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Answers to Questions Posted after Year 5 UGI Pathology Lecture

what are the key distinguishing factors that determine if a histological sample is dysplastic or cancer?
Invasion through the baseman membrane into the underlying connective tissue ( in the stomach that is into the lamina propria).

what causes squamous cell carcinoma? (ie you referenced it occurs more commonly in developing countries).
Smoking and/ or alcohol are important. HPV infection also has a role.

I think I missed it but what is CLO-IM?
Columnar Line Oesophagus- Intestinal Metaplasia

Is there such thing as chronic oesophagitis? Or does the inflammation just progress to Barrett’s over time?
These is, for example, with chronic gastro-oesophageal reflux. This will increase the risk of metaplasia

Are there any practical tests for determining cag-A status of H. pylori infections and are these tests used clinically at all?
The tests exist but are not used in routine clinical practice

How common is shock due to ulcer haemorrhage?
It depends how sever the haemorrhage is. Most bleeding from ulcers do not produce shock.

is there a genetic component? i.e. Japanese man migrating to England? (if that makes sense)
There is, and you give a good example, but environmental factors are also important. For example, even when people move they may take their diet with them.

why is there a high incidence in specifically in japan?
It is not only Japan that has a very high incidence: South Korea and Mongolia have even higher incidences. There are environmental as well as genetic factors but it is known that chronic gastritis with intesitnal metaplasia is commoner and more severe in these areas.

Can intestinal gastric cancer progress to diffuse?
I don’t think so but I know nothing published about this. Mixed intestinal and diffuse cancers are not uncommon.

are giardia and Whipple’s disease also associated with immunosuppression?
They are (as are almost all infections).

Answers to Questions Posted after Year 5 Pancreas and Gall Bladder Pathology Lecture.

How does Hyperlipidaemia result in pancreatitis? Good question, I had to look up the answer. There are 2 theories. The first is that the FFAs directly damage the pancreas and the second that chylomicrons cause increased plasma viscosity causing pancreatic ischemia,

how do these patients present? If you mean acute and/ or chronic pancreatitis, I refer you to any standard clinical textbook.

What’s the difference between a carcinoma and neoplasms? The term neoplasm includes both benign and malignant “new growths) A carcinoma is a malignant neoplasm of epithelial cells. It includes adenocarcinomas and squamous cell carcinoma.

On firms, someone presented a case where a patient had autoimmune pancreatitis, but with normal IgG4 plasma cell levels/serum IgG4 cells. Presumably this is not common, but is this likely to be related to the ‘IgG4 Related Diseases’ or another pathophysiology entirely? There are 2 types of auto-immune pancreatitis; type 1 is part of IgG4-RD and type 2 is not . It sounds like your case was an example of type 2.

What does the PAAN abbreviation stand for? I think you mean PanIN. This stands or Pancreatic Intra-epithelial Neoplasia.

Re Carcinoma of head of pancreas – does that mean they have better prognosis if diagnosed earlier? Or is timing irrelevant to prognosis? The earlier they present the less time there will have been for the cancer to spread. This will make it an earlier stage and early stage cancers have a better prognosis.

how do patients with igg4 related disease present? Wait until my lecture on Systemic Diseases! The pancreas is the commonest site but virtually any organ in the body can be involved.

Why are transplants not so successful in pancreatic cancer? Because they are an aggressive cancer and the immunosuppression for transplantation would mean the tumour would spread more quickly. The same is, of course, true for many other kinds of cancers.

Are thiazide diuretics directly noxious to pancreas or is it because they cause hypercalcaemia? Thiazides cause both hyperlipidaemia and hypercalcaemia either which can lead to pancreatitis

Where can I find your blog? https://blogs-staging.imperial.ac.uk/my-path/author/rdg30/

What textbooks would you recommend to be able to understand histopathology images better (and be able to know what we’re looking at). I think any of the standard undergraduate pathology textbooks would be fine. The latest edition of Muirs has just been published and is a good choice.

What practical do these diverticula have on management? Do you mean Rokitansky-Aschoff Sinuses in the gall bladder. If you do, then they have no impact on management – they are only identified when the gall bladder is removed.

