Systemic Path - Exam 3 Flashcards
What type of glands make up the endocrine system?
Ductless glands
Where are hormones from the endocrine system secreted?
Bloodstream
This organ has both exocrine and endocrine function.
Pancreas
What are mixed function organs?
Has both exocrine and endocrine function.
What are diffuse endocrine systems?
Comprised of scattered cells within organs acting locally on adjacent cells without entry into blood stream.
Which type hormones are biologically active?
Free hormones
Purpose of hormones bound to plasma proteins
Serve as a reserve for acute changes (e.g. thyroid and steroid)
General characteristics of hormones.
- Have a specific rate and pattern of secretion.
- Feedback systems: to maintain an optimal internal environment
- Affect only cells with appropriate receptors
- Excreted by one organ and deactivated by another (e.g. excreted by the kidney, deactivated by the liver or other mechanisms)
Functions of endocrine system.
- Response to stress and injury
- Growth and development
- Reproduction
- Homeostasis
- Energy metabolism
How does the feedback loop mechanism work?
- When biological sensor detects that a hormone level is low, it will cause processes that increase the hormone level.
- When the hormone level is too high, the sensors will cause a decreased in hormonal production.
Analogous to a thermostat and furnace.
Classification of diseases.
- Hyperfunction - overproduction of secretion
- Hypofunction - underproduction
- Mass effects (tumors)
The parathyroid is a derivative of…
Third and forth branchial pouches
How many parathyroid glands does the typical person have?
Most have four glands, but may vary 1-12.
Ectopic locations of the parathyroid
- intrathyroid
- intrathymic
- anterior mediastinum
Location of the parathyroid.
Normally on the posterior thyroid surface.
What cells make up the parathyroid?
- Chief cells
- Oxyphil cells
- Stromal fat
What do chief cells secrete?
parathyroid hormone (PTH)
What controls the activity of the parathyroid gland?
Free (ionized) calcium, not trophic hormones
Where does PTH act?
Bones, kidneys, and intestines
Describe PTH and regulation of systemic calcium homeostasis
- PTH increases bone resorption in bone –> increases plasma Ca++
- PTH decreases PO4 reabsorption, but increases Ca++ reabsorption in the kidney –> increases plasma Ca++
- After hydroxylation in the liver and kidney, active form of vitamin D3 (1,25-dihydroxy-vitamin D3) increases calcium reabsorption in the intestine –> increases plasma Ca++
As plasma calcium increases, this is sensed by the parathyroid glands as negative feedback –> less PTH will be produced, and this is how calcium homeostasis is maintained
What is normal PTH level?
10 to 65 nanomoles/L
What are the causes of hypercalcemia?
1) Due to raised PTH –> hyperparathyroidism (increased production of PTH)
2) Due to decreased PTH: • Hypercalcemia of malignancy • Vitamin D toxicity • Immobilization • Thiazide diuretics • Granulomatous disease (sarcoidosis)
What is hyperparathyroidism?
- Increased production of parathyroid hormone
* Serum calcium may be decreased, increased or normal, depending upon renal function
What is primary hyperparathyroidism?
Excess of parathyroid hormone from adenoma (85 to 95%), hyperplasia (5 to 10%) or carcinoma (1%)
Note: >95% of cases, primary hyperparathyroidism is caused by a sporadic adenoma or sporadic hyperplasia
Scribe note: PTH normal or increased, calcium increased
What is secondary hyperparathyroidism?
Adaptive increase in parathyroid hormone secondary to hypocalcemia and hyperphosphatemia of chronic renal failure
Scribe note: PTH increased, calcium normal or decreased
What is tertiary hyperparathyroidism?
autonomous parathyroid hyperfunction in patients with secondary hyperparathyroidism
Scribe note: Both PTH and calcium are increased since it is autonomous
Signs and symptoms of hyperparathyroidism
- Asymptomatic
* “Bones, stones, abdominal groans, psychic moans”
Effects/symptoms of the main cause of hyperparathyroidism, parathyroid adenoma:
BONE. Excess PTH acts on bone, causing calcium to leech out and cause osteoporosis (prone to fractures) and osteitis fibrosa cystica (radiolucent areas, called brown tumor, due to hemorrhage).
RENAL. Patient may develop kidney stones, frequent urination, and nephrocalcinosis (increased calcium reabsorption in renal tubules causes calcifications).
GI TRACT. Patient may develop peptic ulcer, gallstones, and acute pancreatitis
BRAIN. Hyperparathyroidism can cause depression or seizures
BLOOD. Hypercalcemia, hypophosphatemia
Brown tumor
Osteitis fibrosa cystica
What’s parathyroid adenoma?
- Benign neoplasm
- Involve a single gland, rarely two or more (<1%)
- Major cause of primary hyperparathyroidism
- Any age, F:M 3:1
- Excellent prognosis after excision
Major cause of hyperparathyroidism
Parathyroid adenoma
Appearance of parathyroid adenoma
- Sharply demarcated from the adjacent rim of normal parathyroid
- Predominantly chief cells in sheets or tubules
- Adipose tissue inconspicuous
What’s parathyroid hyperplasia?
- Classically all four parathyroid involved (frequently asymmetrical)
- Sporadic or as a component of MEN syndrome
- 75% of patients – sporadic
- 15% of patients – part of MEN 2A (not MEN 2B)
- 15% of hyperparathyroidism cases
Note: diagnosis of adenoma versus hyperplasia may depend on the size of the other glands
Appearance of parathyroid hyperplasia
- Enlarged parathyroids
- Stromal fat inconspicuous
- Usually chief cell hyperplasia, diffuse or nodular
- Variable oncocytes
- Cystic change in markedly enlarged glands
What’s parathyroid carcinoma?
- Palpable neck mass (75%)
- Excessive PTH secretion, high serum calcium > 14 mg/dl
- Non-functioning tumors are rare
- Diagnosis based on local invasion and metastases (clinical criteria, NOT microscopic criteria)
- 1/3 recur locally, 1/3 have distant metastases
Appearance of parathyroid carcinoma
- Capsular invasion
- Densely adherent to surrounding soft tissue
- Thick fibrous bands
- Predominantly chief cells arranged in solid or trabecular pattern
- Macronucleoli, more than five mitoses per 50 high-power fields, and necrosis associated with aggressive behavior
- Cytological detail, unreliable for the diagnosis of carcinoma
- Vascular invasion and metastasis (ABSOLUTE CRITERIA)
- Local recurrence (1/3 of cases), distant metastasis (in another 1/3)
What is hypoparathyroidism?
- Disorder in which insufficient parathyroid hormone (PTH) is secreted from the parathyroid glands, resulting in abnormally low levels of calcium in the blood
- Far less common
Causes of hypoparathyroidism
- Damage to the gland or its vessels during thyroid surgery
* Idiopathic, autoimmune disease, congenital
Clinical features of hypoparathyroidism
- Tetany
- Convulsion
- Neuromuscular irritability
- Cardiac arrhythmias
- Increased intracranial pressure
- Seizures
MEN stands for?
Multiple Endocrine Neoplasia
What’s MEN I?
- AKA Wermer syndrome
* Neoplasia of: pituitary, parathyroids, pancreas and carcinoids, parathyroid hyperplasia
What’s MEN IIA?
- AKA Sipple’s Syndrome
* Medullary throid carcinoma (c-cell), parathyroid hyperplasia, pheochromocytomas (tumor of adrenal medullary)
What’s MEN IIB?
- Neuromas of the eye, buccal mucosa, and GI mucosa
* There may be medullary thyroid carcinoma and pheochromocytomas
What’s the largest endocrine organ?
Thyroid
What are the thyroid hormones?
• Thyroid hormones (TH):
- Thyroxine (T4) - Triiodothyronine (T3) - Calcitonin
Layers of skin
• Epidermis - top most layer, contains melanocytes (makes pigment) and Langerhans cells (immune cells)
• Dermis - located beneath the epidermis, contains dendritic cells (immune cells) and appendages
- appendages include: hair follicles, sweat glands, Pacinian corpuscles (pressure receptors).
- Red tissue you see when you skin your knee and the epidermis has been removed
• Subcutaneous fat
Where are melanocytes derived from?
- Neural crest derived cells
- Present in epidermal basal layer
- Synthesize melanin
Synthesis of melanin
- Synthesized in melanosomes
- Catalyzed by tyrosine
- Tyrosine -> DOPA –> melanin
- Dendritic processes extend between keratinocytes
- Melanin is transferred from melanocytes to neighboring keratinocytes in melanosomes
Innate immune response: what is it, physical barriers, soluble factors, cells involved?
- Immediate defense; short lived; no memory
- Physical barriers include skin and mucosal epithelia
- Soluble factors include complement, antimicrobial peptides, chemokines, and cytokines
- Cells include monocytes/macrophages, dendritic cells, natural killer cells, and neutrophils
Adaptive immune response
- Has memory; has specificity; long lasting
- Initiated by dendritic antigen-presenting cells
- Langerhan cells in the epidermis
- Dermal dendritic cells in the dermis
- Executed by T cells and antibodies produced by B cells and plasma cells
Which dendritic antigen presenting cell is present in the epidermis?
Langerhans cells
Which dendritic antigen presenting cell is present in the dermis?
Dendritic cells
What are keratinocytes?
- Present in melanosomes
* Secrete cytokines, chemokines, arachidonic acid metabolites, complement components, and antimicrobial peptides
What are Langerhans cells?
- Antigen presenting cells in the epidermis
- Phagocytose antigens
- Migrate via lymphatics to regional lymph nodes
- Expresses protein on its surface to T lymphocytes then undergo clonal proliferation
What do Langerhans cells do, and how do they travel?
- Phagocytose antigens
- Migrate via lymphatics to regional lymph nodes
- Express antigen protein on their surface and present to T lymphocytes, then undergo clonal proliferation
Plays a similar role to Langerhans cells in the dermis…
Dermal dendritiic cells
What are natural killer (NK) cells?
- Survey the body looking for transformed or infected cells
* Kill cells directly or indirectly via the secretion of cytokines
What are macrophages?
- Cutaneous immune surveillance in the dermis
* Phagocytic function (also neutrophils): take up pathogens, recognize them, and destroy them
What is a macule?
- Circumscribed FLAT lesion
* 5mm or smaller in diameter
What is a patch?
- Flat circumscibed lesion
* > 5mm
What is a papule?
- ELEVATED dome-shaped or flat-topped lesion
* 5mm or less across
What is a nodule?
Greater than 5mm
What is a pustule?
Discrete, pus-filled, raised lesion
What is a plaque?
- Elevated flat-topped lesion
* Greater than 5mm across
What is a petechiae?
- Small (1-2mm) red or purple macules due to minor hemorrahage
- Do not blanch with pressure
What is a purpura?
- Large hemorrhagic lesion
- 0.3 - 1cm red or purple macules and patches
- Do not blanch with pressure
These two skin lesions do not blanch with pressure…
Purpura and petechiae
What is a vesicle?
- Fluid-filled raised lesion
* 5mm or less across
What is a bulla?
- Fluid-filled raised lesion
* Greater than 5mm
What is a wheal?
- Itchy, transient, elevated lesion, +/- erythema
* Dermal edema
What is a scale?
- Dry, horny, plate like excrescence
* Imperfect cornification
What is lichenification?
• Caused by repeated rubbing/scratching
• Thickened and rough skin, prominent skin markings
** Looks like lichen
What is ulceration?
Complete loss of the epidermis, revealing dermis or subcutis.
What is eschar?
When tissue dies, turns black, and sloughs.
What is onycholysis?
Nail separates from nail bed.
Microscopic terms used to describe skin findings
- Hyperkeratosis: thickening of the stratum corneum
- Basket weave hyperkeratosis: most normal healthy skin on our body is keratinized in this fashion
- Compact hyperkeratosis: the soles of feet and palms of hands are thicker
- Parakeratosis: keratinization with retained nuclei in the stratum corneum
- Hypergranulosis: hyperplasia of the stratum granulosum
- Spongiosis: intercellular edema of the epidermis
- Hydropic swelling (ballooning): intracellular edema of keratinocytes
- Acanthosis: diffuse epidermal hyperplasia wih thickening of the malphigian layer
- Acantholysis: loss of intercellular cohesion between keratinocytes
- Dysplasia: premalignant proliferation; disorderly, pleomorphic, lacks maturation
- Dyskeratosis: premature keratinization of cells below the stratum granulosum
What is hyperkeratosis?
Thickening of the stratum corneum.
• Basket weave hyperkeratosis: most normal healthy skin on our body is keratinized in this fashion
• Compact hyperkeratosis: the soles of feet and palms of hands are thicker
What is parakeratosis?
Keratinization with retained nuclei in the stratum corneum.
What is hypergranulosis?
Hyperplasia of the stratum granulosum.
What is spongiosis?
Intercellular edema of the epidermis.
What is hydropic swelling (ballooning)?
Intracellular edema of keratinocytes.
What is acanthosis?
Diffuse epidermal hyperplasia with thickening of the malphigian layer.
What is acantholysis?
Loss on intercellular cohesion between keratinocytes
What is dysplasia?
- Premalignant proliferation
* Disorderly, pleomorphic, lacks maturation
What is dyskeratosis?
• Premature keratinization of cells below the stratum granulosum.
Histologic pattern of inflammatory skin disease –> perivascular dermatitis
Can be superficial and deep
Histologic pattern of inflammatory skin disease –> vasculitis
- Injury to blood vessels, causing blood cells to leak out
* Grossly we see petechiae and purpura
Histologic pattern of inflammatory skin disease –> vesicular dermatitis
Blistering diseases like pemphigoid
Histologic pattern of inflammatory skin disease –> diffuse dermatitis
Example: sarcoidosis
Histologic pattern of inflammatory skin disease –> panniculitis
Subcutaneous fat is inflamed.
Group of disorders of differing etiologies that share similar morphologic and histological features spongiotic dermatitis.
Skin rash
Eczematous dermatitis
Acute appearance of eczematous dermatitis
- Erythema
- Aggregates of tiny pruritic vesicles (1mm)
- Itchy, excude clear fluid, and become encrusted
Chronic appearance of eczematous dermatitis
- Scaly and thickened (lichenification) from continued scratching
- Acanthosis: spongiosum layer gets thickened due to causes like rubbing or psoriasis
- Hyperkeratosis: thickening of the stratum corneum
- Dermal scarring
A generic term applied to acute or chronic inflammatory reactions to substances that come in contact with the skin.
Contact dermatitis
Two variants of contact dermatitis
- Allergic contact
* Irritant contact
What is allergic contact dermatitis?
- Idiosyncratic immunological reaction to an environmental allergen
- Cell-mediated, delayed (type IV) hypersensitivity reaction mediated by Langerhans cells and t-cells.
- Ex: poison ivy; nickel; chromates; synthetic rubber; primula; topical creams
What is irritant contact dermatitis?
- Follows exposure to physical or chemical substances capable of direct damage to the skin.
- Mechanisms include keratin denaturation, removal of surface lipids and water, damage to cell membranes, and direct cytotoxic effects
- Ex: Soaps, detergents, acids and alkalis, industrial solvents
What is atopic dermatitis?
- Chronic, relapsing eczematous rash.
- Any age, but often begins in infancy
- In infants it often affects: head, face, neck, diaper area, and extensor aspects
- In childhood it involves flexural aspects (e.g. back and knees).
- Pruritus is intense - scratching leads to lichenification
- Risk of secondary bacterial, dermatophyte and viral infections
- Disease improves during childhood, with >50% clearing by teen years.
Etiology of atopic dermatitis
Multifactorial: • Genetic susceptibility • Abnormal skin barrier function • Abnormal immune system activity • Environmental factors
Personal or family history of asthma or allergies:
• 75% have a family history of atopy (genetic disposition to develop an allergic reaction)
• 50% have associated asthma or hay fever
Associated with dry skin (xerosis): worsens in the winter months
A very common chronic dermatosis characterized by redness and scaling where the sebaceous glands are most active: face, scalp, presternal area, body folds
Seborrheic dermatitis
- Presents in infants; second peak in adults
- Male predominance; often a family history
Skin findings of seborrheic dermatitis
Erythematous or yellowish patches, covered by a greasy scale
Pathogenesis of seborrheic dermatitis
Pathogenesis is unknown.
