What is the pathogenesis of squamous cell carcinoma of the skin?
1. UVB causes mutation in basal cells.
2. Proliferation of abnormal basal cells causes actinic keratosis.
3. Further mutations occur and lead to full thickness dysplasia – see in situ.
4. SCC in situ develops the ability to invade the dermis due to an accumulation of further mutations.
5. In immune suppressed people HPV plays a role; and there are some inherited diseases with an increase in SCC (albinism, xeroderma).
What is the pathogenesis of SCC of the lung?
1. Inhalation of smoke causes squamous metaplasia.
2. Exposure to carcinogens in the smoke causes squamous metaplasia to become dysplastic. This is through accumulation of mutations.
3. The dysplasia progresses to squamous cell carcinoma in situ as the dysplastic cells fill up the entire thickness of the epithelium.
4. By now the genomics is unstable and more mutations mean the cells acquire the ability to invade through the basement membrane.
5. The squamous cell carcinoma expands and invades the bronchus, lung parenchyma, and blood vessels. Metastasis occurs.
What is the pathogenesis sporadic of colonic carcinoma?
1. There is an initiating mutation of the APC gene.
2. A tubular adenoma forms. More mutations occur, particularly in KRAS.
3. The tubular adenoma enlarges and becomes more dysplastic. More mutations occur.
4. A key mutation in P53 means that the tumour progresses to high-grade dysplasia/carcinoma in situ.
5. Accumulation of more mutations results and the ability to invade through the basement membrane and become invasive adenocarcinoma.
What is the pathogenesis of colonic carcinoma in Lynch syndrome?
1. The patient inherits an abnormality of one of the genes used for DNA mismatch repair.
2. The matching gene on the opposite chromosome is lost due to a sporadic mutation. (Two hit hypothesis)
- autosomal dominant
3. DNA repair abnormalities mean that mutations accumulate. A mutation occurs in the APC gene.
4. The APC mutation means that tubulous adenoma’s form. These progress through increasing levels of dysplasia as more mutations occur.
5. High-grade dysplasia develops, which then acquires the ability, through further mutations, to invade through the basement membrane and into the bowel wall.
What is the pathogenesis of urothelial carcinoma of the urinary bladder?
1. Carcinogens such as those found in cigarette smoke or aromatic amines cause mutations in the urothelial cells. This causes them to become dysplastic.
2. The dysplastic cells proliferate and gain more mutations.
3. The proliferation of dysplastic cells can result in either flat atypia or by forming papillary proliferations.
4. When the papillary proliferations grow they can accumulate more mutations and become more dysplastic. This forms urothelial papillary carcinoma, this is an insitu proliferation.
5. With more mutations the cells gain the ability to invade through the basement membrane and an invasive urothelial carcinoma.
What will determine the outcome of a patient with bladder cancer?
Pass must mention stage and grade
Whether the tumour is invasive or in situ (1 mark)
• Depth of invasion
• Extension outside the bladder
• Vascular invasion
• lymph node invasion extension (1 mark for 2 of these things)
High grade has a worse prognosis
What are the risk factors of bladder cancer?
The most important risk factor is cigarette smoking.
Industrial carcinogens, such as naphthylamine and benzidine, play a role among the workers in dye, rubber, plastic, and insulation industries.
Schistosoma haematobium infection in Egypt is associated with an increased incidence of urinary bladder cancer.
What is the pathogenesis of Pagets disease of the bone?
1. The exact initial cause of Paget’s disease is unknown, some people think it might be by rest and others think it might be due to a mutation in the genes such as RANK.
2. The initial activity is increased osteoclastic activity. There is much bone resorption increases in the rate of bone resorption.
3. There is a next phase of osteoclastic, osteoblastic activity. The osteoblasts compensate by an accelerated deposition of lamellar bone. This produces a characteristic mosaic pattern.
4. Osteoblastic activity. The osteoblastic activity predominates. The marrow spaces are filled with blood vessels causing the bone to become hypervascular. The bone become sclerotic.
