Histopathology Flashcards
What is the most common childhood cancer?
Leukaemias (30%). For comparison in adults, leukaemia makes up ~4% of malignancies
What is a Wilms tumour?
A nephroblastoma (kindey tumour). 5% of childhood cancers. Note that cases of any ‘blastoma’ cancers e.g. retinoblastoma, neuroblastoma are rarely seen beyond the age of ~15 years
What is the general difference between the genetic and environmental influences for childhood vs adult cancers?
Childhood cancers are often the result of DNA changes in cells very early in life (some even before birth). Unlike many cancers in adults, childhood cancers are not strongly linked to lifestyle or environmental risk factors (because they didn’t have time to build up)
Do childhood cancers respond well to chemotherapy?
Yes they tend to respond better to treatments such as chemotherapy than adults do. This is because in children the cells are often proliferating more, so when you give them chemotherapy you tend to hit more cells. Nowadays blastomas tend to have a survival rate of up to 80% and leukaemia’s 90%.
What is Hirschsprung’s disease?
A congenital developmental abnormality with an absence of ganglion cells in the distal rectum. Due to failure of neural crest cell migration during development of the enteric nervous system. Progresses from the distal end, but can involve the whole gut.
Some further facts about Hirschsprung’s disease…
Nowadays children can survive this disease with TPN (IV feeding). In a normal gut there will be normal peristalsis, in Hirschsprung’s disease the anus and rectum can narrow (which is where the diseased part is), so it is basically mechanical stenosis: due to the absence of ganglion cells, the parasympathetic fibres are firing and the muscle is constricting and not allowing any faeces past
How might Hirschsprung’s disease present?
Most cases diagnosed first 48 hrs after birth: delayed meconium passage, abdominal distension, bilious vomiting
What do you see histologically in Hirschsprung’s disease?
In the submucosa you will see large nerve trunks (to try and compensate for the absence of ganglion cells)
How might coeliac disease present?
Great spectrum. Young children- failure to thrive, malabsorption, diarrhoea, abdominal distension. Older children- abdominal pain. Long term complications in adults- osteoporosis (due to malnourishment), intestinal T lymphoma
Which antibodies might be raised in the blood in coeliac disease?
Anti-gliadin antibodies (AGA) and anti-tissue-transglutaminase antibodies (TGA).
What features might you see histologically in coeliac disease?
Villous atrophy, increased intraepithelial lymphocytes, increased lamina propria inflammatory cells
Which classification system is used for coeliac disease?
MARSH classification- provides a standard for coeliac disease histological classification and allows clinicians to understand the severity of disease
Tell me the key facts about autosomal recessive polycystic kidney disease…
Most cases result in stillbirth or early neonatal death. It gives an abnormal kidney function in utero. The life-limiting problem is usually the immature lungs at birth. It is the most severe type of PKD. Associated with gene PKHD1 which encodes the protein fibrocystin
Tell me briefly about adult polycystic kidney disease
It is autosomal dominant. It is the most common cystic renal disease. Responsible for 5-10% of chronic renal failure requiring dialysis. Cysts only involve a portion of nephron, so renal function is maintained until 40s-50s. Patients tend to present in 30s-50s.
The perinatal autopsy involves external and internal examination, what is involved in the external examination?
Note: (often have translucent skin). Body weight, head circumference, crown heel and crown rump lengths, foot length, apparent gestation, maceration (aseptic decay in the mother before any formalin fixation- if baby born dead), dysmorphic features, other abnormalities, fractures of long bones and ribs e.g in osteogenesis imperfecta
What is involved in the internal examination (perinatal autopsy)
Comment on cranial, thoracic and abdominal cavities. Systemic description of major organs and tissues. Weights of all major organs on digital balance. Comment on skeleton
What are some of the perinatal autopsy special investigations?
