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Pathology - Parathyroid adenoma
A nonmalignant epithelial tumor of the parathyroid gland.
Epidemiology: Common, constituting approximately 80% of primary hyperparathyroidism. • Peak incidence occurs between the ages of 50 and 60 years. • Women are impacted more significantly than men, at a ratio of 3:1
Aetiology • The underlying causes are inadequately comprehended, however previous irradiation of the neck seems to elevate the risk. The pathogenesis involves the autonomous secretion of parathyroid hormone (PTH) from the adenoma, resulting in hypercalcemia due to uncontrolled calcium mobilization from the bone and increased calcium absorption in the kidneys and gastrointestinal tract.
Presentation • Patients exhibit primary hyperparathyroidism, characterized by hypercalcemia accompanied by an abnormally normal or elevated PTH level. • A multitude of patients are asymptomatic when this is identified inadvertently. • Some individuals may exhibit nonspecific symptoms such as tiredness, nausea, constipation, polyuria, and arthralgia.
Macroscopy: A solitary parathyroid gland exhibits enlargement, measuring over 6mm in size and over 60mg in weight. The adenoma is often smooth, firm, soft, and light brown in hue. Histopathology: The parathyroid gland exhibits a well-defined, often encapsulated mass comprised of parathyroid epithelial cells devoid of adipose tissue. A compressed rim of normal parathyroid tissue frequently exists at one margin. Chief cells typically dominate, however an interspersing of oncocytic cells is also occasionally observed. The cells might be organized into solid sheets, trabeculae, or follicles. Stromal edema, fibrosis, and hemorrhage are frequently observed.
Prognosis: Parathyroid adenomas are benign tumors that can be effectively treated with surgical removal.
A nonmalignant epithelial tumor of the parathyroid gland.
Epidemiology: Common, constituting approximately 80% of primary hyperparathyroidism. • Peak incidence occurs between the ages of 50 and 60 years. • Women are impacted more significantly than men, at a ratio of 3:1
Aetiology • The underlying causes are inadequately comprehended, however previous irradiation of the neck seems to elevate the risk. The pathogenesis involves the autonomous secretion of parathyroid hormone (PTH) from the adenoma, resulting in hypercalcemia due to uncontrolled calcium mobilization from the bone and increased calcium absorption in the kidneys and gastrointestinal tract.
Presentation • Patients exhibit primary hyperparathyroidism, characterized by hypercalcemia accompanied by an abnormally normal or elevated PTH level. • A multitude of patients are asymptomatic when this is identified inadvertently. • Some individuals may exhibit nonspecific symptoms such as tiredness, nausea, constipation, polyuria, and arthralgia.
Macroscopy: A solitary parathyroid gland exhibits enlargement, measuring over 6mm in size and over 60mg in weight. The adenoma is often smooth, firm, soft, and light brown in hue. Histopathology: The parathyroid gland exhibits a well-defined, often encapsulated mass comprised of parathyroid epithelial cells devoid of adipose tissue. A compressed rim of normal parathyroid tissue frequently exists at one margin. Chief cells typically dominate, however an interspersing of oncocytic cells is also occasionally observed. The cells might be organized into solid sheets, trabeculae, or follicles. Stromal edema, fibrosis, and hemorrhage are frequently observed.
Prognosis: Parathyroid adenomas are benign tumors that can be effectively treated with surgical removal.
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Pathology - Parathyroid carcinoma
Definition: A malignant epithelial neoplasm originating from the parathyroid gland.
Epidemiology: Rare, constituting around 1% of primary hyperparathyroidism cases. • The majority manifest in individuals in their 40s and 50s, exhibiting no gender preference.
Aetiology • The cause remains unidentified, however anecdotal evidence suggests a connection with secondary hyperparathyroidism and previous neck irradiation. • Parathyroid cancer has not been associated with MEN 1.
Carcinogenesis • The most commonly observed aberration is the loss of genetic material at chromosome 13q.
