Lymphoblastic Lymphoma

Background

This is a high grade lymphoma which arise from precursors of B or T-cells. The vast majority (90%) are of immature T-cell lineage. Most of these cases occur in children and adolescents.

OUTLINE

Epidemiology

Disease Associations

Pathogenesis

Laboratory/Radiologic/
Other Diagnostic Testing

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Special Stains/
Immunohistochemistry/
Electron Microscopy

Differential Diagnosis

Prognosis

Treatment

Commonly Used Terms

Internet Links

DISEASE ASSOCIATIONS CHARACTERIZATION

CD79a(+) T-cell lymphoblastic lymphoma with coexisting Langerhans cell histiocytosis.

Li S, Borowitz MJ.

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.

Arch Pathol Lab Med 2001 Jul;125(7):958-60 Abstract quote

Although there is a close association between Langerhans cell histiocytosis and malignant neoplasms, simultaneous occurrence of lymphoblastic lymphoma and Langerhans cell histiocytosis in the same lymph node is an extremely rare finding.

Herein, we describe such a case in a 26-year-old woman who presented with progressive cervical lymphadenopathy.

The lymphoma cells have an immature T-cell phenotype (terminal deoxynucleotidyl transferase(+), HLA-DR(+), CD34(+), CD38(+), and CD7(+)) with expression of both CD3 and CD79a on immunohistochemical stain. The Langerhans cells are present focally with the characteristic morphologic features and immunophenotype (CD1a(+) and S100(+)). The significance of CD79a coexpression in T-cell lymphoblastic lymphoma and the association between lymphoblastic lymphoma and Langerhans cell histiocytosis are discussed.

CLINICAL VARIANTS CHARACTERIZATION

BONE

Precursor B-cell lymphoblastic lymphoma/leukemia presenting as osteoblastic bone lesions.

Recine M, Castellano-Sanchez AA, Sheldon J, Schwartz M, Cabello-Inchausti B.

Arkadi M. Rywlin, MD Department of Pathology and Laboratory Medicine, the Department of Radiology, and the Division of Hemato-Oncology, Mount Sinai Medical Center, Miami Beach, FL.
Ann Diagn Pathol 2002 Aug;6(4):236-43 Abstract quote
Lymphoblastic lymphoma is a neoplasm of precursors lymphoid cells morphologically indistinguishable from those of acute lymphoblastic leukemia. Approximately 10% to 20% of cases are of the precursor B-cell (P-BLL) phenotype.

This type of lymphoma most often manifests in the skin and lymph nodes. In recent years more case reports of P-BLL presenting as lytic bone lesions have appeared in the literature.

We describe an interesting case of P-BLL/leukemia that initially presented as an osteoblastic bone lesion and discuss the differential diagnosis from a pathologic-radiologic standpoint.

INFANCY

Primary cutaneous lymphoblastic lymphoma presenting in an 8-week old infant
Jacqueline K. Trupiano
Karen Bringelsen
and Eric D. Hsi J Cutan Pathol 2002;29:107-112 Abstract quote

Background:We report a case of primary cutaneous lymphoblastic lymphoma (LBL) presenting in an 8-week-old infant.
Methods:Histopathology and flow cytometric analysis confirmed the diagnosis of a lymphoblastic lymphoma. The cells expressed CD19, CD20, CD34 and surface immunoglobulin (sIg).

Results:The cells were negative for TdT and CD99. This unusual immunophenotype has been described as transitional pre-B-cell, in that the cells express both immature markers (CD34) and mature markers (sIg).

Conclusions:To our knowledge, only five other cases of sIg positive precursor B-cell LBL have been reported in the literature. This may represent the youngest reported case of primary cutaneous LBL, occurring at 8weeks of age.

HISTOLOGICAL TYPES CHARACTERIZATION

General

VARIANTS

Precursor B-cell Lymphoblastic Lymphoma A Predominantly Extranodal Tumor With Low Propensity for Leukemic Involvement

Pei Lin, M.D.; Dan Jones, M.D., Ph.D.; David M. Dorfman, M.D., Ph.D.; L. Jeffrey Medeiros, M.D.

From the Division of Pathology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A. (P.L., D.J., L.J.M.); and the Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, U.S.A. (D.M.D.).

Am J Surg Pathol 2000;24:1480-1490 Abstract quote

Precursor B-cell lymphoblastic lymphoma (B-LBL) is uncommon and accounts for less than 10% of cases of lymphoblastic lymphoma.

We collected 25 cases of B-LBL, occurring in children and adults, and report the clinical and histologic features.

