Pathology Flashcards
What is the most common type of malignant colonic lesion?
Adenocarcinoma
Rarer malignant colonic lesions?
Melanoma Carcinoid tumours Squamous cell tumours esp distal anal canal
Where are majority of colorectal cancers found?
70% in sigmoid/upper rectum
4 histological features suggestive of Crohn’s?
Transmural inflammation in skip lesions
Non-caseating epithelioid granulomatous inflammation
Giant Langerhans cels
Cobblestoning, aphthoid ulceration
4 histological features suggestive of UC?
Pseudopolyps Red raw mucosa Goblet cells/mucin Crypt abscesses
What is the most common extra-colonic feature of IBD?
Arthritis
Other extra-colonic features of Crohns/UC? Which are more common in each?
Erythema nodosum Episcleritis - more common in Crohns Uveitis - more common in UC PSC - more common in UC Osteoporosis Pyoderma gangrenosum Clubbing
What does barium enema for UC look like?
Loss of haustrations Superficial ulceration with pseudopolyps Drainpipe colon (longstanding disease)
What is the increased risk of colorectal cancer in UC?
6-fold
Describe the organisation of the adrenal glands? What secretes what?
Furthest outside is fibrous capsule
Adrenal cortex is outside and consists of zona glomerulosa (mineralocorticoids), fasciculata (glucocorticoids) and reticuclaris (androgens)
Medulla consists of chromaffin cells secreting Adr and NA
Central adrenomedullar vessels inside
What stimulates release of adrenaline and noradrenaline? Where from? Derived from what?
NA and Adr are derived from tyrosine and exocytotically release from chromaffin cells of adrenal medulla under stimulation of pre-ganglionic sympathetic fibres (splanchnic nerves) from thoracic spinal cord - via ACh
How are thyroid hormones synthesised?
Iodide ions in blood stream actively transported from extracellular space into colloid-filled follicular epithelium
Converted to iodine via oxidisation by peroxide, which combines with tyrosine to form monoiodotyrosine and diiodotyrosine
These combine via thyroglobulin to form triiodothyronine (1 + 2 = T3) and thyroxine (2 + 2 = T4)
What thyroid hormone is active? How? Why aren’t all thyroid hormones like this?
T3 is active component in cells via binding to intracellular nuclear receptors to increase basal metabolic rate, glucose absorption/synthesis rate, fatty acid breakdown and protein turnover as well as RR and HR
T3 has shorter half life so most transported in plasma as T4 bound to albumin or thyroxine binding globulin
How is thyroid hormone secretion stimulated and controlled?
Hypothalamus releases TRH which stimulates anterior pituitary to release TSH
TSH acts directly on thyroid gland to absorb thyroglobulin into follicular cells, which is broken down to release T3 and T4 into systemic circulation
Negative feedback on TRH and TSH release
Investigation of thyroid lesion?
TFTs and USS +/- FNA cytology
What is the pathology of Graves disease?
Stimulatory auto IgG antibodies to TSH receptors on thyroid gland leading to chronic stimulation of gland and release of thyroid hormones, resulting in low TSH and raised T3/4
How much thyroid hormone does the normal thyroid have in reserve?
3 months worth
What histological type are most malignant pancreatic cancers? Where?
Adenocarcinoma, 70% are in head of pancreas
Risk factors for pancreatic cancer?
Smoking
Diabetes
Previous adenomas
FAP
Spread of pancreatic cancer?
Local
+ liver metastases
In which thyroid cancers is FNA not useful? Why?
Follicular or lymphoma
Follicular because need to see whether capsule is invaded; cancer only excludable on formal histological assessment so needs hemithyroidectomy
Lymphoma because consider core biopsy - best treated with chemo/radiotherapy rather than surgery
Outline interpretation of thyroid FNA results?
