Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

B-Cell Lymphoma

  • Author: Ajeet Gajra, MD; Chief Editor: Emmanuel C Besa, MD  more...
 
Updated: Sep 21, 2015
 

Practice Essentials

Non-Hodgkin lymphoma (NHL) is a collective term for a heterogeneous group of lymphoproliferative malignancies with differing patterns of behavior and responses to treatment.[1] Most NHLs (80-85%) are of B-cell origin. See the image below.

Diffuse large B-cell non-Hodgkin lymphoma. Large cDiffuse large B-cell non-Hodgkin lymphoma. Large cells with abundant cytoplasm and large round-ovoid nuclei with thick nuclear membrane and multiple prominent nucleoli.

Signs and symptoms

Lymphadenopathy is the most common manifestation of lymphoma. Lymphadenopathy may wax and wane. Spontaneous remissions have been documented, most commonly in patients with low-grade lymphomas.

Systemic symptoms known to be associated with adverse prognosis include the following:

  • Unexplained fevers
  • Night sweats
  • Weight loss

Organ-specific symptoms that may lead to identification of specific sites of involvement include the following:

  • Shortness of breath, chest pain, cough
  • Abdominal pain and distention
  • Bone pain
  • CNS symptoms

Typical physical examination findings include the following:

  • Pallor (suggesting anemia)
  • Purpura, petechiae, or ecchymoses (suggesting thrombocytopenia)

Findings in patients with an advanced high-grade lymphoma may include the following:

  • High fever
  • Tachycardia
  • Respiratory distress

Examples of findings that might direct further investigations and subsequent therapy include the following:

  • Pharyngeal involvement
  • Thyroid mass
  • Evidence of pleural effusion
  • Abdominal mass
  • Testicular mass
  • Cutaneous lesions

Workup

Laboratory studies are as follows:

  • CBC with differential and examination of a peripheral smear – To assess bone marrow function and rule out the presence of abnormal circulating cells in the peripheral blood
  • Screening chemistries – To assess renal and hepatic function and measure serum glucose, calcium, albumin, lactate dehydrogenase (LDH), and beta2-microglobulin
  • Serum protein electrophoresis – Frequently appropriate
  • HIV serology – Appropriate for patients with risk factors, especially those with large cell or small noncleaved-cell histologies

Imaging studies

  • Chest radiography and CT scans of the thorax, abdomen, and pelvis should be performed at initial evaluation in almost all patients with NHL; CT scanning can identify both nodal and extranodal sites of involvement and can provide an important approach to monitoring response to therapy
  • MRI is useful in identifying bone and CNS involvement and can reveal meningeal involvement when gadolinium is used
  • Gallium scans provide functional information and thus have potential value in resolving difficulties in determining response to therapy

Diagnostic procedures

  • In addition to a diagnostic biopsy, almost all patients should have a bone marrow aspirate and biopsy performed
  • Flow cytometry and immunohistochemical stains of the biopsied material should be performed to confirm the diagnosis and for accurate subtyping
  • Thoracentesis – In patients with a significant pleural effusion
  • Paracentesis – In patients with ascites

Histologic findings

The most common subtypes of B-cell NHL are as follows:

  • Chronic lymphocytic leukemia/small lymphocytic lymphoma
  • Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue
  • Nodal marginal zone lymphoma
  • Follicular lymphoma
  • Mantle cell lymphoma
  • Diffuse large B-cell lymphoma
  • Burkitt lymphoma
  • Primary mediastinal (thymic) large B-cell lymphoma

Management

Modalities of antilymphoma therapy are as follows:

  • Radiation therapy – Used in early-stage limited disease, as consolidative therapy in aggressive lymphomas that respond to chemotherapy, and to manage some complications (eg, superior vena cava syndrome, impending pathologic fracture)
  • Chemotherapy – Curative as well as palliative
  • Biologic therapy – Monoclonal antibody (mAb) therapy (eg, rituximab)

Typical medical therapy by stage is as follows:

