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10 - Small lymphocytic lymphoma and its variants
- from Part II - LYMPHOMA SUBTYPES
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- By Peter Hillmen, Department of Haematology, Leeds Teaching Hospitals, NHS Trust, Leeds, General Infirmary, Great George Street, Leeds, LS1 3EX, UK, Andrew Wotherspoon, Department of Histopathology, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK, Andreas Rosenwald, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany, German Ott, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany
- Edited by Robert Marcus, John W. Sweetenham, Case Western Reserve University, Ohio, Michael E. Williams, University of Virginia
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- Lymphoma: Pathology, Diagnosis and Treatment
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Summary
INTRODUCTION
Small lymphocytic lymphoma (SLL) and chronic lymphocytic leukemia (CLL) are in the midst of a period of huge change due to advances on several fronts. One important development is the appreciation that SLL and CLL are two manifestations of the same disorder. Throughout this review, therefore, it should be assumed that SLL is managed in a similar manner to CLL, though the studies drawn upon and recommendations made will be based mainly on publications on the diagnosis and therapy for CLL.
There have been major advances in our understanding both of the pathophysiology of CLL/SLL and of the mechanism by which the disease becomes resistant to conventional therapies. This has coincided with the application of novel approaches to define remissions including the use of modern imaging techniques, which have never previously been applied in CLL, and the development of techniques to detect minimal residual disease, particularly by multi-parameter flow cytometry. To some extent a major driver of these changes has been the development of novel therapeutic approaches which yield higher proportions of complete remissions. We have now moved from standard therapies which achieve complete responses in less than 10% of patients to novel approaches which result in greater than 70% complete responses. There is now the prospect of achieving response rates which for other hematopoietic malignancies are associated with a prolongation in survival – and even cures! Treatment paradigms are evolving rapidly towards risk stratification by molecular prognostic factors and tailoring therapy to an individual patient's disease.
15 - T-cell lymphoma
- from Part II - LYMPHOMA SUBTYPES
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- By Mujahid A. Rizvi, Division of Hematology/Oncology, Department of Medicine, Northwestern University, Feinberg School of Medicine, 303, E Superior Street, Chicago IL, 60611, USA, Andrew M. Evens, Division of Hematology/Oncology, Department of Medicine, Northwestern University, Feinberg School of Medicine, 303, E Superior Street, Chicago, IL, 60611, USA, Beverly P. Nelson, Section of Hematopathology, Department of Pathology, Northwestern University, Feinberg School of Medicine, 303, E Superior Street, Chicago, IL, 60611, USA, Steven T. Rosen, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine, 303, E Superior Street, Chicago, IL, 60611, USA, Andrew Wotherspoon, Department of Histopathology, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK, Andreas Rosenwald, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany, German Ott, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany
- Edited by Robert Marcus, John W. Sweetenham, Case Western Reserve University, Ohio, Michael E. Williams, University of Virginia
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- Lymphoma: Pathology, Diagnosis and Treatment
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Summary
INTRODUCTION
T-cell non-Hodgkin's lymphomas (NHL) are uncommon malignancies, representing approximately 12% of all lymphomas. Various geographic frequencies of T-cell NHL have been documented, ranging from 18.3% of NHL diagnosed in Hong Kong to 1.5% in Vancouver, Canada. This may in part reflect increased exposure to pathogenic factors such as human T-cell leukemia virus 1 (HTLV-1) and Epstein–Barr virus (EBV) in Asian nations. T-cell NHL commonly presents with extranodal disease and often contains varying amounts of necrosis/apoptosis on biopsy specimens, making differentiation between a reactive process and lymphoma challenging. Immunophenotypic, cytogenetic and molecular analyses have enhanced diagnostic capabilities as well as improved classification and prognostication for T-cell NHL.
