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Pathology - Anemia of chronic illness
Definition: A decrease in hemoglobin concentration associated with chronic inflammatory diseases, persistent infections, and malignancies. Epidemiology: The second most prevalent etiology of anemia.
Aetiology: Any chronic inflammatory condition, persistent infection, or neoplasm. Pathogenesis The underlying mechanisms are intricate and multifaceted. Current evidence indicates that inflammatory cytokines (e.g., IL-6) diminish the sensitivity of the marrow to erythropoietin and hinder the incorporation of iron into developing red blood cells. Consequently, there is a reduction in erythropoiesis, which is frequently ineffective.
Presentation: Fatigue and dyspnea. Complete blood count: Decreased hemoglobin, typically mild to moderate in severity. • MCV is often within the normal range, although it may be diminished.
Peripheral blood film • Red blood cells are typically normal in size, however some may be diminutive. • There is no significant variation in size or morphology. Bone marrow • The marrow typically exhibits normal cellularity. • Stainable iron is present.
Definition: A decrease in hemoglobin concentration associated with chronic inflammatory diseases, persistent infections, and malignancies. Epidemiology: The second most prevalent etiology of anemia.
Aetiology: Any chronic inflammatory condition, persistent infection, or neoplasm. Pathogenesis The underlying mechanisms are intricate and multifaceted. Current evidence indicates that inflammatory cytokines (e.g., IL-6) diminish the sensitivity of the marrow to erythropoietin and hinder the incorporation of iron into developing red blood cells. Consequently, there is a reduction in erythropoiesis, which is frequently ineffective.
Presentation: Fatigue and dyspnea. Complete blood count: Decreased hemoglobin, typically mild to moderate in severity. • MCV is often within the normal range, although it may be diminished.
Peripheral blood film • Red blood cells are typically normal in size, however some may be diminutive. • There is no significant variation in size or morphology. Bone marrow • The marrow typically exhibits normal cellularity. • Stainable iron is present.
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Pathology - von Willebrand disease
Definition: An inherent predisposition to bleeding resulting from a quantitative or qualitative deficiency of von Willebrand factor (vWF).
Epidemiology The most prevalent hereditary coagulopathy. Type 1 (75%) constitutes a quantitative deficiency. Type 2 (20%) constitutes a qualitative flaw. Type 3, albeit less common, represents the most severe manifestation of the disease. The vWF gene resides on chromosome 12. Types 1 and 2 are transmitted in an autosomal dominant manner. Type 3 is an autosomal recessive characteristic.
Pathogenesis • von Willebrand factor (vWF) functions as an adhesion molecule, facilitating platelet attachment to subendothelial structures, and serves as a carrier for factor VIII. • Insufficient vWF activity results in a propensity for bleeding, attributable to impaired platelet adhesion and factor VIII deficiency. Presentation • The primary signs include mucosal hemorrhaging, especially epistaxis, and bleeding subsequent to trauma or surgical procedures.
Joint and muscle hemorrhages are infrequent and manifest solely in type 3 illness. Coagulation assessments • Extended activated partial thromboplastin time (APTT). • Extended hemorrhagic duration. • Normal prothrombin time (PT). Formal diagnosis necessitates the quantification of plasma von Willebrand factor (vWF) and the assessment of vWF functionality, such as through the ristocetin-induced platelet agglutination assay.
Prognosis: Most patients necessitate no further treatment. • Prophylactic therapy is used prior to surgery
Definition: An inherent predisposition to bleeding resulting from a quantitative or qualitative deficiency of von Willebrand factor (vWF).
Epidemiology The most prevalent hereditary coagulopathy. Type 1 (75%) constitutes a quantitative deficiency. Type 2 (20%) constitutes a qualitative flaw. Type 3, albeit less common, represents the most severe manifestation of the disease. The vWF gene resides on chromosome 12. Types 1 and 2 are transmitted in an autosomal dominant manner. Type 3 is an autosomal recessive characteristic.
Pathogenesis • von Willebrand factor (vWF) functions as an adhesion molecule, facilitating platelet attachment to subendothelial structures, and serves as a carrier for factor VIII. • Insufficient vWF activity results in a propensity for bleeding, attributable to impaired platelet adhesion and factor VIII deficiency. Presentation • The primary signs include mucosal hemorrhaging, especially epistaxis, and bleeding subsequent to trauma or surgical procedures.
