Lymphomas PDF

LYMPHOMAS Dept. of Pathology College of Medicine, HMU List of Contents: Definition of lymphoma Classification of lymphoma Histological types Clinical pictures Investigations of lymphoma Summary or conclusion Question Features common to cancer cells Growth in the a...

LYMPHOMAS Dept. of Pathology College of Medicine, HMU List of Contents: Definition of lymphoma Classification of lymphoma Histological types Clinical pictures Investigations of lymphoma Summary or conclusion Question Features common to cancer cells Growth in the absence of “go” signals Growth despite “stop” signals Locally invasive growth and metastases to distant sites the Lymphatic System The tonsils, spleen, liver, bone marrow and a network of lymphatic vessels that connect glands, called lymph nodes Lymph nodes located throughout the body Lymph nodes filter foreign particles out of the lymphatic fluid Contain B and T lymphocytes  Blood Cell and Lymphocyte Development STEM CELLS Multipotential Multipotential myeloid cells lymphocytic cells Differentiate & mature into 6 Differentiate & mature into 3 Types of blood cells Types of lymphocytes red cells basophils T lymphocytes neutrophils monocytes B lymphocytes eosinophils platelets Natural Killer Cells  ALL CLL Lymphomas MM germinal center naïv e B-lymphocytes Plasma Lymphoid cells progenitor T-lymphocytes AML Myeloproliferative disorders Hematopoietic Myeloid Neutrophils stem cell progenitor Eosinophils Basophils Monocytes Platelets Red cells  B-cell development memory B-cell stem CLL germinal mature center cell naive B-cell B-cell lymphoid progenitor MM progenitor-B ALL pre-B Lymphoma immature B-cell plasma cell Bone marrow Lymphoid tissue Lymphocytes Most lymphocytes are in lymph nodes, spleen, bone marrow and lymphatic vessels 20% of white blood cells in blood are lymphocytes Types: T cells, B cells, natural killer cells B cells produce antibodies that help fight infectious agents T cells help B cells produce antibodies and they fight viruses T-Cells and B-Cells - Immature lymphocytes that travel to the thymus differentiate into T-Cells “T” is for thymus - Immature lymphocytes that travel to the spleen or lymph nodes differentiate into B cells "B" stands for the bursa of Fabricius, which is an organ unique to birds, where B cells mature.  Lymphadenopathy Lymphadenopathy refers to nodes that are abnormal in either size, consistency or number. "generalized" if lymph nodes are enlarged in two or more noncontiguous areas "localized" if only one area is involved. Generalized lymphadenopathy almost always indicates the presence of a significant systemic disease. What is Lymphoma Lymphomas are cancers that begin by the “malignant transformation” of a lymphocyte in the lymphatic system Many lymphomas are known to be due to specific genetic mutations Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression  Lymphoma classification (WHO) B-cell neoplasms precursor Non- mature Hodgkin T-cell & NK-cell neoplasms Lymphomas precursor mature Hodgkin lymphoma  Lymphoma PAINLESS PAPLPABLE PERSISITENT PERIPHERAL PROGRESSIVE POLYLYMPHADENOPATHY Hodgkin’s Disease Background first described in 1832 by Dr. Thomas Hodgkin characterized by the presence of Reed-Sternberg cells multinucleated giant cells described by Sternberg in 1898 and Reed in 1902 classified as an infectious disease until 1950’s Hodgkin’s Disease Epidemiology men > women whites > blacks > Asians no clear risk factors, several implicated EBV (pathogen or passenger) HIV woodworking, farming rare familial aggregations A possible model of pathogenesis loss of apoptosis transforming event(s) EBV? cytokine s germinal centre RS cell B cell inflammatory response Reed-Sternberg Cell Hodgkin Biology RS is a “crippled” germinal center B cell does not have normal B cell surface antigens on functional immunoglobulin genes somatic mutations result in stop codon (no sIg) no apoptotic death malignant transformation unclear how this occurs; ? EBV unclear how cells end up with RS phenotype CLINICAL FEATURES