THY1 = inadequate - repeat or follow up US if cyst
THY2 = non-neoplastic e.g. colloid nodule, thyroiditis, cyst (if benign epithelial cells)
THY3 (a/f) = atypical or follicular cells. f needs hemithyroidectomy
THY4 = suspicious for malignancy - surgical resection unless lymphoma - core biopsy
THY5 = diagnostic of malignancy - surgical resection unless lymphoma or non-operable
How do follicular thyroid cancers metastasise? How does this vary from papillary?
Follicular offen haematogenously e.g. to bone
vs papillary where is via lymph
What are medullary thyroid cancers derived from?
Parafollicular c cells - secrete calcitonin
What is this? What are the histological features?
Papillary thyroid cancer - large empty looking nuclei (Orphan Annie), dystrophic calcification, psammoma bodies (calcium deposits) and invasion of surrounding tissue
What are psammoma bodies and Orphan Annie nuclei suggestive of?
Papillary thyroid cancer
In what circumstances is core biopsy better for thyroid lesion than FNA?
Lymphoma - better radio/chemo than surgery
What is the biggest single risk factor for thyroid cancer?
Radiation exposure - dose and how early exposed
What is the most common type of thyroid cancer? What %? Outline features and management
Papillary - 60%
Orphan Annie nuclei, papillary projections, psammoma calcification bodies. Lymph node metastasis common
Hemithyroidectomy for T1, total and central compartmental nodal dissection for T2 and above
Discuss follicular thyroid lesions?
Adenoma = solitary thyroid nodule. Malignancy only excludable via formal histology - needs hemithyroidectomy
Carcinoma = second most common overall. Macroscopic encapsulation with microscopic capsular invasion - spreads haematogenously. If confirmed on hemithyroidectomy needs total thyroidectomy
Discuss anaplastic thyroid cancer? Management?
10% of all cancers. Elderly females, worst prognosis. Commonly locally invasive
Management is resection where possible, or palliation via isthmusectomy and radiotherapy. Local debulking +/- palliative care
Discuss medullary thyroid carcinoma? Associations? Management?
Parafollicular C cell tumour - from neural crest, not thyroid tissue. Secrete calcitonin. Familial genetic in 20% - MEN2, familial medullary thyroid cancer
Spreads via blood and lymph, nodal disease = poor prognosis
Management is via total thyroidectomy
Are pain and abnormal thyroid function features of thyroid cancer?
Not really - most painless and euthyroid
What is Pemberton’s sign?
Elevate arms - venous engorgement suggestive of substernal goitre
What is the most common malignant primary liver tumour? What cells are affected?
Liver hepatocellular carcinoma - hepatocytes
What biochemical marker is used in monitoring HCC and what is it, where is secreted normally?
AFP - fetal equivalent of albumin secreted by yolk sac and foetal liver during embyological development prior to liver maturation
What is the biggest risk factor for hepatocellular carcinoma worldwide?
Hepatitis B
What premalignant lesions are there for hepatocellular carcinoma? What do you do with them?
Liver adenomas - remove them
What is monitoring process for hepatocellular carcinoma in cirrhotics? What suggests possible cancer?
USS and AFP every 6-12 months
If nodule over 1cm with raised AFP, likely HCC
What is the next step if find raised AFP and USS suggestive of discrete liver lesion?
Liver MRI
What is the classical CT picture of hepatocellular carcinoma?
Suspicious hypervascular lesion with hyperintense enhancement in arterial phase with washout during venous phase
Why don’t you generally biopsy liver lesions suspicious for cancer?
May precipitate seeding and cmopromise otherwise curative resection
What is the only malignancy where transplantation is not contraindicated?
Liver - sometimes do resection of entire liver and tranplsntation
2 classification systems for hepatocellular carcinoma staging?
Barcelona clinic liver classification
Child Pugh
Outline the Barcelona Clinic Liver Classification stages for hepatocellular carcinoma? Related Child Pugh stages?