• Linked with the yeast Malessezia, immunologic abnormalities, sebaceous activity, stress, neurological disorders, and AIDS
Course of seborrheic dermatitis
- Self-limited with a good prognosis in infants
* Chronic and relapsing in adults
Delayed hypersensitivity type 4 reaction to photo product of topical or systemic medications and chemicals
Photoallergic reactions
• An allergic reaction to something on skin or in blood, as a result of photochemical reaction
Skin lesions observed in photoallergic reactions
- Eczematous papular, vesicular, scaling, and crusted
* Can persist for months or years
What are phototoxic reactions?
UV radiation associated with use of medications causes formation of toxic photoproducts such as free radicals
• Damages DNA or cell membranes
Skin findings of phototoxic reactions
- Occurs on sun-exposed skin
- Occurs minutes to hours after sun exposure
- Mimics severe sunburn: erythema, edema, and blistering desquamation and post inflammatory hyperpigmentation
An acute self-limited, usually mild, often relapsing mucocutaneous syndrome characterized by presence of target-shaped plaques with or without central blisters, predominantly on face and extremeties.
Erythema multiforme
• Any age, peaks in 20-40s; children
What is erythema multiforme minor?
No mucosal involvement
What is erythema multiforme major?
Mucosal involvement
Pathogenesis of erythema multiforme
Epithelial cells are killed by skin-homing CD8+ cytotoxic T lymphocytes
• Immunologic response, most often, to a recurrent herpes simplex virus
• Can also be stimulated by M. peumoniae, drugs, neoplasia
• Begins a week after a recurrence of herpes
In other words: caused by CD8+ T-cells that kill epithelial cells. This is stimulated by herpes simplex cirus, which makes us attach our own skin.
TARGET LESIONS, macules, papules, vesicles, bullae are associated with which inflammatory skin disease?
Erythema multiforme
Additional skin findings:
• symmetric, extremities, arms, legs, hands, feet, anywhere
• Half have oral or vermillion border lesions
Microscopic appearance of erythema multiforme
- interface dermatitis because vacuolar change and cleft formation occur at the dermal-epidermal junction
- Necrotic basal keratinocytes
- Lymphocytic infiltrates of interface and superficial perivascular zones.
What is Stevens-Johnson Syndrome, aka Toxic Epidermal Necrolysis?
- Acute, life-threatening skin and mucous membrane reaction characterized by extensive necrosis and detachment of the epidermis.
- Previously considered severe variants of erythema multiforme, but now considered a separate entity.
- An epidermal emergency
Stevens-Johnson-Syndrome and Toxic Epidermal Necrolysis are the same process, but vary in the % of involved surface area…
- SJS if involved area < 10% of body surface
- SJS/TEN overlap if 10-30%
- Toxic epidermal necrolysis if > 30%
Risk factors for SJS and TEN
- Rare
- Any age, but risk increases with age
- 2F:1M predilection
- Increased risk: HIV, collagen vascular disease and cancer
Mortality SJS vs TEN
SJS: 5-12%
TEN: > 30%
Skin findings on SJS/TEN
- Confluent, erythematous, purpuric and target-like macules evolve into flaccid blisters and epidermal detachment
- Mostly trunk, extremities, and mucous membranes
Pathogenesis of SJS/TEN
Cell-mediated cytotoxic reaction against keratinocytes leads to massive apoptosis.
Common (1%), pruritic (itchy), symmetrical, papulosquamous dermatosis
Lichen planus
Add’l info:
• Often presents in fourth to sixth decades; uncommon in childhood
• Slight female predominance
• Familial cases reported. Associated with specific HLA types
• Usually self-limiting-lesions clear from weeks to 1 or 2 years. Sometimes protracted.
Skin findings for lichen planus
- Four P’s: polygonal, pruritic, purple papule; few millimeters to 1 cm
- Wickham’s striae - white streaks
Inflammatory skin disease where Wickham’s striae (white streaks) are observed
Lichen Planus
Sites affected by Lichen Planus
- Flexor aspect of the wrists, the forearms, the extensor aspect of the hands and ankles, lumbar area, nails, glans penis and generalized
- Oral involvement common: may involve pharynx, larynx, esophagus, nose, anus, and genitalia; ocular rare
Microscopic appearance of Lichen Planus
- Interface dermatitis
- Dense, band like lymphocytic infiltrate along the D-E junction
- Vacuolar degeneration of the basal layer
- Hypergranulosis, hyperkeratosis and sawtoothing of epidermis
- Necrotic keratinocytes - “Civatte bodies”
Civatte bodies, which are necrotic keratinocytes, are observed in which inflammatory skin disease?
Lichen Planus
Pathogenesis of Lichen Planus
- Possibly expression of altered external antigen stimulus elicits a cell-mediated cytotoxic T-cell immune response at the level of the dermoepidermal junction
- Assoociated with viral infections, metals, and drugs.
- Body mistakes own antigens for external antigens
Course of Lichen planus
- Unpredictable disease
- Typically persists for 1-2 years, but may follow a chronic, relapsing course over many years
- Rx: Topical and systemic glucocorticoids, cyclosporine
- NAILS may be affected: longitudinal ridging, thinning, and distal splitting of the nail plate
Common chronic inflammatory dermatosis characterized by erythmatous scaly plaques of the elbows, knees, scalp, lumbosacral areas and other sites
Psoriasis
Which inflammatory skin disease is this:
- Associated with arthritis, myopathy, enteropathy, joint disease, AIDS.
- Polygenic trait
Psoriasis
Additional info:
• Any age, bimodal
• Often presents in the teens and in early adult life (type I).
• Second peak in sixth decade (type II).
More on polygenic trait: one parent has psoriasis 8% of kids get psoriasis. Both parents have psoriasis, 41% of kids get psoriasis.
Acute form of psoriasis
Eruptive, guttate psoriasis; multiple small lesions; greater tendency toward spontaneous resolution; 2%
Chronic stable plaque psoriasis
- Majority of patients
* Chronic indolent lesions present for months and years
Pathogenesis of psoriasis
- Multifactorial, both genetic and environmental factors
- Interactions between CD4+ T-cells, CD8+ T-cells, dendritic cells, and keratinocytes causing bassal keratinocytes to hyperproliferate
- Strong association with HLA-Cw6; only 10% develop psoriasis
- Systemic glucocorticoids, oral lithium, antimalarial drugs, interferon, adrenergic blockers and alcohol can cause flares
Which inflammatory skin disease has a strong association with HLA-Cw6?
Psoriasis
Skin findings for psoriasis
- Begin as papules, coalesce to form raised, sharply demarcated plaques, silvery scale surface, erythematous base
- Elbows, knees, scalp, lumbosacral areas, intergluteal cleft, and glans penis
- Nail pitting and onycholysis
- Auspitz’s sign: small droplets of blood when removing scales
What is Auspitz’s sign, and in which inflammatory skin disease is it observed?
- Auspitz’s sign is small droplets of blood when removing scales
- Psoriasis
Destruction of the interphalangeal joints resulting in telescoping fingers.
Psoriatic arthritis
Microscopic appearance of psoriasis
- Acanthosis
- Elongation of the rete ridges, suprapapillary thinning, parakeratotic scale, spongiosis and superficial perivascular inflammation
- Munro’s microabscesses - neutrophils aggregates within the parakeratotic stratum corneum
- Spongiform pustules - neutrophils form small aggregates within epidermis
In which inflammatory skin disease are Munro’s microabscesses and spongiform pustules are observed?
Psoriasis
- Munro’s microabscesses: neutrophils aggregates within the parakeratotic stratum corneum
- Spongiform pustules: neutrophils form small aggregates within epidermis
Inflammatory skin diseases include _______ disorders and _______
Blistering disorders; adverse cutaneous drug reactions
Infectious skin diseases can be _____, _____, or _____
Viral, fungal, or infestations
Pemphigus Vulgaris, Bullous Phemphigoid, Dermatitis Herpetiformis
Blistering Disorders
Exanthematous drug eruption, Acute exanthematous pustulosis, Acneiform eruptions, Urticarial eruptions, Fixed drug eruption
Adverse cutaneous drug reactions
Verruca vulgaris, Mulluscum contagiosum, Herpes simplex, Varicella zoster (chickenpox and shingles)
Viral diseases
Dermatophyte infections, pityriasis versicolor, candida infection
Fungal disease
Pediculosis
Infestations
What is pemphigus?
- A serious autoimmune mucocutaeous blistering disorder caused by IgG autoantibodies against desmogleins (proteins involved in cell to cell attachment) causing acantholysis and intraepidermal bullae.
- Disease associated with specific HLA haplotypes.
- Majority fourth to sixth decades; M = F
Net-like pericellular IgG deposit for immunofluorescence indicates this…
Pemphigus
Skin findings for pemphigus vulgaris..
- Superficial vesicles and FLACCID bullae which rupture leaving shallow crusted erosions.
- Commonly involves scalp, face, axilla, groin, trunk, and pressure points.
- Oral ulcers may persist for months before onset of skin involvement.
- Extracutaneous sites include the nasopharynx, larynx, esophagus, ear, eye, urethra, anal, and colonic mucosa.
- Nikolsky sign positive, dislodge epidermis by lateral pressure near lesions.
Which blistering disorder involves positive Nikolsky sign and dislodge epidermis by lateral pressure near lesions?
Pemphigus vulgaris
Treatment for Pemphigus vulgaris
• Systemic corticosteroids, immunosuppressive agents. Manage fluids and infections
Course of Pemphigus vulgaris
- Systemic glucocorticoids and use of immunosuppressive therapy have dramatically improved the prognosis; still significant mortality because patients have trouble maintaining fluid dynamics (ooze causes loss of water) and high risk of infection.
- Before glucocorticoid therapy, almost invariably fatal.
Microscopic appearance of pemphigus vularis
- Acantholysis: the lysis, of the desmosomes connecting squamous cells leads to a suprabasal vesicle.
- Superficial dermal infiltration by lymphocytes, histiocytes, and eosinophils.
What is bullous pemphigoid?
- A bullous autoimmune disease usually in elderly patients.
* Most cases sporadic. Few associated with UV light and medications.
Pathogenesis of bullous pemphigoid
- Auto-antibodies react with basal cell – basement membrane hemidesmosomes involved in dermoepidermal bonding.
- Two forms of antigen recognized: BPAG1 and BPAG2 (collagen type XVIII).
- Causes complement activation, recruitment of neutrophils & eosinophils and injury.
What antigens are recognized in Bullous Pemphigoid?
BPAG1 and BPAG2 (collagen type XVIII).
Skin findings of Bullous Pemphigoid
- TENSE bullae, filled with clear fluid, on normal or erythematous skin usually up to 2 cm or greater in diameter
- Nikolsky sign negative
- Affects any area; lower abdomen, thighs, forearms, axillae, and groin most common
- Oral lesions in 10% to 15%; usually appear after skin lesions
Treatment for bullae pemphigoid
Systemic prednisone alone or combined with azathioprine
Course of bullae pemphigoid
- Patients often go into a permanent remission after therapy.
- Some go into spontaneous remission without therapy.
Microscopic appearance of bullous pemphigoid
- SUBEPIDERMAL BLISTERS containing eosinophils, lymphocytes, and occasional neutrophils.
- Dermal edema, perivascular lymphocytes and eosinophils.
When doing immunoflorescence a linear deposition of IgG and complement in the basement membrane zone…
Bullous pemphigoid
What is dermatitis herpetiformis?
- A rare, chronic, intensely burning, pruritic papulovesicular eruption associated with GLUTIN SENSITIVE ENTEROPATHY AND IgA DEPOSITS in upper dermis.
- all ages, but 20-40 years most common
- Male to female ratio is 2:1
- Caucasians mainly affected; rare in Asians and blacks
- Familial involvement; up to 10% of cases
- Relatives of patients with DH have increased risk for celiac disease.
Relatives of patients with dermatitis herpetiformis have increased risk for this…
celiac disease
Skin findings for dermatitis herpetiformis
- Pruritic papulovesicular and urticarial rash
- Often symmetrical, posterior scalp, shoulders, back, buttocks, and extensor aspects of the limbs; excoriation and/or lichenification
- Occasionally, larger blisters. Oral involvement is rare.
Pathogenesis of dermatitis herpetiformis
- Genetically predisposed patients develop IgA antibodies to gluten in diet
- Antibodies cross-react with reticulin, a component of the fibrils that anchor the epidermal basement membrane to the dermis.
- Asymptomatic patients can develop GI lesions with large gluten intake. Some people with DH and GSE respond to a gluten free diet.
- Increased incidence of thyroid disease, insulin-dependent diabetes mellitus, and connective tissue diseases.
Immunofluorescence reveals discontinuous, granular deposits of IgA localized to the tips of ermal papillae in normal appearing skin.
Dermatitis Herpetiformis
Treatment for dermatitis herpetiformis
Sulfones; gluten free diet
Microscopic findings for dermatitis herpetiformis
- Papillary dermal neutrophilic microabscesses within the tips of the dermal papillae.
- Coalesce to multilocular subepidermal vesicles.
- Dermal mixed inflammatory infiltrate of lymphocytes, histiocytes, and abundant neutrophils.
What are adverse cutaneous drug reactions?
- Mimic virtually all skin rashes.
- First consideration in the DDx (differential diagnosis?) of a suddenly appearing eruption.
- Occur in both systemic or topical administration of a drug.
- Most are mild, pruritic, and resolve after drug discontinued.
- Severe, life-threatening ACDRs do occur.
What causes adverse cutaneous drug reactions?
- Caused by immunologic and nonimmunologic mechanisms.
- The majority are immunologic hypersensitivity reactions and may be of types I, II, III, or IV.
- Nonimmunologic mechanisms include idiosyncratic, irritant toxicity photosensativity reaction, accumulation of drug, atrophy secondary to drug effect.
What is exanthematous drug eruption?
- Exanthem = breaking out in mouth
- Moribiliform = measles-like
- Hypersensitivity reaction to an ingested or parenterally administered drug
- Symmetric; almost always on trunk and extremities
- Intertriginous areas
What are pustular eruptions?
- Acute generalized exanthematous pustulosis
- Acute febrile eruption; often leukocytosis
- Drug or virus can trigger the eruption
Skin findings for pustular eruptions
- Nonfollicular sterile pustules on a diffuse, edematous erythema
- Usually starting in the folds and/or the face
- Resolves spontaneously in two weeks
Acneform eruptions (mimics acne) may appear in atypical areas, such as on the arms and legs, in this adverse cutaneous drug reaction…
Pustular eruptions
What are urticarial eruptions?
- Pruritic red WHEALS, generally last for < 24 hours; new lesions can develop
- Pruritus, cutaneous flushing, nausea, vomiting, diarrhea, abdominal pain, rhinorrhea, laryngeal edema, bronchospasm, hypotension
- Angiodema - deep dermal and subcutaneous tissues swollen, nonpruritic; lasts for 1-2 hours, up to 2-5 days
- Can be IgE-mediated or non-IgE-mediated
- IgE mediated: immediate hypersensitivity reaction: penicillin; ABs
- Non IgE mediated: direct stimulation of mast cells: NSAIDs, ACE-inhibitors and opioids
What are fixed drug eruptions?
- Solitary, erythematous,dusky macules or plaques; May blister
- 30 min to 8-16 hours after ingestion
- ** On rechallenge, lesions recur in same spot; often with new lesions
- Commonly genitalia and perianal area; anywhere
- +/- burning fever, malaise, and abdominal symptoms
- Acute phase lasts days to weeks; residual hyperpigmentation
- Hundreds of drugs can cause fixed eruption
Which adverse cutaneous drug reaction on rechallenge, lesions recur in the same spot?
