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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
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ENDOCRINE SYSTEMDiabetes mellitus
Goiter
Pheochromocytoma
Neuroendocrine
tumors
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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
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DIABETES MELLITUS
Complications
1. Acute complications
• hypoglycemic coma
• hyperglycemic coma
2. Chronic complications
• atherosclerosis
• diabetic microangiopathy
• diabetic nephropathy
• retinopathy
• diabetic foot syndrome
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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)
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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.
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Intercapillary glomerulosclerosis and arteriolosclerosis (HE)
159
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Intercapillary glomerulosclerosis to fibrosis of glomeruli (HE)
159
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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)
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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
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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)
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Diffuse goiter (HE)
Large follicles lined with flattened
epithelium, rich in colloid content
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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
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Nodular goiter (HE) 69
Nodes filled with different sized follicles
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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
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Grave’s disease (HE) 70
Follicles with a small amount of weakly
staining colloid
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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
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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
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Hashimoto’s thyreoiditis (HE) 240
Lymphatic follicles with germinal centersExtinction of thyroid
follicles
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Hashimoto’s thyreoiditis (HE)
Lymphatic follicles
Atrophic thyroid
follicles with missing
colloid
Lymphatic follicles
Thyroid follicles lined with
Hurtle cells
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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
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Pheochromocytoma (HE) 193
Adrenal cortex
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Pheochromocytoma (HE) 193
Vascularized
stroma
Islets of
pleomorphic cells
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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 ..)
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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
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Neuroendocrine tumor in the large intestine (HE) 184
Neuroendocrine tumor
Intestinal mucosa
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Neuroendocrine tumor
gland
Neuroendocrine tumor in the large intestine (HE) 184
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MUSCULO-SKELETAL SYSTEM
Osteomyelitis
Osteodystrophy
Dermatomyositis
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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
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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
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Osteomyelitis (HE) 139
Leukoctytes
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Osteomyelitis (HE) 139
Leukocytes
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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
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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
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Paget’s disease (HE) 156
Fibrosis
Bone bars
Osteoclasts
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Paget’s disease (HE) 156
Fibrosis
Fibrosis
Bone bars
Osteoclasts
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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
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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
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DERMATOMYOSITIS(POLYMYOSITIS)
Microscopic finding - skin
• perivascular and periadnexal lymphocyte infiltrate
• vacuolar epithelial dystrophy, lymphocyte infiltrateat the
dermo-epidermal boundary
• mild epidermal atrophy
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Inflammatory
infiltrate
Muscle
fibers
Dermatomyositis (HE) 226
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Atrophic
epiderma
Lymphocyte infiltrates in
superficial and deep
dermis
Periadnexal
lymphocyte infiltrates
Hair follicles
Dermatomyoistis (HE) 226
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SKIN
Verruca vulgaris
Molluscum contagiosum
Psoirasis
Ateroma
Bazocelular papiloma
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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
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Verruca vulgaris (HE) 197
Hyperkeratosis
with parakeratosis
Epiderma
Derma
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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
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Molluscum contagiosumn (HE) 142
Degenerative changes
of epidermal cells
Calytic lesion
Acanthosis
Central crater with hyperkeratosis
and relaxed molluscum bodies
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Acanthosis of the
epidermis
Molluscum
bodies
Molluscum bodies released
in keratin pulp
Molluscum contagiosumn (HE) 142
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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
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Psoriasis (HE) 318
Hyperkeratosis
with parakeratosis
Regular acanthosis
Papilomatosis
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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
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Atheroma (HE) 200
Epiderma
Cyst filled with
keratin, lined with
squamous
epithelium
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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
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Basocellular papilloma (HE) 178
Keratin pearls
Acanthosis
Hyperkeratosis
Papilomatosis
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Basocellular papilloma (HE) 178
keratin pearls
Acanthosis
Hyperkeratosis
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Basocellular papilloma (HE) 178
Basaloid cells:
Regular, round, basophil
cells with relatively large
nuclei