Lymphoma classification is based on the cell of origin (B-cell, T-cell, NK-cell). Molecular biology techniques including immunophenotyping and genetic studies are important for accurate diagnosis and classification. Immunophenotyping uses cell surface markers identified by clusters of differentiation (CD markers) to determine the cell lineage and stage of differentiation. Common CD markers for B-cells, T-cells, myeloid cells and other lineages are described. Molecular studies can identify genetic abnormalities that help classify specific lymphoma subtypes. Together these molecular techniques provide crucial information beyond what is visible by microscopy alone.
This document provides an approach for evaluating undifferentiated tumors. It begins by categorizing undifferentiated tumors into 4 groups based on morphology: small round cell tumors, epithelioid cell tumors, spindle cell tumors, and pleomorphic tumors. It then outlines the diagnostic algorithm which involves determining the main lineage (epithelial, melanocytic, hematopoietic/lymphoid, or mesenchymal), specifying a diagnosis using immunohistochemistry and clinical correlation, and considering the differential diagnoses for each category. A variety of immunohistochemical markers are also described that can help identify the cell or tumor type.
Soft tissue pathology is rapidly changing
Novel molecular findings
Tumors previously known under one rubric are reclassified with relative frequency
Lesions that for decades were thought to be reactive now are discovered to possess gene rearrangements
Features of previously unknown or incompletely described tumors are coalesced and synthesized into new entities
Relative rarity of soft tissue tumors only adds to the challenge
of keeping abreast of all of these advances
The document discusses minimal residual disease (MRD), which refers to small amounts of malignant cells that remain undetectable by conventional methods but can be detected using highly sensitive techniques like PCR. It provides an overview of techniques used for MRD detection in various hematologic malignancies, including morphology, immunophenotyping, cytogenetics, FISH, and PCR. The sensitivity and limitations of each technique is reviewed. Common genomic targets for MRD detection are discussed for several leukemias and lymphomas. The significance of accurately measuring MRD levels for prognosis, monitoring relapse risk, and guiding treatment is also summarized.
Lab Diagnosis of Chronic lymphoproliferative disorders (CLPD);Flowcytometric...Dr Siddartha
Lab Diagnosis of Chronic lymphoproliferative disorders (CLPD);Flowcytometric Evaluation
Basavatarakam Indo-American Cancer Hospital and Research Institute
various cutaneous lymphomas though having low incidence but need to be diagnosed accurately. they can be mimiced by many non neoplastic conditions of skin. so discussing both T and B cell lymphomas
A comprehensive review of Cutaneous Lymphomas - both B-Cell and T-Cell with latest treatment strategies. Target audience are oncologists, dermatologists, oncology physicians, dermatology and oncology fellows
This is a presentation on the topic of cytology of the breast, prepared by Dr Ashish Jawarkar, he is MD in pathology and a teacher at Parul institute of Medical sciences and research Vadodara.
Molecular profiling of breast cancer can classify tumor types, identify appropriate therapeutic targets, determine prognosis, and predict treatment response. Techniques include immunohistochemistry, fluorescence in situ hybridization, reverse transcription PCR, microarrays, and next generation sequencing to analyze protein expression, gene copy number, mutations, and gene expression levels. Breast cancers are classified into intrinsic subtypes including luminal A/B, HER2-enriched, basal-like, and claudin-low based on distinct gene expression patterns that predict clinical behavior and response to therapy.
This document provides an approach for evaluating undifferentiated tumors. It begins by categorizing undifferentiated tumors into 4 groups based on morphology: small round cell tumors, epithelioid cell tumors, spindle cell tumors, and pleomorphic tumors. It then outlines the diagnostic algorithm which involves determining the main lineage (epithelial, melanocytic, hematopoietic/lymphoid, or mesenchymal), specifying a diagnosis using immunohistochemistry and clinical correlation, and considering the differential diagnoses for each category. A variety of immunohistochemical markers are also described that can help identify the cell or tumor type.
Soft tissue pathology is rapidly changing
Novel molecular findings
Tumors previously known under one rubric are reclassified with relative frequency
Lesions that for decades were thought to be reactive now are discovered to possess gene rearrangements
Features of previously unknown or incompletely described tumors are coalesced and synthesized into new entities
Relative rarity of soft tissue tumors only adds to the challenge
of keeping abreast of all of these advances
The document discusses minimal residual disease (MRD), which refers to small amounts of malignant cells that remain undetectable by conventional methods but can be detected using highly sensitive techniques like PCR. It provides an overview of techniques used for MRD detection in various hematologic malignancies, including morphology, immunophenotyping, cytogenetics, FISH, and PCR. The sensitivity and limitations of each technique is reviewed. Common genomic targets for MRD detection are discussed for several leukemias and lymphomas. The significance of accurately measuring MRD levels for prognosis, monitoring relapse risk, and guiding treatment is also summarized.
Lab Diagnosis of Chronic lymphoproliferative disorders (CLPD);Flowcytometric...Dr Siddartha
Lab Diagnosis of Chronic lymphoproliferative disorders (CLPD);Flowcytometric Evaluation
Basavatarakam Indo-American Cancer Hospital and Research Institute
various cutaneous lymphomas though having low incidence but need to be diagnosed accurately. they can be mimiced by many non neoplastic conditions of skin. so discussing both T and B cell lymphomas
A comprehensive review of Cutaneous Lymphomas - both B-Cell and T-Cell with latest treatment strategies. Target audience are oncologists, dermatologists, oncology physicians, dermatology and oncology fellows
This is a presentation on the topic of cytology of the breast, prepared by Dr Ashish Jawarkar, he is MD in pathology and a teacher at Parul institute of Medical sciences and research Vadodara.
Molecular profiling of breast cancer can classify tumor types, identify appropriate therapeutic targets, determine prognosis, and predict treatment response. Techniques include immunohistochemistry, fluorescence in situ hybridization, reverse transcription PCR, microarrays, and next generation sequencing to analyze protein expression, gene copy number, mutations, and gene expression levels. Breast cancers are classified into intrinsic subtypes including luminal A/B, HER2-enriched, basal-like, and claudin-low based on distinct gene expression patterns that predict clinical behavior and response to therapy.
This document discusses techniques used to study lymphomas, including immunophenotyping, cytogenetics, and molecular analysis. Immunophenotyping helps differentiate benign from malignant processes and B and T cell neoplasms by identifying cell surface markers. Cytogenetics identifies chromosomal translocations which are characteristic of different lymphomas. Molecular analysis finds Ig and TCR gene rearrangements in B and T cell malignancies. The document also summarizes different classifications of lymphomas and characteristics of specific lymphoma types like CLL/SLL, follicular lymphoma, DLBCL, and Burkitt's lymphoma.
1) The document discusses Acute Myeloid Leukemia (AML), including its classification, epidemiology, etiology, clinical presentation, laboratory findings, and specific subtypes defined by genetic abnormalities such as AML with t(8;21), inv(16), and t(15;17).
2) It describes the key features of different AML subtypes including their morphology, immunophenotype, genetics, and prognosis. Specific attention is given to abnormal cells, staining patterns, and genetic translocations that characterize each subtype.
