Pathology Prac.

Theme 2.5

Department of
Anatomical Pathology

Date: 16/08/2021
All 3 three lectures are covered as part
of the Prac:
1.Diseases of the Thyroid

2.Pathology of the Hypothalamus and the

Pituitary Gland

3.Osteoporosis, Osteomalacia, Rickets

• .. First lecture

Diseases of the Thyroid

Thyroid anatomy
• Location
Below and anterior to the larynx
• Two bulky lateral lobes
• Central thin isthmus
• Divided into lobules
- Fibrous septae
Thyroid histology
• Lobules composed of 20-40 evenly dispersed follicles
• Follicles lined by a cuboidal to low columnar epithelium
• Filled with PAS-positive colloid (thyroglobulin)
Physiology
• Secretion of thyroid hormones (T3 & T4)
• Controlled by hypothalamus and the anterior pituitary
• ↓ T3 and T4 levels
╚ Hypothalamus - Thyrotropin-releasing hormone (TRH)
╚ Anterior pituitary - thyroid- stimulating hormone
(TSH)
╚ TSH binds to the TSH receptor - thyroid follicular
epithelium
╚ Synthesis and release of thyroid hormones T3 and T4

• ↑T3 and T4 levels

• Feed back to suppress the secretion of both TRH and
TSH
Physiology
• Peripheral action of T3 and T4
╚ T3/4 - hormone-receptor complex with thyroid hormone receptor (TR)
╚ Complex translocates to the nucleus
╚ Binds to thyroid response elements (TREs) on target genes
╚ Regulates target gene transcription

• Diverse effects
o Up-regulation of carbohydrate and lipid catabolism
o Stimulation of protein synthesis
o Net result : increase in the basal metabolic rate

• In addition
• Plays critical role in brain development in the fetus and neonate
Physiology
• Thyroid gland follicles also contain
• Parafollicular cells / C cells

• Function
• synthesize and secrete calcitonin (hormone)
• Promotes the absorption of calcium by the skeletal system
• And inhibits the resorption of bone by osteoclasts
Hyperthyroidism
• Thyrotoxicosis is a hypermetabolic state caused by elevated circulating levels of free T3 and T4

• Causes
• Hyperfunction (most common)
1. Diffuse hyperplasia; associated with Graves disease (85% of cases)
2. Hyperfunctional multinodular goiter
3. Hyperfunctional thyroid adenoma

• Oversupply
• Excessive release of preformed hormone
• Primary e.g. thyroiditis
• Secondary extrathyroidal source
Clinical features
• Clinical manifestations related to
• Hypermetabolic state due to excess hormone
• Overactivity of sympathetic nervous system

1. Skin
• Soft, warm, and flushed
• Increased blood flow and peripheral vasodilation
• Heat intolerance
• Increased sweating - higher levels of calorigenesis
• Heightened catabolic metabolism
• Weight loss despite increased appetite
Clinical features
2. Cardiac manifestations (earliest and most consistent)

• Elevated cardiac output

• Due to cardiac contractility or increased peripheral oxygen requirements
╚ Tachycardia, palpitations, cardiomegaly
╚ Arrhythmias (esp atrial fibrillation) frequent

• Congestive heart failure may develop

• Especially older patients
• Some individuals develop reversible left ventricular
dysfunction and “low-output” heart failure, so-called thyrotoxic
or hyperthyroid cardiomyopathy.
Clinical features
3. Neuromuscular system

• Sympathetic nervous system overactivity

• Tremor
• Hyperactivity
• Emotional lability
• Anxiety
• Inability to concentrate
• Insomnia

• Thyroid myopathy
• Proximal muscle weakness
• Decreased muscle mass

• GIT hyperstimulation
• Hypermotility
• Diarrhea
• Malabsorption
Clinical features
4. Ocular changes

• Wide, staring gaze

• Lid lag
• Sympathetic overstimulation of superior tarsal muscle

• True thyroid ophthalmopathy associated with proptosis occurs

only in Graves disease
Clinical features
5. Skeletal system
• Thyroid hormone stimulates bone resorption
• Increasing porosity of cortical bone
• Reducing volume of trabecular bone
• Net effect = osteoporosis

• Other findings
• Atrophy of skeletal muscle
• Fatty infiltration and focal interstitial lymphocytic infiltrates
Clinical features
6. Thyroid storm

• Abrupt onset of severe hyperthyroidism

• Most commonly in patients with Graves disease
• Results from an acute elevation in catecholamine levels
• Infection
• Surgery
• Cessation of antithyroid medication
• Any form of stress
• Clinical
• Often febrile
• Tachycardia out of proportion to fever

• Medical emergency
• Significant number of untreated patients die of cardiac arrhythmias
Causes
Diagnosis
• Using both clinical and laboratory findings:
• Serum TSH and T4
• Primary
• Increase T4 and decreased TSH
• Secondary
• Both TSH and T4 increased

• Followed by measurement of radioactive iodine uptake

by the thyroid gland can help to determine the aetiology

• Diffusely increased uptake : Graves disease

• Solitary nodule : toxic adenoma
• Decreased uptake : thyroiditis
Hypothyroidism
A condition caused by a structural or functional derangement that
interferes with the production of thyroid hormone.

• Fairly common

• Prevalence
• Overt hypothyroidism is 0.3%
• Subclinical hypothyroidism can be found in greater than
4%
• Increases with age

• Tenfold more common in women than in men

Primary and secondary forms
• Primary hypothyroidism

• Majority of cases
• May be accompanied by an enlargement in the size of the
thyroid gland (goiter)

• Congenital
• Autoimmune
• Iatrogenic
Congenital hypothyroidism
• Due to endemic iodine deficiency in the diet

• Rare forms
• Inborn errors of thyroid metabolism
• Absence of thyroid parenchyma - Thyroid agenesis
• Greatly reduced in size - thyroid hypoplasia
• (germline mutations in genes responsible for thyroid development)
Autoimmune hypothyroidism
• Most common cause of hypothyroidism in iodine sufficient areas of the world
• Majority - Hashimoto thyroiditis
• Circulating autoantibodies
• Anti- microsomal, antithyroid peroxidase, and antithyroglobulin Ab
• Thyroid is enlarged (goitrous)
Iatrogenic hypothyroidism
• Surgical resection
• treatment of hyperthyroidism or a primary neoplasm

• Radiation-induced ablation
• Radioiodine – treatment of hyperthyroidism
• Exogenous irradiation

• Drugs
• Given intentionally to decrease thyroid secretion
(e.g., methimazole and propylthiouracil)
• For nonthyroid conditions (e.g., lithium, p-
aminosalicylic acid).
Primary and secondary forms
• Secondary (or central) hypothyroidism
• Deficiencies of TSH
• Pituitary: Tumor, postpartum pituitary necrosis, trauma, and
nonpituitary tumors

