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Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are a group of clonal neoplasms Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Bone Tumors with maturation defects characterized by dysplasia, cytopenia, and immature bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow precursors. Myelodysplastic syndromes can be idiopathic Idiopathic Dermatomyositis, or secondary to various injurious exposures such as cytotoxic Cytotoxic Parvovirus B19 chemotherapy Chemotherapy Osteosarcoma, ionizing radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma, or environmental toxins. The median patient age is 70 years old. Presentation includes symptoms of anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types ( fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia), neutropenia Neutropenia Neutrophils are an important component of the immune system and play a significant role in the eradication of infections. Low numbers of circulating neutrophils, referred to as neutropenia, predispose the body to recurrent infections or sepsis, though patients can also be asymptomatic. Neutropenia (infection), or thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia (bleeding). The diagnosis is based on bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow evaluation, which reveals cytopenia, dysplasia in at least 1 lineage, and blast cells in < 20% of marrow cellularity. Cytogenetic and molecular studies are required for classification, prognosis Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas, and therapy-related decisions. An increased cumulative risk of transformation Transformation Change brought about to an organism's genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell's genome. Bacteriology to AML AML Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the uncontrolled proliferation of myeloid precursor cells. Seen predominantly in older adults, AML includes an accumulation of myeloblasts and a replacement of normal marrow by malignant cells, which leads to impaired hematopoiesis. Acute Myeloid Leukemia is present and varies depending on MDS subtype. Management includes supportive care, use of hematopoietic growth factors Hematopoietic growth factors Hematopoietic growth factors are a family of glycoproteins responsible for the proliferation and differentiation of hematopoietic progenitor cells in the bone marrow. Pharmacologic erythropoietin, thrombopoietin, granulocyte colony-stimulating factor (G-CSF), and granulocyte macrophage colony-stimulating factor (GM-CSF) are used in certain cases in which normal hematopoiesis is impaired owing to treatment (e.g., chemotherapy) or underlying disease (e.g., aplastic anemia). Hematopoietic Growth Factors, immunosuppressive therapy, and allogeneic hematopoietic cell transplantation.

Last updated: Oct 24, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Myelodysplastic syndromes (MDS) are clonal, bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow diseases characterized by the presence of dysplastic, immature, bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow precursors and peripheral cytopenias Cytopenias IPEX Syndrome.

Epidemiology

  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency increases significantly with age.
  • Median age of presentation: approximately 70 years old
  • Annual incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in the United States:
    • 1–5 cases per 100,000
    • Individuals > 70 years of age: 20 cases per 100,000
  • Men > women

Etiology

  • Primary or idiopathic Idiopathic Dermatomyositis
  • Secondary (exposure to sources leading to chromosomal damage):
    • Postcancer treatment with alkylating agents (with or without radiotherapy)
    • Prior treatment with topoisomerase II Topoisomerase II DNA topoisomerases that catalyze ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. These enzymes bring about relaxation of the supercoiled DNA and resolution of a knotted circular DNA duplex. Fluoroquinolones inhibitors (anthracycline or etoposide Etoposide A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the g2 and s phases of the cell cycle. Microtubule and Topoisomerase Inhibitors)
    • Prior exposure to certain chemicals:
      • Benzene
      • Insecticides Insecticides Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. Trypanosoma cruzi/Chagas disease, weed killers, fungicides
      • Tobacco
    • Inherited genetic abnormalities (e.g., trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations 21, trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations 8, Fanconi anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types, ataxia-telangiectasia Ataxia-telangiectasia Ataxia-telangiectasia, also known as Louis-Bar syndrome, is a neurocutaneous syndrome, which involves multiple systems but mainly affects the neurological system. Ataxia-telangiectasia is an autosomal recessive genetic disorder caused by a mutation in the ATM gene (ATM serine/threonine kinase or the ataxia-telangiectasia mutated gene). Ataxia-telangiectasia
    • Clonal hematopoiesis Hematopoiesis The development and formation of various types of blood cells. Hematopoiesis can take place in the bone marrow (medullary) or outside the bone marrow (extramedullary hematopoiesis). Bone Marrow: Composition and Hematopoiesis of indeterminate potential 
    • Hematologic conditions (e.g., aplastic anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types, polycythemia vera Polycythemia vera Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the overproduction of RBCs. In addition, the WBC and platelet counts are also increased, which differentiate PV from erythrocytosis seen with chronic hypoxia and other chronic conditions. Polycythemia Vera, paroxysmal nocturnal hemoglobinuria Hemoglobinuria The presence of free hemoglobin in the urine, indicating hemolysis of erythrocytes within the vascular system. After saturating the hemoglobin-binding proteins (haptoglobins), free hemoglobin begins to appear in the urine. Transfusion Reactions, congenital Congenital Chorioretinitis neutropenia Neutropenia Neutrophils are an important component of the immune system and play a significant role in the eradication of infections. Low numbers of circulating neutrophils, referred to as neutropenia, predispose the body to recurrent infections or sepsis, though patients can also be asymptomatic. Neutropenia
    • Familial predisposition ( congenital Congenital Chorioretinitis platelet disorders)