Presentation • In contrast to individuals with parathyroid hyperplasia or adenoma, patients typically exhibit symptomatic primary hyperparathyroidism accompanied by a discernible neck mass. • Calcium concentrations are typically elevated (3.5–4mmol/L), accompanied by symptoms such as polyuria, polydipsia, weakness, renal colic, and ostealgia. Macroscopy: Parathyroid carcinomas are typically significantly larger than adenomas, averaging a weight of 12g. • They may exhibit well-defined margins or possess distinctly infiltrative borders.
Histopathology: Parathyroid carcinomas consist of sheets of epithelial cells that frequently appear deceptively benign. The development of follicles is atypical. • Tumors frequently possess a robust capsule and are interspersed with dense fibrous tissue bands that partition the tumor into several expansive nodules. • Capsular invasion, vascular invasion, tumor necrosis, and an elevated mitotic index are all strongly indicative of malignancy.
Prognosis • The 10-year survival rate is around 50%. • The majority of patients succumb to the unmanageable metabolic consequences of severe hyperparathyroidism caused by recurrent tumors.
Definition: A malignant epithelial neoplasm originating from the parathyroid gland.
Epidemiology: Rare, constituting around 1% of primary hyperparathyroidism cases. • The majority manifest in individuals in their 40s and 50s, exhibiting no gender preference.
Aetiology • The cause remains unidentified, however anecdotal evidence suggests a connection with secondary hyperparathyroidism and previous neck irradiation. • Parathyroid cancer has not been associated with MEN 1.
Carcinogenesis • The most commonly observed aberration is the loss of genetic material at chromosome 13q.
Presentation • In contrast to individuals with parathyroid hyperplasia or adenoma, patients typically exhibit symptomatic primary hyperparathyroidism accompanied by a discernible neck mass. • Calcium concentrations are typically elevated (3.5–4mmol/L), accompanied by symptoms such as polyuria, polydipsia, weakness, renal colic, and ostealgia. Macroscopy: Parathyroid carcinomas are typically significantly larger than adenomas, averaging a weight of 12g. • They may exhibit well-defined margins or possess distinctly infiltrative borders.
Histopathology: Parathyroid carcinomas consist of sheets of epithelial cells that frequently appear deceptively benign. The development of follicles is atypical. • Tumors frequently possess a robust capsule and are interspersed with dense fibrous tissue bands that partition the tumor into several expansive nodules. • Capsular invasion, vascular invasion, tumor necrosis, and an elevated mitotic index are all strongly indicative of malignancy.
Prognosis • The 10-year survival rate is around 50%. • The majority of patients succumb to the unmanageable metabolic consequences of severe hyperparathyroidism caused by recurrent tumors.
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Pathology - Addison's disease
Definition: Primary adrenocortical insufficiency. Epidemiology • Uncommon, with an estimated annual incidence of 1 in 100,000 individuals. • The majority of instances occur in young to middle-aged adults. • Women are disproportionately impacted compared to men.
Etiology • Autoimmune degradation in industrialized nations. • Disseminated TB in underdeveloped nations. • Alternative etiologies, such as adrenal metastases, are infrequent.
Pathogenesis • Addison's disease results in a significant deficiency of glucocorticoid and mineralocorticoid synthesis by the adrenal cortex.
Clinical manifestations do not become apparent until approximately 90% of the gland has been obliterated.
Presentation: Fatigue, lethargy, and debilitation. • Anorexia, nausea, emesis, and diarrhea. • Weight loss may be significant.
The clinical appearance is frequently subtle and non-specific, complicating the diagnosis.
Biochemistry • Sodium and potassium levels. • Urea concentration resulting from dehydration. • As much as fifty percent of patients have hypoglycemia. • Circulating anti-adrenal autoantibodies are frequently observed. Diagnosis • Individuals suspected of having Addison’s disease should undergo dynamic adrenal cortex testing via a Synacthen test. This entails an intramuscular injection of synthetic adrenocorticotropic hormone (ACTH). The typical response is an elevation in plasma cortisol levels. In Addison's disease, there is either an absence of cortisol elevation or merely a negligible increase.
