PATHOLOGY OF ENDOCRINE SYSTEMPATHOLOGY OF MUSCULO-SKELETAL SYSTEM

SKIN PATHOLOGY

General medicine

Diabetes mellitus - kidneys, Goiter, Pheochromocytoma, Carcinoid, Osteomyelitis, Osteodystrophy. Dermatomyositis, Verruca vulgaris,

Molluscum contagiosum, Atheroma, Basocellular papilloma

DEPARTMENT OF PATHOLOGICAL ANATOMY, FACULTY OF MEDICINE , COMENIUS UNIVRES ITY, BRATISLAVA

ENDOCRINE SYSTEMDiabetes mellitus

Goiter

Pheochromocytoma

Neuroendocrine

tumors

DIABETES MELLITUS

• chronic metabolic disease associated with persistent hyperglycemia in relative orabsolute insulin deficiency

• classification1. DM type I

- immune- idiopathic

2. DM type II3. Others specific types DM4. Gestational DM

• complex multifactorial disease with hereditary and genetic predisposition

• a leading cause of morbidity and mortality in the world

DIABETES MELLITUS

Complications

1. Acute complications

• hypoglycemic coma

• hyperglycemic coma

2. Chronic complications

• atherosclerosis

• diabetic microangiopathy

• diabetic nephropathy

• retinopathy

• diabetic foot syndrome

DIABETES MELLITUSDIABETIC NEPHROPATHY

• It is characterized by albuminuria, arterial hypertension and gradual renal failure.

• Diabetic intercapillary glomerulosclerosis is one of the most serious microangiopathiccomplications of DM - Kimmelstein-Wilson nephropathy

Etiology

• hyperglycemia → non-enzymatic glycation of basement membrane and mesangial matrixproteins → thickening of basement membrane

• hypertension → ↑ glomerular plasma flow, hyperfiltration, microalbuminuria → subsequentglomerulosclerosis

Course of the disease – 4 stages (latent, incipient, manifest, chronic renal failure)

DIABETES MELLITUSDIABETIC NEPHROPATHY

Microscopic finding

• Basal membrane thickening,mesangial cell proliferation andmatrix.

• Placement of hyaline materialin afferent and efferent vessels- hyaline arteriolosclerosis.

• Proximal tubule cells are brightfor the stored glycogen therein.

Intercapillary glomerulosclerosis and arteriolosclerosis (HE) 159

Intercapillary glomerulosclerosis to fibrosis of glomeruli (HE) 159

GOITER

= visible thyroid enlargement

• Hashimoto’s goiter (thyreoiditis)

• Basedow’s goiter (Grave’s disease)

• Non-toxic goiter - difuse

- nodular

Diagnostics

• Examination methods - anamnesis, hormone levels, USG, scintigraphy

• Biopsy – fine needle aspiration (FNA)

GOITER

Classification by function

•Goiter with normal function

• hypofunctional goiter - bradycardia, weight gain, growth retardation, failure tothrive, dry skin and hair, facial leakage, eyelid swelling, somnolence, fatigue,inefficiency, constipation, pseudopubertas praecox.

• hyperfunctional goiter - tachycardia, weight loss, failure to thrive, warm, skinsweating, heat intolerance, exophthalm, diarrhea

Pathogenesis

• deficiency of thyroid hormones mainly due to iodine deficiency

GOITERDIFFUSE GOITER

= Non-toxic single or colloidal goiter - diffuse enlargement without changingfunction

Etiology

• endemic - affects more than 10% of the population in the area (low I,strumigens)

• sporadic - if it affects less than 10% in the area, the etiology is unclear

Macroscopic finding

• regular and diffuse enlarged, jelly-shaped, translucent, brown on the cut

Microscopic finding

• hyperplasia - high cylindrical cells in follicles with papillary folds (early stage)

• involution - large follicles with flattened epithelium and colloid content (latestage)

Diffuse goiter (HE)

Large follicles lined with flattened

epithelium, rich in colloid content

GOITERNODULAR GOITER

= more nodular goiter, adenomatous

• from long-running simple goiter

• mostly eufunction, the cause of nodes is not clear

Macroscopic finding

• irregular enlargement, partially delineated nodes, fibrosisand hyalinization, bleeding, plaque calcifications, cystformation