X-ray: mandatory for suspected skeletal dysplasia and multiple malformations. Bacteriology, virology, karyotype if clinically indicated. Storage of fibroblasts/ frozen tissue/ DNA if clinically indicated. Biochemistry and haematology if clinically indicated
What are the main causes of perinatal deaths?
Prematurity- the main cause of early neonatal deaths (62%)
Spontaneous preterm delivery and hypertensive disorders- most common obstetric events leading to perinatal deaths e.g. pre-eclampsia (29%). Death associated with foetal abnormalities (only 12%).
What are the 5 most common chromosomal disorders in foetuses?
Trisomy 21 Trisomy 18 (Edward’s syndrome) Trisomy 13 (Patau’s syndrome) Triploidy Turners syndrome (45, XO)
Of the 5 most common chromosomal disorders in foetuses, which 2 are the only viable ones?
Trisomy 21 and Turner’s syndrome
Tell me about babies of diabetic mothers
Increased somatic size (macrosomia). Increased incidence of perinatal death. Prone to hypoxic complications during childbirth because they are bigger (leading to e.g. cerebral palsy), increased freq of malformation, baby may be producing insulin for the mother, so once they are born they are at risk of hypoglycaemia.
What is often the autopsy finding in pre-eclampsia?
IUGR (intra-uterine growth restriction) and asymmetrical growth restriction. Clinically- maternal ugh BP and proteinuria
What is foetal hydrops?
Generalised oedema of the foetus involving the lungs, abdomen and soft tissues. Many causes.
What might be some findings in oligohydramnios (when there is hardly any fluid in the amniotic cavity)?
Wrinkled glove like skin and potter facies with triangular looking epicanthal folds
How might pre-eclampsia cause IUGR?
In the normal placenta you shouldn’t have any muscular wall in the feeding vessels, whereas in pre-eclampsia they stay muscularised and this can cause them to constrict, causing less continuous blood flow to the baby, causing the baby to have intermittent hypoxia and even continuous hypoxia.
What might you see in a placenta from a mum who had pre-eclampsia?
The spiral arteries of the placenta narrow because of the presence of abnormal smooth muscle, hence you could see the resulting fresh infarcts
What is acute chorioamnionitis?
Acute inflammation of the foetal membranes. Can cause stillbirth or usually pre-term delivery. Common after PROM. Ascending infection- the infection usually ascends from the cervix.
What are three developmental disorders of the skeleton?
Osteogenesis imperfecta, achondroplasia and osteopetrosis
Describe bone structure in simple terms
Cortex- compact bone consisting of a parallel arrangement of osteons.
Cancellous medullary bone composed of sponge like trabecular bone
Describe the structure of the growth plate
Well ordered columns of Chondroctyes in the growth plate hypertrophy as they pass towards the zone of bone formation. As the cells hypertrophy, they become calcified and these calcified cells are then converted to bone. Failure to calcify the chondrocytes leads to failure of bone growth
What type of ossification is primarily responsible for the growth in the length of bone?
Endochondral ossification
Tell me about achondroplasia
It is the most common developmental abnormality of bone, characterised by short limbs (all bones with endochondral ossification are affected). Trident hands. 75% of cases are sporadic, 25% are inherited as autosomal dominant trait (mutation in FGFR3).
Tell me about intramembranous ossification
In fibrous connective tissue, which occurs in the growth of flat bones such as the skull and ribs and also in appositional growth (growth in thickness) of the long bones
Tell me about endochondral ossification
In cartilage growth, which occurs at the epiphyseal growth plates at the ends of long bones, which results in lengthening of the bone. The growth plates are active throughout childhood and fuse ~16 years
Tell me the key facts about osteogenesis imperfecta
Aka. Brittle bones. Abnormality in the synthesis of type 1 collagen (about 90% of the organic matrix of bone). Extreme fragility of the skeleton as a result of defective organic matrix of the bone which leads to defective mineralisation. So the bone will bend and fracture in different areas. ‘Blue sclera sign’ - sign of the mild/moderate form. May also have developmental abnormalities of teeth/maxilla and mandible as well as symptoms affecting the auditory system.
