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LYMPHOID NEOPLASMS. Definitions and Classification One confusing aspect concearns the use of the term LEUKEMIA and LYMPHOMA. LEUKEMIAS present with widespread involvement of the bone marrow and peripheral blood . LYMPHOMA is used for proliferations arising as discrete tissue masses . - PowerPoint PPT Presentation

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LYMPHOID NEOPLASMSDefinitions and Classification

One confusing aspect concearns the use of the term LEUKEMIA and LYMPHOMA.

LEUKEMIAS present with widespread involvement of the bone marrow and peripheral blood.

LYMPHOMA is used for proliferations arising as discrete tissue masses.

Originally, terms LEUKEMIA and LYMPHOMA were consistent distinct entities, but this division has blurred.

Many lymphomas may have leukemic presentations and evolution to leukemias is not unusual.

Conversely, leukemias sometimes arise as soft-tissue masses.

Both terms merely reflect the usual tissue distribution of each disease at presentation.

LYMPHOMAS are known in two categories: Hodgkins Lymphoma, treatable in aunique fashion, and the family of NHL.

The clinical presentation of the various lymphoid neoplasms is most often determined by the anatomic distribution of the disease.2/3 of NHLs and virtually all HL present as enlarged non-tender lymph nodes ( 2 cm).

The remaining 1/3 of NHLs present with symptoms related to involvement of extranodal sites: stomach, intestine, skin, brain.

In NHL an important group of tumors is represented by the plasma cell neoplasms.

Leukemias present with symptoms related to the supression of hematopoesis. Multiple myeloma causes bony destruction or pain due to pathologic fracture. Certain tumors may cause fever (HL) and secretion of circulating factors (e.g.amyloid) from plasma cells.

HISTORY

The oldest classification scheme has used only few terms: lymphosarcoma, reticulosarcoma, lymphogranulatomasis Paltauf-Sternberg, M. Hodgkin.

Rappaport: nodular difuse involvement of the lymph nodes.

During the years 1960 1980 there temporarily existed several national classifications (German, French, English, American (Florida and California) and international (REAL) , introducing new basic and research-based and clinically accepted information. Soon afterwards, at the end of the 20th century, WHO experts from several medical specialities have developed a unified, modern and open international classification system (2001) based on morphological, immunophenotypic, genotypic and clinical features (interdisciplinary acepted).

Lymphoid tumors are sorted into 5 broad categories

1. Precursor B-cell neoplasms (immature B cells)

2. Peripheral B-cell neoplasms (mature B cells)

3. Precursor T- cell neoplasms (immature T cell)

4. Peripheral T cell ad NK-cell neoplasms (mature T cell and NK cell)

5. Hodgkin Lymphoma

The WHO Classification of Lymphoid Neoplasms (2001)I Precursor B Cell Neoplasms B cell acute lymphoblastic leukemia/lymphoma (B - ALL)

II Peripheral B Cell Neoplasms Chronic lymphocytic leukemia/small lymphocytic lymphoma B cell prolymphocytic leukemia Lymphoplasmocytic lymphoma Splenic and nodal marginal zone lymphoma Extranodal marginal zone lymphoma Follicular lymphoma Marginal zone lymphoma Hairy cell leukemia Plasmacytoma/plasma cell myeloma Diffuse large B cell lymphoma Burkitt lymphoma

The WHO Classification of Lymphoid Neoplasms (2001)

III Precursor T cell neoplasms T cell acute lymphoblastic leukemia/lymphoma (T ALL)IV Peripheral T cell and NK cell neoplasms T cell prolymphocytic leukemia Large granular lymphocytic leukemia Mycosis fungoides/Szary syndrome Peripheral T cell lymphoma unspecified Anaplastic large cell lymphoma Angioimmunoblastic T cell lymphoma Enteropathy-associated T cell lymphoma Panniculitic T cell lymphoma Hepatosplenic gamma-delta T cell lymphoma Adult T cell leukemia/lymphoma Extranodal NK/T cell lymphoma NK cell lymphoma

The WHO Classification of Lymphoid Neoplasms (2001)

V Hodgkin lymphoma Classical subtypes Nodular sclerosis type Mixed cellularity type Lymphocyte-rich type Lymphocyte depletion type

Lymphocyte predominance type

Important principles of lymphoid neoplasms

Lymphoid neoplasms may be clinically suspected, but histologic examination is required for diagnosis.

In most lymphoid neoplasms, antigen receptor gene rearrangement presents transformation, hence, all of the daughter cells derived from the malignant progenitor share the same configuration and sequence, and synthesise identical antigen receptor protein (Ig, T cell receptor). In contrast to reactive (polyclonal) proliferations the lymphoid neoplasms are monoclonal lymphoid proliferations.

These antigen gene rearrangement produce a unique DNA sequences that constitute a highly specific clonal marker, detectable by MoAb.

