ERS14 16 Pathology Of Endocrine Disorders I + II Flashcards
Basic ideas of Endocrine system
- Set of glands
- Maintain homeostasis by secreting hormones directly into blood to reach target organs
- Autocrine / Paracrine / Endocrine
Histology of Endocrine glands
- Similar normal histology (regardless of anatomical location)
—> similar arrangement + morphology - ***Nest / Packets of endocrine cells
- Granular cytoplasm with secretory granules
- ***Rich vasculature
Pathologies of Endocrine system
- Functional vs Non-functional
- Hyper / Hypo-function - Neoplastic vs Non-neoplastic
- Benign / Malignant
—> difficult to tell definitely benign / malignant by histology alone
—> integration of Clinical and Pathological findings to arrive diagnosis
Pituitary gland
Anterior lobe (Adenohypophysis) + Posterior lobe (Neurohypophysis) - Histologically distinct
Anterior lobe:
- Positive-acting releasing factors from Hypothalamus except for Prolactin
- ***Nest / Packets of endocrine cells
- Granular cytoplasm with secretory granules
- Rich vasculature
- Acidophils: Somatotroph, Lactotroph
- Basophils: Corticotroph, Thyrotroph, Gonadotroph
- Chromophobes
Posterior lobe:
- **Modified glial cells (Pituicytes) + **Nerve fibres from Hypothalamus
- Less capillaries
- ADH + Oxytocin
Pituitary disorders
- Hyper / Hypopituitarism
—> Hyper / Hypo excess secretion of adenohypophyseal hormones - Endocrine / Local mass effects
Pituitary adenoma (Hyperpituitarism)
- In Adults
- Benign
Classification: - Macroadenoma (> 1cm) / Microadenoma (< 1cm) - Histological cell type —> Lactotroph —> Galactorrhea, Menstrual disturbances —> Somatotroph —> Gigantism / Acromegaly —> Corticotroph —> Cushing’s disease —> Thyrotroph (rare) —> Gonadotroph (rare)
Gross appearance:
- In Sella turcica
- Well circumscribed
Histology:
- Uniform polygonal cells arranged in sheets / cords
- Rare mitosis
- Round regular nuclei
- Little polymorphism (Monotonous)
—> Immunostain: Synaptophysin (staining for endocrine differentiation)
Hypopituitarism
Loss of parenchymal tissue of Pituitary
Causes:
- Tumour / mass lesion (adjacent compression to structure)
- Surgery / radiation
- Trauma
- Ischaemic necrosis, Sheehan syndrome
- Infection / inflammation
Posterior pituitary: Oxytocin + ADH
Oxytocin:
- Contraction of uterine smooth muscle at pregnancy
- Contraction of smooth muscle around lactiferous ducts of mammary glands at lactation
ADH:
- ↓ BP / ↑ Plasma osmotic pressure (high salt) —> ADH release
- Converse water by restricting diuresis
- ↑ Permeability of renal collecting ducts
- ADH deficiency —> Diabetes insipidus
Case 1:
- 40 yo female
- past medical history endometriosis + haemorrhoids
- acromegalic features for 2 years
- coarsening of facial features + shoe size increase
Investigations:
1. P/E: large nose, spade-like hands
- Blood test (anterior pituitary):
- GH ↑
- TSH, Prolactin, LH, FSH, Cortisol normal - Skull X-ray:
- enlarged pituitary fossa - MRI brain:
- 1.2 cm hypo-enhancing nodule in right side of pituitary gland —> suggestive of pituitary adenoma - Transphenoidal (through sphenoid sinus) resection of pituitary tumour with intra-operative frozen section are arranged
- Toludine blue: stain chromosomes - Immunostain: Stain with GH Ab —> diffuse positive staining in cytoplasm
Diagnosis: Pituitary adenoma