3) The FAB and WHO classification systems are introduced and compared, noting the WHO system incorporates immunophenotyping, cytogenetics, and molecular characteristics
Bethesda system for reporting thyroid cytologyariva zhagan
The document discusses the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), which provides a standardized classification system for thyroid fine needle aspiration (FNA) results. The BSRTC aims to improve communication between clinicians by establishing uniform diagnostic terminology. It categorizes FNA results as non-diagnostic, benign, atypia of undetermined significance/follicular lesion of undetermined significance, follicular neoplasm/suspicious for follicular neoplasm, suspicious for malignancy, or malignant. The document outlines the criteria for each category and risk of malignancy. It notes recent enhancements in the 2017 version of BSRTC, including recalculated risk of malignancy and the
1) Flow cytometry is used to measure multiple physical and chemical properties of cells in a fluid stream at a rate of thousands of cells per second. It is used to diagnose and classify leukemias based on antigen expression.
2) In leukemias, abnormal antigen expression patterns can include gain of antigens not normally expressed, abnormally increased or decreased levels of expression, or asynchronous antigen expression.
3) Flow cytometry utilizes light scattering and fluorescence to identify cell size, granularity, lineage, and maturation stage based on antigen expression. This immunophenotyping is essential for diagnosing and distinguishing between different types of leukemias.
This document discusses immunohistochemistry (IHC), which is used to identify tissue antigens through antigen-antibody interactions. It provides details on the IHC process, common antibodies and their targets, and tumor markers. IHC is useful for tumor diagnosis, narrowing differential diagnoses, and detecting unexpected diagnoses. The antibody panels discussed can help determine the primary site of cancers and differentiate between tumor types.
Dr. nahla farahat immunophenotyping of multiple myeloma Hitham Esam
Plasma cell myeloma is a heterogeneous group of neoplasms characterized by expansion of clonal plasma cells in the bone marrow. Flow cytometry is useful for diagnosing and monitoring plasma cell disorders by confirming the clonal nature of plasma cells and differentiating disorders. Normal plasma cells are CD38bright, CD138+, CD19+ and CD45dim, while myeloma cells typically show aberrant expression including CD19, CD27 and CD45 underexpression and CD28, CD33, CD56 and CD117 overexpression. A minimum of 100 clonal plasma cell events should be acquired to accurately assess disease. The presence of more than 5% residual normal plasma cells can differentiate MGUS from myeloma.
Hodgkin's lymphoma, also known as Hodgkin's disease, is a cancer that originates in the lymphatic system. It is characterized by the presence of Reed-Sternberg cells in the lymph nodes and other tissues. The disease has four main subtypes - nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte rich - which are distinguished based on the type of cells in the tissue around the Reed-Sternberg cells. The nodular sclerosis subtype, which involves bands of fibrosis dividing the lymph node tissue into nodules, accounts for about 40-70% of cases. Hodgkin's lymphoma most commonly presents with painless swelling of lymph nodes in the neck,
The document summarizes the role of innate and adaptive immune cells in the tumor microenvironment and their effect on tumor growth. It discusses how the tumor microenvironment can influence immune cells and how immune cells can affect tumor progression. Key cells discussed include macrophages, neutrophils, NK cells, T cells, B cells, dendritic cells, and regulatory T cells. It covers topics like hypoxia, inflammation, immune evasion mechanisms used by tumors, and the pro-tumoral phenotypes that immune cells can adopt in the microenvironment.
Classification and diagnostic approach to fnac of mediastinalIndira Shastry
This document discusses the classification and diagnostic approach to fine needle aspiration cytology (FNAC) of mediastinal tumors. It describes the various tumor types that can occur in the mediastinum, including thymic tumors, germ cell tumors, lymphomas, and others. For each tumor type, it provides details on cytological features, differential diagnoses, immunohistochemistry findings, and other diagnostic information useful for FNAC-based diagnosis of mediastinal masses. The goal is to simplify the classification and provide guidance on distinguishing between benign and malignant mediastinal tumors using cytology samples.
The document discusses immunotherapy and the role of pathologists in assessing tumor samples. It describes how certain tumors express PD-L1 antigens that can be recognized by the immune system, but the tumors also engage immune checkpoint pathways like PD-1 and CTLA-4 to evade the immune response. Immunotherapy drugs target these checkpoint pathways to enhance the immune response. The document outlines the FDA-approved PD-L1 immunohistochemistry assays and biomarkers used to identify cancer patients most likely to respond to immune checkpoint inhibitors for various cancer types including NSCLC, melanoma, bladder cancer, and colorectal cancer.
Giant cell lesions of bone include both reactive and neoplastic conditions characterized by the presence of multinucleated giant cells. Reactive giant cell lesions include giant cell reparative granuloma and brown tumor of hyperparathyroidism. Benign neoplastic giant cell lesions include giant cell tumor and aneurysmal bone cyst. Giant cell tumor is the most common, occurring most frequently in long bones of the extremities in young and middle aged adults. Histologically it is characterized by uniformly distributed osteoclast-like giant cells and mononuclear stromal cells that express RANKL.
This document discusses liquid biopsy, a non-invasive technique to detect tumor biomarkers shed into body fluids like blood. It can identify circulating tumor cells, circulating tumor DNA, exosomes, and newly, tumor educated platelets. Liquid biopsy offers advantages over tissue biopsy like being less invasive, allowing repeated sampling over time. While sensitivity remains a limitation, liquid biopsy shows promise for early cancer detection, monitoring treatment response and tumor evolution, and assessing tumor heterogeneity. The document reviews technologies to analyze various biomarkers and potential clinical applications of liquid biopsy.
Flow cytometry plays an indispensable role in the diagnosis of hematological disorders by providing data on immunophenotype. It is a method that can measure multiple characteristics of single cells using fluorescent markers and lasers. This allows determination of cell size, granularity, protein expression and more. Two cases are described where flow cytometry was used. In case 1, a leukemia sample showed expression of markers consistent with acute promyelocytic leukemia. In case 2, a mediastinal mass sample expressed markers indicating acute T-cell leukemia. Flow cytometry provides valuable immunophenotyping data for diagnosis of hematological malignancies.
Non-Hodgkin's lymphomas arise from monoclonal expansion of malignant B or T cells. There are many subtypes of NHL, classified based on cell lineage and other features. Treatment depends on factors like aggressiveness - indolent NHLs grow slowly while very aggressive NHLs can be life-threatening if not treated rapidly. The most common subtypes are diffuse large B-cell lymphoma and follicular lymphoma. Diagnosis involves biopsy and other tests to identify the histologic subtype and stage of disease. Prognosis and treatment approach are guided by these factors.
The Paris System for Reporting Urinary CytologyRawa Muhsin
The Paris System for Reporting Urinary Cytology provides standardized diagnostic categories for urine cytology specimens. It divides results into negative for high-grade urothelial carcinoma, positive for high-grade urothelial carcinoma, atypical urothelial cells, and suspicious for high-grade urothelial carcinoma based on the number and features of abnormal cells seen. The system aims to determine whether high-grade urothelial carcinoma is present or not, as this has important implications for patient management and prognosis. Risk of malignancy increases from negative to atypical to suspicious to positive categories.