Why is it so common in Chile? You are talking about gall bladder cancer The answer is, as ever, there are environmental (commoner as you go higher up the Andes) and genetic (commoner in the indigenous population).

Is alcohol not a drug? An interesting philosophical question. I think you are right but we tend to look at it separately as it very widely used, self-prescribed and not taken to treat disease.

paan is pancreatic atypical anaplastic neoplasia i’ve found out I am not sure that I understand this but see above. You can get anaplastic (undifferentiated) carcinomas in the pancreas as you can in any other organ,

Neuro-endocrine Tumours ( in less than 500 words)

These tumours arise throughout the body but the gastro-intestinal tract (especially the appendix and rectum), followed by the lung (bronchus), are the commonest sites.
The frequency in these sites reflects the relatively large number of neuro-endocrine cells normally found there. Similarly, in the pancreas, which is another common site for neuro-endocrine tumours (NETs), are commoner in the tail than the head because the Islets of Langerhans are present in a higher density in the tail.

NETs were previously called carcinoid tumours but now the term neuro-endocrine tumours is now preferred except in the lung where the original term is still used.

NETs are graded (1-3) according to their rate of proliferation of the tumour cells which can be assessed either by counting mitoses or using an immunohistochemical marker (Ki-67). The higher the rate, the higher the grade and the greater the risk of metastatic disease although there is no clear cut-off level. The tumours in the appendix and rectum almost always never metastasize. Small intestinal NETs are especially likely to do so. Challengingly the secondary tumours may be larger than the primary they arise from which can make it difficult to identify the latter.

In the gastro-intestinal tract the tumours are usually submucosal although they may ulcerate. They may invade through the wall and may reach the peritoneal surface. They are often associated with a marked desmoplastic reaction. Multiple tumours may be seen; in the ileum 40% are multiple. Spread is to regional lymph nodes and the liver.

Histologically, NETS, are composed of relatively uniform cells arranged, in cords or nests, and have granular cytoplasm. The granules contain a protein, chromogranin, which can be used as an immunohistochemical or serum marker for these tumours.

NETs may secrete a wide range of hormones. The carcinoid syndrome is associated with the secretion of serotonin usually by git tumours. It is characterized by diarrhoea and bronchospasm and may be associated with fibrosis involving the right-hand side of the heart which can produce distortion of the valves. It is only seen in tumours which have spread to the liver as otherwise the serotonin is broken down in the liver.

Below is are images of a rectal carcinoid tumour (made available by the excellent @Patholwalker).

 

Patent Ductus Arteriosus

In the fetus, the ductus arteriosus links the pulmonary artery with the aorta. At this time, the pressure in the pulmonary circulation is greater than in the systemic circulation to that blood flows from right to left i.e. from the pulmonary artery into the aorta.

After birth, the ductus close in response to the raised pO2 in the blood and the fibroses up and becomes the ligamentum arteriosus. The ductus may, however, fail to close and this is termed patent ductus arteriosus. This is the 3rd commonest forms of congenital heart disease after ventricular septal defects and atrial septal defects. Like these conditions, it is associated with a left to right shunt (because of the relatively high pressures in the systemic circulation). The magnitude of the shunt will depend on the diameter of the ductus. With time, as a result of the increased blood flow to the lungs, pulmonary hypertension may develop and if the pressure becomes great enough the shunt will reverse becoming right to left (as in the fetus).

This failure to close is common in premature infants when the ductus will usually, in the end, close spontaneously, in the end. Patent ducts arteriosus is commoner in babies with, e.g., Down’s syndrome and congenital rubella. In term infants, it rarely closes on its own. Treatment may be by instilling prostaglandin inhibitors, which cause contraction, or by surgery. Infective endocarditis may develop in untreated cases.

Medical Liver Biopsies for Trainees.

Acute Hepatitis

Distinguish acute and chronic hepatitis.

Liver disease lasting less (acute) or more (chronic) 6 months.

Describe the natural history of hepatitis.

Acute hepatitis > chronic hepatitis > cirrhosis

Name the 2 commonest causes of acute hepatitis.

  1. Drugs
  2. Viruses

Name 5 viruses which cause acute hepatitis.

HAV, HBV, HCV, HDV and HEV

Name one drug that causes an acute hepatitis.

Paracetamol

Describe the characteristic histological features of an acute hepatitis.