Fixed drug eruptions
What is verruca vulgaris?
- Common wart
* Human papillomavirus (HPV) infection
Common warts (verruca vulgaris) are caused by HPV types…
1, 2, 4, 7, and 26-29
Skin findings for verruca vulgaris
- Firm, flesh colored, keratotic papules 1-10mm
- Anywhere, any age
- Most common location: backs of the hands, fingers and knees
- Persist for months up to years and often regress spontaneously
Microscopic finding for verruca vulgaris
- Acanthosis
- Hyperkeratosis
- Papillomatosis
- Hypergranulosis
- Inward folding of rete
Treatment for verruca vulgaris
- Topical salicylic acid preparations, liquid nitrogen, and very light electrocautery for initial therapy.
- Burn or freeze warts off
HPV types that cause plantar warts
- Plantar surface of feet can get warts
* Caused by HPV 1, 2, 4, 63
HPV types that cause planar warts
HPV 3, 10, 27, 38, 41, 49, 75, 76
HPV types that cause condyloma accuminatum
- Fleshy moist warts on genitalia, can look like syphilis
* HPV 6, 11, 30, 43, 43, 44, 45, 51, 54, 55, 70
HPV types that cause epidermodysplasia verruciformis
- A genetic disease, patient is highly predisposed to HPV infection
- HPV 5
What is mulluscum contagiosum?
Viral skin infection from DNA pox virus
Transmission of mulluscum contagiosum
Direct cutaneous contact; fomites; sexual contact in young adults
Skin findings for mulluscum contagiosum
- Clusters of small 1 to 6 mm white, pink or brown papules with CENTRAL PIT (umbilicated)
- Can be much larger in HIV patients
- Face, trunk, and limbs
• COURSE: may persist for months or occasionally years and remit
Microscopic appearance of Mulluscum Contagiosum
- Proliferation of epidermis in PEAR shaped lobules
* Maturing epidermal cells contain mulluscum bodies, eosinophilic inclusions compressing the nucleus
Which viral skin disease is associated with pear-shaped lobules of epidermal proliferation with pink bodies (mulluscum bodies) that rise into the umbilication?
Mulluscum contagiosum
Are HSV-1 and HSV-2 DNA or RNA viruses?
DNA
HSV-1 usually causes…
• Herpes labialis
HSV-2 usually causes…
• Herpes genitalis
How is HSV transmitted?
- Transmitted through mucosal surfaces or break in skin by contact or exposure to secretions.
- First-episode often with fever and malaise
What is herpetic whitlow?
• HSV infection, involvement of a finger or hand; often healthcare workers, dental practitioners
How to diagnose this is a herpes virus?
- Tzank smear
- Unroof a vesicle and scrape the base onto a slide
- Viral cytopathy present in cells
Skin findings for herpes simplex
- Small grouped vesicles
- +/- erythematous base
- Evolve into pustules, rupture and form a crusted ulcer
- Mucosal lesions ulcerate early
Microscopic findings for herpes simplex
- Ballooning degeneration coalesce to intraepidermal vesicle
- Multinucleation
- Intranuclear inclusions
- Nuclei have a ground-glass look because millions of live virus inside
- Dense red inclusion is a degeneration byproduct
- Nuclear molding
- Margination
- Almost looks like vasculitis, because so much dermal inflammation
Course of herpes simplex
- Primary episode resolve completely in around 15 days
- Virus persists, become latent within the ganglia of the corresponding sensory nerve
- Recurrent HSV lesions are usually less florid than the first infection without general symptoms
- Secondary outbreaks are precipitated by sunlight, fever, menstruation, pregnancy, HIV infection, emotional stress, or local trauma
Treatment ofr herpes simplex
Acyclovir tropical and oral
What is varicella zoster?
- Herpes varicella zoster virus infection
- Chickenpox
- Worldwide, all races, gender and age
- Largely a childhood disease < 10 years of age
- Incubation period 2-3 weeks
- ** Remains in anterior horn cells and be reactivated as herpes zoster infection (shingles)
Mode of transmission of varicella zoster?
- Highly contagious
- Inhaled fomite droplets
- Direct contact with the fluid from the open sores
Used to diagnosis chickenpox/varicella zoster
Tzank smear
Skin findings for chickenpox
- Pruritic red papules & vesicles to crusted ulcer
- Commonly affected areas include trunk, back, face
- Spreads distally (lesions usually start centrally - near bellybutton - then grow out peripherally)
- Can involve palms soles and mouth
- Remain infectious for 4-5 days until vesicles crusted
What are varicella zoster - shingles?
• Reactivation of varicella virus infection manifests as a painful outbreak of papules and vesicle in a dermatome distribution
Shingles, increasing incidence with…
- Age: average 55 y/o
- Immunosuppression
- Malignancy, especially from lymphoproliferative disorders and chemotherapy/radiotherapy
- HIV/AIDS: eightfold increased incidence of HZ
- Most cases triggering factors are not known
What is prodrome?
Shingles may have a prodrome, meaning certain symptoms occur before specific symptoms of shingle occur: • pain in dermatome distribution • fever and headache • lymph nodes enlarged and tender • 1-3 day prior to rash
Skin findings for varicella zoster-shingles
- Crops of red papules, progress to vesicles in a dermatome pattern
- Thoracic, lumbar, facial
- Lesions very painful
Even after rash resolves you can have post-herpetic neuralgia:
• Pain may persist for months or years
Treatment for varicella zoster
- Acyclovir
* Prevention through vaccination
What is impetigo?
- Superficial staph aureus skin infection; strep pyogenes may also be the culprit
- Can occur at any age, but most common in children
How is impetigo spread?
- Contagious
* Spread by close contact through primary breaks in skin or secondary involvement of rash or preexisting lesion
Clinical presentation of impetigo
- Bullous (less common):
- caused by an epidermolytic toxin produced at the site of intefection (bacteria produces toxin that causes epidermal cells to lyse)
- causes intraepidermal cleavage below or within the stratum granulosum
- Nonbullous
Skin findings for impetigo
- Pustules and oozing patches
- Golden yellow honey crusts or blisters (bullous impetigo)
- Most often exposed areas such as the hands and face, or in skin folds (axilla)
Golden yellow honey crusts or blisters observed in …
Impetigo
Microscopic appearance of impetigo…
Neutrophil filled subcorneal vesicle
What is cellulitis?
- Bacterial infection of skin and subcutis
* Usually caused by strep pyogenes (2/3), and staph aureus (1/3)
Skin findings for cellulitis
- Expanding area of redness, swelling, warmth, tenderness, blistering abscess, ulteration
- Often fever and leukocytosis
- Can ascend up lymphatics = lymphangitis
- Infection involves lymphatics
- Red line originates from the cellulitis leading to draining lymph nodes
- Minor trauma to the skin is common cause
- Seen commonly in peripheral vascular disease, diabetes, lymphedema, and alcohol predispose
Treatment for cellulitis
Antibiotics
What is scarlet fever?
• Streptococcus pharyngitis with erythrogenic toxic strains (a streptococcus infection - a toxin causes redness in affected person)
Clinical findings of scarlet fever
- Fever
- Sore throat
- Lymphadenopathy
- Headache
- Vomiting
- Strawberry tongue
- Abdominal pain
- Aches
- Malaise
Manifestation of strawberry tongue
Scarlet fever
What are sand paper rash
- Rashes for scarlet fever
* Begins as scarlet blotches, progresses to look like sunburn with goose pimples
Treatment for scarlet fever
Systemic antibiotic
What’s dermatophyte infections?
- Superficial fungal infection of the keratin of the stratum corneum, hair or nail
- Three species: Microsporum, Trichophyton, and Epidermophyton
- Spread is by contact, animals, or soil
- Favors moist and warm conditions
Skin findings for dermatophyte infections
- Expanding, erythematous, scaly, annular lesions with central clearing (ringworm)
- Less common vesicles, bullae, pustules
Treatment for dermatophyte infections
- Topical antifungals
* Systemic for severe or refractory cases
Microscopic findings for dermatophyte infections
PAS stain will reveal fungal hyphae in the stratum corneum
KOH (potassium hydroxide) prep
- Another test that can be done for dermatophyte infections
- A scraping of the lesion placed on a slide in a drop of KOH
- Visualization of fungal hyphae is a positive test
What’s Wood’s lamp?
- A backlight, which will cause infected lesion to fluoresce
- Pertains to dermatophyte infections
- Can be used for differential diagnosis against psoriasis
Clinical name for dermatophyte infection
• Tinea
Buffet of tinea infections:
• Tinea corporis - when fungal infection involves body
• Tinea capitis - involves scalp
• Tinea pedis - aka athlete’s foot
• Onychomycosis - fungal infection of nails. Less treatable when involves nails
What is pityriasis versicolor?
- Superficial fungal infection by Malassezia furfur
- Often young adults 20-40
- F:M, 2:1
- More common in warm climate
- Children more common in tropics
Skin findings for pityriasis versicolor
- Multiple, oval, well demarcated, hypo- or hyperpigmented macular lesions
- Become confluent and extensive
- Trunk and shoulders most common
Microscopic findings for pityriasis versicolor
Yeast and short septate hyphae, spaghetti and meatballs
Spaghetti and meatballs
Pityriasis versicolor
Treatment for pityriasis versicolor
Tropical antifungals
What is a candida infection?
- Persistent/recurrent infections of the skin, nails, and oropharynx
- Fungal organisms with yeast and pseudohyphal forms
- Candida albicans most common
Predisposing factors for candida infection
- Immunosuppression
- Diabetes
- Cushings disease
- Pregnancy
- Malnutrition
- HIV
- Systemic steroid and antibiotics
- Predelection for moist, occluded skin
- Intertrigo (seen below the breast), occlusive dressings, diaper dermatitis
Skin findings for candida infection
- Erythematous, pruritic, tender, painful rash
* In neonates, curd like pseudomembrane on an erythematous base
Mucosal candiasis
- Oral thrush - white patches inside mouth
- Angular chelitis - inflammation at corners of mouth
- Vulvovaginal trush
Chronic forms of candida infection frequently associated with…
Endocrinopathies
What are scabies?
- Infestation by mite
* Sarcoptes scabiei
Skin findings for scabies
- Papules and burrows between fingers or along the sides of the fingers, soles, and sides of the feet with excoriations and eczematous dermatitis
- Also affects elbows, axillae, scrotum, penis, labia
Transmission of scabies
Close personal contact and sexually transmitted
What is pediculosis?
• An infestation of sucking lice that lay their eggs on hair shafts or in seams of clothing
Species that infest humans to cause pediculosis…
- Pediculus humanus: capitus (headlice) and humanus (bodylice)
- Pthirius pubis: public lice
Transmission of pediculosis
direct contact
Skin lesions associated with pediculosis
- Vary with immune sensitivity
- From subclinical to papules, urticaria and pruritus
- May become secondarily infected
Treatment for pediculosis
- Topical insecticides: malathion, permethrin
- Environment vacuumed, bedding, clothing
- Combs and brushes cleaned
What’s actinic lentigo?
- Benign, irregular, pigmented macular lesions that involves sun-damaged skin of the middle aged and elderly
- Fair skin Caucasians most at risk
- 0.1 to > 1.0 cm
- Not precancerous, needs no Rx
Mimics lentigo maligna
Actinic lentigo
What’s vitiligo?
- Common acquired loss of pigment due to autoimmune destruction of melanocytes by cytotoxic T-cells
- Peak incidence 10 and 30 years
- More common in dark skin
- 15-30% associated autoimmune disease
Skin presentation of vitiligo.
Hyperpigmented macules enlarge and become confluent
Microscopic presentation of vitiligo
Loss of melanocytes and melanin pigment. Perivascular lymphocytic infiltrate.
What is melanocytic nevus?
- “nevus” = “birthmark”
- Benign melanocytic neoplasm; acquired or congenital
- Acquired - present in childhood and adolescence
- Skin, nails, mucosa, conjunctiva, uveal tract
- More common in pale skinned with light colored eyes
- Caucasians average 15-40 nevi
- Related to sun exposure (intermittent intense sunlight) during the first two decades of life. People who burn.
- Rare cases develop melanoma
In what type of people are melanocytic nevus more common in?
- Pale skinned with light colored eyes
* Caucasians average 15-40 nevi
What’s a junctional nevus?
- Ovoid to round, well circumscribed; light to dark brown, macular or slightly raised, up to 0.5 cm, regular border
- Micro –> proliferaion begins in nests at the dermo-epidermal junction
What’s a compound nevus?
- Raised, often warty, often deeply pigmented; circumscribed with a regular border
- Micro –> Nevus cells, still proliferating at the D-E junction, descent into the dermis and form nests
What’s an intradermal nevus?
- Raised
- +/- pigment
- May be dome shaped nodule, papillomatous, or pedunculated
- Micro –> melanocytes are only found in nests in the dermis. Cells “mature” as they descend deeper into the dermis
Congental Nevus
Risk of malignancy (if large) and can be covered with hair
Blue nevus
- Collections of spindled dermal melanocytes
* Tyndall effect: blue light is scattered more passing through the dermis
Halo nevus
A zone of HYPOpigmentation represents immunologic regression seen microscopically as an intense lymphocytic dermal infiltrate
What’s a dysplastic nevi?
- Melanocytic nevi with dysplastic melanocytic proliferation
- Isolated solitary lesions of familial autosomal dominant syndrome
- May progress to melanoma
- Most remain clinically stable and never progress
- In 36% of melanomas we find adjacent dysplastic nevi.
Skin findings for dysplastic nevi
- Large (>6mm)
- Irregular shaped
- Ill-defined border
- Variable shades of browns, tans, and pink
- May be erythematous surround
- Not all clinically atypical nevi are dysplastic
What’s dysplastic nevus syndrome?
• Inherited autosomal dominant syndrome
• Normal at birth, develop large numbers of nevi in early childhood
• Few to > hundred
• Acquire atypical clinical features
around puberty. Predilection for trunk, face, and arms; also buttocks, genitalia, breasts, scalp.
• Histology show dysplastic features.
• Increased incidence of melanoma;
50% by age 60.
• Five dysplastic nevi – relative risk
for melanoma increases to 46%.What’s malignant melanoma?
Malignant transformation of melanocytes.
Highest incidence of malignant melanoma occurs in…
- Fair skinned caucasians - highest incidence.
- The incidence increasing.
- 1 in 50 born in the US in 2010.
- 1 in 1500 in 1935.
- Mean age 52 years; 35% < 45 years of age.
Prognosis of malignant melanoma
- Early detection of melanoma - high cure rates after excision.
- Prognosis directly related to size and depth of invasion.
Etiology and pathogenesis of malignant melanoma
- Sun exposure; Genetic predisposition.
* Germline mutations in the chromosome 9p21 tumor suppressor gene, account for 40% of hereditary melanoma cases.
Risk Factors for Development of Melanoma
- Genetic markers (CDKN2a mutation)
- Skin type I/II (light skin)
- Family history of dysplastic nevi or melanoma
- Personal history of melanoma
- Ultraviolet irradiation; childhood sunburns, intermittent burning exposures
- Number (>50) and size (>5 mm) of melanocytic nevi
- Congenital nevi
- Number of dysplastic nevi (>5)
- Dysplastic melanocytic nevus syndrome
Melanoma signs, ABCDE rule
- Asymmetry: 1/2 unlike the other
- Border: irregular, poorly defined edges
- Color: not uniform; all shades of brown, black, pink
- Diameter: greater than 6.0 mm
- Elevation & enlargement: change in size or shape
Growth phases of melanoma
Most melanomas show an initial radial growth phase followed by a subsequent vertical phase.
- Radial growth: cells are running up and down rete, with upward invasion into epidermis; cells spread out laterally
- Vertical growth phase: loose E-cadherin and express N-cadherin
What is superficial spreading melanoma?
