Pathology Flashcards
Li-Fraumeni Syndrome
Autosomal dominant
Consists of germline mutations to p53 tumour suppressor gene
High incidence of malignancies particularly sarcomas and leukaemias
Diagnosed when:
*Individual develops sarcoma under 45 years
*First degree relative diagnosed with any cancer below age 45 years and another family member develops malignancy under 45 years or sarcoma at any age
BRCA 1 and 2
Carried on chromosome 17 (BRCA 1) and Chromosome 13 (BRCA 2)
Linked to developing breast cancer (60%) risk.
Associated risk of developing ovarian cancer (55% with BRCA 1 and 25% with BRCA 2).
Lynch Syndrome
Autosomal dominant
Develop colonic cancer and endometrial cancer at young age
80% of affected individuals will get colonic and/ or endometrial cancer
High risk individuals may be identified using the Amsterdam criteria
Gardners syndrome
Autosomal dominant familial colorectal polyposis
Multiple colonic polyps
Extra colonic diseases include: skull osteoma, thyroid cancer and epidermoid cysts
Desmoid tumours are seen in 15%
Mutation of APC gene located on chromosome 5
Due to colonic polyps most patients will undergo colectomy to reduce risk of colorectal cancer
Now considered a variant of familial adenomatous polyposis coli
What can increase PSA?
benign prostatic hyperplasia (BPH)
prostatitis and urinary tract infection (NICE recommend to postpone the PSA test for at least 1 month after treatment)
ejaculation (ideally not in the previous 48 hours)
vigorous exercise (ideally not in the previous 48 hours)
urinary retention
instrumentation of the urinary tract
Oesophageal cancer, type, investigation,
Achalasia is a rare condition. However, even once treated there is an increased risk of malignancy. When it does occur it is most likely to be of squamous cell type.
In most cases in the Western world this increase is accounted for by a rise in the number of cases of adenocarcinoma. In the UK adenocarcinomas account for 65% of cases.Barretts oesophagus is a major risk factor for most cases of oesophageal adenocarcinoma.
30 fold increase in cancer risk and if invasive malignancy is diagnosed early then survival may approach 85% at 5 years.
Upper GI endoscopy is the first line test
Contrast swallow may be of benefit in classifying benign motility disorders but has no place in the assessment of tumours
Staging is initially undertaken with CT scanning of the chest, abdomen and pelvis. If overt metastatic disease is identified using this modality then further complex imaging is unnecessary
If CT does not show metastatic disease, then local stage may be more accurately assessed by use of endoscopic ultrasound.
Staging laparoscopy is performed to detect occult peritoneal disease. PET CT is performed in those with negative laparoscopy. Thoracoscopy is not routinely performed.
Surgical management of Oesophageal cancer
Operable disease is best managed by surgical resection. The most standard procedure is an Ivor- Lewis type oesophagectomy. An intrathoracic oesophagogastric anastomosis is constructed.
many patients will be treated with adjuvant chemotherapy.
transhiatal resection (for distal lesions)
left thoraco-abdominal resection (difficult access due to thoracic aorta) and a total oesophagectomy (McKeown) with a cervical oesophagogastric anastomosis.
The biggest surgical challenge is that of anastomotic leak, with an intrathoracic anastomosis this will result in mediastinitis. With high mortality. The McKeown technique has an intrinsically lower systemic insult in the event of anastomotic leakage.
Dukes staging
Dukes A Tumour confined to the bowel but not extending beyond it, without nodal metastasis (95%)
Dukes B Tumour invading bowel wall, but without nodal metastasis (75%)
Dukes C Lymph node metastases (50%)
Dukes D Distant metastases (6%)(25% if resectable)
(5 year survival rate)
Features suggestive of sarcomatous change in a lipoma
Size >5cm
Increasing size
Pain
Deep anatomical location
Pathology of Barrett’s oseophagus
characterised by the metaplastic transformation of squamous oesophageal epithelium to columnar gastric type epithelium
endoscopic features of Barretts oesophagus a
with a deep biopsy that demonstrates
goblet cell metaplasia but also oesophageal glands.
