A 48-year-old HIV-negative female without a significant medical history (except for a head injury one year earlier) presented after she had worsening headaches, nausea, vomiting and dizziness with negative neurological examination. The previous year she underwent a CT scan, which showed neither intracranial expansive lesions nor haemorrhages (after traumatic accident), while the MRI performed after the worsening symptoms revealed an extra-axial mass of about 3 cm within the left lateral ventricle with contrast enhancement (Fig. 1).
Clinically, the most likely diagnoses were represented by an ependymoma, an intraventricular meningioma, a metastasis and less likely by an inflammatory process or a lymphoma.
In November 2021, the patient underwent a total resection of the lesion: it appeared as a whitish lesion with vascularized areas and a hard-friable consistency (Fig. 2).
Microscopic examination showed a diffuse proliferation of lymphoplasmacellular elements within the fragments of a chorioid plexus rich in fibrosclerotic tissue with also the presence of deposits of amorphous material (Fig. 3A-B-C-D). The main diagnostic hypotheses were represented by three main pathological pictures: first of all, a chronic/reactive post-traumatic inflammatory process, rich in plasma cells; secondly, a hereditary transthyretin amyloidosis, that usually has an adult-onset and is characterized by the deposition of a misfolded transthyretin produced by the choroid plexus and its consequent accumulation in the leptomeninges [10]; lastly, an IgG4-related disease. However, the negative Congo red stain and non-specific positivity of plasma cells for IgG and IgG4, together with normal serum IgG4 levels, ruled out the latter two diagnostic hypotheses. The only plausible diagnostic hypothesis was represented by a post-traumatic inflammatory process, but the morphology and distribution pattern of the inflammatory elements were not univocally attributable to such a process. In fact, the lymphoplasmacellular infiltrate was mainly represented by monomorphic small B lymphocytes with a marginal growth pattern and a marked plasma cell differentiation (Fig. 3A-B-C-D). Immunohistochemical examination revealed positivity for CD20 and Bcl2 in small B lymphocytes (Fig. 3E-F) and CD138 positivity (Fig. 3G) with k clonal restriction in plasma cells (Fig. 3H).
CD23, Bcl-6, cyclin D1, SOX-11, CD5 and CD10 were all negative. Ki-67 proliferation index was very low (5–10%). On this basis, the only possible diagnosis was represented by a lymphoproliferative process, both a CNS localization of a systemic disease or a primitive CNS lymphoma. Of note, cytological analysis of cerebrospinal fluid and bone marrow biopsy with flow cytometry and cytogenetics showed no evidence of lymphomatous infiltration and CT and PET scan of the thorax, abdomen and pelvis confirmed the absence of a systemic disease. Therefore, it was a primitive CNS lymphoma. Differential diagnoses included a small lymphocytic lymphoma/chronic lymphocytic leukaemia (CLL/SLL), lymphoplasmacytic lymphoma, follicular lymphoma, mantle cell lymphoma and marginal zone lymphoma. CLL/SLL was unlikely due to absence of peripheral blood or bone marrow involvement, and negativity for CD5 and CD23. Similarly, in the absence of bone marrow involvement, negative PET scan, and no clinical history of Waldenstrom’s macroglobulinemia with the absence of both MYD88 mutation and clonal circulating IgM by serum protein electrophoresis and immunofixation electrophoresis, involvement by lymphoplasmacytic lymphoma was unlikely. Moreover, the lack of an overt morphological follicular appearance and CD10 negativity made follicular lymphoma unlikely. Similarly, negativity for cyclin D1, SOX-11 and CD5 ruled out mantle cell lymphoma. Therefore, the only possible diagnosis was represented by a primary CNS MZBL arising at the base of the chorioid plexuses of the left lateral ventricle. Considering the unusual anatomical site for the localization of such a lymphoproliferative process, a PCR analysis of B lymphocyte clonality was performed. A monoclonal populations of B lymphocytes with a heterologous rearrangement of the IGH gene, FR2/JH and FR3/JH fragments and of the k gene was identified by testing for immunoglobulin heavy chain (IGH) and kappa light chain gene (IGK) rearrangement using the polymerase chain reaction developed by the collaborative European BIOMED-2 Concerted Action Study Group. Therefore, molecular studies led to a diagnosis of primary CNS MZBL with k plasma cell differentiation. The patient received whole brain external beam radiotherapy, with a total dose of 24 Gy after which the gross disease disappeared at follow up MRI (neither a mass effect nor an abnormal enhancement was evident). Currently, she is alive and without symptoms for 12 months up to the date of this report.