Spotty (lobular) hepatocyte necrosis and inflammation

 

Chronic Hepatitis

Name the 3 causes of a chronic hepatitis

  1. Viruses
  2. Drugs
  3. Autoimmune

Define grade with reference to chronic hepatitis.

The activity of the inflammation (portal, interface and lobular).

Define stage with reference to chronic hepatitis.

The degree of fibrosis ranging from portal tract expansion through bridging fibrosis to nodule formation (= cirrhosis).

Name the scoring system for grading and staging chronic hepatitis that you use in your hospital.

Modified HAI (Ishak) / METAVIR

 

Viral Hepatitis

Name 3 viruses which cause chronic hepatitis.

HBV, HCV and HDV (causes co-infection / superinfection with HBV).

Describe the characteristic histological feature of chronic hepatitis B.

Ground glass cells, immunopathic hepatocyte damage

Describe the 3 characteristic histological features of chronic hepatitis C.

Inflammatory bile duct damage, lymphoid follicle formation, fatty change (Genotype 3).

Describe the characteristic histological feature of hepatitis D.

Cytopathic hepatocyte damage

 

Auto-immune Hepatitis

List the main clinical features.

Younger women, often associated with other autoimmune diseases

Classify auto-immune hepatitis.

Type 1 Associated with smooth muscle actin antibodies in adults (and the commonest one we see).

Type 2 associated with liver-kidney microsomal antibodies, commoner in children

Describe the 2 characteristic histological features of auto-immune hepatitis.

Marked, especially interface, inflammation and prominent plasma cells.

Be aware of the existence of overlap syndromes.

With PBC and PSC.

 

Drug induced hepatitis  

and Drug Induced Liver Injury (DILI)

Describe the range of liver diseases that can be caused by a drug.

‘Any kind of liver disease can be caused by a drug”.

Describe 5 characteristic histological features of a drug-induced hepatitis.

Fatty change, eosinophils, granulomas, cholestasis, dropout

Name one drug which causes a chronic hepatitis.

Isoniazid

 

Fatty Liver Disease:

 

Describe the natural history of fatty liver hepatitis.

Fatty change> fatty liver hepatitis > cirrhosis

Describe the 2 morphological types of fatty change.

Small droplet (microvesicular) and large droplet (macrovesicular)

List the 2 common causes of each type of fatty change.

Small droplet: Drugs (e.g. sodium valproate) and pregnancy.

Large droplet: Alcohol and Diabetes (insulin resistance).

List 4 other causes of large droplet fatty change.

Drugs (e.g. steroids), viruses (HCV), starvation and other metabolic diseases (e.g. Wilson’s Disease).

Describe the 4 key histological features of a fatty liver hepatitis.

All changes most marked in Zone 3: ballooning (with or without Mallory-Denk bodies), inflammation (lymphocytic and / neutrophilic, pericellular fibrosis.

Know which histological feature may help distinguish alcoholic from non-alcoholic fatty change.

Nuclear vacuolation which is associated with insulin resistance.

Know the associations of nuclear vacuolation.

Physiological: childhood and young adults.

Pathological:   insulin resistance, Wilson’s Disease and glycogen storage diseases.

Name the 2 commonest causes of a fatty liver hepatitis.

Alcohol and Diabetes / insulin resistance (= Non-Alcoholic Steato-Hepatitis)

These 3 stages may co-exist

Name one drug that causes a fatty liver hepatitis.

Tamoxifen

Name the scoring system for grading and staging chronic hepatitis that you use in your hospital.

Nash Activity Score (NAS) and Stage

 

 

Primary biliary cholangitis (PBC)

List the main clinical features.

Middle aged, females

The presence of anti-mitochondrial antibodies is the key diagnostic test.

Describe the key histological feature.

Inflammatory destruction of bile ducts often associated with granulomas.

General features of chronic cholestatic liver disease (see below).

Progressive portal fibrosis but less than half are cirrhotic at presentation

 

Primary sclerosing cholangitis (PSC)

List the key clinical features.

Younger men

Associated with ulcerative colitis.

Increased risk of cholangiocarcinoma.

Imaging is the key diagnostic test,

Describe the key histological feature.

Fibrotic destruction of bile ducts.