Joint and muscle hemorrhages are infrequent and manifest solely in type 3 illness. Coagulation assessments • Extended activated partial thromboplastin time (APTT). • Extended hemorrhagic duration. • Normal prothrombin time (PT). Formal diagnosis necessitates the quantification of plasma von Willebrand factor (vWF) and the assessment of vWF functionality, such as through the ristocetin-induced platelet agglutination assay.
Prognosis: Most patients necessitate no further treatment. • Prophylactic therapy is used prior to surgery
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Pathology - Idiopathic thrombocytopenic purpura
Definition: A decrease in platelet count resulting from autoimmune damage.
Epidemiology • Rare, with an occurrence of 1 in 100,000. • Affects both adults and children. • Adult idiopathic thrombocytopenic purpura (ITP) exhibits a higher prevalence in women, with a ratio of 3:1. Childhood ITP exhibits a peak incidence between the ages of 2 and 4, with no gender preference.
Aetiology • The formation of platelet autoantibodies occurs for unidentified reasons.
Pathogenesis: Platelets are coated with autoantibodies and subsequently destroyed in the spleen.
Presentation • Abrupt emergence of cutaneous petechiae, epistaxis, and gingival hemorrhage. • A prior viral infection is frequently observed in pediatric cases. Complete blood count • Profound thrombocytopenia. • Normal hemoglobin and leukocyte count.
Peripheral blood smear
A combination of normal and enlarged platelets is observed. Bone marrow findings • Normal or elevated quantities of megakaryocytes.
• Typical megakaryocyte
morphology. • Typical haematopoiesis. 2 ITP is a diagnosis of exclusion when other causes of thrombocytopenia have been eliminated.
Prognosis: Childhood instances often resolve within one to two months. Adult instances are more prone to exhibit a chronic mild-to-moderate bleeding tendency.
Definition: A decrease in platelet count resulting from autoimmune damage.
Epidemiology • Rare, with an occurrence of 1 in 100,000. • Affects both adults and children. • Adult idiopathic thrombocytopenic purpura (ITP) exhibits a higher prevalence in women, with a ratio of 3:1. Childhood ITP exhibits a peak incidence between the ages of 2 and 4, with no gender preference.
Aetiology • The formation of platelet autoantibodies occurs for unidentified reasons.
Pathogenesis: Platelets are coated with autoantibodies and subsequently destroyed in the spleen.
Presentation • Abrupt emergence of cutaneous petechiae, epistaxis, and gingival hemorrhage. • A prior viral infection is frequently observed in pediatric cases. Complete blood count • Profound thrombocytopenia. • Normal hemoglobin and leukocyte count.
Peripheral blood smear
A combination of normal and enlarged platelets is observed. Bone marrow findings • Normal or elevated quantities of megakaryocytes.
• Typical megakaryocyte
morphology. • Typical haematopoiesis. 2 ITP is a diagnosis of exclusion when other causes of thrombocytopenia have been eliminated.
Prognosis: Childhood instances often resolve within one to two months. Adult instances are more prone to exhibit a chronic mild-to-moderate bleeding tendency.
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Pathology - Sickle cell disorders
Definition: A collection of hereditary red blood cell diseases resulting from HbS.
Epidemiology • Most commonly observed in individuals of African heritage and regions with current or historical malaria endemicity. The mutant gene persists as heterozygote carriers are safeguarded against the severe effects of Plasmodium falciparum malaria.
Genetics: HbS results from a point mutation in the β-globin gene located on chromosome 11, leading to a substitution of glutamic acid with valine. Heterozygotes are characterized by possessing sickle cell trait. • Homozygotes experience sickle cell disease or sickle cell anemia. Pathogenesis HbS exhibits a solubility that is 50 times inferior to that of HbA. Under low oxygen tension, HbS polymerizes into rod-like aggregates, resulting in the red blood cell adopting a sickled morphology.
Presentation • Individuals possessing sickle cell trait do not experience sickling due to the presence of normal HbA protein, which diminishes the aggregation of HbS. Patients are typically asymptomatic and exhibit normal hemoglobin levels. They are, nonetheless, genetically significant as carriers of the sickle cell allele. Individuals with sickle cell disease typically manifest symptoms at the age of two, after depleting most of their HbF, resulting in nearly all hemoglobin being HbS. Their red blood cells undergo sickling in venous blood, resulting in chronic hemolysis and episodes of vascular crises.