A painless, non-tender, progressively growing lump (palpable) in the neck is the most usual presentation. enlarged nodes are usually peripheral and may be seen in one or both sides of the neck, in the axillae or in the inguinal or femoral regions. CLINICAL FEATURES Many patients are completely asymptomatic at the time of diagnosis. These are called “A” patients. Left untreated, HD evolves into a debilitating systemic illness with characteristic symptoms. These so called “B” symptoms always predict a more aggressive clinical course and include any of: CLINICAL FEATURES (1) fever of more than 38°C, not due to other causes like infection. (2) drenching night sweats causing the patient to wake up many times at night to change his clothes, and (3) weight loss of more than 10% of the body weight over the last six months. Pruritis, when present is usually generalized and may be severe enough to cause the patient to scratch extensively. Hematological and biochemical findings Normochromic normocytic anemia is most common Neutrophilia and Eosinophilia are frequent Bone marrow involvement is unusual in early disease. If bone marrow is involved then leukoerythroblastic picture will be seen. Hematological and biochemical findings ESR and CRP are raised. Serum lactate dehydrogenase is raised  DIAGNOSIS histological examination of an excised lymph node multinucleate polyploidy Reed Sternberg cell is central to the diagnosis. mononuclear Hodgkin cells are also part of the malignant clone Inflammatory cells consist of lymphocytes, neutrophils, eosinophils, plasma cells and variable fibrosis CLASSIFICATION OF HD Non-Classical: Nodular Lymphocyte Predominant Classical THE "RYE" CLASSIFICATION OF HD Classical Lymphocyte Rich: In this type of HD the nodal architecture is lost and replaced with a homogeneous infiltrate of normal appearing small lymphocytes and normal appearing histiocytes. Reed-Sternberg cells (RSC) are scanty. THE "RYE" CLASSIFICATION OF HD Nodular sclerosis: is characterized by the replacement of the lymph node parenchyma by interconnecting bands of collagenous connective tissue encircling nodular areas of abnormal lymphatic tissue. Mixed cellularity: This is the commonest type seen in the developing world. Reed- Sternberg cells are more numerous and the stroma shows a mixture of neutrophils, normal histiocytes, plasma cells, lymphocytes, eosinophils and fibroblasts. THE "RYE" CLASSIFICATION OF HD Lymphocyte depleted: there is a paucity of lymphocytes and an abundance of Reed-Sternberg cells in this group. HODGKIN’S LYMPHOMA – Nodular Sclerosis This is Hodgkin's disease, nodular sclerosis type. Note the bands of pink collagenous tissue dividing the field in this lymph node.. HODGKIN’S LYMPHOMA – Nodular Sclerosis The aggregates of Reed-Sternberg cells and inflammation are separated by broad bands of fibrosis HODGKIN’S LYMPHOMA – Nodular Sclerosis Broad fibrous bands separating the tumor nodules.  HODGKIN’S LYMPHOMA – Nodular Sclerosis These are the lacunar cells which are characteristic for the nodular sclerosis type of H.L, they are scattered large cells with a surrounding prominent clear space, an artifact of formalin fixation.  Hodgkin’s lymphoma- Mixed cellularity (A) At low power, the NL appears to be effaced by heterogeneous population, giving a slightly pink color to the node. (B) The Reed-Sternberg variants are few and far between (arrow), with a dominant population of eosinophils (arrowhead). Hodgkin’s lymphoma- Mixed cellularity Hodgkin’s lymphoma, mixed cellularity type. Several mononuclear Hodgkin cells and rare classic Reed-Sternberg cells are present. The polymorphous background cells include mature lymphocytes, histiocytes, and plasma cells. Hodgkin’s lymphoma- lymphocyte predominence Numerous mature-looking lymphocytes surround scattered, large, pale-staining lymphohistiocytic variants (“popcorn” cells). Ann Arbor Staging System Stage I: single lymph node region (I) or single extralymphatic organ or site (IE) Stage II: > 2 lymph node regions on same