Progressive portal fibrosis.

Involves mainly the extrahepatic bile ducts.

 

List the diseases that cause bile duct loss.

  1. PBC
  2. PSC
  3. Drug-induced liver disease e.g. ketamine
  4. Chronic liver transplant rejection
  5. Graft versus Host Disease etc.

 

Know the general features of chronic cholestatic liver disease and which special stains are needed to demonstrate them.

  1. Bile duct loss
  2. Proliferation of intermediate-type hepatocyte progenitor cells.
  3. Accumulation of copper and copper associated protein in periportal hepatocytes.
  4. Ballooning degeneration of periportal hepatocytes (with or without Mallory-Denk bodies).

1 and 2 confirmed on CK7 staining.

Copper-associated protein: metallothionine

Copper: rubeanic acid

 

List the features which assess the active damage of biliary tract disease.

  1. bile duct inflammation
  2. interface hepatitis

 

List the features which assess the chronic damage of biliary tract disease.

  1. portal fibrosis
  2. interlobular bile duct loss
  3. deposition of copper associated protein.

 

Wilson ’s disease

List the main clinical features.

Associated with neurological problems (“hepato-lenticular degeneration”) and eye involvement (Kayser-Fleisher rings).

Should always be considered in younger patients with unexplained liver disease.

Describe the underlying pathophysiology

Autosomal recessive with no dominant mutation.

Failure of copper excretion by hepatocytes into the biliary system due the failure to express a transporter protein

Describe the range of histological features.

From fatty liver hepatitis to chronic hepatitis.

Increased copper or copper associated protein can only be demonstrated, histologically, in half of cases:

The gold standard is liver copper measurement.

NB Copper also increased in chronic biliary tract diseases but not the same extent.

 

Haemochromatosis

List the main clinical features

Presents in adults but in men earlier than in women.

Describe the underlying pathophysiology

Autosomal recessive with a single dominant mutation (HFe)

Increased iron absorption from the gut. NB There is no method for excreting iron

Describe the key histological features.

Iron deposition in hepatocytes starting in the periportal hepatocytes and then spreading to the rest of the lobule.

Progressive portal fibrosis.

Be able to distinguish this from other causes of iron overload.

Chronic anaemia, also, leads to increased iron absorption from the gut and deposition in hepatocytes.

Blood transfusion leads to iron deposition in Kupffer cells and does not, usually, lead to fibrosis.

 

Alpha-1 antitrypsin deficiency

List the key clinical features

Associated with emphysema

Describe the key histological feature.

dPAS positive globules in periportal hepatocytes.

 

IgG Related Disease (IgG4)

List the main clinical features

Often part of systemic disorder

Often involves the hepato-biliary (and pancreatic) system producing, e.g.:

  1. A mass lesion in the liver
  2. A PSC like disease

List the 3 key histological features.

  1. Increased numbers of IgG4 expressing plasma cells.
  2. Storiform fibrosis
  3. Vasculo-obliterative lesions

 

Granulomas

Know a classification of granulomas in the liver:

  1. Aetiolgical
  2. Practical
  3. Where you know the cause:

e.g. see a schistosome egg or acid-fast bacilli

  1. Where you can have an educated guess:

e.g. Associated with bile duct damage (PBC) or portal based, fibrotic granuloma with little associated inflammation (Sarcoid) or associated with other features suggesting DILI.

  1. The rest!

 

Vascular Diseases of the Liver

Describe the clinical associations and key histological features of the main vascular diseases of the liver.

  1. Budd Chiari Syndrome

Thromboses of hepatic vein / branches etc.

Associated with pro-thrombotic states

Marked congestion, with extravasation of red cells onto hepatocytes, and patent central veins.

  1. Veno-occlusive disease

Fibrotic obliteration of portal vein branches.

Associated with azathioprine, radiation and Jamaican bush tea

  1. Sinusoidal obstruction syndrome.

Sinusoidal damage with congestion and haemorrhage,

Associated with chemotherapy,

  1. Primary portal hypertension.

Obliteration of hepatic vein branches and sinusoidal herniation.

  1. Nodular regenerative hyperplasia.

Regenerative nodules but no fibrosis.

Associated with systemic diseases

 

 

Cirrhosis

 

Define cirrhosis.

