Polyclonal Plasma Cell Hyperplasia Involving the Meninges (Inflammatory Pseudotumor)
Left Subdural Hematoma
Pars Planitis, Left Eye
This 43 year old veterinarian with progressive headache associated with MRI and CSF evidence of meningeal inflammation, and concomitant pars planitis of the left eye, responded initially to empiric IV steroid treatment. His headaches subsequently worsened, with development of new focal signs on neurologic examination, and deterioration of function in his left eye. No clear infectious cause of his illness had been identified by this time. Repeat MR imaging showed enlargement of a left subdural fluid collection, with mass effect. Due to clinical deterioration attributed to the enlarging subdural, and inability to achieve a definitive diagnosis from less invasive studies, the patient underwent open drainage of the subdural fluid collection, with meningeal biopsy.
At surgery, the dura was very hyperemic, overlying a thick green membrane which was biopsied. Underneath this membrane, a subdural hematoma was identified with evidence of both fresh and clotted blood. Directly against the brain and pia, an inner green membrane was found and biopsied. The underlying brain appeared normal and was not biopsied. Microscopic examination of biopsy specimens revealed granulation tissue admixed with a predominance of plasma cells, foci of lymphocytes, scant numbers of polymorphonuclear cells, focal collections of eosinophils, and numerous activated histiocytes. Well-formed granulomata were not present. The plasma cell infiltrates were polyclonal, exhibiting both kappa and lambda light-chain immunoreactivity. No definite organisms were seen on a number of stains, and no evidence of an associated neoplasm was detected.
Plasma cell proliferation involving the meninges may present clinically with mass effect ("inflammatory pseudotumor") or as a pachymeningitis, as in this case. This uncommon condition is also described as a plasma cell granuloma, inflammatory myofibrohistiocytic proliferation, fibrohistiocytoma, or plasma cell-histiocytoma complex. It is traditionally believed to be an inflammatory reaction to an inciting event, the nature of which is not usually identified at the time of tissue diagnosis. Occasional reports suggest that lesions with similar histologic characteristics may behave as mesenchymal neoplasms with low or indeterminate malignant potential. The histopathology is characterized by an inflammatory cell proliferation, predominantly of plasma cells. In addition to plasma cell proliferation, lymphocytes, histiocytes, polymorphonuclear cells, fibroblasts, and occasional eosinophils are found within the inflammatory lesions.
Included in the differential diagnosis of meningeal plasma cell proliferation or infiltration are a number of neoplastic disorders, including plasmacytoma, lymphoma, meningioma with lymphocytic infiltration ("inflammatory meningioma"), and histiocytosis X, as well as immune-inflammatory disorders such as sarcoidosis and Wegener's granulomatosis. The polyclonal nature of the plasma cell proliferation distinguishes this patient's disease process from a plasmacytoma. The numerous types of inflammatory cells observed also makes lymphoma unlikely. We did not observe psammomatous bodies or other histological features of a meningioma with a secondary inflammatory reaction. In the biopsied lesions, the predominance of plasma cell infiltrates over the histiocytic reaction, and the only occasional foci of eosinophils, was not considered sufficient to support a diagnosis of histiocytosis. Well-formed granulomata were not observed, making sarcoidosis or other systemic granulomatous disorders, such as Wegener's granulomatosis, unlikely. In addition, the lack of pulmonary symptoms or significant chest radiographic abnormalities, as well as the unremarkable serum tests for angiotensin-converting enzyme and anti-neutrophil cytoplasmic antigen (ANCA), did not support the latter diagnoses. The patient did not have a history of oral or genital mucosal ulceration suggestive of Behcet's disease. The patient did not exhibit any clinical evidence of the joint involvement characteristic of rheumatoid arthritis, which can also produce a chronic meningitis, particularly in long-standing cases.
The possibility of mycobacterial disease (tuberculosis or atypical mycobacteria) must be considered in any case of undiagnosed meningeal inflammation. Mycobacterial disease can be challenging to diagnose because of its predilection for the basal meninges, which may be difficult to biopsy. However, in this patient we were unable to find any evidence suggestive of mycobacterial infection on chest X-ray, CSF cultures, or examination and culture of the biopsy material. Although steroid therapy is often indicated as an adjunct to antibiotic treatment of CNS mycobacterial infection, a long-term clinical response in the absence of appropriate antibiotic treatment would be unusual.
We also considered the possibility that the inflammatory reaction noted on biopsy resulted from a spontaneous cerebrospinal fluid leak, or from idiopathic intracranial hypotension (Schaltenbrand's syndrome), acting as the initial inciting event. The literature describes, and we have also observed, cases in which persistent intracranial hypotension is associated with hyperemia and even inflammatory changes in the meninges; in extreme cases, subdural bleeding may occur. In this patient, however, low CSF pressure was never documented, either in the data presented, or during subsequent lumbar punctures. Although the patient's description of the postural component of his headache initially raised the possibility of a low-pressure syndrome, we also noted that maneuvers which increased intracranial pressure also worsened the headache, and the headache did not appear to worsen following lumbar puncture and CSF withdrawal. The existence of a synchronous inflammatory disorder (pars planitis) and the rapid clinical response to steroids was felt to be more typical of a primary inflammatory process, as was the demonstration of a prominent plasma cell component to the inflammation.
Although unlikely in this patient given the history and negative screening studies, a meningeal plasma cell reaction has been described in spirochetal diseases, such as syphilis and Lyme disease. There was no unilateral lymphadenopathy, fever, or encephalopathy to suggest a diagnosis of cat-scratch disease, which may be associated with atypical plasma cells in granulomas, and the causative organism (Bartonella henselae) was not detected in the biopsy material on routine or silver stains. The recurrent aseptic meningitis associated with herpes simplex infection (Mollaret's meningitis) does not typically produce a pachymeningitis with a significant plasma cell reaction, and in this patient, PCR of the CSF for herpes simplex was negative. Finally, some medications, such as phenytoin, may rarely be associated with a prominent inflammatory reaction mimicking a neoplastic process ("pseudolymphoma"), but there was no history of exposure to any of these agents.
Plasma cell proliferation (plasma cell granuloma or inflammatory pseudotumor) frequently occurs in the lung, but it has been described in many other organs, including liver, spleen, stomach, thyroid, kidney, bladder, orbits, and brain. No large series of cases involving the CNS has been published. It is not clear what percentage of total cases of plasma cell hyperplasia involves the CNS in combination with other organs or in isolation, although it is believed to be rare. Involvement of more than one system may be synchronous or metachronous. Vision can be affected, and radiographic abnormalities involving the orbits, chiasm, or optic nerves are often, but not always, seen.
The most common complaint of patients with intracranial plasma cell hyperplasia is headache. Other signs and symptoms, such as weakness and seizures, depend on the size and location of the proliferation. There is no obvious gender predominance, and the mean age of reported cases is about 30.
No clear consensus exists with regards to treatment but most authors advocate surgical excision first, with steroids, radiation, and other immunosuppressives as adjuncts, especially in cases where total resection is not possible. Prognosis is usually good, with recurrences being rare after resection.
Our patient received IV steroid and cyclophosphamide treatment at monthly intervals for three successive months after the surgery, and has been followed for about a year without evidence of recurrence. He continues to have headaches, but his follow up imaging shows only postoperative changes with improving minimal dural enhancement. Repeat spinal fluid studies have been normal. His vision in the left eye has improved, with disappearance of inflammatory cells from the vitreous. To date, a potential infectious cause for his inflammatory process has not been identified, although continued surveillance is warranted.
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