Which important structural proteins determine the structural properties of all tissues?
Glycine
Elastin
Glycosaminoglycans
Collagen structure
Composed of 3 polypeptide strands that are woven into a helix, usually a combination of glycine with either proline or hydroxyproline plus another amino acid
Numerous hydrogen bonds exist within molecule to provide additional strength
Many sub types but commonest sub type is I (90% of bodily collagen), tissues with increased levels of flexibility have increased levels of type III collagen
Vitamin c is important in establishing cross links
Synthesised by fibroblasts
Which subtype of lung cancer is more common?
Non small cell lung cancer is the most common variant and accounts for 80% of all lung cancers.
Non small cell lung cancer includes which subtypes?
Squamous cell carcinoma (25% cases)
Adenocarcinoma (40% cases)
Large cell carcinoma (10% cases)
Paraneoplastic features and early disease dissemination are less likely than with small cell lung carcinoma. Adenocarcinoma is the most common lung cancer type encountered in never smokers.
Small cell lung carcinoma
The neuroendocrine hormones may be released from these cells with a wide range of paraneoplastic associations. These tumours are strongly associated with smoking and will typically arise in the larger airways. They disseminate early in the course of the disease and although they are usually chemosensitive this seldom results in long lasting remissions.
Branchial cyst
Six branchial arches separated by branchial clefts
Incomplete obliteration of the branchial apparatus may result in cysts, sinuses or fistulae
75% of branchial cysts originate from the second branchial cleft
Usually located anterior to the sternocleidomastoid near the angle of the mandible
Unless infected the fluid of the cyst has a similar consistency to water and is anechoic on USS
Pernicious anaemia
chronic illness caused by impaired absorption of vitamin B-12 because of a lack of intrinsic factor (IF) in gastric secretions. It occurs as a relatively common adult form of anaemia that is associated with gastric atrophy and a loss of IF production and as a rare congenital autosomal recessive form in which IF production is lacking without gastric atrophy.
failure of gastric parietal cells to produce sufficient IF (a gastric protein secreted by parietal cells) to permit the absorption of adequate quantities of dietary vitamin B-12. Other disorders that interfere with the absorption and metabolism of vitamin B-12 can produce cobalamin deficiency, with the development of a macrocytic anaemia and neurologic complications. In many cases the underlying cause is autoimmune destruction of the parietal cell mass of the gastric antrum.
monthly treatment of vitamin B12 injections. Folic acid supplementation may also be required.
Histopathology findings in temporal arteritis biopsy?
Vessel wall granulomatous arteritis with mononuclear cell infiltrates and giant cell formation
Risks in GCA/TEMP ART BIOPSY
Injury to facial or auriculotemporal nerve
Papillary carcinoma
Histologically tumour has papillary projections and pale empty nuclei
Seldom encapsulated
Account for 60% of thyroid cancers
Follicular carcinoma
May appear macroscopically encapsulated, microscopically capsular invasion is seen
Anaplastic carcinoma
Most common in elderly females
Local invasion is a common feature
Account for 10% of thyroid cancers
Treatment is by resection where possible, palliation may be achieved through isthmusectomy and radiotherapy. Chemotherapy is ineffective.
Medullary carcinoma
Tumours of the parafollicular cells (C Cells)
C cells derived from neural crest and not thyroid tissue
Serum calcitonin levels often raised
Familial genetic disease accounts for up to 20% cases
Both lymphatic and haematogenous metastasis are recognised, nodal disease is associated with a very poor prognosis.
Adrenal lesions- Incidental Investigation?
Morning and midnight plasma cortisol measurements
Dexamethasone suppression test
24 hour urinary cortisol excretion
24 hour urinary excretion of catecholamines
Serum potassium, aldosterone and renin levels
Adrenal lesions- Incidental
Management
Management
The risk of malignancy is related to the size of the lesion and 25% of all masses greater than 4cm will be malignant. Such lesions should usually be excised. Where a lesion is a suspected metastatic deposit a biopsy may be considered.