Patients with concurrent precursor B-cell acute lymphoblastic leukemia (B-ALL) or a history thereof were excluded. There was no evidence of bone marrow disease at the time of diagnosis in 23 patients; two patients had focal (<5%) involvement. Immunophenotypic analysis was performed in all cases using flow cytometry or immunohistochemical methods. The treatment and survival data available for a subset of patients with B-LBL were compared with those from a series of patients with B-ALL at our institution. The median age was 20 years (range, 5�68 yrs); 22 (88%) patients were younger than 35 years of age. There were 17 males and 8 females. The primary sites of disease were skin (nine cases), bones (five cases), soft tissue (four cases), lymph nodes, (three cases), breast (two cases), stomach and colon (one case), and mediastinum (one case). Clinical stage was stage I in 13 cases, stage II in seven cases, stage III in three cases, and stage IV in two cases.

Histologically, each neoplasm was diffuse and composed of small to medium-sized lymphoid cells with blastic nuclear chromatin and a high mitotic rate. All cases were positive for B-cell antigens and terminal deoxynucleotidyl transferase. Thirteen (76.4%) of 17 cases analyzed were positive for CD10 and 13 (54.1%) of 24 cases assessed were positive for CD20. Of 14 patients with available survival data, all achieved complete clinical response after combination chemotherapy (13 patients) or surgical excision followed by local irradiation (one patient). Five (35.7%) patients subsequently relapsed, including the patient who had received only irradiation, and four of these patients died after a median survival time of 60 months. None of the patients had leukemia, although one patient developed extensive bone marrow involvement. Nine patients remained in complete remission and were alive at the last follow up (range, 6�144 months).

Unlike precursor T-cell lymphoblastic lymphoma, which commonly involves lymph nodes and the mediastinum, B-LBL usually involves extranodal sites, most often the skin, and rarely presents as a mediastinal mass. With aggressive chemotherapy, patients with precursor B-LBL rarely develop leukemia and appear to have a better prognosis than do patients with B-ALL.

Precursor B-Cell Lymphoblastic Lymphoma A Study of Nine Cases Lacking Blood and Bone Marrow Involvement and Review of the Literature

Anirban Maitra, MD, Robert W. McKenna, MD, Arthur G. Weinberg, MD, Nancy R. Schneider, MD, PhD, and Steven H. Kroft, MD

Am J Clin Pathol 2001;115:868-875 Abstract quote

We describe 9 cases of precursor B-cell lymphoblastic lymphoma (LYL) without evidence of marrow or blood involvement. Four patients had superficial nodal disease, 2 cutaneous involvement, and 1 each ovarian, retroperitoneal, or tonsillar primary tumor. Six patients had limited disease; 3 patients were stage III. Immunophenotyping revealed a terminal deoxynucleotidyl transferase (TdT)-positive, immature B-cell population with variable expression of CD10, CD20, and CD45. All patients are in complete clinical remission (median follow-up, 14 months).

A literature review yielded 105 patients with a diagnosis of precursor B-cell LYL based on less than 25% marrow involvement. Of these, 64% were younger than 18 years. Skin, lymph nodes, and bone were the most common sites of disease. Mediastinal involvement was uncommon. TdT, CD19, CD79a, CD10, and HLA-DR were the most frequently expressed antigens, while CD45 and CD20 were expressed in only two thirds of the cases. Cytogenetic analysis showed additional 21q material as a recurring karyotypic abnormality. At a median follow-up of 26 months, 74% of patients were alive; the median survival was 19 months for patients dying of disease. Comparison with precursor B-cell acute lymphoblastic leukemia showed several overlapping features, although distinct differences were identified.

SPECIAL STAINS/
IMMUNOHISTO-CHEMISTRY CHARACTERIZATION

B-lymphoblastic lymphoma Usually CD20 negative
CD19 and CD43 positive
CD79a +

T-lymphoblastic lymphoma Usually CD3+ but some are negative
Usually CD43+ and CD45RO-

TdT

Terminal deoxynucleotidyl transferase-negative acute lymphoblastic leukemia.

Faber J, Kantarjian H, Roberts MW, Keating M, Freireich E, Albitar M.

Division of Pathology and Laboratory Medicine, Section of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

Arch Pathol Lab Med 2000 Jan;124(1):92-7 Abstract quote

OBJECTIVE: Terminal deoxynucleotidyl transferase (TdT) is a useful marker in the diagnosis of acute lymphoblastic leukemia (ALL) (French-American-British [FAB] L1 and L2) and is most useful in distinguishing ALL from mature B-lymphoid neoplasms, such as Burkitt lymphoma (FAB L3) and other lymphoid malignancies. The frequency of TdT-negative ALL is not known. Here we report 3 TdT-negative ALL cases that met the criteria for T-cell ALL.