Tell me the key facts about osteopetrosis
Defect in the osteoclastic arm of the ‘bone forming unit’. So patients will keep producing new bone but not resorting old bone, leads to a ‘cotton white appearance’ of the bone and cannot discriminate between cortex and cancellous bone (everything the same degree of radio-opacity). Little/no space left for bone marrow = disappearance of the marrow cavity and compromised haematopoiesis- pancytopenia, compensatory splenomegaly
Tell me some key facts about osteomyelitis
More common in children (in developing bones). This is because the susceptibility to acute osteomyelitis is related to the nature of the blood supply to the long bones.
Tell me some key facts about osteoporosis
Loss of bone MASS, but the bone is totally normal (i.e. mineralised as it should be etc). The cancellous bone mass is particularly reduced (typically found at the core of vertebral bones in the spine and at the ends of long bones and tends to bear most of the weight). Most important cause is post-menopausal osteoporosis.
Tell me some key facts about osteomalacia and rickets
Metabolic bone diseases caused by inadequate mineralisation of existing organic bone matrix, bones are therefore less calcified and are softer. Lack of activated vitamin D is the most common problem. Rickets in children and osteomalacia in adults.
What is the classical x-ray finding in osteomalacia?
Looser’s zones - they are microfractures which develop due to structural weakness at the sites of bone turnover
How is rickets and osteomalacia treated?
By providing active vitamin D with supplements (and calcium if necessary)
What name(s) is given to the bone disease resulting from the hyperparathyroid state on bone?
Osteitis fibrosa cystica or Von Recklinghausen’s disease of the bone (essentially ‘holes’ in the bone, scattered all over the skeleton).
Tell me briefly about Paget’s disease of bone
Moments of increased bone production and moment of increased bone resorption (essentially increased bone turnover). Increased skull size/ head circumference (patient’s may complain that their hat doesn’t fit). Histologically bone has a ‘mosaic’ pattern which is pathognomonic for Paget’s disease. Patients often have bone pain and may suffer from fractures, but it also puts them at increased risk of osteosarcomas. Unknown pathogenesis.
What is the most common type of bone tumour?
Metastasis
What are the (general) different types of primary bone tumour?
Haemopoietic (plasma cell tumours and leukaemia)
Mesenchymal origin (benign/ malignant tumours producing bone/ cartilage/ fibrous tissue)
Mononuclear/ macrophagic family (i.e. giant cell tumour)
What are the benign and malignant bone forming tumours of mesenchymal origin?
Benign- osteoid osteoma. Osteoblastoma. Both of these tumours can be extremely painful, but respond well to NSAIDs.
Malignant- osteosarcoma. In the elderly is more likely to be associated with previous Paget’s disease.
Tell me briefly about osteosarcomas
They tend to grow on the metaphysis and most commonly they are intramedullary- starting with the cancellous bone and then it can grow towards the periphery of the bone and start to erode to cortex and lift the periosteum. In fact there can be a periosteal reaction (intramembranous ossification underneath the periosteum) which can form the classic sunburst appearance seen on x-ray
What about the subtype of osteosarcoma called high-grade intramedullary osteosarcoma?
Typically occur in the teenage years with a peak ~15 yrs. they are particularly common around the knee. >50% of the tumours arising in the distal femur or the proximal tibia
Name some benign cartilage forming tumours
Enchondroma
Osteochrondroma - chrondromyxoid fibroma and chondroblastoma
What is Ollier’s disease?
= multiple enchondromas (enchondromas are tumours within the bone in the medullary cavity). Remember the picture of the hands in my notes. The tumours deform and expand the bone and can turn malignant (i.e. form a chondrosarcoma).
What is the buzzword to remember with osteochondromas?
‘Mushroom like’ formations of bone, with an irregular cartilaginous cap of top
What is the name given to malignant tumours of cartilage?