Mature T/NK-cell neoplasms can be classified based on the cell of origin. This includes CD4+ T-cell neoplasms such as T-cell prolymphocytic leukemia (T-PLL), adult T-cell leukemia/lymphoma (ATLL), and mycosis fungoides/Sézary syndrome (MF/SS). T-PLL is characterized by chromosomal abnormalities involving chromosome 14 and expression of TCL1. ATLL is caused by HTLV-1 and presents with skin rash, lymphadenopathy, and organomegaly. MF/SS involves the skin and may progress to Sézary syndrome with blood and lymph node
This document provides an overview of Chronic Lymphocytic Leukemia (CLL) presented by Dr. Subhash Thakur. It discusses the incidence, clinical features, diagnosis, staging, management and treatment of CLL at different stages. It also covers complications, response evaluation, and long-term implications. CLL most commonly presents with recurring infections in elderly adults. Physical exams may reveal enlarged lymph nodes and splenomegaly. Peripheral blood flow cytometry is most helpful for diagnosis. Watchful waiting is the recommended strategy for asymptomatic early-stage CLL patients.
The document discusses molecular subtyping of breast cancer through gene expression profiling which has identified major subtypes including luminal A, luminal B, HER2-enriched, and basal-like. It describes the characteristic gene expressions and clinical features of each subtype. Molecular subtyping is shown to have prognostic and predictive relevance for breast cancer outcomes and treatment responses.
This document discusses renal pediatric tumors. It begins by describing the main types of nephroblastic tumors and renal epithelial tumors of childhood. Wilms tumor, or nephroblastoma, comprises over 80% of renal tumors in children and is discussed in detail, including associated syndromes, gross and microscopic pathology, staging, and treatment. Mesoblastic nephroma and clear cell sarcoma are also described as relatively rare but important renal tumors of childhood. The key information provided includes classification, clinical features, histopathology, immunoprofile, differential diagnosis, and prognosis for the major pediatric renal tumors.
CD antigens, also known as clusters of differentiation, are cell surface proteins that are used to identify and characterize cell types. Over 371 CD markers have been identified that serve important functions like cell signaling. CD markers are analyzed using techniques like flow cytometry and help diagnose diseases like leukemia by identifying abnormal levels of specific CD antigens. Key CD markers have been identified for important immune cells like T cells, B cells, granulocytes, and stem cells. Immunophenotyping using CD markers is an important application in diagnosing diseases and monitoring treatment responses.
The document discusses various types of lymphoma and leukemia. It defines lymphoma as lymphoid proliferations in discrete tissue masses, while leukemia involves widespread involvement of the bone marrow and large numbers of tumor cells in the blood. Key types discussed include non-Hodgkin's lymphoma, Hodgkin's disease, follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, Burkitt lymphoma, and mantle cell lymphoma. Classification systems and characteristic features such as morphology, immunophenotype, genetics, and clinical presentation are summarized for several of these.
This document discusses techniques used to study lymphomas, including immunophenotyping, cytogenetics, and molecular analysis. Immunophenotyping helps differentiate benign from malignant processes and B and T cell neoplasms by identifying cell surface markers. Cytogenetics identifies chromosomal translocations which are characteristic of different lymphomas. Molecular analysis finds Ig and TCR gene rearrangements in B and T cell malignancies. The document also summarizes different classifications of lymphomas and characteristics of specific lymphoma types like CLL/SLL, follicular lymphoma, DLBCL, and Burkitt's lymphoma.
1) The document discusses Acute Myeloid Leukemia (AML), including its classification, epidemiology, etiology, clinical presentation, laboratory findings, and specific subtypes defined by genetic abnormalities such as AML with t(8;21), inv(16), and t(15;17).
2) It describes the key features of different AML subtypes including their morphology, immunophenotype, genetics, and prognosis. Specific attention is given to abnormal cells, staining patterns, and genetic translocations that characterize each subtype.
3) The FAB and WHO classification systems are introduced and compared, noting the WHO system incorporates immunophenotyping, cytogenetics, and molecular characteristics
Bethesda system for reporting thyroid cytologyariva zhagan
The document discusses the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), which provides a standardized classification system for thyroid fine needle aspiration (FNA) results. The BSRTC aims to improve communication between clinicians by establishing uniform diagnostic terminology. It categorizes FNA results as non-diagnostic, benign, atypia of undetermined significance/follicular lesion of undetermined significance, follicular neoplasm/suspicious for follicular neoplasm, suspicious for malignancy, or malignant. The document outlines the criteria for each category and risk of malignancy. It notes recent enhancements in the 2017 version of BSRTC, including recalculated risk of malignancy and the
1) Flow cytometry is used to measure multiple physical and chemical properties of cells in a fluid stream at a rate of thousands of cells per second. It is used to diagnose and classify leukemias based on antigen expression.
2) In leukemias, abnormal antigen expression patterns can include gain of antigens not normally expressed, abnormally increased or decreased levels of expression, or asynchronous antigen expression.
3) Flow cytometry utilizes light scattering and fluorescence to identify cell size, granularity, lineage, and maturation stage based on antigen expression. This immunophenotyping is essential for diagnosing and distinguishing between different types of leukemias.
This document discusses immunohistochemistry (IHC), which is used to identify tissue antigens through antigen-antibody interactions. It provides details on the IHC process, common antibodies and their targets, and tumor markers. IHC is useful for tumor diagnosis, narrowing differential diagnoses, and detecting unexpected diagnoses. The antibody panels discussed can help determine the primary site of cancers and differentiate between tumor types.
Dr. nahla farahat immunophenotyping of multiple myeloma Hitham Esam
Plasma cell myeloma is a heterogeneous group of neoplasms characterized by expansion of clonal plasma cells in the bone marrow. Flow cytometry is useful for diagnosing and monitoring plasma cell disorders by confirming the clonal nature of plasma cells and differentiating disorders. Normal plasma cells are CD38bright, CD138+, CD19+ and CD45dim, while myeloma cells typically show aberrant expression including CD19, CD27 and CD45 underexpression and CD28, CD33, CD56 and CD117 overexpression. A minimum of 100 clonal plasma cell events should be acquired to accurately assess disease. The presence of more than 5% residual normal plasma cells can differentiate MGUS from myeloma.
Hodgkin's lymphoma, also known as Hodgkin's disease, is a cancer that originates in the lymphatic system. It is characterized by the presence of Reed-Sternberg cells in the lymph nodes and other tissues. The disease has four main subtypes - nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte rich - which are distinguished based on the type of cells in the tissue around the Reed-Sternberg cells. The nodular sclerosis subtype, which involves bands of fibrosis dividing the lymph node tissue into nodules, accounts for about 40-70% of cases. Hodgkin's lymphoma most commonly presents with painless swelling of lymph nodes in the neck,
The document summarizes the role of innate and adaptive immune cells in the tumor microenvironment and their effect on tumor growth. It discusses how the tumor microenvironment can influence immune cells and how immune cells can affect tumor progression. Key cells discussed include macrophages, neutrophils, NK cells, T cells, B cells, dendritic cells, and regulatory T cells. It covers topics like hypoxia, inflammation, immune evasion mechanisms used by tumors, and the pro-tumoral phenotypes that immune cells can adopt in the microenvironment.