Complete blood count: Decreased hemoglobin, often ranging from 7 to 9 g/dL.
Peripheral blood smear • Sickle-shaped erythrocytes and their variations are present. • In adults, evidence of hyposplenism is present, shown by target cells, Howell–Jolly bodies, and Pappenheimer bodies. Diagnosis • The sickle cell solubility test serves as an effective screening method wherein a reducing agent is included into hemoglobin recovered from erythrocytes. HbS rapidly precipitates, resulting in a turbid solution. Definitive diagnosis necessitates Hb electrophoresis, which reveals a singular predominant HbS band and the absence of normal HbA.
Prognosis: Patients with sickle cell disease exhibit a markedly reduced lifetime. The median age of death is approximately 42 years for males and 48 years for women.
Complications associated with sickle cell disease Childhood: Hand-foot syndrome. • Splenic sequestration crisis. • Cerebrovascular accident. Subsequent years • Bacterial infections. • End-stage renal disease. • Priapism. • Ulceration of the lower extremities. • Pigmentary gallstones. • Avascular necrosis of the femoral head. • Pulmonary syndrome.
Definition: A collection of hereditary red blood cell diseases resulting from HbS.
Epidemiology • Most commonly observed in individuals of African heritage and regions with current or historical malaria endemicity. The mutant gene persists as heterozygote carriers are safeguarded against the severe effects of Plasmodium falciparum malaria.
Genetics: HbS results from a point mutation in the β-globin gene located on chromosome 11, leading to a substitution of glutamic acid with valine. Heterozygotes are characterized by possessing sickle cell trait. • Homozygotes experience sickle cell disease or sickle cell anemia. Pathogenesis HbS exhibits a solubility that is 50 times inferior to that of HbA. Under low oxygen tension, HbS polymerizes into rod-like aggregates, resulting in the red blood cell adopting a sickled morphology.
Presentation • Individuals possessing sickle cell trait do not experience sickling due to the presence of normal HbA protein, which diminishes the aggregation of HbS. Patients are typically asymptomatic and exhibit normal hemoglobin levels. They are, nonetheless, genetically significant as carriers of the sickle cell allele. Individuals with sickle cell disease typically manifest symptoms at the age of two, after depleting most of their HbF, resulting in nearly all hemoglobin being HbS. Their red blood cells undergo sickling in venous blood, resulting in chronic hemolysis and episodes of vascular crises.
Complete blood count: Decreased hemoglobin, often ranging from 7 to 9 g/dL.
Peripheral blood smear • Sickle-shaped erythrocytes and their variations are present. • In adults, evidence of hyposplenism is present, shown by target cells, Howell–Jolly bodies, and Pappenheimer bodies. Diagnosis • The sickle cell solubility test serves as an effective screening method wherein a reducing agent is included into hemoglobin recovered from erythrocytes. HbS rapidly precipitates, resulting in a turbid solution. Definitive diagnosis necessitates Hb electrophoresis, which reveals a singular predominant HbS band and the absence of normal HbA.
Prognosis: Patients with sickle cell disease exhibit a markedly reduced lifetime. The median age of death is approximately 42 years for males and 48 years for women.
Complications associated with sickle cell disease Childhood: Hand-foot syndrome. • Splenic sequestration crisis. • Cerebrovascular accident. Subsequent years • Bacterial infections. • End-stage renal disease. • Priapism. • Ulceration of the lower extremities. • Pigmentary gallstones. • Avascular necrosis of the femoral head. • Pulmonary syndrome.
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Pathology -Glucose-6-phosphate dehydrogenase deficiency
Definition: An hereditary hemolytic disorder resulting from a mutation in the glucose-6-phosphate dehydrogenase (G6PD) gene.
Epidemiology • Prevalent, impacting up to 10% of the global population. • There is significant geographical heterogeneity, with the highest rates observed among Africans, Asians, Italians, and Greeks. The G6PD gene is on the X chromosome. • A solitary mutant allele, consequently, induces G6PD deficiency in males.
Homozygous women are similarly impacted, although such people are rarely observed. Heterozygous women exhibit no clinical signs, as the normal allele generates sufficient enzyme activity.
