lymphomatoid granulomatosis ( lyg ) is a rare angiocentric and angiodestructive lymphoproliferative disease with granulomatous reaction involving the lungs most frequently , however , it may also involve the kidneys , skin and especially the central nervous system4,6,9,11 ) .
lyg is characterized by an infiltration of atypical lymphocytoid and plasmocytoid cells , with granulomatous inflammation in an angiocentric and angiodestructive polymorphic cellular infiltrate6,8 ) .
therefore the purpose of this study is to submit the first report about the case with thoracic spinal lyg after diagnosis with b - precursor childhood acute lymphoblastic leukemia ( all ) .
after surgical decompression with biopsy on the spinal lesion , diagnosis of grade ii lyg was made and rituximab was administered .
the patient is in good neurological condition without recurrence at the 6-year follow - up .
a 4-year - old girl was diagnosed with b - precursor all with the involvement of kidneys and pancreas in november , 2004 .
treatment was initiated according to the pediatric oncology group ( pog ) protocol 900612 ) .
on april 12 , 2006 , the patient was admitted to pediatric clinic with a complaint of intermittent fever for 3 days . on april 19 , 2006 , 7 days after the admission , the patient developed a gait disturbance .
neurological examination revealed paraparesis of grade 3 on medical research council ( mrc ) muscle strength grading scale1 ) with increased deep tendon reflex in both ankles , knee jerks , and bilateral positive babinski sign , but her senses were intact .
cerebrospinal fluid ( csf ) findings were as follows : elevation of protein ( 243.3mg / dl ) , and decrease of glucose ( 44mg / dl ) .
the condition was suspected to be an acute inflammatory demyelinating polyneuropathy and was treated with intravenous immunoglobulin ( 400 mg / kg / day ) for 5 days .
however , her paraparesis was aggravated to grade 1 on mrc muscle strength grading scale from april 26 , 2006 , 14 days after the admission , and spinal mri was performed .
t2 weighted mri demonstrated heterogeneous high signal intensity infiltration on t4 vertebral body and subligamental spreading soft tissue mass on t3 - 5 epidural space from t4 posterior vertebral body , causing spinal cord compression ( fig .
1 ) . on april 27 , 2006 , laminectomy of t3 , 4 with open biopsy were performed .
the epidural mass was encircling the spinal cord mainly on ventral surface and was slightly grey to yellow , solid and compact nature .
a histopathologic examination showed an angiocentric distribution of polymorphous lymphoid infiltrate , with extensive necrosis .
immunohistoche mical staining for cd3 and cd20 showed the predominance of mature t cells and atypical b cells ( fig .
hybridization revealed positivity for epstein - barr virus ( ebv ) encoded rna in a few lymphocytes , confirming the diagnosis of grade ii lyg .
one - week post - operative neurologic examination showed paraparesis grade 3 on mrc scale , and bare independent walking but as she still had gait impairment , she received rehabilitation .
after four weeks of the surgery , she restored her normal state and could walk quite well . at that time
, there were no pulmonary lesions , so we suspected the spinal lesion as the primary involvement site .
two weeks after , chest and abdomen ct revealed multiple low density nodular mass on the liver and the lower lobe of the left lung .
histopathologically , lesions were not blastic in appearance and in immunophenotype , and the lesions were negative for cd10 , tdt , and cd22 , so we ruled out the relapse of all .
she was treated with rituximab ( 275mg / m / day , 4 times per week ) for 4 weeks and intravenous high dose methylprednisolone ( 30mg / kg per day for 3 days , 20mg / kg per day for 2 days and 10mg / kg per day for 2 days ) .
chest and abdomen ct showed marked improvement of the lesions 3 months after the treatment compared with the lesions in the images obtained before the treatment .
a follow - up mri study performed 4 months after the operation documented no evidence of residual mass or recurrence ( fig .