• Or uncommonly TRH
• Hypothalamus : Tumors, trauma, radiation therapy, or infiltrative
diseases
Cretinism
• Hypothyroidism that develops in infancy or early childhood

• In the past
• Commonly in regions of the world with endemic dietary iodine
deficiency e.g. Himalayas, Inland China, Africa, and other
mountainous areas

• Now much less prevalent as a result of the widespread

supplementation of foods with iodine

• Rare : result from genetic defects that interfere with the biosynthesis of thyroid
hormone
Cretinism
• Clinical features
• Impaired development of the skeletal system and
central nervous system
• Severe mental retardation
• Short stature
• Coarse facial features
• Protruding tongue
• Umbilical hernia.
• Maternal T3 and T4
• Cross the placenta
• Critical for fetal brain development
• If there is maternal thyroid deficiency before the
development of the fetal thyroid gland, mental
retardation is severe
Myxedema
• Hypothyroidism developing in the older child or adult
• Clinical manifestations vary with age of onset
• Older children
• Signs and symptoms intermediate between those of the cretinism and
those of the adult
• In the adult - appears insidiously, may take years before diagnosis
Myxedema -Clinical features
• Marked by slowing of physical and mental activity
• Initially
• Generalized fatigue, apathy, mental sluggishness
• May mimic depression
• Slowed speech and intellectual functions
• Listless, cold intolerant, frequently overweight
• Decreased sympathetic activity
• constipation and decreased sweating
• Skin
• cool and pale (decreased blood flow)
•CVS
• Reduced cardiac output, shortness of breath, decreased
exercise capacity
• Increase in total cholesterol and LDL
• Contributes to cardiovascular mortality
Myxedema
•Histologically
•Accumulation of matrix substances

•Such as glycosaminoglycans and hyaluronic acid

•In skin, subcutanous tissue, and a number of visceral sites

•Results in nonpitting edema, a broadening and coarsening of facial features,

enlargement of the tongue, and deepening of the voice.
Diagnosis
Laboratory evaluation:
•Measurement of the serum TSH
•most sensitive screening test

• Primary hypothyroidism
•TSH increased
•Loss of feedback inhibition of TRH and TSH production

•Secondary hypothyroidism
•TSH level not increased
•Primary hypothalamic or pituitary disease (secondary hypothyroidism)

•T4 levels are decreased in individuals with hypothyroidism of any origin.

Thyroiditis
• Inflammation of the thyroid gland
• Three most common and clinically significant subtypes:

(1) Hashimoto thyroiditis

(2) Granulomatous (de Quervain) thyroiditis
(3) Subacute lymphocytic thyroiditis
Hashimoto Thyroiditis
• Autoimmune disease
• Results in destruction of thyroid gland
• Leads to gradual and progressive thyroid failure.
• Most prevalent ages 45 - 65 years
• Gender : female predominance - 10 : 1 to 20 : 1
• Can occur in children
Pathogenesis
• Caused by a breakdown in self tolerance to thyroid autoantigens

• There is a presence of circulating autoAbs against thyroglobulin and

thyroid peroxidase

• Possibilities include
• Abnormalities of regulatory T cells (Tregs)
• Exposure of normally sequestered thyroid antigens

• Hashimoto thyroiditis has a strong genetic component

• Increased susceptibility is associated with
polymorphisms in immune regulation-associated genes
Pathogenesis
• Progressive depletion of thyroid epithelial cells
• Apoptosis
• Replacement of the thyroid parenchyma by
• Mononuclear cell infiltration
• Fibrosis

• Multiple immunologic mechanisms contribute to cell death:

1.CD8+ cytotoxic T cell-mediated cell death
2.Cytokine-mediated cell death
3.Less likely: Binding of antithyroid antibodies followed by
antibody-dependent cell- mediated cytotoxicity
Morphology
Thyroid is diffusely enlarged
• Can be localised in some cases / asymmetrical
• Capsule is intact
• Gland well demarcated from adjacent structures

Cut surface
• Pale, yellow-tan, firm, nodular
Morphology - Microscopy
• Extensive infiltration of parenchyma by mononuclear inflammatory infiltrate
• Lymphocytes, plasma cells
• Well-developed germinal centers
• Thyroid follicles
• Atrophic
• Lined in many areas by Hürthle cells
• Epithelial cells showing abundant eosinophilic, granular cytoplasm
• Metaplastic response to ongoing injury
• Interstitial connective tissue is increased – Fibrosis
• Does not extend beyond the capsule of the gland.
Clinical Course
• Painless enlargement of the thyroid
• Associated with gradual development of hypothyroidism
• Middle-aged woman

• Usually symmetric and diffuse

• Can be localized - suspicion of a neoplasm
• Can be preceded by transient hyperthyroidism
• Disruption of thyroid follicles
• Release of thyroid hormones
• Increased risk for developing other autoimmune diseases
• Endocrine (type 1 diabetes, autoimmune adrenalitis)
• Nonendocrine (systemic lupus erythematosus, myasthenia gravis, and
Sjögren syndrome)
• Possible predisposition to papillary carcinomas
Subacute Lymphocytic (Painless) Thyroiditis
• Mild hyperthyroidism and/or goitrous enlargement
• Any age : more common in middle-aged
• Women > men
Morphology
• Mild symmetric enlargement
• Appears grossly normal.

• Microscopy:
• Lymphocytic infiltration
• Large germinal centers
• Patchy disruption and collapse of thyroid follicles

• Unlike Hashimoto thyroiditis

• Fibrosis and Hürthle cell metaplasia not present
Clinical Course
• May present with a painless goiter
• And/or transient overt hyperthyroidism
• Some patients transition from hyperthyroidism to hypothyroidism before recovery
• Third of affected individuals progress to overt hypothyroidism over a 10-year period
Granulomatous Thyroiditis
• Most common - ages 40 to 50
• Women > men (4:1).

