Pathology Flashcards
what surrounds bundles of muscle fibres?
perimysium
what surrounds an entire muscle?
epimysium
what surrounds individual muscle fibres?
endomysium
what type of stain can be sure to highlight endomysial fibrosis & intracytoplasmic inclusions?
modified gomoritrichrome stain
what are the three types of skeletal muscle fibres?
red fibres (type 1) white fibres (type 2) intermediate fibres
describe red muscle fibres
large mitochondria & lots of myoglobin
describe white muscle fibres
small mitochondria & larger motor end plates
when are red muscle fibres useful?
slow twitch fibres useful for marathon runners
why are red muscle fibres more resistant to fatigue/
have a greater ability to regenerate ATP
when are white muscle fibres useful
fast twitch fibres useful for short bursts of energy
fatigue rapidly
what are the two types of type 2 (white) muscle fibres?
a - fast oxidative glycolytic
b - fast glycolytic
when should a muscle biopsy be done?
if there’s:
- evidence of muscle disease
- presence of neuropathy (+ nerve biopsy)
- presence of a vascular disorder
what evidence of muscle disease would lead you to do a muscle biopsy?
weakness
muscle symptoms (atrophy, fasciculation)
elevated CK
what range is indicative of high CK levels & give an example of what this suggests?
200-300 times the normal
dystrophies
what range is indicative of intermediate CK levels & give an example of what this suggests?
20-30 times the normal
inflammatory myopathy
what range is indicative of low CK levels & give an example of what this suggests?
2-5 times the normal
neurogenic disorders
what is electron microscopy used for?
to examine the ultra-structure of the muscle
what are the two broad categories of muscle pathology?
- those primarily affecting the muscles
- those affecting muscle due to changes in nerves
what are the 5 main groups of myopathies?
Muscular dystrophies Inflammatory myopathies Congenital myopathies Secondary myopathies Metabolic myopathies
name some dystrophic changes
variability in muscle fibre size endomysial fibrosis fat infiltration & replacement myocyte hypertrophy & fibre spilitting (due to actin/myosin bundles splitting in the fibre body) increased central nuclei segmental necrosis regeneration ring fibres
how are muscular dystrophies classified?
according to inheritance pattern, clinical pattern of muscle groups involved and genes responsible
what is the most common inheritance pattern of muscular dystrophies?
x-linked recessive
what are the pathological features of muscular dystrophies?
- destruction of single fibres
- prolonged
- regeneration
- fibrosis
what level of severity will frame shift mutation result in with DMD?
severe
what level of severity will mutations resulting in altered binding result in with DMD?
moderate to severe
what level of severity will middle rod mutations result in with DMD?
mild (Becker)
when will DMD come on?
2-4 years
what is DMD
duchenne muscular dystrophy
what symptoms will be experienced in DMD?
proximal weakness (quadriceps), pseudohypertrophy of calves
what will the CK levels be like in DMD?
raised
what mutation causes DMD?
mutations in dystrophin gene on the long arm of chromosome X
what happens in DMD to cause the symptoms?
alterations in anchorage of actin cytoskeleton to basement membrane so fibres are liable to tearing when contracting
what is the histology seen in DMD?
muscle fibre necrosis & phagocytosis
regeneration
chronic inflammation & fibrosis
hypertrophy
when will BMD come on?
later onset than DMD
what is BMD?
Becker muscular dystrophy
what is the mutation in with BMD?
mutation in dystrophin
what is BMD?
a variant of DMD
what are the most common types of myotonic dystrophy?
DM1 & DM2
what are the clinical features of muscle dystrophy?
muscle weakness
myotonia
non-muscle features
what kind of inheritance is present in myotonic dystrophy?
autosomal dominant
which muscles are affected by myotonic dystrophy in adolescence?
face
distal limbs
which muscles are affected by myotonic dystrophy in life later than adolescence?
respiratory muscles
what are the non-muscle features of myotonic dystrophy?
cataracts
frontal baldness in men
cardiomyopathy
low intelligence
what are the histological features seen in myotonic dystrophy?
atrophy of type 1 fibres centreal nuclei ring fibres fibre necrosis fibrofatty replacement
what is the diagnostic histological feature of myotonic dystrophy?
non-random selective damage to type 1 fibres
what process causes the damage in myotonic dystrophy?
inflammation
what processes causes inflammation in duchennes?
the damage causes inflammation
name the 3 inflammatory myopathies caused by primary inflammation of muscle?
infective agents
polymyositis
dermatomyositis
what is the cause of polymyositis?
unknown
what is polymyositis?
chronic inflammatory disease
what are the clinical features of polymyositis?
progressive muscular weakness
pain
tenderness
which sex is polymyositis more common in?