3 ) . chest and abdomen ct performed 1 year after the operation showed no demonstrable focal lesion in lung field and mediastinum and unremarkable abdominal organs .
her weakness improved and she was able to walk independently and had no gait impairment .
but unfortunately we failed to take additional follow - up of mri for the patient , as she was terrified to take mri and full sedation was not possible .
moreover the parents of the patient did not agree with the idea of taking mri one more time because she was in good state at that time . to date ,
lyg is a rare lymphoproliferative disease characterized by angiocentric and angiodestructive ebv - positive b - cell proliferation of uncertain malignant potential , which might be associated with exuberant reactive t cell infiltration2,9 ) .
lyg affects men more than women with ratio 2 to 1 and presents mainly in adults between the fourth and sixth decades of life , although patients of all ages can be affected .
its occurrence in children is quite rare4 ) . there were three cases of lymphomatoid granulomatosis with onset after all .
two of these patients died of the disease , only one obtained benefit from acyclovir therapy7 ) .
lyg usually affects lungs primarily , and it may also present several significant extrapulmonary manifestations , affecting skin , kidney , spleen , and the central nervous system .
involvement of the spine has been rarely reported . to my best knowledge , this is the first report of thoracic spinal lyg presenting with unique progressive myelopathy .
however , numerous granulomatous lesions in the central nervous system and lungs are highly suggestive of lyg .
lyg with central nervous system involvement , observed in approximately 30% of the affected patients , indicates poor prognosis4,9,11 ) .
there was only one case report about lyg with spinal involvement . in that case ,
lyg involve cervical spinal cord , and the patient submitted four cycles of adjuvant cyclophosphamide , doxorubicin , vincristine and prednisone ( chop ) .
but the patient died 5 months after the treatment due to systemic progression of the disease7 ) .
a grading system of lyg is based on the number of atypical lymphocytes , ebv - positive b - cells and amount of necrosis5 ) .
pathophysiologically , grade i lesions consist of a polymorphous angiocentric and angiodestructive infiltrate of lymphocytes , plasma cells , and histocytes , with or without eosinophils .
large lymphoid cells or immunoblasts were less than five in high power field ( 400 ) or absent . if large lymphoid cells or immunoblasts were present , there would be no cellular atypia and minimal - to - absent necrosis .
grade ii lesions consisted of large lymphoid cells with less than twenty ebv - positive cells in high power field with some cellular atypia in small lymphoid cells , and necrosis was more common .
grade iii lesions , angiocentric lymphomas , consisted of large atypical cells with more than twenty ebv positive cells in high power field with the marked cytologic atypia in both small and large lymphoid cells4,13 ) . to date , no standard treatment has been established for lyg and treatments approach to systemic lyg include drugs acting on the immune system(corticosteroids , interferon alfa-2b ,
cyclosporine a , anti - cd20 monoclonal antibody - rituximab ) , mono- or combined chemotherapy , radiotherapy , and autologous stem cell transplantation .
several treatments with rituximab have been reported , with or without chemotherapy or radiotherapy3,9,10,15 ) .
rituximab was approved for the treatment of recurrent , poorly differentiated refractory or follicular cd20 positive b - cell non - hodgkin 's lymphoma14 ) . in this case , immunohistochemical staining for cd3 and cd20 showed the predominance of mature t cells and atypical b cells .
in situ hybridization revealed positive ebv encoded rna in a few lymphocytes , confirming the diagnosis of grade ii lyg .
the patient experienced rapid worsening of neurological symptoms and absence of systemic involvement on pre - operative laboratory findings and radiological imaging , and she therefore was treated with surgical decompression and biopsy on the t3 - 5 epidural lesion and improved neurologic symptoms .
surgical decompression can improve neurological morbidity of the patient . however , appropriate chemotherapy is highly needed as systemic progression of lyg make poor prognosis .
the patient responded to rituximab therapy well without adverse effects , and her condition remained stable for 6 years .
therefore it was suggestive that decompression and rituximab is suitable as the initial therapy for symptomatic spinal lyg .
this case described an unusual occurrence of thoracic spinal lyg in a 4-year - old girl .
childhood lyg is a rare disease but should be considered in the nodular pulmonary infiltrates and central nervous system manifestations , especially in the past diagnosis of childhood acute lymphoblastic leukemia .
awareness of the features of lyg can lead to earlier diagnosis and prompt appropriate therapy .
 lymphomatoid granulomatosis ( lyg ) is a lymphoproliferative disease involving the lungs most frequently ; however , it may also involve the kidneys , skin and especially the central nervous system . 
 unique initial presentation of spinal involvement is extremely rare and epidural lesion of thoracic spine has not been reported . 
 the prognosis for lyg has been reported to be poor , and there currently exists no satisfactory established treatment protocol . the purpose of this study is to report a case of successful treatment with surgery and rituximab combination therapy in thoracic spinal lyg . 
INTRODUCTION
CASE REPORT
DISCUSSION
CONCLUSION