Pathogenesis:
• Unclear
• Possibly triggered by a viral infection
• History of an upper RTI just before onset of thyroiditis

• Suggested model
• Viral infection leads to exposure to a viral or thyroid antigen
• Secondary to virus-induced host tissue damage
• Antigen stimulates cytotoxic T lymphocytes
Morphology
• Unilaterally / bilaterally enlarged
• Firm
• Intact capsule - may adhere to surrounding structures

• On cut section
• Involved areas are firm and yellow-white
• And stand out from the more rubbery, normal brown thyroid
substance
Morphology
• Microscopy
• Changes are patchy and depend on the stage of the disease

• Early
• Active inflammatory phase
• Scattered follicles may be disrupted and replaced by neutrophils forming
microabscesses

• Mid
• Aggregates of lymphocytes, activated macrophages, and plasma cells
• Damaged thyroid follicles
• Multinucleate giant cells enclose naked pools or fragments of colloid

• Later stages
• Chronic inflammatory infiltrate and fibrosis replace the foci of injury
Clinical Course
• Most common cause of thyroid pain
• Variable enlargement of thyroid
• Hyperthyroidism are transient
• Diminishing in 2 to 6 weeks,
• High serum T4 and T3 levels and low serum TSH levels during this phase
• Radioactive iodine uptake is diminished (vs Graves)
• Recovery in 6 to 8 weeks
• Normal thyroid function returns.
Riedel thyroiditis
• A rare disorder
• Characterized by extensive fibrosis
• Involving the thyroid and contiguous neck structures

• Presence of a hard and fixed thyroid mass

• Clinically simulates a thyroid carcinoma
Graves disease
• Most common cause of endogenous hyperthyroidism
• Peak incidence between 20 - 40 years
• Women 10 times more frequently affected
Graves disease
Triad of clinical findings:

1. Hyperthyroidism
Associated with diffuse enlargement of the gland
2. Infiltrative ophthalmopathy with resultant exophthalmos
3. Localized, infiltrative dermopathy
Pretibial myxedema
Present in a minority of patients
Pathogenesis
• Autoimmune disorder
• Production of autoantibodies against multiple thyroid proteins, most importantly
the TSH receptor

• Most common antibody

• Thyroid- stimulating immunoglobulin (TSI)
• 90% of patients
• Binds to the TSH receptor
• Mimics its actions
• Stimulating release of thyroid hormones

• Genetic factors are important in etiology

Graves ophthalmopathy
• Exopthalmos ; protrusion of the eyeball
• Due to increased volume of retro-orbital connective tissues and extraocular muscles
• displace the eyeball forward
• Interferes with function of extraocular muscles
• Volume increase due to
(1) marked infiltration by mononuclear cells - mostly T lymphocytes
(2) Oedema
(3) Accumulation of extracellular matrix components
(4) Increased numbers of adipocytes (fatty infiltration)
Morphology
• Symmetrically enlarged

• Diffuse hypertrophy and hyperplasia of thyroid follicular epithelial cells

• On cut section
• Soft, meaty appearance
• Resembling muscle
Morphology
• Histologically
• Untreated
• Follicular epithelial cells tall and more crowded
• Formation of small papillae
• That project into the follicular lumen
• Lymphoid infiltrates
• Germinal centres
• Predominantly of T cells
• Scattered B cells and mature plasma cells
• Preoperative therapy (iodine)
• Alters the morphology
• Involution of the epithelium
• Accumulation of colloid
• Propylthiouracil
• Exaggerates epithelial hypertrophy and hyperplasia by
stimulating TSH secretion
“Type a quote here.”
Morphology
• Extrathyroidal tissue

• Lymphoid hyperplasia
• Especially enlargement of the thymus - younger patients.
• Heart: may be hypertrophied with ischemic changes
• Ophthalmopathy – oedema, infiltration by lymphocytes and
fibrosis
• Dermopathy - Thickening of the dermis due to deposition of
glycosaminoglycans and lymphocyte infiltration
Clinical features
• Diffuse enlargement of the thyroid
• Present in all cases

• Symptoms of hyperthyroidism
• Sympathetic overactivity
• wide, staring gaze and lid lag
• Protrusion of the eyeball - exophthalmos
• Infiltrative dermopathy
• Pretibial myxedema
• Most common in the skin overlying the shins
• Scaly thickening and induration

• Patients are at increased risk for other autoimmune diseases

• E.g. SLE, pernicious anemia, type 1 DM, and Addison disease.
Diagnosis
• Elevated free T4 and T3
• Depressed TSH levels.
• Diffusely increased uptake of iodine

• Treatment
• β-blockers
• symptoms related to the increased β-adrenergic tone
• Decreasing thyroid hormone synthesis
• Thionamides (e.g., propylthiouracil)
• Radioiodine ablation
• Thyroidectomy
Goiter
• Enlargement of the thyroid
• Caused by impaired synthesis of thyroid hormone
• Most often the result of dietary iodine deficiency

• Compensatory rise in the serum TSH level

• Hypertrophy and hyperplasia of thyroid follicular cells
• Gross enlargement of the thyroid gland
• Increase in functional mass
• Overcomes the hormone deficiency
• Euthyroid metabolic state
Goiter
• Goiters can broadly be divided into two types
• Diffuse non-toxic
• Multinodular

• Diffuse nontoxic (simple) goiter

• Enlargement of the entire gland
• Without producing nodularity
• AKA Colloid goiter
• Occurs in both an endemic and a sporadic distribution
Goiter
• Endemic goiter
• Geographic areas where the soil, water, and food supply contain low levels of iodine
• Goiters - present in more than 10% of the population in a given region
• Andes and Himalayas
• Lack of iodine  decreased synthesis of thyroid hormone
• Compensatory increase in TSH
• Follicular cell hypertrophy and hyperplasia

Sporadic goiter
• Striking female preponderance
• Peak incidence at puberty or in young adult life
• Caused by several conditions
• Ingestion of goitrogens
• Hereditary enzymatic defects
• Unknown
Goiter
• Goitrogens

• Interfere with thyroid hormone synthesis at some level

• Vegetables belonging to the Brassicaceae (Cruciferae) family (e.g., cabbage, cauliflower, Brussels
sprouts, turnips, and cassava)
• Native populations subsisting on cassava root are particularly at risk.
• Cassava contains a thiocyanate that inhibits iodide transport within the thyroid, worsening any
possible concurrent iodine deficiency.
Morphology
• Hyperplastic phase
• Thyroid gland is diffusely and symmetrically enlarged
• Modest increase, rarely exceeds 100 to 150 gm
• Follicles are lined by crowded columnar cells
• The accumulation is not uniform throughout the gland
• Some follicles are hugely distended, whereas others remain
small.
• If dietary iodine subsequently increases or if the demand for thyroid
hormone decreases
• Stimulated follicular epithelium involutes
• Form an enlarged, colloid-rich gland
• Colloid goitre
• Cut surface is usually brown, somewhat glassy, and translucent
• Histologically the follicular epithelium is flattened and cuboidal,
and colloid is abundant during periods of involution.
Clinical Course
• Simple goiters are clinically euthyroid
• Mass effects from the enlarged thyroid gland
• Serum T3 and T4 levels are normal
• Serum TSH is usually elevated