End stage liver disease:

  1. involving the whole liver,
  2. associated with fibrosis,
  3. nodules of regenerating hepatocytes and
  4. shunting of blood (intrahepatic and extrahepatic)

List the 3 commonest causes of cirrhosis

  1. Viral hepatitis
  2. Alcoholic liver disease
  3. Non- alcoholic fatty liver disease (NAFLD)

List 4 other causes of cirrhosis.

  1. PBC
  2. PSC
  3. DILI
  4. Hemochromatosis

Know how to classify cirrhosis.

  1. According to the aetiology
  2. According to the sizes of the nodules

Micronodular (smaller than a normal liver lobule) – alcohol

Macronodular (bigger than a normal liver lobule) – viral hepatitis

Mixed

 

List 3 complications of cirrhosis.

  1. Portal hypertension.
  2. Liver failure
  3. Liver cell cancer

 

Some Notes on Liver Disease

This was tricky for me to write as the subject is  the closest to my heart! I  really found it hard to leave so much out.

 

Acute hepatitis:

  1. Viruses
  2. Drugs

 

Chronic hepatitis (liver disease lasting more than 6 months)

  1. Viruses
  2. Autoimmune
  3. Drugs

 

Pathological features of chronic hepatitis

Grade = inflammation (can be in 3 places: portal tracts, interface and lobular)

Stage = fibrosis (portal tract expansion > bridging > cirrhosis)

 

The commonest causes of cirrhosis are:

  1. viral hepatitis
  2. alcoholic liver disease
  3. non-alcoholic fatty liver disease

 

Viral hepatitis

There are 5 hepatitis viruses (all RNA except for HBV): A-E

A and E: spread by faecal oral route, cause only an acute hepatitis

B, C and D (which can only infect people who have HBV, as well): spread by blood etc., cause the full range of liver disease:

  1. acute hepatitis
  2. chronic hepatitis – scarring begins
  3. cirrhosis – nodules of hepatocytes surrounded by scar tissue

 

Alcoholic liver disease and non-alcoholic fatty disease (risk factors: obesity, diabetes) produce the same pathological changes:

  1. fatty change
  2. fatty liver hepatitis (alcoholic hepatitis / non-alcoholic steatohepatitis (NASH) respectively): ballooning, neutrophils and scarring
  3. cirrhosis

NB These 3 stages often con-exist

 

There are (many) other liver diseases which may  cause of cirrhosis:

  1. Autoimmune hepatitis: anti smooth muscle actin autoantibodies, plasma cells, associated with other AI diseases, response to steroids
  2. Drug induced liver injury (DILI): “any kind of liver disease can be caused by a drug’
  3. Haemochromatosis = genetic (AR) increased iron absorption from the gut

deposited in the liver and many other organs (including the pancreas).

  1. Wilson’s disease = genetic (AR) decreased copper excretion (by hepatocytes into the bile duct).
  2. Primary sclerosing cholangitis (PSC): sclerosis (= fibrosis) of the bile ducts leading to their loss. Associated with Ulcerative Colitis
  3. Primary biliary cholangitis (PBC): inflammation (with granulomas) of the bile ducts leading to their loss

 

Complications of cirrhosis:

  1. Portal hypertension with varices
  2. Liver failure with hepatic encephalopathy,
  3. Liver cell cancer (the same as hepatocellular carcinoma)

 

Tumours of the liver:

The commonest are secondary tumours (many via the portal vein)

 

Primary tumours

  1. Benign
  2. Bile duct adenomas
  3. Hepatic adenomas (associated with the contraceptive pill)

 

  1. Malignant
  2. Liver cell carcinoma

Most commonly associated with cirrhosis.

Spread via the portal vein.

Carry a poor prognosis.

 

  1. Cholangiocarcinoma (an adenocarcinoma)

Divided into intrahepatic and extra hepatic (including gall bladder)

May be associated with ulcerative colitis and worm infections

Spread to lymph nodes

Carry a poor prognosis

 

 

Some Notes on Cardiac Pathology

Please note that I made these for my own use but thought they may be useful to others!