Hodgkins lymphoma - Presenting features
Asymptomatic lympadenopathy
Cough, Pel Ebstein fever, haemoptysis, dyspnoea
B Symptoms - 10% weight loss, fever, night sweats
Hodgkins lymphoma staging and histology
All patients are staged with CT scanning of the chest, abdomen and pelvis
The Ann Arbor staging system is commonly used
I Single lymph node region
II Two or more regions on the same side of the diaphragm
III Involvement of lymph node regions on both sides of the diaphragm
IV Involvement of extra nodal sites
Reed Sternberg cells may be identified histologically.
Infection with Ebstein Barr virus is linked to the condition (particularly mixed cellularity lymphoma).
Stage I disease is associated with survival figures of up to 85% at 5 years. Nodular sclerosing has the best prognosis. Lymphocyte depleted Hodgkins lymphoma, advancing age, male sex and stage IV disease are all associated with a worsening of prognosis.
Phaeochromocytoma
Neuroendocrine tumour of the chromaffin cells of the adrenal medulla. Hypertension and hyperglycaemia are often found.
10% of cases are bilateral. (Most tumours are unilateral (often right sided) and smaller than 10cm.)
10% occur in children.
11% are malignant (higher when tumour is located outside the adrenal).
10% will not be hypertensive.
Familial cases are usually linked to the Multiple endocrine neoplasia syndromes (considered under its own heading).
Phaeochromocytoma treatmetnt
An irreversible alpha adrenoreceptor blocker should be given, although minority may prefer reversible blockade(1). Labetolol may be co-administered for cardiac chronotropic control. Isolated beta blockade should not be considered as it will lead to unopposed alpha activity.
Merkel cell tumours of the skin
Rare but aggressive tumour.
Develops from intra epidermal Merkel cells.
Usually presents on elderly, sun damaged skin. The periorbital area is the commonest site.
Histologically these tumours appear within the dermis and subcutis. The lesions consist of sheets and nodules of small hyperchromatic epithelial cells with high rates of mitosis and apoptosis. Lymphovascular invasion is commonly seen.
Pre-existing infection with Merkel Cell Polyomavirus is seen in 80% cases.
Treatment &Prognosis of Merkcle cell tumour
Treatment
Surgical excision is first line. Margins of 1cm are required. Lesions >10mm in diameter should undergo sentinel lymph node biopsy. Adjuvant radiotherapy is often given to reduce the risk of local recurrence.
Prognosis
With lymph node metastasis 5 year survival is 50% or less.
Small lesions without nodal spread are usually associated with a 5 year survival of 80%.
Burns pathology
Extensive burns
Haemolysis due to damage of erythrocytes by heat and microangiopathy
Loss of capillary membrane integrity causing plasma leakage into interstitial space
Extravasation of fluids from the burn site causing hypovolaemic shock (up to 48h after injury)- decreased blood volume and increased haematocrit
Protein loss
Secondary infection e.g. Staphylococcus aureus
ARDS
Risk of Curlings ulcer (acute peptic stress ulcers)
Danger of full thickness circumferential burns in an extremity as these may develop compartment syndrome
Klippel-Trenaunay syndrome
Signs and symptoms
The birth defect is diagnosed by the presence of a combination of these symptoms:
One or more distinctive port-wine stains with sharp borders
Varicose veins
Hypertrophy of bony and soft tissues, that may lead to local gigantism or shrinking.
An improperly developed lymphatic system
In some cases, port-wine stains (capillary port wine type) may be absent. Such cases are very rare and may be classified as ‘atypical Klippel-Trenaunay syndrome’.
KTS can either affect blood vessels, lymph vessels, or both. The condition most commonly presents with a mixture of the two. Those with venous involvement experience increased pain and complications.