• In children
• Dyshormonogenetic goiter
• Caused by a congenital biosynthetic defect
• May induce cretinism.
Multinodular goiter
• Recurrent episodes of hyperplasia and involution
• Combine to produce a more irregular enlargement of the thyroid
• All long- standing simple goiters convert into MNGs
• Most extreme thyroid enlargements and frequently mistaken for neoplasms.
• Arise because of variations among follicular cells in their response to external stimuli
• The uneven follicular hyperplasia, generation of new follicles, and accumulation of colloid produce physical
stress-lead to rupture of follicles and vessels
• Followed by haemorrhages, scarring, and calcifications
• With scarring, nodularity appears
Morphology
• Multilobulated, asymmetrically enlarged glands
• Lateral pressure on midline structures, such as the trachea and esophagus
• Intrathoracic / plunging goiter
• Goiter grows behind the sternum and clavicles
• One nodule may stand out-clinical appearance of a solitary nodule
• On cut section, irregular nodules containing variable amounts of brown, gelatinous colloid are present.
• Older lesions have areas of hemorrhage, fibrosis, calcification, and cystic change.
Morphology
Microscopy
• Colloid-rich follicles lined by flattened, inactive epithelium and areas of follicular hyperplasia
• Accompanied by degenerative changes
• In contrast to follicular neoplasms
•A prominent capsule between the hyperplastic nodules and residual compressed thyroid
parenchyma is not present.
Clinical Course
• Airway obstruction, dysphagia, and compression of large vessels in the neck and upper
thorax(superior vena cava syndrome).
• Most patients are euthyroid
• or have subclinical hyperthyroidism
• Minority of patients an autonomous nodule - hyperthyroidism (toxic
multinodular goiter)
• AKA Plummer syndrome
Clinical Course
• Dominant nodules
• can present as a “solitary thyroid nodule”, mimicking a thyroid neoplasm.

• A radioiodine scan demonstrates uneven iodine uptake

• Admixture of hyperplastic and involuting nodules.

• A fine-needle aspiration biopsy is helpful and can often, albeit not always, facilitate the distinction of
follicular hyperplasia from a thyroid neoplasm
Follicular adenoma
• Discrete, solitary masses, derived from follicular epithelium, and hence they are also known as follicular
adenomas.
• Difficult to distinguish from dominant nodules of follicular hyperplasia or follicular carcinomas.
• Although the vast majority of adenomas are nonfunctional
• Small subset produces thyroid hormones and causes clinically apparent thyrotoxicosis.
• Hormone production in functional adenomas (“toxic adenomas”) is independent of TSH
stimulation.
Morphology
• Solitary, spherical, encapsulated lesion
• Demarcated from thyroid parenchyma by a well-defined, intact capsule .
• Average about 3 cm in diameter (≥10 cm in diameter).
• In freshly resected specimens the adenoma bulges from the cut surface and compresses the adjacent thyroid.
• Color ranges from gray-white to red-brown, depending on the cellularity of the adenoma and its colloid content.
• Areas of hemorrhage, fibrosis, calcification, and cystic change.
Morphology
• Microscopically: cells often form uniform- appearing follicles that contain colloid
• The neoplastic cells show little variation in cell size, cell shape, or nuclear morphology
• Mitotic figures are rare.
• Occasionally the neoplastic cells acquire brightly eosinophilic granular cytoplasm (oxyphil or Hürthle cell
change).
• The hallmark of all follicular adenomas: intact, well-formed capsule encircling the tumor.
• Extensive mitotic activity, necrosis, or high cellularity-exclude follicular carcinoma and the follicular variant
of papillary carcinoma.
Clinical features
• Unilateral painless masses that are discovered during a routine physical examination.
• Local symptoms, such as difficulty in swallowing.
• Non-functioning adenomas take up less radioactive iodine than does normal thyroid parenchyma.
• On radionuclide scanning, therefore, non-functioning adenomas appear as cold nodules relative to the
adjacent thyroid tissue.
• Definitive diagnosis=careful examination of resected specimen for capsular invasion
THYROID CARCINOMA
• 1.5% of all carcinomas
• Papillary carcinoma (>85% of cases)
• Follicular carcinoma (5% to 15% of cases)
• Anaplastic (undifferentiated) carcinoma (<5% of cases)
• Medullary carcinoma (5% of cases)
Papillary Carcinoma
• Most common form of thyroid cancer
• 85% of primary thyroid malignancies in the United States
• Ages of 25 and 50, and account for the majority of thyroid carcinomas associated with
previous exposure to ionizing radiation.

Morphology
• May be solitary or multifocal
• Well-circumscribed and even encapsulated; others infiltrate the adjacent parenchyma and
have ill-defined margins.
• May contain areas of fibrosis and calcification and are often cystic.
• The cut surface sometimes reveals papillary foci-point to diagnosis.
Microscopy
• Branching papillae
• having a fibrovascular stalk covered by a single to multiple layers of cuboidal epithelial
cells
• Nuclei
• Dispersed chromatin, which imparts an optically clear or empty appearance
• Ground- glass or Orphan Annie eye appearance
• In addition, invaginations of the cytoplasm may give the appearance of intranuclear
inclusions (“pseudo-inclusions”) or nuclear grooves
• diagnosis of papillary carcinoma can be made based on these nuclear features
• Psammoma bodies are often present, usually within the cores of papillae-almost never found in follicular and
medullary carcinomas
• Foci of lymphatic invasion by tumor are often present, but involvement of blood vessels is relatively
uncommon,
• Metastases to adjacent cervical lymph nodes occur in up to half of cases.
Clinical Course
• Present as asymptomatic thyroid nodules-mas

• Hoarseness, dysphagia, cough, or dyspnea suggests advanced disease

• In a minority of patients
• Hematogenous metastases are present at the time of diagnosis
• most commonly in the lung

• Papillary thyroid cancers have an excellent prognosis

Follicular carcinoma
• Account for 5% to 15% of primary thyroid cancers
• More frequent in areas with dietary iodine deficiency (25% to 40%).
• They are more common in women (3:1)
• Often in older patients than do papillary carcinomas; the peak incidence (40 &60 years).

Morphology
• single nodules that may be well circumscribed or widely infiltrative
• Larger lesions may penetrate the capsule and infiltrate well beyond the thyroid capsule into the adjacent neck.
• Gray to tan to pink on cut section and may be somewhat translucent due to the presence of large, colloid-filled
follicles.
• Degenerative changes, such as central fibrosis and foci of calcification, are sometimes present.
Microscopy
• Fairly uniform cells forming small follicles containing colloid
• Reminiscent of normal thyroid or nests or sheets of cells without colloid.

• Abundant granular, eosinophilic cytoplasm (Hürthle cell or oncocytic variant of follicular carcinoma)

• Nuclei lack the features typical of papillary carcinoma

• Psammoma bodies are not present.

