Lymphoblastic lymphomas are characterized by medium-sized blast cells with a high nuclear to cytoplasmic ratio, fine chromatin, and inconspicuous nucleoli [
5]. As in the present case, immunophenotyping demonstrating CD3 and TdT positivity confirms the diagnosis of T-cell lymphoblastic lymphoma. TPCNSL of the lymphoblastic type is an extremely rare tumor with only five reported cases in the literature (Table ) [
4,
11,
19–
21]. Of the four which provided clinical characteristics, two were supratentorial, one was leptomeningeal, and one was located in the cerebellum. In contrast, the present tumor was located in the pons with diffuse extension to brainstem, cerebellar, and cerebral structures. Taken together, these findings parallel those of the single large multicenter study of TPCNSL, which reported that the majority of these tumors are located supratentorially [
22].
Additional clinical characteristics of the lymphoblastic type are similar to those of TPCNSL. The overall median age of patients with TPCNSL is 60 [
22]. With the exception of one case report describing a 2-year-old female [
4], the remaining cases and ours involve patients in the fifth and sixth decades [
11,
19,
21]. There is a male predominance of TPCNSL [
22]. Including the present report, 3/5 (60%) of the reported cases of lymphoblastic type TPCNSL are male [
19,
21]. In the present report, lumbar puncture revealed an elevated CSF protein, which was true in 79% of TPCNSL [
22].
One previously reported patient with leptomeningeal disease presented with altered mental status, as did the present patient [
21]. The two remaining reports which described presenting symptoms demonstrated focal neurologic deficits: dysphasias and hemiparesis, which were consistent with their locations in the left frontal lobe [
11,
19]. These observations underscore the diversity of presentations possible in this rare disease. Primary CNS lymphoma can be difficult to distinguish from other neurologic diseases [
14]. Interestingly, there is one case report of Lyme neuroborreliosis initially misdiagnosed as CNS lymphoma, which led to delay in treatment [
24]. Conversely, in the present case, the patient presented with a history of positive Lyme serology and MRI findings consistent with cranial neuritis. When the patient failed to respond to antibiotic and corticosteroid treatment, brain biopsy was performed. Since this tumor is responsive to methotrexate and other chemotherapy treatment, it is important to maintain a high index of suspicion when evaluating patients with non-focal neurologic manifestations and diffuse imaging abnormalities. Early brain biopsy should be considered to obtain a definitive diagnosis.
Imaging features of lymphoblastic TPCNSL appear to be variable. Previous reports utilized CT scanning (Table ). One tumor demonstrated enhancement after contrast administration [
11]. One tumor was hyperdense relative to gray matter and one was hypodense [
4,
19]. CT imaging in the present report demonstrated subtle diffuse hypodensity in the brainstem. This variability in CT imaging is in contrast to other primary CNS lymphomas which are generally hyperdense and universally enhancing [
10]. A recent series of MRI analysis of seven patients with TPCNSL reported that the majority of these tumors present radiographically as mass lesions that are hypointense on T1-weighted images and hyperintense on T2-weighted images which enhance [
16]. While imaging in the present study demonstrated high T2 signal intensity, the abnormality was diffusely infiltrative with no enhancement after contrast administration.
Median survival for TPCNSL is 25 months [
22]. A prior case series and literature review suggested that pathology might be predictive of survival, with a higher frequency of long-term survivors having low-grade lymphocytic TPCNSL [
23]. A larger, more recent retrospective study showed no difference in survival based on low-grade versus anaplastic histologic features [
22]. Of the four previous reports of lymphoblastic TPCNSL, only one patient survived for greater than 1 year [
4]. The patient in the present case relapsed after 11 months and succumbed to the disease at 15 months despite salvage therapy. Taken together, these data suggest a shorter survival for patients with TPCNSL of the lymphoblastic type. Recent multicenter studies of primary CNS lymphoma, including patients with TPCNSL treated with high-dose methotrexate in combination with procarbazine and vincristine, have demonstrated prolonged survival relative to single agent therapy [
1,
3,
7,
13]. Others have demonstrated improved survival in patients treated with methotrexate and osmotic blood-brain barrier disruption [
6]. Preliminary analysis of three patients with TPCNSL treated with blood brain barrier disruption and intra-arterial methotrexate showed similar encouraging responses [
8]. Future studies examining the affect of newer treatment regimens such as these would be difficult for TPCNSL of the lymphoblastic type due to the rarity of the disease. However, this type of study would be necessary before definitively designating this histology as a poor prognostic indicator.
1,5 Kangmin Lee,1 William C. Broaddus,1 Mary Jo Martin,2 Nitya R. Ghatak,2 Catherine E. Grossman,3 Sherman Baker, Jr.,3 and Ahmet Baykal4
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