Pathogenesis • G6PD is an enzyme involved in the hexose monophosphate pathway, a metabolic process essential for the production of reduced glutathione. • Reduced glutathione safeguards the red blood cell membrane from oxidative damage. • Individuals with G6PD deficiency experience episodes of hemolysis in response to oxidative stress.
Presentation • The majority of individuals remain asymptomatic with normal hemoglobin levels. • Upon exposure to oxidants, they may experience an acute hemolytic episode characterized by fever, jaundice, and dark urine resulting from hemoglobinuria. • Frequent precipitants include medications (notably anti-malarials) and fava beans, a prevalent food in Mediterranean regions. Complete blood count • decreased hemoglobin during an acute hemolytic event.
Peripheral blood smear • Alteration in erythrocyte morphology (poikilocytosis). • Erythrocytes exhibiting indentations in their peripheries, known as 'bite cells,' are distinctive. Spherocytes may also be observed. Supplementary examinations Screening assays for G6PD deficiency are available that indirectly evaluate G6PD activity by assessing the capacity of red blood cells to decrease dyes. • A definitive diagnosis necessitates direct enzyme assay.
Definition: An hereditary hemolytic disorder resulting from a mutation in the glucose-6-phosphate dehydrogenase (G6PD) gene.
Epidemiology • Prevalent, impacting up to 10% of the global population. • There is significant geographical heterogeneity, with the highest rates observed among Africans, Asians, Italians, and Greeks. The G6PD gene is on the X chromosome. • A solitary mutant allele, consequently, induces G6PD deficiency in males.
Homozygous women are similarly impacted, although such people are rarely observed. Heterozygous women exhibit no clinical signs, as the normal allele generates sufficient enzyme activity.
Pathogenesis • G6PD is an enzyme involved in the hexose monophosphate pathway, a metabolic process essential for the production of reduced glutathione. • Reduced glutathione safeguards the red blood cell membrane from oxidative damage. • Individuals with G6PD deficiency experience episodes of hemolysis in response to oxidative stress.
Presentation • The majority of individuals remain asymptomatic with normal hemoglobin levels. • Upon exposure to oxidants, they may experience an acute hemolytic episode characterized by fever, jaundice, and dark urine resulting from hemoglobinuria. • Frequent precipitants include medications (notably anti-malarials) and fava beans, a prevalent food in Mediterranean regions. Complete blood count • decreased hemoglobin during an acute hemolytic event.
Peripheral blood smear • Alteration in erythrocyte morphology (poikilocytosis). • Erythrocytes exhibiting indentations in their peripheries, known as 'bite cells,' are distinctive. Spherocytes may also be observed. Supplementary examinations Screening assays for G6PD deficiency are available that indirectly evaluate G6PD activity by assessing the capacity of red blood cells to decrease dyes. • A definitive diagnosis necessitates direct enzyme assay.
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Pathology - Megaloblastic anemias
Definition: A decrease in hemoglobin concentration resulting from compromised erythroid DNA synthesis. The majority of instances pertain to deficiencies in either vitamin B12 or folate.
Aetiology
Autoimmune gastritis is the predominant cause of vitamin B12 deficiency. Megaloblastic anemia resulting from autoimmune gastritis is referred to as pernicious anemia. This impacts around 1 in 1000 individuals, with a feminine predisposition
. • An inadequate diet is the predominant cause of folate deficiency. The primary dietary sources of folate are leafy green vegetables. Deficiency is commonly observed in the elderly and individuals with alcohol dependence.
Pathogenesis Vitamin B12 and folate are essential for the conversion of deoxyuridine monophosphate into deoxythymidine monophosphate, a chemical necessary for DNA synthesis. • Developing red blood cells are unable of division due to insufficient DNA synthesis required for the formation of two nuclei. • Consequently, they become stalled in their maturation as giant immature cells (megaloblasts), a significant number of which perish in the bone marrow. •
Certain megaloblasts persist and differentiate into unusually large erythrocytes (macrocytes), which are subsequently discharged into the bloodstream.
Presentation • Symptoms associated with severe anemia. Mild jaundice may occur as a result of hemolysis. Vitamin B12 deficiency may lead to neurological manifestations, such as cognitive impairment, peripheral neuropathy, and subacute combined degeneration of the spinal cord.