• No reliable cytologic difference between follicular adenomas and minimally invasive follicular
carcinomas

• Making this distinction requires extensive histologic sampling of the tumor-capsule-thyroid interface to
exclude capsular and/or vascular invasion
Clinical Course
• Slowly enlarging painless nodules.
• Regional lymph nodes are rarely involved
• Hematogenous dissemination is common
• bone, lungs, liver, and elsewhere

• The prognosis depends largely on the extent of invasion and stage at presentation.
• Widely invasive follicular carcinoma often presents with systemic metastases, and as
many as half of affected patients succumb to their disease within 10 years.
• This is in sharp contrast to minimally invasive follicular carcinomas, which have a 10-year
survival rate of greater than 90%.
Treatment
• Most are treated with total thyroidectomy
• Followed by the administration of radioactive iodine, identify metastases and ablate such lesions
• Residual follicular carcinoma may respond to TSH stimulation
• Patients are usually treated with thyroid hormone after surgery to suppress endogenous
TSH levels
• Serum thyroglobulin levels are used for monitoring tumor recurrence, because this thyroid protein should be
barely detectable in a patient who is free of disease.
Anaplastic (Undifferentiated) Carcinoma
• Undifferentiated tumors of the thyroid follicular epithelium (<5% of thyroid tumors)
• Aggressive: mortality rate approaching 100%
• Older - mean age of 65 years.

Morphology
• highly anaplastic cells, with variable morphology:
(1)large, pleomorphic giant cells,: osteoclast-like multinucleate giant cells
(2)spindle cells with a sarcomatous appearance
(3) mixed spindle and giant cells.

• The neoplastic cells express epithelial markers like cytokeratin, but are usually negative for
markers of thyroid differentiation, like thyroglobulin.
Clinical Course
• Anaplastic carcinomas usually present as a rapidly enlarging bulky neck mass
• In most cases
• Disease has already spread beyond the thyroid capsule into adjacent neck structures
• or has metastasized to the lungs at the time of presentation

• Symptoms related to compression and invasion

• Dyspnea, dysphagia, hoarseness, and cough, are common

• No effective therapies
• Disease is almost uniformly fatal
Medullary Carcinoma
• Neuroendocrine neoplasms derived from the parafollicular cells, or C cells
• 5% of thyroid neoplasms.
• About 70% of tumors arise sporadically.
• The remainder: MEN syndrome 2A or 2B or as familial tumors without an associated MEN
syndrome (familial medullary thyroid carcinoma, or FMTC;
• MEN types 2A or 2B occur in younger patients, and may even arise during the first decade of life.
• Sporadic as well as familial medullary carcinomas : lesions of adulthood, with a peak incidence in
the 40s and 50s.
Morphology
• Sporadic as solitary nodule
• Bilaterality and multicentricity are common in familial cases
• Larger lesions often contain areas of necrosis and hemorrhage and may extend through the capsule of the
thyroid.
• The tumor tissue is firm, pale gray to tan, and infiltrative.
Morphology
Microscopically
• composed of polygonal to spindle-shaped cells
• Form nests, trabeculae, and even follicles

• Acellular amyloid deposits

• derived from calcitonin polypeptide
• are present in the stroma in many cases

• Calcitonin is readily demonstrable within the cytoplasm of the tumor cells

• Features of familial medullary cancers

• Presence of multicentric C-cell hyperplasia in the surrounding thyroid parenchyma,
Clinical Course
• Sporadic cases
• mass in the neck
• sometimes associated with dysphagia or hoarseness.

• In some instances
• Initial manifestations are those of a paraneoplastic syndrome
• Caused by the secretion of a peptide hormone (e.g., Cushing syndrome due to ACTH).

• Familial syndromes
• Symptoms localized to the thyroid
• result of endocrine neoplasms in other organs (e.g., adrenal or parathyroid glands).
The end
…Next lecture
Pathology of the Hypothalamus and the Pituitary Gland

Dr BB Bungane
Anatomical Pathology
NHLS
IALCH
UKZN
11/08/2021
REVISION
 Embryology
 Anatomy
 Histology
 Pathology
Objectives

 Revise the embryology and anatomy of the Pituitary gland

 Revise the basic histology of the hypothalamus and the pituitary gland
 Clinical manifestations of pituitary adenomas
 Pathology of anterior pituitary adenoma
 Pathology of posterior pituitary adenoma
 Pathology of the hypothalamus
Pituitary gland - Hypophysis

• Consists of:
• Anterior lobe (adenohypophysis)
• Intermediate lobe
• Posterior lobe (neurohypophysis)
 Pituitary gland - Hypophysis
Consists of:
1. Anterior lobe (adenohypophysis)
Originates from Ectoderm
• 3rd week GA - thickening of oral ectoderm
• Invagination of the thickened plate in a cephalad direction to form the Rathke's pouch
» connected to the stomodeum via a narrow stalk
• 6 week GA, the stalk becomes so attenuated that the pouch loses its stomodeal attachment as it
th

comes into contact with the infundibulum

• Anterior wall proliferates and forms Rathke's pouch - pars distalis
» tongue like extension of pars distalis - the pars tuberalis

2. Intermediate lobe
Posterior portion of Rathke's pouch gives rise pars intermedia.
 Pituitary gland - Hypophysis
3. Posterior lobe (neurohypophysis)
4th week GA - Neuroectodermal bud on floor of diencephalon

6th week GA - Grows ventrally to abut the posterior portion of

Rathke's pouch

Axons from brain extend through infundibular stalk and

terminate in the pars nervosa
Anatomy

 Bean shaped organ at base of brain

 1cm
 Sella turcica
 0.5 - 1g

Connected to hypothalamus
 Infundibulum
• Vascular network
• Neurons
Anterior Pituitary

 Epihtelial origin – Ectoderm of oral cavity

 Morphologically 3 cell types
• Acidophils – Cells have an eosinophilic cytoplasm
• Basophils – Cells have a basophilic cytoplasm
• Chromophobes – Cells with poorly staining cytoplasm

 Functionally 6 cell types

• Can help identify origin of tumour
 The Normal Anterior Pituitary: Morphologic and Functional Features of Secretory Cells
% of
Cell Type Product Location Special Stains IHC
Cells
Somatotroph
Acidophilic
(MammotrophGrowth hormone (GH) Lateral wings 50 GH
PAS (-)
)

Resting cells generalized

Lactotroph Acidophilic
Prolactin (PRL); Secreting cells postero-lateral 15 to 20 PRL
(Mammotoph) PAS (-)
wings

