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Pathology - Thyroid carcinomas
Definition • A collection of malignant epithelial tumors originating in the thyroid gland. Four principal kinds are identified: papillary, follicular, medullary, and anaplastic.
Epidemiology • Rare, constituting around 1% of all cancers in wealthy nations. The average age of diagnosis is mid-40s to early 50s for the papillary type, 50s for the follicular and medullary forms, and 60s for the anaplastic type. Aetiology • Radiation exposure is a recognized risk factor for thyroid carcinoma, particularly papillary carcinoma. Iodine deficiency is also a contributing factor, especially in follicular carcinomas. Approximately 25% of medullary carcinomas are associated with inherited disorders, specifically multiple endocrine neoplasia (MEN) types 2A and 2B, as well as familial medullary thyroid cancer (FMTC).
Carcinogenesis: RET and TRK mutations are characteristic of papillary carcinomas. Follicular carcinomas typically exhibit RAS mutations. TP53 mutations are prevalent in anaplastic carcinomas. Presentation: Most well-differentiated thyroid carcinomas manifest as a solitary thyroid nodule. Thyroid function is typically normal.
Anaplastic carcinoma typically manifests as a swiftly expanding cervical mass; encroachment on adjacent structures results in hoarseness, dysphagia, and dyspnea. Macroscopy: Papillary carcinomas typically present as firm, grey-white lumps with uneven boundaries. They are frequently multifocal.
Follicular carcinomas are typically encapsulated, spherical solid tumors exhibiting a tan to brown hue.
Medullary carcinomas are solid grey-white to tan tumors, frequently characterized by a gritty texture.
Anaplastic carcinomas are substantial necrotic tumors that typically supplant the thyroid and extensively infiltrate surrounding tissues.
Cytopathology
Papillary carcinoma aspirates comprise papillaroid fragments of follicular epithelial cells exhibiting the distinctive nuclear characteristics of papillary carcinoma, such as powdered chromatin, thick nuclear membranes, nuclear grooves, and nuclear pseudoinclusions. Multinucleated giant cells, psammoma bodies, and dense colloid may be observed.
Follicular carcinoma aspirates are cellular, comprising follicular epithelial cells found individually and in microfollicular configurations. It is important to note that these appearances are indistinguishable from follicular adenomas; cytological analysis cannot differentiate between these entities
Medullary carcinoma aspirates are cellular, with loosely cohesive epithelial cells that may be either round or spindle-shaped. Certain cells may have eccentric nuclei, resulting in a plasmacytoid morphology. The nuclei have coarsely granular chromatin. Amyloid fragments may be observed.
Anaplastic carcinoma aspirates have considerable cellularity, with significantly abnormal malignant cells.
Histopathology
Papillary carcinoma is characterized by distinct nuclear features: oval form, overlapping, chromatin clearance, nuclear grooves, and pseudoinclusions. While the majority of tumors exhibit a papillary form, this characteristic is not essential for diagnosis.
Follicular carcinoma is an invasive follicular tumor devoid of the nuclear characteristics associated with papillary thyroid carcinoma. Follicular carcinomas are categorized into two primary types: slightly invasive and broadly invasive.
Minimally invasive tumors have restricted capsular invasion and/or vascular invasion.
Extensively invasive tumors exhibit extensive infiltration of the thyroid and/or vascular structures.
Medullary carcinoma exhibits sheets, nests, or trabeculae of rounded or spindle-shaped neoplastic cells characterized by granular cytoplasm and nuclei containing coarse chromatin. Amyloid deposits may be observed. The diagnosis can be validated by immunoreactivity for calcitonin.
Anaplastic carcinomas consist of extremely pleomorphic epithelioid and spindle-shaped cells. Significant necrosis is observed, and vascular blockage by tumor is prevalent.
Prognosis: Papillary carcinomas and less invasive follicular carcinomas are low-grade malignancies characterized by an excellent prognosis. Extensively invasive follicular carcinomas and medullary carcinomas are intermediate-grade neoplasms associated with an elevated risk of metastasis and mortality. Anaplastic carcinomas are exceedingly malignant and nearly usually result in death within months of diagnosis.