Complete blood count • Hemoglobin concentration is generally exceedingly low, nearing only 2 g/dL. • MCV is generally elevated. Peripheral blood smear • Notable anisocytosis and poikilocytosis characterized by big oval macrocytes. Nucleated red blood cells may be observed. • Hypersegmented neutrophils. The bone marrow is hypercellular, with numerous immature big erythroid blasts (megaloblasts) and massive metamyelocytes.
Definition: A decrease in hemoglobin concentration resulting from compromised erythroid DNA synthesis. The majority of instances pertain to deficiencies in either vitamin B12 or folate.
Aetiology
Autoimmune gastritis is the predominant cause of vitamin B12 deficiency. Megaloblastic anemia resulting from autoimmune gastritis is referred to as pernicious anemia. This impacts around 1 in 1000 individuals, with a feminine predisposition
. • An inadequate diet is the predominant cause of folate deficiency. The primary dietary sources of folate are leafy green vegetables. Deficiency is commonly observed in the elderly and individuals with alcohol dependence.
Pathogenesis Vitamin B12 and folate are essential for the conversion of deoxyuridine monophosphate into deoxythymidine monophosphate, a chemical necessary for DNA synthesis. • Developing red blood cells are unable of division due to insufficient DNA synthesis required for the formation of two nuclei. • Consequently, they become stalled in their maturation as giant immature cells (megaloblasts), a significant number of which perish in the bone marrow. •
Certain megaloblasts persist and differentiate into unusually large erythrocytes (macrocytes), which are subsequently discharged into the bloodstream.
Presentation • Symptoms associated with severe anemia. Mild jaundice may occur as a result of hemolysis. Vitamin B12 deficiency may lead to neurological manifestations, such as cognitive impairment, peripheral neuropathy, and subacute combined degeneration of the spinal cord.
Complete blood count • Hemoglobin concentration is generally exceedingly low, nearing only 2 g/dL. • MCV is generally elevated. Peripheral blood smear • Notable anisocytosis and poikilocytosis characterized by big oval macrocytes. Nucleated red blood cells may be observed. • Hypersegmented neutrophils. The bone marrow is hypercellular, with numerous immature big erythroid blasts (megaloblasts) and massive metamyelocytes.
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Pathology - Thalassemias
Definition • A collection of hereditary erythrocyte diseases resulting from the insufficient synthesis of alpha or beta globin chains. Pathogenesis • Insufficient production of either A- or B-globin chains results in the accumulation of surplus unpaired chains. • This culminates in the destruction of developing erythrocytes and the premature elimination of circulating erythrocytes in the spleen. The anemia in thalassaemia results from a combination of inadequate erythropoiesis and splenic haemolysis. Beta-thalassemia major • Resulting from mutations in both B-globin genes.
• Complications arise within the initial months of life as HbF levels diminish and surplus A-chains start to build in erythrocytes. • Deteriorating anaemia results in heightened erythropoietic stimulation, causing an increase in the bone marrow volume and the reactivation of extramedullary haematopoiesis.
• Manifestations in infancy include pallor, inadequate feeding, and growth failure. • The complete blood count indicates hypochromic, microcytic anemia. • The diagnosis is corroborated by the nearly absent HbA on hemoglobin electrophoresis. Beta-thalassemia minor • Resulting from mutations in a single B-globin gene.
• Asymptomatic silent carriers exhibit moderate microcytic anemia. • An elevated HbA2 level on hemoglobin electrophoresis is a critical diagnostic indicator. Alpha-thalassemia • A-chains are essential for both adult and fetal hemoglobin. • In the fetus, surplus G-chains aggregate to form tetramers referred to as Hb Bart's. In adulthood, surplus B-chains aggregate to form tetramers referred to as HbH. The deletion of all four A-globin genes results in severe fetal anemia, widespread edema, major hepatosplenomegaly, and fetal demise between 28 and 40 weeks of gestation. The deletion of three alpha-globin genes results in HbH illness, characterized by varying degrees of persistent hemolysis. The majority of individuals experience moderate chronic hemolytic anemia throughout their lives (Hb 7–10 g/dL) accompanied by splenomegaly. Deletion of one or two alpha-globin genes results in alpha-thalassemia minor, which is typically asymptomatic. A minor case of microcytic anemia may be present.