  • Indolent stage I and contiguous stage II adult NHL – Radiation therapy
  • Aggressive stage I and contiguous stage II adult NHL – Radiation therapy, chemotherapy with adjuvant radiation therapy
  • Indolent, noncontiguous stage II/III/IV adult NHL – Controversial; treatment options range from watchful waiting to aggressive myeloablative therapy with hematopoietic precursor cell rescue
  • Aggressive noncontiguous stage II/III/IV adult B-cell lymphoma – Doxorubicin-based combination chemotherapy, with or without supplemental local field radiation

Typical therapy for specific subtypes of lymphoma is as follows:

  • Follicular lymphoma - Watchful waiting, for asymptomatic patients with normal blood cell counts and no critical visceral involvement; medical treatments include alkylating agents (eg, chlorambucil or cyclophosphamide; cornerstone of treatment) and rituximab
  • Splenic marginal zone lymphoma – Splenectomy
  • Extranodal B-cell lymphoma of MALT – Antibiotic treatment of Helicobacter pylori infection; surgical excision; systemic chemotherapy for widespread disease
  • Mantle cell lymphoma – Combination chemotherapy; bortezomib for relapsed disease
  • Diffuse large B-cell lymphoma – Current standard therapy is rituximab with cyclophosphamide, hydroxydaunorubicin, vincristine (Oncovin), prednisone, and bleomycin (R-CHOP)
  • Mediastinal diffuse large B-cell lymphoma – CHOP with adjuvant field radiation therapy
  • Burkitt lymphoma – Most adult treatment regimens include brief high-dose combination chemotherapy with CNS prophylaxis with and without cranial irradiation
Next

Background

Non-Hodgkin lymphoma (NHL) is a collective term for a heterogeneous group of lymphoproliferative malignancies with differing patterns of behavior and responses to treatment.[1] NHL must be distinguished from Hodgkin lymphoma with certainty before therapy is initiated.

NHL usually originates in the lymphoid tissues and can spread to other organs. However, compared with Hodgkin lymphoma, NHL is much less predictable and has a far greater predilection to disseminate to extranodal sites. The prognosis depends on the histologic type, stage, and treatment.

Most NHLs (80-85%) are of B-cell origin. Accordingly, the following discussion pertains to B-cell NHL, although the classification as outlined below includes all lymphoproliferative diseases. Furthermore, management discussed in this article refers only to B-cell NHL in previously healthy individuals and is not applicable to patients with HIV or other immunocompromised conditions.

NHL can be divided into two general prognostic groups: indolent lymphomas and aggressive lymphomas. Indolent lymphomas carry a relatively good prognosis, with median survival time as long as 10 years, but they are not usually curable in advanced stages. Early-stage (stage I and II) indolent NHL can be treated effectively with radiation therapy alone. Most of the indolent types are nodular (or follicular) in morphology. The aggressive type of NHL has a shorter natural history, but a significant number of cases are curable with combination chemotherapy regimens.

Special care is necessary when multiagent chemotherapy is administered. The specific regimen should be clearly documented and the plan outlined in the patient’s chart. The dosage should be calculated carefully and always cross-checked by the pharmacist. The total and cumulative anthracycline dose should be clearly charted.

Oncologic emergencies, such as tumor lysis syndrome, spinal cord compression, ureteric obstruction, lymphomatous meningitis, and superior vena cava syndrome, though infrequent in terms of overall incidence, are observed relatively commonly in NHL as compared with other malignancies; a high index of clinical suspicion and early confirmatory tests are essential.

In general, with modern treatment of patients with NHL, the overall survival rate at 5 years is approximately 70%.[2] Most relapses occur in the first 2 years after therapy. The risk of late relapse is higher in patients with a divergent histology of both indolent and aggressive disease.

Whereas indolent NHL is responsive to radiation therapy and chemotherapy, a continuous rate of relapse is usually observed in advanced stages. However, patients can often be retreated with considerable success as long as the disease histology remains low grade.