ACTH
LPH
Adrenocorticotrophic hormone Basophilic MSH
Corticotroph Mucoid wedge 15 to 20
(ACTH) PAS and lead hematoxylin (+) Endorphin
enkephali
n
Basophilic (+)
PAS (+)
Follicle stimulating & luteinizing FSH and
Gonadotroph Generalized 10 lead hematoxylin (+)
hormone (FSH & LH) LHc
aldehyde fuchsin (+)
aldehyde thionine (+)
Thyrotroph Thyrotrophic hormone (TSH) Anterior mucoid wedge <5 Same as for gonadotroph TSH
 Major Hypothalamic Hormones: Their Composition and Localization
Hormone Abbreviations Hypothalamic Sites

Growth hormone-releasing hormone GHRH Arcuate nucleus

Thyrotopin-releasing hormone TRH Widely distributed in CNS

Gonadotropin-releasing hormone or luteinizing hormone- Arcuate, ventromedial, dorsal,

GnRH or LHRH
releasing hormone and paraventricular nuclei

Corticotropin-releasing hormone CRH Periventricular

Somatostatin or Growth hormone-release inhibiting hormone Periventricular nucleus,

Dopamine Arcuate nucleus

Paraventricular, supraoptic
Arginine vasopressin AVP
nuclei
Paraventricular, supraoptic
Oxytocin OT
nuclei
Posterior Pituitary

 Neural tissue origin - Neuroectodermal bud of diencephalon

• Modified glial cells termed pituicytes
o Axons extending from the hypothalamus through the infundibulum to
the pars nervosa (axon terminals).

 Two peptide hormones are secreted:

 Oxytocin
 ADH/Vasopressin
PATHOLOGY

Disease – epidemiology, pathogenesis, morphology, clinical features, current therapy

• General manifestations
• Anterior pituitary
• Posterior pituitary
• Hypothalamus
 Clinical manifestations of pituitary disease
1. Anterior pituitary
Functional or Mass effect
Functional
 Hyperpituitarism - excess secretion of hormones
 Hyperplasia, adenoma, carcinoma of pituitary gland
 Secretory non-pituitary tumour

 Hypopituitarism - deficiency of hormones

 Non-functional pituitary tumour , ischemia, surgery, radiation, inflammation.

Mass effect
 Close proximity to chiasm at the Sella turcica
 Compression of optic chiasm – bitemporal hemianopia.
 Increased ICP
 haemorrhage of pituitary tumour– pituitary apoplexy

2. Posterior pituitary
 Increased or decreased secretion of ADH
 Fluid and electrolyte imbalance
 Pituitary Adenomas and Hyperpituitarism
Pituitary adenoma of the anterior lobe
 Most common cause of Hyperpituitarism

Classification
 Hormones produced
 Cell type
 May show 2 or more hormones and cell types (plurihormonal)

Hypopituitarism
 Compression and atrophy of adjacent glands

Pituitary adenomas can be:

 Functional - associated with hormone excess and clinical manifestations
 Non-functioning - immunohistochemical or ultra structural demonstration of hormone production at the tissue level, without clinical symptoms of hormone
excess
 Pituitary adenoma: Epidemiology
 Affect adults commonly
 Peak age = 35 – 60
 Most occur in isolation
 Prevalence = 14%, but
 pituitary incidentaloma – small non-functional tumour seen at autopsy
 Pituitary adenoma: Pathogenesis

 mutations in cancer genes

 Acquired somatic mutations
 Germline mutations
Pituitary adenoma: Morphology

Gross vs Microscopic

 Gross
 Microadenomas < 1 cm in diameter
 Macroadenomas ≥ 1 cm in diameter
o Non functional adenomas
Pituitary adenoma: Morphology
 Soft, well-circumscribed lesion
 Small - Confined to the Sella turcica
 large – erode Sella, Mass effects
 Unencapsulated in 30% of cases
o Infiltration of adjacent tissues
• Aggressive adenomas
Pituitary adenoma: Morphology
 Microscopic
 Sheets or cords
 Monomorphic, polygonal cells
 Cytoplasm – A, B, C
 Nuclei - uniform or pleomorphic
Pituitary adenoma: Clinical features

Functional vs Mass effect

 Functional
 Hyperpituitarism - excess secretion of hormones
o Hyperplasia, adenoma, carcinoma of pituitary gland.
o Secretory non-pituitary tumour.

 Hypopituitarism - deficiency of hormones

o Non-functional pituitary tumour, Ischemia, surgery, radiation, inflammation.

 Mass effect
 Close proximity to chiasm at the Sella turcica
 Compression of optic chiasm – bitemporal hemianopia.
 Increased ICP
 haemorrhage of pituitary tumour – pituitary apoplexy
Pituitary adenoma: Types
1. Lactotroph Adenoma
 “Prolactinoma”
 PRL
 most common hyperfunctioning pituitary adenoma

Microscopic
 Sparsely granulated Lactotroph adenomas
• Chromophobe cytoplasm
 Densely granulated Lactotroph adenomas
• Eosinophilic cytoplasm
 Dystrophic calcification
• Isolated psammoma bodies
• pituitary stone
Stains
 PRL
 Erα, Cytoplasmin PIT-1 = Lactotroph
differentiation.

Clinical features
Functional
 Prolactinemia
• Amenorrhea, galactorrhea, loss of libido, and infertility
• Other causes – pregnancy, lactation, stress response,
lactotroph hyperplasia, drugs

Mass effect
 Close proximity to chiasm at the Sella turcica
 Compression of optic chiasm – bitemporal hemianopia.
 Increased ICP
 haemorrhage of pituitary – pituitary apoplexy
Pituitary adenoma
2. Somatotroph Adenoma
 GH
 second most common hyperfunctioning pituitary
adenoma

Microscopic
 Sparsely granulated adenomas
• Chromophobe cytoplasm
• paranuclear glossy inclusion
o Fibrous body – intermediate filaments
 Densely granulated adenomas
• Eosinophilic cytoplasm
• Large central nucleus
o Prominent nucleolus
Microscopy
 Mixed Somatotroph – GH/PRL in different cells
 Mammotroph – GH/PRL in same cell
Clinical features
Functional
 Gigantism in children – Epiphyses still open
 Generalized increase in body size with disproportionately long arms and legs.