Classification and diagnostic approach to fnac of mediastinalIndira Shastry
This document discusses the classification and diagnostic approach to fine needle aspiration cytology (FNAC) of mediastinal tumors. It describes the various tumor types that can occur in the mediastinum, including thymic tumors, germ cell tumors, lymphomas, and others. For each tumor type, it provides details on cytological features, differential diagnoses, immunohistochemistry findings, and other diagnostic information useful for FNAC-based diagnosis of mediastinal masses. The goal is to simplify the classification and provide guidance on distinguishing between benign and malignant mediastinal tumors using cytology samples.
The document discusses immunotherapy and the role of pathologists in assessing tumor samples. It describes how certain tumors express PD-L1 antigens that can be recognized by the immune system, but the tumors also engage immune checkpoint pathways like PD-1 and CTLA-4 to evade the immune response. Immunotherapy drugs target these checkpoint pathways to enhance the immune response. The document outlines the FDA-approved PD-L1 immunohistochemistry assays and biomarkers used to identify cancer patients most likely to respond to immune checkpoint inhibitors for various cancer types including NSCLC, melanoma, bladder cancer, and colorectal cancer.
Giant cell lesions of bone include both reactive and neoplastic conditions characterized by the presence of multinucleated giant cells. Reactive giant cell lesions include giant cell reparative granuloma and brown tumor of hyperparathyroidism. Benign neoplastic giant cell lesions include giant cell tumor and aneurysmal bone cyst. Giant cell tumor is the most common, occurring most frequently in long bones of the extremities in young and middle aged adults. Histologically it is characterized by uniformly distributed osteoclast-like giant cells and mononuclear stromal cells that express RANKL.
This document discusses liquid biopsy, a non-invasive technique to detect tumor biomarkers shed into body fluids like blood. It can identify circulating tumor cells, circulating tumor DNA, exosomes, and newly, tumor educated platelets. Liquid biopsy offers advantages over tissue biopsy like being less invasive, allowing repeated sampling over time. While sensitivity remains a limitation, liquid biopsy shows promise for early cancer detection, monitoring treatment response and tumor evolution, and assessing tumor heterogeneity. The document reviews technologies to analyze various biomarkers and potential clinical applications of liquid biopsy.
Flow cytometry plays an indispensable role in the diagnosis of hematological disorders by providing data on immunophenotype. It is a method that can measure multiple characteristics of single cells using fluorescent markers and lasers. This allows determination of cell size, granularity, protein expression and more. Two cases are described where flow cytometry was used. In case 1, a leukemia sample showed expression of markers consistent with acute promyelocytic leukemia. In case 2, a mediastinal mass sample expressed markers indicating acute T-cell leukemia. Flow cytometry provides valuable immunophenotyping data for diagnosis of hematological malignancies.
Non-Hodgkin's lymphomas arise from monoclonal expansion of malignant B or T cells. There are many subtypes of NHL, classified based on cell lineage and other features. Treatment depends on factors like aggressiveness - indolent NHLs grow slowly while very aggressive NHLs can be life-threatening if not treated rapidly. The most common subtypes are diffuse large B-cell lymphoma and follicular lymphoma. Diagnosis involves biopsy and other tests to identify the histologic subtype and stage of disease. Prognosis and treatment approach are guided by these factors.
The Paris System for Reporting Urinary CytologyRawa Muhsin
The Paris System for Reporting Urinary Cytology provides standardized diagnostic categories for urine cytology specimens. It divides results into negative for high-grade urothelial carcinoma, positive for high-grade urothelial carcinoma, atypical urothelial cells, and suspicious for high-grade urothelial carcinoma based on the number and features of abnormal cells seen. The system aims to determine whether high-grade urothelial carcinoma is present or not, as this has important implications for patient management and prognosis. Risk of malignancy increases from negative to atypical to suspicious to positive categories.
Mature T/NK-cell neoplasms can be classified based on the cell of origin. This includes CD4+ T-cell neoplasms such as T-cell prolymphocytic leukemia (T-PLL), adult T-cell leukemia/lymphoma (ATLL), and mycosis fungoides/Sézary syndrome (MF/SS). T-PLL is characterized by chromosomal abnormalities involving chromosome 14 and expression of TCL1. ATLL is caused by HTLV-1 and presents with skin rash, lymphadenopathy, and organomegaly. MF/SS involves the skin and may progress to Sézary syndrome with blood and lymph node
This document provides an overview of Chronic Lymphocytic Leukemia (CLL) presented by Dr. Subhash Thakur. It discusses the incidence, clinical features, diagnosis, staging, management and treatment of CLL at different stages. It also covers complications, response evaluation, and long-term implications. CLL most commonly presents with recurring infections in elderly adults. Physical exams may reveal enlarged lymph nodes and splenomegaly. Peripheral blood flow cytometry is most helpful for diagnosis. Watchful waiting is the recommended strategy for asymptomatic early-stage CLL patients.
The document discusses molecular subtyping of breast cancer through gene expression profiling which has identified major subtypes including luminal A, luminal B, HER2-enriched, and basal-like. It describes the characteristic gene expressions and clinical features of each subtype. Molecular subtyping is shown to have prognostic and predictive relevance for breast cancer outcomes and treatment responses.
This document discusses renal pediatric tumors. It begins by describing the main types of nephroblastic tumors and renal epithelial tumors of childhood. Wilms tumor, or nephroblastoma, comprises over 80% of renal tumors in children and is discussed in detail, including associated syndromes, gross and microscopic pathology, staging, and treatment. Mesoblastic nephroma and clear cell sarcoma are also described as relatively rare but important renal tumors of childhood. The key information provided includes classification, clinical features, histopathology, immunoprofile, differential diagnosis, and prognosis for the major pediatric renal tumors.
CD antigens, also known as clusters of differentiation, are cell surface proteins that are used to identify and characterize cell types. Over 371 CD markers have been identified that serve important functions like cell signaling. CD markers are analyzed using techniques like flow cytometry and help diagnose diseases like leukemia by identifying abnormal levels of specific CD antigens. Key CD markers have been identified for important immune cells like T cells, B cells, granulocytes, and stem cells. Immunophenotyping using CD markers is an important application in diagnosing diseases and monitoring treatment responses.
The document discusses various types of lymphoma and leukemia. It defines lymphoma as lymphoid proliferations in discrete tissue masses, while leukemia involves widespread involvement of the bone marrow and large numbers of tumor cells in the blood. Key types discussed include non-Hodgkin's lymphoma, Hodgkin's disease, follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, Burkitt lymphoma, and mantle cell lymphoma. Classification systems and characteristic features such as morphology, immunophenotype, genetics, and clinical presentation are summarized for several of these.
This document discusses T-cell and NK-cell neoplasms. It begins by describing NK cells and their morphology as large granular lymphocytes that lack T-cell receptors and CD3 expression but express CD56 and CD16. The document then covers the various types of T-cell and NK-cell neoplasms including their morphology, immunophenotype, and genetics. Key neoplasms discussed are T-cell lymphoblastic leukemia/lymphoma, T-cell prolymphocytic leukemia, T-cell large granular lymphocytic leukemia, and extranodal NK/T-cell lymphoma among others. The document provides details on the diagnostic criteria for each type of neoplasm.
