martes, 30 de julio de 2019

Adult Non-Hodgkin Lymphoma Treatment - National Cancer Institute 2/9

Adult Non-Hodgkin Lymphoma Treatment - National Cancer Institute

National Cancer Institute



Adult Non-Hodgkin Lymphoma Treatment (PDQ®)–Health Professional Version



Cellular Classification of Adult NHL

A pathologist should be considered for consultation before a biopsy because some studies require special preparation of tissue (e.g., frozen tissue). Knowledge of cell surface markers and immunoglobulin and T-cell receptor gene rearrangements may help with diagnostic and therapeutic decisions. The clonal excess of light-chain immunoglobulin may differentiate malignant from reactive cells. Since the prognosis and the approach to treatment are influenced by histopathology, outside biopsy specimens should be carefully reviewed by a hematopathologist who is experienced in diagnosing lymphomas. Although lymph node biopsies are recommended whenever possible, sometimes immunophenotypic data are sufficient to allow diagnosis of lymphoma when fine-needle aspiration cytology is preferred.[1,2]

Historical Classification Systems

Historically, uniform treatment of patients with non-Hodgkin lymphoma (NHL) has been hampered by the lack of a uniform classification system. In 1982, results of a consensus study were published as the Working Formulation.[3] The Working Formulation combined results from six major classification systems into one classification. This allowed comparison of studies from different institutions and countries. The Rappaport classification, which also follows, is no longer in common use.
Table 1. Historical Classification Systems for Non-Hodgkin Lymphoma (NHL)
Working Formulation [3]Rappaport Classification
Low grade 
A. Small lymphocytic, consistent with chronic lymphocytic leukemiaDiffuse lymphocytic, well-differentiated
B. Follicular, predominantly small-cleaved cellNodular lymphocytic, poorly differentiated
C. Follicular, mixed small-cleaved, and large cellNodular mixed, lymphocytic, and histiocytic
Intermediate grade 
D. Follicular, predominantly large cellNodular histiocytic
E. Diffuse, small-cleaved cellDiffuse lymphocytic, poorly differentiated
F. Diffuse mixed, small and large cellDiffuse mixed, lymphocytic, and histiocytic
G. Diffuse, large cell, cleaved, or noncleaved cellDiffuse histiocytic
High grade 
H. Immunoblastic, large cellDiffuse histiocytic
I. Lymphoblastic, convoluted, or nonconvoluted cellDiffuse lymphoblastic
J. Small noncleaved-cell, Burkitt, or non-BurkittDiffuse undifferentiated Burkitt or non-Burkitt

Current Classification Systems

As the understanding of NHL has improved and as the histopathologic diagnosis of NHL has become more sophisticated with the use of immunologic and genetic techniques, a number of new pathologic entities have been described.[4] In addition, the understanding and treatment of many of the previously described pathologic subtypes have changed. As a result, the Working Formulation has become outdated and less useful to clinicians and pathologists. Thus, European and American pathologists have proposed a new classification, the Revised European American Lymphoma (REAL) classification.[5-8] Since 1995, members of the European and American Hematopathology societies have been collaborating on a new World Health Organization (WHO) classification, which represents an updated version of the REAL system.[9,10]
The WHO modification of the REAL classification recognizes three major categories of lymphoid malignancies based on morphology and cell lineage: B-cell neoplasms, T-cell/natural killer (NK)-cell neoplasms, and Hodgkin lymphoma (HL). 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 example, B-cell chronic lymphocytic leukemia (CLL) and B-cell small lymphocytic lymphoma are simply different manifestations of the same neoplasm, as are lymphoblastic lymphomas and acute lymphocytic leukemias. Within the B-cell and T-cell categories, two subdivisions are recognized: precursor neoplasms, which correspond to the earliest stages of differentiation, and more mature differentiated neoplasms.[9,10]