Cardiac Pathology

 

Divided into diseases of the:

  1. Coronary arteries
  2. Endocardium (including valves)
  3. Myocardium (including congenital heart disease)
  4. Pericardium

 

  1. Coronary arteries

 

Any vascular disease can involve these (e.g. vasculitis) but atheroma is the important one.

Clinically: angina, unstable angina and myocardial infarction (due to superimposed thrombosis secondary to ulceration or fissuring).

 

Left coronary artery >

  • anterior descending > anterior septum and wall of left ventricle
  • circumflex branch > lateral wall of left ventricle

 

Right coronary artery > posterior septum and wall of left ventricle

 

Distribution of infarction:

  1. Subendocardial infarction due to severe, generalized disease.
  2. Focal due to blockage of a major artery.

 

 Complications of myocardial infraction:

 

Minutes:

Arrhythmias: ventricular fibrillation / heart block

Acute cardiac failure / cardiogenic shock

 

Days:

Thromboses:

  • Mural (over the infract) which may be followed by systemic embolisation
  • Atrial thrombus (due to atrial fibrillation)
  • (DVT which may be followed by pulmonary embolization)

 

Week:

Rupture (due to softening of muscle):

  • Myocardium (leading to cardiac tamponade and death)
  • Papillary muscle (mitral incompetence)
  • Septum (left to right shunt)

 

Pericarditis

 

Weeks:

  • Chronic cardiac failure.
  • Immune pericarditis (Desslers’s syndrome)

 

Months:

Cardiac aneurysm (due to fibrosis)

 

At any time:

Another infarct

 

  1. B) Myocardium

 

Myocarditis

Causes:

Infectious:

  • Viral e.g. Coxsackie
  • Bacterial e.g. Borrelia (Lyme Disease)

 

Toxic: e.g. Diphtheria

 

Immunological e.g. Rheumatic fever

 

Cardiomyopathy:

Definition: Heart muscle disease not due to ischaemia, hypertension, valvular disease or inflammation

 

  1. Dilated cardiomyopathy: end stage of the above (which has burnt out), alcohol or pregnancy
  2. Hypertrophic cardiomyopathy: autosomal dominant
  3. Restrictive cardiomyopathy: endomyocardial, fibro-elastosis, amyloid, haemochromtosis

 

Rheumatic fever

Preceded by streptococcal sore throat.

Type 2 hypersensitivity reaction (antibodies to streptococci cross react with antibodies to myocardium.

 

Clinical features

  • General: fever etc.
  • Skin: nodules
  • CNS: chorea
  • Heart:
  • Pericarditis
  • Myocarditis (Aschoff bodies- collections of macrophages)
  • Endocarditis including valves – may lead to chronic valve disease (see below)

 

Congenital Heart Disease

 

Risk factors: e.g. Down’s syndrome, rubella, thalidomide

 

  1. Left to right shunts e.g. atrial or ventricular septal defects ( if untreated may reverse
  2. Right to left shunt “ Cyanotic”

e.g. Tetralogy of Fallot:

  • large ventricular septal defect
  • pulmonary stenosis

3)  overriding of the aorta

4)  right ventricular hypertrophy

 

 

  1. C) Endocardium

 

Valve disease

 

Mitral valve:

 

Leads to dilation and hypertrophy of the left atrium

In incompetence there is, also, dilatation of the left ventricle

 

Incompetence:

  • Post -inflammation: rheumatic fever
  • Infective endocarditis
  • Left ventricular failure
  • Myocardial infarction
  • “Floppy mitral valve syndrome”

 

Stenosis:

  • Post-inflammation: rheumatic fever

 

Complications:

  • Atrial fibrillation
  • Infective endocarditis

 

 

Aortic valve:

 

Stenosis:

  • Age related calcification
  • Calcification of abnormal valve:

Congenital bicuspid

Post -inflammation: rheumatic fever

 

Leads to marked cardiac hypertrophy and the risk of sudden death

 

Incompetence

  • Post -inflammation: rheumatic fever
  • Infective endocarditis
  • Dilatation of valve ring e.g. Marfan’s syndrome

 

Leads to dilatation and hypertrophy

 

 

Infective endocarditis

 

Vegetations form on the valves

 

  1. Acute:

Pathogenic organism (e.g. staphylococcus aureus) and normal valve

 