Flow cytometry allows for the analysis of physical and chemical properties of cells as they flow in a single file through an illuminated light path. It can be used to identify cell types based on relative size, granularity, and fluorescent marker expression. In this document, applications of flow cytometry are discussed, including immunophenotyping cells to identify antigen expression, cell sorting, DNA content analysis, and cell cycle analysis. Clinical uses in hematological malignancies, transplantation, and sepsis are also described. Key markers for identifying and classifying acute leukemias, including ALL, AML, and myelomonocytic leukemia are provided.
This document provides an overview of lymphoid leukemias. It begins with an introduction to lymphoid leukemias and compares them to myeloid leukemias. It then discusses the subtypes of acute and chronic lymphoid leukemias in more detail. Key points include distinguishing between B-cell and T-cell acute lymphoblastic leukemias, important genetic alterations in ALL, and initial therapy approaches. Chronic lymphoid leukemias such as CLL are also reviewed, covering topics like diagnostic criteria, prognostic factors, and standard treatment regimens.
This document provides an overview of flow cytometry, including its principles, instrumentation, applications in hematology and oncology, and techniques for analyzing results. Flow cytometry works by passing single cells in a fluid stream through a laser beam, which detects cellular properties like size, structure, and antigen expression. It allows for multiparametric analysis of up to 12 parameters simultaneously on thousands of cells. Key applications include immunophenotyping of leukemias and lymphomas, DNA analysis, and monitoring of minimal residual disease.
Non-Hodgkin lymphoma (NHL) is a heterogeneous group of cancers of the lymphatic system characterized by abnormal B cell or T cell proliferation. NHL causes accumulation of cancerous lymphocytes in lymph nodes and extralymphatic organs. The highest rates are seen in North America and Europe, while Asia has lower rates. NHL is primarily a disease of older populations, with median age of 65. Common symptoms include lymphadenopathy, fever, night sweats, and weight loss. Diagnosis involves biopsy and staging includes imaging and bone marrow biopsy. Prognosis depends on histology, stage, and IPI score. Treatment involves chemotherapy, immunotherapy, radiation, stem cell transplant, or a combination depending on risk
This document discusses the classification and diagnosis of non-Hodgkin lymphoma (NHL) using cytology. It begins by outlining the WHO classification system for lymphomas which incorporates cytology, immunophenotype, genetics, and clinical findings. Flow cytometry is the main diagnostic tool for NHL classification. The document then describes the normal histology and cytology of lymph nodes before focusing on the cytological features and immunophenotypes of common B-cell and T-cell NHL subtypes such as follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma. Accurate classification requires integrating cytological findings with immunophenotyping and genetics.
Non Hodgkin Lymphoma treatment update (1).pptxDoQuyenPhan1
The document discusses treatment strategies for non-Hodgkin lymphoma (NHL). It summarizes the evolution of classification systems for NHL from Rappaport in 1966 to the current WHO system from 1999. It also summarizes treatment approaches that have improved outcomes over time, from first generation CHOP chemotherapy in the 1990s, to second and third generation intensive regimens, to the addition of rituximab to chemotherapy in 2002. The addition of rituximab to CHOP was shown to improve long-term event-free and overall survival compared to CHOP alone in diffuse large B-cell lymphoma based on 10-year follow-up results from a pivotal trial.
This document provides an overview of chronic lymphocytic leukemia (CLL). It defines CLL as the accumulation of mature B lymphocytes in the blood, bone marrow, lymph nodes, and spleen. CLL most commonly affects older adults and has an unknown cause. The document outlines the clinical presentation, diagnostic criteria, staging systems, complications, treatment approaches, and poor prognostic factors of CLL. It also discusses new therapies that aim to induce complete remission and eliminate minimal residual disease to improve survival outcomes in CLL patients.
1. Lymphoma refers to cancers that develop from lymphocytes in the lymph nodes and other lymphoid tissues. The document discusses the classification, clinical features, pathogenesis, and pathology of various types of lymphoma including Hodgkin lymphoma and non-Hodgkin lymphomas such as chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, and Burkitt lymphoma.
2. Hodgkin lymphoma is characterized by the presence of Reed-Sternberg cells amidst an inflammatory background. The four major histologic subtypes are nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte rich classical Hodgkin lymphoma.
3. Non-
This document provides an overview of non-Hodgkin lymphoma (NHL) classification systems. It discusses how NHL classification has evolved over time from descriptive systems based mainly on morphology to current systems that incorporate immunophenotype and genetic data. The Working Formulation (WF-NCI) classification from 1982 categorized NHL into low, intermediate, and high grade. The Revised European-American Lymphoma (REAL) classification built on WF-NCI with additional markers. The current WHO system is based on cell lineage and recognizes many distinct NHL subtypes including several types of B-cell and T-cell lymphomas. Common aggressive B-cell lymphomas covered include diffuse large B-cell lymphoma and Burkitt lymphoma.
Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the proliferation of immature lymphocytes in the bone marrow. Diagnosis requires identifying at least 20% lymphoblasts in the bone marrow. Testing includes bone marrow biopsy and aspiration with immunophenotyping, cytogenetics, lumbar puncture and other studies. Proper classification is important for determining prognosis and selecting optimal treatment strategies.
Leukaemia is a group of malignant blood disorders affecting the bone marrow and blood-forming tissues. There are four main types classified by whether the affected cells are lymphoid or myeloid, and whether the disease course is acute or chronic. Acute leukemias involve immature blast cells and a rapid progression, while chronic leukemias involve more mature cells and a slower course. The document defines each type and discusses their signs, symptoms, diagnosis, prognostic factors and treatment approaches.
Timeliness in diagnosis of acute leukemia in paediatric age groupkamali purushothaman
The document discusses acute leukemia in pediatric patients. It notes that leukemia and lymphoma are the most common cancers in children globally. It describes some of the typical presentations of acute leukemia in children, which can include symptoms like fatigue, fever, bruising, and organ enlargement due to infiltration of leukemia cells. The document outlines some potential life-threatening complications and discusses tests that are used in the diagnosis of childhood leukemia, including blood tests, bone marrow aspiration and biopsy, lumbar puncture, and cytogenetic testing.
There are two main types of chronic leukemia: chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). CML accounts for around 15% of leukemia cases and results from a genetic abnormality known as the Philadelphia chromosome. It commonly presents in middle age with symptoms of excessive white blood cell production. CLL is the most common chronic lymphoid leukemia, typically affecting older adults, and is characterized by the accumulation of abnormal lymphocytes in the blood and bone marrow. Staging systems such as Rai or Binet are used to determine prognosis and treatment approaches for CLL patients.
This document provides information on the diagnosis and management of various types of leukemia. It discusses the main types of leukemia - acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML). For AML and ALL, it describes the diagnostic criteria, risk factors, immunophenotyping, cytogenetics, molecular genetics, treatment approaches including induction and consolidation chemotherapy. It also discusses newer targeted therapies like CAR T-cells and CRISPR for leukemia treatment. For CML, it explains the defining Philadelphia chromosome and BCR-ABL fusion gene which causes the disease.
