the multiple myeloma is a hematological malignancy characterized by the development of a clone of plasma tumor invading hematopoietic marrow . in its usual form , it involves bone marrow plasma cell infiltration , a monoclonal immunoglobulin in blood and/or urine , and bone involvement .
meningeal localization of myeloma is a rare presentation and poor prognosis 14 . a high myeloma burden , stage iii disease , high labeling index , circulating plasma cells in the peripheral blood , and iga or igd m protein were the most frequent clinical features of these patients .
we report a case of a patient who developed meningeal involvement 3  months after achieving complete remission after autologous stem cell through multiple myeloma revealed by a nasopharyngeal mass and discuss the presumed mechanism of meningeal involvement .
we also speculate that meningeal involvement may occur also in cases with a low myeloma mass and with a disease apparently well controlled by high - dose therapy 4,5 , but who had initially an infiltration from contiguous structures when lytic lesions erode skull and dura mater 6 .
we report a case of a 41-year - old man who was admitted in our institution for multiple igg kappa myeloma iss3 score , in a context of general alteration with 9  kg weight loss , dysphagia to solids , a left laryngeal immobility . the physical examination found a large mass in the nasopharyngeal .
brain magnetic resonance imaging ( mri ) rating extensive homogeneous cell mass developed at the expense of nasopharyngeal extending into the oropharynx , invading the soft parts of the cranio - spinal shower hinge , part of the skull base , the predominant left temporal fossae , large sphenoid wings being crossed by the tumor process ( fig.1 ) .
the microscopic examination of the tumor 's biopsy showed a fragment consisting of nasopharyngeal cohesive sheets of small cells overwritten .
immunohistochemistry noted of cd145 + cells , cd20 , cd3 , cd138 + , monotypic lambda with an estimated of 90% proliferation index .
the pet scanner showed a large mass developed at the expense of nasopharyngeal extending the skull base and oropharynx .
sagittal view of a 3d - t1-weighted mri with gadolinium shows extensive homogeneous cell mass invading the soft parts of the cranio - spinal shower hinge , part of the skull base , the predominant left temporal fossae , large sphenoid wings being crossed by the tumor process . the complete blood count on presentation demonstrated a white blood cell count of 8.1  g / l ( segmented neutrophils 61% ; band neutrophils 0% ; lymphocytes 28% ; monocytes 9% ; eosinophils 1% ; basophils 1% ) with hemoglobin level of 9.8  g / dl , and platelets levels of 283 
bone marrow aspiration indicated marrow involvement due to the presence of 40% of plasma cells .
lumbar puncture including electrophoresis of proteins of the cerebrospinal fluid ( csf ) was normal .
the patient was treated with vcd regimen , melphalan autograft , radiotherapy of nasopharyngeal and spine .
autograft was complicated by ( 1 ) pulmonary infection , ( 2 ) a significant mucositis grade 4 with major malnutrition , and ( 3 ) weight loss of 10  kg .
the patient was readmitted to the emergency department with intensive headache , dysarthria , unsteady gait , and limb weakness , without nuchal rigidity or fever .
a brain mri demonstrated a contrast - enhanced dural multinodular thickening next to the right parietal lobe , with focal extensions to the subarachnoid space and vasogenic edema of the underlying brain parenchyma ( fig.2 ) . the adjacent inner table and diploe of the skull were not involved . a bilateral parenchymal enhancement of the superior cerebellar peduncle was also observed .
axial view of a 3d t1-weighted mri with gadolinium ( a ) and flair ( b ) shows an enhanced dural thickening ( arrowheads ) with a parenchymal edema of the underlying cortex and subcortical white matter ( double arrow ) .
coronal view ( c ) also reveals an involvement of the subarachnoid space ( arrowhead ) . an axial view of the brain stem shows bilateral parenchymal enhancement of the cerebellar peduncles ( arrows ) .