Patients who present with or convert to aggressive forms of NHL may achieve complete remission with combination chemotherapy regimens, with or without aggressive high-dose consolidation therapy with marrow or stem cell support. Aggressive lymphomas are increasingly observed in patients who are HIV positive, and treatment of these patients requires special consideration.

Go to Non-Hodgkin Lymphoma and Cutaneous B-Cell Lymphoma for complete information on these topics.

For patient education resources, see the Blood and Lymphatic System Center, as well as Lymphoma.

Previous
Next

Classification

B-cell and T/natural killer (NK)-cell neoplasms are clonal tumors of mature and immature B cells, T cells or NK cells at various stages of differentiation. B-cell neoplasms tend to mimic stages of normal B-cell differentiation, and the resemblance to normal cell stages is a major basis for their classification and nomenclature.[3]

Per the 2008 revised World Health Organization (WHO) classification, B-cell malignancies are divided into two broad categories[3] : (1) precursor B-cell neoplasms, which include B lymphoblastic leukemia/lymphoma with or without recurrent genetic abnormalities, and (2) mature B-cell neoplasms.

The following classification deals with only the mature B-cell neoplasms. Both lymphomas and lymphoid leukemias are included in this classification because both solid and circulating phases are present in many lymphoid neoplasms and distinction between them is artificial. For instance, B-cell chronic lymphocytic leukemia (CLL) and B-cell small lymphocytic lymphoma (SLL) are different manifestations of the same neoplasm, as are lymphoblastic lymphomas and T-cell acute lymphocytic leukemias.

The WHO classification of mature B-cell neoplasms is as follows[3] :

  • CLL/SLL
  • B-cell prolymphocytic leukemia
  • Splenic marginal zone lymphoma
  • Hairy cell leukemia
  • Splenic lymphoma/leukemia, unclassifiable
  • Lymphoplasmacytic lymphoma
  • Heavy chain diseases
  • Plasma cell neoplasms
  • Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)
  • Nodal marginal zone lymphoma
  • Follicular lymphoma
  • Primary cutaneous follicle center cell lymphoma
  • Mantle cell lymphoma
  • Diffuse large B-cell lymphoma (DLBCL), not otherwise specified
  • T-cell/histiocyte rich large B-cell lymphoma
  • Primary DLBCL of the central nervous system (CNS)
  • Epstein-Barr virus (EBV)-positive DLBCL of the elderly
  • DLBCL associated with chronic inflammation
  • Lymphomatoid granulomatosis
  • Primary mediastinal (thymic) large B-cell lymphoma
  • Intravascular large B-cell lymphoma
  • Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma
  • Plasmablastic lymphoma
  • Large B-cell lymphoma arising in human herpesvirus 8 (HHV-8)–associated multicentric Castleman disease
  • Primary effusion lymphoma
  • Burkitt lymphoma
  • B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma
  • B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma
Previous
Next

Pathophysiology and Etiology

There are several known associations and genetic abnormalities that may play a role in the etiology of non-Hodgkin lymphoma (NHL) in a particular patient. These include genetic abnormalities, environmental factors, viruses, immunodeficiency states, and connective-tissue disorders.

Chromosomal translocations and molecular rearrangements

Nonrandom chromosomal and molecular rearrangements (see the table below) play an important role in the pathogenesis of many lymphomas and correlate with histology and immunophenotype.

Table 1. Chromosomal Abnormalities in B-Cell Non-Hodgkin Lymphoma (Open Table in a new window)

Cytogenetic AbnormalityHistologyAntigen RearrangementOncogene Expression
t(14;18)(q32;q21)Follicular, diffuse large cellIgH*bcl- 2
t(11;14)(q13;q32)Mantle cellIgHcyclin-D1/bcl-1
t(1;14)(p22;q32)MALT lymphomaIgHbcl- 10
t(11;18)(q21;q21)MALT lymphomaIgHUnknown
t(9;14)(p13;q32)Lymphoplasmacytic lymphomaIgHPAX-5
8q24 translocations



t(8;14)(q24;q32)



t(2;8)(p11-12;q24)



t(8;22)(q24;q11)



Burkitt lymphomaIgH



Ig-8



Ig-6



c-myc
Trisomy 12, deletion 11q22-23, 17p13, and 6q21CLL
*Immunoglobulin H (IgH)



MALT = Mucosa-associated lymphoid tissue.