DESIGN: We reviewed approximately 200 cases of ALL retrieved from the database at our institution. All cases were evaluated using Wright-Giemsa, myeloperoxidase, butyrate, and TdT staining; immunophenotyped using flow cytometry; and studied using Southern blot analyses for T-cell receptors and immunoglobulin gene rearrangement.

RESULTS: All ALL cases (L1 and L2) were TdT-positive, except for 3 cases that were of early T-cell lineage. None of the 3 cases demonstrated positivity for TdT in immunofluorescence staining with polyclonal antibodies or flow cytometry with monoclonal antibodies. Flow cytometric analysis confirmed a pre-T-cell immunophenotype in all 3 cases. One of the cases showed rearrangement of a T-cell antigen receptor and immunoglobulin heavy chain (J(H)). A second case showed germline configuration of T-cell receptors, but also showed rearrangement of the J(H), despite the expression of T-cell markers only.

Terminal Deoxynucleotidyl Transferase–Positive Lymphoid Cells in Reactive Lymph Nodes From Children With Malignant Tumors
Incidence, Distribution Pattern, and Immunophenotype in 26 Patients

Mihaela Onciu, MD, Robert B. Lorsbach, MD, PhD, E. Charlene Henry, HTL(ASCP)QIHC, and Frederick G. Behm, MD

Am J Clin Pathol 2002;118:248-254 Abstract quote

The presence of terminal deoxynucleotidyl transferase (TdT)-positive lymphoid precursors in benign lymph nodes from children has been characterized insufficiently. By using single- and double-labeling immunohistochemical analysis, we examined the frequency, distribution, morphologic features, and immunophenotype of TdT-positive cells in benign lymph nodes from 26 consecutive pediatric patients (4 boys, 22 girls; age, 10 weeks-17 years; median, 4.5 years), 23 of whom had a history of malignant neoplasm.

We identified TdT-positive lymphoid cells in all 26 cases. These cells were found adjacent to medullary and cortical sinuses, with a frequency of 1 to 180 cells per high-power field (median, 20 cells), and were present singly and in small clusters. They were morphologically heterogeneous and showed a precursor B-cell immunophenotype including colocalization with CD34 by single-antibody immunohistochemical analysis and coexpression of variable levels of CD79a and CD10 and lack of CD3 expression by double immunostaining.

These features should aid in the evaluation of pediatric lymph nodes for partial involvement by lymphoblastic lymphoma/ leukemia.

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES

Blastoid mantle cell lymphoma Always consider this diagnosis before making a diagnosis of a B-cell lymphoblastic lymphoma

Thymoma If flow cytometric analysis of a mediastinal tumor shows a predominant population of T cells (Tdt+, CD1a+) consider a thymoma as well as a T-lymphoblastic lymphoma

Differentiating Lymphoblastic Lymphoma and Ewing�s Sarcoma: Lymphocyte Markers and Gene Rearrangement

Metin Ozdemirli, M.D, Ph.D., Julie C. Fanburg-Smith, M.D., Dan-Paul Hartmann, Ph.D., Norio Azumi, M.D., Ph.D. and Markku Miettinen, M.D.

Department of Pathology (MO, DH, NA), Georgetown University Medical Center, Washington, D.C.; and Department of Soft Tissue Pathology (JCF-S, MM), Armed Forces Institute of Pathology, Washington, D.C

Mod Pathol 2001;14:1175-1182 Abstract quote

We encountered a child with an intraosseous small round cell tumor that was negative for LCA, CD20 (L26), and CD3 and positive for vimentin, CD99 (MIC-2), and periodic acid-Schiff. The tumor exhibited rosette-like formations.

This case was initially interpreted as Ewing�s sarcoma (ES); however, additional studies revealed positivity for CD79a, CD43, and TdT expression, and an immunoglobulin heavy chain gene rearrangement (IgH-R) by polymerase chain reaction (PCR) established this to be a precursor B-lymphoblastic lymphoma.

Because the differential diagnosis of ES and lymphoblastic lymphoma can be difficult and the differential diagnostic value of leukocyte antigens and immunoglobulin heavy chain gene rearrangement studies have not been fully evaluated, we conducted a more extensive investigation on 33 (21 soft tissue and 12 intraosseous) ES cases.