- 70% of melanomas
- Any site, lower extremities, trunk
- Radial growth phase - Months to 2 years
Microscopic appearance of superficial spreading melanoma
- Neoplastic melanocytes proliferate along D-E junction
- Pagetoid invasion of epidermis
- Severe atypia. Inflammation
- Gas not invaded dermis, so this is called melanoma in situ
What’s Nodular melanoma?
- 15% of melanomas
- Any site, trunk, head, neck
- Arises rapido; NO RADIAL GROWTH PHASE
- Brown, black, or pink, nodule
What’s lentigo maliga melanoma?
- Occurs in older patients with heavily sundamaged skin; mean age 65
- Flat, irregular variably pigmented macule or patch
- Face, neck, dorsa of hand
- 5% of melanomas
- Radial growth phase - very long; years
What’s Acral Lentiginous melanoma?
- 5-10% of melanomas
- Asians, Africans, and African Americans most common
- 50-70% of the melanomas found in these populations
- Palms, soles, subungual (nails?)
- Radial growth phase - months to years
What is mucosal melanoma?
- Can be seen in the mouth
* Biopsy patient if present
What’s Amelanotic melanoma?
• Little to no pigment - bizarre giant cells with prominent nucleoli.
Which type of melanoma is most common?
Superficial spreading melanoma (70% of melanomas)
Which type of melanoma is most commonly observed in palms, soles, subungual (nails)?
Acral lentiginous melanoma
Which type of melanoma is most commonly observed on the face, neck, dorsa of hand?
Lentigo maligna melanoma
Which type of melanoma affects any site, but more commonly the trunk, head, neck?
Nodular melanoma
Which type of melanoma affects any site, but more commonly the lower extremities, trunk?
Superficial spreading melanoma
Compare and contrast the radial growth phases of the different types of melanoma
- Superficial spreading melanoma –> radial growth phase: months to 2 years
- Nodular melanoma –> arises rapidly, no radial growth phase
- Lentigo maligna melanoma –> radial growth phase: very long; years
- Acral lentiginous melanoma –> growth phase: months to years
What is staging?
- T Staging is based on tumor thickness and +/- ulceration.
- T1: < 1.0mm
- T2: 0.1-2.0mm
- T3: 2.01-4.0mm
- T4: >4.0mm
Treatment for melanoma
- Surgical excision with 1.0 cm. Margin
- Sentinel node biopsy in lesions > 1.0mm thickness
- Complete lymph node dissection for metastatic disease
- Chemotherapy, immunotherapy for higher stage disease
Survival rates for melanoma (general idea)
- Lymph node involvement and metastasis indicates very poor prognosis.
- Presence of any mitosis (?) means only 10% survival.
What is seborrheic keratoses?
- Most common BENIGN epithelial tumor seen in middle-aged or older
- Trunk most common, also extremities, head, and neck
Skin findings for seborrheic keratoses
- Sharply delineated
- Round or oval
- Brown-black or flesh-colored warty plaques
- Millimeters to several centimeters
Activitating mutations in which growth factor is though to drive the growth of the tumor in seborrheic keratoses?
Fibroblast growth factor receptor-3
Seborrheic keratoses occur explosively in large numbers associated with gastric adenocarcinoma…
Leser-Trelat sign
Microscopic appearance of seborrheic keratoses
- Exophytic and sharply demarcated proliferation of small basal like keratinocytes
- Hyperkeratotic with horn cysts
What is dermatoheliosis?
- Means chronic photodamage
- Involves epidermis, vascular system, and dermal connective tissue
- Severity depends on duration, intensity, skin color, tanning capacity
What is Fitzpatrick’s skin phototypes?
• Lists different skin types and how they tan/damage
Which type in Fitzpatrick’s skin phototypes is most susceptible to chronic photodamage (dermatoheliosis)?
- Type 1 will get the worst
- Pale skin, blue/hazel eyes, blond/red hair
- Always burns, does not tan
- Photodamage occurs mostly in types 1-3, and also 4 with heavy exposure
- SPT I and II make up 25% of the white population in the US
Which is the most damaging UV radiation?
UVB
Pathogenesis of chronic photodamage/dermatoheliosis
UVB is the most damaging UV radiation
Skin findings for chronic photodamage/dermatoheliosis
- Epidermal atrophy
- Wrinkles
- Telangiectasia
- Hypo/hyperpigmentation
- Solar lentigines
Microscopic appearance of chronic photodamage/dermatoheliosis
- Acanthosis hyperkeratosis
* Elastosis
Treatment for chronic photodamage/dermatoheliosis
- Protective sunblocks
- Change of behavior
- Topical sun-protective lotions
- SPT I and II persons should avoid the peak hours of sun 10-2:00
What is actinic keratosis?
- Sun induced dysplasia of the epidermis.
- Excessive exposure to UV radiation, particularly UVB.
- Males > females
- Middle aged or elderly
- Fair complexions that burn rather than tan
- 2-5% of cases develop an invasive squamous cell carcinoma. Numerous lesions for many years have higher risk.
- Predictor of risk for melanoma and other skin cancers.
2-5% of cases of Actinic keratosis develop this…
- Invasive squamous cell carcinoma
- Numerous lesions for many years have higher risk
- Predictor of risk for melanoma and other skin cancers
Appearance of actinic keratosis
- Erythematous or yellow-brown, flat, rough, scaly papules
- 2 mm to > cm
- Sun exposed surfaces: face and neck, dorsal hands and forearms
- Sun damaged of surrounding skin
Microscopic appearance of actinic keratosis
Epithelial dysplasia with alternating parakeratosis and orthokeratosis
Etiology for squamous cell carcinoma in situ
- Ultraviolet radiation
- Chronic arsenicism
- Immunosuppression
- Ionizing radiation, HPV, PUVA Rx
- 3-5% progress to invasive carcinoma
Treatment for squamous cell carcinoma in situ
- Excision
- Mohs micrographic surgery
- Histopathologic evaluation to exclude invasive SCC
What’s invasive squamous cell carcinoma?
- Malignant tumor of keratinocytes, arising in the epidermis
- Usually arises in epidermal precancerous lesions
- M>F, except legs
- Age of onset - >55 in the US
- 20s & 30s in Florida, Southwest, Southern California, Australia, New Zealand
- Incidence varies with sun exposure
- Continental US: 7-12/100,000
- Hawaii: 62/100,000 whites
Aggressiveness of invasive squamous cell carcinoma
- Aggressiveness varies with etiology and differentiation
- Sun induced lesions low rate of metastasis
- Immunosuppressed –> more aggressive more often metastasizes
Skin findings for invasive squamous cell carcinoma
- Indurated erythematous, yellowish or skin tone papule, plaque or nodule
- Keratotic scale
- Eroded or ulcerated, firm elevated margin
Etiology of invasive squamous cell carcinoma
- Ultraviolet radiation
- HPV
- Immunosuppression
- Chronic inflammatory and scarring conditions
- Industrial carcinogens
- Inorganic arsenic
Cellular process in the development of invasive squamous cell carcinoma
- Multistep process that involves:
- p53
- cyclin D1
- human telomerase reverse transcriptase
- p16
- thrombospondin
- Dysregulation of p53 and other apoptotic regulatory proteins
Factors for high risk of invasive squamous cell carcinoma
- diameter > 2cm
- depth > 4mm
- bone, muscle, nerve involvement
- location on ear, lip
- tumor arising in scar
- high grade
- immunosuppression
- absence of inflammation
Treatment for invasive squamous cell carcinoma
- Conventional surgical excision
- Mohs micrographic surgery
- Radiation therapy
What’s the most common invasive cancer in humans?
Basal cell carcinoma
What is Basal cell carcinoma?
- Most common invasive cancer in humans; 1 million per yer in US
- Slow growing, locally invasive, and destructive; METASTASIS rare
- Tendency to sun-exposed sites and in lightly pigmented people
- Males > females, usually > 40 years
- Increased and younger in immunosuppression and inherited defects in DNA repair (xeroderma pigmentosum)
Pathogenesis for basal cell carcinoma
- Derived from an undifferentiated pluripotent epithelial germ cell
- Exposure to UVL, particularly UVB induces mutations in tumor suppressor genes
- Also arise in scars, stasis ulcers, surgical, burn, and post vaccination, and healed infectious diseases such as leuishmania and chickenpox
Clinical types of basal cell carcinoma
- Nodular
- Ulcerating
- Pigmented variant
- Superficial variant
- Sclerosing variant
Treatment for basal cell carcinoma
- Surgical excision
- Mohs micrographic surgery
- Electrodesiccaiton
- Curettage
Microscopic appearance of basal cell carcinoma
- Proliferating monotonous hyperchromatic, basaloid cells attached to epidermis
- Peripheral palisading
- Infrequent mitoses
Pheripheral palisading is important in the diagnosis for…
Basal cell carcinoma
What is Kaposi’s sarcoma?
• Multifocal tumor of endothelial origin development linked to Human herpesvirus (HHV)-8 infection
Compare the clinical variants of Kaposi’s sarcoma
- Classical KS - extremities of old mediterranean male, slow growing
- Endemic African KS - Central African countries; rapidly progressive lymphadenopathic variant, extracutaneous sites
- AIDS-related KS - rapidly progressive form with early involvement of extracutaneous sites
- KS associated with immunosuppressive therapy - organ transplant recipients. Course varies from slow or rapid
Treatment for Kaposi’s sarcoma
Chemotherapy and radiation therapy
Small, reddish-blue macules or flat plaques, often multiple, gradually enlarge. May become nodular, pigmented, coalesce or fungate.
Kaposi’s sarcoma
Microscopic appearance of kaposi’s sarcoma
Spindle cell proliferation with blood percolating between slits
What is Langerhans Cell Histiocytosis?
- Group of idiopathic disorders characterizes by infiltration of tissues by Langerhans cells.
- Varies from localized self-healing forms to generalized and fatal
Pathogenesis of Langerhans cell Histiocytosis
- Unclear
- Debate whether LCH is a neoplasm, a reactive disorder, or immune dysfunction
- Viral involvement?
Clinical syndromes of Langerhans Cell Histiocytosis
- Eosinophilic granuloma: unifocal skin, mucous membranes, bone, or soft tissue lesions; childhood and young adult
- Hand-Schuller-Christian: chronic, progressive multifocal form of LCH; childhood and adult
- Letterer-Siwe Disease: the most aggressive multifocal LCH form, with skin and internal organ involvement. Infant and child
Which of the Langerhans Cell Histiocytosis syndromes is the most aggressive?
- Letterer-Siwe-Disease
- Mutlifocal
- Skin and internal organ involvement
- Infant and child
Single system disease of Langerhans Cell Histiocytosis
- Eosinophilic granuloma: unifocal
* Hand-Schuller-Christian disease: multifocal
Multisystem disease of Langerhans Cell Histiocytosis
- Letterer-Siwe Disease
- And more extensive presentations of Hand-Schuller-Christian disease
** Can be low risk (involve skin, bone, lymph node, pituitary) or high risk (involve hematopoietic system, lungs, liver, spleen)
Skin findings range from soft tissue swelling, to dermatitis to papules, pustules, erosions, and shallow punched out ulcers
Langerhans cell histiocytosis
How many bones comprise the skeletal system?
206 bones connect by joints
Inorganic mineral of skeletal system consists mainly of…
Calcium hydroxyapatite
Organic portion of the skeletal system includes…
The bone cells and osteoid
What are osteoprogenitor cells
- Pluripotent mesenchymal stem cells found in the vicinity of all bony surfaces
- When appropriately stimulated by growth factors they produce offspring that differentiate into osteoblasts
What are osteoblasts
• Synthesize, transport, and arrange the many proteins of matrix and initiate the process of mineralization
What are osteoclasts?
Responsible for bone resorption
What are osteocytes?
- Help to control calcium and phosphate levels in the microenvironment (responsible for homeostasis)
- Detech mechanical forces and translate them into biologic activity
What factors regulate bone remodeling?
- RANK
- RANK Ligand (RANKL)
- Osteoprotegerin
What is RANK?
- Receptor activator for nuclear factor kB
- Member of the TNF family
- Expressed on cell membranes of preosteoclasts and mature osteoclasts
- Stimulated by RANKL
What is RANK Ligand (RANKL)?
- Expressed by osteoblasts and marrow stromal cells
* Stimulates RANK which leads to activation of NF-kB which in turn stimulates osteoclasts
What is osteoprotegerin?
Blocks the actions of RANKL
RANK and RANKL relation to bone resorption
- RANKL present on osteoblasts
- RANK present on osteoclasts and preosteoclasts
- Increase in RANK and RANKL = increase in bone resorption
What is osteogenesis imperfecta?
- AKA brittle bone disease
- a phenotypically diverse disorder caused by deficiencies in the synthesis of type 1 collagen
- Principally affects bone, but also impacts other tissues rich in type 1 collagen (joints, eyes, ears, skin, and teeth)
- Usually results from autosomal dominant mutations in the genes that encode the alpha1 and alpha2 chains of type 1 collagen.
Caused by deficiencies in the synthesis of type 1 collagen
Osteogenesis imperfecta
Most common inherited disorder of connective tissue.
Osteogenesis imperfecta
Usually results from autosomal dominant mutations in the genes that encode the alpha 1 and alpha 2 chains of type 1 collagen.
Osteogenesis imperfecta
Subtypes of osteogenesis imperfecta
- Type I, or mild OI, is the most common form. Persons with this type can live a normal lifespan.
- Type II is a severe form that usually leads to death in the first year of life.
- Type III is also called severe OI. Persons with this type have many fractures starting very early in life and can have severe bone deformities. Many become wheelchair bound and usually have a somewhat shortened life expectancy.
- Type IV, or moderately severe OI, is similar to type I, although persons with type IV often need braces or crutches to walk. Life expectancy is normal or near normal.
What’s the most common form of osteogenesis imperfecta?
- Type I.
* Persons with this type can live a normal lifespan.
What’s the most severe form of osteogenesis imperfecta?
- Type III (severe OI)
- Persons with this type have many fractures starting very early in life and can have severe bone deformities
- Many become wheelchair bound and usually have a somewhat shortened life expectancy.
The fundamental abnormality in osteogenesis imperfecta is…
- Too little bone.
* Body is not laying down enough matrix to form proper bone.
Classic gross finding of blue sclera is a flag for…
osteogenesis imperfecta
Most common disease of the growth plate.
Achondroplasia
Most common form of dwarfism.
Achondroplasia
What is Achondroplasia?
- Most common form of dwarfism; affects all bones which undergo endochondral ossification
- Autosomal dominant; almost 80% are new mutations and most of these are paternally derived
- Caused by an activating point mutation in fibroblast frowth factor receptor 3 (FGFR3)
What is Thanatophoric dwarfism?
- Lethal variant of dwarfism
- Affects 1 in every 20,000 live births
- Caused by missense or point mutations in FGFR3
- Has extreme shortening of limbs, frontal bossing of the skull, extremely small thorax
What is osteopetrosis?
- AKA marble bone disease and Albers-Schonberg disease
- A group of rare genetic diseases that are characterized by abnormal osteoclast function
- The term osteopetrosis reflects the stonelike quality of the bones, but the bones are abnormally brittle and fracture easily, like a piece of chalk. They lack a medullary canal and Ehrlenmeyer flask deformity is common.
- The autosomal recessive severe type and the autosomal dominant mild type are the most common variants.
In which congenital disorder of bone and cartilage lacks a medullary canal and has a Ehrlenmeyer flask deformity?
Osteopetrosis
Other effects of osteopetrosis includes..
- cranial nerve palsies (due to compression of nerves within cranial foramina)
- infections (due to reduced marrow size and activity)
- hepatosplenomegaly (due to extramedullary hematopoiesis)
What is osteoporosis?
- Characterized by porous bones and decreased bone mass
- Postmenopausal women are most commonly affected, and Caucasian women more than African-American women
- In postmenopausal women, bones with high surface area, such as vertebral bodies, become thinned and the trabeculae are fine.