The current World Health Organization/European Organisation for Research and Treatment of Cancer (WHO/EORTC) classification recognizes nine distinct clinicopathologic peripheral T-cell NHLs. The broad spectrum of pathologic subtypes with varied clinical behavior poses a challenge to the systematic study of these diseases. Furthermore, these distinct T-cell NHL subtypes have unique characteristics and often warrant individualized diagnostic and therapeutic treatment strategies. The primary cutaneous T-cell lymphomas are reviewed in Chapter 16. Here we review the etiology, pathology, diagnosis and treatment strategies for patients with peripheral T-cell lymphomas (Table 15.1).
ETIOLOGY
Genetic alterations involved in lymphoma oncogenesis include chromosome rearrangements, disruption of tumor suppressor genes and an increase in the number of copies of genes (gene amplification). Moreover, infection of cells by viruses and bacteria such as HTLV-I, human herpesvirus 8 (HHV-8), hepatitis C and Helicobacter pylori may also contribute to lymphomagenesis.
14 - Central nervous system lymphoma
- from Part II - LYMPHOMA SUBTYPES
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- By Andrés J. M. Ferreri, Medical Oncology Unit, Department of Oncology, San Raffaele H. Scientific Institute Via Olgettina 60, 20132, Milan, Italy, Lisa M. DeAngelis, Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275, York Avenue, New York, NY, 10021, USA, Andrew Wotherspoon, Department of Histopathology, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK, Andreas Rosenwald, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany, German Ott, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany
- Edited by Robert Marcus, John W. Sweetenham, Case Western Reserve University, Ohio, Michael E. Williams, University of Virginia
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Summary
INTRODUCTION
A variety of lymphomas can involve the central nervous system (CNS), at different phases of their evolution, in both immunocompetent and immunocompromised individuals. They represent a heterogeneous group of malignancies, with variable clinical and behavioral characteristics, requiring different therapeutic approaches. In this chapter, the therapeutic management of these malignancies will be analyzed separately in three main entities: primary CNS lymphomas (PCNSL), secondary CNS lymphomas (SCNSL) and other, less common, forms of CNS lymphomas.
PATHOLOGY
The vast majority of CNS lymphomas are diffuse large B-cell lymphomas (DLBCL) that share the morphological and immunophenotypic characteristics similar to those of DLBCLs encountered elsewhere. They may show a perivascular growth pattern. The perivascular infiltrate is associated with increased reticulin fibres and the periphery of areas of involvement frequently shows astrocyte gliosis. Many immunocompromised patients show features similar to Burkitt's lymphoma, while others show a more immunoblastic morphology.
Rare cases of small lymphocytic, lymphoplasmacytic and T-cell lymphoma similar to those seen in tissue outside the CNS have been described. Secondary involvement by lymphoma originating elsewhere is also encountered.
Immunophenotypically CNS lymphomas recapitulate the staining pattern of similar lymphomas encountered outside the CNS. The DLBCLs are positive for CD20 and CD79a with expression of bcl-2 protein. A proportion express CD10 and bcl-6, but they are usually negative for CD5 and CD23. Large B-cell lymphomas in immunocompromised patients frequently contain Epstein–Barr virus (EBV).
7 - Hodgkin's lymphoma
- from Part II - LYMPHOMA SUBTYPES
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- By Stephanie Sasse, First Department of Internal Medicine, University Hospital, Cologne, 50924, Cologne, Germany, Andreas Engert, First Department of Internal Medicine, University Hospital, Cologne 50924, Cologne, Germany, Andrew Wotherspoon, Department of Histopathology, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK, Andreas Rosenwald, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany, German Ott, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany
- Edited by Robert Marcus, John W. Sweetenham, Case Western Reserve University, Ohio, Michael E. Williams, University of Virginia
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Summary
INTRODUCTION
Hodgkin's lymphoma (HL) is a malignant lymphoma. The classical variant (cHL) is characterized by the presence of mononucleated Hodgkin and multinucleated Reed–Sternberg (HRS) cells, while lymphocytic and histiocytic (L&H) cells (“popcorn cells”) are pathognomonic for nodular lymphocyte-predominant HL (NLPHL). After the first description of patients suffering from enlarged lymph nodes and spleen by Thomas Hodgkin in 1832, it took more than 150 years finally to prove the malignant character of these pathognomonic cells and to show their origin from a germinal-center B cell in the majority of cases. Many questions concerning the pathogenesis of Hodgkin's lymphoma are still unanswered; an important step in the pathogenesis of classical HL seems to be the constitutive activation of the NF-κB pathway.
