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Pathology - Acute B-lymphoblastic leukemia
Definition: A hematological neoplasm consisting of malignant B-lymphoid blasts.
Epidemiology: Rare occurrence. • Predominantly a pediatric ailment (75% of cases occur in those under 6 years of age)
Aetiology • Predominantly unknown, although there is an indication of a hereditary component in certain instances. Pathogenesis: Mutations in a hematopoietic stem cell result in the clonal proliferation of immature B-lymphoid blasts. • Lymphoid blasts proliferate rapidly, overwhelming normal bone marrow, entering peripheral circulation, and infiltrating other organs.
Presentation: • Abrupt development of bone marrow failure characterized by severe anemia and thrombocytopenia. The leukocyte count may be diminished, normal, or elevated. Infiltration of other organs is prevalent, resulting in lymphadenopathy, hepatosplenomegaly, bone pain, headache, vomiting, and cranial nerve palsies.
Microscopy • By definition, more than 20% of cells in the peripheral blood or bone marrow are lymphoid blasts. Lymphoid blasts are medium to large cells characterized by a high nuclear-to-cytoplasmic ratio. The immunophenotype of B-lymphoid blasts often includes the expression of CD19, CD79a, CD10, Pax5, and TdT.
Prognosis: Contemporary treatment protocols exhibit remarkable success rates, with complete remission attained in over 95% of pediatric patients.
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Pathology - Essential thrombocythemia
Definition: A myeloproliferative neoplasm mostly affecting the megakaryocytic lineage.
Epidemiology: Estimated incidence ranges from 0.5 to 2.5 cases per 100,000 individuals annually. • The majority of occurrences occur in adults aged 50 to 60. • There is no gender preference.
Aetiology: Unknown. Genetics • No established molecular genetic or cytogenetic abnormalities have been identified.
Presentation • Approximately fifty percent of patients are diagnosed incidentally due to a significantly elevated platelet count identified in a complete blood count. • The remaining patients exhibit symptoms associated with vascular occlusion or hemorrhage, including transient ischemic attacks, digital ischemia and gangrene, as well as major arterial and venous thrombosis. • Splenomegaly occurs in only a minority of patients. Complete blood count • Persistently high platelet count (> 450 × 10^9/L). The leukocyte and erythrocyte counts are typically within normal limits. The bone marrow has normal cellularity, although displays an elevated presence of huge and enormous megakaryocytes characterized by ample cytoplasm and severely lobated 'stag-horn' nuclei. There is no significant proliferation of erythroid or granulocytic lineages.
Prognosis: A rather indolent disease with a median survival of 10 to 15 years. • A minimal percentage of patients advance to bone marrow fibrosis or acute myeloid leukemia.
Definition: A myeloproliferative neoplasm mostly affecting the megakaryocytic lineage.
Epidemiology: Estimated incidence ranges from 0.5 to 2.5 cases per 100,000 individuals annually. • The majority of occurrences occur in adults aged 50 to 60. • There is no gender preference.
Aetiology: Unknown. Genetics • No established molecular genetic or cytogenetic abnormalities have been identified.
Presentation • Approximately fifty percent of patients are diagnosed incidentally due to a significantly elevated platelet count identified in a complete blood count. • The remaining patients exhibit symptoms associated with vascular occlusion or hemorrhage, including transient ischemic attacks, digital ischemia and gangrene, as well as major arterial and venous thrombosis. • Splenomegaly occurs in only a minority of patients. Complete blood count • Persistently high platelet count (> 450 × 10^9/L). The leukocyte and erythrocyte counts are typically within normal limits. The bone marrow has normal cellularity, although displays an elevated presence of huge and enormous megakaryocytes characterized by ample cytoplasm and severely lobated 'stag-horn' nuclei. There is no significant proliferation of erythroid or granulocytic lineages.
Prognosis: A rather indolent disease with a median survival of 10 to 15 years. • A minimal percentage of patients advance to bone marrow fibrosis or acute myeloid leukemia.
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Pathology - Polycythemia vera
A myeloproliferative neoplasm primarily affecting the erythroid lineage, typically linked to a somatic gain-of-function mutation in the JAK2 gene. Epidemiology: Incidence ranges from 1 to 2.5 cases per 100,000 individuals annually. The median age upon diagnosis is 60 years. • There is a minor masculine predominance.
Aetiology: Unknown. Genetics: Over 95% of cases exhibit the JAK2 V617F mutation, resulting in uncontrolled proliferation of all myeloid cells, particularly affecting the erythroid lineage. The advancement of the disease correlates with the development of chromosomal abnormalities.
