Plasma cell dyscrasias are a spectrum of monoclonal gammopathies involving overproduction of myeloma proteins by plasma cells. Key points include:
- Plasma cells normally secrete antibodies but in plasma cell dyscrasias a clone overproduces a single antibody type.
- Risk factors include radiation exposure and genetic predispositions. Cytogenetic abnormalities involving immunoglobulin loci and cell cycle genes contribute to pathogenesis.
- Presentations include bone pain, fatigue, infections due to anemia or renal impairment. Investigations show monoclonal protein and clonal bone marrow plasma cells.
- Multiple myeloma, monoclonal gammopathy of unknown significance (MGUS), and smoldering
This document summarizes a study on acute myeloid leukemia (AML) in children. It discusses:
1. AML arises from mutations in hematopoietic precursors that confer proliferation/survival advantages and impair differentiation/apoptosis.
2. Treatment involves intensive chemotherapy induction followed by consolidation therapy, with improved outcomes over decades from 60% survival rates.
3. However, questions remain about optimal drug doses and timing, as well as the role of stem cell transplantation and risk-directed therapy.
1. The document discusses the management of various types of leukemia including acute lymphoblastic leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, and chronic myelogenous leukemia.
2. For acute lymphoblastic leukemia, treatment involves induction chemotherapy followed by consolidation therapy and maintenance treatments, sometimes including bone marrow transplantation.
3. Chronic lymphocytic leukemia treatment focuses on suppressing the disease for many years using chemotherapy with drugs like chlorambucil or cyclophosphamide along with corticosteroids.
4. Acute myelogenous leukemia treatment relies on combination chemotherapy during induction followed by additional chemotherapy phases.
5. Chronic myelogenous leukemia's standard treatment is imatinib therapy, and bone marrow transplantation
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults. It has an average incidence of 2.7 per 100,000 people in the US and is more common in older men. CLL accounts for about 0.8% of all cancers and 30% of leukemias. The neoplastic cells are typically B-cell lymphocytes. Farming exposure and hepatitis C may play a role in etiology. CLL has various genetic abnormalities that affect prognosis. Clinical features include lymphadenopathy, fatigue, infections. Diagnosis requires a sustained lymphocytosis above 5000/uL. Treatment is indicated for symptomatic disease, doubling time under 6 months, or disease complications. Prognostic factors
Multiple myeloma is a cancer of plasma cells that accumulate in the bone marrow. It accounts for 1.8% of cancers and commonly affects people aged 65-74. The cancerous plasma cells produce abnormal antibodies that can cause tumors, kidney damage, bone destruction, and weakened immunity. A diagnosis is suspected with elevated antibodies in blood and urine, and confirmed via bone marrow biopsy showing at least 10% plasma cells. While incurable, treatment advances have significantly prolonged survival, including chemotherapy, steroids, monoclonal antibodies, stem cell transplants, and newer drugs targeting myeloma cells. Complications can include fractures, kidney problems, infections, and amyloidosis.
https://www.medicalnewstoday.com/articles/323444.php
https://ascopubs.org/doi/full/10.1200/JCO.2008.16.0333
https://journals.lww.com/co-hematology/Abstract/2007/03000/Influence_of_new_molecular_prognostic_markers_in.5.aspx
Influence of new molecular prognostic markers in patients with karyotypically normal acute myeloid leukemia: recent advances
Mrózek, Krzysztofa; Döhner, Hartmutb; Bloomfield, Clara Da
Current Opinion in Hematology: March 2007 - Volume 14 - Issue 2 - p 106–114
doi: 10.1097/MOH.0b013e32801684c7
Myeloid disease
Purpose of review Molecular study of cytogenetically normal acute myeloid leukemia is among the most active areas of leukemia research. Despite having the same normal karyotype, adults with de-novo cytogenetically normal acute myeloid leukemia who constitute the largest cytogenetic group of acute myeloid leukemia, are very diverse with respect to acquired gene mutations and gene expression changes. These genetic alterations affect clinical outcome and may assist in selection of proper treatment. Herein we critically summarize recent clinically relevant molecular genetic studies of cytogenetically normal acute myeloid leukemia.
Recent findings NPM1 gene mutations causing aberrant cytoplasmic localization of nucleophosmin have been demonstrated to be the most frequent submicroscopic alterations in cytogenetically normal acute myeloid leukemia and to confer improved prognosis, especially in patients without a concomitant FLT3 gene internal tandem duplication. Overexpressed BAALC, ERG and MN1 genes and expression of breast cancer resistance protein have been shown to confer poor prognosis. A gene-expression signature previously suggested to separate cytogenetically normal acute myeloid leukemia patients into prognostic subgroups has been validated on a different microarray platform, although gene-expression signature-based classifiers predicting outcome for individual patients with greater accuracy are still needed.
Summary The discovery of new prognostic markers has increased our understanding of leukemogenesis and may lead to improved prognostication and generation of novel risk-adapted therapies.
http://www.bloodjournal.org/content/127/1/53?sso-checked=true
An update of current treatments for adult acute myeloid leukemia
Hervé Dombret and Claude Gardin
Abstract
Recent advances in acute myeloid leukemia (AML) biology and its genetic landscape should ultimately lead to more subset-specific AML therapies, ideally tailored to each patient's disease. Although a growing number of distinct AML subsets have been increasingly characterized, patient management has remained disappointingly uniform. If one excludes acute promyelocytic leukemia, current AML management still relies largely on intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), at least in younger patients who can tolerate such intensive treatments. Nevertheless, progress has been made, notably in terms of standard drug dose in ...
The document summarizes Hanahan and Weinberg's hallmarks of cancer. It describes the six original hallmarks proposed in 2000 of self-sufficiency in growth signals, insensitivity to growth-inhibitory signals, evading apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis. In 2011, they added two emerging hallmarks of deregulating cellular energetics and avoiding immune detection, as well as two enabling characteristics of genome instability and tumor-promoting inflammation.
Leukemia is a cancer of the blood or bone marrow characterized by an abnormal proliferation of white blood cells. It is classified based on the speed of progression and the affected cell line. The main types are acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia. Symptoms vary depending on the subtype but can include fatigue, fever, bleeding, anemia, and infections. Diagnosis involves blood and bone marrow tests. Treatment involves chemotherapy, immunotherapy, stem cell transplants, and newer targeted therapies depending on the subtype and risk level. Nursing care focuses on managing side effects like nausea, infections, and myelosuppression.
This document discusses monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), which are precursor states of multiple myeloma. It provides definitions and risk factors for progression from MGUS to myeloma. Genetic and molecular insights into disease progression are explored, including primary and secondary genetic events. Management strategies for MGUS and SMM are reviewed, including risk stratification and criteria for high-risk SMM. Ongoing research into clonal evolution and the tumor microenvironment shed light on myelomagenesis. The first randomized trial to show a benefit of early treatment in high-risk SMM is summarized.
This document summarizes a study on acute myeloid leukemia (AML) in children. It discusses:
1. AML arises from mutations in hematopoietic precursors that confer proliferation/survival advantages and impair differentiation/apoptosis.
2. Treatment involves intensive chemotherapy induction followed by consolidation therapy, with improved outcomes over decades from 60% survival rates.
3. However, questions remain about optimal drug doses and timing, as well as the role of stem cell transplantation and risk-directed therapy.
1. The document discusses the management of various types of leukemia including acute lymphoblastic leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, and chronic myelogenous leukemia.
2. For acute lymphoblastic leukemia, treatment involves induction chemotherapy followed by consolidation therapy and maintenance treatments, sometimes including bone marrow transplantation.
3. Chronic lymphocytic leukemia treatment focuses on suppressing the disease for many years using chemotherapy with drugs like chlorambucil or cyclophosphamide along with corticosteroids.
4. Acute myelogenous leukemia treatment relies on combination chemotherapy during induction followed by additional chemotherapy phases.
5. Chronic myelogenous leukemia's standard treatment is imatinib therapy, and bone marrow transplantation
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults. It has an average incidence of 2.7 per 100,000 people in the US and is more common in older men. CLL accounts for about 0.8% of all cancers and 30% of leukemias. The neoplastic cells are typically B-cell lymphocytes. Farming exposure and hepatitis C may play a role in etiology. CLL has various genetic abnormalities that affect prognosis. Clinical features include lymphadenopathy, fatigue, infections. Diagnosis requires a sustained lymphocytosis above 5000/uL. Treatment is indicated for symptomatic disease, doubling time under 6 months, or disease complications. Prognostic factors
Multiple myeloma is a cancer of plasma cells that accumulate in the bone marrow. It accounts for 1.8% of cancers and commonly affects people aged 65-74. The cancerous plasma cells produce abnormal antibodies that can cause tumors, kidney damage, bone destruction, and weakened immunity. A diagnosis is suspected with elevated antibodies in blood and urine, and confirmed via bone marrow biopsy showing at least 10% plasma cells. While incurable, treatment advances have significantly prolonged survival, including chemotherapy, steroids, monoclonal antibodies, stem cell transplants, and newer drugs targeting myeloma cells. Complications can include fractures, kidney problems, infections, and amyloidosis.
https://www.medicalnewstoday.com/articles/323444.php
https://ascopubs.org/doi/full/10.1200/JCO.2008.16.0333
https://journals.lww.com/co-hematology/Abstract/2007/03000/Influence_of_new_molecular_prognostic_markers_in.5.aspx
Influence of new molecular prognostic markers in patients with karyotypically normal acute myeloid leukemia: recent advances
Mrózek, Krzysztofa; Döhner, Hartmutb; Bloomfield, Clara Da
Current Opinion in Hematology: March 2007 - Volume 14 - Issue 2 - p 106–114
doi: 10.1097/MOH.0b013e32801684c7
Myeloid disease
Purpose of review Molecular study of cytogenetically normal acute myeloid leukemia is among the most active areas of leukemia research. Despite having the same normal karyotype, adults with de-novo cytogenetically normal acute myeloid leukemia who constitute the largest cytogenetic group of acute myeloid leukemia, are very diverse with respect to acquired gene mutations and gene expression changes. These genetic alterations affect clinical outcome and may assist in selection of proper treatment. Herein we critically summarize recent clinically relevant molecular genetic studies of cytogenetically normal acute myeloid leukemia.