The prognosis of patients with HL depends on the stage of disease and clinical risk factors. The development of stage- and risk-adapted treatment regimens based on modern polychemotherapy and radiotherapy has improved the outcome dramatically over the past few decades. Current strategies aim at reducing therapy-associated complications while maintaining high cure rates.
EPIDEMIOLOGY
HL has an annual incidence of 2–3 per 100 000 in Europe and the USA, and accounts for approximately one-sixth of all lymphoma. Slightly more men than women are affected. In industrialized countries the onset of disease shows a bimodal distribution, with a first peak in the third decade and a second, much smaller, peak after the age of 60.
11 - Mantle cell lymphoma
- from Part II - LYMPHOMA SUBTYPES
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- By Martin Dreyling, University Hospital, Grosshadern Department of Internal Medicine, III, Ludwig Maximilians University, 81377, Munich, Germany, Michael E. Williams, Hematology/Oncology Division, University of Virginia Health System, Jefferson Park Avenue, Charlottesville, VA 22908, USA, Andrew Wotherspoon, Department of Histopathology, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK, Andreas Rosenwald, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany, German Ott, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany
- Edited by Robert Marcus, John W. Sweetenham, Case Western Reserve University, Ohio, Michael E. Williams, University of Virginia
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INTRODUCTION
Mantle cell lymphoma (MCL) is a unique subtype of non-Hodgkin's lymphoma (NHL) characterized in almost all cases by the chromosomal translocation t(11;14)(q13;q32) and nuclear cyclin D1 overexpression. Most patients present with advanced-stage disease, often with extranodal dissemination, and typically pursue an aggressive clinical course, with median survival historically averaging 3–4 years. No standard curative therapy exists, even with intensive induction regimens followed by autologous stem-cell transplantation. However, a number of recent insights into the molecular and cellular biology of the disease, as well as combined immunochemotherapy and novel therapeutic approaches, hold promise for improved outcomes. Importantly, MCL provides a paradigm for therapeutic targeting in neoplasms with dysregulated cell cycle and apoptotic pathways.
MCL comprises approximately 4–8% of all NHL, with a preponderance of older males relative to other lymphoma subtypes. The male-to-female ratio is 2–3 : 1 and median age at presentation is 60–65 years. No specific etiologic factors have been identified for this disease. An increased risk of lymphoid neoplasms has been reported in first-degree relatives of MCL patients, although MCL occurrence among multiple family members appears to be quite rare.
CLINICAL PRESENTATION
MCL typically presents in advanced stage; over 90% of patients are stage III–IV at diagnosis, frequently with B symptoms. Splenomegaly is seen in half or more of patients, often in association with a leukemic phase.
17 - Lymphoma in the immunosuppressed
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- By Michele Spina, Division of Medical Oncology, A National Cancer Institute Via Pedemontana occidentale, 12, 33081, Aviano (PN), Italy, Robert Marcus, Department of Haematology, Addenbrooke's NHS Trust, Cambridge, CB2 2QQ, UK, Umberto Tirelli, Division of Medical Oncology A National Cancer Institute Via Pedemontana occidentale 12 33081 Aviano (PN) Italy, Andrew Wotherspoon, Department of Histopathology, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK, Andreas Rosenwald, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany, German Ott, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany
- Edited by Robert Marcus, John W. Sweetenham, Case Western Reserve University, Ohio, Michael E. Williams, University of Virginia
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INTRODUCTION
Immunodepleted patients are at higher risk for developing lymphoproliferative disorders (LPD), above all non-Hodgkin's lymphomas (NHL). Even though the association between primary immunodeficiency diseases (e.g. X-linked lymphoproliferative syndrome, common variable immunodeficiency, ataxia telangiectasia and Wiskott–Aldrich syndrome) and LPDs, on the one hand, and between LPDs and autoimmune diseases, on the other, is well known, the leading causes of immunosuppression are considered at present to be organ transplantation and HIV infection. Generally, lymphomas in immunocompromised hosts differ from lymphomas in the general population in histopathological findings, increased extranodal involvement, a more aggressive clinical course, poorer response to conventional therapies and poorer outcome.