- Kyphosis (curving of the spine) and rib fractures are common.
Treatment for osteoporosis.
- Exercise
- Appropriate calcium and vitamin D intake
- Pharmacologic agents, most commonly bisphosphonates
What happens in menopause that increases risk for osteoporosis?
- Decreased serum estrogen
- Increased IL-1, IL-6, TNF levels
- Increased expression of RANK, RANKL
- Increased osteoclast activity
Aging and osteoporosis
- Decreased replicative activity of osteoprogenitor cells
- Decreased synthetic activity of osteoblasts
- Decreased biologic activity of matrix-bound growth factors
- Reduced physical activity
Honeycomb pattern
• Osteoporosis, much, much more porous than normal bone matrix.
Thin trabeculae (thin bony spaces with lots of fat and marrow in between), unfilled spaces cause porous appearance in this…
Osteoporosis
What is Paget disease of bone?
- Also known as osteitis deformans.
- Separated into three phases: an initial osteolytic stage, followed by a mixed osteolytic/osteoblastic phase, and ending in a quiescent osteosclerotic stage.
- Common in whites in England, France, Austria, regions of Gernamny, Australia, New Zealand, and the United States.
What is the hallmark of Paget’s disease?
• Mosaic pattern of lamellar bone, which is linked to a jigsaw puzzle and is produced by prominent cement lines that anneal haphazardly oriented units of lamellar bone.
Most common cause of rickets and osteomalacia?
• Malabsorption of vitamin D
What is rickets?
Rickets occurs in children and results in derangement of bone growth.
What is osteomalacia?
Osteomalacia occurs in adults and results in remodeled bone which is poorly mineralized. Osteopenia and insufficiency fractures result.
In children with rickets you can experience…
- Genu varum - bow leggedness
- Windswept deformity
- Genu valgum - knock knees
Histological appearance of rickets and osteomalacia
- Normal bone has slight areas of remodeling
* In osteomalacia and rickets, there are large areas of poor mineralization, which can lead to fracture.
What is hyperparathyroidism?
- Increased PTH concentrations are detected by receptors on osteoblasts, which release factors that stimulate osteoclast activity.
- Skeletal manifestations of hyperparathyroidism are caused by unabated osteoclastic bone resorption.
- The entire skeleton can be affected.
- The bone loss leads to microfractures and secondary hemorrhages that elicit an influx of macrophages and an ingrowth of reparative fibrous tissue, creating a mass of reactive tissue, known as a brown tumor.
PTH concentrations are detected by receptors on …
Osteoblasts
Increased bone cell activity + peritrabecular fibrosis + cystic brown tumors =
Generalized osteitis fibrosa cystica (von Recklinghausen disease of bone)
What is a pathologic fracture?
If the break occurs in bone altered by a disease process.
What is a stress fracture?
A slowly developing fracture that follows a period of increased physical activity in which the bone is subjected to new repetitive loads.
Classification of fractures
- Complete or incomplete
- Closed (simple) when the overlying tissue is intact
- Compound, when the fracture site communicates with the skin surface
- Comminuted when the bone is splintered
- Displaced when the ends of the bone at the fracture site are not aligned
Process of fractures and healing…
- When you fracture a bone, you create a hematoma.
- Pooling blood around ends of fracture allows bone building proteins to gather.
- Osteoprogenitor cells are activated to make osteoblasts.
- First lay down cartilage in long bones (endochondral ossification) or fibrous tissue (intramembranous ossification).
- Cartilage lets bone fill in to create a fracture callous (bony callous).
Nonunion of fractures
Displaced (ends of bones at fracture site not aligned) and comminuted (bone is splinteered) fractures frequently result in some deformity, and inadequate immobilization permits constant movement at the fracture site, so that the normal constituents of callus do not form, resulting in delayed union and nonunion.
What is pseudoarthrosis?
- False joint
- If a nonunion allows too much motion along fracture gap, the central portion of the callus undergoes cystic degeneration, and the luminal surface can actually become lined by synovial-like cells, creating a false joint.
- Scribe: […] no proper callous formation/healing… these cases often need repeat surgery… ends of the bone do not join and you get what is called a false joint.
What is avascular necrosis?
- Osteonecrosis
- Infarct of bone or marrow which occurs in the medullary cavity
- Fracture, corticosteroid use, and idiopathic causes are most common
- Geographic in appearance
- Eventually results in collapse of the bone with possible distortion and fracture of the bone and sloughing of the articular cartilage.
A wedge shape infarct is commonly observed in…
• Avascular necrosis (osteonecrosis)
Histology of osteonecrosis
- Dead bone with empty lacunae
- Fat necrosis
- Insoluble calcium soaps
What is osteomyelitis?
- Bone infection.
- Most common infectious agent is S. aureus.
- Common infectious agent seen in sickle cell-disease is Salmonella.
- Acute, subacute, and chronic
- Acute is almost always caused by bacteria, which reach the bone via 3 routes - hematogenous, direct extension, and trauma.
How to distinguish between tumor and osteomyelitis?
We know it is not a tumor if, upon inserting a needle, pus sprays everywhere.
What are bone tumors?
- Very diverse and rare group of diseases
- Accurate diagnosis is essential for survival and also to maintain optimal function
- Correlation with radiological images is of utmost importance
- Classification is based on cell of origin, connective tissue matrix they produce and differentiate
Clinical findings for bone forming tumors
- Common lesions are most often asymptomatic and are detected as incidental findings.
- Some tumors produce pain and are slow growing - but pain does not always indicate malignancy.
What may be the first evidence of a bone tumor?
Pathologic gracture
Multidisciplinary team required to diagnose and treat patients with bone tumors…
- Oncologist
- Radiologist
- Pathologist to read biopsy
- Orthopedic surgeon
Tumors occur at different places depending on age…
- Younger patient –> more likely to be primary tumor
* Older patient –> more likely from metastasis
Osseous lesions must be __-__% destructive before they can be seen on plain films
40-50%
Purpose of x-rays
• to localize and assist in the biopsy of a lesion
Purpose of computed tomography (CT) scans
• Good evaluation of bone, but not soft tissue
Purpose of magnetic resonance imaging (MRI)
• Good evaluation of soft tissue but not bone
What is osteoma?
- Bosselated, round to oval sessile tumors that project from the surface of the cortex
- M:F ratio approximately 2:1
- Usually solitary, detected in middle age
- Most often arise on or inside the skull and facial bones
- Multiple osteomas are seen in the setting of Gardner syndrome
- Of little clinical significance unless a vital structure is impinged upon
Xray findings for osteoma
• dense radioopaque circumscribed mass
What is osteoid osteoma?
- Classic lesion
- 75% occur between 5 and 25 years old
- M:F ratio 2:1 to 3:1
- Any bone; commonly long tubular bones, diaphyseal, cortical
- Histologically, the nidus is surrounded by osteoblasts which are variably mineralized
Bone forming tumor characterized by painful lesion (relieved by aspirin), and pain most common at night.
Osteoid osteoma
X-ray finding for osteoid osteoma
Central lucent nidus surrounded by dense sclerosis
Treatment for osteoid osteoma
Excision of nidus is curative
What is osteoblastoma?
- Same thing as osteoid osteoma, except it’s larger than 2 cm.
- Occurs between 10 and 35 years.
- Axial skeleton - spine common.
- Pain is NOT relieved by aspirin
- X-ray is not specific - mimics other lesions
- Complete excision is curative-rare local aggressiveness.
- Again, size >2cm - histologically identical to osteoid osteoma
Histologically identical to osteoid osteoma, except size > 2cm
Osteoblastoma
Most common primary malignant tumor of bone.
Osteosarcoma
Skip lesions are prognostically grave for this disease…
Osteosarcoma
What is osteosarcoma?
- Most common primary malignant tumor of bone
- Bimodal age distribution - second and fifth decades
- Site of predilection is proportional to the rate of skeletal growth (distal femur and proximal tibia are the commonest sites)
- Often present clinically as pain present for several months.
- Radiographic presentation can vary greatly (lytic or sclerotic or mixed).
- Accompanying soft tissue mass is common.
Site of predilection is proportional to the rate of skeletal growth (distal femur and proximal tibia are commonest sites)
Osteosarcoma
Thin lace like woven osteoid/bone is hallmark of this…
Osteosarcoma
Most common treatment modality for osteosarcoma
- Chemotherapy followed by a limb sparing resection and post operative chemotherapy
- Aggressive and highly lethal neoplasm
Common sites of metastasis include the lungs (most common), liver, and skeletal system for …
osteosarcoma
Most common primary benign bone tumor
Osteochondroma (Exostosis)
What is osteochondroma?
- Cartilaginous lesions
- Most common primary benign bone tumor
- 85% are solitary; the remainder are part of the multiple hereditary exostosis syndrome, an autosomal dominant syndrome
- Inactivation of EXT1 and EXT2 is seen in syndromic and hereditary osteochondromas
- Develop only in bones with enchondral ossification
- Present more commonly in the syndrome because of bony deformity
Treatment for osteochondroma
Excision is curative
Histologic appearance of osteochondroma
- Pedunculated or sessile
- Range in size from 1-20 cm
- Cap is constructed of hyaline cartilage
- Cartilage undergoes endochondral ossification, resulting in the bone in the center of the lesion
Neoplasm consisting of mature hyaline cartilage
Enchondroma
Enchondromas can appear as part of syndromes involving…
- Multiple enchondromas - Ollier’s Disease
* Enchondromas and soft tissue hemangiomas - Mafucci’s syndrome
X-ray appearance –> radiolucent lesions with ring like calcification
Enchondroma
Histologic appearance of enchondroma
Mature hyaline cartilage (grey-blue) with calcifications
Enchondroma is most commonly found on…
- Encondromas-metaphyseal ends of tubular bones
* Common in hands and feet
What is chondrosarcoma?
- Malignant tumor of cartilage
- Second most common primary malignant tumor of bone
- Adults - 40 and older. Males more common
- Location: pelvis, ribs, shoulder, long bones
- Dull aching pain waking the patient at night
- Classification - Location: intramedullary and juxtacortical
- Survival and tumor progression are based on grade.
Histology: conventional, clear cell, mesenchymal, and dedifferentiated
Chondrosarcoma
Hypercellular lesion containing numerous malignant chondrocytes in a pale grey cartilaginous background is observed in this disease…
Chondrosarcoma
Chondrosarcoma may appear in these two locations…
- Intramedullary (center)
2. Juxtacortical (edge)
What is a benign lesion of bone made up of fibro-osseous tissue proliferating in an irregular manner; some think of as localized developmental arrest…
Fibrous dysplasia
• It is a fibro-osseous lesion
What are the two forms of fibrous dysplasia?
• Monostotic
- Single bone, 70% of all cases)
• Polyostotic
- Multiple bones, 27% of all cases
What is McCune-Albright syndrome?
• 3% of cases of fibrous dysplasia is part of McCune-Albright syndrome
Characterized by:
• Polyostotic fibrous dysplasia
• Precocious puberty
• Cafe-au-lait spots
Due to a somatic mutation of guanine-nucleotide binding protein (G-protein), encoded by the GNAS gene.
This has a female predominance.
Which gender is more likely to get Albright’s syndrome?
Female
Fibrous dysplasia affects which gender more?
- Males more than females
* Young adults
Which bones are involved in fibrous dysplasia?
• Any bone can be involved
X-ray appearance of fibrous dysplasia
X-ray lucent lesion with “ground glass” appearance
How frequently does fibrous dysplasia transform to sarcoma?
RARE
Fibrous stroma containing osteoid and woven bone - “Chinese letters” associated with which disease?
Fibrous dysplasia
Note: we almost never see mitotic figures in the background, as it is generally benign
Malignant small blue cell tumor
Ewing sarcoma
Promiscuous gene (EWS), characterized by unique chromosomal translocation t(11;22)(q24;q12)(EWS-FLI-1)
Ewing sarcoma
Most common chromosomal translocation for Ewing sarcoma
t(11;22)
Result is a fusion of EWS gene to FLI1 gene.
EWS is a promiscuuous gene because it has a lot of partners.
Treatment for Ewing sarcoma
- Radiation and chemotherapy
* 5 year survival about 70%
Commonly affected areas of the skeleton for Ewing sarcoma
Axial and appendicular skeleton
Permeative with “onion-skin” periosteal reaction observed in which disease…
Ewing Sarcoma
Histological appearance of Ewing Sarcoma
- Sheets of small round blue cells, not much larger than lymphocytes make up the lesion.
- Scant cytoplasm with white halos due to glycogen production
- Necrosis may be prominent
Most common joint disorder
Osteoarthritis
In what age range is osteoarthritis most commonly seen?
- Most commonly seen in patients over 65
* Most commonly appears with advancing age and without cause (primary OA)
Which joint disorder is primarily a degenerative disorder of articular cartilage?
Osteoarthritis
• Chondroid matrix is broken down
What is eburnation?
Eburnation is identified as holes in the articular surface
Histologic appearance of osteoarthritis
- The surface cartilage appears chewed, compatible with the gross finding of eburnation
- Eburnation: holes in the articular surface
Which joint disorder is a systemic, chronic inflammatory autoimmune disease which principally attacks the joints?
Rheumatoid Arthritis
When extraarticular involvement develops in this joint disorder, it may resemble lupus or scleroderma.
Rheumatoid arthritis
What happens in rheumatoid arthritis
Causes a nonsuppurative proliferative synovitis that frequently progresses to destroy articular cartilage and underlying bone with resulting disabling arthritis.
Incidence of rheumatoid arthritis
- Relatively common condition, with a prevalence of approximately 1%
- Three to five times more common in women than in men
- Peak incidence is in the second to fourth decades of life
Pathologic changes in rheumatoid arthritis are caused mainly by…
Cytokine-mediated inflammation, with CD4+ T cells being the principal source of the cytokines
Risk factors for rheumatoid arthritis
- Estimated that 50% of the risk of developing RA is related to genetic factors
- Susceptibility to RA is linked to the HLA-DRB1 locus
- Inflammatory and environmental insults such as smoking and infections may induce the citrullination of some self proteins, creating new epitopes that trigger autoimmune reactions.
Histologic appearance of rheumatoid arthritis
- On histologic examination, the affected joints show chronic papillary synovitis
- The classic appearance is that of a pannus, formed by proliferating synovial lining cells admixed with inflammatory cells, granulation tissue, and fibrous connective tissue
Incidence of gout
Affects about 1% of the population, and shows a predilection for males.
What causes gout?
- Caused by excessive amounts of uric acid, an end product of purine metabolism, within tissues and body fluids
- Monosodium urate crystals precipitate from supersaturated body fluids and induce an acute inflammatory reaction
- Recurrent episodes of acute arthritis, sometimes accompanied by the formation of large crystalline aggregates called tophi, and eventual permanent joint deformity (joint deformity can occur if not treated)
T/F: Although an elevated level of uric acid is an essential component of gout, not all such persons develop gout, and genetic and environmental factors also contribute to pathogenesis
True
What increases urate level? (Related to gout)
Increase in urate level due to:
• Dietary purine load
• Endogenous purine synthesis
Excretion:
• Renal excretion
• Gut
In gout:
• Urate supersaturation and crystallization
Histologic appearance of gout…
- Aggregations of urate crystals surrounded by an intense inflammatory reaction of lymphocytes, macrophages, and foreign-body giant cells, attempting to engulf the masses of crystals
- Under polarized light, the crystals are needle shaped and demonstrate negative birefringence
Which joint disorder is also known as chondrocalcinosis and calcium pyrophosphate crystal deposition disease?
Pseudogout
This joint disorder most commonly occurs in people over 50, with no race or gender predilection..
Pseudogout
What happens in pseudogout?
- Crystals first appear in structures composed of cartilage.
* When the deposits enlarge enough they may rupture, resulting in inflammation.