Pathophysiology

The majority of MDS is attributed to chromosomal deletions and translocations, or gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics mutations.

  • Chromosomal abnormalities:
    • Deletion of chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 5 (del(5q)): 
      • Most common (15% of cases)
      • Women > men
      • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types with normal or ↑ platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology
    • Chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 7 involvement:
      • Monosomy Monosomy The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2n-1. Types of Mutations 7 (-7) or deletion of chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 7 (del(7q)) long arm Arm The arm, or “upper arm” in common usage, is the region of the upper limb that extends from the shoulder to the elbow joint and connects inferiorly to the forearm through the cubital fossa. It is divided into 2 fascial compartments (anterior and posterior). Arm: Anatomy
      • 10% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with de novo MDS
    • Trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations 8: < 10% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
    • Deletion of chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 20 (del(20q)): < 5% of cases
    • Loss of Y chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics
  • Gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics mutations:
    • Affected genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure are involved in:
      • Messenger RNA Messenger RNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure ( mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure) splicing
      • DNA methylation DNA methylation Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using s-adenosylmethionine as the methyl group donor. Epigenetic Regulation
      • Chromatin Chromatin The material of chromosomes. It is a complex of dna; histones; and nonhistone proteins found within the nucleus of a cell. DNA Types and Structure modification
      • Transcription factors Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Stages of Transcription (loss-of-function mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations of RUNX1)
    • Loss-of-function mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in TP53 (< 10% of cases)

Clinical Presentation

  • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types (most common):
    • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
    • Dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea
    • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children or signs of congestive heart failure Congestive heart failure Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Congestive Heart Failure 
  • Leukopenia (↓ WBC, WBC dysfunction): 
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Recurrent bacterial infection ( skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions most affected)
  • Thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia
  • Symptoms of autoimmune disease: approximately 25% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship (e.g., rheumatoid arthritis Rheumatoid arthritis Rheumatoid arthritis (RA) is a symmetric, inflammatory polyarthritis and chronic, progressive, autoimmune disorder. Presentation occurs most commonly in middle-aged women with joint swelling, pain, and morning stiffness (often in the hands). Rheumatoid Arthritis, psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis)
  • Acquired α-thalassemia (due to abnormal presence of hemoglobin H Hemoglobin H An abnormal hemoglobin composed of four beta chains. It is caused by the reduced synthesis of the alpha chain. This abnormality results in alpha-thalassemia. Thalassemia)
  • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions disease: Sweet syndrome Sweet syndrome Condition characterized by large, rapidly extending, erythematous, tender plaques on the upper body usually accompanied by fever and dermal infiltration of neutrophilic leukocytes. It occurs mostly in middle-aged women, is often preceded by an upper respiratory infection, and clinically resembles erythema multiforme. Sweet syndrome is associated with leukemia. Hematopoietic Growth Factors (acute febrile neutrophilic dermatosis Neutrophilic Dermatosis Rheumatoid Arthritis)
Sweet syndrome