In patients who undergo solid-organ transplantation, the risk for lymphoma is strongly influenced by the type of organ transplanted: during the first year after kidney or heart transplantation it is 20 and 120 times higher, respectively, than in the general population. The majority of lymphomas develop within the first three months after transplantation, even if some cases are reported after prolonged immunodepression. Overall the risk of cancer in organ-transplant recipients is well known: the frequency of cancer after renal transplantation was reported to be 6% in the United States and 8.3% in the Nordic countries, that is 4.5–6.3 times higher than in the general population. In a large series of 1844 renal-transplant recipients in Italy a significantly increased incidence of Kaposi's sarcoma, cancers of the lip, liver and kidney, and NHL was observed.
The incidence of HIV-related NHLs (HIV-NHL) has increased since 1981.
16 - Cutaneous lymphoma
- from Part II - LYMPHOMA SUBTYPES
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- By Julia Scarisbrick, St John's Institute of Dermatology, Guy's and St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, UK, Sean Whittaker, St John's Institute of Dermatology, Guy's and St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, UK, Andrew Wotherspoon, Department of Histopathology, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK, Andreas Rosenwald, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany, German Ott, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany
- Edited by Robert Marcus, John W. Sweetenham, Case Western Reserve University, Ohio, Michael E. Williams, University of Virginia
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INTRODUCTION
The skin is the second most frequent extranodal site, after the gastrointestinal tract, for lymphoma. Cutaneous lymphomas have an annual incidence of 0.5–1.0 per 100 000, although recent Scandinavian studies have suggested an incidence of 4 per 100 000, possibly due to improved diagnosis and registration.
Primary cutaneous T-cell lymphoma (CTCL) comprises a heterogeneous group of non-Hodgkin's lymphomas, of which mycosis fungoides (MF) is the most common clinicopathologic subtype. Mycosis fungoides typically has an indolent course, but disease progression may occur in approximately 25% of patients. Sézary syndrome (SS), a leukemic form of CTCL, is very closely related to MF and has a poor prognosis, with a median survival of less than three years.
Primary cutaneous B-cell lymphomas (CBCL) are less common, comprising approximately 20% of all primary cutaneous lymphomas. They typically present with cutaneous papules, plaques or nodules and can be broadly divided into follicle center cell lymphoma, marginal zone lymphoma and large B-cell lymphoma.
The recent publication of the WHO EORTC classification system (Table 16.1) has clarified the classification of primary cutaneous lymphomas. The distinction of rare CTCL variants from MF/SS is critical, as the prognosis is poorer and treatment options are different.
PRIMARY CUTANEOUS T-CELL LYMPHOMAS (CTCL)
Mycosis fungoides
Mycosis fungoides (MF) is the commonest variant of primary CTCL, and it is generally associated with an indolent clinical course. The disease is characterized by cutaneous polymorphic atrophic erythematous patches and scaly plaques.