Presentation • May be incidentally detected with a full blood count or manifest with symptoms associated with hyperviscosity (headache, dizziness, visual disturbances, venous or arterial thrombosis). • The majority of individuals exhibit plethoric conditions and hepatosplenomegaly. Complete blood count: elevated hemoglobin, increased red cell count, heightened hematocrit (HCT), and augmented packed cell volume (PCV). • Frequently, I monitor white blood cell count and platelet levels. The bone marrow exhibits hypercellularity resulting from an elevation in all myeloid lineages, termed 'panmyelosis.' Erythroid progenitors and megakaryocytes are the most prominent cell types. Megakaryocytes exhibit loose clustering and frequently demonstrate considerable variation in size and morphology.
Prognosis: Median survival exceeds 10 years with treatment. The majority of patients succumb to thrombosis or hemorrhage. Approximately 20% succumb to the progression of myelodysplasia or acute myeloid leukemia (AML).
A myeloproliferative neoplasm primarily affecting the erythroid lineage, typically linked to a somatic gain-of-function mutation in the JAK2 gene. Epidemiology: Incidence ranges from 1 to 2.5 cases per 100,000 individuals annually. The median age upon diagnosis is 60 years. • There is a minor masculine predominance.
Aetiology: Unknown. Genetics: Over 95% of cases exhibit the JAK2 V617F mutation, resulting in uncontrolled proliferation of all myeloid cells, particularly affecting the erythroid lineage. The advancement of the disease correlates with the development of chromosomal abnormalities.
Presentation • May be incidentally detected with a full blood count or manifest with symptoms associated with hyperviscosity (headache, dizziness, visual disturbances, venous or arterial thrombosis). • The majority of individuals exhibit plethoric conditions and hepatosplenomegaly. Complete blood count: elevated hemoglobin, increased red cell count, heightened hematocrit (HCT), and augmented packed cell volume (PCV). • Frequently, I monitor white blood cell count and platelet levels. The bone marrow exhibits hypercellularity resulting from an elevation in all myeloid lineages, termed 'panmyelosis.' Erythroid progenitors and megakaryocytes are the most prominent cell types. Megakaryocytes exhibit loose clustering and frequently demonstrate considerable variation in size and morphology.
Prognosis: Median survival exceeds 10 years with treatment. The majority of patients succumb to thrombosis or hemorrhage. Approximately 20% succumb to the progression of myelodysplasia or acute myeloid leukemia (AML).
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Pathology - Chronic myelogenous leukemia
A myeloproliferative neoplasm mostly affecting the granulocytic lineage, consistently related with the BCR-ABL1 fusion gene on the Philadelphia chromosome.
Epidemiology • Incidence ranges from 1 to 2 per 100,000 individuals annually. • The peak age of onset is between 50 and 70 years old.
Aetiology: Unknown. Genetics • Chronic myelogenous leukaemia (CML) is typically characterized by the t(9;22) translocation, which produces the Philadelphia chromosome. • This translocation fuses the BCR gene on chromosome 22 with the ABL1 gene on chromosome 9. • The resulting BCR-ABL1 protein exhibits increased tyrosine kinase activity, resulting in the persistent activation of signal transduction pathways and uncontrolled proliferation of myeloid cells.
Presentation • The majority of patients receive a diagnosis during the chronic phase of the disease, characterized by an elevated white cell count. • Hepatosplenomegaly frequently accompanies the diagnosis.
Peripheral blood • Leukocytosis resulting from elevated neutrophil counts at various maturation phases. • Basophilia and eosinophilia are prevalent. No dysplasia is observed.
Bone marrow • Bone marrow trephines exhibit hypercellularity attributed to elevated quantities of neutrophils and their precursors. • Megakaryocytes are generally diminutive and hypolobated. • Blasts constitute less than 5% of marrow cells throughout the chronic phase.
Prognosis • The outcome has significantly improved following the introduction of the tyrosine kinase inhibitor, imatinib, resulting in 5-year survival rates of 80–90%. • Disease progression is typically indicated by an elevation in circulating blasts to over 10% (accelerated phase) and culminates in acute leukemia when blasts constitute more than 20% of circulating cells.
A myeloproliferative neoplasm mostly affecting the granulocytic lineage, consistently related with the BCR-ABL1 fusion gene on the Philadelphia chromosome.