Prognosis: Favorable if diagnosis is established and lifetime replacement medication is initiated with synthetic glucocorticoid (hydrocortisone) and mineralocorticoid (fludrocortisone). It is essential for patients to comprehend the necessity of augmenting their hydrocortisone dosage throughout any concurrent illness. 3 Untreated or inadequately treated Addison's disease may lead to abrupt adrenal failure ('Addisonian crisis'), characterized by a perilous combination of hypovolemic shock, significant hypoglycemia, and hyponatremia
Definition: Primary adrenocortical insufficiency. Epidemiology • Uncommon, with an estimated annual incidence of 1 in 100,000 individuals. • The majority of instances occur in young to middle-aged adults. • Women are disproportionately impacted compared to men.
Etiology • Autoimmune degradation in industrialized nations. • Disseminated TB in underdeveloped nations. • Alternative etiologies, such as adrenal metastases, are infrequent.
Pathogenesis • Addison's disease results in a significant deficiency of glucocorticoid and mineralocorticoid synthesis by the adrenal cortex.
Clinical manifestations do not become apparent until approximately 90% of the gland has been obliterated.
Presentation: Fatigue, lethargy, and debilitation. • Anorexia, nausea, emesis, and diarrhea. • Weight loss may be significant.
The clinical appearance is frequently subtle and non-specific, complicating the diagnosis.
Biochemistry • Sodium and potassium levels. • Urea concentration resulting from dehydration. • As much as fifty percent of patients have hypoglycemia. • Circulating anti-adrenal autoantibodies are frequently observed. Diagnosis • Individuals suspected of having Addison’s disease should undergo dynamic adrenal cortex testing via a Synacthen test. This entails an intramuscular injection of synthetic adrenocorticotropic hormone (ACTH). The typical response is an elevation in plasma cortisol levels. In Addison's disease, there is either an absence of cortisol elevation or merely a negligible increase.
Prognosis: Favorable if diagnosis is established and lifetime replacement medication is initiated with synthetic glucocorticoid (hydrocortisone) and mineralocorticoid (fludrocortisone). It is essential for patients to comprehend the necessity of augmenting their hydrocortisone dosage throughout any concurrent illness. 3 Untreated or inadequately treated Addison's disease may lead to abrupt adrenal failure ('Addisonian crisis'), characterized by a perilous combination of hypovolemic shock, significant hypoglycemia, and hyponatremia
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Pathology - Neuroblastoma
Definition • A malignant pediatric tumor originating from neural crest-derived cells of the sympathetic nervous system. Most originate in the adrenal medulla or paraspinal sympathetic ganglia.
Epidemiology: The third most prevalent malignant neoplasm in pediatric populations. • Incidence of 1 in 10,000 live births annually. • Predominantly occur throughout the first four years of life.
Aetiology: Unknown. Genetics • Tumor genetics possess significant prognostic consequences. Amplification of MYCN, diploidy, and deletions on chromosome 1p are all correlated with a worse prognosis. Presentation • The majority of children exhibit symptoms of illness characterized by weight loss, fever, watery diarrhea, and a discernible abdominal mass. Biochemistry • Elevated urinary levels of catecholamines and their metabolites, vanillylmandelic acid (VMA) and homovanilic acid (HMA), serve as a significant diagnostic tool. Macroscopy • A lobulated, soft, gray tumor mass of approximately 6–8 cm, closely associated with the adrenal gland or sympathetic chain.
