Introduction

Primary dural lymphoma is a rare form of PCNSL, mostly described by case reports. The incidence of PDL is reported as 0.6–3 % of all primary central nervous system lymphomas (incidence variable in studies) [1, 2]. Aggressive NHL dural subtypes are unique as most aggressive lymphomas of the meninges are associated with brain parenchymal or systemic involvement. The majority of PDL are low-grade, B-cell marginal zone lymphoma (MZL) with rare cases of low-grade follicular subtypes reported [1]. Aggressive dural lymphomas including diffuse large B-cell lymphoma (DLBCL) and lymphoblastic subtypes are limited to case reports and small case series [1, 3–6] (Table 1). PDL have favorable outcomes and the indolent forms are biologically distinct from parenchymal PCNSL or systemic lymphoma metastatic to the CNS [1]. Whether B-lymphoblastic subtypes will follow this favorable trajectory remains unclear. The paucity of dural lymphoblastic lymphoma cases in the literature make standardized treatment and prognostication difficult.

Table 1 Previous reports of primary CNS aggressive dural-based lymphomas
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Case history

A 42-year-old immunocompetent male presented with several weeks of a left frontal headache, lack of coordination, and tendency to drift to the left while driving. Magnetic resonance imaging (MRI) revealed a large enhancing extra-axial mass along the right posterior superior parietal convexity invading the calvarium (Fig. 1a). A second 18-mm focus of enhancement was also noted within the left parietal calvarium distinct from the tumor bulk (Fig. 1b). The tumor was protruding from the outer table of the calvarium and in areas, invaded the meninges and infiltrated into the subdural space. Excision of the tumor was performed and submitted for pathology. A diagnosis of B-LBL was rendered. Complete blood count was only notable for a mild thrombocytosis: platelet count 454,000/μL which was present since 2007. His thrombocytosis fluctuated in the range of 450,000–650,000/μL. Computed tomography (CT) of the chest, abdomen, and pelvis and positron emission tomography (PET) revealed no abnormalities. Cerebrospinal fluid examination was unremarkable.

Fig. 1
figure 1

MRI (T1 axial flare, post-contrast). a Large extra-axial enhancing mass along the right parietal convexity measuring 8.7 × 5.9 × 6.6 cm. b Separate abnormal foci of enhancement within the left calvarium distinct from the larger mass

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The patient was treated with hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with high-dose cytarabine and methotrexate in conjunction with prophylactic intrathecal methotrexate and cytarabine. Six months since diagnosis, he has tolerated 7 cycles of treatment without complication and will receive consolidative radiation therapy at systemic therapy completion. MRI of the brain after 5 months showed no evidence of recurrence.

Results

Tumor resection pathology

Touch imprint from the brain tumor biopsy revealed numerous small to medium-sized lymphoid cells with scant cytoplasm, irregular nuclei with open vesicular chromatin, and occasional prominent nucleoli resembling blasts (Fig. 2a). Hematoxylin and eosin (H&E) stain showed sheets of numerous small/medium lymphoid cells with frequent apoptotic bodies and occasional mitosis (Fig. 2b). Immunohistochemistry (IHC) was performed on deparaffinized, formalin-fixed brain tissue and showed the lymphoma cells to be diffusely positive for CD45, BCL-2, CD79a, PAX5, CD 10, and TDT and negative for CD20, CD3, CD5, BCL-6, BCL-1, and EBER (EBV by in situ hybridization) (Fig. 2c). Ki-67 showed high proliferation index. Fluorescence in situ hybridization (FISH) analysis on paraffin-embedded sections of brain tissue showed copy gain of BCL-2 (81 % cells) and MALT1 (77 % cells) with loss of CEP9 (65 % cells) and ETV6 (68 % cells). No BCL-6, CCND1/IGH, or MYC/IGH rearrangements were found.

Fig. 2
figure 2

a Touch imprint showing multiple lymphoblasts with small- to medium-sized cells, scant cytoplasm and open vesicular chromatin (original magnification ×1000). b Hematoxylin and eosin stains showing sheets of small lymphoid cells with frequent apoptotic bodies and occasional mitosis (original magnification ×500). c The tumor cells are diffusely reactive for CD79a, PAX5, and TDT and negative for CD20 (original magnification ×200)

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Bone marrow biopsy

Bone marrow biopsy revealed trilineage hematopoiesis and slight megakaryocytic hyperplasia without morphologic or immunophenotypic evidence of a hematolymphoid neoplasm. Bone marrow molecular studies performed by polymerase chain reaction (PCR) were negative for JAK2 V617F, calreticulin and MPL codon 505 and 515 gene mutations, cytogenetics showed 46, XY [7], myeloproliferative disorder FISH panel showed normal signal patterns for CHIC2, PDGFRB, FGFR1, and BCR/ABL.

Peripheral blood

Molecular studies by PCR were negative for JAK 2 exon 12 mutation.

Discussion

Primary dural-based lymphoblastic lymphoma are sparsely reported in the literature. The pathogenesis of PDL is poorly understood as the dura is devoid of lymphoid tissue. Postulated mechanisms, although this has not been definitively proven, include the action of an antigen-independent environmental stimulus or an autoimmune mechanism that could initiate an inflammatory response with subsequent selection of a clonal lymphoid population [1, 8].

The optimal induction therapy for adult B-LBL has not been fully delineated. The most commonly used induction regimes are derived from pediatric protocols and include intensive chemotherapy with CNS prophylaxis followed by prolonged maintenance therapy. ALL (acute lymphoblastic leukemia)-specific chemotherapy regimens have been favored over lymphoma-specific regimens for high risk patients with LBL [9–11].

In our case, complete resection of the tumor was performed followed by treatment with an ALL protocol using hyper-CVAD chemotherapy and intrathecal CNS prophylaxis with each course. He also underwent surveillance with bone marrow biopsy after four courses of treatment which remained negative. The role of consolidative radiation therapy in our particular case is less well defined. Prior reports of patients with B-LBL of various sites reveal high rates of complete remission and overall survival [12]. The prognosis of dural DLBCL based on limited case reports, appears favorable [6]. An interesting aspect of our case was the patient’s history of thrombocytosis and findings of slight megakaryocytic hyperplasia on bone marrow biopsy. This raised initial concern for an underlying myeloproliferative disorder (MPD). Concurrence of B-lymphoblastic leukemia and myeloproliferative neoplasm harboring a MPL W515S mutation has been previously reported [13]. However, the MPL mutation was not detected in our patient.

To our knowledge, this is the second reported case of B-LBL with isolated dural involvement in the absence of other systemic sites of disease. The majority of B-LBL present systemically with concomitant bone marrow involvement and/or leukemic component. As we gain further insight into the natural history and pathogenesis of primary (aggressive) dural lymphoma, our understanding of its behavior will broaden and improve our therapeutic approach.