Epidemiology • Incidence ranges from 1 to 2 per 100,000 individuals annually. • The peak age of onset is between 50 and 70 years old.
Aetiology: Unknown. Genetics • Chronic myelogenous leukaemia (CML) is typically characterized by the t(9;22) translocation, which produces the Philadelphia chromosome. • This translocation fuses the BCR gene on chromosome 22 with the ABL1 gene on chromosome 9. • The resulting BCR-ABL1 protein exhibits increased tyrosine kinase activity, resulting in the persistent activation of signal transduction pathways and uncontrolled proliferation of myeloid cells.
Presentation • The majority of patients receive a diagnosis during the chronic phase of the disease, characterized by an elevated white cell count. • Hepatosplenomegaly frequently accompanies the diagnosis.
Peripheral blood • Leukocytosis resulting from elevated neutrophil counts at various maturation phases. • Basophilia and eosinophilia are prevalent. No dysplasia is observed.
Bone marrow • Bone marrow trephines exhibit hypercellularity attributed to elevated quantities of neutrophils and their precursors. • Megakaryocytes are generally diminutive and hypolobated. • Blasts constitute less than 5% of marrow cells throughout the chronic phase.
Prognosis • The outcome has significantly improved following the introduction of the tyrosine kinase inhibitor, imatinib, resulting in 5-year survival rates of 80–90%. • Disease progression is typically indicated by an elevation in circulating blasts to over 10% (accelerated phase) and culminates in acute leukemia when blasts constitute more than 20% of circulating cells.
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Pathology - Thrombophilia
Definition • An hereditary susceptibility to venous thrombosis.
Exposition • Recurrent deep vein thrombosis or pulmonary embolism. Venous thrombosis may also manifest at atypical locations, such as the axillary or cerebral veins.
Resistance to activated protein C
The predominant kind of thrombophilia, impacting 5–10% of the population. • Resulting from a point mutation in the factor V gene, referred to as the factor V Leiden mutation. Factor V Leiden protein exhibits typical procoagulant activity; however, it is not appropriately controlled by activated protein C, leading to a predisposition to thrombosis.
Prothrombin G20210A mutation
• Impacts around 1–5% of the population. • Resulting from a single nucleotide substitution of guanine for adenine at position 20210 of the PT gene. • Correlated with heightened PT levels and an augmented risk of venous thrombosis, potentially attributable to elevated thrombin production, excessive fibrin clot proliferation, and possibly enhanced platelet activation.
Deficiency of Protein C and S
• Impacts approximately 0.2% of the population. Protein C and S are endogenous anticoagulants that inactivate coagulation factors and regulate proper hemostasis. Deficiencies in these proteins thus predispose individuals to thrombosis.
Definition • An hereditary susceptibility to venous thrombosis.
Exposition • Recurrent deep vein thrombosis or pulmonary embolism. Venous thrombosis may also manifest at atypical locations, such as the axillary or cerebral veins.
Resistance to activated protein C
The predominant kind of thrombophilia, impacting 5–10% of the population. • Resulting from a point mutation in the factor V gene, referred to as the factor V Leiden mutation. Factor V Leiden protein exhibits typical procoagulant activity; however, it is not appropriately controlled by activated protein C, leading to a predisposition to thrombosis.
Prothrombin G20210A mutation
• Impacts around 1–5% of the population. • Resulting from a single nucleotide substitution of guanine for adenine at position 20210 of the PT gene. • Correlated with heightened PT levels and an augmented risk of venous thrombosis, potentially attributable to elevated thrombin production, excessive fibrin clot proliferation, and possibly enhanced platelet activation.
Deficiency of Protein C and S
• Impacts approximately 0.2% of the population. Protein C and S are endogenous anticoagulants that inactivate coagulation factors and regulate proper hemostasis. Deficiencies in these proteins thus predispose individuals to thrombosis.
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Pathology - Chronic lymphocytic leukemia
A malignant tumor consisting of tiny mature B-cells that typically coexpress CD5 and CD23.
Epidemiology The predominant leukemia, occurring at a rate of 5 per 100,000 individuals. • A condition prevalent among older persons, with a peak incidence occurring between the ages of 60 and 80 years. • Males are impacted twice as frequently as females.
Aetiology • Unidentified.
Pathogenesis The oncogenic B-cells progressively infiltrate the bone marrow and subsequently enter the peripheral circulation. • As the condition advances, lymph nodes become affected, followed by the liver and spleen. • In the terminal phases of the disease, the neoplastic cells dominate the bone marrow, resulting in bone marrow failure.
