MATURE LYMPHOID NEOPLASMS

• Mature lymphoid neoplasms


  Diverse collection of disease entities with varying clinical presentations and natural histories, identified with a particular lineage
• Neoplastic transformation


  Abnormal changes in growth and differentiation patterns, resulting in disease
• Lymphoproliferative disorders


  • Leukemias (primary site is blood or bone marrow)
  • Lymphomas (primary site is lymph nodes and spleen)
• There are disorders, such as chronic lymphocytic leukemia (CLL), in which the neoplastic cells are prominent in the blood yet also involve the spleen and lymph nodes
• Lymphomas may have a leukemic phase in which the malignant cells are found in the peripheral blood
• Plasma cell neoplasms (e.g., multiple or plasma cell myeloma) tend to be bone marrow based, although extramedullary involvement may be an important part of the clinical presentation
• Immunologic diversity


  The generation of immunologic diversity is an inherently complex process with many steps, which lends itself to error
• Genetic abnormalities that characterize the B cell lymphomas often involve the immunoglobulin genes
• Common examples of translocated genes

  • MYC (stimulates entry into cell cycle)
  • BCL2 (suppresses apoptosis)
  • BCL6 (can suppress transcription of other genes necessary for cell growth)
• Examination of the morphology is the first step in interpreting patterns of involvement, but it is imperfect because different diseases may present with similar appearances
• Flow cytometry and immunohistochemistry are important methodologies to identify disorders using the differentiation schema
• Acute lymphoid leukemia (ALL), with a stem cell or precursor phenotype, is more commonly found in the pediatric population
• Diseases at the terminal end of differentiation, such as plasma cell myeloma or Burkitt lymphoma, can also be clinically aggressive
• Natural history and clinical behavior are not reflective of the phenotype of the particular disorder, but of the underlying genetic changes that determine tumor growth and response to therapy
• Typical clinical behaviors of some common mature lymphoid neoplasms

  • Aggressive disease
  • Indolent disease
• Clinical signs and symptoms range from asymptomatic disease detected on a screening complete blood count (CBC) to fulminant illness characterized by symptoms such as fever, weight loss, night sweats, and adenopathy, in addition to severe functional compromise
• Lymphadenopathy is a common presentation for non-Hodgkin lymphoma but may also be seen in reactive conditions involving infection or inflammation
• Presenting symptoms may be nonspecific but are often reflective of tumor involvement of a particular organ system
• Development of B symptoms in a patient with low-grade lymphoma or CLL who previously had been without complaints may indicate transformation to a more aggressive disease
• Gastrointestinal (GI) symptoms often relate to direct involvement of the GI tract with tumor, but hepatosplenomegaly may be an indirect cause
• Skin infiltration can occur diffusely or may be localized and appear as nodules, and is more common in T cell disorders but can also be seen in B cell diseases
• Analysis of the cerebrospinal fluid (CSF) or pleural fluid to look for tumor involvement is important for patients presenting with central nervous system (CNS) symptoms or potential extranodal involvement or dyspnea due to pleural effusion
• Cytopenias can occur when lymphoma is in the bone marrow or as a result of myelosuppressive therapy
• A normal lymphocyte count, automated differential, or absence of morphologic flags does not rule out the presence of abnormal cells in the peripheral blood
• Manual review of the peripheral blood film to detect abnormal lymphoid cells may be required when there is lymphadenopathy or other symptoms suggestive of a lymphoid neoplasm
• Mature T cell lymphoid neoplasms

  • Adult T cell leukemia/lymphoma
  • Extranodal NK/T cell lymphoma, nasal type
  • Enteropathy-associated T cell lymphoma
  • Monomorphic epitheliotropic intestinal T cell lymphoma
  • Indolent T cell lymphoproliferative disorder of the gastrointestinal tract
  • Hepatosplenic T cell lymphoma
  • Subcutaneous panniculitis-like T cell lymphoma
  • Mycosis fungoides
  • Sézary syndrome
  • Primary cutaneous CD30+ T cell lymphoproliferative disorders
  • Lymphoid papulosis
  • Primary cutaneous anaplastic large cell lymphoma
  • Primary y T cell lymphoma
  • Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T cell lymphoma
  • Primary cutaneous acral CD8+ T cell lymphoma
  • Primary cutaneous CD4+ small/medium T cell lymphoproliferative disorder
  • Peripheral T cell lymphoma-not otherwise specified (NOS)
  • Angioimmunoblastic T cell lymphoma
  • Follicular T cell lymphoma
  • Nodal peripheral T cell lymphoma with TFH phenotype
  • Anaplastic large cell lymphoma, ALK+
  • Anaplastic large cell lymphoma, ALK-
  • Breast implant-associated anaplastic large cell lymphoma
• Hodgkin Lymphoma


  • Nodular lymphocyte predominant Hodgkin lymphoma
  • Classic Hodgkin lymphoma
  • Nodular sclerosis classic Hodgkin lymphoma
  • Lymphocyte-rich classic Hodgkin lymphoma
  • Mixed cellularity classic Hodgkin lymphoma
  • Lymphocyte-depleted classic Hodgkin lymphoma
• Posttransplant Lymphoproliferative Disorders (PTLD)

  • Plasmacytic hyperplasia PTLD
  • Infectious mononucleosis PTLD
  • Florid follicular hyperplasia PTLD
  • Polymorphic PTLD
  • Monomorphic PTLD (B and T/NK cell types)
  • Classic Hodgkin lymphoma PTLD
• *Discussed in the chapter text.
• **Also called multiple myeloma
• B Symptoms


  • Unexplained weight loss (>10% body weight) in 6 months prior to staging
  • Unexplained, persistent, or recurrent fever (>38° C) in prior month
  • Recurrent drenching night sweats during prior month
• The presence of these cells may prompt further diagnostic procedures, such as flow cytometry and biopsy of the bone marrow or an enlarged lymph node.
• An example of a potential disparity between the automated and manual differentials is illustrated in Figure 34.1.
• Flow cytometry is often used to document clonality associated with lymphoid malignancies.
• Immunophenotyping is undertaken with standard consensus panels, and the pattern of staining with a series of monoclonal antibodies (MoAbs) associated with lineages and degree of maturation establishes an immunologic (CD) profile.
• Conventional cytogenetics (karyotyping) and fluorescent in situ hybridization (FISH) detect genetic changes associated with these diseases.
• Biochemical analysis may be useful for three purposes: (1) evaluating organ systems for compromise due to tumor involvement, (2) serving as an indirect measure of tumor burden, and (3) assessing prognosis.
• Serum creatinine levels are used to assess renal function in patients receiving treatment known to affect the kidneys.
• Baseline measurement of uric acid is performed in disorders with high tumor cell turnover.
• Patients may undergo assessment for a monoclonal protein with serum protein electrophoresis, immunofixation, and serum free light chain analysis.