5. Burned out. The osteoblastic activity eventually decreases leaving dense bone which is very thick for example in the skull
Describe the pathogenesis of the aortic aneurysm. (6 marks) What would have caused the femoral artery occlusion. (4 marks)
MUST say: The aneurysm is caused by atherosclerosis weakening the wall. The hydrostatic pressure then causes the aorta to dilate. ( 2 marks)
Atherosclerosis causes weakening oft he wall by the following mechanism; ½ mark for each point.
- Endothelium is injured
- Dysfunctional endothelial cells are more permeable to lipids.
- Oxidation of lipids and an invasion of the vessel wall by macrophages.
- Accumulation and attachment of platelets to the vessel wall; platelets degranulate, releasing growth factors and permeability factors, and also help recruit macrophages into the site of vascular injury.
Oxidation of lipids deposited in the stroma; macrophages releasing reactive free oxygen radicals injure the muscular wall
Macrophages die and release cell debris, enzymes, and lipids that form the semiliquid core of atheromas.
The underlying media is injured by the inflammation and becomes weak and thin.
The aorta dilated because of luminal pressure.
Ulceration and thrombosis of the atheroscleotic plaque ( in the Aorta).
The aortic plaque ulcerates exposing the thrombogenic lipid core. (1 mark)
A thrombus forms. (1 mark)
Embolism of the thrombus (1 mark)
Thrombus occludes the femoral artery (1 mark)
An arterial dissection arises when blood enters the arterial wall itself, as a hematoma dissecting between its layers.
Dissections are often but not always aneurysmal (see also below).
- In contrast, a false aneurysm (also called pseudo-aneurysm) is a defect in the vascular wall leading to an extravascular hematoma that freely communicates with the intravascular space (“pulsating hematoma”).
Both true and false aneurysms as well as dissections can rupture, often with catastrophic consequences.
More common (and dangerous) proximal lesions (called type A dissections), involving either both the ascending and descending aorta or just the ascending aorta (types I and II of the DeBakey classification)
Hypertension is the major risk factor in aortic dissection.
- suggesting that pressure-related mechanical injury is contributory.
A considerably smaller number of dissections are related to inherited or acquired connective tissue disorders causing abnormal vascular ECM (e.g., Marfan syndrome, Ehlers-Danlos syndrome, vitamin C deficiency, copper metabolic defects).
Regardless of the underlying etiology causing medial weakness, the trigger for the intimal tear and initial intramural aortic hemorrhage is not known in most cases. Nevertheless, once the tear has occurred, blood flow under systemic pressure dissects through the media, fostering progression of the medial hematoma.
Accordingly, aggressive pressure-reducing therapy may be effective in limiting an evolving dissection. In some cases disruption of penetrating vessels of the vasa vasorum can give rise to an intramural hematoma without an intimal tear.
In lobar pneumonia, four stages of the inflammatory response have classically been described; congestion, red hepatization, gray hepatization, and resolution.
In the first stage of congestion the lung is heavy, boggy, and red. It is characterized by vascular engorgement, intra-alveolar fluid with few neutrophils, and often the presence of numerous bacteria.
The stage of red hepatization that follows is characterized by massive confluent exudation with neutrophils, red cells, and fibrin filling the alveolar spaces. On gross examination, the lobe now appears distinctly red, firm, and airless, with a liver-like consistency, hence the term hepatization.
The stage of gray hepatization follows with progressive disintegration of red cells and the persistence of a fibrinosuppurative exudate, giving the gross appearance of a grayish brown, dry surface.
In the final stage of resolution the consolidated exudate within the alveolar spaces undergoes progressive enzymatic digestion to produce granular, semifluid debris that is resorbed, ingested by macrophages, expectorated, or organized by fibroblasts growing into it. Pleural fibrinous reaction to the underlying inflammation, often present in the early stages if the consolidation extends to the surface (pleuritis), may similarly resolve. More often it undergoes organization, leaving fibrous thickening or permanent adhesions.
