Snježana Dotlić

Redefining a diagnosis: from meningeal plasma cell granuloma to rheumatoid meningitis. Report of a patient follow-up

Sir, In one of the previous issues of your Journal, we presented a patient with non-infectious meningitis, histologically characterized as plasma cell granuloma [1]. During the further months of follow-up, the patient developed mild normocytic anemia and a moderately elevated level of C reactive protein (CRP, 43.3 mg/l, normal values\5.0 mg/l) with unequivocally elevated levels of the rheumatoid factor (RF, 171.7 IU/ml, normal values \15.0 IU/ml) and antibodies against cyclic citrullinated peptides (anti-CCP, 405.3 IU/ml, normal values\7.0 IU/ ml). Although she was initially without signs and symptoms of arthritis, during the following weeks after obtaining these laboratory results the patient developed gradually worsening pain, swelling and morning stiffness of several joints, including both radiocarpal joints, the right elbow, right knee, as well as bilateral talocrural joints (Fig. 1). The clinical presentation consistent with polyarthritis in addition to elevated CRP levels and pronouncedly increased levels of RF and anti-CCP were sufficient for the diagnosis of rheumatoid arthritis. The patient was started on a regimen of a gradually tapered daily dose of methylprednisolone in addition to weekly methotrexate. Treatment led to stable remission of arthritis and further regression of the previously noted neurological deficit. The clinical course of the patient’s disease was followed by the development of our understanding of the clinical context in which the meningeal lesions took place. Although we previously concluded that the plasma cell granulomatous meningitis in our patient was an isolated finding and a primary disease of the meninges, the further disease course warranted a redefinition of the patient’s diagnosis, making rheumatoid arthritis the primary disease and (rheumatoid) meningitis its central nervous system manifestation. Rheumatoid meningitis (RM) is an extremely rare manifestation of rheumatoid arthritis (RA). The largest case series ofRM [2] involved 19 patients,most ofwhichwere diagnosed with RM post mortem based on autopsy findings (17 of 19 patients). That would probably not be the case nowadays, given the availability and development of sophisticated imaging methods, primarily magnetic resonance imaging. Patients from the case series [2] developed RM late in course of RA (after amedian of 14 years following diagnosis of RA). This makes the occurrence of RM as the initial disease manifestation evenmore unusual, although it was described in the literature in the recent years [3]. Both the leptoand the pachymeninges may be affected in patients with rheumatoid meningitis [2]. It is interesting tomention that the neurological manifestations observed in our patient (predominantly including seizures and paresis) are considered to be consistent with leptomeningitis, while symptoms such as headache and cranial neuropathies are ascribed to pachymeningitis [4]. Despite the unquestionable utility of imaging methods and I. Padjen (&) M. Mayer Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, University Hospital Centre Zagreb, Kispaticeva 12, Zagreb, Croatia e-mail: ivan_padjen@yahoo.ca

Isolated plasma cell granuloma of the meninges

A 77-year-old female with hypertension, presented with right partial motoric seizures. Neurological examination showed right hemiparesis. Brain MRI revealed extensive post-contrast interhemispheral dural, pachymeningeal and leptomeningeal enhancement of the left cerebral hemisphere (Fig. 1), which were initially interpreted as meningeal carcinomatosis. However, CSF analysis performed on two occasions, with normal cell count, glucose and protein levels, did not show malignant cells. Chest and abdominal CT scan and mammography were normal. Brain and meningeal biopsies were performed and histological findings (Fig. 2) were consistent with plasma cell granuloma. Following this bone marrow biopsy, skeletal X-rays survey, peripheral blood cell count, renal function, calcium and protein electrophoresis were normal. The patient was treated with corticosteroids without any neurological sequel and significant improvement of MRI findings. This case emphasizes how the diagnosis of leptomeningeal carcinomatosis remains challenging, as neither CSF cytology nor MRI is adequately sensitive for the diagnosis. Plasma cell granulomas are uncommon, benign inflammatory masses of unknown etiology [1]. They are histologically characterized by polyclonal plasma cells, large histiocytes with lymphophagocytosis and fibrosis [1]. There are only few reports of isolated CNS plasma cell granuloma in the literature [1]. Based on similar histological features, plasma cell granulomas, Rosai–Dorfman disease, and idiopathic hypertrophic pachymeningitis are now believed to form a spectrum of inflammatory or reactive conditions with, probably, the same unknown etiology [2, 3]. Rosai–Dorfman disease, or sinus histiocytosis, with massive lymphadenopathy, is a benign idiopathic histiocytic proliferative disease with pathognomonic histological and immunohistochemical characteristics. Extranodal involvement occurs in 43 % of cases [4], and by December 2008 111 cases of Rosai–Dorfman disease involving the central nervous system had been reported in the literature [5]. The main histopathological differentiation between plasma cell granuloma and Rosai–Dorfman disease is a careful appraisal of the morphological features together with the absence of emperipolesis in the S100-positive D. Kolenc S. Dotlic Department of Pathology, University Hospital Center Zagreb, Zagreb, Croatia