG) is a rare disease characterized by infiltration of various organs by atypical lymphocytoid and plasmocytoid cells, showing granulomatous inflammation in an angiocentric and angiodestructive pattern.1 This multisystem disease involves the lung, kidney and skin most frequently; central nervous system (CNS) localization is reported in one-third of patients.1 Spinal involvement has been described rarely.2–4 To our knowledge, we report the first patient with cervical extramedullary LYG submitted to surgical removal of a lesion, and review the pertinent literature.
2. Case report A 60-year-old man was admitted to our department because of a 4-month history of neck and right arm pain unresponsive to medical therapy. He had complained of right arm weakness and gait disturbance 3 weeks prior to admission. Neurological examination showed mild spastic paraparesis, weakness of the right arm, and C5–T1 right hypoesthesia. Past medical anamnesis was unremarkable. Routine blood and urine laboratory studies showed no pathological findings and his chest radiograph was normal. Spinal MRI revealed a right extra- and intra-dural–extramedullary enhancing mass at the C5–T1 levels, compressing the spinal cord, with para⇑ Corresponding author. Tel.: +39 0630154120; fax: +39 063051343. E-mail address:
[email protected] (N. Montano).
vertebral extension through the neural foramina (Fig. 1). The patient underwent a C5–C6–C7 and partial T1 laminectomy, and removal of the extra- and intra-dural component of the mass with spinal cord decompression was performed. His post-operative course was uneventful with neck and right arm pain remission; progressive improvement of neurological deficits was observed. On histological examination, a mass consisting of small CD3positive lymphocytes, with many clusters of PAX-5 and LMP-1 positive immature cells, was evident (Supplementary Fig. 1). The cells showed uniform expression of CD20, BCL-6 and MUM-1 and frequent expression of CD38 and CD138. Many PGM-1-positive histiocytes were observed. Cell proliferation had a perivascular distribution with angiocentric and angiodestructive patterns. These findings were suggestive of a grade III lymphomatoid granulomatosis (Supplementary Fig. 1, Fig. 2). A post-operative total body CT-scan showed swelling of submandibular, jugular, mediastinal and inguinal lymph nodes without other systemic pathological findings. However, systemic involvement was documented on bone marrow biopsy. As a result, the patient was submitted to four cycles of adjuvant cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy. At 6-month follow-up, the patient was in good neurological condition. Nevertheless, a repeat total-body CT-scan and a whole body 18-fluoro-2-deoxyglucose positron emission tomography scan documented systemic progression of the disease, with multiple pathological lesions of bone, lymph nodes and spleen. No progression of the residual cervical lesion was documented. The patient died 5 months later due to systemic progression of the disease.
0967-5868/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2010.08.042
Please cite this article in press as: Montano N et al. Cervical extramedullary lymphomatoid granulomatosis. J Clin Neurosci (2011), doi:10.1016/ j.jocn.2010.08.042
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Case Report / Journal of Clinical Neuroscience xxx (2011) xxx–xxx
Fig. 1. (A) Coronal, (B) sagittal and (C) axial spinal T1-weighted with gadolinium MRI showing the enhancing mass (black arrows) compressing and displacing the spinal cord; extradural extension through the neural foramina (B, C) is evident.
3. Discussion LYG is an angiocentric and angiodestructive process and it is characterized by B cell proliferation of uncertain malignant potential, associated with a T cell infiltration.5 The disease shows inflammatory granulomatous as well as lymphoproliferative features and it is considered an Epstein-Barr virus (EBV)-positive B-cell proliferation associated with an exuberant T cell reaction. A grading system of LYG (from I to III) is based on the number of atypical lymphocytes, EBV-positive B-cells and amount of necrosis.6 LYG involves the lungs in most patients, but may also involve several extrapulmonary sites, including the CNS.1,7 Spinal involvement of LYG is rare, however, there are a few reports (Supplementary Table 1).2–4 In the literature, patients were diagnosed by lung biopsy and spinal involvement ranged from a large intra-axial mass lesion3 to cervical spotty lesions4; thickening of the posterior meninges was also described.2 In our patient, an enhancing extramedullary mass with intra– and extra-dural components and extension in the paravertebral space through the neural foramina with compression of spinal cord was evident. Thus, because of rapid worsening of neurological symptoms and absence of systemic involvement on routine pre-operative laboratory and radiological examination, the patient was treated with surgical removal of the lesion to decompress the spinal cord and improve neurological deficits, as well obtaining tissue for histological diagnosis. Although stable neurological disease has been reported for a patient undergoing rituximab therapy at 18-month follow-up,4 surgery can rapidly improve pain relief and neurological morbidity of LYG for patients with spinal cord compression. However, the prognosis of patients with spinal LYG remains poor,3 due to systemic progression of disease, as shown by our patient.
Fig. 2. Tissue sections of the cervical mass showing (A, B) massive proliferation and angiocentric distribution of lymphoid cells (hematoxylin and eosin; [A] 200, [B] 400). (This figure is available in colour at www.sciencedirect.com)
Appendix A. Supplementary material Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.jocn.2010.08.042. References 1. Katzenstein AL, Carrington CB, Liebow AA. Lymphomatoid granulomatosis: a clinicopathologic study of 152 cases. Cancer 1979;43:360–73. 2. Collins S, Helme RD. Lymphomatoid granulomatosis presenting as a progressive cervical cord lesion. Aust N Z J Med 1989;19:144–6. 3. Herderscheê D, Troost D, de Visser M, et al. Lymphomatoid granulomatosis: clinical and histopathological report of a patient presenting with spinal cord involvement. J Neurol 1988;235:432–4. 4. Ishiura H, Morikawa M, Hamada M, et al. Lymphomatoid granulomatosis involving central nervous system successfully treated with rituximab alone. Arch Neurol 2008;65:662–5. 5. Heslop HE. Biology and treatment of Epstein-Barr virus-associated non-Hodgkin lymphomas. Hematology Am Soc Hematol Educ Program 2005;1:260–6. 6. Lipford Jr EH, Margolick JB, Longo DL, et al. Angiocentric immunoproliferative lesions: a clinicopathologic spectrum of post-thymic T-cell proliferations. Blood 1988;72:1674–81. 7. Liebow AA, Carrington CR, Friedman PJ. Lymphomatoid granulomatosis. Hum Pathol 1972;3:457–558.
Please cite this article in press as: Montano N et al. Cervical extramedullary lymphomatoid granulomatosis. J Clin Neurosci (2011), doi:10.1016/ j.jocn.2010.08.042