Histopathology • Neuroblastoma is classified into four categories based on the degree of development of primitive neuroblasts into ganglion cells. • Undifferentiated neuroblastoma consists of undifferentiated neuroblasts lacking any signs of ganglionic differentiation. They resemble several other 'small round blue cell tumors' of childhood, necessitating other procedures to confirm the diagnosis (e.g., antibody for brain markers such as CD56 and synaptophysin). Poorly differentiated neuroblastoma exhibits minimal ganglionic differentiation (<5% of cells) and comprises neurofibrillary stroma. • differentiated neuroblastoma numerous ganglionic cells (> 5%, but
Definition • A malignant pediatric tumor originating from neural crest-derived cells of the sympathetic nervous system. Most originate in the adrenal medulla or paraspinal sympathetic ganglia.
Epidemiology: The third most prevalent malignant neoplasm in pediatric populations. • Incidence of 1 in 10,000 live births annually. • Predominantly occur throughout the first four years of life.
Aetiology: Unknown. Genetics • Tumor genetics possess significant prognostic consequences. Amplification of MYCN, diploidy, and deletions on chromosome 1p are all correlated with a worse prognosis. Presentation • The majority of children exhibit symptoms of illness characterized by weight loss, fever, watery diarrhea, and a discernible abdominal mass. Biochemistry • Elevated urinary levels of catecholamines and their metabolites, vanillylmandelic acid (VMA) and homovanilic acid (HMA), serve as a significant diagnostic tool. Macroscopy • A lobulated, soft, gray tumor mass of approximately 6–8 cm, closely associated with the adrenal gland or sympathetic chain.
Histopathology • Neuroblastoma is classified into four categories based on the degree of development of primitive neuroblasts into ganglion cells. • Undifferentiated neuroblastoma consists of undifferentiated neuroblasts lacking any signs of ganglionic differentiation. They resemble several other 'small round blue cell tumors' of childhood, necessitating other procedures to confirm the diagnosis (e.g., antibody for brain markers such as CD56 and synaptophysin). Poorly differentiated neuroblastoma exhibits minimal ganglionic differentiation (<5% of cells) and comprises neurofibrillary stroma. • differentiated neuroblastoma numerous ganglionic cells (> 5%, but
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Pathology- Iron deficiency anemia
Definition: A decrease in hemoglobin (Hb) concentration resulting from insufficient iron availability.
Epidemiology The predominant etiology of anemia. Etiology Chronic gastrointestinal blood loss is the predominant etiology. • Globally, this is typically associated with hookworm infection. • Frequent causes in affluent nations encompass peptic ulcers, gastric cancer, sigmoid diverticular disease, and colorectal carcinoma. Excessive menstrual bleeding in women may result in iron deficiency. Gastrointestinal disorders that lead to iron malabsorption can result in iron deficiency, such as celiac disease. 1 Excluding a gastrointestinal tract malignancy is essential in any adult patient presenting with unexplained iron deficiency anemia. Pathogenesis Iron is a vital component of the heme group in hemoglobin. Chronic iron deficiency disrupts the final stage in heme production.
Presentation • May be asymptomatic and identified with routine complete blood count. • Symptoms encompass fatigue and dyspnea during activity. • Certain cases may present with additional manifestations such as koilonychia, angular cheilitis, and glossitis. Complete blood count • reduced Hemoglobin. • reduced Mean corpuscular volume (MCV). • Decreased serum ferritin, decreased serum iron, decreased transferrin saturation, increased total iron binding capacity (TIBC).
Peripheral blood smear • Microcytic red blood cells. • Hypochromic pale red cells. • Heterogeneity in erythrocyte dimensions (anisocytosis) and morphology (poikilocytosis). • Elongated elliptical red blood cells, commonly referred to as 'pencil cells,' are frequently observed.
Bone marrow
Mild to moderate erythroid hyperplasia. • Lack of detectable iron
Definition: A decrease in hemoglobin (Hb) concentration resulting from insufficient iron availability.