LYMPHOBLASTIC LYMPHOMA BURKITT LYMPHOMA

NUCLEI Round or convoluted, usually no significant molding Usually round, but occasionally may show nuclear protrusions
Prominent nuclear molding, with squaring of nuclear membrane

CHROMATIN PATTERN Fine, dusty Coarsely granular

NUCLEOLI Inconspicuous Distinct, 2-5 nucleoli, often not membrane bound

CYTOPLASM
Scanty and barely visible in routine histologic sections
In Giemsa stained touch preparations, cytoplasm is apparently found only around part of the perimeter of the nucleus
Definite rim of basophilic to plasmacytoid cytoplasm, with squaring of cytoplasmic outline
In Giemsa-stained touch preparations, small lipid vacuoles are found in the basophilic cytoplasm

LINEAGE Usually T-lineage, sometimes B or NK lineage Always B lineage

TdT Positive Negative

Ki-67 High, usually <80% ~100%

PROGNOSIS AND TREATMENT CHARACTERIZATION

PROGNOSIS B lymphoblastic lymphomas have a better prognosis with a high remission rate, especially for early stage disease

Non-Hodgkin's lymphoma protocols in the treatment of patients with Burkitt's lymphoma and lymphoblastic lymphoma: a report on 58 patients.

Kaiser U, Uebelacker I, Havemann K.

Philipps-Universitat Marburg, Dept of Hematology/Oncology, Germany.

Leuk Lymphoma 1999 Dec;36(1-2):101-8 Abstract quote

Lymphoblastic lymphoma (LBL) and Burkitt's lymphoma belong to the very aggressive lymphomas requiring intensive therapy.

We retrospectively analyzed 29 patients with Burkitt's lymphoma and 29 patients with LBL who received induction therapy with a CHOP-like lymphoma protocol. Patients with Burkitt's lymphoma (with a median age of 54.5 years) have a CR rate of 72% and a lymphoma free long-time survival of 55%.

The International Prognostic Index was the most valuable prognostic factor for survival. Patients with LBL with a median age of 45 years had a CR rate of 55% and a lymphoma-free survival of 38%. Stage was the most predictive prognostic factor. Our data suggest that for older patients (>50) treatment with lymphoma protocols may yield response rates that are comparable to the results of patients with disseminated diffuse large cell lymphoma. Younger patients with risk factors should be treated with more intensive therapy like ALL-protocols.

The role of auto-transplantation after high dose therapy (HDT) however as part of primary treatment still needs to be evaluated in clinical trials. One of four patients with LBL who received HDT and one of four patients with Burkitt's lymphoma who received HDT achieved long-term remission.

TREATMENT

Value of high-dose cytarabine during interval therapy of a Berlin-Frankfurt-Munster-based protocol in increased-risk children with acute lymphoblastic leukemia and lymphoblastic lymphoma: results of the European Organization for Research and Treatment of Cancer 58881 randomized phase III trial.

Millot F, Suciu S, Philippe N, Benoit Y, Mazingue F, Uyttebroeck A, Lutz P, Mechinaud F, Robert A, Boutard P, Marguerite G, Ferster A, Plouvier E, Rialland X, Behard C, Plantaz D, Dresse MF, Philippet P, Norton L, Thyss A, Dastugue N, Waterkeyn C, Vilmer E, Otten J;

Children's Leukemia Cooperative Group of the European Organiztaion for Research and Treatment of Cancer. Department of Pediatrics, University Hospital of Poitiers, France.

J Clin Oncol 2001 Apr 1;19(7):1935-42 Abstract quote

PURPOSE: The European Organization for Research and Treatment of Cancer 58881 study was designed to test in a prospective multicentric randomized trial the value of high-dose (HD) intravenous (IV) cytarabine (Ara-C) added to HD IV methotrexate (MTX) to reduce the incidence of CNS and systemic relapses in children with increased-risk acute lymphoblastic leukemia (ALL) or stage III and IV lymphoblastic lymphoma treated with a Berlin-Frankfurt-Munster (BFM)-based regimen.

PATIENTS AND METHODS: After completion of induction-consolidation phase, children with increased-risk (risk factor > 0.8 or T-lineage) ALL or stage III and IV lymphoblastic lymphoma were randomized to receive four courses of HD MTX (5 g/m(2) over 24 hours every 2 weeks) and four intrathecal administrations of MTX (Arm A) or the same treatment schedule with additional HD IV Ara-C (1 g/m(2) in bolus injection 12 and 24 hours after the start of each MTX infusion) (Arm B).

RESULTS: Between January 1990 and January 1996, 653 patients with ALL (593 patients) or lymphoblastic lymphoma (60 patients) were randomized: 323 were assigned to Arm A (without Ara-C) and 330 to Arm B (with Ara-C). A total of 190 events (177 relapses and 13 deaths without relapse) were reported, and the median follow up was 6.5 years (range, 2 to 10 years). The incidence rates of CNS relapse were similar in both arms whether isolated (5.6% and 3.3%, respectively) or combined (5.3% and 4.6%, respectively). The estimated 6-year disease-free survival (DFS) rate was similar (log-rank P =.67) in the two treatment groups: 70.4% (SE = 2.6%) in Arm A and 71.0% (SE = 2.5%) in Arm B. The 6-year DFS rate was similar for ALL and LL patients: 70.2% (SE = 1.9%) versus 76.3% (SE = 5.6%).