Recent findings NPM1 gene mutations causing aberrant cytoplasmic localization of nucleophosmin have been demonstrated to be the most frequent submicroscopic alterations in cytogenetically normal acute myeloid leukemia and to confer improved prognosis, especially in patients without a concomitant FLT3 gene internal tandem duplication. Overexpressed BAALC, ERG and MN1 genes and expression of breast cancer resistance protein have been shown to confer poor prognosis. A gene-expression signature previously suggested to separate cytogenetically normal acute myeloid leukemia patients into prognostic subgroups has been validated on a different microarray platform, although gene-expression signature-based classifiers predicting outcome for individual patients with greater accuracy are still needed.
Summary The discovery of new prognostic markers has increased our understanding of leukemogenesis and may lead to improved prognostication and generation of novel risk-adapted therapies.
http://www.bloodjournal.org/content/127/1/53?sso-checked=true
An update of current treatments for adult acute myeloid leukemia
Hervé Dombret and Claude Gardin
Abstract
Recent advances in acute myeloid leukemia (AML) biology and its genetic landscape should ultimately lead to more subset-specific AML therapies, ideally tailored to each patient's disease. Although a growing number of distinct AML subsets have been increasingly characterized, patient management has remained disappointingly uniform. If one excludes acute promyelocytic leukemia, current AML management still relies largely on intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), at least in younger patients who can tolerate such intensive treatments. Nevertheless, progress has been made, notably in terms of standard drug dose in ...
The document summarizes Hanahan and Weinberg's hallmarks of cancer. It describes the six original hallmarks proposed in 2000 of self-sufficiency in growth signals, insensitivity to growth-inhibitory signals, evading apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis. In 2011, they added two emerging hallmarks of deregulating cellular energetics and avoiding immune detection, as well as two enabling characteristics of genome instability and tumor-promoting inflammation.
Leukemia is a cancer of the blood or bone marrow characterized by an abnormal proliferation of white blood cells. It is classified based on the speed of progression and the affected cell line. The main types are acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia. Symptoms vary depending on the subtype but can include fatigue, fever, bleeding, anemia, and infections. Diagnosis involves blood and bone marrow tests. Treatment involves chemotherapy, immunotherapy, stem cell transplants, and newer targeted therapies depending on the subtype and risk level. Nursing care focuses on managing side effects like nausea, infections, and myelosuppression.
This document discusses monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), which are precursor states of multiple myeloma. It provides definitions and risk factors for progression from MGUS to myeloma. Genetic and molecular insights into disease progression are explored, including primary and secondary genetic events. Management strategies for MGUS and SMM are reviewed, including risk stratification and criteria for high-risk SMM. Ongoing research into clonal evolution and the tumor microenvironment shed light on myelomagenesis. The first randomized trial to show a benefit of early treatment in high-risk SMM is summarized.
Secondary Extramedullary Plasmacytoma Diagnosed by Fine Needle Aspiration Cyt...Apollo Hospitals
This case report describes a 33-year old female patient who presented with multiple subcutaneous lumps. Fine needle aspiration cytology of the lumps revealed sheets of plasmacytoid cells, indicating a diagnosis of secondary extramedullary plasmacytoma. Further investigations including immunoglobulin profile, serum protein electrophoresis and bone marrow biopsy confirmed the presence of multiple myeloma. While extramedullary plasmacytomas usually represent systemic multiple myeloma, cytological diagnosis allows for timely treatment.
This document provides an overview of multiple myeloma, including its definition, clinical presentation, workup, staging, management, and treatment regimens. Key points include:
- Multiple myeloma is a malignant neoplasm of plasma cells that accumulate in the bone marrow, leading to bone destruction.
- Workup involves blood and urine tests, bone marrow biopsy, skeletal survey, and imaging to determine disease severity and stage according to the Durie-Salmon or ISS staging systems.
- Treatment may include chemotherapy, steroids, immunomodulators, stem cell transplantation, and supportive care. The goal of initial therapy is to achieve remission prior to stem cell transplantation in eligible patients.
multiple myloma
By: Nader Amir Al-assadi
Supervised by : Dr/ Ghazi Alariqe
taiz university
Multiple myeloma (MM) is a plasma cell malignancy in which monoclonal plasma cells proliferate in bone marrow, resulting in an over abundance of monoclonal para protein (M protein), destruction of bone, and displacement of other hematopoietic cell lines.
The precise etiology of MM has not yet been established.
Roles have been suggested for a variety of factors, including genetic causes, environmental or occupational causes,radiation, chronic inflammation, and infection .
- Acute myeloid leukemia (AML) is a heterogeneous clonal hematopoietic stem cell malignancy characterized by proliferation and accumulation of immature hematopoietic cells in bone marrow, peripheral blood, and other tissues, resulting in bone marrow failure.
- Prognosis is determined by several factors including age, cytogenetics, and molecular genetics. Patients with t(15;17), t(8;21), and inv(16) have favorable prognoses while those with complex karyotypes or monosomal karyotypes have poor prognoses. Mutations in genes like NPM1, FLT3, and CEBPA provide prognostic information.
- Treatment involves induction chemotherapy with anthracy
This document summarizes research on the effect of bacteria on healthy and cancerous cells. It finds that while most bacteria do not cause disease, some types of bacteria can increase the risk of cancer, such as Helicobacter pylori which increases the risk of stomach cancer. The document also discusses how some bacterial infections can transform into malignant tumors through genetic mutations. It provides background on cancer development and the role of genetic and epigenetic factors in normal cells transforming into cancerous cells.
Cancer is the name given to a collection of related diseases. In all types of cancer, some of the body's cells begin to divide without stopping and spread into surrounding tissue.
Cytogenetic and Molecular Characterization of Hematological Neoplasm in an Ec...Andresz26
This study characterized the cytogenetic and molecular features of hematological malignancies in an Ecuadorian population. The researchers analyzed over 4,000 patients between 1984-2012, detecting chromosome abnormalities in around 46% via conventional cytogenetics. Specific genetic fusions were also identified, including BCR-ABL (present in 95% of CML patients as the b2/a2 transcript), PML-RARA (showing the bcr2 and bcr3 transcripts but not bcr1), CBFB-MYH11 (all cases exhibited the F transcript), and MLL-AF4 (all cases displayed the e7-e8 transcript). The frequencies of some fusion gene subtypes differed from
Tuberculosis is a lung disease caused by the bacterium Mycobacterium tuberculosis. It remains a major global health problem. In 2020, there were an estimated 10 million new TB cases and 1.5 million TB deaths worldwide, making it one of the top 10 causes of death globally. The disease disproportionately affects low and middle income countries. Key risk factors include poverty, HIV infection and indoor air pollution. Early diagnosis and complete treatment are important for controlling the spread of the disease.
This document provides an overview of mantle cell lymphoma (MCL), including its pathogenesis, clinical features, diagnosis, prognosis, and treatment approaches. MCL is an aggressive subtype of non-Hodgkin lymphoma characterized by cyclin D1 overexpression. Diagnosis involves immunophenotyping showing expression of B-cell markers along with CD5 and CD43. The Mantle Cell Lymphoma International Prognostic Index (MIPI) helps predict outcomes. First-line treatment typically involves chemotherapy with consolidation and maintenance therapies. Relapsed disease is often treated with Bruton tyrosine kinase inhibitors or chimeric antigen receptor T-cell therapies.
Burkitt lymphoma is an aggressive B-cell lymphoma associated with translocations involving the c-MYC gene. There are three main types: endemic, sporadic, and HIV-associated. Endemic Burkitt lymphoma most commonly presents as an abdominal mass in children in Africa and is strongly associated with Epstein-Barr virus. The tumor cells are intermediate in size with vacuolated cytoplasm, giving the characteristic "starry sky" appearance. Burkitt lymphoma is highly aggressive but responsive to chemotherapy.
Burkitt lymphoma is an aggressive B-cell lymphoma associated with translocations involving the c-MYC gene. There are three main types: endemic, sporadic, and HIV-associated. Endemic Burkitt lymphoma most commonly presents as an abdominal mass in children in Africa and is strongly associated with Epstein-Barr virus. The tumor cells are intermediate in size with vacuolated cytoplasm, giving the characteristic "starry sky" appearance. Burkitt lymphoma is highly aggressive but responsive to chemotherapy.
My son had Wiskott Aldrich Syndrome (WAS). He had a bone marrow transplant in August 2006. His WAS is healed. This presentation was designed by some grad students. Some of the content is from my blog and it pictures my son, David. http://www.davidmcnally.blogspot.com
Basic concept of Cancer and cancer cell.Madhur sharma
Cancer is a genetic disease caused by alterations in genes that can result from mutations during cell division, exposure to external agents, or randomly. There are four main types of cancer - carcinomas, sarcomas, lymphomas, and leukemias. Cancer is characterized by cellular changes that promote uncontrolled growth. Some key cancer genes include oncogenes that promote growth and tumor suppressor genes that normally inhibit growth. Examples are discussed like MYC, RAS, P53, and RB. New strategies to treat cancer focus on immunotherapy, inhibiting cancer-promoting proteins, and blocking angiogenesis within tumors.
This document discusses lymphoma and its classification. It notes that lymphoma arises from lymphoid tissue and is the most common hematologic malignancy in developed countries. There are two main types, Hodgkin's and non-Hodgkin's lymphoma, with non-Hodgkin's lymphoma accounting for about 85% of cases. The two most common forms of non-Hodgkin's lymphoma are follicular lymphoma and diffuse large B-cell lymphoma. Classification of lymphoma has evolved based on immunophenotypic and genetic features. Many lymphomas express the antigen CD20, which has made it a target for developing monoclonal antibody therapies.
This document provides an introduction to lymphoma and radioimmunotherapy. It discusses that lymphoma originates from lymphoid tissue and is the most common hematologic malignancy. It describes the classification of lymphomas and focuses on two common types - follicular lymphoma and diffuse large B-cell lymphoma. It then introduces radioimmunotherapy as a targeted treatment approach using radiolabeled monoclonal antibodies, with a focus on the anti-CD20 antibody rituximab which is commonly used to treat CD20-positive lymphomas.
1) The document discusses cancer and the immune system, covering topics like tumor antigens, immune responses to tumors, and tumor escape mechanisms.
2) It provides an overview of tumor immunology, including how tumors evade the immune system through mechanisms like down-regulating class I MHC expression and antigen modulation.
3) The document also summarizes different immunotherapy approaches, such as treatments using cytokines, monoclonal antibodies, and vaccination strategies using isolated tumor peptides or transfected tumor cells.