Asbestosis and sequalae
Asbestosis is marked by diffuse pulmonary interstitial fibrosis, which is indistinguishable from diffuse interstitial fibrosis resulting from other causes, except for the presence of multiple asbestos bodies.
They arise when macrophages attempt to phagocytose asbestos fibers; the iron is presumably derived from phagocyte ferritin.
Asbestosis begins as fibrosis around respiratory bronchioles and alveolar ducts and extends to involve adjacent alveolar sacs and alveoli; eventually the affected regions become honeycombed.
The scarring may trap and narrow pulmonary arteries and arterioles, causing pulmonary hypertension and cor pulmonale.
Both lung carcinomas and mesotheliomas (pleural and peritoneal) develop in workers exposed to asbestos. The risk of lung carcinoma is increased about fivefold for asbestos workers; the relative risk of mesotheliomas, normally a rare tumor (2 to 17 cases per 1 million persons), is more than 1000-fold greater.
Concomitant cigarette smoking greatly increases the risk of lung carcinoma but not that of mesothelioma.
The alveolar capillary membrane is formed by two separate barriers; the microvascular endothelium and the alveolar epithelium. In ARDS the integrity of this barrier is compromised by either endothelial or epithelial injury or, more commonly, both.
Markers of endothelial injury and activation such as endothelin and von Willebrand factor can be detected at high levels in the serum of patients with ARDS.
The acute consequences of damage to the alveolar capillary membrane include increased vascular permeability and alveolar flooding, loss of diffusion capacity, and widespread surfactant abnormalities caused by damage to type II pneumocytes.
Endothelial injury also triggers the formation of microthrombi that add the insult of ischemic injury. Hyaline membranesso characteristic of ALI/ARDS result from inspissation of protein rich edema fluid that entraps debris of dead alveolar epithelial cells.
Diffuse alveolar damage: what is it and describe the pathological features (a) immediately and (b) at 6 months
Diffuse alveolar damage is a histological pattern in lung disease. It is seen in acute respiratory distress syndrome (ARDS), transfusion related acute lung injury (TRALI) and acute interstitial pneumonia (AIP).
Macroscopic findings: The lungs are heavy, filled with fluid, firm, red, and boggy.
Microscopic findings in acute stage: There is congestion, interstitial and intraalveolar edema, inflammation, and fibrin deposition along the inside of alveoli in form of hyaline membranes
Must mention fibrosis (1 mark) 1/2 mark for any of the ones below.
• Marked thickening of the alveolar septa.
• Lungs are stiff.
• Alveoli are smaller and can resemble a honeycomb
What is the pathogenesis of coronary artery atheroma?
1. There is endothelial cell injury by a variety of mechanisms including hypertension and turbulent blood flow. Chemicals in the blood such as homocystine and high blood glucose and free radicals can also damage it.
2. The damaged endothelial cells are leaky and admit lipids. The lipids sit under the endothelium forming a fatty streak.
3. Macrophages and other white blood cells are attracted by the damaged endothelium. They migrate into the fatty streak and cause release of cytokines which means that there are more inflammatory cells attracted. They ingest lipid.
4. The cytokines also cause smooth-muscle migration and proliferation. The end result is an atheroma with endothelium overlying a fibrous and smooth-muscle cap, with a lipid core. And associated chronic inflammation. The outside smooth-muscle wall can become thin.
5. If the atheroma is unstable because they are fibrous cap is thin than it can rupture and thrombus can form on it.
What is the pathogenesis of MI?
1. An unstable atheroma forms in a coronary artery.
2. The thin cap overlying the lipid core ruptures exposing the thromobogenic.lipid.
3. Platelets adhere and the clotting cascade is initiated.
4. The coronary artery is occluded by thrombus . This results in ischaemia to the myocardium supplied by the coronary artery.
5. The myocardium undergoes coagulative necrosis.
What is the pathogenesis of heart valve damage in chronic rheumatic fever?