The most common chromosomal abnormality associated with NHL is the t(14;18)(q32;q21) translocation that is found in 85% of follicular lymphomas and 25-30% of intermediate-grade NHLs. This translocation results in the juxtaposition of the bcl -2 apoptotic inhibitor oncogene at band 18q21 to the heavy-chain region of the immunoglobulin (Ig) locus within band 14q32, resulting in its overexpression.

The t(11;14)(q13;q32) translocation results in overexpression of bcl -1 (cyclin-D1/PRAD1), a cell cycle control gene on band 11q13, and is diagnostic of mantle cell lymphoma.

For work up of any high grade B-cell lymphoma of germinal center origin typically FISH studies for evaluation of both myc and bcl-2 should be ordered in order to establish classification of " double hit" lymphomas. Double hit B-cell lymphomas are specific subtype of diffuse large B-cell lymphomas which have a much more aggressive clinical course and are assocaited with both translocations of the myc and bcl-2 oncogene.

Environmental factors

Certain workers have a slightly increased risk of NHL, including farmers; pesticide applicators; flour millers; meat workers; painters; mechanics; and workers in the petroleum, rubber, plastics, and synthetics industries.

Chemicals that have been linked to the development of NHL include a variety of pesticides and herbicides (eg, organophosphates, chlorophenols), solvents and organic chemicals (eg, benzene, carbon tetrachloride), and wood preservatives.

Patients who receive cancer chemotherapy, radiation therapy, or both are at increased risk of developing NHL.

Viruses

Several viruses have been implicated in the pathogenesis of NHL, including the Epstein-Barr virus (EBV) in Burkitt lymphoma (especially in endemic areas of Africa), sinonasal lymphoma in Asia and South America, and lymphomas in immunocompromised patients; human T-lymphotropic virus 1 (HTLV-1) in adult T-cell lymphoma/leukemia; and human herpesvirus 8 (HHV-8) in body cavity–based lymphomas in patients with HIV infection.

Immunodeficiency states

Immunodeficiency states that seem to predispose to NHL include congenital immunodeficiency states (eg, ataxia telangiectasia, Wiskott-Aldrich syndrome, common variable hypogammaglobulinemia, and severe combined immunodeficiency), as well as acquired immunodeficiency states (eg, HIV infection and iatrogenic immunosuppression for solid organ or bone marrow transplant recipients).

Connective-tissue disorders

Certain connective-tissue disorders are also associated with an increased risk of NHL. These include Sjögren syndrome, rheumatoid arthritis, chronic lymphocytic thyroiditis, and systemic lupus erythematosus (SLE).

Other disease states

Increased incidence of gastrointestinal (GI) lymphomas is observed in patients with celiac sprue and inflammatory bowel disease. Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is observed most frequently, but not exclusively, in association with Helicobacter pylori infection.

Previous
Next

Epidemiology

United States statistics

After a striking increase in incidence rates between 1970 and 1995 (which may in part have reflected improved diagnosis), the rates for new cases of non-Hodgkin lymphoma (NHL) have remained stable for more than a decade, and death rates have not changed significantly since 2002. The lifetime risk of being diagnosed with NHL is 2.1%. It has been estimated that in 2015, 71,850 new cases of NHL will be diagnosed, with 19,790 deaths. NHL is the seventh most common cancer in the US, accounting for 4.3% of new cancers and 3.4% of all cancer-related deaths.[2]

International statistics

In Europe, NHL is the 11th most common cancer, representing 3% of the total cancer diagnoses in 2012.[4]

Certain endemic geographical factors appear to influence the development of NHL in specific areas. For example, in equatorial Africa, a variant of Burkitt lymphoma associated with Epstein-Barr virus (EBV) is the most common childhood malignancy.