women
which clinical features of polymyositis are uncommon in dystrophies?
pain & tenderness
what is the hallmark clinical feature of polymyositis?
pain
what is polymyositis mediated by?
cell-mediated immune response to muscle antigens
what infiltrates and invasions are seen in the muscle in polymyositis?
edomysial lymphocytic infiltrate
invasion by CD8+ T lymphocytes
what histological features are seen polymyositis?
segmental fibre necrosis
what is dermatomyositis?
skin changes plus polymyositis
what are the clinical features of dermatomyositis?
upper body erythema
swelling of eyelids with purple discolouration
is dermatomyositis associated with malignancy?
yes in 10%
what are the histological features of dermatomyositis seen around the capillaries in muscle?
immune complex & complement deposition within & around capillaries within muscles
what other histological features of dermatomyositis?
perifascicular muscle fibre injury
B-lymphocytes & CD4+ T cells
how do you distinguish between dermatomyositis & polymyositis?
look at immunoglobulins
histologically indistinguishable
how is dermatomyositis mediated?
cell mediated component
antibody mediated component
what is stereotypically seen in neurogenic disorders of muscle?
changes after nerve damage with subsequent re-innervation
what are the 4 neurogenic disorders of muscle?
motor neurone disease
spinal muscular atrophy
peripheral neuropathies
miscellaneous spinal disorders
what is seen histologically in neurogenic disorders of muscle?
- small, angulated muscle fibres (adults)
- smal, round muscle fibres (infants)
- target fibres
- fibre type grouping
- grouped atrophy
what is motor neuron disease?
progressive degeneration of anterior horn cells
what is seen clinically in motor neuron disease?
dennervation atrophy
fasciculation
weakness
what is fasciculation?
uncontrollable twitching in the muscle
what inherited pattern is seen in spinal muscular atrophy?
autosomal recessive
what is myasthenia gravis?
autoimmune disorder of muscle function
what are the clinical features of myasthenia gravis?
weakness
proptosis
fatigue
dysphagia
in which demographic group is myasthenia gravis seen in?
women between 20 - 40
what is an uncommon feature of myasthenia gravis?
thymic hyperplasia
what happens in rhabdomyolysis?
breakdown of skeletal muscle
what does the breakdown of skeletal muscle in rhabdomyolysis lead to?
myoglobinuria
hyperkalaemia
necrosis & shock
what is a big trigger of rhabdomyolysis?
crush injury
e.g. RTA
drug addicts
what renal outcome can occur because of rhabdomyolysis?
acute renal failure
what metabolic outcomes can occur because of rhabdomyolysis?
hypovolaemia
hyperkalaemia
metabolic acidosis
what haematological outcome can occur because of rhabdomyolysis?
disseminated intravascular coagulation
what are the common multi-system features of connective tissue disorders?
joint problems
skin
subcutaneous tissues
immunological abnormalities
which sex are connective tissue diseases more common in?
women
what kind of drugs do connective tissue disorders usually respond to?
anti-inflammatory drugs
what are the connective tissue disease major conditions?
- RA
- SLE
- polyarteritis nodosa
- dermatomyositis & polymyositis
- polymyalgia rheumatica
- temporal arteritis
- scleroderma (systemic sclerosis)
what is SLE?
autoimmune multisystem disorder
which antibody is specific to SLE?
anti-nuclear antibodies
which sex is SLE more common in?
females
what SLE features can you see in the skin?
- butterfly rash on sun exposed areas
- discoid lupus erythematosus
what SLE features can you see in the joints?
arthralgia
what SLE features can you see in the kidneys?
glomerulonephritis
what SLE features can you see in the CNS?
- psychiatric symptoms
- focal neurological symptoms
what SLE features can you see in the CVS?
- pericarditis
- myocarditis
- necrotising vasculitis
what SLE features can you see in the lymphoreticular?
- lymphadenopathy
- splenomegaly
what SLE features can you see in the lungs?
- pleuritis
- pleural effusions
what haematological features do you see in SLE?
- anaemia
- leucopenia
- thombophilia
what are the visceral lesions in SLE mediated by?
type 3 hypersensitivity in renal, skin & joints
what do you see in biopsies of visceral SLE lesions?
IgG & C3 in skin
what are the haematological effects in SLE mediated by?
type 2 hypersensitivity
what happens to red blood cells in SLE to cause the haematological effects?
direct antibody lysis of RBC
what is PAN?
inflammation & fibrinoid necrosis of small/medium arteries
what are the major organs targeted in PAN?
kidneys
heart
liver
GI tract
what are the minor organs targeted in PAN?
skin joints muscles nerves lungs
what are the clinical features of PAN?