Sweet syndrome: painful, erythematous, pseudovascular plaques of acute febrile neutrophilic dermatosis

Image: “Sweet’s syndrome–a comprehensive review of an acute febrile neutrophilic dermatosis” by Cohen PR. License: CC BY 2.0

Diagnosis

Diagnostic characteristics

  • Cytopenia in at least 1 blood lineage
  • ≥ 10% of nucleated cells with dysplasia (disordered differentiation) in at least 1 lineage
  • < 20% blasts Blasts Injuries resulting when a person is struck by particles impelled with violent force from an explosion. Blast causes pulmonary contusion and hemorrhage, laceration of other thoracic and abdominal viscera, ruptured ear drums, and minor effects in the central nervous system. Blunt Chest Trauma in blood and bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow
  • Characteristic cytogenetic or molecular findings
  • No evidence of an alternate cause

Diagnostic evaluation

  • History:
    • Alcohol and drug use
    • Medications
    • Exposure to toxic chemicals
    • Prior chemotherapy Chemotherapy Osteosarcoma or exposure to radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma
  • CBC:
    • Macrocytic anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types: ↑ MCV, ↓ Hb Hb The oxygen-carrying proteins of erythrocytes. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements. Gas Exchange
    • Thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia: ↓ platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology
    • Leukopenia: ↓ WBC
    • Circulating immature neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation: myelocytes, promyelocytes, myeloblasts
  • Peripheral blood smear Blood smear Myeloperoxidase Deficiency:
    • RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology: macrocytes, ringed sideroblasts, irregularly-shaped cells
    • WBCs: dysplastic, hyposegmented neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation (pseudo–Pelger-Huët abnormality)
    • Platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology: thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia
  • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma (Wright-Giemsa and iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements stains):
    • Hypercellular bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow
    • Dysplastic cells in 1 or more lineages
    • Increased myeloblasts (< 20% to differentiate from AML AML Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the uncontrolled proliferation of myeloid precursor cells. Seen predominantly in older adults, AML includes an accumulation of myeloblasts and a replacement of normal marrow by malignant cells, which leads to impaired hematopoiesis. Acute Myeloid Leukemia)
    • Ringed sideroblasts
    • Myelofibrosis of various degrees
  • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow karyotype Karyotype The full set of chromosomes presented as a systematized array of metaphase chromosomes from a photomicrograph of a single cell nucleus arranged in pairs in descending order of size and according to the position of the centromere. Congenital Malformations of the Female Reproductive System
  • Cytogenetic analysis Cytogenetic analysis Examination of chromosomes to diagnose, classify, screen for, or manage genetic diseases and abnormalities. Following preparation of the sample, karyotyping is performed and/or the specific chromosomes are analyzed. Non-Hodgkin Lymphomas:
    • Gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics microarray studies for genomic abnormalities
    • FISH FISH A type of in situ hybridization in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei. Chromosome Testing for chromosomal abnormalities
    • PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) for gene rearrangements Gene rearrangements The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development. Humoral Adaptive Immunity

Classification

After MDS confirmation, patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are categorized based on the 2016 WHO classification, which is important for treatment selection Selection Lymphocyte activation by a specific antigen thus triggering clonal expansion of lymphocytes already capable of mounting an immune response to the antigen. B cells: Types and Functions and prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas determination.

Classification is based on:

  • Dysplastic lineage(s)
  • Number of cytopenias Cytopenias IPEX Syndrome:
    • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types: Hb Hb The oxygen-carrying proteins of erythrocytes. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements. Gas Exchange < 10 g/dL
    • Leukopenia: absolute neutrophil count Absolute neutrophil count The number of neutrophils (as opposed to the percentage of WBCs) circulating per µL of blood . Neutropenia < 1.8 × 10⁹/L
    • Thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia: platelet count < 100 × 10⁹/L
  • Percentage of blasts Blasts Injuries resulting when a person is struck by particles impelled with violent force from an explosion. Blast causes pulmonary contusion and hemorrhage, laceration of other thoracic and abdominal viscera, ruptured ear drums, and minor effects in the central nervous system. Blunt Chest Trauma in the blood and bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow
  • Percentage of ring sideroblasts Ring Sideroblasts Sideroblastic Anemia
  • Cytogenetic findings