In the Middle East, heavy-chain disease (alpha) is a disorder of B-lymphoid cells that is characterized by diffuse thickening of the small intestine caused by a lymphoplasmacytic infiltrate with secretion of incomplete immunoglobulin A (IgA) heavy chains. This clinicopathologic entity is rarely encountered in individuals who are not of Mediterranean ethnicity.

Follicular lymphomas are more common in North America and Europe but are rare in the Caribbean, Africa, China, Japan, and the Middle East.

Age-, sex-, and race-associated differences in incidence

NHL is most frequently diagnosed in  persoms 65-74 years old. High-grade lymphoblastic and small noncleaved-cell lymphomas are the only subtypes of B-cell NHL that are observed more commonly in children and young adults.

NHL is more common in male subjects: the reported incidence is 23.9 cases per 100,000 population in men, compared with 16.3 cases per 100,000 population in women. However, the incidence of NHL in some anatomic sites, such as the thyroid, may be higher in women.[2]

The incidence of NHL is highest in white people: it is reported to be 24.9 cases per 100,000 population in white men, compared with 20.6 and 17.8 cases per 100,000 population in Hispanic and African-American men, respectively. The incidence rates are lowest among Asians, Pacific Islanders and Native Americans.ref2}

Previous
Next

Prognosis

Overall, the prognosis for non-Hodgkin lymphoma (NHL) varies with the histology, the stage of disease at diagnosis, the response of disease to therapy, and other factors as listed in the International Prognostic Index (IPI) score.

 The IPI was originally designed as a prognostic factor model for aggressive NHL, but can be useful for predicting the outcome of patients with low-grade lymphoma. This index is also used to identify patients at high risk of relapse based on specific sites of involvement, including bone marrow, central nervous system, liver, testis, lung, and spleen.[5] Separate indices have been developed for follicular and mantle cell lymphoma.[6, 7, 8]

The IPI includes the following risk factors (for each factor that is present, the patient receives 1 point)[5] :

  • Age ≥60 y
  • Elevated lactate dehydrogenase (LDH) level
  • Stage III or IV disease
  • Eastern Cooperative Oncology Group (ECOG) performance status ≥2
  • Two or more extranodal sites

Based on the IPI score, patients can be categorized as follows:

  • Low risk (0-1)
  • Low-intermediate risk (2)
  • High-intermediate risk (3)
  • High risk (4-5)

With this model, relapse-free and overall survival rates at 5 years are as follows:

  • 0-1 risk factors - 75%
  • 2-3 risk factors - 50%
  • 4-5 risk factors - 25%
Previous
 
 
Contributor Information and Disclosures
Author

Ajeet Gajra, MD Associate Professor of Medicine, Director of Hematology/Oncology Fellowship Program, State University of New York Upstate Medical University; Consulting Staff, Department of Internal Medicine, Division of Hematology and Oncology, Veterans Affairs Medical Center

Ajeet Gajra, MD is a member of the following medical societies: American Association for Cancer Research, American Medical Association, American Society of Hematology

Disclosure: Nothing to disclose.

Coauthor(s)

Neerja Vajpayee, MD Associate Professor, Department of Pathology, State University of New York Upstate Medical University

Neerja Vajpayee, MD is a member of the following medical societies: American Society of Hematology, College of American Pathologists, United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Sara J Grethlein, MD, and Uzma Athar, MD, to the development and writing of the source article.

References
  1. Armitage JO. Treatment of non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8. 328(14):1023-30. [Medline].

  2. SEER Cancer Statistics Factsheets: Non-Hodgkin Lymphoma. National Cancer Institute: Surveillance, Epidemiology, and End Results Program. Available at http://seer.cancer.gov/statfacts/html/nhl.html. Accessed: September 7, 2015.