Non-specific +/- organ specific features
e.g. hypertension, haematuria, abdominal pain, melaena, diarrhoea, mononeuritis multiplex, rash, cough, dyspnoea
how is PAN diagnosed?
biopsy
serology
what is seen on biopsy in PAN?
fibrinoid necrosis of vessels
what is seen on serology in PAN
serum contains pANCA
which demographic group is polymyalgia rheumatica seen in?
elderly
what are the clinical features of polymyalgia rheumatica?
pain swelling stiffness in shoulder pelvic girdles no muscle weakness
which drug type does polymyalgia rheumatica respond to?
corticosteroids
what is temporal arteritis also known as?
giant cell arteritis
what is temporal arteritis?
inflammation affecting cranial vessels
what is a patient with temporal arteritis particularly at risk of?
blindness of terminal due to the branches of ophthalmic artery being affected
what are the clinical features of temporal arteritis?
headache
scalp tenderness
how is temporal arteritis diagnosed?
raised ESR
temporal artery biopsy
what is seen on biopsy of temporal artery in temporal arteritis?
inflammation +/- giant cells, fragmentation of internal elastic lamina
what is scleroderma?
excessive fibrosis of organs and tissues due to excessive collagen production
what are the skin features of scleroderma?
- tight
- tethered
- decreased joint movement
what are the GI tract features of scleroderma?
fibrous replacement of muscularis
what are the heart features of scleroderma?
- pericarditis
- myocardial fibrosis
what are the lung features of scleroderma?
interstitial fibrosis
what are the kidney features of scleroderma?
- affects arteries
- leads to hypertension
what are the MSK features of scleroderma?
- polyarteritis
- myositis
what is CREST syndrome?
- calcinosis
- Raynaud’s
- oesophageal dysfunction
- sclerodactyly
- telangectasia
what is CREST syndrome associated with?
scleroderma
what can death be due to in scleroderma?
- renal failure secondary to malignant hypertension
- severe respiratory compromise
- cor pulmonale
- cardiac failure or arrhythmias secondary to myocardial fibrosis
what are the common benign bone tumours?
osteochondroma
enchondroma
osteoid osteoma
chondroblastoma
what is an osteochondroma?
Cartilage capped bony projection arising on external surface of bone containing a marrow cavity that is continuous with that of the underlying bone.
what symptoms can osteochondromas sometimes cause which lead to surgical removal of the tumour?
pain & irritation
what is an enchondroma?
Benign hyaline cartilage tumour arising in medullary cavity of bones of hands and feet
what is the eponymous name for a single enchondroma?
ollier’s disease
what is the eponymous name for multiple enchondromas?
mafucci’s syndrome
what mafucci’s syndrome associated with?
multiple angiomas
which demographic group are enchondromas seen in?
young adults
more common in men
what is ollier’s disease?
rare developmental disorder resulting in an enchondroma in a metaphases & diaphyses
what is the normal pattern of ollie’s disease?
typically unilateral & involving one extremity
what is maffucci’s syndrome?
multiple enchondromatosis with soft tissue and visceral haemangiomas
who is at a greater risk of malignant transformation, patients with Maffucci’s syndrome or patients with Ollier’s disease?
those with Maffucci’s syndrome
what are the histological features of enchondromas under low power?
lobules of varying size
what are the histological features of enchondromas not under low power?
Chondrocytes with small, round, pyknotic nuclei inside hyaline cartilage – no atypia.
Variable cellularity
what is an osteoid osteoma?
benign osteoblsatic tumour of the bone normally found in femur, tibia, hands/feet & axial skeleton (spine)
what demographic are osteoid esteems mostly found in?
children & young adults, more common in male
what do osteoid osteomas look like?
central core of vascular osteoid and peripheral zone of sclerotic bone
what is the clinical picture of an osteoid osteoma?
dull pain
worse at night
characteristically relieved by aspirin or other NSAIDs
what do osteoid osteomas look like on X-ray?
radiological nidus surrounded by reactive sclerosis in cortex of bone
what are the histological features of osteoid osteomas?
Nidus consists of osteoid and woven bone surrounded by osteoblasts.
Central nidus of an osteoid osteoma composed of irregular reactive new bone
what is a chondroblastoma?
rare benign cartilage tumour arising in bone which can occasionally be more aggressive
where are chondroblastomas found?
at epiphysis of long bones
which age group are chondroblastomas found in?
in the second decade of life
what do chondroblastomas look like on X-ray?
Spherical and well-defined osteolytic foci, sometimes extending into the subarticular bone, joint space or metaphysis
what do chondroblastomas look like histologically?
much more densely cellular than normal cartilage
Closely packed polygonal cells plus areas of immature chondroid.