Proteomics Exploration of Chronic Lymphocytic Leukemia_Crimson PublishersCrimsonpublishersCancer
Chronic Lymphocytic Leukemia (CLL) is an adult heme malignancy characterized by the presence of mature-appearing CD5+ B cells in the blood, bone marrow, and secondary lymphoid organs [1]. In the United States, there will be an estimate of 20,720 new cases and 3,930 deaths according to the American Cancer Society statistics. Symptoms include swollen lymph nodes, frequent infections, and fatigue which negatively impacts the quality of life of people affected [1]. CLL is heterogeneous in its progression and clinical outcomes. Factors that contribute to the heterogeneity include the immunoglobulin heavy chain (IGHV) status and chromosomal aberrations [2,3]. There are two subtypes of CLL: Unmutated(U-CLL) and Mutated CLL(M-CLL). 40% and 60% of patients are diagnosed with unmutated and mutated CLL. U-CLL is characterized by the presence of CLL cells that have less than two percent of their IGHV mutated, whereas M-CLL cells have more than two percent mutated [4]. U-CLL is the more aggressive phenotype [2]. These cells have increased responsiveness to antigens that bind the B cell receptor (BCR) versus M-CLL cells [5]. M-CLL is the more indolent phenotype. Increased BCR signaling results in increased cell survival and proliferation [5].
This document discusses tumor cell proliferation and immunotherapy for cancers. It provides details on the cell cycle phases (M, G1, S, G2, G0) and how they relate to tumor growth and response to treatment. It also discusses cell kinetics, the growth fraction, and cancer stem cells. Targeted therapies discussed include those that inhibit angiogenesis by targeting VEGF, as well as EGFR inhibitors. Bevacizumab is highlighted as an anti-angiogenic therapy shown to improve outcomes for ovarian cancer both as a single agent and in combination with other drugs.
The study analyzed gene expression profiles of MPN leukemia stem cells (LSCs) compared to normal hematopoietic stem cells (HSCs) to identify genes and pathways involved in MPN development. When comparing MPN LSCs to HSCs, differentially expressed genes were identified, including MAMDC2, ABCA13, IFIT2, and IL1RAP, which are involved in interferon response and cytokine signaling pathways. Analysis indicated that cytokine signaling and immune response pathways may be dysregulated in MPN LSCs. This suggests that anti-inflammatory or immunomodulatory drugs could be effective MPN treatments.
Cancer is uncontrolled cell growth that can lead to tumor formation and be either benign or malignant. It will affect 1 in 3 people during their lifetime. Increased life expectancy and modern lifestyles contribute to higher cancer rates, which are expected to increase by 50% to 15 million new cases annually by 2020 according to a global report. Prevention through healthy lifestyle choices and public health action could reduce cancer incidence by a third worldwide.
1) The document discusses the cell cycle, which includes interphase and the M phase. Interphase consists of G1, S, and G2 phases where the cell grows and replicates its DNA in preparation for division.
2) The M phase is when the cell divides, known as mitosis, which has four stages - prophase, metaphase, anaphase, and telophase. During these stages the chromosomes condense and align, separate, and decondense respectively.
3) Cell division, along with DNA replication and growth, must be coordinated through the cell cycle to ensure daughter cells receive intact genomes. The cycle allows a single cell to multiply into millions through repeated growth and division.
The document discusses principles and methods of immobilization in radiotherapy. It describes the role of immobilization in reducing geometric uncertainties and lists the ideal properties of an immobilization device. The history of immobilization devices is explored, from early uses of plastic cups and masking tapes to today's body conformal devices and stereotactic equipment. Various head and neck immobilization tools are presented, including thermoplastic molds, base plates, and accessories like mouth bites. Body conformal devices like alpha cradles and vacuum-lock bags are explained. Immobilization methods for specific treatment sites like breast, prostate, and intracranial regions are outlined.
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Secondary Extramedullary Plasmacytoma Diagnosed by Fine Needle Aspiration Cyt...Apollo Hospitals
This case report describes a 33-year old female patient who presented with multiple subcutaneous lumps. Fine needle aspiration cytology of the lumps revealed sheets of plasmacytoid cells, indicating a diagnosis of secondary extramedullary plasmacytoma. Further investigations including immunoglobulin profile, serum protein electrophoresis and bone marrow biopsy confirmed the presence of multiple myeloma. While extramedullary plasmacytomas usually represent systemic multiple myeloma, cytological diagnosis allows for timely treatment.
This document provides an overview of multiple myeloma, including its definition, clinical presentation, workup, staging, management, and treatment regimens. Key points include:
- Multiple myeloma is a malignant neoplasm of plasma cells that accumulate in the bone marrow, leading to bone destruction.
- Workup involves blood and urine tests, bone marrow biopsy, skeletal survey, and imaging to determine disease severity and stage according to the Durie-Salmon or ISS staging systems.
- Treatment may include chemotherapy, steroids, immunomodulators, stem cell transplantation, and supportive care. The goal of initial therapy is to achieve remission prior to stem cell transplantation in eligible patients.
multiple myloma
By: Nader Amir Al-assadi
Supervised by : Dr/ Ghazi Alariqe
taiz university
Multiple myeloma (MM) is a plasma cell malignancy in which monoclonal plasma cells proliferate in bone marrow, resulting in an over abundance of monoclonal para protein (M protein), destruction of bone, and displacement of other hematopoietic cell lines.
The precise etiology of MM has not yet been established.
Roles have been suggested for a variety of factors, including genetic causes, environmental or occupational causes,radiation, chronic inflammation, and infection .
- Acute myeloid leukemia (AML) is a heterogeneous clonal hematopoietic stem cell malignancy characterized by proliferation and accumulation of immature hematopoietic cells in bone marrow, peripheral blood, and other tissues, resulting in bone marrow failure.
- Prognosis is determined by several factors including age, cytogenetics, and molecular genetics. Patients with t(15;17), t(8;21), and inv(16) have favorable prognoses while those with complex karyotypes or monosomal karyotypes have poor prognoses. Mutations in genes like NPM1, FLT3, and CEBPA provide prognostic information.
- Treatment involves induction chemotherapy with anthracy
This document summarizes research on the effect of bacteria on healthy and cancerous cells. It finds that while most bacteria do not cause disease, some types of bacteria can increase the risk of cancer, such as Helicobacter pylori which increases the risk of stomach cancer. The document also discusses how some bacterial infections can transform into malignant tumors through genetic mutations. It provides background on cancer development and the role of genetic and epigenetic factors in normal cells transforming into cancerous cells.
Cancer is the name given to a collection of related diseases. In all types of cancer, some of the body's cells begin to divide without stopping and spread into surrounding tissue.
Cytogenetic and Molecular Characterization of Hematological Neoplasm in an Ec...Andresz26
This study characterized the cytogenetic and molecular features of hematological malignancies in an Ecuadorian population. The researchers analyzed over 4,000 patients between 1984-2012, detecting chromosome abnormalities in around 46% via conventional cytogenetics. Specific genetic fusions were also identified, including BCR-ABL (present in 95% of CML patients as the b2/a2 transcript), PML-RARA (showing the bcr2 and bcr3 transcripts but not bcr1), CBFB-MYH11 (all cases exhibited the F transcript), and MLL-AF4 (all cases displayed the e7-e8 transcript). The frequencies of some fusion gene subtypes differed from
Tuberculosis is a lung disease caused by the bacterium Mycobacterium tuberculosis. It remains a major global health problem. In 2020, there were an estimated 10 million new TB cases and 1.5 million TB deaths worldwide, making it one of the top 10 causes of death globally. The disease disproportionately affects low and middle income countries. Key risk factors include poverty, HIV infection and indoor air pollution. Early diagnosis and complete treatment are important for controlling the spread of the disease.
This document provides an overview of mantle cell lymphoma (MCL), including its pathogenesis, clinical features, diagnosis, prognosis, and treatment approaches. MCL is an aggressive subtype of non-Hodgkin lymphoma characterized by cyclin D1 overexpression. Diagnosis involves immunophenotyping showing expression of B-cell markers along with CD5 and CD43. The Mantle Cell Lymphoma International Prognostic Index (MIPI) helps predict outcomes. First-line treatment typically involves chemotherapy with consolidation and maintenance therapies. Relapsed disease is often treated with Bruton tyrosine kinase inhibitors or chimeric antigen receptor T-cell therapies.
Burkitt lymphoma is an aggressive B-cell lymphoma associated with translocations involving the c-MYC gene. There are three main types: endemic, sporadic, and HIV-associated. Endemic Burkitt lymphoma most commonly presents as an abdominal mass in children in Africa and is strongly associated with Epstein-Barr virus. The tumor cells are intermediate in size with vacuolated cytoplasm, giving the characteristic "starry sky" appearance. Burkitt lymphoma is highly aggressive but responsive to chemotherapy.
Burkitt lymphoma is an aggressive B-cell lymphoma associated with translocations involving the c-MYC gene. There are three main types: endemic, sporadic, and HIV-associated. Endemic Burkitt lymphoma most commonly presents as an abdominal mass in children in Africa and is strongly associated with Epstein-Barr virus. The tumor cells are intermediate in size with vacuolated cytoplasm, giving the characteristic "starry sky" appearance. Burkitt lymphoma is highly aggressive but responsive to chemotherapy.
My son had Wiskott Aldrich Syndrome (WAS). He had a bone marrow transplant in August 2006. His WAS is healed. This presentation was designed by some grad students. Some of the content is from my blog and it pictures my son, David. http://www.davidmcnally.blogspot.com
Basic concept of Cancer and cancer cell.Madhur sharma
Cancer is a genetic disease caused by alterations in genes that can result from mutations during cell division, exposure to external agents, or randomly. There are four main types of cancer - carcinomas, sarcomas, lymphomas, and leukemias. Cancer is characterized by cellular changes that promote uncontrolled growth. Some key cancer genes include oncogenes that promote growth and tumor suppressor genes that normally inhibit growth. Examples are discussed like MYC, RAS, P53, and RB. New strategies to treat cancer focus on immunotherapy, inhibiting cancer-promoting proteins, and blocking angiogenesis within tumors.
This document discusses lymphoma and its classification. It notes that lymphoma arises from lymphoid tissue and is the most common hematologic malignancy in developed countries. There are two main types, Hodgkin's and non-Hodgkin's lymphoma, with non-Hodgkin's lymphoma accounting for about 85% of cases. The two most common forms of non-Hodgkin's lymphoma are follicular lymphoma and diffuse large B-cell lymphoma. Classification of lymphoma has evolved based on immunophenotypic and genetic features. Many lymphomas express the antigen CD20, which has made it a target for developing monoclonal antibody therapies.