Histologic appearance of pseudogout
- Numerous foci of calcification are identified in the cartilage
- The crystals are rhomboid in shape and demonstrate positive birefringence under polarized light
What are soft tissue tumors?
- Proliferations occuring in the extraskeletal, nonepithelial tissues of the body
- Classified according to the normal tissues they recapitulate (muscle, fat, etc)
- Some of these have no normal histologic counterpart
- Benign outnumber malignant 100:1
Location of soft tissue tumors
- Lower extremity: 40%
- Upper extremity: 20%
- Trunk and retroperitoneum: 30%
- Head and neck: 10%
Most common tissue tumor of adulthood
Lipoma
Treatment for lipoma
Simple excision is curative
Conventional lipomas show genetic rearrangements in which chromosomes?
Chromosome 12q13-15
Incidence of lipoma more common in which gender?
Male preponderance most striking in spindle cell variant (9:1 M:F ratio)
One of the most common sarcomas of adulthood
Liposarcoma
Age range that liposarcoma most commonly appears in…
40s-60s
Where does liposarcoma usually arise?
Usually arise in the deep soft tissues of the proximal extremities and retroperitoneum
Well differentiated liposarcoma contains mutations in which gene and chromosome?
Well differentiated liposarcoma contains mutations in MDM2 gene on 12q14-q15.
Well documented translocation, t(12;16)(q13;p11) occurs in what type of liposarcomas?
Myxoid and round cell liposarcomas
Histologic hallmark: lipoblasts - mimic fetal fat cells is observed in which adipose tissue tumor?
Liposarcoma
Most common of the reactive pseudosarcomas
Modular fasciitis
Most common location of nodular fasciitis
Most often occurs in adults on the forearm, chest, and back
Histologic appearance of nodular fasciitis
- Cellular lesion with plump myofibroblasts in an often myxoid stroma
- Stroma contains lymphocytes and extravasated blood cells
Variants of superficial fibromatoses include…
- Palmar (Dupuytren contracture)
- Plantar
- Penile (Peyronie disease) fibromatoses
Characteristic of superficial fibromatoses
• All variants are characterized by nodular thickenings of the affected area
Which variant of superficial fibromatoses is bilateral in 1/2 of cases?
Palmar variant
Which gender does superficial fibromatoses occur more in?
All variants affect males more than female
T/F: For superficial fibromatoses, some recur after excision, particularly the palmar variant
True
Also known as desmoid tumors
Deep fibromatoses
Which fibrous tumor presents as large infiltrative masses, most commonly abdominal, and recur after excision, but the cells appear benign
Deep fibromatoses
Gender predilection of deep fibromatoses
- Extraabdoominal variants affect men and women equally
* The abdominal variant is most commonly seen in women after pregnancy
The intra-abdominal variant of deep fibromatoses occurs most frequently in..
- Mesentery and pelvic walls
* Associated with Gardner syndrome
What mutation is observed in deep fibromatoses?
Mutatioons in beta-catenin are seen in these lesions regardless of the presence of Gardner syndrome.
Gross appearance of deep fibromatoses
- Tumorss appear as grey/white, firm, poorly demarcated masses
- Very rubbery when cut
Histologic appearance of deep fibromatoses
- Composed of plump benign fibroblasts arranged in broad fascicles that invade the surrounding tissue
- Mitoses may be frequent
Where does fibrosarcoma occur in the body?
Occur anywhere in the body; most common in the deep soft tissues of the extremities
Which fibrous rumor appears most often unencapsulated, infiltrative, soft fleshy masses demonstrating areas of hemorrhage and necrosis?
Fibrosarcoma
Spindle cells grow in a herringbone fashion in this tumor…
fibrosarcoma
Benign fibrous histiocytoma usually occurs in…
- Skin and subcutis
* Lesion is often pigmented
Incidence of benign fibrous histiocytoma
- Relatively common
* Presents in mid-adult life as firm small nodule (usually < 1cm)
Gross appearance of benign fibrous histiocytoma.
- firm small nodule (usually <1 cm)
- Lesion is often pigmented
- Overlying hyperpigmented squamous mucosa is also evident
Microscopic appearance of benign fibrous histiocytoma
Composed of crossing spindle cells in a background of sclerotic collagen
What are the different types of pleomorphic undifferentiated sarcoma?
- Inflammatory
- Myxoid
- Angiomatoid
- Giant cell
- Storiform-pleomorphic
What appears as a grey/white fleshy tumor with infiltrative margins, unencapulated, hemorrhage/mecrosis may be present
Pleomorphic undifferentiated sarcoma (formerly malignant fibrous histiocytoma)
Histologic appearance of pleomorphic spindle cell tumor with necrosis and numerous mitoses is found in this…
Pleomorphic undifferentiated sarcoma
Most common soft tissue sarcoma of childhood and adolescence (usually presents before 20 years of age)
Rhabdomyosarcoma
In which location does rhabdomyosarcoma occur?
- May arise in any location
- Most occur in the head, neck, or genitourinary tract
- Only appear in relation to skeletal muscle in the extremities
Treatment for rhabdomyosarcoma
Usually treated with surgery and chemotherapy with or without radiation
Types of rhabdomyosarcma
- Embryonal rhabdomyosarcoma
- Alveolar rhabdomyosarcoma
- Pleomorphic rhabdomyosarcoma
All contain rhabdomyoblasts in variable quantities
Most common type of rhabdomyosarcoma
- Embryonal rhabdomyosarcoma
* Accounts for 60%
Subtypes of embryonal rhabdomyosarcoma
- Sarcoma botryoides
- Spindle cell
- Anaplastic
Present as soft grey, infiltrative masses…
Embryonal rhabdomyosarcoma
Age range for embryonal rhabdomyosarcoma..
•Typically arises in children <10 years old in head and neck, prostate, and paratesticular areas
Round and spindled cells may be present in this type of rhabdomyosarcoma…
Embryonal rhabdomyosarcoma
Accounts for 20% of rhabdomyosarcomas
Alveolar rhabdomyosarcoma
This rhabdomyosarcoma tends to develop in early to middle adolescence and commonly arises in the deep muscle of the extremities…
Alveolar rhabdomyosarcoma
Translocations that are diagnostic for alveolar rhabdomyosarcoma
- t(2;13)(q35;q14)
* t(1;13)(p36;q14)
Rhabdomyosarcoma that is seen more often in adults than children
Pleomorphic rhabdomyosarcoma
Rhabdomyosarcoma that can resemble pleomorphic undifferentiated sarcoma
Pleomorphic rhabdomyosarcoma
Characterized by numerous large, sometimes multinucleated bizarre eosinophilic tumor cells
Pleomorphic rhabdomysarcoma
What is Leiomyoma?
- Benign smooth muscle tumors
- Most commonly seen in the uterus
- May also arise from erector pili muscles of the skin, nipples, scrotum, and labia
- Also occur in the deep soft tissues and wall of the GI tract
Multiple cutaneous leiomyomas in some individuals are associated with …
- Renal cell carcinomas
- Hereditary leiomyomatosis and renal cell carcinoma syndrome transmitted as autosomal dominant
- Associated with chromosome 1q42.3
Histologic appearance of leiomyoma
Composed of fascicles of spindle cells that tend to intersect each other at right angles
Histologically consist of cigar shaped nuclei arranged in interweaving fascicles…
Leiomyosarcoma
Gender predilection of leiomyosarcoma
Afflict women more frequently than men
Where does leiomyosarcoma most commonly occur?
Vast majority occur in the skin and deep soft tissues of the extremities and retroperitoneum
A special subgroup of leiomyosarcoma exists in what type of patients?
- HIV positive patients
* Occurs in unusual sites such as the liver
Represent 10-20% of soft tissue sarcomas
Leiomyosarcoma
Characteristic translocation for synovial sarcoma
t(X,18)(p11.2;q11.2)
Treatment for synovial sarcoma
Treated with preoperative chemotherapy followed by wide resection
Histologic appearance of synovial sarcoma
- Monophasic: consist of only spindle cells (could also be only epithelioid cells)
- Biphasic: contains both spindle and epithelioid cells
- Stain with epithelial and mesenchymal markers
Where does synovial sarcoma occur?
- Majority arise in the deep soft tissues, and 60-70% occur in the thigh
- Less than 10% are extra articular
Thyroid physiology
- Hypothalmus releases TRH which acts on the pituitary, which then releases TSH to stimulate the thyroid to make hormones
- Free hormones act to inhibit the pituitary from releasing TSH to stimulate the thyroid
- Thyroid binding proteins come from the liver to bind to T4 or T3, this plays a role in equilibrium of free hormones and bound hormones
Most common site of heterotopic thyroid
- Most frequent –> base of tongue (lingual thyroid)
- Total migration failure
- 75% of patients with lingual thyroid have no other thyroid tissue
Other sites of heterotopic thyroid
- Anterior tongue
- Larynx
- Trachea
- Mediastinum - if it descends too far
- Heart
Embryology of thyroid
- Foramen cecum is located at the midline between the anterior 2/3 and posterior 1/3 of the tongue
- This is where the thyroid tissue starts developing
- Thyroglossal duct forms and descends down to its normal position in front of the larynx
- In other words: foramen cecum to suprasternal notch
Thyroglossal duct cyst
- Occurs when the thyroglossal duct does not obliterate
- Occurs in the midline of neck (looks like Adam’s apple)
- Asymptomatic unless infected
- Moves when swallowing
- Squamous or respiratory epithelium lining cyst
What is hypothyroidism?
- Underactive thyroid
* High TSH, but low T3 and T4
Hypothyroidism in infants cause…
Cretinism:
• Poor growth
• Results in short stature, delayed development of permanent teeth, delayed puberty, poor mental development
Hypothyroidism in adults results in…
Myxedema:
• Periorbital and pretibial edema due to mucopolysaccharide deposition underneath skin
Treatment for hypothyroidism
Synthetic thyroid hormone
Cause of primary hypothyroidism
Loss of thyroid tissue due to surgery or radiation therapy
Most common cause of hypothyroidism in the USA
Hashimoto’s thyroiditis, an autoimmune disease
Most common cause of hypothyroidism worldwide…
Iodine deficiency, specially in endemic areas
Cause of secondary hypothyroidism
- Pituitary or hypothalamic failure
* Causes no hormone to be secreted
Most common cause of goiter in the United States
Goiter –> swelling of the neck due to enlarged thyroid gland
Hashimoto thyroiditis
Histologic diagnostic triad for Hashimoto thyroiditis (Stuma Lymphomatosa)
- Lymphocytic infiltrate
- Lymphoid follicles with germinal centers
- Hurthle cell metaplasia of follicular epithelium
Patients with Hashimoto thyroiditis are high risk for…
- B-cell lymphoma
- Papillary carcinoma
- Hurthle cell neoplasm
What presents as a painless enlargement, believed to represent a disease of autoimmune origin, has variable functional status, diffuse nontender rubbery thyroid enlargement, with flashy cut surface?
Hashimoto thyroiditis (Stuma lymphomatosa)
• Variable functional status: euthyroid, hyperthyroid (Hashitoxicosis), or hypothyroid
What’s believed to be the cause of subacute thyroiditis (granulomatous thyroiditis or De Quervain thyroiditis)?
• Viral infection
Clinical course of subacute thyroiditis (granulomatous thyroiditis or De Quervain thyroiditis)…
- Onset often acute, with fever and malaise
* Triphasic clinical course of hyperthyroidism, hypothyroidism, and return to normal thyroid function (within 6-8 weeks)
Most common cause of painful thyroid
Subacute thyroiditis (granulomatous thyroiditis or De Quervain thyroiditis)
Histologic appearance of subacute thyroiditis
- Disruption of follicles with inflammation
- Granulomatous reaction to colloid
- Multinucleated giant cells
Stony, hard, painless thyroid gland observed in…
Riedel’s thyroiditis
Thyroiditis that clinically resembles carcinoma, compress trachea…
Riedel’s thyroiditis
Obliterating phlebitis, where vein is obliterated by infiltrate and surrounded by dense collagen, is observed in which thyroiditis?
Riedel’s thyroiditis
Gross appearance of Riedel’s thyroiditis (Riedel’s struma, fibrous thyroiditis)
- Extensive fibrosis involving thyroid and contiguous neck structures
- Broad brands of fibrosis with keloid like fibers
Microscopic appearance of Riedel’s thyroiditis (Riedel’s struma, fibrous thyroiditis)
- Follicles are obliteraed
* Patchy lymphocytes, plasma cells, and eosinophils
Incidence of Riedel’s thyroiditis
Rare, suggest autoimmune etiology
What is thyrotoxicosis?
Hypermetabolic state caused by increased T4 and T3
What is primary thyrotoxicosis?
Grave’s disease
What is secondary thyrotoxicosis?
TSH secreting pituitary adenoma
Clinical picture of thyrotoxicosis
- Heat intolerance, sweating, warm skin, malabsorption
- Cardiac: palpitation, tachycardia, CHF
- Menstrual disturbances
- Neuromuscular: Tremor, muscle weakness
- Ocular: thyroid ophthalmopathy
Lab findings for Graves’ Disease (diffuse goiter)
- Increased T4
- Increased T3
- Decreased TSH
Radioactive findings for Graves’ Disease (Diffuse goiter)
Diffuse uptake of radioactive iodine
What Is Graves’ disease (diffuse goiter)?
- Thyrotoxicosis with smooth symmetrical enlargement of thyroid
- Infiltrative ophthalmopathy with exophthalmus in 40% of patients
Most common cause of endogenous hyperthyroidism
Diffuse goiter (Graves’ disease)
Triad of clinical findings for Graves’ disease (Diffuse goiter)
- diffuse enlargement of thyroid
- infiltrative ophthalmopathy (exophthalmos)
- infiltrative dermatopathy (periorbital myxedema)
Histologic appearance of diffuse goiter (Graves’ disease)
- Diffuse hyperplasia of thyroid follicular cells
- Papillary hyperplasia
- Scalloped appearance of the edges of the colloid
- Lymphoid follicles
• Scribe: We do not see round follicles lined by epithelial cells. Instead we see papillary projections in the lumen.
Which type of nodule in the thyroid is more likely to be neoplastic?
- Solitary nodule is more likely to be neoplastic than multiple
- Nodules in younger patients are more likely to be neoplastic
- Nodules in males are more likely to be neoplastic
Which nodules in the thyroid are more likely to be benign?