side of diaphragm (II) or with limited, contiguous extra lymphatic tissue involvement (IIE) Stage III: both sides of diaphragm involved, may include spleen (IIIS) or local tissue involvement (IIIE) Stage IV: multiple/disseminated foci involved with >1 extralymphatic organs (i.e. bone marrow) (A) or (B) designates absence/presence of “B” symptoms Staging of lymphoma Stage I Stage II Stage III Stage IV A: absence of B symptoms B: fever, night sweats, weight loss Treatment with radiotherapy, chemotherapy or a combination of both Approximate 5-year survival rates range from 50% to over 90% depending on age, stage and histology. NON-HODGKIN LYMPHOMAS (NHL) are a large group of lymphoid tumours, most commonly of B-cell origin, 17 in 100,000 Causes are unknown NHL: Epidemiology Most common hematologic malignancy 60,000 new cases annually 6th leading cause of cancer death incidence rising overall incidence up by 73% since 1973 “epidemic” 2nd most rapidly rising malignancy NHL: Epidemiology Why the increase? Increase noted mostly in farming states possible role of herbicides, insecticides, etc. Other environmental factors? NHL: Epidemiology Other risk factors immunodeficiency states AIDS, post-transplant, genetic autoimmune diseases Sjogrens Sprue infections EBV NON-HODGKIN LYMPHOMAS (NHL) Patients with NHL usually present with features indistinguishable on clinical ground from that of HD Persistent, painless, palpable, progressive, peripheral, non-tender, rubbery poly-lymphadenomegaly are characteristic. Low- and high-grade NHL the low­grade disorders are relatively indolent, but are very difficult to cure high-grade lymphomas are aggressive and need urgent treatment but are often curable.  Clinical features Superficial lymphadenopathy asymmetric painless enlargement of lymph nodes in one or more peripheral lymph node regions. Constitutional symptoms Oropharyngeal involvement Presenting features Anemia, neutropenia with infections or thrombocytopenia Abdominal disease Other organs Skin, brain, testis or thyroid Haematological and biochemical findings normochromic, normocytic anemia autoimmune hemolytic anemia If bone marrow involvement (leukoerythroblastic) Lymphoma may be found in the peripheral blood in some patients Trephine biopsy of marrow is valuable to find if it is involved or not. (LDH) level is raised Chromosomal Abnormalities in NHL frequent chromosomal translocations into Ig gene loci t(8;14), t(2;8), t(8;22) Burkitt’s t(14;18) follicular NHL Low-grade NHL Follicular lymphoma This is the most common form of NHL and is associated with the t(14; 18) characterized by a benign course for many years The median survival from diagnosis is approximately 10 years Lymphocytic lymphoma this lymphoma appear to be a tissue phase of CLL. Lymphoplasmacytoid lymphomas Often associated with the production of monoclonal IgM in which case they tend to be termed Waldenstrom’s macroglobulinemia (hyperviscosity) Mantle cell lymphoma is derived from pre-germinal center cells Marginal zone lymphomas are typically extranodal and are usually localized. Mucosa associated lymphoid tissue (MALT) lymphomas. High grade non-Hodgkin's lymphoma Diffuse large B-cell lymphomas: (DLCL) are a heterogeneous group of disorders. rapidly progressive lymphadenopathy associated with a fast rate of cellular proliferation. Burkitt's lymphoma is occurs in endemic or sporadic forms associated with Epstein-Barr virus (EBV) infection Burkitt's lymphoma Burkitt's lymphoma Diffuse large B cell lymphoma Diffuse large B cell lymphoma T -cell lymphomas Mycosis fungoides Sezary syndrome Summary or Conclusion: Lymphoma simply means cancer of the lymph nodes and the lymphatic tissues of the body. Lymphomas are divided into two main groups: the best- known group is called “Hodgkin Lymphomas”; what is left constitutes a collection of conditions called “Non- Hodgkin Lymphomas (NHL)”. Questions? DEFINE LYMPHOMA WHAT ARE THE TYPES OF LYMPHOMA WHAT ARE CLINICAL FEATURES OF LYMPHOMA? WHAT ARE HEMATOLOGICAL FINDINGS OF LYMPHOMA?