Mr. Salim, a 62-year-old man, presented with right neck and left groin swelling for 3 months along with 7-8 kg of weight loss. Biopsy revealed diffuse large B-cell non-Hodgkin lymphoma (NHL). He was diagnosed with stage IV NHL and treated with rituximab and CHOP chemotherapy. The presentation discusses lymphadenopathy causes, lymphoma types and differences between Hodgkin and non-Hodgkin lymphomas, risk factors, investigations and treatments. Key points include distinguishing reactive from tumoral lymph nodes, indolent versus aggressive NHL subtypes, common genetic abnormalities in lymphomas, and involvement of Epstein-Barr virus in certain malignancies.
Similar to Molecular pathology of lymphoma by dr ramesh (20)
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kol...rightmanforbloodline
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Versio
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Version
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Version
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
3. Thirty diseases, one name:
Try to imagine a single type of cell giving rise to nearly thirty different
types of cancer - all with one name. Lymphoma - simply in the nodes, a
mass in your brain, a disease of your stomach, or lesions all over your
skin. It's not simply a matter of location. The behavior changes with the
type and so does the treatment and the outcome.
The microscope isn't enough:
Even a couple of decades back, what the pathologist saw under the
microscope with simple stains was all that we had to identify the type of
lymphoma. And there were only a few types of lymphoma that could be
distinguished. However, it often turned out that the behavior of the
same type of tumor was different in different individuals. Clearly, we
were missing something.
The clue is in the molecules: MOLECULAR BIOLOGY (including
Immunophenotyping and Genetic studies)
4. Use of Immunophenotyping and Genetic Studies in
the Diagnosis of Lymphoid Neoplasms
The lymphoid neoplasms each have a characteristic morphology,
which is sometimes sufficient to permit diagnosis and classification if
well-prepared adequately sized sections are available.
However, there are many pitfalls in the histologic diagnosis of
malignant lymphoma, immunophenotyping and genetic studies are
extremely useful for resolving differential diagnostic problems.
Immunophenotyping and genetic studies are also developing key
roles in patient management beyond diagnosis, including
• identification of prognostic molecules,
• detection of minimal residual disease, and
• assessment of appropriate molecules for targeted therapy.
5. Need for Molecular Diagnosis
Rule out other disorders associated with lymphocytosis
If lymphoproliferative disorder remains a significant possibility after
clinical evaluation, cell surface phenotyping of lymphocytes should be
performed.
Usually performed on peripheral blood using flow cytometry.
Technique provides percentage of lymphocytes positive for a
particular antigen and density of antigens.
Normal peripheral blood lymphocytes consist of approximately 10%
B-cells, 80% T-cells and 10% NK-cells
6. Flow Cytometry
to see markers on the surface of
the cells.
This is a test that uses
fluorescent antibodies to tag
molecules on the surface of cells.
The flow cytometer has a teeny
tube that allows the cells to flow
one at a time past a laser beam.
In addition to telling what kinds of
markers a cell has, you can also
sort cells by size and complexity.
7. CD Markers
The “CD” stands for “cluster designation / cluster of differentiation”
It’s just a way of referring to the different molecules on the surface of cells
so that instead of having all kinds of different names for these molecules,
there is just one name (a number, actually) for each molecule.
It’s used for lots of different purposes,
one of the most common (in hospital practice, anyway) being to find out
what markers are on the surface of cells.
e.g. In a g leukemia case, the cells expressed CD 13 and CD 33, you’d
know the cells were myeloid, and that it was most likely an acute myeloid
leukemia.
sometimes it’s the absence of a marker that helps you with the diagnosis.
e.g. if you have a lymphoid neoplasm in which the cells are small and
mature looking, and by flow those cells are CD5 positive but CD23
negative, you’d be able to rule out chronic lymphocytic leukemia and lean
towards a diagnosis of mantle cell lymphoma.
Flow cytometry is super helpful with making a specific diagnosis.
9. CD Markers
CD1a, CD207: Langerhan cell histiocytosis cells
CD2, CD3, CD4, CD5, CD7, CD8: T cells
CD10: Early pre-B cells (immature B cells)
CD11c, CD25, CD103, CD123: Hairy cell leukemia cells
CD13, CD33, CD117: Myeloid cells
CD14, CD64: Monocytic cells (positive in AML-M4 and AML-M5)
CD15 :Reed-Sternberg cells, neutrophils
CD16, CD56: Natural killer cells
CD19, CD20, CD21, CD22 : B cells
CD23 and CD5 : Chronic lymphocytic leukemia/small lymphocytic
lymphoma
CD23 negative and CD5 positive: Mantle cell lymphoma cells
10. CD Markers
CD30 and CD15: Reed-Sternberg cells
CD30 positive and CD15 negative: Anaplastic large cell lymphoma
CD31: Endothelial cells (positive in angiosarcoma)
CD33: Myeloid cells and precursors
CD34: Stem cells (also positive in angiosarcoma)
CD41, CD61: Megakaryocytes and platelets (positive in AML-M7)
CD45 : All leukocytes (except Reed-Sternberg cells!)
CD45 RO: Memory T cells
CD45 RA: Naive T cells
CD68: Histiocytes (positive in malignant fibrous histiocytosis)
CD99: Ewings sarcoma cells
CD117: Gastrointestinal stromal tumor (GIST) cells, mast cells
(positive in mastocytosis), myeloid cells
11. Stages of Maturation/Differentiation
Lineages
Lymphoid Myeloid
• cells are defined by lineage and stage of maturation/differentiation
• regulated by signaling pathways and transcription factors
•cell “identity” may be determined using morphology, immunophenotyping and
molecular/genetic studies
14. B-Lineage Lymphopoiesis
Morphology / Immunophenotyping / Molecular Studies
Markers are helpful in determining:
1. Lineage (ex. CD19)
2. Maturation (ex. TdT, CD34, CD10)
3. Both (ex. sIg)
Status of immunglobulin genes (i.e., germline, rearranged,
somatic mutations) has implications for both
lineage and maturation.
15. B-cell lymphoproliferative disorders
Probable if immunoglobulin light chain restriction is demonstrated by surface typing of
kappa or lambda
B-cell CLL or mantle cell lymphomas (MCL) are suspected if CD5 is positive and
CD10 is negative
Circulating MCL can be mistaken morphologically for B-cell CLL or B-cell
prolymphocytic leukemia (B-PLL)
MCL considered in the following
CD20, CD19 – strong intensity
Surface immunoglobulin – strongly expressed
CD23 – absent
Diagnosis
Molecular and FISH testing
Requires t(11;14) translocation demonstration
CLL is more likely when
CD20 – weak intensity
Surface immunoglobulins – weakly expressed
CD23 – present
CD200 – present
16. B-cell lymphoproliferative disorders
Circulating germinal center cell-derived lymphoma is probable if CD10 is positive
and CD5 is negative
Germinal center lymphomas – follicular, Burkitt lymphoma, diffuse large B-cell
lymphoma (DLBCL)
Diagnosis
Some cases can be confirmed by demonstration of t(14;18) breakpoint by
PCR or FISH testing
PCR detects approximately 80% of t(14;18) translocations found in follicular
lymphoma
FISH is more sensitive for this translocation in fixed tissue
FISH can also detect an MYC or BCL6 rearrangement for BL or DLBCL
Marginal zone lymphoma should be considered if both CD5 and CD10 are negative
Hairy cell leukemia (HCL) has a characteristic phenotype that is CD5-, CD10-,
CD11c+, CD22+, CD25+, and CD103+
CD103 antigen (also known as B-ly7) is present in virtually all cases
CD11c and CD25 are less specific but present in almost all cases of hairy cell
leukemia
HCL variant can be considered in otherwise typical cases of HCL when CD25-
17. T-cell lymphoproliferative disorders
Most show abnormalities of pan T-cell antigens CD2, 3, 5, or CD7
T-cell disorders
Proliferating lymphocytes are usually positive for CD3
Most common form is large granular lymphocytosis
Usually show rearrangement of TCR locus
Clonality assessed by flow cytometry, PCR or next generation
sequencing (NGS)
Large granular lymphocytosis is suspected if percentage of CD16+,
CD56+, or CD57+ T cells is >50% or if absolute count of these cells
>2,000/μL
Angioimmunoblastic lymphoma has characteristic CD10+ and CD4+, and
CD52-, CD56-, and CD16-
Anaplastic large cell lymphoma – CD30+ and ALK(+)
Some pan T-cell antigens are frequently deleted
Sézary syndrome should be considered if CD4+, CD7-, and CD26-
19. Immunophenotyping in Hodgkin’s
Lymphoma
NLPHL is immunophenotypically distinct from other types of HL.