  1. Subacute:

Less pathogenic organism (e.g. streptococcus viridans, from the mouth, or enterococci, from the gut) and an abnormal valve

 

 

Complications:

  • Systemic features: Fever etc.
  • Embolisation of vegetations

Infected infarcts in the brain or kidneys

Splinter haemorrhages

 

 

Other causes of valve vegetations

e.g. marantic in patients with cancer

 

 

  1. D) Pericardium

 

Classified according to appearance

  1. Fibrinous e.g. myocardial infarction
  2. Serous e.g. rheumatic fever
  3. Purulent e.g. bacterial infection
  4. Haemorrhagic e.g. traumatic, tumour
  5. Fibrotic +/- calcification (chronic) = constrictive pericarditis g. TB

 

 

Pericardial haemorrhage:

  1. Myocardial infarction
  2. Dissecting aortic aneurysm

 

Undergraduate Pathology: The Pathology of Neoplasia

This is the text of the first year cellular pathology course lecture which I am giving tomorrow.
I hope that it might act as a focus for interaction with the students.

The Pathology of Neoplasia

Tumour: Any kind of massforming lesion. May be neoplastic (see below), hamartomatous (see below) or inflammatory (e.g. nasal polyps).

Neoplasm: The autonomous growth of tissue which have escaped normal constraints on cell proliferation.
Neoplasms may be either benign (remain localised) or malignant (invade locally and/or spread to distant sites).

Cancers are malignant neoplasms.

Hamartomas are localised benign overgrowths of one of more mature cell types e.g. in the lung. They represent architectural but not cytological abnormalities. For example: lung hamartomas are composed of cartilage and bronchial tissue.

Heterotopias are normal tissue being found in parts of the body where they are no normally present. For example: pancreas in the wall of the large intestine.

Important to note that many malignant tumours rarely cause death (especially skin cancers) and that some benign tumours do kill (usually because of their location, e.g. the brain)

Classification of neoplasms

The primary description of a neoplasm is based on the cell origin and the secondary description is whether it is benign or malignant.

For example, tumours of cartilage are either chondromas (if benign) and chondrosarcomas (if malignant.) The “chondro” stem means derived from cartilage the suffix “oma” means a benign tumour and the suffix ”sarcoma” means a malignant (soft tissue) tumour.

Type of epithelium Benign Tumour Malignant Tumour Example(s)
Squamous Squamous epithelioma or papilloma Squamous cell carcinoma Skin, oesophagus, cervix,

Glandular Adenoma Adenocarcinoma Breast, colon, pancreas, thyroid
Transitional Transitional papilloma Transitional cell carcinoma Bladder

Type of connective tissue Benign Tumour Malignant Tumour Example(s)
Smooth muscle Leiomyoma Leiomyosarcoma Uterus, colon
Bone Osteoma Osteosarcoma
(Osteogenic sarcoma) Arm, leg

Haematological neoplasms Benign Tumour Malignant Tumour Example(s)
Lymphocytes Extremely uncommon Lymphoma Lymphoma
Stomach
Bone marrow Extremely
uncommon Leukaemia Acute lymphoblastic leukaemia,
Chronic myeloid leukaemia

Teratomas

These are tumours derived from germ cells and can contain tissue derive from all three for 3 germ cell layers. They may contain mature and / or mature tissue and even cancers.
Malignant tumours with the suffix “oma”:

1. (Malignant) Lymphoma
2. (Malignant) Melanoma
3. Hepatoma (better called liver cell cancer).
4. Teratoma (not all, see above)

What are the differences between benign and malignant tumours?

1. Invasion: This means direct extension into the adjacent connective tissue and /or other structures e.g. blood vessels. This is what distinguishes dysplasia/ carcinoma in situ from cancer (see next lecture).
2. Metastasis: This means spread via blood vessels etc (see below) to other parts of the body.
NB All malignant tumours have the capacity to metastasise although they may be diagnosed before they have done so
3. Differentiation: This means how much do the cells of the tumour resemble the cells of the tissue it is derived from.
Tumour cells tend to have larger nuclei (and hence a higher nuclear-cytoplasmic ratio) and more mitoses than the normal tissue they are derived from. They may have abnormal mitoses (e.g. tripolar) and marked nuclear pleomorphism (variability in nuclear size and shape).
4. Growth pattern: This means how much does the architecture of the tumour resembles the architecture of the tissue it is derived from.
Tumours have less well defined architecture than the tissue they are derived from.