Definition • A collection of hereditary erythrocyte diseases resulting from the insufficient synthesis of alpha or beta globin chains. Pathogenesis • Insufficient production of either A- or B-globin chains results in the accumulation of surplus unpaired chains. • This culminates in the destruction of developing erythrocytes and the premature elimination of circulating erythrocytes in the spleen. The anemia in thalassaemia results from a combination of inadequate erythropoiesis and splenic haemolysis. Beta-thalassemia major • Resulting from mutations in both B-globin genes.
• Complications arise within the initial months of life as HbF levels diminish and surplus A-chains start to build in erythrocytes. • Deteriorating anaemia results in heightened erythropoietic stimulation, causing an increase in the bone marrow volume and the reactivation of extramedullary haematopoiesis.
• Manifestations in infancy include pallor, inadequate feeding, and growth failure. • The complete blood count indicates hypochromic, microcytic anemia. • The diagnosis is corroborated by the nearly absent HbA on hemoglobin electrophoresis. Beta-thalassemia minor • Resulting from mutations in a single B-globin gene.
• Asymptomatic silent carriers exhibit moderate microcytic anemia. • An elevated HbA2 level on hemoglobin electrophoresis is a critical diagnostic indicator. Alpha-thalassemia • A-chains are essential for both adult and fetal hemoglobin. • In the fetus, surplus G-chains aggregate to form tetramers referred to as Hb Bart's. In adulthood, surplus B-chains aggregate to form tetramers referred to as HbH. The deletion of all four A-globin genes results in severe fetal anemia, widespread edema, major hepatosplenomegaly, and fetal demise between 28 and 40 weeks of gestation. The deletion of three alpha-globin genes results in HbH illness, characterized by varying degrees of persistent hemolysis. The majority of individuals experience moderate chronic hemolytic anemia throughout their lives (Hb 7–10 g/dL) accompanied by splenomegaly. Deletion of one or two alpha-globin genes results in alpha-thalassemia minor, which is typically asymptomatic. A minor case of microcytic anemia may be present.
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Pathology - Hereditary spherocytosis
Definition: An inherited hemolytic disorder resulting from mutations in genes that encode proteins essential for preserving the integrity of the red blood cell membrane.
Epidemiology • Prevalent, with an incidence rate of up to 1 in 2,000. Aetiology: Mutations in genes that encode red blood cell membrane proteins. Pathogenesis: Mutations induce instability of the red blood cell membrane, resulting in lipid leakage from the membrane. The decrease in the membrane's surface area compels red blood cells to adopt a spherical configuration (spherocyte). Spherocytes exhibit reduced deformability compared to normal erythrocytes, rendering them vulnerable to entrapment in the spleen and subsequent destruction by splenic macrophages. The extent of haemolysis exhibits significant variability. • The majority of patients exhibit mild to severe anemia (Hb 8–12 g/dL). • Splenomegaly is prevalent.
Complete blood count • Mild to severe anemia (Hb 8–12 g/dL). • Elevated reticulocyte count. Peripheral blood smear Spherocytes are easily identifiable. • are furthermore present.
Supplementary examinations
The negative direct antiglobulin test differentiates spherocytosis from immunological hemolytic anemia, which exhibits analogous blood film findings. Prognosis • The majority of individuals exhibit well-compensated disease and necessitate just folate supplementation to prevent megaloblastic anemia. • Acknowledged consequences encompass gallstone disease (resulting from pigment gallstones) and aplastic crisis induced by parvovirus B19 infection. The latter may be lethal.
Definition: An inherited hemolytic disorder resulting from mutations in genes that encode proteins essential for preserving the integrity of the red blood cell membrane.
Epidemiology • Prevalent, with an incidence rate of up to 1 in 2,000. Aetiology: Mutations in genes that encode red blood cell membrane proteins. Pathogenesis: Mutations induce instability of the red blood cell membrane, resulting in lipid leakage from the membrane. The decrease in the membrane's surface area compels red blood cells to adopt a spherical configuration (spherocyte). Spherocytes exhibit reduced deformability compared to normal erythrocytes, rendering them vulnerable to entrapment in the spleen and subsequent destruction by splenic macrophages. The extent of haemolysis exhibits significant variability. • The majority of patients exhibit mild to severe anemia (Hb 8–12 g/dL). • Splenomegaly is prevalent.