Types:

  • < 5% blasts Blasts Injuries resulting when a person is struck by particles impelled with violent force from an explosion. Blast causes pulmonary contusion and hemorrhage, laceration of other thoracic and abdominal viscera, ruptured ear drums, and minor effects in the central nervous system. Blunt Chest Trauma in the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow:
    • MDS with single lineage dysplasia (SLD)
    • MDS with multiple lineage dysplasia ( MLD MLD Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disorder that affects myelin in the brain and spinal cord. Genetic mutations result in the creation of a dysfunctional arylsulfatase a (arsa) enzyme, which is unable to break down cerebroside sulfate. The accumulation of this metabolite results in permanent damage to oligodendroglial and schwann cells (myelin). Metachromatic Leukodystrophy)
    • MDS with ringed sideroblasts-SLD (sideroblasts ≥ 15%)
    • MDS with ringed sideroblasts-MLD (sideroblasts ≥ 15%)
    • MDS with isolated del(5q)
  • 5%–19% blasts Blasts Injuries resulting when a person is struck by particles impelled with violent force from an explosion. Blast causes pulmonary contusion and hemorrhage, laceration of other thoracic and abdominal viscera, ruptured ear drums, and minor effects in the central nervous system. Blunt Chest Trauma in the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow:
    • MDS with excess blasts Blasts Injuries resulting when a person is struck by particles impelled with violent force from an explosion. Blast causes pulmonary contusion and hemorrhage, laceration of other thoracic and abdominal viscera, ruptured ear drums, and minor effects in the central nervous system. Blunt Chest Trauma ( EB EB Chlamydia)-1: 5%–9% blasts Blasts Injuries resulting when a person is struck by particles impelled with violent force from an explosion. Blast causes pulmonary contusion and hemorrhage, laceration of other thoracic and abdominal viscera, ruptured ear drums, and minor effects in the central nervous system. Blunt Chest Trauma
    • MDS with EB-2: 10%–19% blasts Blasts Injuries resulting when a person is struck by particles impelled with violent force from an explosion. Blast causes pulmonary contusion and hemorrhage, laceration of other thoracic and abdominal viscera, ruptured ear drums, and minor effects in the central nervous system. Blunt Chest Trauma
  • MDS unclassifiable

Management

Management approach

  • Dependent on clinical presentation and comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus
  • Determine risk stratus (lower risk vs. higher risk) based on prognostic variables with higher risk for the following:
    • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow blasts Blasts Injuries resulting when a person is struck by particles impelled with violent force from an explosion. Blast causes pulmonary contusion and hemorrhage, laceration of other thoracic and abdominal viscera, ruptured ear drums, and minor effects in the central nervous system. Blunt Chest Trauma: > 5%
    • Cytopenias Cytopenias IPEX Syndrome: 2 or 3
    • Cytogenetics: Certain mutations (e.g., -7 or del(7q)) have a poorer prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas.
    • Higher risk group:
      • Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas is worse.
      • Higher incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of transformation Transformation Change brought about to an organism’s genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell’s genome. Bacteriology to AML AML Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the uncontrolled proliferation of myeloid precursor cells. Seen predominantly in older adults, AML includes an accumulation of myeloblasts and a replacement of normal marrow by malignant cells, which leads to impaired hematopoiesis. Acute Myeloid Leukemia
  • Determine physiological fitness: 
    • Presence of comorbid diseases 
    • Physical performance tests: ability to perform activities of daily living (ADLs)
    • Cognition
  • Determine goals of care:
    • Cure is rarely feasible.
    • Discuss personal preferences and values.
    • Goals: 
      • ↓ Symptoms and provide comfort.
      • Prolong survival.
      • Enhance the quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life.
      • Minimize therapy-related toxicity Toxicity Dosage Calculation.