CONCLUSION: Prevention of CNS relapse was satisfactorily achieved with HD IV MTX and intrathecal injections of MTX in children with increased-risk ALL or stage III and IV lymphoblastic lymphoma treated with our BFM-based treatment protocol in which cranial irradiation was omitted. Disappointingly, with the dose schedule used in this protocol, HD Ara-C added to HD MTX, although well tolerated, failed to further decrease the incidence of CNS relapse or to improve the overall DFS.

Taken from Chan JKC. Practical Lymphoma Diagnosis: A Simplified Approach. Presented at the 111th Semi-Annual California Tumor Tissue Registry. December 2001.
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

Commonly Used Terms

Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation

Commonly Used Terms
This is a glossary of terms often found in a pathology report.

Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscope

Surgical Pathology Report
Examine an actual biopsy report to understand what each section means

Special Stains
Understand the tools the pathologist utilizes to aid in the diagnosis

How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate

Got Path?
Recent teaching cases and lectures presented in conferences

Internet Links

Pathologists Who Make A Difference
Search for a Physician Specialist

Last Updated 1/5/2004

Send mail to The Doctor's Doctor with questions or comments about this web site.
Read the Medical Disclaimer.

Copyright © The Doctor's Doctor

SPECIAL STAINS/ IMMUNOHISTO-CHEMISTRY	CHARACTERIZATION
B-lymphoblastic lymphoma	Usually CD20 negative CD19 and CD43 positive CD79a +
T-lymphoblastic lymphoma	Usually CD3+ but some are negative Usually CD43+ and CD45RO-
TdT
Terminal deoxynucleotidyl transferase-negative acute lymphoblastic leukemia. Faber J, Kantarjian H, Roberts MW, Keating M, Freireich E, Albitar M. Division of Pathology and Laboratory Medicine, Section of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.	Arch Pathol Lab Med 2000 Jan;124(1):92-7 Abstract quote OBJECTIVE: Terminal deoxynucleotidyl transferase (TdT) is a useful marker in the diagnosis of acute lymphoblastic leukemia (ALL) (French-American-British [FAB] L1 and L2) and is most useful in distinguishing ALL from mature B-lymphoid neoplasms, such as Burkitt lymphoma (FAB L3) and other lymphoid malignancies. The frequency of TdT-negative ALL is not known. Here we report 3 TdT-negative ALL cases that met the criteria for T-cell ALL. DESIGN: We reviewed approximately 200 cases of ALL retrieved from the database at our institution. All cases were evaluated using Wright-Giemsa, myeloperoxidase, butyrate, and TdT staining; immunophenotyped using flow cytometry; and studied using Southern blot analyses for T-cell receptors and immunoglobulin gene rearrangement. RESULTS: All ALL cases (L1 and L2) were TdT-positive, except for 3 cases that were of early T-cell lineage. None of the 3 cases demonstrated positivity for TdT in immunofluorescence staining with polyclonal antibodies or flow cytometry with monoclonal antibodies. Flow cytometric analysis confirmed a pre-T-cell immunophenotype in all 3 cases. One of the cases showed rearrangement of a T-cell antigen receptor and immunoglobulin heavy chain (J(H)). A second case showed germline configuration of T-cell receptors, but also showed rearrangement of the J(H), despite the expression of T-cell markers only.
Terminal Deoxynucleotidyl Transferase–Positive Lymphoid Cells in Reactive Lymph Nodes From Children With Malignant Tumors Incidence, Distribution Pattern, and Immunophenotype in 26 Patients Mihaela Onciu, MD, Robert B. Lorsbach, MD, PhD, E. Charlene Henry, HTL(ASCP)QIHC, and Frederick G. Behm, MD	Am J Clin Pathol 2002;118:248-254 Abstract quote The presence of terminal deoxynucleotidyl transferase (TdT)-positive lymphoid precursors in benign lymph nodes from children has been characterized insufficiently. By using single- and double-labeling immunohistochemical analysis, we examined the frequency, distribution, morphologic features, and immunophenotype of TdT-positive cells in benign lymph nodes from 26 consecutive pediatric patients (4 boys, 22 girls; age, 10 weeks-17 years; median, 4.5 years), 23 of whom had a history of malignant neoplasm. We identified TdT-positive lymphoid cells in all 26 cases. These cells were found adjacent to medullary and cortical sinuses, with a frequency of 1 to 180 cells per high-power field (median, 20 cells), and were present singly and in small clusters. They were morphologically heterogeneous and showed a precursor B-cell immunophenotype including colocalization with CD34 by single-antibody immunohistochemical analysis and coexpression of variable levels of CD79a and CD10 and lack of CD3 expression by double immunostaining. These features should aid in the evaluation of pediatric lymph nodes for partial involvement by lymphoblastic lymphoma/ leukemia.