Microscopic finding

•incompletely encapsulated nodes, various large follicles withepithelium from flat to cylindrical, hemorrhagic lesions, MAwith hemosiderin, scarring and calcification, micro- andmacrocystic transformation

Nodular goiter (HE) 69

Nodes filled with different sized follicles

GOITERGRAVES BASEDOWOV DISEASES

= autoimmune toxic goiter, exophthalmic goiter• arises on an autoimmune substrate

Clinical finding• Triad of symptoms = hyperthyroidism, diffuse enlargement of TG, exophthalmus•diffuse goiter, symptoms of thyrotoxicosis (temperature, nervousness, sweating, heatintolerance, tachycardia, dysrhythmia, diarrhea, hand tremor, myopathy, osteoporosis,exophthalm, pretibial myxedema, lagophthalm)

Diagnostics• increased serum T3 and T4, low TSH, Ab versus TSH receptors, USG

Etiology•genetics, other autoimmune diseases, smoking, stress, autoantibodies

Macroscopic finding• diffuse, regular magnification, homogeneous in cut, fleshy, brown-red

Microscopic finding• hyperplasia and hypertrophy of follicular bb with papillary processes (Sanders cushions),pale vacuolized colloid, vascularized stroma with lymphocytes

Grave’s disease (HE) 70

Follicles with a small amount of weakly

staining colloid

Small follicles lined with high cylindrical

epithelium with pale cytoplasm

A small amount of aqueous

vacuolized colloid

Papillary processes of the

epithelium (Sanders

cushions)

Grave’s disease (HE) 70

GOITERHASHIMOTO’S DISEASE

= chronic autoimmune lymphocyte goiter, the most common cause of hypothyroidism

Clinical finding

• Triad of symptoms = diffuse enlargement of TG, infiltration of Lyme, + autoAb against LW,

hypothyroidism, moderate goiter

Diagnostics

• Ab against aTG, against thyroperoxidase aTPO, Ab against TSH receptors, USG

Macroscopic finding

• classical - diffuse, symmetrical gland enlargement, gummy consistency

• fibrotizing - stiff, very large

Microscopic finding

• classical - infiltration of TG with lymphocytes, MA, formation of lymphatic follicles with

germinal centers, follicles of lymphomas are atrophic without colloid, oxyphilic conversion of

follicular bb to Hurthle cells (granular eosinophilic cytoplasm with numerous mitochondria),

finely coarse fibrous septum

• fibrotizing - replacement of parenchyma by fibrous connective tissue, less lymphocyte

infiltrate

Hashimoto’s thyreoiditis (HE) 240

Lymphatic follicles with germinal centersExtinction of thyroid follicles

Hashimoto’s thyreoiditis (HE)

Lymphatic follicles

Atrophic thyroid

follicles with missing

colloid

Lymphatic follicles

Thyroid follicles lined with

Hurtle cells

PHEOCHROMOCYTOMA• generally rare benign tumor of the adrenal medulla from chromaffin cells• 10% is malignant, DNA ploidy or mitotic index examination is used to distinguishthem• often found as part of familial syndromes (MEN 2A, 2B, neurofibromatosis type I,von Hippel-Lindau i.)

Diagnostics• CT, MRI, PET, SPECT

Clinical finding• clinical symptoms associated with overproduction of catecholamines (hypertension,congestive heart failure, MI, IC bleeding to sudden death)

Macroscopic finding• soft, spherical, of varying size, black-brown color

Microscopic finding• nests bb bounded by vascularized stroma, arranged in columns, beams and clumps• tumor cells are large, polygonal and pleomorphic with granular amphophilic,basophilic cytoplasm

Pheochromocytoma (HE) 193

Adrenal cortex

Pheochromocytoma (HE) 193

Vascularized

stroma

Islets of

pleomorphic cells

NEUROENDOCRINETUMORS

• a group of tumors capable of secreting biogenicamines

• part of the APUD, thus, the diffuse neuroendocrinesystem

• predominantly in the GIT and respiratory tract -depending on the location, the appropriateclassification

• always malignant tumors

• they mainly secrete hormones in GIT, mainlyserotonin (glucagonoma, insulinoma .....)

Clinical finding• carcinoid syndrome (tachycardia, face and chestflash, diarrhea ..)