Pancreas
Exocrine + Endocrine components
Endocrine components:
Islets of Langerhans
- β (Insulin), α (Glucagon), δ (Somatostatin), PP (pancreatic polypeptide) cells
- intermixed with exocrine components (acini)
Diabetes Mellitus
Abnormal metabolic state characterised by glucose intolerance due to inadequate insulin action
Biochemical features:
- Inability to utilise + overproduction of glucose
- ↓ Protein synthesis
- Lipolysis —> Hyperlipidaemia
Type 1:
- childhood
- inadequate insulin secretion
Type 2:
- middle age onset
- ↓ sensitivity to insulin
Histology:
- ***↓ Number + Size of islets
- ***Leukocytic infiltrate in islets (Insulitis) —> T cells + Eosinophils
- Amyloid deposition within islets, around capillaries / between cells (Type 2 DM)
Pancreas: Islet cell tumours
Functional / Non-functional (asymptomatic)
-
Functional:
1. Insulinoma —> Hypoglycaemia
2. Glucagonoma —> Secondary diabetes
3. Gastrinoma —> Severe peptic ulcer (Zollinger-Ellison syndrome) (G cells in pancreas secrete Gastrin)
4. VIPoma (**vasoactive intestinal peptide) —> Water diarrhoea
Histology:
- Arranged in ribbons + anastomosing trabeculae
- Richly vascularised
- Round nuclei, Fine chromatin, Eosinophilic cytoplasm (Monotonous cell)
***Adrenal glands
Cortex:
- derived from ***mesoderm
- Zona glomerulosa (closest to capsule) —> Mineralocorticoid
- Zona fasciculata —> Glucocorticoid
- Zona reticularis —> Sex steroids
Medulla:
- derived from ***neural crest, part of SNS
- Chromaffin cells (rich in Sympathetic nerve endings)
- Catecholamines (mainly E) synthesis + secretion
Adrenal gland Hypofunction
- Primary / Secondary:
Primary: Etiology in adrenal gland
Secondary: Etiology resides higher up in axis - Acute / Chronic
- Acute primary insufficiency (Waterhouse-Friderichsen syndrome):
- Overwhelming bacterial infection
- Rapidly progression to hypotension + shock
- DIC
- Massive adrenal haemorrhage - Chronic primary adrenocortical insufficiency (Addison’s disease):
Causes (destroy normal parenchyma of adrenal cortex):
- Autoimmune adrenalitis
- TB / other infections
- Amyloidosis
- Metastatic cancers
***Adrenal gland Hyperfunction
- Hyperplasia
- Cortical adenomas
- Phaeochromocytoma (tumour in adrenal ***medulla)
Example:
1. Cushing’s syndrome (Glucocorticoid hypersecretion)
- Central obesity, Hypertension, DM, Osteoporosis
- Causes:
—> Adrenal cortical neoplasm (e.g. adenoma)
—> Excess ACTH by pituitary —> Excess adrenal androgens —> Hirsutism
—> Iatrogenic effects (ACTH / steroid administration)
- Conn’s syndrome / Primary aldosteronism (Mineralocorticoid hypersecretion)
- Autonomous secretion of excess Aldosterone (Primary)
- Causes: Cortical adenoma - Secondary aldosteronism
- Causes: ↓ Glomerular perfusion (may due to ↓ CO)
—> Stimulation of RAAS system
—> ↑ Aldosterone secretion (try to conserve Na, H2O)
***Adrenal gland Neoplasms
Cortex:
- Adenoma / Adrenocortical adenoma (benign)
- Carcinoma / Adrenocortical carcinoma (malignant)
Medulla:
- Phaeochromocytoma
- Neuroblastoma
Cortical adenoma
Histology:
- cells arranged in packets
- rich vasculature
- granular cytoplasm
- central regular nuclei
- fine chromatin
- pale to clear cytoplasm
Phaeochromocytoma (Adrenal medulla)
- Peak at 40-60 yo
- ↑↑ Sympathetic response: Hypertension, Tachycardia, Palpitations, Headache, Sweating, Tremor, Sense of apprehension