It is important to note that benign tumours may become malignant.

By which routes do tumours spread?

1. Direct extension. This is associated with a stromal response to the tumour. This includes fibroblastic proliferation (“ a desmoplastic response”), vascular proliferation (angiogenesis) and an immune response.
2. Haematogenous (via blood vessels). The blood vessels usually invaded are the venules and capillaries because they have thinner walls. Most sarcomas metastasise first via the blood vessels.
3. Lymphatic (via lymphatics to lymph nodes and beyond) The pattern of spread is dictated by the normal lymphatic drainage of the organ in question. Most epithelial cancers metastasise first via the lymphatics.
4. Transcoelomic (seeding of body cavities). The commonest examples are the pleural cavities (for intrathoracic cancers) and the peritoneal cavities (for intra-abdominal cancers)
5. Perineural (via nerves) This is an underappreciated route of cancer spread.

How do we assess tumour spread?

1. Clinically
2. Radiologically
3. Pathologically

How do we describe tumour spread (stage)?

T= Tumour: the tumour size or extent of local invasion
N= Nodes : number of lymph nodes involved
M = Metastases: presence of distant metastases

This is called the TNM system and the details are different for each kind of cancer

Grade = how differentiated is the tumour (see Differentiation, above)?
Stage = how far as the tumour spread (see TNM above)?

In terms of tumour prognosis, Stage is more important than Grade.

Benign Vascular Tumours

These are common but remember that a tumour is just a swelling and they are not all neoplastic.
Capillary haemangiomas are composed of small blood vessels with inconspicuous lumina. They occur in all organs but particularly come to notice when they involve the skin. A “port wine stain” and a “strawberry mark” are examples of these. The latter initially grow rapidly, soon after birth, and then may regress completely, usually by 10 years. Whether they should be considered as true neoplasms is not clear.
Angiomas may, also, be seen in the placenta (chorangiomas) and, because of the increased blood flow, cause fetal heart failure.
Following trauma some patients develop pyogenic granulomas. This is sometimes called a lobular haemangiomas because of the lobular arrangement of the blood vessels in them. This is a reactive not and not a neoplastic process and is commoner in pregnancy.
Bacillary angiomatosis is another non-neoplastic vascular proliferation that is most commonly seen in association with AIDS and which is due to infection with Bartonella.
Unlike capillary haemangiomas, cavernous haemangiomas, contain prominent vascular spaces containing blood. They carry a significant risk of rupture and bleeding and hence of intracerebral haemorrhage, when they occur in the brain, or intraperitoneal haemorrhage, when they occur in the liver
Vascular hamartomas (malformed) blood vessels may be seen in a number of syndromes such as the von-Hipple-Lindau Disease and the Sturge-Weber Syndrome.
Glomus tumours, which are derived from glomus bodies (which are in the skin, are composed of an arterio-venous shunt and are involved in temperature regulation )may have a variable amount of angioma mixed in with them; if this is marked they are called glomangiomas. The purer form mostly involves the extremities and are extremely tender.

Eosinophils

This post was stimulated by a case of eosinophilic colitis I reviewed at an MDT this morning. The images are below.

They show sheets of eosinophils in the lamina propria and infiltrating crypts. They are easily recognised by their bilobed nuclei and prominent red granules.

 

 

 

This was an opportunity to review eosinophils.

Eosinophils are conspicuous in inflammatory reactions triggered by IgE, such as asthma, and by parasites and are increased by TH-2 activation.  IL-5 and GM-CSF increase the production of eosinophils by the bone marrow. They are associated are recruited into the tissue by eotaxins which are CC chemokines.

Eosinophils have 2 types of effector function:

  1. they release toxic granule proteins  (e.g. major basic protein which is toxic to parasites) and free radicals.
  2. they synthesise prostaglandins, leukotrienes and cytokines.

In the context of this case, likely causes include gut parasites, such as schistosomiasis, and allergic reactions to drugs.

If you want to read more try the excellent British Society of Immunology Website: https://www.immunology.org/public-information/bitesized-immunology/cells/eosinophils