NEUROENDOCRINE TUMORS

Macroscopic finding

• usually 2 cm, yellow-yellow-white, covered by ulcerated or intact mucosa

Microscopic finding

• small blue cells with a core of salt and pepper, solid growth

Neuroendokrinný tumor

Neuroendocrine tumor in the large intestine (HE) 184

Neuroendocrine tumor

Intestinal mucosa

Neuroendocrine tumor

gland

Neuroendocrine tumor in the large intestine (HE) 184

MUSCULO-SKELETAL SYSTEM

Osteomyelitis

Osteodystrophy

Dermatomyositis

OSTEOMYELITIS

• acute, subacute and chronic• acute osteomyelitis is a purulent process in the bone caused by pyogenic organisms affecting the pre-infectious metaphysis of long bones

Way of spread• hematogenous spread of infection (rather younger children), bacteraemia, septicemia, transfer of infectionfrom another lesion (elderly patients), direct introduction of MO into bone (trauma, during surgery)

Patogenesis• penetration under the periosteum creates subperiostal pus (the pineal gland is a resistant barrier to thespread of infection, therefore the infection passes into the medullary cavity, or in childhood under theperiostium for cartilage vascularization)

Etiology• MRSA, Strept B, pneumonia a pyogenes

Diagnostics• RTG, blood examination + Bch, MRI, punction – aspiration form periostal abscess and clean needle fromthe joint, blood culture

OSTEOMYELITIS

Clinical finding

• manifestation of septic shock (febrility, nausea,vomiting, dehydration, chills) bone pain, pseudo-paralysis, swelling, pain and redness of the area

Complication

• pathological fracture, bone shortening anddeformities, arthritis, chr. osteomyelitis withsequestering

Microscopic findig

• several stages - festering, ischemic necrosis,healing, fibrosis, bone repair

Osteomyelitis (HE) 139

Leukoctytes

Osteomyelitis (HE) 139

Leukocytes

OSTEODYSTROPHYOSTITIS DEFORMANS PAGET

= osteolytic and osteosclerotic bone disease affecting one or morebones

Etiology

• nejasná, predpokladá sa infekcia paramyxovirusom, AD dedičnosťa genetická vnímavosť

Complications

• formation of osteosarcoma

Diagnosttics

• positive RA, X-ray, CT, radioisotope. bone scan, bone resorptionmarkers, ALP marker, serum Ca, P, PTH serum levels may be normal

• monoostotic form: may be asymptomatic and appear randomly

• polyostotic form: pain, fractures, skeletal deformities, increasedalkaline phosphatase

Morphology

1. Initial osteophytic st. - osteoclastic bone resorption- many osteoclasts

2. Mixed osteolytic-osteoblastic st. - imbalancebetween new bone formation and bone resorption -mosaic-like appearance;

3. Osteosclerotic st. - denser bone, which is slightlymineralized, soft, breaks easily, as X-rays as cottonwool

Microscopic finding

resorption lacquers, osteoid, irregularly coarsenedcompaction, fibrous pulp

OSTEODYSTROPHYOSTITIS DEFORMANS PAGET

Bone resorption

Bone resorption

Bone formation

Paget’s disease (HE) 156

Fibrosis

Bone bars

Osteoclasts

Paget’s disease (HE) 156

Fibrosis

Fibrosis

Bone bars

Osteoclasts

DERMATOMYOSITIS(POLYMYOSITIS|)

= idiopathic chronic inflammatory disease of striatedmuscles

The exact etiology is unknown, immunological mechanism isassumed - autoimmune mechanisms directed againstendothelial endothelial capillaries → microangiopathy →hypoperfusion

Diagnostics

• symmetrical proximal muscle weakness, elevated creatinekinase (MM), aldolase or myoglobin, signs of myopathy forEMG, muscle biopsy with signs of inflammatory myopathy,typical skin manifestations

Clinical finding

• skin erythema with heliotropic erythema and periorbitaledema, dysphagia, respiratory dysfunction, internal organmalignancies

DERMATOMYOSITIS(POLYMYOSITIS)

Microscopic finding - muscle

• occlusive perivescular lymphocytitic infiltrate

• noticeable vacuolization and fragmentation ofmuscle fibers with inflammatory cells