Chondrosarcoma.
They are classified according to site. Can be very aggressive if they grow in the pelvis or shoulders where they have more space to grow internally. 15% arise from osteochondromas.
What are the primary immune system organs?
The thymus and bone marrow. Remember that the bone marrow is where the B-cells stay to mature, whereas the T-cells go to the thymus to mature
What happens once the B and T-cells are mature?
They exit the primary immune organs (thymus and bone marrow) and take up residence in the secondary immune organs in the body, which are areas of concentrated immune cells i.e. the lymph nodes, spleen, GI system (and other epithelial surfaces where they reside as extra-nodal lymphoid aggregates such as the Peyer’s patches and appendix).
Are most lymphomas B or T-cell ?
They are mostly B-cell lymphomas
Tell me briefly about immunoglobulin gene rearrangement in B-cells.
B lymphoblasts undergo rearrangement of the immunoglobulin gene (in the bone marrow) to increase the diversity of the immunoglobulins they produce. When they mature (after undergoing the immunoglobulin gene rearrangement) naive cells exit the bone marrow and enter the blood and secondary lymphoid organs where they express their immunoglobulin on their surface as a receptor (B-cell receptor).
How can we utilise the fact that immunoglobulin gene rearrangement should produce gene segments of different length in every cell in the normal polyclonal population?
Because we can look at the gene segments using PCR (doing clonality studies) and if the majority of the population in the lymphoid cell population have the same length of this gene, then it means it’s a clonal population and therefore a neoplasm/ lymphoma
Outline the process of B-cell activation in the lymph nodes
The B cells sit in the secondary B-lymphoid follicles as naive (meaning they haven’t encountered an antigen yet). When the B-cells get stimulated in the follicle (which is a process depends on T-cell help and is antigen dependent) the B-cells enter the germinal centre from the mantle zone (in the unstimulated form). In the germinal centre they undergo rapid proliferation (in dark zone and referred to as ‘centroblasts’. Then they go into the light zone where they undergo affinity maturation (referred to as ‘centrocytes’). They then exit the germinal centre as plasma cells or memory cells.
Where does the process previously described of B-cell activation and proliferation etc occur?
Usually happens in the lymph nodes, but there is extra nodal tissue in which this process can also occur. One of the largest extra-nodal lymphoid organs is the Peyer’s patches in the small bowel and they function in a similar way as the lymph node.
Which antibody type is the usually excreted one?
IgA
What is mucosa associated lymphoid tissue (MALT)?
The largest secondary lymphoid organ committed to local immunity. First and best described in the Peyer’s patches in the ileum.
What are the tertiary immune system (organs)?
The tertiary immune system is areas of the body where under normal circumstances there aren’t many immune cells, but if there is immune stimulation they can easily acquire lymphoid cells and almost become like extra-nodal lymphoid tissue. Typically, this may include the skin.
What is the usual presentation for T-cell acute lymphoblastic lymphoma?
They often present wit a mediastinal mass (they will usually get bone marrow involvement at some point), but it’s usually a mediastinal mass which is the first presenting site because the immature T-cells mature in the thymus.
Are the majority of malignant lymphomas nodal or extra-nodal?
The majority (60%) are nodal, with 40% being extranodal
Viruses can be a very important driving factor for many types of lymphoma, can you give some examples?
EBV- Burkitt lymphoma (EBV is associated with a proportion of Burkitt lymphomas, especially the endemic subtype and HIV-associated subtype). Also associated with Hodgkin lymphoma and post-transplant and AIDS-related lymphoma.
HTLV1- associated with T cell NHL (non-Hodgkin lymphoma).
Hepatitis C- associated with low grade B cell NHL
Human herpes virus 8 or Kaposi sarcoma virus- associated with plasma cell malignancy
At every stage of B-cell maturation and activation (described previously) you can get lymphomas which are sort of the counterpart of that normal stage. Give the examples.