Management options

  • Observation: lower-risk, asymptomatic patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Low-intensity therapy:
    • Erythropoiesis Erythropoiesis The production of red blood cells (erythrocytes). In humans, erythrocytes are produced by the yolk sac in the first trimester; by the liver in the second trimester; by the bone marrow in the third trimester and after birth. In normal individuals, the erythrocyte count in the peripheral blood remains relatively constant implying a balance between the rate of erythrocyte production and rate of destruction. Erythrocytes: Histology/ myelopoiesis Myelopoiesis Formation of myeloid cells from the pluripotent hematopoietic stem cells in the bone marrow via myeloid stem cells. Myelopoiesis generally refers to the production of leukocytes in blood, such as monocytes and granulocytes. This process also produces precursor cells for macrophage and dendritic cells found in the lymphoid tissue. White Myeloid Cells: Histology stimulating factors (e.g., erythropoietin Erythropoietin Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology
    • Del(5q): lenalidomide Lenalidomide Has immunomodulatory (↓ tumor necrosis factor-⍺, ↑ natural killer cells and IL-2) and antiangiogenic activity. Induces cell-cycle arrest and death → inhibiting tumor cell growth. Cancer Immunotherapy 
    • RBC/platelet transfusion as needed
    • Hypomethylating agents (e.g., azacitidine, decitabine) 
  • High-intensity therapy:
    • Chemotherapy Chemotherapy Osteosarcoma (e.g., cytarabine Cytarabine A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the s phase of the cell cycle. It also has antiviral and immunosuppressant properties. Antimetabolite Chemotherapy + anthracycline)
    • Allogeneic hematopoietic cell transplantation (HCT) for young and medically-fit patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
    • Targeted therapy Targeted Therapy Targeted therapy exerts antineoplastic activity against cancer cells by interfering with unique properties found in tumors or malignancies. The types of drugs can be small molecules, which are able to enter cells, or monoclonal antibodies, which have targets outside of or on the surface of cells. Targeted and Other Nontraditional Antineoplastic Therapy for specific mutations