This document provides an introduction to lymphoma and radioimmunotherapy. It discusses that lymphoma originates from lymphoid tissue and is the most common hematologic malignancy. It describes the classification of lymphomas and focuses on two common types - follicular lymphoma and diffuse large B-cell lymphoma. It then introduces radioimmunotherapy as a targeted treatment approach using radiolabeled monoclonal antibodies, with a focus on the anti-CD20 antibody rituximab which is commonly used to treat CD20-positive lymphomas.
1) The document discusses cancer and the immune system, covering topics like tumor antigens, immune responses to tumors, and tumor escape mechanisms.
2) It provides an overview of tumor immunology, including how tumors evade the immune system through mechanisms like down-regulating class I MHC expression and antigen modulation.
3) The document also summarizes different immunotherapy approaches, such as treatments using cytokines, monoclonal antibodies, and vaccination strategies using isolated tumor peptides or transfected tumor cells.
Proteomics Exploration of Chronic Lymphocytic Leukemia_Crimson PublishersCrimsonpublishersCancer
Chronic Lymphocytic Leukemia (CLL) is an adult heme malignancy characterized by the presence of mature-appearing CD5+ B cells in the blood, bone marrow, and secondary lymphoid organs [1]. In the United States, there will be an estimate of 20,720 new cases and 3,930 deaths according to the American Cancer Society statistics. Symptoms include swollen lymph nodes, frequent infections, and fatigue which negatively impacts the quality of life of people affected [1]. CLL is heterogeneous in its progression and clinical outcomes. Factors that contribute to the heterogeneity include the immunoglobulin heavy chain (IGHV) status and chromosomal aberrations [2,3]. There are two subtypes of CLL: Unmutated(U-CLL) and Mutated CLL(M-CLL). 40% and 60% of patients are diagnosed with unmutated and mutated CLL. U-CLL is characterized by the presence of CLL cells that have less than two percent of their IGHV mutated, whereas M-CLL cells have more than two percent mutated [4]. U-CLL is the more aggressive phenotype [2]. These cells have increased responsiveness to antigens that bind the B cell receptor (BCR) versus M-CLL cells [5]. M-CLL is the more indolent phenotype. Increased BCR signaling results in increased cell survival and proliferation [5].
This document discusses tumor cell proliferation and immunotherapy for cancers. It provides details on the cell cycle phases (M, G1, S, G2, G0) and how they relate to tumor growth and response to treatment. It also discusses cell kinetics, the growth fraction, and cancer stem cells. Targeted therapies discussed include those that inhibit angiogenesis by targeting VEGF, as well as EGFR inhibitors. Bevacizumab is highlighted as an anti-angiogenic therapy shown to improve outcomes for ovarian cancer both as a single agent and in combination with other drugs.
The study analyzed gene expression profiles of MPN leukemia stem cells (LSCs) compared to normal hematopoietic stem cells (HSCs) to identify genes and pathways involved in MPN development. When comparing MPN LSCs to HSCs, differentially expressed genes were identified, including MAMDC2, ABCA13, IFIT2, and IL1RAP, which are involved in interferon response and cytokine signaling pathways. Analysis indicated that cytokine signaling and immune response pathways may be dysregulated in MPN LSCs. This suggests that anti-inflammatory or immunomodulatory drugs could be effective MPN treatments.
Cancer is uncontrolled cell growth that can lead to tumor formation and be either benign or malignant. It will affect 1 in 3 people during their lifetime. Increased life expectancy and modern lifestyles contribute to higher cancer rates, which are expected to increase by 50% to 15 million new cases annually by 2020 according to a global report. Prevention through healthy lifestyle choices and public health action could reduce cancer incidence by a third worldwide.
Similar to Epidemiology, Etiopathogenesis, Pathology, Staging of Plasma Cell Dyscrasias.pptx (20)
1) The document discusses the cell cycle, which includes interphase and the M phase. Interphase consists of G1, S, and G2 phases where the cell grows and replicates its DNA in preparation for division.
2) The M phase is when the cell divides, known as mitosis, which has four stages - prophase, metaphase, anaphase, and telophase. During these stages the chromosomes condense and align, separate, and decondense respectively.
3) Cell division, along with DNA replication and growth, must be coordinated through the cell cycle to ensure daughter cells receive intact genomes. The cycle allows a single cell to multiply into millions through repeated growth and division.
The document discusses principles and methods of immobilization in radiotherapy. It describes the role of immobilization in reducing geometric uncertainties and lists the ideal properties of an immobilization device. The history of immobilization devices is explored, from early uses of plastic cups and masking tapes to today's body conformal devices and stereotactic equipment. Various head and neck immobilization tools are presented, including thermoplastic molds, base plates, and accessories like mouth bites. Body conformal devices like alpha cradles and vacuum-lock bags are explained. Immobilization methods for specific treatment sites like breast, prostate, and intracranial regions are outlined.
This document discusses cytotoxic drugs and the origins of chemotherapy. It provides information on various classes of cytotoxic drugs including alkylating agents, antimetabolites, plant alkaloids, and mitotic inhibitors. Key events in the development of chemotherapy are noted, such as the observation that nitrogen mustards caused bone marrow destruction in WWII, which led to their application against Hodgkin's disease. The mechanisms of cytotoxic drugs and their effects on the cell cycle are also summarized.
This document discusses brachytherapy techniques for treating carcinoma of the cervix. It describes the advantages of brachytherapy including its ability to deliver high radiation doses to tumors while sparing surrounding normal tissues. Several historical brachytherapy systems are summarized, including the Stockholm, Paris, and Manchester systems. The Manchester system defines dosimetry points A and B and provides rules for standardized applicator placement and radioactive source loading to achieve consistent dose distributions.
Radioisotopes such as cesium-137, iridium-192, and gold-198 have replaced radium in brachytherapy sources. Brachytherapy involves placing sealed radioactive sources close to or inside a tumor and can be delivered at low, medium, or high dose rates. Key factors in choosing radioisotopes include half-life, radiation output, specific activity, and photon energy. Proper selection of radioisotopes and dose rates optimizes treatment effectiveness while minimizing radiation exposure.
This document discusses the late effects of radiotherapy. It notes that while radiotherapy effectively treats cancer by damaging DNA in cancer cells, it can also affect normal cells, leading to both acute and late effects. Late effects occur more than 3 months after treatment and involve tissues with slow turnover rates. Common late effects include fibrosis, atrophy, necrosis, vascular damage, and secondary malignancies. The document outlines late effects for various organs and tissues. It emphasizes the importance of prevention strategies like treatment planning and education to minimize complications and improve patient outcomes and quality of life.
Colorectal cancer begins in the inner lining of the colon or rectum and can spread deeper into the wall of the colon/rectum and to other parts of the body. Risk factors include increasing age, family history, lifestyle factors like smoking, obesity, and lack of physical activity. Symptoms often include changes in bowel habits and bleeding. Screening is recommended regularly beginning at age 50. Treatment depends on the stage and may include surgery, radiation, chemotherapy, and targeted therapies. Prognosis depends on tumor stage and extent at diagnosis.
This document provides information on principles of chemotherapy. It discusses how chemotherapy works by damaging rapidly dividing cells like cancer cells, outlines the cell cycle and phases cells go through when dividing, and explains how chemotherapy targets specific phases to kill cancer cells. It also describes common side effects of chemotherapy like nausea, vomiting, fatigue, bone marrow depression leading to neutropenia, thrombocytopenia and anemia. The document discusses approaches to managing these side effects.
Brachytherapy involves placing small radioactive sources inside or near a tumor. It allows a high radiation dose to be delivered to the tumor while sparing surrounding normal tissues. There are several types of brachytherapy classified by source placement (interstitial, intracavitary), loading pattern (pre-loading, after-loading), dose rate (LDR, HDR), and duration of implant (temporary, permanent). Common radioactive sources used include cesium-137, iridium-192, and iodine-125 seeds. Brachytherapy provides advantages of high tumor control with minimal side effects due to rapid dose fall-off and short treatment times.
This document discusses gastrointestinal stromal tumors (GISTs). It defines GISTs as mesenchymal neoplasms that originate in the interstitial cells of Cajal in the gut wall. The majority of GISTs have a mutation in either the KIT or PDGFRA gene. KIT mutations are present in around 95% of cases and result in uncontrolled KIT signaling. Treatment involves surgical resection with adjuvant imatinib therapy for higher risk cases. For advanced or imatinib-resistant GISTs, other tyrosine kinase inhibitors like sunitinib may be used.
Vulvar cancer is a rare malignancy that represents less than 1% of cancers in women. It occurs most commonly in two age groups - younger women who smoke and are HPV-positive, and older women who may have epithelial dystrophies as risk factors. Lymphatic drainage is primarily to the superficial inguinal lymph nodes, with potential spread to deep femoral and pelvic nodes. Positive lymph nodes, particularly those over 5mm or with extracapsular spread, are the strongest prognostic factors and reduce 5-year survival by 50%. Surgical margins of at least 8mm are also important to reduce the risk of local recurrence after resection. Radiation may help reduce recurrence risk when margins are close. Distant metastases generally occur
1. Carcinoma of the oral cavity is most commonly found on the tongue, floor of mouth, and lips. It spreads locally and via lymphatics, most often to cervical lymph nodes. Distant metastases occur in 15-20% of cases, most commonly to lungs.
2. Diagnosis involves history, physical exam, biopsy of the lesion and lymph nodes, imaging like OPG, CT/MRI to assess bone and lymph node involvement. Staging helps determine prognosis and management.
3. Treatment involves surgery, radiation, chemotherapy depending on stage. Close surveillance is needed due to high risk of recurrence and second primary cancers.
The document discusses radiation and its effects on the human body. It provides information on deterministic effects, which have a threshold dose below which no effect is observable, and severity increases with dose. Examples of deterministic effects like cataracts and sterility are given along with their dose thresholds. International standards from organizations like ICRP, IAEA, and UNSCEAR are mentioned. Occupational and public dose limits are provided. Methods of measuring radiation exposure through film, TLD and electronic dosimeters are listed. Information is also given on calculating effective dose and the tissues and organs considered. Background radiation exposures from cosmic, terrestrial and internal sources are detailed. Finally, fatal accident rates per million workers are shown for different occupations along with the radiation
- The document provides information on Acute Myeloid Leukemia (AML), including its etiology, pathogenesis, signs and symptoms, diagnosis, classification, and treatment.