Neoplasms of the precursor B-cells- gives rise to BLL (B-cell lymphoblastic leukaemia/ lymphoma) which is very aggressive.
When B-cells are in the naive stage before they enter the germinal centre- gives rise to mantle cell lymphoma.
From the germinal centre you can get very aggressive lymphomas, the most common being the DLBCL (diffuse large B-cell lymphoma) - composed of cells that look like cells from the germinal centre (e.g. centroblasts). But from the germinal centre can also get Hodgkin lymphoma, Burkitt lymphoma and follicular lymphoma.
After the germinal centre there are memory B-cells which give rise to marginal zone lymphomas and MALT lymphomas. The long-lived plasma cells give rise to plasma cell myeloma (which is a pure plasma cell neoplasm).
Are follicular lymphomas high/low grade?
They are lower grade/ more indolent and try to reproduce the normal architecture.
Which cellular marker do we look for to inform us about cellular proliferation with regards to lymphomas?
KI-67. Process called the KI-67 immunisation. It will highlight the nuclei of every cell that is actively dividing. Remember that how many lymphoma cells in a particular lymphoma are actually dividing can give us an indication of how aggressive it is (because in aggressive lymphomas almost all the cells will be dividing at the same time). So e.g. in follicular lymphoma which is more indolent there is low KI-67 staining.
In which condition might you see a classic ‘pepper-pot’ skull and why?
Plasma cell myeloma - they have got plasma cell deposits in the skull causing small lytic lesions throughout the skull
What name is given to the light chains of a myeloma which are excreted in the urine?
Bence jones protein
Tell me briefly about Hodgkin lymphoma
It is a very particular type of lymphoma. Bimodal age distinction (peak in children/young adults and a peak in the elderly). Characteristic clinical B symptoms (weight loss, fever, night sweats). Nodal disease (almost never arises from an extra-nodal site unless it is very advanced disease and has spread). Role of EBV virus in 35% of cases.
What are the malignant cells in Hodgkin lymphoma referred to?
Reed Sternberg cells. They are believed to be derived from the B-cells from the germinal centre. Typical morphology where the malignant cells only make up about 1-5% of the tumour (see in a background of inflammatory infiltrate).
Hodgkin lymphoma typically causes a very nodular appearance of the lymph node where you get lots of pale nodules, what are these described as?
Fish flesh appearance
What do Reed Sternberg cells look like?
Very large binucleate cells with prominent nucleoli (which make them look like owl eyes). They can be single nuclei as well, or multiple nuclei. (Note that when they are single nucleate we call then Hodgkin cells).
There are various diagnostic methods for diagnosing lymphoma including morphology, immunohistochemistry, flow cytometry and molecular techniques such as PCR and FISH. Which is the most important diagnostic method?
Morphology (actually looking at the cells) as looking at the tumour under the microscope is then what determines all the subsequent investigations
What is the most important stain/marker used to determine whether the lymphoma is a B-cell lymphoma?
CD20 (it is a surface antigen of the B-cells)
What chromosomal translocation is seen in Burkitt’s lymphoma?
T(8,14)
What method might we use to look at whether the chromosomes are translocated or not?
FISH
What are the layers of the GI tract?
Mucosa: epithelium, lamina propria, muscularis mucosa
Submucosa
Muscularis propria- circular muscle and longitudinal muscle
Serosa/ adventitia
What is the distance between the top front incisors and the GOJ (gastro-oesophageal junction)?
40cm (and the length of the oesophagus is fairly equal between different people of different heights- this measurement is useful to know especially when you are mapping out Barrett’s).
What is the histological lining of the oesophagus?
Non-keratinised stratified squamous epithelium
Give some of the risk factors for reflux oesophagitis
Hiatus hernia, peptic ulcer, smoking and alcohol, excessive vomiting, pregnancy, diabetes, surgery of/around GOJ
What is the histological trio that forms the hallmark of reflux oesophagitis?