  3. Swerdlo SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. 4th Edition. Lyon, France: IARC; 2008.

  4. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013 Apr. 49 (6):1374-403. [Medline].

  5. International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med. 1993 Sep 30. 329(14):987-94. [Medline].

  6. Federico M, Bellei M, Marcheselli L, Luminari S, Lopez-Guillermo A, Vitolo U, et al. Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. J Clin Oncol. 2009 Sep 20. 27 (27):4555-62. [Medline]. [Full Text].

  7. Solal-Celigny P, Roy P, Colombat P, et al. Follicular lymphoma international prognostic index. Blood. 2004 Sep 1. 104(5):1258-65. [Medline]. [Full Text].

  8. Hoster E, Dreyling M, Klapper W, et al. A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood. 2008 Jan 15. 111(2):558-65. [Medline].

  9. [Guideline] NCCN Clinical Practice Guidelines in Oncology: Non-Hodgkin’s Lymphoma, Version 2, 2015. National Comprehensive Cancer Network. Available at http://www.nccn.org/professionals/physician_gls/pdf/nhl.pdf. Accessed: September 8, 2015.

  10. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20. 32 (27):3059-68. [Medline]. [Full Text].

  11. Choi WW, Weisenburger DD, Greiner TC, et al. A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res. 2009 Sep 1. 15(17):5494-502. [Medline].

  12. American Joint Committee on Cancer, American Cancer Society, American College of Surgeons. Non-Hodgkin's lymphoma. Fleming ID, Cooper JS, Henson DE, Hutter RVP, Kennedy BJ, Murphy GP, O'Sullivan B, Sobin LH, Yarbro JW, eds. AJCC Cancer Staging Manual. 5th ed. Philadelphia, Pa: Lippincott-Raven; 1997. 289-294.

  13. Jaffe ES. The 2008 WHO classification of lymphomas: implications for clinical practice and translational research. Hematology Am Soc Hematol Educ Program. 2009. 523-31. [Medline]. [Full Text].

  14. Brice P, Bastion Y, Lepage E, Brousse N, Haïoun C, Moreau P, et al. Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d'Etude des Lymphomes Folliculaires. Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 1997 Mar. 15 (3):1110-7. [Medline].

  15. [Guideline] Dreyling M, Ghielmini M, Marcus R, Salles G, Vitolo U, Ladetto M, et al. Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014 Sep. 25 Suppl 3:iii76-82. [Medline]. [Full Text].

  16. Colombat P, Salles G, Brousse N, et al. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation. Blood. 2001 Jan 1. 97(1):101-6. [Medline].

  17. Hainsworth JD, Litchy S, Shaffer DW, Lackey VL, Grimaldi M, Greco FA. Maximizing therapeutic benefit of rituximab: maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin's lymphoma--a randomized phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Feb 20. 23 (6):1088-95. [Medline].

  18. [Guideline] Zucca E, Copie-Bergman C, Ricardi U, Thieblemont C, Raderer M, Ladetto M, et al. Gastric marginal zone lymphoma of MALT type: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013 Oct. 24 Suppl 6:vi144-8. [Medline].

  19. [Guideline] Dreyling M, Geisler C, Hermine O, Kluin-Nelemans HC, Le Gouill S, Rule S, et al. Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014 Sep. 25 Suppl 3:iii83-92. [Medline]. [Full Text].

  20. Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, et al. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31. 369(18):1681-90. [Medline].

  21. Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jun 20. 346 (25):1937-47. [Medline].

  22. Zhou Z, Sehn LH, Rademaker AW, Gordon LI, Lacasce AS, Crosby-Thompson A, et al. An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era. Blood. 2014 Feb 6. 123 (6):837-42. [Medline].

  23. [Guideline] Tilly H, Vitolo U, Walewski J, da Silva MG, Shpilberg O, André M, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012 Oct. 23 Suppl 7:vii78-82. [Medline]. [Full Text].

  24. Swerdlo SH, Campo E, Harris NL, Jaffe ES, Pileri SA, STein H, et al. WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. Fourth Edition. Lyon, France: IARC; 2008.