Mitotic activity is low.
Distinct cytoplasmic borders with foci of “chicken-wire” calcification.
what is the treatment of chondrocostomas?
Biopsy and curettage plus adjuvant liquid nitrogen
which 3 types of tumour are being but locally aggressive?
Giant cell tumour
Osteoblastoma
Chordoma
which cell is presumed to be the cell of origin of giant cell tumours?
osteoclast
which age group are giant cell tumours usually found in?
25-40 years
which sex are giant cell tumours more common in?
women
what sites in the body are giant cell tumours found?
long bones, often around the knee
what do giant cell tumours look like on X-ray?
Radiolucent with increasing density towards periphery.
what is the gross appearance of giant cell tumour?
irregular haemorrhagic mass in the epiphyseal region of proximal femur
what are the histological features of giant cell tumours?
multi-nucleated giant cells in a sea of round to oval mononuclear cells
what do osteoblastomas look like on X-ray?
Solitary, benign and self-limited tumour that produces osteoid and bone at the metaphysis or diaphysis of long bones
what do osteoblastomas look like histologically?
Irregular spicules of mineralised bone and osteoid surrounded by osteoblasts, vascular stroma with pleomorphic spindle cells & osteoid and woven bone are seen
what is the treatment of osteoblastomas?
surgical resection by curettage, intralesional excision or en bloc resection
what are chordomas?
Very rare tumour arising from notocord remnants - precursor of your vertebral bodies & intervertebral discs (midline tumour, often in sacral region)
in which demographic group do chordomas occur in?
older adults (40+yrs), more common in females
are chordromas benign or malignant?
benign but local destructive and invasive
what is the macroscopic appearance of chordromas?
Soft, blue-gray, lobulated tumours
Gelatinous translucent areas and often a capsule is present
Lesion often tracks along nerve roots in the sacral plexus or out the sciatic notch in planes of least resistance.
what do chordromas look like on x-ray?
On plain x-ray - appear as a solitary mid-line lesion with bony destruction, often an accompanying soft tissue mass. Approximately half of the time focal calcifications are present
what do chordromas look like histologically?
Lobules and fibrous septa. The malignant cell has eosinophilic cytoplasm & prominent vacuoles of mucus push the nuclei to the side.
what is the treatment of chordromas?
Difficult to resect
Radiation may be helpful
Chemotherapy for late stage disease
what is an osteosarcoma?
commonest primary malignant tumour formed by malignant osteoblasts forming osteoids
which demographic group are osteosarcomas commonly seen in?
young adults (
where are osteosarcomas found in the body?
Ends of long bones particularly distal femur, proximal tibia, and proximal humerus
what do osteosarcomas look like on x-rays?
tumours erode & destroy the bone cortex, extending into soft tissue where irregular tumor bone with calcification is seen
what is essential for the diagnosis of an osteosarcoma?
osteoid production
what are the 3 histological variants of conventional osteosarcoma?
osteoblastic, chondroblastic, and fibroblastic
what is the treatment of an osteosarcoma?
Biopsy, CT, bone scan
Pre-operative chemotherapy
Surgical resection
Post-operative chemotherapy
what is a chondrosarcoma?
second commonest primary malignant tumour of bone, exhibits pure hyaline cartilage differentiation
what are chondrosarcomas composed of?
malignant chondrocytes
what is the treatment of chondrosarcomas?
wide surgical excision, limited use of chemotherapy & radiotherapy
are Ewing’s sarcomas malignant or benign?
highly malignant
what is a Ewing’s sarcoma?
peripheral primitive neuroectodermal tumour
where do Ewing’s sarcomas usually occur?
in the metaphysics & diaphysis of femur, tibia, then humerus
in what demographic group are Ewing’s sarcomas occur?
in second decade of life
more common in males
what do Ewing’s sarcomas look like histologically?
one of the “small round blue cell” tumours
what is the treatment of Ewing’s sarcomas?
Surgery
Radiation therapy
Chemotherapy with vincristine, dactomycin and cyclophosphamide
Post-operative adjuvant chemotherapy
what are the most commonly metastasising cancers?
Thyroid , breast, lung (particularly small cell), kidney and prostate
what kind of lesion is found at the site of metastases?
osteolytic lesions
what kind of lesion is found at the site of metastases from prostate cancer?
osteosclerotic
what is multiple myeloma?
Malignant proliferation of plasma cells in bone marrow
which age group does multiple myeloma commonly occur in?
old age
what does multiple myeloma often cause?
renal failure
what does multiple myeloma result in?
bone destruction of axial skeleton, pathological/compression fractures
what are the histological features of multiple myeloma?
abnormal plasma cells that may be poorly differentiated or resemble normal plasma cells
