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Non-Hodgkin Lymphoma: the Clinician&Rsquo;S Perspective&Mdash;A View from the Receiving

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Non-Hodgkin Lymphoma: the Clinician&Rsquo;S Perspective&Mdash;A View from the Receiving Modern Pathology (2013) 26, S111–S118 & 2013 USCAP, Inc. All rights reserved 0893-3952/13 $32.00 S111 Non-Hodgkin lymphoma: the clinician’s perspective—a view from the receiving end Joseph M Connors British Columbia Cancer Agency Centre for Lymphoid Cancer, Vancouver, BC, Canada Optimal treatment of non-Hodgkin lymphoma depends on establishing an accurate diagnosis and determining the stage or anatomic extent of the lymphoma. With this information, the treating clinician can assign the lymphoma to a subgroup characterized by expected natural history: indolent, aggressive, acute leukemia-like or viral, which generally reflects the typical behavior of the disease unmodified by treatment and indicates the urgency with which intervention must be offered. Finally, a number of special circumstances and problems posed by specific lymphomas must be anticipated and the therapeutic plan altered to accommodate them. After primary treatment, special secondary events such as transformation to more aggressive histologic types must be recognized and the treatment plan must be altered to address these events. This article reviews standard diagnostic grouping of lymphomas, special problems encountered during primary diagnosis and subsequent clinical evolution and emphasizes the cooperative interaction between the hematopathologist and the treating clinician that underlies optimal management. Modern Pathology (2013) 26, S111–S118; doi:10.1038/modpathol.2012.184 Keywords: lymphoid cancer treatment; lymphoma classification; non-Hodgkin lymphoma When asked to assess and treat a patient with a non- divided into two groups on the basis of Ann Arbor Hodgkin lymphoma, the clinician must consider stage,4 bulk or size of tumor and presence of B specific information about the disease, its extent and symptoms (Table 2). the patient’s physical condition to plan optimal treatment. After reviewing the available referral What does the clinician do: treatment data, the clinician initiates an orderly search to determine the patient’s status and disease stage. choice This essential information is shown in Table 1. Clinicians initially group the lymphomas into A standard treatment plan crucially relies on an major subgroups that reflect their typical behavior accurate histologic diagnosis. If not already available, if not treated, that is, their unmodified natural an adequate biopsy of involved tissue must be history: indolent, aggressive, very aggressive or obtained. Most desirable is an excisional or incisional acute leukemia-like and virally induced. In this biopsy with adequate material for detailed immuno- sense, the indolent lymphomas typically threaten a histochemical, cytogenetic and flow cytometric 1–3 patient’s life over years, the aggressive lymphomas study. In exceptional circumstances, such as in months and the leukemia-like lymphomas in clinical urgency or patient frailty, multiple core weeks. This subgrouping is very useful in deter- biopsies may be substituted. Aspiration cytology is mining the basic treatment plan and the urgency inadequate for definitive diagnosis and can only with which it must be started. Table 3 shows the provide a rough guide to a probable diagnosis. It adult lymphomas arranged by major treatment- should not be relied on for primary diagnosis if oriented subtype using the nomenclature of the avoidable. Later in this article, we address several WHO classification.5 special aspects of initial histopathologic diagnosis of lymphoid cancer that also guide choice of treatment. In contrast to the complexity of classification, the Treatment approach to non-Hodgkin staging of NHL is straightforward. Patients can be lymphoma, by major subgroup, with associated exceptions Correspondence: Dr JM Connors, MD, British Columbia Cancer Agency Centre for Lymphoid Cancer, 600 West 10th Avenue, Indolent Lymphoma Vancouver, BC V5Z 4E6, Canada. E-mail: [email protected] Except for the uncommon (o10%) patients with Received 12 September 2012; accepted 12 September 2012 proven limited stage disease, patients with indolent www.modernpathology.org Clinician’s perspective of non-Hodgkin lymphoma S112 JM Connors Table 1 Essential information needed to formulate a treatment Table 3 A clinically oriented classification of the lymphomas plan for a patient with lymphoid cancer based on natural history, mode of presentation and immunophe- notype using the terminology of the 2008 WHO classification 1. History searching for constitutional symptoms, localized pain scheme or obstructive symptoms. 