12 - Diffuse large B-cell lymphoma
- from Part II - LYMPHOMA SUBTYPES
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- By John W. Sweetenham, Cleveland Clinic Foundation, Hematology and Oncology/R35 9500, Euclid Avenue, Cleveland, OH, 44195, USA, Andrew Wotherspoon, Department of Histopathology, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK, Andreas Rosenwald, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany, German Ott, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany
- Edited by Robert Marcus, John W. Sweetenham, Case Western Reserve University, Ohio, Michael E. Williams, University of Virginia
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INTRODUCTION
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma (NHL), accounting for 35–40% of all cases of NHL. Despite high reported response rates to anthracycline-based combination chemotherapy regimens, only 50–65% of patients with this disease have achieved long-term disease-free survival with this approach. The emergence of new strategies, including monoclonal antibodies, dose-dense chemotherapy approaches and the identification of new rational therapeutic targets by gene expression profiling, has resulted in improvements in outcome for patients with this disease in recent years.
Involvement of extranodal sites, either as a primary site of disease or as sites of dissemination, is relatively common in DLBCL. With the exception of primary central nervous system lymphoma (see Chapter 14) and some other specific anatomic sites, treatment recommendations for DLBCL are generally identical for nodal and extranodal disease, with the exception of single-site non-lower limb DLBCL of the skin (see Chapter 16).
CLINICAL PRESENTATION
The clinical presentation of DLBCL, as with other types of NHL, is most commonly with painless lymphadenopathy. Approximately 25% of patients present with anatomically limited stage disease (clinical stage I or II), with the remaining 75% having more advanced disease (bulky stage II, or stage III–IV). Many patients will also experience constitutional (“B”) symptoms including drenching night sweats, unexplained fevers and unexplained weight loss of more than 10% of body weight. Since extranodal disease is relatively common in DLBCL, and since almost any organ can be affected by this disease, presenting symptoms may mimic many other diseases.
8 - Follicular lymphoma
- from Part II - LYMPHOMA SUBTYPES
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- By Kristian Bowles, Department of Haematology, Addenbrooke's NHS Trust, Cambridge, CB2 2QQ, UK; Norfolk & Norwich NHS Trust, Norwich, NR4 7UY, UK, Daniel Hodson, Department of Haematology, Addenbrooke's NHS Trust, Cambridge, CB2 2QQ, UK, Robert Marcus, Department of Haematology, Addenbrooke's NHS Trust, Cambridge, CB2 2QQ, UK, Andrew Wotherspoon, Department of Histopathology, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK, Andreas Rosenwald, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany, German Ott, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany
- Edited by Robert Marcus, John W. Sweetenham, Case Western Reserve University, Ohio, Michael E. Williams, University of Virginia
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INTRODUCTION
Follicular lymphoma (FL) is the second most common lymphoma after diffuse large B-cell lymphoma (DLBCL). It has an annual incidence of 4 per 100 000 and accounts for 30% of all cases of non-Hodgkin's lymphoma. The disease is generally characterized by the insidious onset of lymphadenopathy usually without extranodal disease or B symptoms. Although long-term disease-free survival is seen in some patients treated for early-stage disease the majority of patients are incurable with conventional therapy. Although usually readily responsive to treatment, remissions are temporary and the disease follows a relapsing and remitting course. Successive remissions become harder to achieve and of shorter duration. Most patients receive several lines of treatment before finally succumbing to refractory disease or high-grade transformation. In addition a small proportion of patients die from complications of therapy.
The behavior of follicular lymphoma shows considerable variability. In some cases the disease follows an aggressive chemo-refractory course, while in other patients the disease can be controlled for 15 years or more. This variable prognosis can be in part predicted by the recently devised FLIPI prognostic index and by sub-classification of the disease by gene expression microarray. This disease heterogeneity and the multiple lines of treatment received by most patients make treatment of follicular lymphoma a complex and contentious area. Little improvement in treatment outcomes had been seen over the last few decades and until recently median survival remained between 8 and 10 years.