Differential Diagnosis

  • Isolated cytopenias Cytopenias IPEX Syndrome: defects in 1 cell line (isolated anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types, leukopenia, or thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia). Evaluation requires a detailed medical history: dietary practices (e.g., folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12, vitamin B12 Vitamin B12 A cobalt-containing coordination compound produced by intestinal microorganisms and found also in soil and water. Higher plants do not concentrate vitamin B 12 from the soil and so are a poor source of the substance as compared with animal tissues. Intrinsic factor is important for the assimilation of vitamin B 12. Folate and Vitamin B12, and/or copper Copper A heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55. Trace Elements deficiency), travel (e.g., acquired parasitic infection), chronic blood loss, medications, alcohol consumption, toxic exposures, chronicity of cytopenia, family history Family History Adult Health Maintenance, and GI, autoimmune, or neoplastic disorders. In most cases, diagnosis is established with history, peripheral smear, and bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma (if needed). 
  • Primary myelofibrosis Primary myelofibrosis Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by chronic myeloproliferation with nonclonal fibroblastic deposition, resulting in bone marrow fibrosis. The abnormality stems from genetic mutations of the hematopoietic stem cells (typically, JAK2 mutation). Primary symptoms are anemia and extramedullary hematopoiesis,. Primary Myelofibrosis: a chronic myeloproliferative neoplasm characterized by bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans and extramedullary hematopoiesis Hematopoiesis The development and formation of various types of blood cells. Hematopoiesis can take place in the bone marrow (medullary) or outside the bone marrow (extramedullary hematopoiesis). Bone Marrow: Composition and Hematopoiesis in the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy and liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy. The abnormality stems from genetic mutations Genetic Mutations Carcinogenesis of hematopoietic stem cells Hematopoietic stem cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Bone Marrow: Composition and Hematopoiesis (JAK2, CALR, or MPL mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations). Clinical findings are fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly, hepatomegaly, and anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types. Peripheral smear shows leukoerythroblastosis and contains precursors of WBCs, RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology, nucleated RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology, and teardrop cells Teardrop Cells Primary Myelofibrosis. Diagnosis is made by bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow examination and molecular testing. Management includes allogeneic HCT and medication ( ruxolitinib Ruxolitinib Targeted and Other Nontraditional Antineoplastic Therapy and fedratinib).
  • Acute myeloid leukemia Acute Myeloid Leukemia Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the uncontrolled proliferation of myeloid precursor cells. Seen predominantly in older adults, AML includes an accumulation of myeloblasts and a replacement of normal marrow by malignant cells, which leads to impaired hematopoiesis. Acute Myeloid Leukemia ( AML AML Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the uncontrolled proliferation of myeloid precursor cells. Seen predominantly in older adults, AML includes an accumulation of myeloblasts and a replacement of normal marrow by malignant cells, which leads to impaired hematopoiesis. Acute Myeloid Leukemia): the malignant and uncontrolled proliferation of myeloid precursors, resulting in cytopenias Cytopenias IPEX Syndrome and increased numbers (> 20%) of immature myelocytes (i.e., blasts Blasts Injuries resulting when a person is struck by particles impelled with violent force from an explosion. Blast causes pulmonary contusion and hemorrhage, laceration of other thoracic and abdominal viscera, ruptured ear drums, and minor effects in the central nervous system. Blunt Chest Trauma) in the peripheral circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment and bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow. The finding of Auer rods Auer Rods Acute Myeloid Leukemia (linear inclusions in the cytoplasm of blast cells) is pathognomonic of AML AML Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the uncontrolled proliferation of myeloid precursor cells. Seen predominantly in older adults, AML includes an accumulation of myeloblasts and a replacement of normal marrow by malignant cells, which leads to impaired hematopoiesis. Acute Myeloid Leukemia. Leukemic cells can infiltrate various organs, causing organomegaly and neurologic sequelae. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with MDS are at high risk of transformation Transformation Change brought about to an organism’s genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell’s genome. Bacteriology to AML AML Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the uncontrolled proliferation of myeloid precursor cells. Seen predominantly in older adults, AML includes an accumulation of myeloblasts and a replacement of normal marrow by malignant cells, which leads to impaired hematopoiesis. Acute Myeloid Leukemia.
  • Chronic myelomonocytic leukemia (CMML): a rare myelodysplastic/myeloproliferative neoplasm with increased production of maturing monocytic cells and, sometimes, dysplastic neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation. Chronic myelomonocytic leukemia is often accompanied by constitutional symptoms Constitutional Symptoms Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis, splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly, anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types, and/or thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia. The bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow morphology shows prominent dysplasia in at least 2 of the 3 myeloid lineages. Management is supportive care, hydroxyurea Hydroxyurea An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. Antimetabolite Chemotherapy, a hypomethylating agent, and allogeneic HCT.

References

  1. Aster, J.C., Stone, R.M. (2021). Clinical manifestations and diagnosis of myelodysplastic syndromes (MDS). UpToDate. Retrieved April 26, 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-myelodysplastic-syndromes-mds
  2. Besa, E.C. (2021). Myelodysplastic Syndrome (MDS). Medscape. Retrieved April 26, 2021, from https://reference.medscape.com/article/207347-overview
  3. Estey, E.H., Negrin, R.S. (2021). Treatment of high or very high risk myelodysplastic syndromes. UpToDate. Retrieved April 26, 2021, from https://www.uptodate.com/contents/treatment-of-high-or-very-high-risk-myelodysplastic-syndromes
  4. Estey, E.H., Sekeres, M.A. (2021). Overview of the treatment of myelodysplastic syndromes. UpToDate. Retrieved April 26, 2021, from: https://www.uptodate.com/contents/overview-of-the-treatment-of-myelodysplastic-syndromes
  5. Hasserjian, R.P. (2019). Myelodysplastic Syndrome Updated. Pathobiology. 86(1),7–13. https://doi.org/10.1159/000489702

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