The vast majority (85-90%) of lymphoid neoplasms are of B-cell origin.

Important principles of lymphoid neoplasms

NK tumors are rare. B cell and T cell represent some recognizable stage of B or T cell differentiation, a feature used in their nomenclature/terminology. Benign counterparts of lymphomas do not exist.

Neoplastic B and T cells recapitulate the behaviour of their normal counterparts. Examples: follicular lymphomas home to germinal centers, cutaneous lymphomas home to the skin. This is governed by particular adhesion molecules and chemokine receptors.

Variable numer of B or T cells recirculate through the lymphatics and blood vessels, so that at time of diagnosis most tumors are widely disseminated. Exceptions: Hodgkin lymphoma and Marginal zone B cell lymphoma. This feature reminds of the physiological daily repeating multiple recirculation of lymphocytes between the central and peripheral lymphatic organs.

Hodgkin lymphoma spreads in an orderly fashion. In contrast, most forms of NHL spread widely early in their course in a less predictable fashion. Therefore, staging is of most utility in HL.

PRECURSOR B cell and T cell neoplasms

are composed of immature B and T cells (lymphoblasts). About 85% are B-ALL and it is the most common cancer of children up to 15 years. Adults are affected less frequently. Individual cases may be more or less immature or mature, so that various CD markers: B: CD 10, 19, 20 and T: CD 1,2,3, 4, 5, 7 and 8 may be expressed in tumor cells.

Approximately 90% of ALLs have various numerical or structural chromosomal changes.

Pediatric ALL is one of the great success stories of oncology with complete remission in 95% of children and 30-40% of adults.

Clinical features: abrupt onset, depression of bone marrow functions, mass effect, CNS manifestations.

Peripheral B-cell NeoplasmsChronic lymphocytic Leukemia (CLL)/Small lymphocytic Lymphoma (SLL)

Represents the most common adult leukemia with median age at diagnosis being 60 years, 2:1 male preponderance in Western countries comparing with Asian countries and Japan.

Microscopically: diffuse infiltration with small lymphocytes with proliferation centers in the lymph nodes, bone marrow, spleen and liver.

Expression of CD 19, 20, 23 and 5, surface IgM.

Clinically, fatigability, anorexia, weight loss, lymphadenopathy, hepatosplenomegaly, hypogammaglobulinemia, relatively slow course , tendency to transformation to more aggressive forms (Richter syndrome). Possible use of immunotherapy, chemotherapy and transplantation.Follicular Lymphoma

An indolent ,most common NHL in middle age with uneven frequency in the Word.

Typical cell is a small lymphocyte with irregular/cleaved nuclei (centrocyte) in predominant follicular arrangement.

Immunophenotype:CD 10, 19, 20, surface Ig, BCL 6.

Clinically: generalized, painless lymphoadenopathy, and relatively uncommon involvement of extranodal sites. Median survival: 7-9 years, with possible transformation to diffuse large B cell lymphoma (duration less than 1 year).

Diffuse large B-cell Lymphoma

The most common NHL with median age of 60 years, may affect even children.

Microscopically these tumors grow diffusely and contain relatively large cells.

Immunophenotype: CD 19, 20, sometimes also CD10 and BCL-6.

Cytogenetic gene expression is heterogenous.

Special forms: Immunodeficiency-associated large B cell Lymphoma and Primary effusion lymphoma in AIDS and elderly.

If untreated, is an aggressive tumor affecting many sites and rapidly fatal.

Immunotherapy improves responses and outcome/prognosis.

Burkitt Lymphoma (BL)

African (endemic) BLSporadic (non-endemic) BLAggressive lymphoma in AIDS

Microscopically: a starry-sky appearance, high mitotic index

Immunophenotype: CD 10, 19, 20, BCL-6, sIgM

Molecular pathogenesis: Translocations of the C MYC gene on chromosome 8

Endemic and sporadic BLs are formed mainly in children and young adults mostly in extranodal sites (mandible, kidneys, ovaries, adrenals) Tumors are aggresive but treatablePlasma Cell Neoplasms and Related Disorders (dyscrasias)

Contain plasma cells secreting monoclonal Ig or a Ig fragment. The worst type is Multiple myeloma (plasma cell myeloma). Special terms are used for these neoplasms: monoclonal gammopathy, dysproteinemia, paraproteinemia, primary amyloidosis or immunocyte-associated amyloidosis.

Plasmocytoma (solitary myeloma) is an infrequent variant that represents as a single (isolated) mass in bone or in soft tissue. Smoldering myeloma with lack of symptoms and high plasma M. component.

Waldenstrm macroglobulinemia is a syndrome: monoclonal gammopathy, blood hyperviscosity and incurable lympho-plasmocytic lymphoma .

Heavy chain disease and Monoclonal gammopathy of undetermined significance (MGUS), common

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