- Diagnosis: ↑ urine Catecholamines + Vanillylmandelic acid
- Complication: MI due to vasoconstriction
Gross appearance:
- Pale gray / brown
- Haemorrhage, Necrosis, Cystic change
Histology (resemble endocrine glands):
- Zellballen / Trabecular / Solid pattern
- Polygonal / Spindle cells
- Rich vascular network
- Finely granular basophilic / amphophilic cytoplasm (“dirty blue” cytoplasm)
- Vague packets
Neuroblastoma (Adrenal medulla)
- Malignant
- Infants, children before 3
- Often metastasise
- Histology (NO classical appearance): ***Small blue round cell tumour (primitive appearance)
Case 2:
- 48 yo teacher
- hypertension, hyperlipidaemia
- incidental finding of right adrenal mass (2cm)
- BP 130/90
- BMI 26
- 24 hour urine free cortisol: ↑
- ONDST: non-suppressive
- Aldosterone: normal
ONDST: non-suppressive
—> ONDST: suppress ACTH
—> If non-suppressive (i.e. Cortisol still high) —> 唔關ACTH事
Right Adrenalectomy:
- 15.6g
- 5x4x2 cm
- Cut section: 2cm nodule with golden yellow surface
Histology:
- lesion in Cortex
- packets of cells
- round regular nuclei
- fine chromatin
- granular cytoplasm
- rich vasculature
Diagnosis: Adrenocorticol adenoma
Thyroid gland
Histology:
- Lobules divided by thin fibrous septa
- Each lobule consists of 20-40 follicles
- Follicles lined by cuboidal / low columnar epithelium: Follicular cells
- Parafollicular cells (C cells): Calcitonin
Thyroid gland pathologies
- Hyperplasia (Diffuse / Nodular goitre)
- Adenoma
- Carcinoma
Diffuse simple goitre, Multinodular goitre
Diffuse nontoxic (simple) goitre
- Involves entire gland (Both lobes)
- Endemic goitre due to **Iodine deficiency and **compensatory TSH ↑ (e.g. ***Primary Hypothyroidism)
- Nodular appearance on external surface
Multinodular goitre
- Prominent nodular formations (macroscopic, microscopic)
- Multi-lobulated enlarged glands
- Asymmetrical lobes (often)
Histology:
- ***~ Normal gland
- Variably sized colloid-filled follicles
- Nodular hyperplasia (much bigger sized colloids)
Clinical symptoms:
- Toxic / Non-toxic
- Euthyroid / Subclinical hyperthyroidism
- Pressure symptoms
- Cosmetic effects
Thyroid gland Neoplasms
Benign
1. Follicular adenoma
Malignant (collectively called Thyroid cancers)
1. Papillary carcinoma (>85%)
2. Follicular carcinoma (5-15%)
3. Anaplastic (poorly differentiated) carcinoma (<5%)
4. Medullary carcinoma (arise from ***Parafollicular cells) (5%)
—> all similar macroscopically —> need histological confirmation
Follicular adenoma
- Discrete solitary mass
- From Follicular cells
- Nodular enlargement (~ Multinodular goitre but ONLY with ***SINGLE nodule / mass)
- Most ***non-functional (NO hypersecretion of thyroid hormone, only a mass)
- Benign version of Follicular carcinoma
Histology:
- ***Encapsulated nodule (must have capsule)
- Colloid-containing follicles / microfollicles
- Mild cytological atypia
- No capsular / vascular invasion (distinguish from Follicular carcinoma)
- Absence of papillary carcinoma features
- Hurthle cell / Oncocytic change (sometimes)
Papillary carcinoma
- Young, 25-50 yo
- Risk factor: Ionising radiation exposure
Clinical symptoms:
- Asymptomatic thyroid nodules (~ goitre, adenoma)
- Mass in cervical LN (nodal metastasis)
- Pressure symptoms: hoarseness, dysphagia, cough, dyspnea in advanced disease