- AML arises from the abnormal clonal expansion of immature myeloid precursors in the bone marrow that have impaired differentiation. It is diagnosed based on finding at least 20% myeloid blasts in the bone marrow.
- Classification involves cytogenetic and molecular testing to identify recurrent genetic abnormalities that inform prognosis and treatment approach.
Radiation therapy has evolved significantly in its use and techniques for managing Hodgkin lymphoma over the past century. Early approaches used low dose X-rays to treat only involved lymph node regions, but this led to high recurrence rates. Later approaches in the 1950s used extended field radiation therapy to treat both involved and adjacent uninvolved lymph node regions, improving outcomes. However, this also increased long-term toxicity risks. More recent decades have seen a shift to involved node radiation therapy and combined modality treatment with chemotherapy to improve cure rates while reducing radiation doses and volumes to minimize side effects like secondary cancers. Ongoing clinical trials continue refining therapies to maximize benefit and safety.
This randomized controlled trial compared preoperative chemoradiotherapy to immediate surgery for resectable or borderline resectable pancreatic cancer. It found no significant difference in overall survival between the two groups based on intention-to-treat analysis. However, the preoperative chemoradiotherapy group had higher R0 resection rates and more favorable pathological outcomes. Compliance with preoperative treatment was also better. For borderline resectable disease specifically, preoperative chemoradiotherapy showed a prolonged overall survival compared to immediate surgery.
Concomitant chemotherapy provides the greatest benefit for patients with locally advanced head and neck cancer according to the MACHNC 2021 meta-analysis. It improves 5-year overall survival by 6.5% and event-free survival by 5.8%, with the greatest decrease in locoregional failure rates. Induction chemotherapy provides smaller benefits of 2.2% for overall survival and 1.45% for event-free survival, as well as a significant decrease in distant failure rates. Adjuvant chemotherapy does not improve survival and increases 120-day mortality. Cisplatin-based regimens are preferred for concomitant and induction chemotherapy. This may be the final MACHNC analysis as no new patients have been
This study retrospectively analyzed exclusive radiotherapy (ERT), surgery, and both as local regional therapies (LRT) for denovo metastatic breast cancer patients. It found that both ERT and surgery plus radiotherapy (BMT) were associated with improved overall survival compared to no LRT or surgery alone. ERT showed similar overall survival as BMT and could be an acceptable alternative to avoid invasive surgeries. However, the study had limitations as a retrospective analysis and larger prospective studies are still needed to provide stronger evidence and guidelines on the role of LRT like ERT for metastatic breast cancer.
Hypofractionation delivers a full course of radiation treatment over a shorter period by using larger daily doses compared to conventional fractionation. Several trials have shown hypofractionation to be as effective as conventional fractionation for early stage breast cancer patients, with acceptable toxicity and cosmetic outcomes. Hypofractionation schedules of 42.9Gy/13#/5wk and 39Gy/13#/5wk were found to have 10-year local relapse rates of 9.6% and 14.8% respectively in one trial, comparable to the conventional dose of 50Gy/25#/5wk which had a rate of 12.1%. Other trials have also found hypofractionation to have similar rates of locoregional
1) BRCA1 and BRCA2 are tumor suppressor genes whose mutations significantly increase the risk of breast and ovarian cancers. Testing for BRCA mutations can help determine appropriate cancer screening and prevention strategies.
2) The HER2 receptor promotes cancer cell growth in around 20-30% of breast cancers. Drugs like trastuzumab, pertuzumab, lapatinib, and T-DM1 target HER2 and have improved outcomes for HER2-positive breast cancer.
3) Newer agents for breast cancer treatment include CDK4/6 inhibitors, PI3K inhibitors, everolimus, neratinib and immunotherapies which are being used alone or in combination with other drugs for
Or: Beyond linear.
Abstract: Equivariant neural networks are neural networks that incorporate symmetries. The nonlinear activation functions in these networks result in interesting nonlinear equivariant maps between simple representations, and motivate the key player of this talk: piecewise linear representation theory.
Disclaimer: No one is perfect, so please mind that there might be mistakes and typos.
dtubbenhauer@gmail.com
Corrected slides: dtubbenhauer.com/talks.html
Unlocking the mysteries of reproduction: Exploring fecundity and gonadosomati...AbdullaAlAsif1
The pygmy halfbeak Dermogenys colletei, is known for its viviparous nature, this presents an intriguing case of relatively low fecundity, raising questions about potential compensatory reproductive strategies employed by this species. Our study delves into the examination of fecundity and the Gonadosomatic Index (GSI) in the Pygmy Halfbeak, D. colletei (Meisner, 2001), an intriguing viviparous fish indigenous to Sarawak, Borneo. We hypothesize that the Pygmy halfbeak, D. colletei, may exhibit unique reproductive adaptations to offset its low fecundity, thus enhancing its survival and fitness. To address this, we conducted a comprehensive study utilizing 28 mature female specimens of D. colletei, carefully measuring fecundity and GSI to shed light on the reproductive adaptations of this species. Our findings reveal that D. colletei indeed exhibits low fecundity, with a mean of 16.76 ± 2.01, and a mean GSI of 12.83 ± 1.27, providing crucial insights into the reproductive mechanisms at play in this species. These results underscore the existence of unique reproductive strategies in D. colletei, enabling its adaptation and persistence in Borneo's diverse aquatic ecosystems, and call for further ecological research to elucidate these mechanisms. This study lends to a better understanding of viviparous fish in Borneo and contributes to the broader field of aquatic ecology, enhancing our knowledge of species adaptations to unique ecological challenges.
Travis Hills' Endeavors in Minnesota: Fostering Environmental and Economic Pr...Travis Hills MN
Travis Hills of Minnesota developed a method to convert waste into high-value dry fertilizer, significantly enriching soil quality. By providing farmers with a valuable resource derived from waste, Travis Hills helps enhance farm profitability while promoting environmental stewardship. Travis Hills' sustainable practices lead to cost savings and increased revenue for farmers by improving resource efficiency and reducing waste.
The ability to recreate computational results with minimal effort and actionable metrics provides a solid foundation for scientific research and software development. When people can replicate an analysis at the touch of a button using open-source software, open data, and methods to assess and compare proposals, it significantly eases verification of results, engagement with a diverse range of contributors, and progress. However, we have yet to fully achieve this; there are still many sociotechnical frictions.
Inspired by David Donoho's vision, this talk aims to revisit the three crucial pillars of frictionless reproducibility (data sharing, code sharing, and competitive challenges) with the perspective of deep software variability.
Our observation is that multiple layers — hardware, operating systems, third-party libraries, software versions, input data, compile-time options, and parameters — are subject to variability that exacerbates frictions but is also essential for achieving robust, generalizable results and fostering innovation. I will first review the literature, providing evidence of how the complex variability interactions across these layers affect qualitative and quantitative software properties, thereby complicating the reproduction and replication of scientific studies in various fields.
I will then present some software engineering and AI techniques that can support the strategic exploration of variability spaces. These include the use of abstractions and models (e.g., feature models), sampling strategies (e.g., uniform, random), cost-effective measurements (e.g., incremental build of software configurations), and dimensionality reduction methods (e.g., transfer learning, feature selection, software debloating).
I will finally argue that deep variability is both the problem and solution of frictionless reproducibility, calling the software science community to develop new methods and tools to manage variability and foster reproducibility in software systems.
Exposé invité Journées Nationales du GDR GPL 2024
Authoring a personal GPT for your research and practice: How we created the Q...Leonel Morgado
Thematic analysis in qualitative research is a time-consuming and systematic task, typically done using teams. Team members must ground their activities on common understandings of the major concepts underlying the thematic analysis, and define criteria for its development. However, conceptual misunderstandings, equivocations, and lack of adherence to criteria are challenges to the quality and speed of this process. Given the distributed and uncertain nature of this process, we wondered if the tasks in thematic analysis could be supported by readily available artificial intelligence chatbots. Our early efforts point to potential benefits: not just saving time in the coding process but better adherence to criteria and grounding, by increasing triangulation between humans and artificial intelligence. This tutorial will provide a description and demonstration of the process we followed, as two academic researchers, to develop a custom ChatGPT to assist with qualitative coding in the thematic data analysis process of immersive learning accounts in a survey of the academic literature: QUAL-E Immersive Learning Thematic Analysis Helper. In the hands-on time, participants will try out QUAL-E and develop their ideas for their own qualitative coding ChatGPT. Participants that have the paid ChatGPT Plus subscription can create a draft of their assistants. The organizers will provide course materials and slide deck that participants will be able to utilize to continue development of their custom GPT. The paid subscription to ChatGPT Plus is not required to participate in this workshop, just for trying out personal GPTs during it.
When I was asked to give a companion lecture in support of ‘The Philosophy of Science’ (https://shorturl.at/4pUXz) I decided not to walk through the detail of the many methodologies in order of use. Instead, I chose to employ a long standing, and ongoing, scientific development as an exemplar. And so, I chose the ever evolving story of Thermodynamics as a scientific investigation at its best.
Conducted over a period of >200 years, Thermodynamics R&D, and application, benefitted from the highest levels of professionalism, collaboration, and technical thoroughness. New layers of application, methodology, and practice were made possible by the progressive advance of technology. In turn, this has seen measurement and modelling accuracy continually improved at a micro and macro level.
Perhaps most importantly, Thermodynamics rapidly became a primary tool in the advance of applied science/engineering/technology, spanning micro-tech, to aerospace and cosmology. I can think of no better a story to illustrate the breadth of scientific methodologies and applications at their best.
Phenomics assisted breeding in crop improvementIshaGoswami9
As the population is increasing and will reach about 9 billion upto 2050. Also due to climate change, it is difficult to meet the food requirement of such a large population. Facing the challenges presented by resource shortages, climate
change, and increasing global population, crop yield and quality need to be improved in a sustainable way over the coming decades. Genetic improvement by breeding is the best way to increase crop productivity. With the rapid progression of functional
genomics, an increasing number of crop genomes have been sequenced and dozens of genes influencing key agronomic traits have been identified. However, current genome sequence information has not been adequately exploited for understanding
the complex characteristics of multiple gene, owing to a lack of crop phenotypic data. Efficient, automatic, and accurate technologies and platforms that can capture phenotypic data that can
be linked to genomics information for crop improvement at all growth stages have become as important as genotyping. Thus,
high-throughput phenotyping has become the major bottleneck restricting crop breeding. Plant phenomics has been defined as the high-throughput, accurate acquisition and analysis of multi-dimensional phenotypes
during crop growing stages at the organism level, including the cell, tissue, organ, individual plant, plot, and field levels. With the rapid development of novel sensors, imaging technology,
and analysis methods, numerous infrastructure platforms have been developed for phenotyping.