 Acromegaly in adults – Closed epiphyses

 Growth of skin and soft tissues, viscera (thyroid, heart, liver, and adrenals), and the bones of the face, hands, and feet.
 Hyperostosis – Increased bone density increases in both the spine and the hips.
 Prognathism – Enlargement of the jaw leading to protrusion
 Broadening of the lower face.
 The feet and hands are enlarged, and the fingers become thickened and sausage-like.
Mass effect
 Close proximity to chiasm at the Sella turcica
 Compression of optic chiasm – bitemporal hemianopia.
 Increased ICP
 haemorrhage of pituitary tumour– pituitary apoplexy
3. Corticotroph Adenoma
 ACTH

Microscopic
 Microadenomas
 Sparsely granulated adenomas
 Chromophobe cytoplasm
 Densely granulated adenomas
 Basophillic cytoplasm
 Crooke cell adenoma
 Crooke change - ringlike deposition of
cytokeratin
 Aggressive
Stains
 PAS
 Carbohydrate in proopiomelanocortin
(POMC)
• Precursor of ACTH
 ACTH
 Nuclear TPIT-1 = Corticotroph differentiation
 Pituitary adenoma
Clinical features
Functional or Mass effect
Functional
 Cushing disease
 Hypercortisolism due to excessive production of ACTH
 Nelson syndrome
 Pituitary MACROADENOMA following surgical removal of the adrenal glands for treatment of Cushing syndrome
 Loss of negative feedback on microadenoma
 No Hypercortisolism – NB – adrenal glands removed
 Melanotropin leads to hyperpigmentation
 Also see mass effects

Mass effect
 Close proximity to chiasm at the Sella turcica
 Compression of optic chiasm – bitemporal hemianopia.
 Increased ICP
 haemorrhage of pituitary – pituitary apoplexy
 The Normal Anterior Pituitary: Morphologic and Functional Features of Secretory Cells
% of
Cell Type Product Location Special Stains IHC
Cells
Somatotroph
Acidophilic
(MammotrophGrowth hormone (GH) Lateral wings 50 GH
PAS (-)
)

Resting cells generalized

Lactotroph Acidophilic
Prolactin (PRL); Secreting cells postero-lateral 15 to 20 PRL
(Mammotoph) PAS (-)
wings

ACTH
LPH
Adrenocorticotrophic hormone Basophilic MSH
Corticotroph Mucoid wedge 15 to 20
(ACTH) PAS and lead hematoxylin (+) Endorphin
enkephali
n
Basophilic (+)
PAS (+)
Follicle stimulating & luteinizing FSH and
Gonadotroph Generalized 10 lead hematoxylin (+)
hormone (FSH & LH) LHc
aldehyde fuchsin (+)
aldehyde thionine (+)
Thyrotroph Thyrotrophic hormone (TSH) Anterior mucoid wedge <5 Same as for gonadotroph TSH
Hypopituitarism

Deficiency of pituitary hormones

 Non-functional pituitary tumour , Ischemia, surgery, radiation,
inflammation, mass effects
 Pituitary apoplexy
 Diseases of the hypothalamus
• Affects anterior and posterior pituitary
 Diseases of the pituitary

 Occurs when approximately 75% of the parenchyma is lost or absent

 Hypopituitarism
Clinical manifestations
 Failure of lactation – PRL

 Pituitary dwarfism – Growth failure in children due to GH deficiency

 Remember Gigantism

 Hypothyroidism – TSH

 Hypoadrenalism – ACTH
 Posterior Pituitary Syndromes
Diabetes insipidus
 ADH deficiency
 inability of the kidney to concentrate urine – Failure of water reabsorption
 causes – Trauma, Tumour, Hypothalamic disease, genetic
 Polyuria, polydipsia

Syndrome of inappropriate ADH (SIADH) secretion

 ADH excess
 Over-resorption of free water
 causes: Exogenous ADH (Tumour), drugs, trauma
 hyponatremia, cerebral oedema, neurological dysfunction
 Hypothalamic Suprasellar Tumours
 Hypofunction / hyperfunction of the anterior pituitary
 Diabetes insipidus

Epidemiology
• Bimodal age distribution
• 5 to 15 years
• >65 years of age
Aetiology
• Glioma
• Craniopharyngioma
Craniopharyngioma
Morphology
Gross vs Microscopic
Gross
 3 to 4 cm in diameter
 encapsulated and solid, or cystic and multiloculated

Microscopic
Histological variants:
 Adamantinomatous craniopharyngioma
• Calcifications

 Papillary craniopharyngioma
• rare calcification
Craniopharyngioma
Morphology
1. Adamantinomatous craniopharyngioma
 Nests and cords
 Stratified squamous epithelium
• Peripheral palisading morphology
• Lamellar “wet keratin”
 Cysts formation
• Containing brown yellow oily fluid – “machine oil”
 Spongy reticulum
 Dystrophic calcification
Craniopharyngioma
Adamantinomatous craniopharyngioma
 Background
• Fibrosis
• Chronic inflammation
Craniopharyngioma
2. Papillary craniopharyngioma
 Sheets and papillae
 Stratified squamous epithelium
• Peripheral palisading morphology
• Lamellar “wet keratin”
 Cysts formation
• Containing brown yellow oily fluid – “machine oil”
 Spongy reticulum
 Dystrophic calcification

 Background
• Fibrosis
• Chronic inflammation
Clinical manifestations

 Headaches
 Visual disturbances
 Pituitary hypofunction as outlined in hypopituitarism
 Conclusion
Anterior pituitary
Functional or Mass effect
Functional
 Hyperpituitarism - excess secretion of hormones
• Hyperplasia, adenoma, carcinoma od pituitary gland
• Secretory non-pituitary tumour
• Cell types

 Hypopituitarism - deficiency of hormones

• Non-functional pituitary tumour – Ischemia, surgery, radiation, inflammation, mass effects

Mass effect
 Close proximity to chiasm at the Sella turcica
• Compression of optic chiasm – bitemporal hemianopia.
 Increased ICP
 haemorrhage of pituitary – pituitary apoplexy

Posterior pituitary
 Increased or decreased secretion of ADH
• Fluid and electrolyte imbalance
THE END
…Next lecture
Osteoporosis
Osteomalacia
Rickets
Dr S. Olivier
Department of Anatomical
Pathology
Date: 16/08/2021
Osteopenia and Osteoporosis

• Osteopenia - decreased bone mass

• Osteoporosis - osteopenia severe enough to increase the risk of
fracture.
WHO Definition 1994:

• A skeletal disease characterized by low bone mass and deterioration

of the microarchitecture of bone tissue with a consequent increase in
bone fragility and susceptibility to low trauma fractures.
Osteopenia and Osteoporosis

• Radiographically, Osteopenia is 1-2.5 standard deviations below the

mean bone density and Osteoporosis as at least 2.5 SD below mean
bone density.
• Presence of atraumatic or vertebral compression signifies
osteoporosis.
• May be localised to a certain bone or region, or involve entire skeleton
Categories of Generalised Osteoporosis

• PRIMARY
• Postmenopausal
• Senile
• Idiopathic
Categories of Generalised Osteoporosis
SECONDARY • Gastrointestinal
• Malnutrition
• Endocrine Disorders • Malabsorption
• Hyperparathyroidism • Hepatic insufficiency
• Hyperthyroidism • Vitamin C, D deficiencies
• Hypothyroidism • Drugs
• Hypogonadism • Anticoagulants
• Pituitary tumors • Chemotherapy
• Corticosteroids
• Diabetes, type 1
• Anticovulsants
• Addison disease
• Alcohol
• Neoplasia • Miscellaneous
• Multiple myeloma • Osteogenesis imperfecta
• Carcinomatosis • Immobilization
• Pulmonary disease
• Homocystinuria
• Anemia
Pathogenesis

• Peak bone mass is achieved during young adulthood.