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/ Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

CLINICAL VARIANTS	CHARACTERIZATION
BONE
Precursor B-cell lymphoblastic lymphoma/leukemia presenting as osteoblastic bone lesions. Recine M, Castellano-Sanchez AA, Sheldon J, Schwartz M, Cabello-Inchausti B. Arkadi M. Rywlin, MD Department of Pathology and Laboratory Medicine, the Department of Radiology, and the Division of Hemato-Oncology, Mount Sinai Medical Center, Miami Beach, FL.	Ann Diagn Pathol 2002 Aug;6(4):236-43 Abstract quote Lymphoblastic lymphoma is a neoplasm of precursors lymphoid cells morphologically indistinguishable from those of acute lymphoblastic leukemia. Approximately 10% to 20% of cases are of the precursor B-cell (P-BLL) phenotype. This type of lymphoma most often manifests in the skin and lymph nodes. In recent years more case reports of P-BLL presenting as lytic bone lesions have appeared in the literature. We describe an interesting case of P-BLL/leukemia that initially presented as an osteoblastic bone lesion and discuss the differential diagnosis from a pathologic-radiologic standpoint.
INFANCY
Primary cutaneous lymphoblastic lymphoma presenting in an 8-week old infant Jacqueline K. Trupiano Karen Bringelsen and Eric D. Hsi	J Cutan Pathol 2002;29:107-112 Abstract quote Background:We report a case of primary cutaneous lymphoblastic lymphoma (LBL) presenting in an 8-week-old infant. Methods:Histopathology and flow cytometric analysis confirmed the diagnosis of a lymphoblastic lymphoma. The cells expressed CD19, CD20, CD34 and surface immunoglobulin (sIg). Results:The cells were negative for TdT and CD99. This unusual immunophenotype has been described as transitional pre-B-cell, in that the cells express both immature markers (CD34) and mature markers (sIg). Conclusions:To our knowledge, only five other cases of sIg positive precursor B-cell LBL have been reported in the literature. This may represent the youngest reported case of primary cutaneous LBL, occurring at 8weeks of age.

HISTOLOGICAL TYPES	CHARACTERIZATION
General
VARIANTS
Precursor B-cell Lymphoblastic Lymphoma A Predominantly Extranodal Tumor With Low Propensity for Leukemic Involvement Pei Lin, M.D.; Dan Jones, M.D., Ph.D.; David M. Dorfman, M.D., Ph.D.; L. Jeffrey Medeiros, M.D. From the Division of Pathology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A. (P.L., D.J., L.J.M.); and the Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, U.S.A. (D.M.D.).	Am J Surg Pathol 2000;24:1480-1490 Abstract quote Precursor B-cell lymphoblastic lymphoma (B-LBL) is uncommon and accounts for less than 10% of cases of lymphoblastic lymphoma. We collected 25 cases of B-LBL, occurring in children and adults, and report the clinical and histologic features. Patients with concurrent precursor B-cell acute lymphoblastic leukemia (B-ALL) or a history thereof were excluded. There was no evidence of bone marrow disease at the time of diagnosis in 23 patients; two patients had focal (<5%) involvement. Immunophenotypic analysis was performed in all cases using flow cytometry or immunohistochemical methods. The treatment and survival data available for a subset of patients with B-LBL were compared with those from a series of patients with B-ALL at our institution. The median age was 20 years (range, 5�68 yrs); 22 (88%) patients were younger than 35 years of age. There were 17 males and 8 females. The primary sites of disease were skin (nine cases), bones (five cases), soft tissue (four cases), lymph nodes, (three cases), breast (two cases), stomach and colon (one case), and mediastinum (one case). Clinical stage was stage I in 13 cases, stage II in seven cases, stage III in three cases, and stage IV in two cases. Histologically, each neoplasm was diffuse and composed of small to medium-sized lymphoid cells with blastic nuclear chromatin and a high mitotic rate. All cases were positive for B-cell antigens and terminal deoxynucleotidyl transferase. Thirteen (76.4%) of 17 cases analyzed were positive for CD10 and 13 (54.1%) of 24 cases assessed were positive for CD20. Of 14 patients with available survival data, all achieved complete clinical response after combination chemotherapy (13 patients) or surgical excision followed by local irradiation (one patient). Five (35.7%) patients subsequently relapsed, including the patient who had received only irradiation, and four of these patients died after a median survival time of 60 months. None of the patients had leukemia, although one patient developed extensive bone marrow involvement. Nine patients remained in complete remission and were alive at the last follow up (range, 6�144 months). Unlike precursor T-cell lymphoblastic lymphoma, which commonly involves lymph nodes and the mediastinum, B-LBL usually involves extranodal sites, most often the skin, and rarely presents as a mediastinal mass. With aggressive chemotherapy, patients with precursor B-LBL rarely develop leukemia and appear to have a better prognosis than do patients with B-ALL.
Precursor B-Cell Lymphoblastic Lymphoma A Study of Nine Cases Lacking Blood and Bone Marrow Involvement and Review of the Literature Anirban Maitra, MD, Robert W. McKenna, MD, Arthur G. Weinberg, MD, Nancy R. Schneider, MD, PhD, and Steven H. Kroft, MD	Am J Clin Pathol 2001;115:868-875 Abstract quote We describe 9 cases of precursor B-cell lymphoblastic lymphoma (LYL) without evidence of marrow or blood involvement. Four patients had superficial nodal disease, 2 cutaneous involvement, and 1 each ovarian, retroperitoneal, or tonsillar primary tumor. Six patients had limited disease; 3 patients were stage III. Immunophenotyping revealed a terminal deoxynucleotidyl transferase (TdT)-positive, immature B-cell population with variable expression of CD10, CD20, and CD45. All patients are in complete clinical remission (median follow-up, 14 months). A literature review yielded 105 patients with a diagnosis of precursor B-cell LYL based on less than 25% marrow involvement. Of these, 64% were younger than 18 years. Skin, lymph nodes, and bone were the most common sites of disease. Mediastinal involvement was uncommon. TdT, CD19, CD79a, CD10, and HLA-DR were the most frequently expressed antigens, while CD45 and CD20 were expressed in only two thirds of the cases. Cytogenetic analysis showed additional 21q material as a recurring karyotypic abnormality. At a median follow-up of 26 months, 74% of patients were alive; the median survival was 19 months for patients dying of disease. Comparison with precursor B-cell acute lymphoblastic leukemia showed several overlapping features, although distinct differences were identified.