a lumbar puncture was performed and showed a low  level of glucose ( 0.4  mmol / l ) , a high protein level ( 2.1 
g / l ) , and a high white cell count composed almost exclusively by plasmas cells ( fig.3 ) , all with neoplastic phenotype cd138 positive .
plasma cells in the cerebrospinal fluid may grunwald giemsa ( mgg )    100 .
he received intrathecal administration of 12  mg of methotrexate , 40  mg of cytarabine , and 40  mg of prednisolone , three times per week , and pad regimen ( bortezomib  adriamycine 
about 65 cases were reported in the literature 13 and reviewed by peterson et  al .
the largest series including 14 patients was reported by chamberlain et  al . 1 . a high myeloma burden , stage iii disease , high labeling index , circulating plasma cells in the peripheral blood , and iga or igd m protein were the most frequent clinical features of these patients .
a hematogenous spread can be hypothesized in plasma cell leukemia , and an infiltration from contiguous structures is possible when lytic lesions erode skull and dura mater 6 .
otherwise , a few patients with a cns relapse had circulating plasma cells ( pc ) at the first recognition of multiple myeloma ( mm ) : in these patients , pc might have infiltrated the meninges at diagnosis and might have grown during the course of the disease since most of the drugs used in mm treatment and even high - dose melphalan can not overcome the blood  brain barrier .
this complication appeared in the majority of the patients as a terminal event 7 , but it was also reported as a presenting feature of mm 5 .
moreover , a few cases of meningeal involvement were reported in patients who had been successfully treated with high - dose therapy and stem cell rescue and had no overt medullary plasmacytosis 4,5 .
four patients were described : all presented meningeal involvement a few months ( 2 or 3 ) after an autologous stem cell transplant ( asct ) with the attainment of a complete remission and no evidence of residual disease in the bone marrow .
the conditioning regimen was high - dose melphalan in three cases and total body irradiation ( tbi ) plus melphalan in the fourth .
these data confirm that meningeal involvement may  occur also in cases with a low myeloma mass and with a disease apparently well controlled by high - dose therapy .
our report describes a patient with meningeal involvement who had not detectable disease after vcd regimen , melphalan autograft , radiotherapy of nasopharyngeal and spine but who had initially a nasopharyngeal mass invading the base of the skull .
although pc can be seen in the csf in other conditions , both infectious and noninfectious 8 , the presence of pc in the csf of a patient with mm supports the diagnosis of myelomatous meningitis .
the definitive proof is the definition of monoclonality of the pc obtained by immunophenotyping or the immunoelectrophoresis of csf showing an m component 9 .
the prognosis of meningeal and cerebral involvement of mm is very poor . on the basis of the 65 cases of meningeal myelomatosis reported mainly as case reports in the literature , with available information about survival , the median overall survival ( kaplan  meyer ) from the time of the diagnosis of the meningitis was 6  weeks 4 .
the it given included methotrexate , cytarabine , thiotepa , and hydrocortisone and in some cases it was associated with systemic chemotherapy . in conclusion , the occurrence of neurological symptoms in a patient with myeloma requires an accurate evaluation with mr and lumbar puncture to detect a possible meningeal or cerebral involvement , when metabolic factors ( hypercalcemia , uremia ) , hyperviscosity , or medullary compression can be excluded .
herein , we confirmed that this hypothesis has to be considered also in patients with a disease apparently responsive to standard or high- dose therapy .
there is no consensus toward the modalities of treatment ; in our experience , it chemotherapy and systemic chemotherapy did not have the expected result .
 key clinical messagea patient with multiple myeloma with a mass in the nasopharyngeal was diagnosed . 
 he received melphalan autograft and radiotherapy , and obtained complete remission . 
 he relapsed 3  months later , with meningeal involvement and without systemic relapse . 
 he received intrathecal and systemic chemotherapy , without neurological improvement and died 4  weeks after relapse . 
Introduction
Case Report
Discussion
Conflict of Interest