1. A streptococcus infection in the throat generates antibodies.
2. These cross-react with proteins in the heart valve. Inflammation occurs by activation of the complement cascade, recruitment of inflammatory cells. The mitral valve is particularly affected.
3. Cytokines produced by the inflammatory cells cause fibrosis by activation of fibroblasts.
4. Repeat infections mean that this cycle is repeated resulting in marked fibrosis of the valve with shortening of the cordi tendonae.
5. The repeated cycles of fibrosis result in a markedly distorted valve with a gaping fishlike mouth. The distorted valve is incompetent and regurgitatent.
What is the pathogenesis of Coal miners pneumoconiosis?
1. The coalminer breathes in coal dust and silica.
2. This is not able to be cleared by the lung cilia, or by the type 2 pnuemocytes. It accumulates in the interstitium of the lungs.
3. The silica and carbon cause activation of fibroblasts and chronic inflammation resulting in fibrosis and expansion of the alveolar walls.
4. The fibroblasts produce collagen which then organises and contracts.
5. As the as spaces contracts the become smaller with very wide alveolar walls. This is honeycomb lung. Gas exchange is unable to occur over the thick walls. The patient becomes very short of breath.
What is the pathogenesis of cervical cancer?
1. Human papilloma virus of a high risk type such as 16 or 18 infects squamous cells. This particularly happens at the transformation zone.
2. Initially the infection is episomal, and produces a low grade squamous intraepithelial lesion. Eventually, HPV DNA integrates into the nuclear DNA of the squamous cell.
3. The HPV oncogenes E6 and E7 are transcribed and block the retinoblastoma and P 53 pathways. This allows proliferation of atypical cells.
4. The atypical cells accumulate to fill up the entire thickness of the epithelium. This is high-grade squamous intraepithelial lesion. HS I L.
5. More mutations accumulate in the cell and the cell has the ability to invade through the basement membrane forming a large tumour mass of squamous cell carcinoma.
Cytoplasmic changes in CIN
Atypical cells with:
- High N/C ratio
- Increased mitotic activity
- Nuclear atypia
- Koilocytic change (structural changes in a cell as a result of HPV infection)
What is the pathogenesis of endometrioid carcinoma of the ovary?
Endometrioid tumors are distinguished from serous and mucinous tumors by the presence of tubular glands bearing a close resemblance to benign or malignant endometrium
1. Endometriosis occurs and endometrial glands and stroma are deposited in the ovary.
2. The ectopic endometrium is exposed to unopposed oestrogen, such as from oestrogen made in fat, or iaterogenic sources
3. There is hyperplasia of the endometrium, mutations occur in some cells and this becomes atypical hypoplasia.
4. Further mutations occur and small foci of endometrioid adenocarcinoma form in the ovary.
5. This grows and becomes a large tumour which can metastasise by invasion of blood vessels and transit coelomic spread.
What is the pathogenesis of hepatocellular carcinoma caused by hepatitis B?
1. Hepatocellular carcinoma is caused by hepatitis B in two ways. The hepatitis B has a direct carcinogenic effect by integrating its DNA and a into the nucleus of the cell. The cirrhosis caused by chronic hepatitis B infection also helps cause hepatocellular carcinoma.
2. Hepatitis B integration into the nucleus of a cell causes of activation of oncogenes. This causes the cell to proliferate abnormally and the DNA to become unstable so that more mutations occur.
3. The chronic inflammation from cirrhosis causes increased cell turnover. This means that any cells that have abnormal mutations are given the opportunity to proliferate more
4. Eventually the atypical cells which are caused by this process form a nodule. Initially this may be an adenoma. As the mutations accumulate, this progress is to carcinoma.
5. The carcinoma cells grow uncontrollably and form a large tumour mass. This can invade blood vessels and metastasise.
What is the pathogenesis of alcoholic cirrhosis?
1. Alcohol causes injury to cells resulting in cell death and fatty change within the remainder of cells.
2. The cell death and fatty change attract inflammatory cells. This forms steatohepatitis.
3. The inflammatory cells release cytokines which causes fibroblast proliferation. Preparative processes mean that the liver regenerate and forms small nodules.