  25. Castillo JJ, Winer ES, Olszewski AJ. Population-based prognostic factors for survival in patients with Burkitt lymphoma: an analysis from the Surveillance, Epidemiology, and End Results database. Cancer. 2013 Oct 15. 119 (20):3672-9. [Medline].

Previous
Next
 
Expansile follicles of varying sizes and complete effacement of the normal lymph node architecture.
Neoplastic follicles (40×).
Neoplastic follicles comprising cleaved cells (centrocytes) and larger cells with vesicular nuclei and prominent 2-3 nucleoli (centroblasts).
Monotonous small round lymphoid cells with clumped chromatin admixed with a few larger paraimmunoblasts (prolymphocytes).
Mantle cell lymphoma. Small lymphoid cells with oval to slightly irregular nuclei and clumped chromatin and rare admixed pink histiocytes.
Small neoplastic marginal zone lymphocytes with slightly irregular nuclear borders and moderate clear cytoplasm (monocytoid appearance).
Diffuse large B-cell non-Hodgkin lymphoma. Large cells with abundant cytoplasm and large round-ovoid nuclei with thick nuclear membrane and multiple prominent nucleoli.
Burkitt lymphoma. Normal architecture is entirely replaced by lymphoma cells and evenly dispersed macrophages, starry sky (250×).
Burkitt lymphoma cells with round noncleaved nuclei and strongly basophilic cytoplasm (1000×).
Compartmentalizing fibrosis and infiltrate of medium-sized to large lymphoid cells.
Lymphoma cells show strong membranous positivity with CD20 indicative of B-cell origin.
Table 1. Chromosomal Abnormalities in B-Cell Non-Hodgkin Lymphoma
Cytogenetic AbnormalityHistologyAntigen RearrangementOncogene Expression
t(14;18)(q32;q21)Follicular, diffuse large cellIgH*bcl- 2
t(11;14)(q13;q32)Mantle cellIgHcyclin-D1/bcl-1
t(1;14)(p22;q32)MALT lymphomaIgHbcl- 10
t(11;18)(q21;q21)MALT lymphomaIgHUnknown
t(9;14)(p13;q32)Lymphoplasmacytic lymphomaIgHPAX-5
8q24 translocations



t(8;14)(q24;q32)



t(2;8)(p11-12;q24)



t(8;22)(q24;q11)



Burkitt lymphomaIgH



Ig-8



Ig-6



c-myc
Trisomy 12, deletion 11q22-23, 17p13, and 6q21CLL
*Immunoglobulin H (IgH)



MALT = Mucosa-associated lymphoid tissue.



Table 3. Characteristic Immunophenotypes of Major Subtypes of Lymphoma
LymphomaImmunophenotype
FollicularCD20+, CD3-, CD10+, CD5-, BCL2+, CD23-/+, CD43-, cyclinD-1-, BCL6+
Small lymphocyticCD 20+, CD3-, CD10-, CD5+, CD23+,
MALTCD20+, CD3-, CD 10-, CD5-, CD23-/+, BCL2+
Marginal zoneCD20+, CD3-, CD 10-, CD5-, CD23-/+, CD43-/+, cyclinD-1-, BCL2
Mantle cellCD20+, CD23-/+, CD10-/+, CD5+, CD43-/+, cyclinD-1+
Mediastinal large B-cellCD20+, CD30+, MUM-1+
Burkittslg+,CD20+, Tdt-, CD10+, BCL2--, BCL6+, Ki-67+ (≥95%)
B-lymphoblasticslg-, CD19+, CD10-/+, CD20-/+, TdT+
MALT = mucosa-associated lymphoid tissue. 
Table3. Lugano Modification of the Ann Arbor Staging System.
StageArea of InvolvementExtranodal (E) Status
ISingle node or adjacent group of nodesSingle extranodal lesions without nodal involvement
IIMultiple lymph node groups on same side of diaphragmStage I or II by nodal extent with limited contiguous extranodal involvement
II bulky*Multiple lymph node groups on same side of diaphragm with “bulky disease”.N/A
IIIMultiple lymph node groups on both sides of diaphragm; nodes above the diaphragm with spleen involvementN/A
IVMultiple noncontiguous extranodal sitesN/A
*Stage II bulky disease considered limited or advanced as determined by histology and a number of prognostic factors.