13 - Burkitt's and lymphoblastic lymphomas
- from Part II - LYMPHOMA SUBTYPES
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- By Alan S. Wayne, Pediatric Oncology, Branch Center for Cancer Research National Cancer Institute, 9000, Rockville Pike, Bethesda, MD 20892, USA, Wyndham H. Wilson, Lymphoma Therapeutics Section, Metabolism Branch Center for Cancer Research, National Cancer Institute, 9000, Rockville, Pike Bethesda, MD, 20892, USA, Andrew Wotherspoon, Department of Histopathology, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK, Andreas Rosenwald, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany, German Ott, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany
- Edited by Robert Marcus, John W. Sweetenham, Case Western Reserve University, Ohio, Michael E. Williams, University of Virginia
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INTRODUCTION AND PRESENTATION
Burkitt's (BL) and lymphoblastic lymphomas (LBL) are highly aggressive diseases with distinct natural histories and clinical presentations. BL mostly occurs in the first two decades of life and accounts for 1–2% of all lymphomas. Three clinical variants are recognized: endemic BL, which is primarily found in equatorial Africa and Papua New Guinea, sporadic BL, which presents worldwide but is the most common type in Western countries, and immunodeficiency-associated BL, which is associated with HIV infection. There are important clinical differences in these variants (Table 13.1), with endemic BL involving the jaw, orbit and paraspinal regions in half of the cases as well as the mesentery and gonads, while sporadic BL mostly involves the distal ileum, cecum and/or mesentery, and rarely the jaw. When bulky or disseminated disease is present, extranodal involvement of the ovaries, kidney, breasts and/or central nervous system (CNS) may be seen. Clinical presentation in a Berlin–Frankfurt–Munster Group (BFM) series of 152 pediatric patients included advanced-stage (III/IV) disease in 38%, bone-marrow involvement in 33% and CNS disease in 4%. Overall, 27% of the patients in this series presented as acute leukemia and are usually referred to as the L3 subtype of acute lymphoblastic leukemia (ALL) within the French–American–British (FAB) classification. BL infrequently presents in adults, but does occur with increased frequency in patients with HIV infection.
LBL is most commonly a malignancy of T-cell precursor cells, and as such it is identical to T-cell acute lymphoblastic leukemia (T-ALL).
2 - Pathology and cytogenetics
- from Part I - LYMPHOMA OVERVIEW
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- By Andrew Wotherspoon, Department of Histopathology, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK, German Ott, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2 Würzburg, 97080, Germany, Eugenia Haralambieva, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany, Andreas Rosenwald, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany
- Edited by Robert Marcus, John W. Sweetenham, Case Western Reserve University, Ohio, Michael E. Williams, University of Virginia
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Summary
PREPARATION OF SPECIMENS FOR HISTOLOGY AND CYTOLOGY
The diagnosis of hematolymphoid tumors requires a combination of morphological, immunophenotypic, molecular genetic and clinical data. Successful morphological analysis is easiest to achieve by examination of intact lymph nodes that have been excised whole with the capsule intact. Fragmentation, while difficult to avoid in some areas (such as the mediastinum), inhibits analysis. Core biopsies are increasingly used for the diagnosis of lymphoid-related conditions, but these should be restricted to cases in which nodal excision is difficult or impossible, due either to access-related problems (intra-abdominal location) or to patient-related factors. Core biopsies, by their very nature, represent a small percentage of the lesional tissue and may fail to demonstrate focal variations in the tumor such as a diffuse component in follicular lymphoma. Fine needle aspiration (FNA) cytology has a role to play in the diagnosis of lymphoid pathology, but is best performed where there is access to high-quality flow cytometry that allows immunophenotyping of the lymphoid cells. FNA is particularly useful in the head and neck region for the exclusion of metastatic tumour.
Choice of the lymph node for sampling is of great importance. Where there is choice of areas the inguinal region is best avoided, as these nodes frequently show distortion of the normal architecture by fibrosis. Cervical lymph nodes are most easily interpreted.