0 - CP A - single lesion less than 2cm with normal portal pressures
A - CP A/B - single lesion over 3cm or 2-3 nodules
B - CP A/B - more than 3 modules
C - CP A/B - advanced tumours with portal vein invasion
D - CP C - advanced tumours for best supporitve care
General principles of management of hepatocellular carcinoma by stage?
Stage 0 disease - resect aiming for cure
Stage A - consider RF ablation or transplantation
Stage B - TACE, with doxorubicin
Stage C - Sorafenib - oral TK inhibitor may extend survival
Stage D - best supportive care
No adjuvant chemo, aim at least 2cm anatomical resection margins
What is the only drug shown to extend survival in hepatocellular carcinoma?
Sorafenib - oral TK inhibitor
What is a sarcoma? Common subtypes?
Malignant tumour arising from mesenchymal (multipotent stromal cells) tissue e.g. adipocytes, chondrocytes, bone
Common subtypes of bone/cartilage origin sarcoma?
Osteosarcoma
Ewing’s sarcoma
Chondrosarcoma
Common subtypes of soft tissue sarcoma?
Liposarcoma
Rhabdomyosarcoma (striated muscle)
Leiomyosarcoma (smooth muscle)
Synovial sarcoma
What are the main differences between sarcomas and carcinomas?
Sarcoma much rarer
Cell of origin different
Sarcoma more in young
Sarcoma more commonly haematogenous metastases
4 features suggestive of soft tissue mass being sarcoma?
Over 5cm
Deep location
Fixed to adjacent tissues
Rapid/progressive/invasive growth
What considerations must be made when considering biopsying potential sarcoma?
Propensity for seeding and local recurrence along tract, so if turns out to be sarcoma biopsy tract would also need excising
Describe Ewings sarcoma?
More common in males aged 10-20, affects typically femoral diaphysis
blue cell tumour histologically
needs chemo and surgery, haemotogenous mets common
Describe osteosarcoma?
Mesenchymal cells with osteoblastic differentiation
More common in males age 15-30
May be able to do limb preserving surger alongside chemo
What is the most common soft tissue sarcoma? Describe it?
Liposarcoma - malignancy of adipocytes typically seen in deep e.g. retroperitoneum in older patients
May be slow growing
Resistant tot radiotherapy, has pseudocapsule which can lead to local recurrence
What cells do GIST tumours arise from?
Interstitial pacemaker cells of Cajal
What may advanced GIST tumours look like macroscopically? Where are they found?
Smooth, exophytic mass - may have ulceration or bleeding if very advance
Most are found in stomach, some in small intestine
What is the mainstay of management of GIST tumours? What kind of surgery is potentially curative and what are the other options?
Surgical resection - not radical as rarely diffuse submucosal infiltration
2cm margins potentially curative but high local recuurrence rate
Alternatives include imatinib - TK inhibitor for metastatic or locally unresectable disease
What are the cells of origin of carcinoid tumours?
Neuroendocrine cells
Most common sites for carcinoid tumours?
Appendix
Terminal ileum
Caecum
What do carcinoid tumours secrete to cause carcinoid syndrome?
Vasoactive peptides such as 5-HT
Diagnosis of carcinoid tumours?
5-HIAA in 24 hour urine collection
Also somatostatin receptor scintigraphy, CT and serum chromogranin A
What do neuroendocrine tumours look like macroscopically?
Mass lesion with normal overlying GI mucosa, because neuroendocrine cells are located beneath the mucosal layer and invasion into this is a late feature
How would you manage a post op appendix that turned out to be a neuroendocrine tumour?
Ensure full resection
Discuss at MDT
If less than 2cm and margins not involved don’t need anything
If not may need right hemicolectomy
How would you manage small bowel carcinoid presenting with obstruction?
Small bowel resction and primary anastomosis
What is carcinoid syndrome?
Metastatic carcinoid tumour where vasoactive peptides enter systemic circulation to cause flushing, diarrhoea, bronchoconstriction, heart failure
How do you manage a carcinoid crisis?
Octreotide,lanreotide, somatostatin analogues which suppress hormone release