Basal hyperplasia
Increased numbers of lymphocytes and eosinophils in the epithelium
Vascular papillae (bits of stroma that stick upwards into the squamous epithelium).
What are the complications of reflux oesophagitis?
Stricture (due to the chronic inflammation and fibrosis)- causing dysphagia
Barrett’s oesophagus
Neoplasia (Barrett’s predisposes to neoplasia)
Tell me about eosinophilic oesophagitis
Aetiology unknown. ? An allergic reaction. Presence of eosinophils. Classic presentation of dysphasia with a normal looking oesophagus at OGD or sometimes it may have a corrugation or ‘feline’ appearance. Biopsy look for: lots of eosinophils (clusters of eosinophils can be called eosinophilic ‘micro-abscesses’, the eosinophils start to degranulate, and you also get basal hyperplasia. Treatment is steroid based
What is achlasia
It is a rare condition of unknown aetiology (?autoimmune). You get targeted inflammatory destruction of the myenteric ganglion cells. (they are neural structures which regulate peristalsis in the oesophagus). Tends to affect the lower oesophagus and you tend to get a lack of relaxation (essentially a stricture formation).
What is a complication of achalasia and what is the implication of this?
Because you get a build up of content within the squamous epithelium-lined oesophagus (and the oesophagus doesn’t like chemical insult) it becomes inflamed, so long term complication is squamous cell carcinoma. Therefore patients with known achalasia get surveillance endoscopies.
Name the infections of the oesophagus (in order of commonality if possible)
Candida
Herpes simplex virus
Trypanosomiasis
(Candida and herpes are linked to immunosuppression)
Tell me briefly about Candida infection of the oesophagus
Looks like cottage cheese lining the inside of the oesophagus
Histologically you get spores and so-called pseudohyphae
The patient is treated with anti-fungals
Tell me briefly about herpes simplex virus (HSV) infection of the oesophagus
Because herpes is a virus, you don’t see it down the microscope, you see changes to the nucleus (cytopathic changes) of the cells which include: multinucleation and nuclear inclusion. Once this is suspected, can use an immunostain which should light up and confirm the diagnosis.
What type of people do you see HSV oesophagitis in?
Immunosuppressed individuals (people don’t get HSV oesophagitis unless they are immunosuppressed).
Tell me about Chagas disease.
It is rare, caused by the parasite Trypansoma cruzi. Transmitted in the faeces of ‘blood sucking’ reduviid bug via its bite. The parasite likes muscle (cardiac muscle)- causing cardiomyopathy. It also likes smooth muscle of the GI tract and you can get benign strictures forming e.g. of the oesophagus, so its a form of achalasia known as pseudo-achalasia.
Tell me about Barrett’s oesophagus
Definition: metaplastic replacement of oesophageal lining by glandular mucosa (columnar epithelium). Aetiology: reflux of gastric (acid) and duodenal (bile) contents into the oesophagus. Endoscopically squamous epithelium is white and glandular mucosa looks pink/red (projecting out in star like shape)
What is the length of Barrett’s (hint: not looking for a value)
The distance between the SCJ and the GOJ
SCJ = squamocolumnar junction - junction between the normal squamous epithelium and abnormal columnar epithelium
GOJ = gastrooesophageal junction
In most people the SCJ is at the same level as the GOJ (because it is where the stomach starts)
What type of Barrett’s is most likely to turn into a neoplasia? Options are: gastric cardia, gastric body, pancreatic and intestinal. (Note, this is how we subdivide the epithelium histologically)
Intestinal
What are the two types of oesophageal carcinoma and which is more common?
Adenocarcinoma (80%) and squamous cell carcinoma (20%)
Does the cardia have any specialised glands? Where does? What can this tell you?