The lymphocytic and histiocytic (L&H) cells usually express
• LCA (CD45),
• immunoglobulin J chain,
• B-cell antigens (CD19, CD20, CD22, CD79A, and BCL-6),
• and epithelial membrane antigen (EMA) and are
negative for CD15 and CD30 (Fig. 7-1 C and D ).
These results suggest that the L&H cells are B cells that arise from the
germinal center.
The L&H cells are negative for T-cell antigens but are often surrounded
by a rosette of small, reactive T cells that may be positive for pan–T-cell
antigens and CD57.
Epstein-Barr virus (EBV) is almost always absent in the L&H cells of
NLPHL
20. Immunophenotypic Findings in
Classical Hodgkin's Lymphoma
positive for CD15 and CD30 and
negative for LCA (CD45) and EMA .
B-cell antigens—such as CD20, CD79A, PAX-5/BSAP, and
MUM1/IRF4—are expressed in a subset of cases.
CD20 expression is often weak.
T-cell antigens are usually not expressed by the neoplastic cells.
BCL-2 is positive in up to half the cases and has been correlated
with poorer prognosis.
EBV is common in the Reed-Sternberg and Hodgkin cells of
classic HL
21. Hodgkin's Lymphoma and Cell Lineage
both NLPHL and classical types of HL, the neoplastic cells arise from B-cell
precursors .
neoplastic cells of HL carry monoclonal immunoglobulin (Ig) gene
rearrangements.
In NLPHL, the Ig gene rearrangements are usually functional, and Ig mRNA
transcripts can be identified in most L&H cells. The Ig gene variable regions
also carry somatic mutations. As the process of somatic mutation is restricted
to the germinal center of secondary lymphoid follicles, the presence of somatic
mutations suggests that NLPHL arises from germinal center B cells.
In classical HL, over 95% of cases carry monoclonal Ig gene
rearrangements, with somatic mutations in the variable regions suggesting
germinal center B-cell origin. However, unlike the case in NLPHL, there are
defects in Ig transcription, and thus Ig mRNA transcripts are often absent. In
25% of cases, the mutations are extensive or involve stop codons, so-called
"crippling mutations.”
23. Follicular Lymphoma
FL is a neoplasm of mature B-cell lineage
Most grade 1 and 2 tumors express immunoglobulin, but a subset of FLs,
mostly grade 3, may be immunoglobulin-negative.
All FLs express pan–B-cell markers, and typically express immunoglobulin
and B-cell antigens at high density ("bright" immunofluorescence by flow
cytometry).
These neoplasms also express the germinal center-associated markers
CD10 and BCL-6 and are negative for T-cell antigens.
BCL-2 is expressed in 80 to 90% of FLs and is most often negative in
grade 3 neoplasms.
As BCL-2 is negative in reactive germinal centers, this marker is helpful in
differential diagnosis
24. Follicular Lymphoma
The cytogenetic hallmark of FL is the t(14;18)(q32;q21), which is
identified in 80 to 90% of neoplasms.
However, a small subset of FLs lack the t(14;18) including
• grade 3B nodal FL
• FLs arising in extranodal sites, such as skin,
• and FLs occurring in children.
Other cytogenetic abnormalities have been reported in FL. Of these,
trisomy 7 and 18, abnormalities of 3q27-28 and 6q23-26, and 17p
deletions are most frequent.
Abnormalities of 3q27-28 involve the bcl-6 gene and most often occur
in the form of translocations .
25. Diffuse large B-cell lymphoma
DLBCLs are of mature B-cell lineage. Approximately two-thirds of cases
express monotypic immunoglobulin (Ig);
approximately one-third of DLBCLs are Ig-negative.
These tumors express pan-B-cell antigens, 60 to 70%
express BCL-2, and a subset is positive for CD10 and BCL-6.
Most DLBCLs have a high proliferation rate.
Diffuse large B-cell lymphomas are heterogeneous at the molecular
level.
A subset of cases carries the t(14;18) involving the bcl-2 gene,
26. Diffuse large B-cell lymphoma
Another subset of DLBCLs has translocations or other
abnormalities involving the bcl-6 gene at chromosome 3q27.
The bcl-6 gene is rearranged in approximately 20 to 40% of
DLBCLs, more often in tumors arising in extranodal sites
Gene-expression profiling studies performed in recent years have
suggested that DLBCLs can be divided into three groups:
o germinal center cell type,
o activated B-cell type, and a third,
o noncharacteristic group.
Patients with the germinal center type of DLBCL have a better
prognosis independent of the IPI
27. Mantle cell lymphoma
Immunophenotypic studies have shown that MCLs express monotypic Ig light chain
(more often Ig λ), IgM, IgD, pan-B-cell antigens, BCL-2, alkaline phosphatase, and CD5
(23).
Unlike CLL/SLL, MCL is often positive for CD79B and FMC-7 and typically is negative
for CD10, CD23, and BCL-6. However, approximately 10% of MCLs can be CD23-
positive.
The t(11;14)(q13;q32) is present in virtually all cases of MCL (100). In this
translocation the ccnd-1 gene (also known as PRAD1 and bcl-1) on 11q13 is juxtaposed
with the Ig heavy chain gene on 14q32, resulting in overexpression of cyclin D1. Cyclin
D1 facilitates cell cycle transition from G1 to S phase (101).
Although the t(11;14) is central to the pathogenesis of MCL, the t(11;14) is not
sufficient to cause lymphomagenesis. Other molecular abnormalities are also required
like mutations in the atm, p16, and p53 genes.
28. Burkitt lymphoma
Burkitt's lymphomas of endemic, sporadic, and AIDS-associated
types are of mature B-cell lineage
They express Ig, pan-B-cell antigens, CD10, and BCL-6.
Burkitt's lymphomas have a very high proliferation rate, >99%,
using an antibody specific for Ki-67.
These tumors are negative for IgD, CD21, CD23, lymphocyte
homing receptors, and T-cell antigens. They are usually negative
for BCL-2.