Epidemiology The predominant etiology of anemia. Etiology Chronic gastrointestinal blood loss is the predominant etiology. • Globally, this is typically associated with hookworm infection. • Frequent causes in affluent nations encompass peptic ulcers, gastric cancer, sigmoid diverticular disease, and colorectal carcinoma. Excessive menstrual bleeding in women may result in iron deficiency. Gastrointestinal disorders that lead to iron malabsorption can result in iron deficiency, such as celiac disease. 1 Excluding a gastrointestinal tract malignancy is essential in any adult patient presenting with unexplained iron deficiency anemia. Pathogenesis Iron is a vital component of the heme group in hemoglobin. Chronic iron deficiency disrupts the final stage in heme production.
Presentation • May be asymptomatic and identified with routine complete blood count. • Symptoms encompass fatigue and dyspnea during activity. • Certain cases may present with additional manifestations such as koilonychia, angular cheilitis, and glossitis. Complete blood count • reduced Hemoglobin. • reduced Mean corpuscular volume (MCV). • Decreased serum ferritin, decreased serum iron, decreased transferrin saturation, increased total iron binding capacity (TIBC).
Peripheral blood smear • Microcytic red blood cells. • Hypochromic pale red cells. • Heterogeneity in erythrocyte dimensions (anisocytosis) and morphology (poikilocytosis). • Elongated elliptical red blood cells, commonly referred to as 'pencil cells,' are frequently observed.
Bone marrow
Mild to moderate erythroid hyperplasia. • Lack of detectable iron
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Pathology - Pituitary adenoma
Definition • A benign epithelial neoplasm of the anterior pituitary gland. • The majority are functioning tumors that excessively secrete prolactin, growth hormone (GH), or adrenocorticotropic hormone (ACTH), in that order of prevalence. • Functional adenomas that produce thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), or luteinizing hormone (LH) are exceedingly rare.
Epidemiology: Rare, having an incidence of 1 in 100,000 annually. • Predominantly occur in middle-aged individuals. • Women are more frequently afflicted than males.
Aetiology • Predominantly unknown in most instances. A minor percentage is observed in conjunction with hereditary tumor disorders, such as MEN. 1. Genetics • The two most well-characterized genetic anomalies are MEN 1 and gsp, a mutation in the G-protein alpha subunit.
Presentation • Characteristics of endocrine hyperfunction vary according to the hormone produced, such as galactorrhea and sexual dysfunction in prolactin-secreting cases, acromegaly in growth hormone-secreting instances, or Cushing's syndrome in adrenocorticotropic hormone-secreting scenarios. • Large adenomas can induce mass effect symptoms, including headache, nausea, and visual field disturbances, due to compression of the optic chiasm. • Numerous people may exhibit symptoms and indications of hypopituitarism, but it is infrequently the presenting complaint.
Macroscopy: Pituitary adenomas are soft tumors that can be classified as small microadenomas (less than 10 mm in size) or bigger macroadenomas (greater than 10 mm in size). Histopathology The tumors consist of solid nests or trabeculae of neoplastic cells characterized by homogeneous round nuclei, stippled chromatin, and subtle nucleoli. Immunohistochemistry employing antibodies targeting prolactin, growth hormone, and adrenocorticotropic hormone can be utilized to ascertain the hormone synthesized by the tumor. Prognosis: Generally favorable after suitable medicinal or surgical intervention, although some patients may experience recurrences. 2 The endocrine repercussions of these tumors may, however, yield significant consequences, such as cardiovascular disease in acromegaly.
Definition • A benign epithelial neoplasm of the anterior pituitary gland. • The majority are functioning tumors that excessively secrete prolactin, growth hormone (GH), or adrenocorticotropic hormone (ACTH), in that order of prevalence. • Functional adenomas that produce thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), or luteinizing hormone (LH) are exceedingly rare.
Epidemiology: Rare, having an incidence of 1 in 100,000 annually. • Predominantly occur in middle-aged individuals. • Women are more frequently afflicted than males.
Aetiology • Predominantly unknown in most instances. A minor percentage is observed in conjunction with hereditary tumor disorders, such as MEN. 1. Genetics • The two most well-characterized genetic anomalies are MEN 1 and gsp, a mutation in the G-protein alpha subunit.
