Lymphoblastic lymphoma (LBL) accounts for approximately 2% of all non-Hodgkin lymphoma (NHL) [1], and approximately 90% are of immature T-cell lineage [2]. Precursor B-cell LBL (B-LBL) is uncommon and accounts for less than 10% of total LBL cases and 0.3% of adult NHL [1, 3].

The term LBL is used when the disease is confined to mass lesions including the lymph nodes and extranodal organs with no or minimal evidence of bone marrow (BM) involvement [4]. The disease presents mainly with extranodal involvement, sparing the BM. The most commonly involved sites include the skin (33%), lymph nodes (22%), bone (19%), and mediastinum (5%), while hepatomegaly, splenomegaly, a leukemic picture, or involvement of the central nervous system have been reported infrequently [5, 6, 7]. The natural history of adult B-LBL has not been well defined because of its rarity.

From January 2007 to March 2012, 1,230 adult patients presented with NHL at the Asan Medical Center, Seoul, Korea. Among the 27 (2.2%) patients diagnosed with LBL, only 3 (0.2%) had B-LBL. In this report, we aimed to summarize the clinical characteristics and clinical course of these 3 B-LBL cases.

B-LBL, which constitutes less than 10% of all LBL, very rarely presents with BM involvement [1]. In this report of 3 B-LBL cases, all had stage IV disease, good performance status, and a low International Prognostic Index (IPI) score (Table 1). These clinical features were similar to those observed in another report, also from Korea [4]. In contrast, however, 2 patients had lymphoma involvement at multiple extranodal sites including the acetabulum and lung, and BM involvement was noted in all patients.

T-LBL patients, compared to those with B-LBL, are known to be younger and have a higher rate of mediastinal tumors or BM involvement [3, 9]. In the vast majority of B-LBL patients, mediastinal masses and BM involvement are rare, but lymph nodes and extranodal sites, such as skin, bone, and soft tissue are more frequently involved than in T-cell LBL (T-LBL) [3, 5, 9]. In most cases, B-LBL and T-LBL cannot be distinguished on histologic features alone without immunophenotyping [10].

In B-LBL, tumor cells are virtually always positive for B cell markers CD19, CD22, and CD79a. In most cases, they are also positive for CD10, CD24, PAX5, and TdT, while the expression of CD20 and CD34 is variable [9]. In case 1 presented here, small malignant cells were positive for CD20 and PAX5; in case 2, they were positive for CD10, CD20, LCA, and TdT; and in case 3, they were positive for CD10, PAX5, and TdT. These IHC findings were consistent with B-LBL. In case 3, the laboratory findings, which included mild anemia and a normal platelet count (with the normal range of megakaryocytes in the BM biopsy) supported the diagnosis of B-LBL with leukemic manifestation, rather than B-ALL.

Of the 2 patients who received VPDL chemotherapy [8, 11], 1 achieved CR and the other PR. Although case 2 received 1 R-CHOP cycle because of the initial misdiagnosis, he also achieved PR after 6 R-CHOP cycles. As LBL is highly aggressive, intensive multi-drug leukemia chemotherapy protocols are usually recommended [9]. Intensive protocols designed for aggressive NHL improve the CR rate, but survival is poorer than that obtained using regimens designed for other aggressive lymphomas [12]. Improvements in longterm LBL outcome have been achieved with ALL-type regimens [13]. As chemotherapy intensity correlates with outcome in LBL, more intensive NHL regimens fare better than conventional NHL regimens [14].

In summary, the cases presented indicate that B-LBL can involve multiple extranodal sites and BM involvement may not be as infrequent as previously reported. Furthermore, intensive chemotherapy seems to be effective in this disease.

(A) Post-contrast T2-weighted coronal pelvic magnetic resonance image showing a high T2 signal and enhancement in the left acetabulum and iliac bone. (B) A positron emission tomography (PET) image showing inhomogeneous hypermetabolic activity (maximum SUV=5.6) in the left ilium and acetabulum. (C) PET image showing the disappearance of a hypermetabolic lesion in the left ilium and acetabulum after vincristine, methylprednisolone, daunorubicin, and L-asparaginase (VPDL) induction chemotherapy.

(A) Microscope analysis of the biopsy specimen revealing diffuse infiltration of small-to-medium sized lymphocytes with massive necrosis (×100; hematoxylin and eosin [H&E]). (B) High magnification shows monotonous tumor cells with a moderate amount of cytoplasm, round-to-oval shaped indented nuclei, condensed chromatin and inconspicuous nucleoli (lymphoblast), and nuclear debris with necrosis (×400; H&E). (C) The neoplastic cells show nuclear staining for PAX5, and (D) diffuse membranous staining for CD20.

(A) Chest computed tomography showing conglomerated enlarged lymph nodes in the bilateral mediastinum causing compression of the central airway, and encasement of the left pulmonary artery and descending aorta. (B) A positron emission tomography (PET) image showing a hypermetabolic central lung mass in the left lung with direct invasion of the mediastinum and post-obstructive atelectasis. (C) PET image showing decreased extent and activity of hypermetabolic lesions after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy.

(A) High magnification shows diffuse infiltration of monotonous tumor cells with a moderate amount of cytoplasm, round-to-oval shaped indented nuclei, condensed chromatin and inconspicuous nucleoli (lymphoblast), and nuclear debris with necrosis (×400; hematoxylin and eosin). (B) The neoplastic cells show diffuse membranous staining for CD20, (C) cytoplasmic staining for CD10, and (D) diffuse membranous staining for leukocyte common antigen (LCA).

Table 1 Characteristics of patients.