TNM 7 pathological staging of thyroid carcinomas Primary tumour (T)
pT1a: tumour d 10mm in size, limited to the thyroid.
pT1b: tumour d 20mm, but > 10mm in size, limited to the thyroid.
pT2: tumour > 20mm, but d 40mm in size, limited to the thyroid.
pT3: tumour > 40mm in size, limited to thyroid, or any tumour with
minimal extrathyroid extension.
pT4a: tumour of any size extending beyond the thyroid capsule to
invade subcutaneous soft tissues, the larynx, trachea, oesophagus, or
recurrent laryngeal nerve.
pT4b: tumour invades the prevertebral fascia, mediastinal vessels, or
encases the carotid artery.
2 Note that all anaplastic tumours are considered T4.
Regional lymph nodes (N)
pN0: no regional lymph node metastasis.
pN1a: metastases in level VI cervical lymph nodes.
pN1b: metastases in levels I–V cervical, retropharyngeal, or superior
mediastinal lymph nodes
Definition • A collection of malignant epithelial tumors originating in the thyroid gland. Four principal kinds are identified: papillary, follicular, medullary, and anaplastic.
Epidemiology • Rare, constituting around 1% of all cancers in wealthy nations. The average age of diagnosis is mid-40s to early 50s for the papillary type, 50s for the follicular and medullary forms, and 60s for the anaplastic type. Aetiology • Radiation exposure is a recognized risk factor for thyroid carcinoma, particularly papillary carcinoma. Iodine deficiency is also a contributing factor, especially in follicular carcinomas. Approximately 25% of medullary carcinomas are associated with inherited disorders, specifically multiple endocrine neoplasia (MEN) types 2A and 2B, as well as familial medullary thyroid cancer (FMTC).
Carcinogenesis: RET and TRK mutations are characteristic of papillary carcinomas. Follicular carcinomas typically exhibit RAS mutations. TP53 mutations are prevalent in anaplastic carcinomas. Presentation: Most well-differentiated thyroid carcinomas manifest as a solitary thyroid nodule. Thyroid function is typically normal.
Anaplastic carcinoma typically manifests as a swiftly expanding cervical mass; encroachment on adjacent structures results in hoarseness, dysphagia, and dyspnea. Macroscopy: Papillary carcinomas typically present as firm, grey-white lumps with uneven boundaries. They are frequently multifocal.
Follicular carcinomas are typically encapsulated, spherical solid tumors exhibiting a tan to brown hue.
Medullary carcinomas are solid grey-white to tan tumors, frequently characterized by a gritty texture.
Anaplastic carcinomas are substantial necrotic tumors that typically supplant the thyroid and extensively infiltrate surrounding tissues.
Cytopathology
Papillary carcinoma aspirates comprise papillaroid fragments of follicular epithelial cells exhibiting the distinctive nuclear characteristics of papillary carcinoma, such as powdered chromatin, thick nuclear membranes, nuclear grooves, and nuclear pseudoinclusions. Multinucleated giant cells, psammoma bodies, and dense colloid may be observed.
Follicular carcinoma aspirates are cellular, comprising follicular epithelial cells found individually and in microfollicular configurations. It is important to note that these appearances are indistinguishable from follicular adenomas; cytological analysis cannot differentiate between these entities
Medullary carcinoma aspirates are cellular, with loosely cohesive epithelial cells that may be either round or spindle-shaped. Certain cells may have eccentric nuclei, resulting in a plasmacytoid morphology. The nuclei have coarsely granular chromatin. Amyloid fragments may be observed.
Anaplastic carcinoma aspirates have considerable cellularity, with significantly abnormal malignant cells.
Histopathology
Papillary carcinoma is characterized by distinct nuclear features: oval form, overlapping, chromatin clearance, nuclear grooves, and pseudoinclusions. While the majority of tumors exhibit a papillary form, this characteristic is not essential for diagnosis.
Follicular carcinoma is an invasive follicular tumor devoid of the nuclear characteristics associated with papillary thyroid carcinoma. Follicular carcinomas are categorized into two primary types: slightly invasive and broadly invasive.
Minimally invasive tumors have restricted capsular invasion and/or vascular invasion.
Extensively invasive tumors exhibit extensive infiltration of the thyroid and/or vascular structures.
Medullary carcinoma exhibits sheets, nests, or trabeculae of rounded or spindle-shaped neoplastic cells characterized by granular cytoplasm and nuclei containing coarse chromatin. Amyloid deposits may be observed. The diagnosis can be validated by immunoreactivity for calcitonin.
Anaplastic carcinomas consist of extremely pleomorphic epithelioid and spindle-shaped cells. Significant necrosis is observed, and vascular blockage by tumor is prevalent.