The cardia has similar mucosa to the antrum and the pylorus (there are no specialised glands). The specialised glands are only present in the body and the fundus, so it is possible to tell roughly where a gastric biopsy has been taken (in relation to the stomach) when looking at the biopsy histology.
Tell me about chemical/ reactive gastritis.
It is now the commonest form of ‘chronic’ gastritis. Bile reflux, drugs- aspirin and other NSAIDs, alcohol. Histologically we look for: foveolar hyperplasia (foveal cell hyperplasia) and lamina propria changes - look for oedema and dilated blood vessels. Tx- remove the insult causing it.
Tell me briefly about autoimmune/ atrophic gastritis
E.g. pernicious anaemia. Typically Caucasian older women who get autoimmune gastritis. You get destruction of the body mucosa, and whenever the stomach destroys its mucosa (which normally produces acid) you get a condition called achlorhydria, where you lose the acidic environment in the stomach and you replace the lost mucosa with intestinal mucosa (intestinal metaplasia) and this can turn neoplastic.
What are the diseases called by H.pylori?
Gastritis (reddening of the gastric epithelium with some erosions which appear white)
Ulcer
MALT lymphoma
Carcinoma
What are foveolar cells?
Also known as surface mucous cells, they are mucus-producing cells
How is H.pylori considered protective against Barrett’s?
As helicobacter becomes pangastric it destroys acid production (so you get achlorhydria) and as Barrett’s is caused by reflux of acid, it has been said that helicobacter causing achlorhydria therefore protects against Barrett’s.
Tell me about MALT lymphoma caused by H.pylori
Lymphoid aggregates form due to H.pylori and if lymphocytes are stimulated enough times to proliferate, there is always the risk of lymphoma (remember that all chronic inflammatory conditions potentially can predispose to lymphoma). H.pylori can therefore predispose to MALT lymphoma. Many of these lymphomas can be treated effectively with antibiotics (because you knock out H.pylori which reduces the drive for lymphocytes to proliferate) and in most cases this cures the MALT lymphoma.
How can H.pylori cause carcinoma?
Helicobacter causes superficial gastritis, followed by atrophic gastritis (causing achlorhydria), so you then get intestinal metaplasia and this can predispose to dysplasia, which can evolve into carcinoma. Helicobacter tends to colonise the distal stomach first, so most cancers which develop in H.pylori infected patients tend to occur distally.
Name the various gastric neoplasia’s
Adenocarcinoma
Lymphoma
Neuro-endocrine tumour
GIST (gastrointestinal stromal tumour)
Tell me about adenocarcinoma of the stomach
Particularly common in Japan, Korea and Chile. M:F= 3:1 Risk factors: diet (high salt, low diary products) and helicobacter and intestinal metaplasia. We can subdivide into: intestinal-type carcinomas or diffuse-type carcinomas. Diffuse-type carcinomas of the stomach rarely express HER-2, whereas one third of intestinal-type gastric cancers express HER-2. Herceptin (transtuzumab) is licensed for use in advanced gastric cancer.
Tell me about GIST
Gastrointestinal stromal tumour. Rare. Stomach > small intestine > oesophagus and large bowel. Mutations in tyrosine kinase genes. Management is therefore surgery +/- TKI (tyrosine kinase inhibitors) e.g. imatinib. Patients are genotyped to look for GIST mutations
What is the mucosa of the small intestine? (Histological lining)
Lined by simple columnar epithelium. Presence of villi and crypts
Tell me about coeliac disease (histopathology)
May see flat mucosa if really severe. Reduction in the normal villus height to crypt depth ratio from 5:1 to <3:1. (So the villus should normally be >3 times as tall as the crypt length, and any reduction is called villus atrophy/blunting). Also see: crypt hyperplasia, increased intraepithelial lymphocytes, infiltration of the lamina propria by plasma cells and lymphocytes
What are some of the complications of coeliac disease?