Presentation • Numerous people are diagnosed incidentally when a complete blood count indicates leukocytosis. The remainder exhibits lymphadenopathy or autoimmune manifestations, such autoimmune hemolytic anemia or autoimmune thrombocytopenia.
Peripheral blood film: Excess of mature lymphocytes. Smear cells are indicative of chronic lymphocytic leukaemia (CLL); they are neoplastic cells that get blurred during film preparation. Histopathology • Lymph nodes are substituted by small, slightly atypical B-cells exhibiting varied quantities of proliferation centers comprising bigger lymphoid cells. • Affected bone marrow contains aggregates of neoplastic lymphoid cells. Immunophenotype: Positive for PAX5, CD20, CD79a, CD5, and CD23. • Cyclin D1 is negative.
Prognosis • Typically exhibits an indolent course, with several patients surviving for several years post-diagnosis, frequently without intervention. • A minority of cases are compounded by the emergence of diffuse large B-cell lymphoma (Richter’s syndrome), which carries a bad prognosis.
A malignant tumor consisting of tiny mature B-cells that typically coexpress CD5 and CD23.
Epidemiology The predominant leukemia, occurring at a rate of 5 per 100,000 individuals. • A condition prevalent among older persons, with a peak incidence occurring between the ages of 60 and 80 years. • Males are impacted twice as frequently as females.
Aetiology • Unidentified.
Pathogenesis The oncogenic B-cells progressively infiltrate the bone marrow and subsequently enter the peripheral circulation. • As the condition advances, lymph nodes become affected, followed by the liver and spleen. • In the terminal phases of the disease, the neoplastic cells dominate the bone marrow, resulting in bone marrow failure.
Presentation • Numerous people are diagnosed incidentally when a complete blood count indicates leukocytosis. The remainder exhibits lymphadenopathy or autoimmune manifestations, such autoimmune hemolytic anemia or autoimmune thrombocytopenia.
Peripheral blood film: Excess of mature lymphocytes. Smear cells are indicative of chronic lymphocytic leukaemia (CLL); they are neoplastic cells that get blurred during film preparation. Histopathology • Lymph nodes are substituted by small, slightly atypical B-cells exhibiting varied quantities of proliferation centers comprising bigger lymphoid cells. • Affected bone marrow contains aggregates of neoplastic lymphoid cells. Immunophenotype: Positive for PAX5, CD20, CD79a, CD5, and CD23. • Cyclin D1 is negative.
Prognosis • Typically exhibits an indolent course, with several patients surviving for several years post-diagnosis, frequently without intervention. • A minority of cases are compounded by the emergence of diffuse large B-cell lymphoma (Richter’s syndrome), which carries a bad prognosis.
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Pathology - Acute myeloid leukemia
Definition: A collection of hematological neoplasms consisting of malignant myeloid blasts.
Epidemiology The global incidence is 3 cases per 100,000 individuals annually. • Primarily, a condition affecting adults (average age at diagnosis is 65 years).
Aetiology • Acute myeloid leukaemias (AML) can be either spontaneous or arise as a consequence of prior treatment or as a final manifestation of an existing myeloproliferative or myelodysplastic disorder.
Pathogenesis • Mutations in a hematopoietic stem cell result in the clonal proliferation of immature myeloid blasts. • Rapidly proliferating myeloid blasts saturate the bone marrow and enter the peripheral blood. • Infiltration of organs by myeloid blasts may occur in acute myeloid leukemia (AML), although this is less frequent than in acute B-lymphoblastic leukemia.
Presentation • The majority of patients manifest as bone marrow failure, resulting in anaemia, thrombocytopenia, and neutropenia. Leukocytosis may be present.
Microscopy • By definition, over 20% of the cells in peripheral blood or bone marrow are myeloid blasts. • The blasts are medium to large cells characterized by a high nuclear-to-cytoplasmic ratio. Certain myeloid blasts possess cytoplasmic granules or Auer rods. Immunophenotype • Myeloid blasts typically exhibit expression of CD13, CD117, CD33, and CD34. • They lack expression of B-lymphoid markers, including CD79a.
The prognosis is contingent upon the specific subtype of AML; still, the majority are aggressive conditions necessitating rigorous ablative treatments to attain remission. Acute myeloid leukemia (AML) linked to prior treatment or an existing myeloid disease typically exhibits a dismal prognosis.