- Hot nodules are more likely to be benign
- Up to 10% of cold nodules prove to be malignant
- History of previous radiation to the neck is associated with increased risk of malignancy
Incidence of multinodular goiter
Incidence 3-5%, and 50% in autopsy cases
Location and effect of multinodular goiter
- Sometimes extends in the mediastinum
- Pressure effect on trachea
- Can arise sporadically or endemic (iodine deficiency)
Histological appearance of multinodular goiter
- Distended follicles of various sizes, filled with colloid, flat follicular epithelium
- Focal hyperplasia, scalloping
- Calcification
- Fibrosis
- Hemorrhage
Most common endocrine malignancy
Thyroid neoplasm
• Less than 2% of all human cancers
Gender predilection of thyroid neoplasm
Generally more common in women
Benign to malignant ratio of thyroid neoplasm
10:1
Neoplasm associated with radiation exposure and endemic goiters
Thyroid neoplasm
Clinical manifestations include:
• Most patients are euthyroid and present with thyroid nodule
• Symptoms such as dysphagia, dyspnea, and hoarseness usually indicate advanced disease
• Ipsilateral cervical lymph nodes may be present
Thyroid neoplasm
Definitive diagnosis for thyroid neoplasm
Fine needle aspiration biopsy
Subcategories of thyroid neoplasms
- Follicle derived
* C-cell derived
Most common thyroid neoplasm
Follicular adenoma
Thyroid neoplasm that is almost always solitary, well capsulated, has uniform follicles within the lesion, compress adjacent normal thyroid tissue, no vascular or capsular invasion…
Follicular adenoma
Make up 10-15% of thyroid cancer
Follicular carcinoma
Thyroid neoplasm that usually shows as “cold” on radionuclide scan
Follicular carcinoma
Thyroid neoplasm that is: • more aggressive • hematologic spread • architectural patterns, follicular, or solid • Capsular invasion • Vascular invasion beyond the capsule
follicular carcinoma
Prognosis for follicular carcinoma
60% 10 year survival
Most common malignant thyroid tumor (75%)
Papillarry carcinoma
How papillary carcinoma spreads…
Spread via lymphatics - propensity for lymph node metastasis
Thyroid neoplasm that’s associated with prior radiation…
Papillary carcinoma
Which thyroid neoplasm has this histologic finding:
• Branching papillae with fibrovascular core, lined by cuboidal to columnar epithelial cells and psammoma bodies
• Optically clear nuclei (Orphan Annie)
Papillary carcinoma
Prognosis for papillary carcinoma depends on SAGES…
- Sex: women better prognosis
- Age: children better prognosis
- Grade: dedifferentiation, poor prognosis
- Extent: extrathyroid extension, poor prognosis
- Size: large lesions, poor prognosis
Thyroid neoplasm that’s a neuroendocrine neoplasm…
Medullary carcinoma
Thyroid neoplasm that originate from the calcitonin producing parafollicular C-cells
Medullary carcinoma
Thyroid neoplasm that: • solitary or multiple lessons • 5-10% of all thyroid cancers • 80% Sporadic • 20% occurs in the setting of MEN syndrome 2A or 2B or as familial tumors
Medullary carcinoma
Thyroid neoplasm that is congo red positive (acellular amyloid deposits) and tumor cells positive to Calcitonin immunostain
Medullary carcinoma
Thyroid neoplasm that has polygonal to spindle-shaped cells, and form nests, trabeculae or follicles
Medullary carcinoma
Which thyroid neoplasm grows rapidly, spreads locally, invades trachea, esophagus, mediastinum b local invasion?
Anaplastic carcinoma
Which thyroid neoplasm originates from follicular cells?
Differentiated:
• Papillary (75%)
• Follicular (10%)
• Hurthle cell (5%)
Undifferentiated:
• Anaplastic (5%)
Which thyroid neoplasm is highly fatal, most patients die within one year?
Anaplastic carcinoma
Gross presentation of anaplastic carcinoma (thyroid neoplasm).
Large solid tumor with necrosis and hemorrhage.
Incidence of anaplastic carcinoma
- Constitutes 5-10% of all thyroid carcinomas
* Peak incidence - 7th decade
Different histological morphologies of anaplastic carcinoma.
- Multinucleated osteoclast - type giant cells
- Spindle cell sarcoma-like morphology
- Squamoid morphology
Compare and contrast the prognosis of the various thyroid carcinomas.
- Papillary - excellent
- Follicular - good
- Anaplastic - poor
- Medullary - varies
Compare and contrast the method of spread for each thyroid carcinoma.
- Papillary - lymph
- Follicular - blood vessel
- Anaplastic - local (grows so fast it has no time to spread)
- Medullary - all
Compare and contrast the age incidence for each thyroid carcinoma.
- Papillary - young < 45 years (75% of all thyroid carcinomas)
- Follicular - middle age (15%)
- Anaplastic - Elderly (5%)
- Medullary - Elderly, familial (5%)
Structure and location of pituitary gland.
- Present in the sphenoid bone, inside a cup-shaped space in the bone called the sella turcica.
- Weighs about 0.5 g.
- Connected to the hypothalamus with stalk.
- Composed of:
- Anterior - adenohypophysis (80%)
- Posterior - neurohypophysis
Function of the neurohypophysis?
• Small posterior lobe of pituitary
• Stores hormones secreted by the hypothalamus:
1. Oxytocin
2. Anti-diuretic hormone (ADH)
Function of adenohypophysis
• Large anterior lobe
• Releases hormone:
- Follicle stimulating hormone (FSH)
- Melanocyte stimulating hormone (MSH)
- Lutenizing hormone (LH)
- Growth hormone (GH)
- Adenocorticotropic hormone (ACTH)
- Thyroid stimulating hormone (TSH)
- Prolactin (PRL)Pituitary disease pertaining to TSH
- Hypersecretion = hyperthyroidism
* Hyposecretion = hypothyroidism
Pituitary diseases pertaining to ACTH
- Hypersecretion = Cushing’s disease
* Hyposecretion = Addison’s disease
Pituitary diseases pertaining to FSH
• Hyposecretion
- M = poor sperm production
- F = low estrogen, amenorrhea
• Hypersecretion
- F = menopausePituitary diseases pertaining to LH
• Hyposecretion
- F = no ovulation - M = low testosterone
Pituitary diseases pertaining to MSH
• Hypersecretion = excess pigment
Pituitary diseases pertaining to GH
• Hypersecretion
- during growth = gigantism
- after growth = acromegaly
• Hyposecretion = dwarfism
Pituitary disease pertaining to PRL
- Hypersecretion = galactorrhea (excess milk production), infertility
- Hyposecretion = poor milk production
Pituitary disease pertaining to ADH
• Hypersecretion = SIADH
- Syndrome of inappropriate ADH secretion
• Hyposecretion = diabetes insipidus
Histology of anterior pituitary
• Pink acidophils secrete: growth hormone (GH) and prolactin
• Dark purple basophils secrete:
- corticotrophin (ACTH)
- thyroid stimulating hormone (TSH)
- gonadotrophins
- follicle stimulating hormone (FSH)
- luteinizing hormone (LH)
• Pale staining chromophobes have few cytoplasmic granules, but may have secretory activity
Acidophils of the anterior pituitary secrete…
- Growth hormone
* Prolactin
Basophils of the anterior pituitary secrete…
- Follicle stimulating hormone (FSH)
- Corticotrophin (ACTH)
- Thyroid stimulating hormone (TSH)
- Luteinizing hormone (LH)
Chromophobes of the anterior pituitary secrete…
- Have few cytoplasmic granules
* May have secretory activity
General diseases of the pituitary
- Hyperpituitarism: excessive secretion of tropic hormones; most often secondary to a benign tumor (adenoma) arising in the anterior lobe –> called anterior pituitary adenomas
- Hypopituitary: deficiency of tropic hormones because pituitary gland is destroyed by destructive process such as injury, inflammation, surgery or radiation
- Local mass effect: tumors compress adjacent structures - such as the optic chiasm - causing headache, loss of vision, and hydrocephalus
Hyperpituitarism, in most cases, excess is due to __________ arising in the __________ lobe.
adenoma; anterior
Benign (pituitary) adenomas have symptoms that fall into 2 main categories:
• Pressure symptoms from glandular enlargement
- Headache, seizures, drowsiness, visual defects
• Hormonal effects
- Usually stimulatory if functional tumor
- May be inhibitory (non-functional with pressure necrosis)
Most common hormonally active adenomas
Prolactinoma
Features common to all pituitary adenomas
- 10% of all intracranial neoplasms & 25% incidental findings
- Usually benign and sporadic
- 3% occur with MEN syndrome
- May or may not be functional
- Functional - the clinical effects are secondary to the hormone produced
- Non-functional - large size, hypopituitarism (destroy adjacent ant. pituitary), visual field abnormalities
Hormones most commonly over-produced by adenomas…
Prolactin and GH
Sizes of pituitary adenoma
- Microadenoma, < 10mm, may cause focal bulging
* Macroadenoma, > 10mm, cause problem related to mass effect
How to diagnose pituitary adenoma
- Imaging: MRI brain with and without IV contrast
- Labs: check the levels of different hormones to determine which type of tumor it is
- Visual fields: to be performed by ophthalmologist, to see if tumor is causing visual symptoms
Gross appearance of pituitary adenomas are usually…
- Well circumscribed, invasive in up to 30%
- Size 1cm or more, specially in nonfunctioning tumor
- Hemorrhage & necrosis seen in large tumors
Uniform cells, one cell type (monomorphic/monomorphism), absent reticulin network, rare or absent mitosis are histologic characteristic of…
Pituitary adenomas
Most common pituitary adenoma…
PRL secreting adenoma
Type of immunostain that can be done for GH
- Immunoperoxidase
- Hormone will light up
Note: this stain is not necessary, since GH can be detected in serum
Growth hormone producing adenoma
Can result in:
• Gigantism: if hypersecretion occurs before puberty
• Acromegaly: if hypersecretion occurs after puberty
Name condition:
• High linear growth due to excessive action of insulin-like growth factor I (IGF-I) while the epiphyseal growth plates are open during childhood
• Very tall, very long legs, and arms
Acromegaly/Gigantism (growth hormone producing adenoma)
• Other symptoms include: diabetes, hypertension, heart failure, increased blood pressure, arthritis, osteoporosis, large jaw & hands, etc.
Excessive action of insulin growth factor - I (IGF-I) is related to…
Acromegaly or gigantism
Physical features of acromegaly
- Enlarged hands, feet, tongue
- Enlarged liver, heart, kidney, spleen, and other organs
- Coarsened, enlarged facial features
- Increased chest size (barrel chest)
- Impaired vision
- Headaches
- Menstrual cycle irregularities in women
- Erectile dysfunction in men
What are non-functioning adenomas (null cell adenoma)?
- Do not function and so do not secrete hormone (25-30% of patients)
- May grow to a large size before they are detected (mass effect)
- Patient can experience: visual deficits, hormone deficiency
Hypopituitarism symptoms occur only when there is a loss of greater than __% of ________ pituitary
75%, anterior pituitary
Acquired causes of hypopituitary
- Nonsecretory pituitary adenoma
- Ischemic necrosis, e.g. postpartum
- Iatrogenic by radiation or surgery
- Autoimmune (lymphocytic) hypophysitis
- Inflammatory e.g. sarcoidosis or TB…
T/F: Hypopituitarism can be congenital or acquired
True
Symptoms of _______ include dwarfism & effect of individual hormone deficiencies. Ex: Loss of MSH —> decreased pigmentation
Hypopituitarism
Medical condition in which the pituitary gland does not produce enough growth hormones
Pituitary dwarfism
Height of the affected individuals who have pituitary dwarfism
2’8” to 4’8”
Histologic appearance of posterior pituitary
Modified glial cells (pituicytes) and axonal process
Posterior pituitary syndromes include…
- Abnormal oxytocin secretion
- ADH deficiency
- ADH hypersecretion
Effects of abnormal oxytocin secretion…
Abnormalities of synthesis & release have NOT been associated with an significant abnormality
ADH deficiency causes…
Diabetes insipidus:
• excessive urination, dilute urine, due to inability to reabsorb water from the collecting tubules
Secretion of inappropriately high level of ADH secretion (SIADH-syndrome of inappropriate ADH) causes…
Excessive resorption of water –> hyponatremia:
• So much water in the blood results in a low sodium concentration
Which lobe of the pituitary is most commonly affected in metastic tumors…
- Posterior lobe mostly affected
- Anterior lobe rarely affected
• Metastic tumor comes from breast, lung, GI tract
What is a benign, slow growing tumor, that is derived from remnants of Rathke’s pouch? It can be suprasellar or intrasella, often presenting with cystic calcification.
Craniopharyngioma
Age range of patients most commonly affected by craniopharyngioma, and the symptoms they experience.
- Children or adolescents most affected
* Symptoms of hypofunction or hyperfunction of pituitary and/or visual disturbances, diabetes insipidus.
Stellate reticulum and wet keratin are prominent features
Craniopharyngioma
Gross appearance: low grade circumscribed epithelial tumor, partly cystic and calcified mass.
Craniopharyngioma
Histological appearance showing squamoid and columnar epithelium lining cystic spaces filled with oily fluid…
Craniopharyngioma
Most common cause of hyperpituitarism is…
An anterior lobe pituitary adenoma
Two distinctive morphologic features of most (pituitary) adenomas are…
- Absence of reticulin network
* Cellular monomorphism
Function and location of adrenal glands.
- Pair of endocrine glands just above the kidney
* They secrete steroids from cortex and catecholamines from medulla.
Layers of the adrenal cortex
- Zona glomerulosa –> mineralcorticoids (aldosterone) – SALT
- Zona fasiculata –> glucocorticoids (cortisol) – SUGAR
- Zona reticularis –> estrogens & androgens – SEX
What does the zona glomerulosa secrete?
• Mineralocorticoids (aldosterone) –> SALT
What does the zona fasiculata secrete?
• Glucocorticoids (cortisol) – SUGAR
What does the zona reticularis secrete?
• Estrogens and androgens – SEX
Syndromes associated with adrenal cortical hyperfunction:
- Cushing’s syndrome (excess of cortisol)
- Hyperaldosteronism
- Adrenogenital or virilizing syndrome (excess of androgen)
Elevation of cortisol level
Cushing’s syndrome
Recall: zona fasiculata –> glucocorticoids (cortisol) –> sugar
Most common exogenous cause of hypercortisolism (elevation of cortisol level, aka Cushing’ Syndrome)
Steroid therapy
Most common endogenous cause of hypercortisolism (elevation of cortisol level – Cushing’ Syndrome)
Pituitary Cushing Syndrome - hypersecretion of ACTH (70%)
Other endogenous causes include:
• Ectopic secretion of ACTH by non-pituitary neoplasm (10%)
• Primary adrenocortical neoplasm and rarely hyperplasia (15-20%)
What’s Pituitary Cushing Syndrome?
- Tumor in anterior pituitary secretes too much ACTH
* Causes cortex to thicken (hyperplasia) and results in excess cortisol secretion
What’s Adrenal Cushing Syndrome?
Adenocortical adenoma or hyperplasia increases cortisol level.
What is Paraneoplastic Cushing Syndrome?
- Neuroendocrine carcinoma of lung (or other nonendrocrine cancer) can secrete ACTH
- Results in hyperplasia and excess cortisol
- Most common site of these paraneoplasms is lung
What is Iatrogenic Cushing Syndrome?
Taking a lot of steroids causes adrenal ATROPHY and elevated cortisol.
Clinical features of Cushing Syndrome
- Central obesity (85-90%)
- Moon face (85%)
- Weakness and fatigability (85%)
- Hirsutism (abnormal hair growth, esp. in women) (75%)
- Hypertension (75%)
- Glucose intolerance/diabetes (75%)
- Osteoporosis (75%)
- Menstrual abnormalities (70%)
- Cutaneous striae (50%)
What happens in hyperaldosteronism?
Increase in aldosterone causes sodium retention and potassium excretion, increased blood pressure, hypokalemia
What is primary hyperaldosteronism?
- Adrenal gland hypersecretes aldosterone
* distinguished by decreased plasma renin
Potential causes for primary hyperaldosteronism?
- Nodular hyperplasia (60%)
- Neoplasm (35%)
- Rarely familial
What is secondary hyperaldosteronism?
- Hypersecretion is caused by something outside the adrenal gland
- Distinguished by increased plasma renin
Potential causes of secondary hyperaldosteronism
- Decreased renal perfusion
- Arterial hypovolemia and edema
- Pregnancy
What is virilizing syndromes?
- Overproduction of sex hormones in the zona reticularis, the innermost layer
- Virilization, precocious puberty, ambiguous genitalia
- Neoplasms can occur at any age, frequently malignant
Patients who have this syndrome have increased risk for acute adrenocortical insufficiency
Virilizing syndromes
Causes of virilizing syndromes
- Primary gonadal disorders
- Adrenocortical neoplasms
- Congenital adrenal hyperplasia
Gross appearance of adrenal cortical tumors.
• Encapsulated, solitary, usually yellow
• Size variable
• Can be nonfunctioning or functioning
• Can be benign or malignant:
- Malignant tumors with necrosis, hemorrhage (>= 300 g)How to tell if an adrenal cortical tumor is malignant or benign…
Local invasion, & the presence of metastases differentiate benign from malignant tumors
Histology of this type of tumor shows:
• Capsulated tumor with uniform or slightly pleomorphic cells, may be eosinophilic or clear cell type
• Spironolactone bodies [DIAGNOSTIC]
Adrenal cortical adenoma
• If tumor is mineralocorticoid, you will see spironolactone bodies (in hyperaldosteronism)
How does an adrenal cortical carcinoma differ from an adenoma?