- Magnitude determined largely by hereditary factors
• Physical activity, muscle strength, diet, and hormonal state
• Resorption and formation cycle
• Age-related bone loss, which may average 0.7% per year
Pathogenesis

• Age-related changes: Osteoblasts from older individuals have

reduced proliferative and synthetic potential and are less responsive
to growth factors. Net result is reduced capacity to make bone.
• Reduced physical activity- Mechanical forces stimulate normal bone
modelling , inactivity results in increased rate of bone loss.
Pathogenesis

• Genetic factors: Single gene defects (eg LRP5) - small fraction of

cases
Polymorphism in other genes accounts for differences in peak bone
density –RANK, RANKL, OPG
• Calcium nutritional state: calcium deficiency may occur during
periods of rapid bone growth
• Hormonal influences: post-menopausal period associated with
increased osteoclastic activity caused by the relative absence of
oestrogen
Morphology

• Histologically normal bone that is decreased in quantity, which tends

to be most conspicuous in parts of the skeleton containing abundant
trabecular bone.
Morphology

• Vertebrae shortened by compression fractures

• Loss of horizontal trabeculae and thickened vertical trabeculae
• Cortex and trabeculae are thinned and Haversian systems are
widened.
Microscopy

• Thin trabeculae are disconnected from each other

• Increase in osteoclastic activity
Clinical course

• Depends on bone involved

• May be asymptomatic
• Vertebral fractures common in the lumbar and thoracic spine
• Complications of fractures of femoral neck, pelvis or spine such as
pulmonary embolism
• Plain X-ray can detect osteoporosis when 30-40% of bone mass is
lost.
• Calcium, phosphate, alkaline phosphatase and PTH are not
diagnostic.
Diagnostic Studies

• Best estimates of bone loss

Bone Histomorphometry (rarely done)
DEXA scans
Radiographic Absorptiometry
Single Photon X-ray absorptiometry (SPA)
Quantitative Computer tomography
Quantitative Ultrasound
Prevention and treatment

• Prevention
• Adequate dietary calcium intake
• Vitamin D supplementation
• Regular exercise regimen (starting before the age of 30 to increase peak bone
density)
• Bisphosphonates
• Decrease bone resorption by reducing osteoclast activity and inducing
apoptosis.
• Selective oestrogen receptor modulators.
• Increased risk of DVT and stroke
• Parathyroid hormone.
RICKETS & OSTEOMALACIA

• Definition: Interruption of orderly mineralisation and development of

growth plate due to disorder in calcium, phosphate and vitamin D
metabolism
Osteomalacia & Rickets

Osteomalacia: Defective bone mineralization in adults

Rickets: Defective bone and cartilage mineralization in children

Frequently results from either vitamin D or phosphate depletion

Vitamin D regulation and calcium homeostasis

• Vitamin D has essential role in calcium homeostasis

• Calcium homeostasis is maintained by parathyroid hormone
(PTH) and calcitonin
• Vitamin D synthesis is strictly controlled in the kidneys by PTH
• Hydroxylation of 25-hydroxycholecalciferol is PTH-dependent in
kidneys
• Calcium absorption in the gut:
• Indirectly depends on PTH
• Directly depends on vitamin D
 Causes
1. Nutritional deficiency
1. Vitamin D
2. Chelators of calcium- phytates, oxalates, phosphorus
3. Antacid abuse, causing reduced dietary phosphate binding
2. GI absorption defects
1. Post gastrectomy
2. Biliary disease (reduced absorption of vitamins)
3. Small bowel disease
4. Liver disease
3. Renal tubular defects
4. Renal osteodystrophy
5. Miscellaneous causes - inadequate sunlight
Pathology

Sufficient osteoid but poor mineralization

to:
Rickets
• Children - prior to the closure of the growth plates,

Osteomalacia
• Any age
Microscopy in children
• Thick, poorly defined growth plates
• Uncalcified cartilage extends into metaphysis
Clinical Features in Rickets

Dependent on severity and duration, and stresses to which individual

bones are subjected

Nonambulant:
Head:
Flattening of occiput
Elastic parietal bones that spring back after application of pressure
(craniotabes)
Frontal bossing and squared appearance to head
Chest:
Pigeon chest (pectus carinatum) due to inward bend of ribs
Rachitic (rickety) rosary: overgrowth at costochondral junction
Thickening of wrists from epiphyseal overgrowth,
Stunted growth,
Clinical Features in Rickets

Ambulant:
Spine, pelvis, tibia
Lumbar lordosis
Thickening of wrists
Bowing of legs
Stunted growth
Coxa vara
Fractures
Frontal blossing
( due to excess osteoid )

Widening of wrist.
• Rachitic Rosary
• Harrison’s sulcus
• Pigeon chest deformity
Osteomalacia

• Aches and pains

• Muscle weakness
• Loss of height
• Fractures
• Gross or microfractures
• Commonly involving vertebrae and femoral necks
RICKETS & OSTEOMALACIA

X-RAY FINDINGS:

RICKETS
Thickening and
widening of physes,
Cupping of
metaphysis, Wide
metaphysis,
Bowing of diaphysis,
Blurred trabeculae
RICKETS & OSTEOMALACIA

X-RAY FINDINGS:

OSTEOMALACIA
Loosers zones - incomplete
stress # with healing
lacking calcium, on
compression side of long
bones.
Codfish vertebrae due to
pressure of discs
Trefoil pelvis, due to
indentation of acetabulae
stress #s
Investigations

Blood Tests:
Low calcium
Low phosphate
Increased alkaline phosphatase
Increased PTH secretion

Urinary excretion of calcium diminished

RICKETS, OSTEOMALACIA

MANAGEMENT:
Depends on the cause

Eg Nutritional
Vitamin D deficiency
Dietary chelators of calcium
Phytates
Oxalates
Phosphorus deficiency (unusual)
Antacid abuse
 Treatment- vitamin D (5000u) and Calcium
(3g/day)
References

• Robbins & Cotran Pathologic Basis of Disease, 9th edition.

THANK YOU
The end