Current Ms word generated power point presentation covers major details about the micronuclei test. It's significance and assays to conduct it. It is used to detect the micronuclei formation inside the cells of nearly every multicellular organism. It's formation takes place during chromosomal sepration at metaphase.
Describing and Interpreting an Immersive Learning Case with the Immersion Cub...Leonel Morgado
Current descriptions of immersive learning cases are often difficult or impossible to compare. This is due to a myriad of different options on what details to include, which aspects are relevant, and on the descriptive approaches employed. Also, these aspects often combine very specific details with more general guidelines or indicate intents and rationales without clarifying their implementation. In this paper we provide a method to describe immersive learning cases that is structured to enable comparisons, yet flexible enough to allow researchers and practitioners to decide which aspects to include. This method leverages a taxonomy that classifies educational aspects at three levels (uses, practices, and strategies) and then utilizes two frameworks, the Immersive Learning Brain and the Immersion Cube, to enable a structured description and interpretation of immersive learning cases. The method is then demonstrated on a published immersive learning case on training for wind turbine maintenance using virtual reality. Applying the method results in a structured artifact, the Immersive Learning Case Sheet, that tags the case with its proximal uses, practices, and strategies, and refines the free text case description to ensure that matching details are included. This contribution is thus a case description method in support of future comparative research of immersive learning cases. We then discuss how the resulting description and interpretation can be leveraged to change immersion learning cases, by enriching them (considering low-effort changes or additions) or innovating (exploring more challenging avenues of transformation). The method holds significant promise to support better-grounded research in immersive learning.
2. Intoduction
Plasma cell dyscrasias are a spectrum of progressively more severe monoclonal gammopathies in
which a clone or multiple clones of pre-malignant or malignant plasma cells (sometimes in
association with lymphoplasmacytoid cells or B lymphocytes) over-produce and secrete into the
blood stream, a myeloma protein.
Plasma cells are differentiated B-lymphocyte white blood cells capable of secreting immunoglobulin, or
antibody.
These develop from antigen-activated B lymphocytes in secondary lymphoid organs, such as the
spleen and lymph nodes, after encountering the appropriate antigen.
3. PLASMA CELLS
Each clonal plasma cell line is committed to synthesizing
one specific immunoglobulin antibody that consists of 2
identical heavy chains (gamma [γ], mu [μ], alpha [α], delta
[δ], or epsilon [ε]) and 2 identical light chains (kappa [κ]
or lambda [λ]).
A slight excess of light chains is normally produced, and
urinary excretion of small amounts of free polyclonal light
chains (≤ 40 mg/24 hours) is normal.
4.
5. The most immature blood cell of plasma cell lineage is the plasmablast.
Plasmablasts Proliferate
Secrete small amounts of antibodies.
Mature plasma cells Terminally differentiated
Non-proliferating, larger than B cells
Secrete large amounts of antibodies
Plasma cells are important contributors to humoral immunity.
7. HISTORY
Earliest Egyptian mummies
1845 Dr. William Macintrye, London
patient presented with c/o fatigue, bone pain and urinary frequency
detected a urinary protein with peculiar heat properties
named “mollities and fragilitas ossium”, published report in 1850
1845 Dr. Bence Jones examined the urinary proteins and published the report
1846 surgeon Dr. John Dalrymple
◦ examined several bones
◦ gross and microscopic examination consistent with presence of myeloma cells
8. 1873 Rustizky coined the term ‘multiple myeloma’
1889 Kahler published review popular in Europe as ‘Kahler’s disease’
1899 Ellenger described increased serum proteins and ESR in myeloma
1900 Wright described involvement of plasma cells and also described the X ray
findings which till date are hallmark of the disease
9. 1929 bone marrow aspiration
1937 protein electrophoresis later report of the γ globulin region spike
1953 Graber confirmed the monoclonality of the cells by detection of monoclonal
proteins via immunoelectrophoresis
10. .
In the second half of last century much came to be known regarding the pathogenesis of MM; important among them
were the role of the bone marrow microenvironment in myeloma cell growth, survival and antiapoptosis properties of
plasma cells and development of drug resistance through cell–cell interaction and activation of cytokine networks.
11. Recent advances which improved understanding of the disease and development of
various treatment modalities:
Marrow micro-environment
Development of resistance by cell – cell interactions
Role of chromosomal translocations
Gene expression profiling and genome sequencing molecular pathobiology of disease
13. The worldwide Age Standardized Rate (ASR) for incidence of MM as per the GLOBOCAN/IARC data
is 1.4/1,00,000 population accounting to 1,00,000 new cases every year.
In the US as per the SEER data, the ASR for incidence is higher at 5.8/1,00,000 population
accounting for 21,000 new cases each year.
The ASR for MM incidence in India is 0.7/1,00,000 population amounting to about 6,800 new
cases a year
*Swerdlow SH, Campo E, Harris NL. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC; 2008:200-213. 4th ed. Lyon, France: IARC; 2008.
GLOBOCAN Country Fast Stat.htm.
14. Worldwide the 5 year prevalence of the disease is 2,10,697 or 4.3/1,00,000 population.
In India it is 11,602 or 1.4/1,00,000 population.
As per the SEER data the complete prevalence of MM in USA is around 71,000 cases.
The estimated mortality rate from MM worldwide is 72,453 which accounts for 1% of all cancer
related deaths.
In India it accounts for around 5,900 deaths every year.
*seer_cancer_gov.html. 2020.
**P Gupta. A twelve year study of multiple myeloma at the all india institute of medical sciences, new delhi, india. Indian Journal of Medical and Paediatric Oncology. 1995 Jun;16(2):108–14.
Rasool MT, Lone MM, Wani ML, Afroz F, Zaffar S, Mohib-ul Haq M. Cancer in Kashmir, India: burden and pattern of disease. J Cancer Res Ther. 2012 Jun;8(2):243–6.
15. The USA SEER data shows that the Age Adjusted Death Rate was 3.4/1,00,000 population.
The disease is slightly more prevalent in males with an M:F ratio of 1.2:1(SEER data) and 1.1:1
worldwide.
In India it is 1.3:1. But other single institution studies from India showed a higher M:F ratio of
2.2:1
The disease is more common among the black Americans than the white in USA(14.3 vs.
6.9/1,00,000 new cases every year.
*seer_cancer_gov.html. 2020.
**P Gupta. A twelve year study of multiple myeloma at the all india institute of medical sciences, new delhi, india. Indian Journal of Medical and Paediatric Oncology. 1995 Jun;16(2):108–14.
Rasool MT, Lone MM, Wani ML, Afroz F, Zaffar S, Mohib-ul Haq M. Cancer in Kashmir, India: burden and pattern of disease. J Cancer Res Ther. 2012 Jun;8(2):243–6.
16. The median age in USA is 74 years as per SEER data, whereas in various single institute data across
India it is 1-2 decades lower at around 52-61 years.
The incidence of MM increases with age. More than 75% cases occurring between the age group of 55-
85 years.
There are only few cases reported below 20 years of age.
The Annual Percentage Change (APC) of Incidence of MM from 2000 to 2009 is an insignificant -0.1%
indicating very minimal change, whereas the APC in mortality over the same period is a very significant
-1.8% indicating better survival from newer modalities of treatment.
*seer_cancer_gov.html. 2020.
**P Gupta. A twelve year study of multiple myeloma at the all india institute of medical sciences, new delhi, india. Indian Journal of Medical and Paediatric Oncology. 1995 Jun;16(2):108–14.
Rasool MT, Lone MM, Wani ML, Afroz F, Zaffar S, Mohib-ul Haq M. Cancer in Kashmir, India: burden and pattern of disease. J Cancer Res Ther. 2012 Jun;8(2):243–6.
18. ETIOPATHOGENESIS
Exposure to ionizing radiation strongest single factor linked to an increased risk of
multiple myeloma.
People exposed to low levels of radiation also demonstrate an increased incidence of
myeloma, including radiologists, employees in the nuclear industry, or those handling
radioactive materials.
19. Potential risk factors metals, especially nickel; agricultural chemicals; benzene and
petroleum products; other aromatic hydrocarbons; agent orange; and silicon
Alcohol and tobacco consumption has not been clearly linked to myeloma
Mineral oil used as a laxative has been reported to be associated with an increased
risk of multiple myeloma in some patients
20. Hereditary and genetic factors may predispose patients to myeloma development direct genetic
linkage has not been established
Myeloma risk also appears to be enhanced by the presence of HLA-Cw2 in both African American
and Caucasian populations
A meta-analysis of two genome wide association studies (GWAS) in myeloma showed that the
t(11;14)(q13;q32) translocation is associated with a constitutive genetic factor.
21. MGUS has been considered to be a premalignant condition rate of conversion to myeloma
remains extremely low often associated with additional genetic changes.
Recent study indicates that the diagnosis of symptomatic MM is always preceded by MGUS by 2 or
more years
Development of MGUS has also been reported with T-cell deficiency disorders as in AIDS
Repeated infections or antigenic stimulation of the plasma cell compartment proposed as a
possible predisposing condition for developing myeloma
22. ETIOPATHOGENESIS
Transition of normal plasma cells to mgus malignancy
Antigenic stimulation
Unlike normal plasma cells, human myeloma cell lines and primary myeloma cells
express a broad range of toll-like receptors (tlrs).
Tlrs are normally expressed by b lymphocytes essential for these cells to recognize
infectious agents and pathogen-associated molecular patterns (pamp) initiates the host-
defense response.
23. Aberrant expression of TLRs
cells respond to specific ligands
abnormal and sustained response to infection
TLR specific ligands cause increased myeloma
proliferation, survival and resistance to dexamethasone induced
apoptosis
Autocrine IL-6 also plays imp role in mediating these effects (growth
factor for myeloma cells)
24. Immunosuppression
By promoting evasion of tumor surveillance or by promoting antigenic stimulation may
also contribute to the initiation of monoclonal gammopathies.
Monoclonal proteins have been reported in the context of immunosuppressive states
such as bone marrow/stem cell transplantation, organ transplantation, and HIV
infection.
Patients undergoing renal transplantation develop M proteins depending on the level of
immunosuppression to which they are subjected.