- Larger than adenoma
* Non-capsulated with nuclear pleomorphism, mitoses, and necrosis
When acute adrenocortical insufficiency is caused by infection it is called…
Waterhouse-Frederickson syndrome
Causes of acute adrenocortical insufficiency
- Massive adrenal hemorrhage as in anticoagulant therapy, DIC, sepsis by N. meningitidis, pseudomonas
- Sudden withdrawal of steroid therapy
- Stress in a patient with underlying chronic insufficiency
Causes of chronic (Addison’s disease) adrenocortical insufficiency
- Autoimmune disorder: 75-90%, may be sporadic
- Infections, e.g. Tuberculosis, fungi (AIDS)
- Metastatic tumors destroying adrenal, e.g. lung, breast, … others
What is chronic adrenocortical insufficiency (Addison’s disease)?
Progressive destruction of the adrenal
What cells make up the adrenal medulla, and what does it secrete?
Composed of Chromaffin cells secreting catecholamines.
Adrenal medulla are derived from…
- Neural crest
* Part of sympathetic system
Diseases of the adrenal medulla…
Mainly tumors:
• Pheochromocytoma
• Neuroblastoma
Neuroendocrine tumor of the medulla of the adrenal glands, secretes excessive amounts of adrenaline and noradrenaline
Pheochromocytoma
Diagnosis of pheochromocytoma…
Increased urinary excretion of free catecholamine and their metabolites (VMA and metanephrins)
Three familial syndromes that predisposes to catecholamine secreting tumors like Pheochromocytoma…
- MEN2
- Neurofibromatosis type 1 (NF1)
- von Hippel-Lindau syndrome (VHL)
Where does Pheochromocytoma originate…
Originates from the chromaffin cells along the paravertebral SYMPATHETIC CHAIN extending from pelvis to base of skull…
• >95% are abdominal
• >90% in adrenal medulla
Pheochromocytoma “rule of 10”
- 10% extra-adrenal (closer to 15%)
- 10% occur in children
- 10% familial (closer to 20%)
- 10% bilateral or multiple (more if familial)
- 10% recur (more if extra-adrenal)
- 10% malignant
- 10% discovered incidentally
Pheochromocytoma, signs & symptoms, the five P’s
- Pressure (HTN) 9%
- Pain (headache) 80%
- Perspiration 71%
- Palpitation 64%
- Pallor 42%
- Paroxysms (the sixth P!): symptoms come and go
Classical triad for pheochromocytoma
- Pain (headache), perspiration, palpitations
* Lack of all 3 virtually excluded diagnosis of pheo in a series of > 21,000 patients
Zellballen (small nests or alveolar pattern), trabecular or solid patterns of polygonal/spindle shaped cells in rich vascular network is the histologic appearance of…
Pheochromocytoma (adrenal medulla tumor)
Benign vs malignant pheochromocytoma
- May have mitoses and marked pleomorphism
- Capsular and vascular invasion common in benign behaving tumor
- Definitive Dx of malignancy - presence of metastasis
Second most common solid childhood neoplasm, after CNS tumors…
Neuroblastoma
Treatment for neuroblastoma…
- Surgery
- Radiation therapy
- Chemotherapy
Adrenal medulla tumor associated with the deletion of short arm of chromosome 1…
Neuroblastoma
Some differentiate into ganglioneuroblastoma and spontaneously regress…
Neuroblastoma
What helps in the diagnosis of neuroblastoma?
VMA excreted in 24 hr. urine helpful in diagnosis
Small round blue cell tumor with rosettes indicates…
Neuroblastoma
Add’l info:
• Large mass with necrosis
• Areas of necrosis and calcification
What is MEN Syndrome?
- Multiple Endocrine Neoplasia Syndrome
- Inherited diseases resulting in hyperplasia, adenomas, and carcinomas
- Younger age
- Multiple endocrine involvement (synchronous or metachronous)
- Asymptomatic stage of endocrine hyperplasia
- More aggressive and recur
Which organ secretes insulin?
Pancreas
This hormone reduces the level of sugar (glucose) in the blood…
- Insulin
* Secreted by the pancreas
Parts of the pancreas…
Head, neck, body and tail
Location of the pancreas
- Retroperitoneum, 2nd lumbar vertebral level
* Extends in an oblique, transverse position
Gland with both exocrine and endocrine function
Pancreas
Blood sugar and health…
- Sugar (glucose) is an important source of energy
- What is eaten is absorbed into the blood
- Insulin is produced by the pancreas when blood sugar is high
- Insulin keeps blood sugar level within the normal range for health
Different cells within the islets of Langerhans of the pancreas
- beta cells –> insulin
- alpha cells –> glucagon
- delta cells –> somatostatin
- pancreatic polypeptide (PP) –> VIP
Which hormone does the alpha cells of the islets of Langerhans of the pancreas secrete?
- Glucagon
* Effect: glucose synthesis & glycogen breakdown in the liver –> increases blood glucose concentration
Which hormone do beta cells of the pancreas secrete?
- Insulin
* Effect: stimulation of lipids & glycogen storage & formation –> decreases blood glucose concentration
Which hormone do delta cells of the pancreas secrete?
- Somatostatin
* Effect: inhibits secretion of insulin & glucagon
Islet cell diseases include..
- Diabetes
* Islet cell tumors
Normal blood glucose level
Homeostasis –> about 90 mg/100 mL
How insulin and glucagon function…
Stimulus: rising blood glucose level (e.g. after eating a carbohydrate rich meal) –> high blood glucose level –> beta cells of the pancreas stimulated to release insulin into the blood –>
• liver takes up glucose and stores it as glycogen
• body cells take up more glucose
–> blood glucose level decline to a set point; stimulus for insulin release diminishes
Stimulus: declining blood glucose level (e.g. after skipping a meal) –> alpha cells of pancreas stimulated to release glucagon into the blood –> liver breaks down glycogen and releases glucose to the blood –> blood glucose level rise to set point; stimulus for glucagon release diminishes
Where is glycogen stored?
- Glycogen = store of glucose
* Stored in the liver
Leading cause of end stage liver disease, adult-onset blindness, and non-traumatic lower extremity amputation in the US.
Diabetes Mellitus
What is diabetes mellitus?
- Metabolic disorders
- Hyperglycemia
- Defects in insulin secretion, insulin action, or most commonly, both
- Affects multiple organ systems: kidneys, eyes, nerves, blood vessels
- Affects over 20 million in adults and children
Diabetes classification
• Causes could be primary in the pancreas, or secondary to other disease conditions
• Primary diabetes is classified into:
A- Type 1 (approximately 10%)
B- Type 2 (approximately 90%)
C- Genetic & miscellaneous causes
• Whatever the type, complications are the same.
Type 1 Diabetes
- Develops in childhood
- Autoimmune destruction of islet cells
- Heavy lymphocytic (CD4, CD8) infiltrates appear in and around islets (insulitis)
- The islets of Langerhans are destroyed (>90% of beta cells lost before metabolic changes appear)
- 3P’s: polyuria (excessive urination), polydipsia (excessive thirst), polyphagia (excess hunger)
- Metabolic acidosis, weight loss, dehydration, and electrolyte imbalance
In which type of diabetes is ketoacidosis common?
- Ketoacidosis is common in type 1
* In type 2 ketoacidosis is rare
Which type of diabetes develops in childhood and involves the autoimmune destruction of islet cells?
Type 1
Type 2 diabetes
- Age > 30 years, often present incidentally
- Sedentary life style and overwight
- Insulin resistance & beta cells dysfunction, resulting in relative insulin deficiency
- Fibrosis and deposition of amylin polypeptide within islets
- 3 P’s +/- symptoms of complications
- Rare ketoacidosis
Which type of diabetes involves insulin resistance & beta cells dysfunction, resulting in relative insulin deficiency…
Type 2
Secondary miscellaneous causes of diabetes…
- Diseases of exocrine pancreas (e.g. chronic pancreatitis)
- Endocrinopathies (e.g. Cushing’s Syndrome, Acromegaly)
- Infections (e.g. CMV)
- Drugs (e.g. glucocorticoids)
- Gestational diabetes
Common differences between type 1 and type 2 diabetes
Type 1
• Often diagnosed in childhood
• Not associated with excess body weight
• Often associated with higher than normal ketone levels at diagnosis
• Treated with insulin injections or insulin pump
• Cannot be controlled without taking insulin
Type 2
• Usually diagnosed in over 30 year olds
• Often associated with excess body weight
• Often associated with high blood pressure and/or cholesterol levels at diagnosis
• Is usually treated initially without medication or with tablets
• Sometimes possible to come off diabetes medication
Laboratory diagnosis for diabetes
- Random glucose >/= 200 g/dL + symptoms
- Fasting glucose >/= 126 g/dL on more than one occasion
- Abnormal oral glucose tolerance test when glucose level is more than 200 g/dL 2 hours after standard glucose load of 75g.
What is glycosylated hemoglobin, HbA1c?
- Blood test that measures the amount of glucose that has been incorporated into the hemoglobin protein of the red blood cell (RBC).
- HbA1c levels remain more stable than sugar levels.
- Not affected by short-term fluctuations in sugar
- Normal is 4-6%
- Evaluated periodically (1-2 per year)
Normal HbA1c
4-6% is normal
A1C% of 6.5 or above corresponds with…
- Diabetes
- Fasting glucose 126 mg/dL or above
- Oral glucose tolerance test 200 mg/dL or above
A1C% of 5.7 to 6.4 corresponds with…
- Prediabetes
- Fasting plasma glucose of 100 to 125 mg/dL
- Oral tolerance test of 144-199 mg/dL
A1C% of about 5 corresponds with…
- Normal (not diabetes)
- Fasting glucose of 99 mg/dL or below
- Oral glucose tolerance test 139 mg/dL or below
Renal complications associate with diabetes
- Both nodular (Kimmelstiel - Wilson lesion) and diffuse glomerulosclerosis
- Chronic renal failure
- Infections - pyelonephritis (bacterial and fungal infections)
Ocular complications associated with diabetes
- diabetic retinopathy (one of the leading causes for irreversible blindness) in the United States
- cataract
- glaucoma
- blindness
What is one of the leading causes for irreversible blindness in the US?
Diabetic retinopathy
What is cataracts?
- Complication from diabetes
* Protein deposits cloud the lens
What is retinopathy?
- Complication of diabetes
* Exudate from blood vessels on retina
What is glaucoma?
- Complication of diabetes
* Increased intraocular pressure, which can lead to blindness
What’s a vascular complication of diabetes?
Atherosclerosis:
• Early and accelerated atherosclerosis
• Hypertension
• Heart disease, cerebrovascular disease, and renal disease
• The most common cause of death - myocardial infarction
• Peripheral vascular disease
• Diabetic neuropathy, leading to propensity for injury
What’s the most common cause of death?
Myocardial infarction
Treatment for diabetes mellitus type 1
Insulin administration
Treatment for diabetes type 2
- Diet and exercise
- Oral hypoglycemics
- Insulin
What are pancreatic neuroendocrine tumors (PanNETs)?
- AKA islet cell tumors
- 2% of all pancreatic neoplasms
- Common in adults, and in the body/tail of the pancreas where there are more islet cells
- Single or multifocal
- Functional (excessive hormone production) and nonfunctional (without hormone production) larger
- Slow growing, metastases to nodes, liver, bone
- 80% occur in MEN1 patients
Most common type of pancreatic neuroendocrine tumor
Insulinomas are the most common, followed by gastrinomas
Types of islet cell tumors
- Insulinoma - beta cells
- Gastrinoma - delta cells
- Somasostatinoma - delta cells
- Glucagonoma - alpha cells
- VIPoma - delta cells
- Nonfunctional
Which type of islet tumor cells affects beta cells?
Insulinoma
Which type of islet cell tumor affects delta cells?
- Gastrinoma
- VIPoma
- Somasostatinoma
Which type of islet cell tumor affects alpha cells?
Glucagonoma
Islet cell tumor histology
- Solid, gyriform, trabecular and grandular patterns
- Nests of polygonal cells with moderate to abundant eosinophilic cytoplasm
- Amyloid is produced by insulin-secreting tumors (from amylin or somatostatin)
Important neuroendocrine markers for islet tumor cells
- Synaptophysin
- Chromogranin
Electron microscopy reveals dense core granules
WHO grading system
• Low grade (G1): if 20 mitoses
Treatment for insulinoma
90% cured by resection
Symptoms of insulinoma…
- Hypoglycemia </= 50 mg/dL
* Attack precipitated by fasting or exercise, relieved by eating or glucose administration
Lab findings for insulinoma…
- Decreased serum glucose
* Increased serum insulin
Are insulinomas mostly benign or malignant?
- Majority are benign, 10% can be malignant
* Most tumors solitary (< 2cm), can be multiple.
Which islet cell tumor is “histologically bland”?
Gastrinoma
Are gastrinomas mostly benign or malignant?
2/3 of cases malignant
Lab findings for gastrinoma…
Marked elevation of serum gastrin (>1000 pg/ml)
Which islet cell tumor presents with Zollinger-Ellison syndrome?
- Gastrinoma
- Triad: hypersecretion of gastric acid, severe peptic ulceration, presence of non-beta cell tumor of the pancreas or duodenum
- May also be associated with MEN1
Treatment for gastrinoma…
Medical therapy for control of the acid hypersecretion
Nonfunctional islet cell tumors
- 25% of islet cell tumors
- 90% malignant
- Age 50 year, female predominance
- Compression related symptoms
- Treatment - surgery
Layers of our head, from the outside to inside…
- Skin
- Bone
a. Epidural space (potential space if pathology occurs) - Dura mater (attached to bone)
a. Subdural space - Arachnoid mater
a. Subarachnoid space - Pia mater
- Brain (with specialized blood vessels that prevent many substances from entering brain)
Which cells of the CNS are derived from neuroectoderm?
- Oligodendrocytes
- Neurons (nerve cells)
- Ependymal cells
- Astrocytes
Which cells of the CNS are derived from mesoderm?
- Microglial cells
* Endothelial cells
What makes up the meninges?
- Dura
- Arachnoid
- Pia mater
What are the longest cells of the body?
Motor neurons
Which neurons are most susceptible to hypoxia?
- Most susceptible: pyramidal neurons of Sommer’s Sector (CA1) of hippocampus
- Also highly susceptible: Purkinje cells of cerebellum
- Also susceptible: pyramidal neurons in middle layers (III, IV, V) of cerebral cortex, neurons in basal ganglia
Which neurons are relatively resistant to hypoxia?
Neurons in brainstem and cerebellum.
What do oligodendrocytes produce?
- Myelin
* Help transmit electrical impulses and supports axons.
Shape of microglial cells.
- Rod-shaped cells
* Enlarge in a disease state
Purpose of Ricinus communis agglutinin 1 (RCA-1)
Highlights microglial cells that are at rest
What are microglial nodules?
Clusters that form in viral diseases as a defense mechanism. This is a hallmark of viral infections of the CNS.
Hallmark of viral infections in the CNS.
Microglial nodules
Two components of the blood brain barrier, separated by a basement membrane…
- Capillary endothelial cells
* Foot processes of astrocytes
Disruption of the blood brain barrier causes…
Vasogenic edema
Appearance of endothelial cells…
- Specialized
- Reduced numbers of pinocytotic vesicles
- Many mitochondria
- Tight junctions
How do tumors cause edema in the brain?
- They produce their own blood vessels
* New vasculature does not have a normal blood brain barrier –> edema –> headache or even seizure
What is glioblastoma?
- An aggressive tumor with dark area of hemorrhage and necrosis.
- Edema around tumor causes a midline shift (impinges onto opposite hemisphere).