Refractory sprue (non-responsive to gluten restriction)- can be due to the lymphocytes causing coeliac disease becoming clonal i.e. constant stimulation even though gluten has been withdrawn. Ulcerative jejunitis (usually a sign the patient is starting to develop lymphoma. Neoplasia: enteropathy-associated T-cell lymphoma (EATL) and small intestinal adenocarcinoma.
Tell me about giardiasis in relation to the intestine.
Giardia lamblia. Commonest small intestine protozoal infection worldwide (but rare in the UK). Contaminated water (person to person) spread by faecal-oral transmission. Immunocompromised patients more likely to be infected. Histology: small intestinal mucosa may be normal or inflamed. Giardia organisms histologically can look like small flecks.
What are the types of small intestine neoplasia?
Adenomas- duodenal (FAP)- adenomas are the most common type of neoplasia in the large bowel but they are very rare in the small bowel (so if adenomas are found in the small bowel you start to wonder whether the patient might have FAP which is a genetic condition caused by an APC gene mutation).
Adenocarcinoma- rare so consider predisposing factors: coeliac disease, Crohn’s disease, FAP
Lymphoma- B-cell lymphoma (e.g. Burkitt’s lymphoma in ileum). T-cell lymphomas e.g. EATL.
GIST
Neuroendocrine tumours
Tell me about (neuro)endocrine tumours
Most common in the appendix and small intestine. Used to call the entities in the gut ‘carcinoids’. Typically, NETs of the small bowel are very small, but can give rise to big metastases in the mesentery and the liver.
What is the commonest cause of hypothyroidism?
Hashimoto’s thyroiditis. (Atrophic process)
Tell me more about Hashimoto’s thyroiditis
Autoimmune: anti-thyroid peroxidase antibodies (anti-TPO).
Lymphocytic destruction of the thyroid (aka. Chronic lymphocytic thyroiditis).
F:M = 10:1.
Other than Hashimoto’s what are the causes of hypothyroidism?
Removal of the thyroid, radioiodine treatment (iatrogenic causes)
What are the clinical signs and symptoms of hypothyroidism?
Myxoedema (the clinical syndrome of under active thyroid):
Weight gain, constipation, cold intolerance, tiredness, depression, thin hair, weak heartbeat, slow reflexes
What neoplasm is someone with Hashimoto’s thyroiditis prone to?
Lymphoma (thyroid lymphoma)- because they have got a chronic, proliferative and destructive lymphoid infiltrate occurring in the thyroid
What is the most common cause of hyperthyroidism?
Grave’s disease (85% of cases)
Other than Grave’s disease, what can cause hyperthyroidism?
Hyperfunctional MNG (multinodular goitre) Hyperfunctional adenoma (benign follicular tumour)
What are some of the symptoms of hyperthyroidism?
Sweating, heat intolerance, weight loss despite increased appetite, diarrhoea, tachycardia, arrhythmia (often AF), tremor, anxiety, hyperactivity, brisk reflexes. Exophthalmos (in Grave’s)
Tell me about Grave’s disease
F:M = 10:1
Autoimmune
Thyroid stimulating antibodies (TSH receptor autoantibodies)
Symmetrical enlargement of the thyroid (diffuse toxic goitre)
Exophthalmos- deposition of connective tissue behind the eyeball, causing the eye to protrude.
Tell me about multi-nodular goitre (MNG)
Usually euthyroid. We don’t really understand why it occurs. Large goitre may cause tracheal compression or dysphagia.
Tell me about follicular adenomas of the thyroid
Benign tumour, usually euthyroid. Rarely hyperfunctional (‘toxic’ nodule). Tx: thyroid lobectomy
What are the 4 types of carcinoma of the thyroid?
Papillary (most common)
Follicular
Anaplastic
Medullary
Which of the thyroid carcinomas have a good prognosis and which have a bad prognosis?
Papillary and follicular carcinomas have a very good prognosis and are well differentiated. Anaplastic and medullary carcinomas have a very poor prognosis and are poorly differentiated.