4. Continued cell death, reparative growth and fibrosis result in bands appearing between the portal tracts and the central veins. This is called bridging fibrosis.
5. These fibrous band expand to surround nodules of regenerating liver cells are form the characteristic appearance of cirrhosis.
What is the pathogenesis of gallstone induced pancreatitis?
1. Gallstone travels down the common bile duct and blocks the pancreatic duct.
2. There is some reflux of bile into the pancreatic duct. This causes activation of the pancreatic enzymes lipase amylase within the duct.
3. The enzymes start to auto digests the adjacent pancreatic acini. This releases more enzymes and a positive cycle of enzyme release and inflammation occurs.
4. If this settles down it will become chronic fibrotic pancreatitis.
5. If the positive reinforcement cycle continues there will be continuing digestion and fat necrosis, protein necrosis in collagen from proteases, ascites, haemorrhage as blood vessels are digestive and eventually acute haemorrhagic pancreatitis and shock.
A 69 year old man is involved a severe motorcycle crash. He is admitted to ICU with multiple fractures. On day 3 he has develops low blood pressure, a and tense abdomen. Ascitic fluid is drained and is cloudy…..his amylase is 8765. 1. Describe the sequence of events leading to his acute decline. (5 marks) 2. Describe the typical sequence for healing of his tibeal fracture (4 marks)
---Part 1 (5 marks)---
To pass MUST say (2 marks)
The patient has acute pancreatitis.
The inappropriate activation of enzymes inside the pancreas leading to autodigestion is thought to occur in the following sequence (1 mark for each of these)
▪ Shock damages the pancreas through ischaemia.
▪ Rupture of damaged acinar cells leading to a release of digestive enzymes into the interstitial spaces and peripancreatic tissue
▪ Autodigestion of proteins, lipids, and carbohydrate in of cells forming the pancreas, peripancreatic fat tissue, and blood vessels
---Part 2--- 1 mark for explaining each part of the healing sequence
Bone healing can be divided into four stages:
• soft callus formation;
• hard callus formation;
What is granulation tissue and its constituents? What are the 4 stages of tissue repair from scarring
Granulation tissue: is new connective tissue and tiny blood vessels that form on the surfaces of a wound during the healing process
- contains new vessels, fibroblasts laying down collagen, and ECM
(1) Formation of new blood vessels ; angiogenesis
(2) Migration and proliferation of fibroblasts -> laying down collagen
(3) Deposition of ECM
(4) Maturation and organisation of fibrous scar
Describe the two types of skin healing
Primary intention: edges are brought together by suturing; no apparent deficit of flesh
Secondary intention: close apposition of wound not possible
- large deficit
4 stages of bone healing
(1) Haematoma formation: the initial trauma will damage blood vessels, leading to clot formation around the site of injury. In this and other early phases of healing there will also be necrosis and phagocytosis of damaged tissues.
(2) Granulation tissue/soft callous: growth of new blood vessels/angiogenesis, influx of macrophages and fibroblasts.
- This occurs early in healing [2-5 days] and prepares the area for osteogenesis; fibrogenesis will only deposit a small amount of collagen before chondrocytes and osteoblasts become the main ECM secreting cells.
(3) Hard callous formation: where cartilage and bone is laid down
- Cartilage formation: laid down by chondrocytes/chondroblasts.
- Bone formation: progenitor cells migrate in from the periosteum and differentiate into osteoblasts → extracellular matrix proteins (including collagen) → mineralised to form bone.
(4) Remodelling: both osteoblasts and osteoclasts [which break down bone] will be active to convert woven/spongy bone [Weak] to cortical/compact bone.