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
Blastoid mantle cell lymphoma	Always consider this diagnosis before making a diagnosis of a B-cell lymphoblastic lymphoma
Thymoma	If flow cytometric analysis of a mediastinal tumor shows a predominant population of T cells (Tdt+, CD1a+) consider a thymoma as well as a T-lymphoblastic lymphoma
Differentiating Lymphoblastic Lymphoma and Ewing�s Sarcoma: Lymphocyte Markers and Gene Rearrangement Metin Ozdemirli, M.D, Ph.D., Julie C. Fanburg-Smith, M.D., Dan-Paul Hartmann, Ph.D., Norio Azumi, M.D., Ph.D. and Markku Miettinen, M.D. Department of Pathology (MO, DH, NA), Georgetown University Medical Center, Washington, D.C.; and Department of Soft Tissue Pathology (JCF-S, MM), Armed Forces Institute of Pathology, Washington, D.C	Mod Pathol 2001;14:1175-1182 Abstract quote We encountered a child with an intraosseous small round cell tumor that was negative for LCA, CD20 (L26), and CD3 and positive for vimentin, CD99 (MIC-2), and periodic acid-Schiff. The tumor exhibited rosette-like formations. This case was initially interpreted as Ewing�s sarcoma (ES); however, additional studies revealed positivity for CD79a, CD43, and TdT expression, and an immunoglobulin heavy chain gene rearrangement (IgH-R) by polymerase chain reaction (PCR) established this to be a precursor B-lymphoblastic lymphoma. Because the differential diagnosis of ES and lymphoblastic lymphoma can be difficult and the differential diagnostic value of leukocyte antigens and immunoglobulin heavy chain gene rearrangement studies have not been fully evaluated, we conducted a more extensive investigation on 33 (21 soft tissue and 12 intraosseous) ES cases.

	LYMPHOBLASTIC LYMPHOMA	BURKITT LYMPHOMA
NUCLEI	Round or convoluted, usually no significant molding	Usually round, but occasionally may show nuclear protrusions Prominent nuclear molding, with squaring of nuclear membrane
CHROMATIN PATTERN	Fine, dusty	Coarsely granular
NUCLEOLI	Inconspicuous	Distinct, 2-5 nucleoli, often not membrane bound
CYTOPLASM	Scanty and barely visible in routine histologic sections In Giemsa stained touch preparations, cytoplasm is apparently found only around part of the perimeter of the nucleus	Definite rim of basophilic to plasmacytoid cytoplasm, with squaring of cytoplasmic outline In Giemsa-stained touch preparations, small lipid vacuoles are found in the basophilic cytoplasm
LINEAGE	Usually T-lineage, sometimes B or NK lineage	Always B lineage
TdT	Positive	Negative
Ki-67	High, usually <80%	~100%