Definition: A collection of hematological neoplasms consisting of malignant myeloid blasts.
Epidemiology The global incidence is 3 cases per 100,000 individuals annually. • Primarily, a condition affecting adults (average age at diagnosis is 65 years).
Aetiology • Acute myeloid leukaemias (AML) can be either spontaneous or arise as a consequence of prior treatment or as a final manifestation of an existing myeloproliferative or myelodysplastic disorder.
Pathogenesis • Mutations in a hematopoietic stem cell result in the clonal proliferation of immature myeloid blasts. • Rapidly proliferating myeloid blasts saturate the bone marrow and enter the peripheral blood. • Infiltration of organs by myeloid blasts may occur in acute myeloid leukemia (AML), although this is less frequent than in acute B-lymphoblastic leukemia.
Presentation • The majority of patients manifest as bone marrow failure, resulting in anaemia, thrombocytopenia, and neutropenia. Leukocytosis may be present.
Microscopy • By definition, over 20% of the cells in peripheral blood or bone marrow are myeloid blasts. • The blasts are medium to large cells characterized by a high nuclear-to-cytoplasmic ratio. Certain myeloid blasts possess cytoplasmic granules or Auer rods. Immunophenotype • Myeloid blasts typically exhibit expression of CD13, CD117, CD33, and CD34. • They lack expression of B-lymphoid markers, including CD79a.
The prognosis is contingent upon the specific subtype of AML; still, the majority are aggressive conditions necessitating rigorous ablative treatments to attain remission. Acute myeloid leukemia (AML) linked to prior treatment or an existing myeloid disease typically exhibits a dismal prognosis.
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Pathology - Diffuse large B-cell lymphoma
A mature B-cell neoplasm characterized by big B-lymphoid cells exhibiting a diffuse growth pattern.
Epidemiology: Represents 25–30% of all non-Hodgkin lymphomas. • Primarily impacts senior individuals over the age of 60.
Aetiology • Often unidentified in numerous instances. • Significant correlation with immunodeficiency conditions, including HIV or post-transplant scenarios, where the lymphoma is induced by EBV, HHV-8, or both.
Genetics • Several genetic modifications have been identified in diffuse large B-cell lymphoma (DLBCL). The most prevalent translocation pertains to a segment of 3q that encodes the BCL6 gene.
Presentation: A rapidly enlarging mass that may be nodal (60%) or extranodal (40%). The gastrointestinal system is the most prevalent extranodal site, however almost any location may be involved.
Histopathology • Affected tissues are substituted by extensive sheets of giant atypical lymphoid cells, typically exceeding twice the size of a normal lymphocyte. • Apoptotic debris is commonly observed, and confluent regions of tumor necrosis may be present. Immunophenotype: Positive for B-cell markers PAX5, CD20, and CD79a. Cyclin D1 is absent. • Elevated proliferation index (typically 40–90% of cells).
Prognosis: Survival rates have significantly improved with the introduction of the anti-CD20 inhibitor, rituximab, achieving long-term survival rates of approximately 60–75%. Bone marrow involvement is typically linked to a bad prognosis.
A mature B-cell neoplasm characterized by big B-lymphoid cells exhibiting a diffuse growth pattern.
Epidemiology: Represents 25–30% of all non-Hodgkin lymphomas. • Primarily impacts senior individuals over the age of 60.
Aetiology • Often unidentified in numerous instances. • Significant correlation with immunodeficiency conditions, including HIV or post-transplant scenarios, where the lymphoma is induced by EBV, HHV-8, or both.
Genetics • Several genetic modifications have been identified in diffuse large B-cell lymphoma (DLBCL). The most prevalent translocation pertains to a segment of 3q that encodes the BCL6 gene.
Presentation: A rapidly enlarging mass that may be nodal (60%) or extranodal (40%). The gastrointestinal system is the most prevalent extranodal site, however almost any location may be involved.
Histopathology • Affected tissues are substituted by extensive sheets of giant atypical lymphoid cells, typically exceeding twice the size of a normal lymphocyte. • Apoptotic debris is commonly observed, and confluent regions of tumor necrosis may be present. Immunophenotype: Positive for B-cell markers PAX5, CD20, and CD79a. Cyclin D1 is absent. • Elevated proliferation index (typically 40–90% of cells).
Prognosis: Survival rates have significantly improved with the introduction of the anti-CD20 inhibitor, rituximab, achieving long-term survival rates of approximately 60–75%. Bone marrow involvement is typically linked to a bad prognosis.