Complete blood count • Mild to severe anemia (Hb 8–12 g/dL). • Elevated reticulocyte count. Peripheral blood smear Spherocytes are easily identifiable. • are furthermore present.
Supplementary examinations
The negative direct antiglobulin test differentiates spherocytosis from immunological hemolytic anemia, which exhibits analogous blood film findings. Prognosis • The majority of individuals exhibit well-compensated disease and necessitate just folate supplementation to prevent megaloblastic anemia. • Acknowledged consequences encompass gallstone disease (resulting from pigment gallstones) and aplastic crisis induced by parvovirus B19 infection. The latter may be lethal.
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Pathology - Proliferative breast diseases
Definition: A heterogeneous collection of intraductal proliferative lesions of the breast linked to a variable risk for the later emergence of invasive breast cancer. Epidemiology • Extremely prevalent. • Incidence has increased following the implementation of breast screening programs.
Aetiology • Comparable to invasive breast carcinoma (see p. 226). Genetics • The majority of instances of flat epithelial atypia and in situ lobular neoplasia exhibit genetic anomalies, particularly the loss of heterozygosity on chromosome 16p. A fraction of typical epithelial hyperplasia instances exhibit genetic abnormalities.
Macroscopy: The majority are detected through screening mammography or accidentally during the excision of breast tissue for other purposes. Histopathology • Usual epithelial hyperplasia is characterized by a disorganized proliferation of juvenile ductal epithelial cells that create slit-like spaces. • Flat epithelial atypia involves a consistent proliferation of moderately atypical ductal epithelial cells, not exceeding five cells in thickness. This is considered the earliest morphological precursor of low-grade ductal carcinoma in situ. In situ lobular neoplasia is characterized by a proliferation of tiny, weakly cohesive epithelial cells, marked by the loss of E-cadherin expression as determined immunohistochemically.
Prognosis • Typical epithelial hyperplasia is not regarded as a direct precursor lesion for invasive breast carcinoma; however, it serves as an indicator of a modestly elevated risk (relative risk of 1.5–2.0) for subsequent invasive carcinoma. • Currently, there is no quantitative data regarding the relative risk for the future development of invasive breast carcinoma in patients with flat epithelial atypia.
Recent genetic findings indicate that flat epithelial atypia may serve as the initial morphological precursor to low-grade ductal carcinoma in situ. Current research indicates that in situ lobular neoplasia poses a risk for eventual invasive breast carcinoma in either breast in a minority of women. The relative risk is reported to be between 7 and 12 times greater than that anticipated in women devoid of lobular neoplasia.
Definition: A heterogeneous collection of intraductal proliferative lesions of the breast linked to a variable risk for the later emergence of invasive breast cancer. Epidemiology • Extremely prevalent. • Incidence has increased following the implementation of breast screening programs.
Aetiology • Comparable to invasive breast carcinoma (see p. 226). Genetics • The majority of instances of flat epithelial atypia and in situ lobular neoplasia exhibit genetic anomalies, particularly the loss of heterozygosity on chromosome 16p. A fraction of typical epithelial hyperplasia instances exhibit genetic abnormalities.
Macroscopy: The majority are detected through screening mammography or accidentally during the excision of breast tissue for other purposes. Histopathology • Usual epithelial hyperplasia is characterized by a disorganized proliferation of juvenile ductal epithelial cells that create slit-like spaces. • Flat epithelial atypia involves a consistent proliferation of moderately atypical ductal epithelial cells, not exceeding five cells in thickness. This is considered the earliest morphological precursor of low-grade ductal carcinoma in situ. In situ lobular neoplasia is characterized by a proliferation of tiny, weakly cohesive epithelial cells, marked by the loss of E-cadherin expression as determined immunohistochemically.
Prognosis • Typical epithelial hyperplasia is not regarded as a direct precursor lesion for invasive breast carcinoma; however, it serves as an indicator of a modestly elevated risk (relative risk of 1.5–2.0) for subsequent invasive carcinoma. • Currently, there is no quantitative data regarding the relative risk for the future development of invasive breast carcinoma in patients with flat epithelial atypia.