Prognosis: Papillary carcinomas and less invasive follicular carcinomas are low-grade malignancies characterized by an excellent prognosis. Extensively invasive follicular carcinomas and medullary carcinomas are intermediate-grade neoplasms associated with an elevated risk of metastasis and mortality. Anaplastic carcinomas are exceedingly malignant and nearly usually result in death within months of diagnosis.
TNM 7 pathological staging of thyroid carcinomas Primary tumour (T)
pT1a: tumour d 10mm in size, limited to the thyroid.
pT1b: tumour d 20mm, but > 10mm in size, limited to the thyroid.
pT2: tumour > 20mm, but d 40mm in size, limited to the thyroid.
pT3: tumour > 40mm in size, limited to thyroid, or any tumour with
minimal extrathyroid extension.
pT4a: tumour of any size extending beyond the thyroid capsule to
invade subcutaneous soft tissues, the larynx, trachea, oesophagus, or
recurrent laryngeal nerve.
pT4b: tumour invades the prevertebral fascia, mediastinal vessels, or
encases the carotid artery.
2 Note that all anaplastic tumours are considered T4.
Regional lymph nodes (N)
pN0: no regional lymph node metastasis.
pN1a: metastases in level VI cervical lymph nodes.
pN1b: metastases in levels I–V cervical, retropharyngeal, or superior
mediastinal lymph nodes
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Pathology - Parathyroid hyperplasia
Definition: An augmentation of parathyroid cell mass without an identifiable trigger.
Epidemiology • Rare, constituting around 20% of primary hyperparathyroidism. • Women are impacted more significantly than men, at a ratio of 3:1.
Aetiology • The majority of patients exhibit sporadic hyperplasia without a discernible etiology. • Approximately 20% of cases are attributed to family illness, predominantly Multiple Endocrine Neoplasia (MEN). 1.
Pathogenesis • Parathyroid hyperplasia results in excessive secretion of parathyroid hormone (PTH). Elevated PTH levels induce hypercalcemia via enhancing calcium absorption from the gastrointestinal tract and kidneys, as well as by augmenting osteoclastic activity in bone.
Presentation • individuals exhibit primary hyperparathyroidism, a biochemical illness characterized by hypercalcemia and an abnormally normal or elevated PTH level. • Numerous individuals are asymptomatic when this condition is identified accidentally. • Some individuals may exhibit nonspecific symptoms such as tiredness, nausea, constipation, polyuria, and arthralgia.
Macroscopy • All parathyroid glands exhibit hypertrophy, with weights exceeding 60 mg and dimensions surpassing 6 mm, but with variability among the glands.
Histopathology • The principal characteristic is an augmentation of cellular mass within the gland, correlated with a reduction in adipose content. • Typically, there is an elevation in both primary and oncocytic cell types. Secondary fibrosis and hemorrhage are prevalent observations.
Prognosis: Excellent after subtotal parathyroidectomy.
Definition: An augmentation of parathyroid cell mass without an identifiable trigger.
Epidemiology • Rare, constituting around 20% of primary hyperparathyroidism. • Women are impacted more significantly than men, at a ratio of 3:1.
Aetiology • The majority of patients exhibit sporadic hyperplasia without a discernible etiology. • Approximately 20% of cases are attributed to family illness, predominantly Multiple Endocrine Neoplasia (MEN). 1.
Pathogenesis • Parathyroid hyperplasia results in excessive secretion of parathyroid hormone (PTH). Elevated PTH levels induce hypercalcemia via enhancing calcium absorption from the gastrointestinal tract and kidneys, as well as by augmenting osteoclastic activity in bone.
Presentation • individuals exhibit primary hyperparathyroidism, a biochemical illness characterized by hypercalcemia and an abnormally normal or elevated PTH level. • Numerous individuals are asymptomatic when this condition is identified accidentally. • Some individuals may exhibit nonspecific symptoms such as tiredness, nausea, constipation, polyuria, and arthralgia.
Macroscopy • All parathyroid glands exhibit hypertrophy, with weights exceeding 60 mg and dimensions surpassing 6 mm, but with variability among the glands.
Histopathology • The principal characteristic is an augmentation of cellular mass within the gland, correlated with a reduction in adipose content. • Typically, there is an elevation in both primary and oncocytic cell types. Secondary fibrosis and hemorrhage are prevalent observations.
Prognosis: Excellent after subtotal parathyroidectomy.
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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- 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 - 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 - 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 - 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.
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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