Blood test in DIC
prolonged clotting times, thrombocytopenia, decreased fibrinogen, increased fibrinogen degradation products
Antiphospholipid syndrome
Multi organ disease
Pregnancy involvement common
Arterial and venous thromboses
Either Lupus anticoagulant or Anti cardiolipin antibodies
APTT usually prolonged
Antibodies may be elevated following surgery, drugs or malignancy
Need anticoagulation with INR between 3 and 4
Gastrointestinal stromal tumour
GIST’s are not common tumours (10 per million) and originate primarily from the interstitial pacemaker cells (of Cajal). Up to 70% occur in the stomach, the remainder occurring in the small intestine (20%) and the colon and rectum (5%). Up to 95% are solitary lesions and most are sporadic. The vast majority express CD117 which is a transmembrane tyrosine kinase receptor and in these there is a mutation of the c-KIT gene.
The goal of surgery is resection of the tumour with a 1-2cm margin of normal tissue. As a result extensive resections are not required. Unfortunately there is a high local recurrence rate, the risk of which is related to site, incomplete resections and high mitotic count. Salvage surgery for recurrent disease is associated with a median survival of 15 months.
The prognosis in high risk patients is greatly improved through the use of imatinib, which in the ACOSOG trial (imatinib vs placebo) improved relapse rates from 17% to 2%.
In the UK it is advocated by NICE for use in patients with metastatic disease or locally unresectable disease.
Wound healing - 1) Haemostasis
Minutes to hours following injury
Vasospasm in adjacent vessels, platelet plug formation and generation of fibrin rich clot.
Wound healing 2) Inflammation
Typically days 1-5
Neutrophils migrate into wound (function impaired in diabetes).
Growth factors released, including basic fibroblast growth factor and vascular endothelial growth factor.
Fibroblasts replicate within the adjacent matrix and migrate into wound.
Macrophages and fibroblasts couple matrix regeneration and clot substitution.
Wound healing 3) Regeneration
Typically days 7 to 56
Platelet derived growth factor and transformation growth factors stimulate fibroblasts and epithelial cells.
Fibroblasts produce a collagen network.
Angiogenesis occurs and wound resembles granulation tissue.
Wound healing 4) Remodeling
From 6 weeks to 1 year
Longest phase of the healing process and may last up to one year (or longer).
During this phase fibroblasts become differentiated (myofibroblasts) and these facilitate wound contraction.
Collagen fibres are remodeled.
Microvessels regress leaving a pale scar.
Carcinoid syndrome
Carcinoid tumours secrete serotonin
Originate in neuroendocrine cells mainly in the intestine (midgut-distal ileum/appendix)
Clinical features
Onset: insidious over many years
Flushing face
Palpitations
Pulmonary valve stenosis and tricuspid regurgitation causing dyspnoea
Asthma
Severe diarrhoea (secretory, persists despite fasting)
Investigation
5-HIAA in a 24-hour urine collection
Somatostatin receptor scintigraphy
CT scan
Blood testing for chromogranin A
Treatment
Octreotide
Surgical removal
Post transplant complications
CMV: 4 weeks to 6 months post transplant
EBV: post transplant lymphoproliferative disease. > 6 months post transplant
Types of carotid body tumour
rare tumours. However, they typically account for around 60% of head and neck paraganglionomas.
Types of carotid body tumour
Sporadic - Accounts for 85% of cases
Familial - Seen in around 10% of cases and usually in younger patients
Hyperplastic - Seen in those at high altitude or in those with COPD
A 56 year old man from Ghana has suffered from recurrent attacks of haematuria for many years. He presents with suprapubic discomfort and at cystoscopy is found to have a mass lesion within the bladder. What is the most likely diagnosis?