List 4 factors which may result in delayed or abnormal bone healing
Movement: too much will disrupt callous but too little will reduce the size and delay healing
Medication: e.g. corticosteroids
Diabetes and other medical conditions
Types of bone healing failures (2); and subsequent treatment
Non-union: bone ends are too far apart
Surgery: to remove the excess fibrous tissue, correct alignment and possible add a bone graft
- reproducing haemotoma to start the healing process
What is the pathogenesis of oesophageal adenocarcinoma?
1. There is damage to the normal oesophageal squamous epithelium at the gastro-oesophageal junction by reflux.
2. The squamous epithelium undergoes metaplasia to intestine or type. There is chronic inflammation. This is called Barrett’s oesophagus.
3. There is an accumulation of mutations, some of which is due to the increased cell turnover caused by the inflammation, this causes dysplasia within the intestinal epithelium.
4. More mutations accumulate and the epithelium undergoes severe dysplasia and carcinoma in situ
5. Further accumulation of mutations results in cells being able to invade through the basement membranes and proliferate forming a large mass which is oesophageal adenocarcinoma.
What is the pathogenesis of duodenal peptic ulcer? -> gastric cancer
1. Helicobacter pylori causes 90% of duodenal ulcers.
2. With Helicobacter inflammation of the stomach mucosa is more marked in the distal (antral) region, with relative sparing of body (acid-secreting)
3. This pattern results in increased gastrin release, which makes the acid secretion in the stomach go up.
4. High acid output from the stomach is dumped in the duodenum. There are other factors that can increase rapid emptying.
5. The high acid erodes the relatively unprotected duodenal mucosa and an ulcer forms.
Helicobacter causes antral gastritis by
- Releasing urease and breaking down the protective mucus layer
- Causing an antigenic reaction – T cells which cause epithelial damage
- Causing inflammation which kills the epithelial cells
- Causes gastric atrophy.
Must say the ulcer is malignant, that there is intestinal metaplasia and dysplasia leading to carcinoma. (3 marks)
+ Gastric atrophy and inflammation lead to intestinal metaplasia
Further exposure to inflammation and carcinogens lead to dysplasia
An accumulation of mutations lead to high grade dysplasia and carcinoma
What is the pathogenesis of a haemorrhagic stroke?
1. An embolus from a more proximal artery lodges in a cerebral vessel.
2.The vessel occludes and the area of the brain it supplies becomes ischaemic. The vessels in the iscaemic area are damaged too with the iscaemia.
3.The embolus dissolves and blood flows back into the vessels
4.The damaged vessels rupture and blood flows into the brain
5. With no blood supply and the haemorrhage the infarct becomes established
What is the pathogenesis of a subarachnoid haemorrhage?
1. There is a congenital weakness at the branch point of a circle of Willis vessel – a defect in the media.
2. The weakness bulges out and forms a small berry aneurism
3. A combination of hypertension, which increases the pressure and la place’s law means the aneurism expands like a balloon
4. The larger it gets the easier it is to expand and the wall becomes very thin
5. the berry anuerism bursts and hoses blood into the subarachnoid space.
What is the pathogenesis of acute death following an ischaemic stroke?
1. The blood vessels around the stroke and damaged and become leaky
2. The fluid leaking out of them causes the brain to swell.
3. The cranium has a limited volume so the brain starts to push through the tentorium
4. The herniation (uncal herniation, the uncus is part of the temporal lobe) compresses vital midbrain structures.
5. With increasing pressure and progression of the hernia there will be distortion of the brainstem leading to Duret hemorrhages (tearing of small vessels in the parenchyma) in the pons., respiratory center depression and death.
What is the pathogenesis of renal failure in diabetes?
1. The basement membrane of glomeruli becomes thickened by complex glycosylation products
2. There is increase in the mesangial matrix by increased matrix production or glycation of matrix proteins. If they are nodular they are called Kimmelsteil-Wilson nodules.
3. Hyalinisation of arterioles narrows them and leads to glomerular ischaemia
4. Narrowing of larger vessels leads to global ischaemia and loss of tubules with interstitial scarring.
5. The glomeruli become sclerosed and there is extensive renal scarring
What is the pathogenesis of lytic bone lesions in a patient with prostate cancer?