Suffixes A and B are not required



X for bulky disease replaced with documenting of largest tumor diameter



Definition of “Bulky” disease varies depending on lymphoma histology.



Table 4. Combination therapy for non-Hodgkin lymphoma
Regimen Agents
CHOPCyclophosphamide, doxorubicin, vincristine, prednisone
R-CHOPRituximab, cyclophosphamide, doxorubicin, vincristine, prednisone
CVPCyclophosphamide, vincristine, prednisone
R-CVPRituximab, cyclophosphamide, vincristine, prednisone
CHOEPCyclophosphamide, doxorubicin, vincristine, etoposide, prednisone
DHAPDexamethasone, cisplatin, cytarabine
EPOCHEtoposide. prednisone, vincristine, cyclophosphamide, doxorubicin
R-EPOCHRituximab, etoposide. prednisone, vincristine, cyclophosphamide, doxorubicin
ESHAPEtoposide, methylprednisolone, cytarabine, cisplatin
ICEIfosfamide, carboplatin, etoposide
Hyper-CVADCyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose methotrexate and cytarabine
GemOXGemcitabine, oxaliplatin
GDPGemcitabine, dexamethasone, cisplatin
MINEMesna, ifosfamide, mitoxantrone, etoposide
R-CEPPRituximab, cyclophosphamide, etoposide, prednisone, procarbazine
R-CDOPRituximab, cyclophosphamide, liposomal doxorubicin, vincristine, prednisone
R-CNOPRituximab, cyclophosphamide, mitoxantrone, vincristine, prednisone
R-CEOPRituximab, cyclophosphamide, etoposide, vincristine, prednisone
Table 5. Monoclonal Antibodies for Treatment of NHL.
AntibodyAntigenConjugate
Rituximab (Rituxan)* CD20None
Ibritumomab tiuxetan (Zevalin)* CD20Yttrium-90
Epratuzumab (Lymphocide) CD22Yttrium-90
Obinutuzumab (Gazyva)* CD20None
Bevacizumab (Avastin)VEGFNone
*Approved by the US Food and Drug Administration (FDA) for use in non-Hodgkin lymphoma; VEGF= Vascular endothelial cell growth factor 
Table 7. Mantle Cell Lymphoma International Prognostic Index.
PointsAge (Y)ECOG PSLDH ULN (mg/dL)WBC (109/L)
0<500-1<0.67<6.7
150-590.67-0.996.7-9.9
260-692-41.0-1.4910-14.9
3≥70≥1.5≥15
ECOG=Eastern Cooperative Oncology Group; LDH=lactate dehydrogenase; PS=performance status; ULN=upper limit of normal' WBC=white blood cell count
Table.
Table 8. Age-adjusted International Prognostic Index
Risk Factor  (1 point given for each factor present)Risk Group
Elevated lactate dehydrogenase (LDH) level



Stage III or IV disease



Eastern Cooperative Oncology Group (ECOG)performance status ≥2



Low Risk = 0



Low-intermediate risk = 1



High-intermediate risk = 2



High risk = 3



Table 9. Age-adjusted International Prognostic Index
Risk Factor  Risk Group (points)
Age:



>40 to ≤ 60 years  = 1 point



>60 to <75 years = 2 points



≥75 years = 3 points



LDH:



>1 to ≤3 = 1 point



>3 = 2 points



Ann Arbor Stage III-IV = 1 point



Extranodal disease = 1 point



Performance Status ≥ 2 = 1 point



Low risk = 0-1



Low-intermediate risk = 2-3



High-intermediate risk = 4-5



High risk ≥6



Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.