25. Cytogenetic abnormalities
The pathogenesis is associated with frequent rearrangements involving the IgH
locus and various proto-oncogenes
Loci that are recurrently involved in translocations with the Ig heavy-chain gene
on chromosome 14q32 are the cell cycle-regulatory genes cyclin D1 on chromosome
11q13 and cyclin D3 on chromosome 6p21.
Deletions of chromosome 17p that involve the TP53 tumor suppressor locus also
occur and are associated with a poor outcome.
26. By conventional cytogenetics, the 14q32 region is involved in translocation in 20% to
40% of cases, and by molecular and FISH techniques it is detectable at higher frequency,
ranging from 50% in MGUS to 90% in advanced myeloma.
Approximately 45% of cases of MGUS are associated with trisomies, usually of the odd
numbered chromosomes with the exception of 13
27. Late-stage, highly aggressive forms of the disease such as plasma cell leukemia are
associated with acquisition of rearrangements involving MYC.
More recent deep sequencing of myeloma genomes has identified frequent mutations
involving components of the NF-κB pathway, which supports B-cell survival.
28.
29. PATHOGENESIS OF BONE
LESIONS
The complex pathogenetic mechanisms involve a combination of osteoclast activation
coupled with osteoblast inhibition.
increase in the receptor activator of nuclear factor κB (NF-κB) ligand (RANKL) expression
by osteoblasts and possibly plasma cells.
accompanied by decreased stromal cell secretion of the RANKL decoy receptor
osteoprotegerin (OPG)
the binding of OPG to RANKL is also inhibited by syndecan-1 (CD138) secreted and or
shed by myeloma cells increase in the RANKL/OPG ratio increased osteoclast
activation mediated through the NF-KB pathway.
30. Second factor release of macrophage inflammatory protein (MIP)- 1α and MIP-1β by
myeloma cells osteoclast activation
Also increased expression of stromal derived factor1α (SDF-1α) by stromal cells and
myeloma cells increased osteoclast activity
Osteoblast inhibition in myeloma is believed to be primarily related to increased DKK1
expression by myeloma cells inhibition of Wnt signaling preventing stabilization and
promoting degradation of β-catenin osteoblast activator
31.
32. Symptomatology
Around one third of patients may have another PCD before the diagnosis of MM, in the form of
MGUS(20%), SMM(9%), and the rest being plasmacytomas and amyloidosis.
• Bone pain, Fatigue and recurrent infections are the most common symptoms of MM.
• Bone pains are present in around 60-90% of patients.
• Anaemia and fatigue was present in about 70% of the patients with the median Hemoglobin (Hb)
of around 10gm%.
• Mild elevation of Serum Creatinine is found in around 50% patients while levels above 2mg/dl
are found in 20% patients.
• Hypercalcemia is found in 25%. Conventional skeletal survey is abnormal in about 80% patients.
35. Investigations
Investigations in any suspected Monoclonal Gammopathy should include to accurately classify the
disorder:
• Complete Blood Count ( look for anemia)
• Comprehensive Metabolic Panel – Look for renal insufficiency, hypercalcemia and subtle clues like
decreased anion gap .
– Total protein and albumin level.
- Determine Globulin component.
- Too low globulin ( < 2gm%) or Elevated Globulin ( > 3.5gm%) is concerning :
Determine if Polyclonal vs. Monoclonal.
Evaluate further with : » Quantitative Immunoglobulins : Increase in all components usually,
polyclonal.
Increase in single component with reciprocal decrease of uninvolved globulin usually may suggest
monoclonal .
36. Serum Protein Electrophoresis with immunofixation if monoclonal gammopathy is suspected.
» 24Hr-Urine protein electrophoresis with urine immunofixation ( Serum Free Light Chain assay (κ/λ
ratio) may be used in place of UPEP}
» Bone marrow biopsy to evaluate % plasma cells if there is monoclonal protein or abnormal UPEP or
Light chain assay or if strong clinical picture of myeloma.
» Skeletal survey if monoclonal gammopathy has been established ( Bone scans are usually, negative
in MM)
» Beta-2 microglobulin and Albumin for staging and prognosis in MM ( once diagnosis is made).
37. IHC of PLASMA CELLS
• All plasma cells, whether normal or malignant, are distinguished by their expression of CD38 and
CD138, also CD79a.
• CD38
Catalyzes synthesis and hydrolysis of cyclic ADP-ribose, resulting in the maintenance of intracellular
calcium levels.
• CD138/ syndecan-1
Allows for the plasma cell to attach to extracellular matrix proteins.
Recent research has found it plays a further role in acting as a co-receptor for epithelial growth factor
(EGF), particularly in the context of multiple myeloma.
38. A distinguishing characteristic unique to malignant plasma cells is the loss of CD19
expression alongside the possible aberrant expression of CD56, a marker characteristic of
natural killer (NK) cells.
CD79a plays a critical role in B-lymphocyte antigen signal transduction and overall B-
lymphocyte development and stabilization.
Though CD79a is present in the cytoplasm of both precursor B-lymphocytes and mature,
differentiated plasma cells, its aberrant loss of expression has been noted in certain samples
of plasma cell neoplasms.
39. Plasma cell neoplasms represent a spectrum of diseases characterized by clonal proliferation and the
accumulation of immunoglobulin-producing terminally differentiated B cells.
It considered to originate from a single B cell resultnt monoclonal protein secretion that characterizes
its type.
The plasma cells sectrete 5 major Ig IgA, IgG, IgM, IgD and IgE
Dysfunctional plasma cells secrete one of these intact Ig molecules there may be discrepancy in
heavy chain and light chain production imbalance with excess κ or λ light chains which are
excreted in urine bence jones proteins or only production of excess κ or λ light chains
There can also be production of no paraproteins non – secretory myeloma
40. Type of Monoclonal Paraproteins and Percentage
IgG 52%
IgA 21%
IgD 2%
IgE <0.01 L chains ( K or L) only 11%
H chain (G or A) only <12%
No monoclonal paraprotein 1%
IgM 12%
41. Serum Protein Electrophoresis
• Serum is placed on special paper treated with
agarose gel and exposed to an electric current.
- This separates the serum protein components into
five classifications by size and electrical charge :
serum albumin, alpha-1 globulins, alpha-2 globulins,
beta globulins, and gamma globulins.
• Immunoglobulins ( IgG, IgM, IgA) usually migrate to
gamma region but may sometimes extend to beta
region.
• SPEP should always be performed in combination
with serum immunofixation in order to determine
clonality
42. •SPEP showing Monoclonal Gammopathy
• Shows a tall “narrow” band in gamma region –
“M-Spike”
• Also, note reduction in the normal polyclonal
gamma band
43. SPEP showing Polyclonal Gammopathy
• Shows a broadbased peak in gamma
region .
• Seen in chronic infections,
inflammation, connective tissue
disease, lymphoproliferative disease.
44. Immunofixation
• More sensitive than SPEP
• Immunofixation is performed when SPEP shows a
sharp “peak” or a plasma cell disorder is suspected
despite a normal SPEP
• Immunofixation always done to confirm the presence of
M-Protein and to determine the type (IgM or IgG etc and
the light chain restriction : k or λ)
• Why do both SPEP and IF ? Why not just IF in initial
diagnosis ?
• Unlike SPEP, immunofixation does not give an estimate
of the size of the M protein (ie, its serum concentration),
and thus should be done in conjunction with
electrophoresis.
45. Evaluation of bone marrow (BM) plasma cell infiltration by BM aspiration and/or biopsy.
- BM for cytogenetic/fluorescence in situ hybridization (FISH) studies
- Evaluation of lytic bone lesions: a radiological skeletal bone survey, including spine, pelvis, skull, humeri and femurs.
- MRI or computed tomography (CT) scan may be needed to evaluate symptomatic bony sites, even if the skeletal
survey is negative and the patient has symptoms suggesting bone lesions.
- MRI provides greater detail and is recommended whenever spinal cord compression is suspected.
- FDG PET scan is currently under evaluation and should be used fro evaluation of all patients
49. MGUS (Monoclonal gammopathy of unknown significance)
In almost all cases multiple myeloma is preceded by a premalignant asymptomatic stage termed as monoclonal
gammopathy of undetermined significance.
In population over the age of 50 year MGUS is present in 3-4% cases.
MGUS can progress to multiple myeloma at the rate of 1% per year.
Diagnosis of MGUS requires the absence of hypercalcaemia, renal failure, anaemia, and bone lesions (referred to
(referred to as CRAB features) that can be attributed to the underlying plasma cell disorder
51. Diagnostic criteria for MGUS
All three criteria must be met:
• _ Serum monoclonal protein <3 gm/dL
• _ Clonal bone marrow plasma cells <10%,
• _ Absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia, and bone
lesions (CRAB) that can be attributed to the plasma cell proliferative disorder; or in the case of IgM
MGUS no evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or
hepatosplenomegaly that can be attributed to the underlying lymphoproliferative disorder.
Considering this high risk of plasma cell disorder, persons found to have MGUS should be
monitored stringently lifelong.
52. Various studies from Asian countries have documented a similar percentage (varying from 2.3-
6.3%) of MGUS among the general population but are yet to publish their results regarding
progression to Plasma cell dyscrasias (PCD).
Data from India regarding MGUS is not available.
There was an increased incidenceof MGUS among people exposed to radiation after the Nagasaki
atom bomb explosion especially those living within 1.5 km of the epicentre.
But this study did not reveal an increased rate of progression to PCD
53. IgM MGUS
All three criteria must be met:
◦ Serum IgM M protein < 3 g/dL
◦ Bone marrow lymphoplasmacytic infiltration < 10%
◦ No evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or
hepatosplenomegaly that can be attributed to the underlying lymphoproliferative disorder
54. Multiple Myeloma
Bone marrow plasma cells ≥10% or bony or biopsy proven extramedullary plasmacytoma and
any one or more of myeloma defining evens including:
• Myeloma defining events: •
• Clonal bone marrow plasma cells ≥ 60%
• Free light chain ratio ≥ 100
•>1 focal lesions on MRI
55. •Evidence of end organ damage due to underlying plasma cell proliferative disorder (CRAB)
• Hypercalcemia: Calcium>1 mg/dl higher than upper limit or >11 mg/dl
• Renal insufficiency:
•Serum creatinine increased in > 50% at diagnosis Creatinine >2g/dL in 20% of patients
•Renal failure may be presenting manifestation
•Major Causes : –
•Myeloma cast nephropathy
•Hypercalcemia
•Amyloidosis
56. •Anemia :
•hb < 10gm%, Normochromic /normocytic anemia occurs in 75% patients
• Bone lesion:
•one or more osteolytic lesions skeletal radiography, CT or PET-CT •
57. Bone Lesions :
Conventional radiographs (Skeletal Survey) abnormal in 80% of patients who present with
multiple myeloma.