2. Physical examination searching for lymphadenopathy, Type B cell T cell palpable masses, abdominal organomegaly or focal neurologic signs. Indolent Small lymphocytic/CLL Mycosis fungoides 3. Computed tomographic (CT) scan of the neck, chest, abdomen Lymphoplasmacytica Primary cutaneous and pelvis. Follicular, grades 1, 2 anaplastic large cell 4. Fluorodeoxyglucose positron emission tomographic (FDG- or 3A PET)/CT whole body scan for all lymphomas except marginal Marginal zone zone, small lymphocytic/chronic lymphocytic leukemia, MALT lymphoplasmacytic lymphoma or mycosis fungoides, for Nodal which FDG uptake is not a reliable determinant of disease Splenic involvement. Aggressive Mantle cell Peripheral T-cell, not 5. Complete blood counts, serum creatinine, bilirubin, alkaline Diffuse large cellb, any otherwise specified phosphatase, lactate dehydrogenase (LDH), protein subtype Peripheral T-cell, electrophoresis, calcium. B-cell lymphoma, specified 6. Hepatitis B surface antigen, hepatitis B core antibody, hepatitis unclassifiable with features Angioimmunoblastic C antibody. intermediate between DLBCL Nasal NK/T-cell-type 7. Diagnostic biopsy results. and Burkitt lymphoma Subcutaneous 8. Bone marrow biopsy and aspiration. panniculitis-like Enteropathy- Additional selectively useful tests associated Hepatosplenic 1. Human immunodeficiency virus (HIV) antibody. Anaplastic large cell 2. Human T-cell lymphotropic virus type 1 (HTLV-1) antibody. Acute Lymphoblastic Lymphoblastic 3. Cytologic assessment of potentially involved fluids, for leukemia- Burkitt example, spinal fluid, ascites, pleural effusion. like ‘Double hit’ lymphomas (see text) Viral Primary effusion HTLV-1 associated (HHV-8 associated) Table 2 Stage grouping relevant to treatment planning for non- Abbreviations: HHV-8, human herpes virus type 8; HTLV-1, human Hodgkin lymphoma T-cell lymphotropic virus type 1. aFormerly plasmacytoid small lymphocytic±IgM paraprotein (Wal- Limited stage Advanced stage denstro¨m’s macroglobulinemia). bImmunoblastic, primary mediastinal, T-cell-rich B-cell, intravascu- Ann Arbor I, II Ann Arbor III, IVa lar, testicular, primary effusion and primary CNS subtypes. and or Bulk o10 cm Bulk 410 cm and or stomach and peri-gastric lymph nodes, treatment No B symptoms B symptoms with antibiotics and H2 blockers can eliminate the organism-related antigenic stimulus and the lym- a In the Ann Arbor staging system4 stages I and II identify disease phoma may regress permanently.8,9 This is quite confined to one or more lymph node groups all on one side of the diaphragm; stage III to lymph node disease on both sides of the unlikely to happen if t(11;18) is present, which diaphragm; and stage IV to disease that has spread into extranodal testing should be included in processing of gastric sites such as bone marrow, liver, lungs or other sites. MALT lymphomas.10 2. Splenic marginal zone lymphoma lymphoma usually present with advanced stage Splenectomy is often the best choice of primary disease (490%).5 Advanced stage indolent lymp- treatment of splenic marginal zone lymphoma homa is not curable with currently available because splenectomy:11,12 standard treatment; however, these lymphomas can be managed as chronic diseases with short courses a Provides a firm diagnosis. of systemic treatment interrupted by long periods of b Eliminates 490% of the total body tumor burden freedom from symptoms or need for treatment for in one simple step. the large majority of patients. Today, such patients c Corrects associated cytopenias, allowing other can anticipate a 10-year overall survival 480% for systemic treatments to be given. younger patients (ageo60 years) and 460% for d Has little consequence for the patient because full older patients (age460 years) and treatment splenic function has already been lost because of outcomes are steadily improving.6,7 infiltration by the lymphoma. 3. Mycosis fungoides Important exceptions. Some specific indolent lym- This uncommon T-cell lymphoma of the skin phomas require type-specific treatment. typically pursues a very indolent course and is 1. MALT lymphoma of the stomach best treated with a collection of remedies specific If coincident infection with Helicobacter pylori is to the entity including skin irradiation, topi- present and the lymphoma is localized to the cal chemotherapy, psoralen-associated ultraviolet Modern Pathology (2013) 26, S111–S118 Clinician’s perspective of non-Hodgkin lymphoma JM Connors S113 exposure, bexarotene, interferon and histone deace- dose radiation used for lymphomas.23,24 Patients tylase inhibitors.13 with localized disease require high-dose radiation, a dose similar to that used for nasopharyngeal carcinoma. Patients with advanced stage disease Aggressive Histology Lymphoma have a particularly poor prognosis and should be considered for experimental treatments.25 In contrast to the indolent lymphomas the working 3. Anaplastic large cell lymphoma (ALCL) assumption for the aggressive histology lymphomas ALCL can be
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