29. Burkitt lymphoma
C-myc translocations are characteristic of Burkitt's lymphoma.
Approximately 80% of cases carry the t(8;14)(q24;q32),
the remaining cases having one of two variant translocations,
t(2;8)(p11;q24) or
t(8;22)(q24;q11).
Common to each of these translocations is involvement of
chromosome region 8q24, the site of the c-myc gene, which is
deregulated.
Via these translocations, c-myc is juxtaposed with the Ig heavy
chain on the derivative chromosome 14, or with the Ig κ and
Ig λ genes on the derivative chromosome 8.
30. stem
cell
lymphoid
precursor
progenitor-B
pre-B
immature
B-cell
mature
naive
B-cell
germinal
center
B-cell
memory
B-cell
MZL
CLL
plasma cell
DLBCL,
FL, BL, HL
LBL, ALL
CLL
MCL
MM
32. NHL: A heterogeneous group of diseases
deriving from
Mature B cells 85% and
T cells 15%.
Among B-NHL, most histologic subtypes arise
from germinal center (GC) or post-GC B cells,
33. In contrast with neoplasms of precursor
lymphoid cells, chromosomal translocations
associated with mature B and T-cell
malignancies do not generally lead to coding
fusions between two genes.
They juxtapose the proto-oncogene to
heterologous regulatory sequences derived
from the partner chromosome.
35. Two exceptions to the deregulation
model of NHL translocations:
t(2;5) of T-cell anaplastic large cell lymphoma
and
t(11;18) of MALT lymphoma,
These cause gene fusions coding for chimeric
proteins.
38. Molecular Testing in Lymphoma
1. Establishing a diagnosis of lymphoma
•What is the significance of clonality?
2. Classification of lymphoma
3. Discovery and future developments
•Refining prognostic and diagnostic categories
•Developing new therapeutic regimens
39. In the presence of antigen T- and B-lymphocytes
B
T
combine to produce:
B
B B
B
Plasma cells/specific antibody
An expanded
clone of
memory B-cells
40. A reactive lymphocyte proliferation is polyclonal;
Each expanded clone has different gene re-arrangement
41. A neoplastic lymphocyte proliferation is clonal
•Same gene rearrangement
•Same chromosomal abnormality
42. Polymerase Chain Reaction for IGH chain gene
(and TCR gene) re-arrangement can be used to
determine pattern of clonality within a lymphoid
infiltrate
•Implication:
clonality = malignancy
primers
Products:
Same size in monoclonal population
Different sizes in polyclonal population
43. Limitations and Pitfalls of Molecular Clonality Studies
1. Limited sensitivity
2. Clonality does not equate with malignancy
3. Ig & TCR re-arrangements are not markers of lineage
4. Pseudoclonality
5. Oligoclonality
6. False positive results
7. False negative results
44. Disruption of TS loci in NHL:
leads to biallelic inactivation, through deletion
of one allele and mutation the other.
The TS genes in NHL: p53, p16, and ATM.
45. IGH gene rearrangement
DEATH
No encounter with antigen
Naïve B-cell
Encounter with appropriate antigen
SURVIVAL
CD34+
Progenitor B cell
Pre-B cell
L gene rearrangement
Immature B cell:
IgM+/IgD-IGK+/-
Mature B cell:
IgM+/IgD+
Immunoglobulin gene rearrangements
46. ALL MCL, CLL Burkitts, FL, DLBCL WM MM
Stem cell Pre-B Early B Mature B Activated B Plasmacytoid B
Plasma
Germinal center
Type of B cell lymphoma is a function of:
1) Where the cell was in development/maturation when it went “bad”
2) What molecular derangement occurred
Origin of lymphoid neoplasms. Stages of B- and T-cell differentiation from which specific lymphoid and tumors emerge are shown. CD, cluster of differentiation; DR, human lymphocyte antigen-class II antigens; Ig, immunoglobulin; TCR, T-cell receptor; TdT, terminal deoxyribonucleotidyl transferase.
All NHL translocations that have been cloned to date have a proto-oncogene in the vicinity of 1 of 2 chromosomal recombination sites.
As shown on the left side of this slide, chromosomal translocations in mature B- and T-cell malignancies juxtapose the proto-oncogene to heterologous regulatory sequences derived from the partner chromosome, resulting in deregulated expression of the proto-oncogene.
The 2 exceptions to the deregulation model are translocation t(2;5) of T-cell anaplastic large-cell lymphoma (ALCL) and translocation t(11;18) of mucosa-associated lymphoid tissue (MALT) type lymphoma, both of which result in gene fusions coding for chimeric proteins, as shown on the right side of this slide.
Harris NL, Stein H, Coupland SE, et al. New approaches to lymphoma diagnosis. Hematology (Am Soc Hematol Educ Program). 2001:194-220.
Chromosomal translocations are commonly associated with activation or worse prognosis in B-cell malignancies. The table reviews some of the more common translocations associated with different B-cell malignancy histologies and the relationship of the translocation to the corresponding oncogene.
MCL frequently has chromosomal translocation t(11;14)(q13;q32). This juxtaposes the bcl1 locus with the IgG locus. Such an alteration results in deregulation of the bcl1 locus and expression of its gene product cyclin D1 which is not normally expressed in B cells. Activation of bcl1 appears to be critical in the pathogenesis of MCL. Cyclin D1 is important in cell cycle control, and bcl1 is considered a proto-oncogene.
A translocation of t(14;18) (q32;q21) is present in approximately 85% of cases FL and 15%-20% of DLBCL cases. This change results in rearrangement of the bcl2 gene, leading to activated forms of NHL.
Some translocations are very frequent and highly associated with a particular histology and prognosis; in DLBCL, which is an aggressive heterogeneous lymphoma, there are several different translocations observed, each with a different prognosis. Examples include: 30% of cases have t(14;18) with bcl2 overexpression, 35% have 3q27 rearrangements with bcl6 overexpression, and rare cases have t(8;14) with c-myc overexpression.
Individual stages of B-cell differentiation are identified by characteristic morphology and expression patterns of cell-surface antigens (CDs). CD19 is a marker of B-cell commitment, and its expression is first detected during the pre–B-cell stage.1
Changes in morphology and antigen expression during B-cell differentiation are reflected in the malignant counterparts of individual B cells. Detection of specific subsets of antigens has become an important method for identifying leukemia and lymphoma subtypes. For example, chronic lymphocytic leukemia (CLL) is a malignancy of intermediate B cells characterized by expression of CD19, CD20, CD23, and CD5 antigens.2 The malignant clone of follicular lymphoma (FL) is a more mature B cell, expressing CD19, CD20, and CD22, but not CD5.
Several CD20, CD22, and CD52 monoclonal antibodies (mAbs) are currently being investigated for the treatment of B-cell malignancies.
With the advent of mAb therapy, understanding of specific patternsof antigen expression will be critical for successful treatments.
The hashed lines on the bars depict lower or variable expression levels.
ALL = acute lymphoblastic leukemia; MCL = mantle cell lymphoma; PLL = prolymphocytic leukemia; DLBCL = diffuse large B-cell lymphoma; HCL = hairy cell leukemia; WM = Waldenström’s macroglobulinemia; MM = multiple myeloma.