Other characteristics:
- may present as Multifocal tumours (multiple tumour nodules at the same time involving both lobes ~ Multinodular goitre)
- prone to ***Lymphatic metastasis (vs Follicular carcinoma: via Bloodstream)
- excellent prognosis (10 year survival rate >95%)
- prognostic factors: age, stage/metastasis, extra-thyroidal extension (by imaging / histological examination)
Histology:
- ***Nuclear inclusions (defining feature)
- ***Nuclear grooves (defining feature) (internal folding of nuclear envelope)
- Overlapping ***ground-glass nuclei
- ***Psammoma bodies
- ***Multinucleated giant cells
- Papillary structures (sometimes not prominent)
Follicular carcinoma
- 40-60 yo
- Prone to ***Haematogenous metastasis (bone, liver, lungs) (LN metastasis rare)
Histology (Malignant version of Follicular adenoma):
- Encapsulated
- Colloid-containing follicles / microfollicles
- Cytological atypia (can be mild)
- ***Capsular / Vascular invasion (defining malignancy, distinguish from Follicular adenoma)
Anaplastic carcinoma
- Also called undifferentiated carcinoma
- Mortality rate ~100%
- 65 yo
- Preceding / Concurrent well-differentiated Thyroid carcinoma (progress to undifferentiated)
Histology:
- Markedly Pleomorphic cells / Spindle cells
Medullary carcinoma
- From Parafollicular C cells
- 70% sporadic; 30% as part of MEN syndrome
Histology:
- ~ Typical endocrine histology (packets of cells, vasculature etc.)
- ***NO follicles (∵ not originate from Follicular cells)
- ***Immunostain for Calcitonin (tumour cells still functionally secreting Calcitonin)
Case 3:
- 59 yo female
- clear cell carcinoma of ovary with operation and adjuvant chemotherapy done
- presents with multinodular goitre
- TSH, T4 normal
- Total Thyroidectomy done (∵ size, cosmetic reasons)
Gross specimen:
- Multiple colloid nodules
- Largest one measures 1.5cm located in left lower pole
- A separate 0.5cm well circumscribed nodule with tan cut surface noted in left mid pole
- 5 cm nodule:
- ~ Normal gland
- Variably sized colloid-filled follicles
- Nodular hyperplasia (much bigger sized colloids) - 5 cm nodule:
- **Nuclear inclusions
- **Multinucleated giant cells
Diagnosis: Incidental Papillary carcinoma in background of Mutilnodular hyperplasia (not a risk factor for Papillary carcinoma)
Multiple Endocrine Neoplasia (MEN) syndromes
- Clinical syndrome
- A group of genetically inherited diseases resulting from proliferative lesions (hyperplasia, adenomas, carcinomas) of multiple endocrine organs
Characteristics:
- Younger age
- ***Multiple organs
- ***Multifocal
- Synchronous / Metachronous
Significance:
- Diagnosis is possible with molecular technologies (∵ genetic in nature)
- More aggressive + Recur (compared to sporadic tumours)
- May want to screen family members
2 types
MEN1 (Wermer Syndrome)
- Defective gene: MEN1 encoding MENIN protein
1. Pituitary: Adenoma (frequency Prolactinoma)
2. Parathyroid: Adenoma / Hyperplasia
3. Pancreas: Islet cell tumours
(記: PPP)
MEN2A - Defective gene: RET 1. Thyroid: Medullary carcinoma 2. Adrenal: Phaeochromocytoma 3. Parathyroid: Hyperplasia (記: TAP)
MEN2B - Defective gene: RET 1. Thyroid: Medullary carcinoma 2. Adrenal: Phaeochromocytoma 3. GI tract / Skin / Respiratory tract etc.: Neuromas, Ganglioneuromas (記: TAG)