9 - MALT lymphoma and other marginal zone lymphomas
- from Part II - LYMPHOMA SUBTYPES
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- By Emanuele Zucca, Lymphoma Unit Oncology, Institute of Southern Switzerland, Ospedale San Giovanni 6500, Bellinzona, Switzerland, Francesco Bertoni, Functional Genomics Unit, Laboratory of Experimental Oncology, Oncology, Institute of Southern Switzerland, 6500, Bellinzona, Switzerland, Andrew Wotherspoon, Department of Histopathology, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK, Andreas Rosenwald, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany, German Ott, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany
- Edited by Robert Marcus, John W. Sweetenham, Case Western Reserve University, Ohio, Michael E. Williams, University of Virginia
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Summary
EXTRANODAL MARGINAL ZONE B-CELL LYMPHOMA (MALT LYMPHOMA): CLINICAL FEATURES
Lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) comprises about 7–8% of all non-Hodgkin's lymphomas. It is a neoplasm of adults with a median age at presentation of about 60 years and with a slightly higher proportion of females than males. The presenting symptoms are essentially related to the primary location. Few patients present with elevated lactate dehydrogenase (LDH) or β2 microglobulin levels. Constitutional B symptoms are extremely uncommon. MALT lymphoma usually remains localized for a prolonged period within the tissue of origin, but dissemination to multiple sites is not uncommon and has been reported in up to one-quarter of cases, with either synchronous or metachronous involvement of multiple mucosal sites or non-mucosal sites such as bone marrow, spleen or liver. Regional lymph nodes can also be involved. Bone-marrow involvement is reported in up to 20% of cases. The stomach is the commonest localization, representing about one-third of the cases. Other typical presentation sites include the salivary glands, the orbit, the thyroid and the lung; the frequency at different organs is shown in Table 9.1.
Within the stomach, MALT lymphoma is often multifocal, possibly explaining the reports of relapses in the gastric stump after surgical excision. Gastric MALT lymphoma can often disseminate to the small intestine and to the splenic marginal zone. Concomitant GI and non-GI involvement can be detected in approximately 10% of cases. Disseminated disease appears to be more common in non-GI MALT lymphomas.
7 - Gene expression profiling in lymphoid malignancies
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- By Christof Burek, Institute of Pathology, University of Wuerzburg, Germany, Elena Hartmann, Institute of Pathology, University of Wuerzburg, Germany, Zhengrong Mao, Institute of Pathology, University of Wuerzburg, Germany, German Ott, Institute of Pathology, University of Wuerzburg, Germany, Andreas Rosenwald, Institute of Pathology, University of Wuerzburg, Germany
- Edited by Wolf-Karsten Hofmann
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Summary
Introduction
The development of high throughput technologies and, in particular, of DNA microarrays led to a great leap forward in the understanding of complex biological processes, as highlighted in the previous chapters. Not surprisingly, this technology has also revealed exciting new insights in the field of lymphoid malignancies. Specifically, first steps have been taken towards a molecular classification of lymphomas, and gene expression-based survival predictors for lymphoma patients have been created that may prove useful in guiding future treatment decisions. Importantly, oncogenic pathways and relevant biological features of various lymphoma subtypes have been uncovered that may facilitate new targeted treatment approaches.
Traditionally, lymphoma classifications have been a topic of hot debate, and various conceptual frameworks have been used in the past to classify lymphomas in a clinically and biologically meaningful way [1]. Early attempts of lymphoma classification relied heavily on either morphological or clinical aspects (e.g., in the Rappaport classification or in the Working Formulation, respectively). In the Kiel classification, cytological and immunologic criteria were applied for the first time to classify lymphomas according to their derivation from the B- or T-cell lineage. The latest approaches to lymphoma classification, the Revised European-American Lymphoma (REAL) and World Health Organization (WHO) classifications, include morphological aspects, immunophenotype and clinical features, but also underlying genetic alterations to define lymphoma subtypes [2, 3]. For example, mantle cell lymphoma (MCL) is now regarded as a distinct subgroup of B-cell non-Hodgkin's lymphoma (B-NHL), characterized by the reciprocal chromosomal translocation t(11;14) that is present in virtually all cases [4].