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSIS	B lymphoblastic lymphomas have a better prognosis with a high remission rate, especially for early stage disease
Non-Hodgkin's lymphoma protocols in the treatment of patients with Burkitt's lymphoma and lymphoblastic lymphoma: a report on 58 patients. Kaiser U, Uebelacker I, Havemann K. Philipps-Universitat Marburg, Dept of Hematology/Oncology, Germany.	Leuk Lymphoma 1999 Dec;36(1-2):101-8 Abstract quote Lymphoblastic lymphoma (LBL) and Burkitt's lymphoma belong to the very aggressive lymphomas requiring intensive therapy. We retrospectively analyzed 29 patients with Burkitt's lymphoma and 29 patients with LBL who received induction therapy with a CHOP-like lymphoma protocol. Patients with Burkitt's lymphoma (with a median age of 54.5 years) have a CR rate of 72% and a lymphoma free long-time survival of 55%. The International Prognostic Index was the most valuable prognostic factor for survival. Patients with LBL with a median age of 45 years had a CR rate of 55% and a lymphoma-free survival of 38%. Stage was the most predictive prognostic factor. Our data suggest that for older patients (>50) treatment with lymphoma protocols may yield response rates that are comparable to the results of patients with disseminated diffuse large cell lymphoma. Younger patients with risk factors should be treated with more intensive therapy like ALL-protocols. The role of auto-transplantation after high dose therapy (HDT) however as part of primary treatment still needs to be evaluated in clinical trials. One of four patients with LBL who received HDT and one of four patients with Burkitt's lymphoma who received HDT achieved long-term remission.
TREATMENT
Value of high-dose cytarabine during interval therapy of a Berlin-Frankfurt-Munster-based protocol in increased-risk children with acute lymphoblastic leukemia and lymphoblastic lymphoma: results of the European Organization for Research and Treatment of Cancer 58881 randomized phase III trial. Millot F, Suciu S, Philippe N, Benoit Y, Mazingue F, Uyttebroeck A, Lutz P, Mechinaud F, Robert A, Boutard P, Marguerite G, Ferster A, Plouvier E, Rialland X, Behard C, Plantaz D, Dresse MF, Philippet P, Norton L, Thyss A, Dastugue N, Waterkeyn C, Vilmer E, Otten J; Children's Leukemia Cooperative Group of the European Organiztaion for Research and Treatment of Cancer. Department of Pediatrics, University Hospital of Poitiers, France.	J Clin Oncol 2001 Apr 1;19(7):1935-42 Abstract quote PURPOSE: The European Organization for Research and Treatment of Cancer 58881 study was designed to test in a prospective multicentric randomized trial the value of high-dose (HD) intravenous (IV) cytarabine (Ara-C) added to HD IV methotrexate (MTX) to reduce the incidence of CNS and systemic relapses in children with increased-risk acute lymphoblastic leukemia (ALL) or stage III and IV lymphoblastic lymphoma treated with a Berlin-Frankfurt-Munster (BFM)-based regimen. PATIENTS AND METHODS: After completion of induction-consolidation phase, children with increased-risk (risk factor > 0.8 or T-lineage) ALL or stage III and IV lymphoblastic lymphoma were randomized to receive four courses of HD MTX (5 g/m(2) over 24 hours every 2 weeks) and four intrathecal administrations of MTX (Arm A) or the same treatment schedule with additional HD IV Ara-C (1 g/m(2) in bolus injection 12 and 24 hours after the start of each MTX infusion) (Arm B). RESULTS: Between January 1990 and January 1996, 653 patients with ALL (593 patients) or lymphoblastic lymphoma (60 patients) were randomized: 323 were assigned to Arm A (without Ara-C) and 330 to Arm B (with Ara-C). A total of 190 events (177 relapses and 13 deaths without relapse) were reported, and the median follow up was 6.5 years (range, 2 to 10 years). The incidence rates of CNS relapse were similar in both arms whether isolated (5.6% and 3.3%, respectively) or combined (5.3% and 4.6%, respectively). The estimated 6-year disease-free survival (DFS) rate was similar (log-rank P =.67) in the two treatment groups: 70.4% (SE = 2.6%) in Arm A and 71.0% (SE = 2.5%) in Arm B. The 6-year DFS rate was similar for ALL and LL patients: 70.2% (SE = 1.9%) versus 76.3% (SE = 5.6%). CONCLUSION: Prevention of CNS relapse was satisfactorily achieved with HD IV MTX and intrathecal injections of MTX in children with increased-risk ALL or stage III and IV lymphoblastic lymphoma treated with our BFM-based treatment protocol in which cranial irradiation was omitted. Disappointingly, with the dose schedule used in this protocol, HD Ara-C added to HD MTX, although well tolerated, failed to further decrease the incidence of CNS relapse or to improve the overall DFS.