Focal lytic lesions – 57%
Osteopenia, osteoporosis – 20%
Pathologic fractures – 20%
Vetebral body comression fractures – 20%
58. Round lesions filled with a soft
reddish material are indicative of
foci of myeloma in this section of
vertebral bone.
60. PLASMABLAST
• Diffuse chromatin pattern
• Nucleus >10 μm
• Nucleolus greater than 2 μm
• Concentrically placed nucleus with little or
no hof
61. Plasma Cell:
• Plasma Cell Plasma cells
• Terminally differentiated B- cells
• Not normally found in peripheral blood .
• Account for less than 3.5% of nucleated cells in
the bone marrow
• Oval cells with low N:C ratio.
Cytoplasm is basophilic blue.
Nucleus (30-40% of the cell) is oval or round and
typically placed eccentrically (to one side) of the
cell. .
62. Russell bodies :
Globules (2-3 μm) of accumulated immunoglobulins
in the cytoplasm of plasma cells
• Usually round
• May be found in normal bone marrow
• 1st described by William Russell
65. BONE MARROW
At low power, the abnormal
plasma cells of multiple myeloma
fill the marrow.
BONE MARROW
At high power, the plasma cells
of multiple myeloma here are very
similar to normal plasma cells, but
they may also be poorly
differentiated.
66. PATTERNS OF BONE MARROW INVOLVEMENT IN MYELOMA
• Interstitial
• Focal
• Mixed
• Diffuse
67. MM & Skeletal Complications
~ 80% of patients with multiple
myeloma will have evidence of skeletal
involvement on skeletal survey
– Vertebrae: 65%
– Ribs: 45%
– Skull: 40%
– Shoulders: 40%
– Pelvis: 30%
– Long bones: 25%
* Dimopoulos MA, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer EA, Petrucci MT, Yu
Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM. Long-term follow-up on overall survival
from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in
patients with relapsed or refractory multiple myeloma. Leukemia. 2009 Nov;23(11):2147-52.
doi: 10.1038/leu.2009.147. Epub 2009 Jul 23. PMID: 19626046.
68.
69. Smoldering multiple myeloma (asymptomatic)
This is an intermediate during the transition from MGUS to frank symptomatic MM.
The monoclonal plasmacytosis and gammopathy has increased to MM levels but the end
organ damage that defines MM has not yet occurred.
The accepted diagnostic criteria for SMM is:
• Serum monoclonal protein (IgG or IgA) ≥ 3gm/dl or 24 hr urinary monoclonal protein ≥500
mg and/ or bone marrow plasma cells 10-60%
• Absence of myeloma defining event or amyloidosis
70. Solitary Plasmacytoma
This occurs around a decade younger than MM and is more common in males.
The sites commonly affected are the axial skeleton more than the appendicular skeleton.
It should be accompanied with a normal skeletal radiograph.
SPEP is ideally negative but in around 50% patients a low level of M protein might be present.
BM should not show increased plasma cells.
Care should be taken not to do a BM biopsy from an iliac crest or sternum if they are the
involved area for the plasmacytoma.
MRI might show 9 Consensus Document for Management of Multiple Myeloma other
asymptomatic lesions, but still it needs to be taken as a solitary plasmacytoma if X-ray doesn’t
show any other lesions.
71. Rate of progression to multiple myeloma is 10% in 3 years.
Solitary plasmacytoma is diagnosed by:
• Biopsy-proven solitary lesion of bone or soft tissue with evidence of clonal plasma cells
• Normal bone marrow with no evidence of clonal plasma cells
• Normal skeletal survey and MRI (or CT) of spine and pelvis (except for the primary solitary lesion)
• Absence of end-organ damage such as hypercalcaemia, renal insuffi ciency, anaemia, or bone
lesions (CRAB) that can be attributed to a lymphoplasma cell proliferative disorder
72. Extramedullary Plasmacytoma
The common sites of involvement are the nasal cavity, nasopharynx, larynx and sinuses.
It can happen in any location in the body and is commonly of the IgA subtype.
Other evidence of systemic MM should not be present.
The diagnostic criteria is:
• No M-protein in serum and/or urine
• Extramedullary tumour of clonal plasma cells
• Normal bone marrow
• Normal skeletal survey
• No related organ or tissue impairment (end organ damage including bone lesions)
73. Multiple Solitary Plasmacytomas:
This entity constitutes less than 5% of all PCDs.
The diagnostic criteria for this entity are as follows:
• No M-protein in serum and/or urine
• More than one localized area of bone destruction or extramedullary tumour of clonal plasma
cells which may be recurrent
• Normal bone marrow
• Normal skeletal survey and MRI of spine and pelvis if done
• No related organ or tissue impairment (no end organ damage other than the localized bone
lesions)
* Small elevation of M protein may be seen
74. Waldenström macroglobulinemia
All criteria must be met:
◦ IgM monoclonal gammopathy (regardless of the size of the M protein)
◦ ≥ 10% bone marrow lymphoplasmacytic infiltration (usually intertrabecular) by small lymphocytes
that exhibit plasmacytoid or plasma cell differentiation and a typical immunophenotype (e.g.,
surface IgM+, CD5±, CD10−, CD19+, CD20+, CD23−) that satisfactorily excludes other
lymphoproliferative disorders, including CLL and mantle cell lymphoma
◦ Evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or
hepatosplenomegaly that can be attributed to the underlying lymphoproliferative disorde
75. Smoldering Waldenström macroglobulinemia (also referred to as indolent or asymptomatic
Waldenström macroglobulinemia)
Both criteria must be met:
◦ Serum IgM M protein ≥ 3 g/dL and/or bone marrow lymphoplasmacytic infiltration ≥ 10%
◦ No evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or
hepatosplenomegaly that can be attributed to the underlying lymphoproliferative disorde
76. Light Chain MGUS
All criteria must be met:
◦ Abnormal free light chain (FLC) ratio ( 1.65)
◦ Increased level of the appropriate involved light chain (increased κ FLC in patients with ratio >
1.65 and increased λ FLC in patients with ratio < 0.26)
◦ No immunoglobulin heavy-chain expression on immunofixation
◦ Absence of end organ damage such as hypercalcemia, renal insufficiency, anemia, and bone
lesions (CRAB) that can be attributed to the plasma cell proliferative disorder
77. Systemic AL Amyloidosis
All four criteria must be met:
◦ Presence of an amyloid-related systemic syndrome (e.g., renal, liver, heart, gastrointestinal
tract, or peripheral nerve involvement)
◦ Positive amyloid staining by Congo red in any tissue (e.g., fat aspirate, bone marrow, or organ
biopsy)
◦ Evidence that amyloid is light-chain related established by direct examination of the amyloid
(possibly using mass spectrometry (MS)–based proteomic analysis, or immunoelectron
microscopy
◦ Evidence of a monoclonal plasma cell proliferative disorder (serum or urine M protein,
abnormal free light chain ratio, or clonal plasma cells in the bone marrow)
◦ Note: 2 to 3% of patients with AL amyloidosis will not meet the requirement for evidence of a
monoclonal plasma cell disorder listed above; the diagnosis of AL amyloidosis must be made
with caution in these patients.
78. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein,
skin changes)
All four criteria must be met
◦ Polyneuropathy
◦ Monoclonal plasma cell proliferative disorder (almost always λ)
◦ Any one of the following three other major criteria:
1. Sclerotic bone lesions
2. Castleman disease
3. Elevated levels of vascular endothelial growth factor (VEGF)
• Any one of the following six minor criteria:
1. Organomegaly (splenomegaly, hepatomegaly, or lymphadenopathy)
2. Extravascular volume overload (edema, pleural effusion, or ascites)
3. Endocrinopathy (adrenal, thyroid, pituitary, gonadal, parathyroid, pancreatic)
4. Skin changes (hyperpigmentation, hypertrichosis, glomeruloid hemangiomata, plethora, acrocyanosis, flushing,
white nails)
5. Papilledema
6. Thrombocytosis/polycythemia
81. The DSS provides a good estimate of tumor burden but has some limitations, especially in
the categorization of bone lesions.
Greipp and colleagues subsequently developed an International Staging System (ISS)
overcomes the limitations of the DSS and divides patients into three distinct stages and
prognostic groups based solely on the β2-microglobulin and albumin levels in the serum.
The ISS cannot be considered a true staging system, because it is influenced by overall
health and comorbidities, tumor burden, as well as renal function.
82.
83.
84. PROGNOSTIC FACTORS
Major Independent Prognostic Factors
◦ Performance status
◦ Stage (International Staging System)
◦ Cytogenetic changes
◦ Abnormal cytogenetics by karyotyping (especially deletion 13 or hypodiploidy)
◦ Translocations t(4;14) or t(14;16) or t(14;20) on fluorescent in-situ hybridization
◦ Deletion 17p on fluorescent in-situ hybridization
◦ Serum lactate dehydrogenase
◦ Plasmablastic morphology
◦ Increased plasma cell proliferative rate
◦ Plasma cell leukemia
◦ Other Prognostic
Markers
◦ Advanced age
◦ Stage (Durie-Salmon
stage)
◦ C-reactive protein
◦ Serum creatinine
◦ Platelet count
◦ Increased circulating
plasma cells by flow
cytometry
Blimp-1, IRF4, and XBP-1 transcription factors are known to be essential for the differentiation of mature B cells into plasma cells.
In 1844, Samuel Solley reported a case of myeloma in Sarah Newbury. He described it as “mollitis ossium”. Together with Bence Jones, he found that the urinalysis of the patient showed a protein with the heat properties often observed for urinary light chains. It later on came to be known as the Bence Jones Protein.
Monoclonal gammopathy of undetermined significance
TOLL LIKE RECEPTORS
NF-κB (nuclear factor kappa light chain enhancer of activated B cells)
Rouleaux formation is the linking of RBCs into chains resembling stacks of coins. The flat surface of the discoid RBCs gives them a large surface area to make contact with and stick to each other; thus forming a rouleau. They occur when the plasma protein concentration is high, and, because of them, the ESR (erythrocyte sedimentation rate) is also increased. This is a nonspecific indicator of the presence of disease