Updated REAL/WHO classification

B-cell neoplasms
  1. Precursor B-cell neoplasm: precursor B-acute lymphoblastic leukemia/lymphoblastic lymphoma (LBL).
  2. Peripheral B-cell neoplasms.
    1. B-cell CLL/small lymphocytic lymphoma.
    2. B-cell prolymphocytic leukemia.
    3. Lymphoplasmacytic lymphoma/immunocytoma.
    4. Mantle cell lymphoma.
    5. Follicular lymphoma.
    6. Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphatic tissue (MALT) type.
    7. Nodal marginal zone B-cell lymphoma (± monocytoid B-cells).
    8. Splenic marginal zone lymphoma (± villous lymphocytes).
    9. Hairy cell leukemia.
    10. Plasmacytoma/plasma cell myeloma.
    11. Diffuse large B-cell lymphoma.
    12. Burkitt lymphoma.
T-cell and putative NK-cell neoplasms
  1. Precursor T-cell neoplasm: precursor T-acute lymphoblastic leukemia/LBL.
  2. Peripheral T-cell and NK-cell neoplasms.
    1. T-cell CLL/prolymphocytic leukemia.
    2. T-cell granular lymphocytic leukemia.
    3. Mycosis fungoides (including Sézary syndrome).
    4. Peripheral T-cell lymphoma, not otherwise characterized.
    5. Hepatosplenic gamma/delta T-cell lymphoma.
    6. Subcutaneous panniculitis-like T-cell lymphoma.
    7. Angioimmunoblastic T-cell lymphoma.
    8. Extranodal T-/NK-cell lymphoma, nasal type.
    9. Enteropathy-type intestinal T-cell lymphoma.
    10. Adult T-cell lymphoma/leukemia (human T-lymphotrophic virus [HTLV] 1+).
    11. Anaplastic large cell lymphoma, primary systemic type.
    12. Anaplastic large cell lymphoma, primary cutaneous type.
    13. Aggressive NK-cell leukemia.
HL
  1. Nodular lymphocyte-predominant HL.
  2. Classical HL.
    1. Nodular sclerosis HL.
    2. Lymphocyte-rich classical HL.
    3. Mixed-cellularity HL.
    4. Lymphocyte-depleted HL.
The REAL classification encompasses all the lymphoproliferative neoplasms. Refer to the following PDQ summaries for more information:

PDQ modification of REAL classification of lymphoproliferative diseases

  1. Plasma cell disorders. (Refer to the PDQ summary on Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment for more information.)
    1. Bone.
    2. Extramedullary.
      1. Monoclonal gammopathy of undetermined significance.
      2. Plasmacytoma.
      3. Multiple myeloma.
      4. Amyloidosis.
  2. HL. (Refer to the PDQ summary on Adult Hodgkin Lymphoma Treatment for more information.)
    1. Nodular sclerosis HL.
    2. Lymphocyte-rich classical HL.
    3. Mixed-cellularity HL.
    4. Lymphocyte-depleted HL.
  3. Indolent lymphoma/leukemia.
    1. Follicular lymphoma (follicular small-cleaved cell [grade 1], follicular mixed small-cleaved, and large cell [grade 2], and diffuse, small-cleaved cell).
    2. Chronic lymphocytic leukemia/small lymphocytic lymphoma. (Refer to the PDQ summary on Chronic Lymphocytic Leukemia Treatment for more information.)
    3. Lymphoplasmacytic lymphoma (Waldenström macroglobulinemia).
    4. Extranodal marginal zone B-cell lymphoma (MALT lymphoma).
    5. Nodal marginal zone B-cell lymphoma (monocytoid B-cell lymphoma).
    6. Splenic marginal zone lymphoma (splenic lymphoma with villous lymphocytes).
    7. Hairy cell leukemia. (Refer to the PDQ summary on Hairy Cell Leukemia Treatment for more information.)
    8. Mycosis fungoides (including Sézary syndrome). (Refer to the PDQ summary on Mycosis Fungoides (Including Sézary Syndrome) Treatment for more information.)
    9. T-cell granular lymphocytic leukemia. (Refer to the PDQ summary on Chronic Lymphocytic Leukemia Treatment for more information.)
    10. Primary cutaneous anaplastic large cell lymphoma/lymphomatoid papulosis (CD30-positive).
    11. Nodular lymphocyte–predominant Hodgkin lymphoma. (Refer to the PDQ summary on Adult Hodgkin Lymphoma Treatment for more information.)
  4. Aggressive lymphoma/leukemia.
    1. Diffuse large cell lymphoma (includes diffuse mixed-cell, diffuse large cell, immunoblastic, and T-cell rich large B-cell lymphoma).
      Distinguish:
      1. Mediastinal large B-cell lymphoma.
      2. Follicular large cell lymphoma (grade 3).
      3. Anaplastic large cell lymphoma (CD30-positive).
      4. Extranodal NK-/T-cell lymphoma, nasal type/aggressive NK-cell leukemia/blastic NK-cell lymphoma.
      5. Lymphomatoid granulomatosis (angiocentric pulmonary B-cell lymphoma).
      6. Angioimmunoblastic T-cell lymphoma.
      7. Peripheral T-cell lymphoma, unspecified.
        • Subcutaneous panniculitis-like T-cell lymphoma.
        • Hepatosplenic T-cell lymphoma.
      8. Enteropathy-type T-cell lymphoma.
      9. Intravascular large B-cell lymphoma.
    2. Burkitt lymphoma/Burkitt cell leukemia/Burkitt-like lymphoma.
    3. Precursor B-cell or T-cell lymphoblastic lymphoma/leukemia. (Refer to the PDQ summary on Adult Acute Lymphoblastic Leukemia Treatment for more information.)
    4. Primary central nervous system (CNS) lymphoma. (Refer to the PDQ summary on Primary CNS Lymphoma Treatment for more information.)
    5. Adult T-cell leukemia/lymphoma (HTLV 1+).
    6. Mantle cell lymphoma.
    7. Posttransplantation lymphoproliferative disorder.
    8. AIDS-related lymphoma. (Refer to the PDQ summary on AIDS-Related Lymphoma Treatment for more information.)
    9. True histiocytic lymphoma.
    10. Primary effusion lymphoma.
    11. B-cell or T-cell prolymphocytic leukemia. (Refer to the PDQ summary onChronic Lymphocytic Leukemia Treatment for more information.)
    12. Plasmablastic lymphoma.
References
  1. Zeppa P, Marino G, Troncone G, et al.: Fine-needle cytology and flow cytometry immunophenotyping and subclassification of non-Hodgkin lymphoma: a critical review of 307 cases with technical suggestions. Cancer 102 (1): 55-65, 2004. [PUBMED Abstract]
  2. Young NA, Al-Saleem T: Diagnosis of lymphoma by fine-needle aspiration cytology using the revised European-American classification of lymphoid neoplasms. Cancer 87 (6): 325-45, 1999. [PUBMED Abstract]
  3. National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas: summary and description of a working formulation for clinical usage. The Non-Hodgkin's Lymphoma Pathologic Classification Project. Cancer 49 (10): 2112-35, 1982. [PUBMED Abstract]
  4. Pugh WC: Is the working formulation adequate for the classification of the low grade lymphomas? Leuk Lymphoma 10 (Suppl 1): 1-8, 1993.
  5. Harris NL, Jaffe ES, Stein H, et al.: A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 84 (5): 1361-92, 1994. [PUBMED Abstract]
  6. Pittaluga S, Bijnens L, Teodorovic I, et al.: Clinical analysis of 670 cases in two trials of the European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group subtyped according to the Revised European-American Classification of Lymphoid Neoplasms: a comparison with the Working Formulation. Blood 87 (10): 4358-67, 1996. [PUBMED Abstract]
  7. Armitage JO, Weisenburger DD: New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project. J Clin Oncol 16 (8): 2780-95, 1998. [PUBMED Abstract]
  8. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood 89 (11): 3909-18, 1997. [PUBMED Abstract]
  9. Pileri SA, Milani M, Fraternali-Orcioni G, et al.: From the R.E.A.L. Classification to the upcoming WHO scheme: a step toward universal categorization of lymphoma entities? Ann Oncol 9 (6): 607-12, 1998. [PUBMED Abstract]
  10. Society for Hematopathology Program: Society for Hematopathology Program. Am J Surg Pathol 21 (1): 114-121, 1997.
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