Recent genetic findings indicate that flat epithelial atypia may serve as the initial morphological precursor to low-grade ductal carcinoma in situ. Current research indicates that in situ lobular neoplasia poses a risk for eventual invasive breast carcinoma in either breast in a minority of women. The relative risk is reported to be between 7 and 12 times greater than that anticipated in women devoid of lobular neoplasia.
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Pathology - Ductal carcinoma in situ
Definition: Neoplastic intraductal epithelial proliferation in the breast, possessing an inherent but not guaranteed risk of development to invasive breast cancer.
Epidemiology
• Prevalent. • The incidence has significantly risen following the implementation of breast screening programs. Aetiology: Risks analogous to invasive breast carcinoma
Genetics • Low-grade ductal carcinoma in situ (DCIS) frequently exhibits loss of homozygosity at 16p. High-grade DCIS has genetic distinctiveness characterized by a more intricate karyotype.
Presentation: 85% are identified on mammography as regions of microcalcification. • Ten percent exhibit clinical manifestations include a lump, nipple discharge, or eczematous alterations of the nipple (Paget's disease of the nipple). • Five percent are detected inadvertently in breast specimens excised for alternative purposes.
Macroscopy :DCIS is frequently macroscopically imperceptible, even to a seasoned pathologist. Extensive high-grade DCIS may present as gritty yellow flecks resulting from calcified necrotic debris within the affected ducts.
Histopathology: DCIS is categorized into low, middle, and high nuclear grades. Low-grade DCIS is characterized by small, uniform cells exhibiting cribriform, solid, or micropapillary patterns, with pronounced cellular polarization, wherein the nuclei are basally located and the apical cytoplasm is oriented towards the duct lumen. Central necrosis within the duct is unusual. Intermediate-grade DCIS exhibits cells characterized by moderately large nuclei and coarse chromatin, proliferating in solid, cribriform, or micropapillary architectures with a moderate level of cellular polarization. Central necrosis may be observed. High-grade DCIS exhibits cells characterized by big, significantly pleomorphic nuclei, clumped chromatin, conspicuous nucleoli, and diminished cellular polarization. Central necrosis is prevalent.
Prognosis: Complete surgical excision with clear margins is curative. The prognosis is contingent upon the persistence of malignant cells following treatment. Recurrence is more probable in cases of severe illness, elevated nuclear grade, and the existence of comedo necrosis.
Definition: Neoplastic intraductal epithelial proliferation in the breast, possessing an inherent but not guaranteed risk of development to invasive breast cancer.
Epidemiology
• Prevalent. • The incidence has significantly risen following the implementation of breast screening programs. Aetiology: Risks analogous to invasive breast carcinoma
Genetics • Low-grade ductal carcinoma in situ (DCIS) frequently exhibits loss of homozygosity at 16p. High-grade DCIS has genetic distinctiveness characterized by a more intricate karyotype.
Presentation: 85% are identified on mammography as regions of microcalcification. • Ten percent exhibit clinical manifestations include a lump, nipple discharge, or eczematous alterations of the nipple (Paget's disease of the nipple). • Five percent are detected inadvertently in breast specimens excised for alternative purposes.
Macroscopy :DCIS is frequently macroscopically imperceptible, even to a seasoned pathologist. Extensive high-grade DCIS may present as gritty yellow flecks resulting from calcified necrotic debris within the affected ducts.
Histopathology: DCIS is categorized into low, middle, and high nuclear grades. Low-grade DCIS is characterized by small, uniform cells exhibiting cribriform, solid, or micropapillary patterns, with pronounced cellular polarization, wherein the nuclei are basally located and the apical cytoplasm is oriented towards the duct lumen. Central necrosis within the duct is unusual. Intermediate-grade DCIS exhibits cells characterized by moderately large nuclei and coarse chromatin, proliferating in solid, cribriform, or micropapillary architectures with a moderate level of cellular polarization. Central necrosis may be observed. High-grade DCIS exhibits cells characterized by big, significantly pleomorphic nuclei, clumped chromatin, conspicuous nucleoli, and diminished cellular polarization. Central necrosis is prevalent.
Prognosis: Complete surgical excision with clear margins is curative. The prognosis is contingent upon the persistence of malignant cells following treatment. Recurrence is more probable in cases of severe illness, elevated nuclear grade, and the existence of comedo necrosis.