Presentation • Characteristics of endocrine hyperfunction vary according to the hormone produced, such as galactorrhea and sexual dysfunction in prolactin-secreting cases, acromegaly in growth hormone-secreting instances, or Cushing's syndrome in adrenocorticotropic hormone-secreting scenarios. • Large adenomas can induce mass effect symptoms, including headache, nausea, and visual field disturbances, due to compression of the optic chiasm. • Numerous people may exhibit symptoms and indications of hypopituitarism, but it is infrequently the presenting complaint.
Macroscopy: Pituitary adenomas are soft tumors that can be classified as small microadenomas (less than 10 mm in size) or bigger macroadenomas (greater than 10 mm in size). Histopathology The tumors consist of solid nests or trabeculae of neoplastic cells characterized by homogeneous round nuclei, stippled chromatin, and subtle nucleoli. Immunohistochemistry employing antibodies targeting prolactin, growth hormone, and adrenocorticotropic hormone can be utilized to ascertain the hormone synthesized by the tumor. Prognosis: Generally favorable after suitable medicinal or surgical intervention, although some patients may experience recurrences. 2 The endocrine repercussions of these tumors may, however, yield significant consequences, such as cardiovascular disease in acromegaly.
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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 - 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 - 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 - Thrombotic thrombocytopenic purpura
Definition: A thrombotic microangiopathy resulting from a deficiency of ADAMTS13.
Epidemiology • Uncommon.
Aetiology
Inherited instances result from genetic mutations in ADAMTS13. Sporadic cases result from autoantibodies targeting ADAMTS13.
Pathogenesis ADAMTS13 is a metalloproteinase that cleaves von Willebrand factor (vWF) into smaller fragments.
Deficiency of ADAMTS13 results in the accumulation of ultra-high molecular weight variants of vWF, which adhere to endothelial cells and promote microthrombus development in tiny arteries.
Microthrombi induce organ dysfunction, particularly impacting the brain and kidneys. • Platelets are swiftly depleted in the microthrombi, resulting in thrombocytopenia. Red blood cells traversing the microthrombi are fragmented, resulting in anemia.
Clinical Manifestation • Pyrexia, petechial rash, and hemorrhage. • Neurological manifestations are generally pronounced. • Acute renal failure may also manifest. Hematology • Decreased hemoglobin with normal mean corpuscular volume. •
Reticulocyte count. • Platelet count. • Standard coagulation. Blood film • Anisocytosis of red blood cells. • Notable schistocytes (fragmented erythrocytes).
Prognosis: Survival rates range from 80% to 90% with prompt diagnosis and plasma exchange. Approximately one-third of individuals experience relapses within two years.
Definition: A thrombotic microangiopathy resulting from a deficiency of ADAMTS13.
Epidemiology • Uncommon.
Aetiology
Inherited instances result from genetic mutations in ADAMTS13. Sporadic cases result from autoantibodies targeting ADAMTS13.
Pathogenesis ADAMTS13 is a metalloproteinase that cleaves von Willebrand factor (vWF) into smaller fragments.
Deficiency of ADAMTS13 results in the accumulation of ultra-high molecular weight variants of vWF, which adhere to endothelial cells and promote microthrombus development in tiny arteries.
Microthrombi induce organ dysfunction, particularly impacting the brain and kidneys. • Platelets are swiftly depleted in the microthrombi, resulting in thrombocytopenia. Red blood cells traversing the microthrombi are fragmented, resulting in anemia.
Clinical Manifestation • Pyrexia, petechial rash, and hemorrhage. • Neurological manifestations are generally pronounced. • Acute renal failure may also manifest. Hematology • Decreased hemoglobin with normal mean corpuscular volume. •
Reticulocyte count. • Platelet count. • Standard coagulation. Blood film • Anisocytosis of red blood cells. • Notable schistocytes (fragmented erythrocytes).
Prognosis: Survival rates range from 80% to 90% with prompt diagnosis and plasma exchange. Approximately one-third of individuals experience relapses within two years.