In Ghana, Schistosomiasis is more common than in the UK and may cause recurrent episodes of haematuria. In those affected with the condition who develop a bladder neoplasm, an SCC is the most common type.
desmoid tumour
s low grade fibrosarcomas or non aggressive fibrous tumours. They commonly present as large infiltrative masses. They may be divided into abdominal, extra abdominal and intra abdominal. All types share the same biological features. Extra abdominal desmoids have an equal sex distribution and primarily arise in the musculature of the shoulder, chest wall, back and thigh. Abdominal desmoids usually arise in the musculoaponeurotic structures of the abdominal wall. Intra abdominal desmoids tend to occur in the mesentery or pelvic side walls and occur most frequently in patients with familial adenomatous polyposis coli syndrome.
Koebner phenomenon
The Koebner phenomenon describes skin lesions which appear at the site of injury. It is seen in:
Psoriasis
Vitiligo
Warts
Lichen planus
Lichen sclerosus
Molluscum contagiosum
Popcorn cells
small cells with hyper-lobulated nucleus and small nucleoli. They are the lymphohistiocytic (L-H) variant of Reed Sternberg cells and are associated with nodular lymphocyte predominant Hodgkin lymphoma
Leriche syndrome
atherosclerotic occlusive disease involving the abdominal aorta and/or both of the iliac arteries
- Claudication of the buttocks and thighs
- Atrophy of the musculature of the legs
- Impotence (due to paralysis of the L1 nerve)
Diagnostic work up will include angiography, where feasible, iliac occlusions are usually treated with endovascular angioplasty and stent insertion.
Management involves correcting underlying risk factors such as hypercholesterolaemia and stopping smoking
Papillary carcinoma histology
Histologically, they may demonstrate psammoma bodies (areas of calcification) and so called ‘orphan Annie’ nuclei
Psammoma bodies consist of clusters of microcalcification.
Hydatid cysts causative orgnaism?
tapeworm parasite Echinococcus granulosus.
Multiple Endocrine Neoplasia Type 1
Autosomal Dominant
3Ps
Parathyroid (95%): Parathyroid adenoma
Pituitary (70%): Prolactinoma/ACTH/Growth Hormone secreting adenoma
Pancreas (50%): Islet cell tumours/Zollinger Ellison syndrome
also: Adrenal (adenoma) and thyroid (adenoma)
What is the gene involved in MEN type 1 and what is a common presentation?
MENIN Gene - Chr 11
Hypercalcaemia
MEN type IIa
RET ONCOGENE CHR10
Phaeochromocytoma
Medullary thyroid cancer (70%)
Hyperparathyroidism (60%)
MEN Type 2
Same as MEN IIa with addition of:
Marfanoid body habitus
Mucosal neuromas
What cells make PTH
Chief cells in 4 glands parathyroid
Where does PTH work to reabsorb calcium in the kidney?
works in the kidney in the distal convoluted tubule to reabsorb calcium.
When PTH binds to the receptor, it will then increase the amount of cyclic AMP within your nephron.
What cell is involved in Foreign body reaction
Giant cells
What does Entameoba Histolica cause
Accounts for 10% of liver abscesses, world wide - commonest cause of liver absess is amoebic
Commonest cause of liver abscess in developed countries
Coliforms eg) E coli, Klebsiella
Usually due to cholangitis w/bilary stones following diverticulitis
Physiological and histological features of ARDS ?
Increased capillary permeability
Interstitial and alveolear oedema
Capillary permeability
Interstitial and alveolar oedema
Later - diffuse late interstitial and alveolar fibrosis
What are Kupffer cells?
Specialised phagocytic cells that line the hepatic sinusoids
What immune mechanism is involved in Graft vs Host disease?
- Immunocompetent stem cells are transplanted to an individual
eg) bone marrow attacks the recipient
How does LMWH affect coag
Classic radiological finding most commonly seen in Ewing’s sarcoma
Malignant cround cell tumour of the long bones (onion sign)
Poor porgnosis with mets
80% mortality in 5 ytears
Classical radiological finding of common primary bone malignancy
Signs of bone destruction and new bone formation - sunray sign
What is Functional residual capacity and what conditions affect it?
FRC is volume of bgas remaining in the lung after a normal expiration
ERV+RV
Occurs in reduced lung compliance -> intersitial fibrosis