• later replaced by fibrous and adipose tissue

DERMATOMYOSITIS(POLYMYOSITIS)

Microscopic finding - skin

• perivascular and periadnexal lymphocyte infiltrate

• vacuolar epithelial dystrophy, lymphocyte infiltrateat the dermo-epidermal boundary

• mild epidermal atrophy

Inflammatory

infiltrate

Muscle

fibers

Dermatomyositis (HE) 226

Atrophic

epiderma

Lymphocyte infiltrates in

superficial and deep

dermis

Periadnexal

lymphocyte infiltrates

Hair follicles

Dermatomyoistis (HE) 226

SKIN

Verruca vulgaris

Molluscum contagiosum

Psoirasis

Ateroma

Bazocelular papiloma

VERRUCA VULGARIS

= most common viral skin disease - benign squamous cell papillomatouslesion• belongs to infectious dermatoses• transmission by direct contact or autoinococulation• from a clinical point of view, we divide them into several species

Verruca vulgaris•most common, HPV 1-2, multiple, smaller than 1cm, bounded, firmconsistency pardoning the skin on the hands• biopsy - skin excision

Macroscopic finding• Raised bumps with a rough surface formed by a layered crackedhorn. The size ranges from a pinhead to a few centimeters.

Microscopic finding• hyperkeratosis (thickening of the stratum corneum) with parakeratosis(abnormal cornering when the nuclei of the bb remain in the upperlayers), papillomatosis (fingertip extension of the corium papillae withbranching), acanthosis (enlargement of stratum spinosum), epidermalpineal extension, in the cytoplasm of kerathyaline granules

Verruca vulgaris (HE) 197

Hyperkeratosis

with parakeratosis

Epiderma

Derma

MOLLUSCUM CONTAGIOSUM

• DNA poxyvirus, human to human transmission

• eyelids, neck, genitals, anal opening

Macroscopic finding

• multiple papules, hemispherical, as smooth as a pin head, the colors of the skin leakafter gray-white cheese

Microscopic findind

• demarcated skin lesion with degeneration of epidermal cells. Moluscum bodies -eosinophilic intracytoplasmic inclusions in degenerate cells

Molluscum contagiosumn (HE) 142

Degenerative changes

of epidermal cells

Calytic lesion

Acanthosis

Central crater with hyperkeratosis

and relaxed molluscum bodies

Acanthosis of the

epidermis

Molluscum

bodies

Molluscum bodies released

in keratin pulp

Molluscum contagiosumn (HE) 142

PSORIASIS

= noninfectious inflammatory autoimmune skindisease

• chronic course and propensity for relapses

•the most common manifestation is peeling of the skinas it changes up to seven times more often thannormal

•dermatosis with corneal disorder

• Microscopic finding

-hyperkeratosis with focal or confluent parakeratosis

-regular psoriasiform acanthosis - epidermalprocesses

-dermal papilla edema

-suprapapillary thinning of the epidermis

- stratum granulare is missing

- Munro’s microabsces in parakeratotic horn layer -dg criterion

Psoriasis (HE) 318

Hyperkeratosis

with parakeratosis

Regular acanthosis

Papilomatosis

ATHEROMA

= epidermal cyst

• if intradermal or subcutaneous - sebaceous cyst

Macroscopic findins

• size of peas or eggs

Microscopic finding

• wall formed by epidermis with layered keratin, rupture causes granulomatous reaction around foreign body

Atheroma (HE) 200

Epiderma

Cyst filled with

keratin, lined with

squamous

epithelium

BASOCELLULAR PAPILLOMA

= senile verruca, seborrhoic keratosis

• frequent benign skin tumor growing exophitically

• older people

• there is no malignant change

Macroscopic finding

• often multiple, papillary, sharply bounded, gray-brown toblack color, skin without inflammation

Microscopic finding

• hyperkeratosis, acanthosis, papillomatosis, sharp border ofthe tumor from the environment, keratin pearls in theepidermis

Basocellular papilloma (HE) 178

Keratin pearls

Acanthosis

Hyperkeratosis

Papilomatosis

Basocellular papilloma (HE) 178

keratin pearls

Acanthosis

Hyperkeratosis

Basocellular papilloma (HE) 178

Basaloid cells:

Regular, round, basophil

cells with relatively large

nuclei