1. The prostate cancer metastasises to bone
2. The cancer cells release cytokines that cause osteoclast proliferation and activation
3. The osteoclasts destroy the bony trabeculae
4.The loss of calcified bone leads to radiolucency
What is the pathogenesis of unstable metacarpophalangeal joints in rheumatoid arthritis?
1. Complex autoimmune activation of B and T cells and cytokines results in joint inflammation
2. Inflammatory cells infiltrate the synovial membrane and cause synovitis.
3. Pannus forms and destroys bone, enzymes secreted by synoviocytes and chondrocytes degrade cartilage
4. The inflammation also weakens the tendons and ligaments
5. Combined they lead to malformation of the MCP joint.
What is the pathogenesis of bullus formation in pemphigoid?
1. Auto-antibodies form against the basement membrane ( hemidesmosomes)
2. These bind to the skin basement membrane
3. Complement is activated and the hemidesmosomes are destroyed
4. The epidermis separates from the dermis
5. Fluid accumulate in the gap and causes a bulla
Invasive ductal carcinoma of no special type and high-grade ductal carcinoma in situ (DCIS).
The invasive ductal carcinoma will have developed from preceding high-grade ductal carcinoma in situ.
High-grade and extensive ductal carcinoma in situ has a relatively high risk of progression to invasive ductal carcinoma
Ductal carcinoma in situ arises as a result of clonal proliferations due to accumulated DNA alterations/abnormalities and epigenetic changes in epithelial cells
Further DNA alterations in abnormal intraductal epithelial cell clones, as well as changes in the adjacent stroma, lead to stromal invasion i.e the development of invasive ductal carcinoma.
Describe pathological changes in osteolytic metastatic cancer
The osteolytic lesions are almost certainly due to metastatic breast cancer
Cytokines released by the metastatic cancer cells activate osteoclast activity in the site of metastases leading to osteolysis in these sites.
Typical pathology of these lesions would be of groups of malignant epithelial cells (metastatic carcinoma) in the marrow spaces.
Bony trabeculae are thin or absent
Osteoclast activity leading to decreased thickness of the adjacent bone trabeculae and no significant increased osteoblastic activity.
Bone metastases are typically multifocal and most commonly involve the axial skeleton.
Triple assessment: Clinical and radiological examination supplemented with tissue diagnosis is the standard of care for all.
Hereditary Breast and Ovarian Cancer Syndrome
60-80% lifetime risk breast cancer
20-40% lifetime risk ovarian cancer
40-60% lifetime risk breast cancer (5-10% male)
10-20% lifetime risk ovarian cancer
Pancreas and prostate cancer
O and G: Abnormal Uterine Bleeding Diagnosis and investigations
AUB in women >40 yr requires an endometrial biopsy to rule out cancer even if known to have fibroids
O and G: Abnormal Uterine Bleeding Management
Adenomyosis: surgery is the only definitive
- iron suppliments, analgesia and NSAIDs, Depo-Provera/Mirena or a progesterone type non-phasic contraceptive
Fibroid: Only needs treatment if symptomatic; e.g. rapidly enlarging
- treat anemia if present
- medical approach; antiprostaglandins (ibuprofen, other NSAIDs) and tranexamic acid
- Interventional radiology (embolise blood supply), or surgery
O and G: Abnormal Uterine Bleeding Treatment
resuscitate patient if hemodynamically unstable
treat underlying disorders; if anatomic lesions and systemic disease have been ruled out, consider DUB
Mild DUB (dysfunctional uterine bleeding): not attributable to organic (anatomic/systemic) disease DUB is a diagnosis of exclusion. Anovulatory AUB often used synonymously with DUB
- combined OCP
- progestins (Provera®) on first 10-14 d of each month or every 3 mo if oligomenorrheic
- Mirena® IUD
- endometrial ablation; consider pretreatment with danazol or GnRH agonists
- if finished childbearing
- repeat procedure may be required if symptom reoccur especially if over 40 YOA