Upper gastrointestinal pathology
Dr N Scott , Dr N Mapstone & Professor Neil A Shepherd Leeds Teaching Hospitals, Manchester Royal Infirmary & Gloucester & Cheltenham, UK
FRCPath Part 2 Surgical Course Gloucestershire Cellular Pathology Laboratory
About the exam • it is difficult (long, timed, lots to do) • it is not impossible • it is a general competency test • College wants you to pass, but only if they think you’re safe • appropriate preparation: do exam practices • write quickly enough and keep calm • nine minutes per case – ensure timing….. Gloucestershire Cellular Pathology Laboratory
About the exam
• a structured answer = a structured mind
• short summary of proffered data; nice description of the salient pathology; summary • each title: Information or Clinical Data, Histology, Summary underlined in red?
Gloucestershire Cellular Pathology Laboratory
You, the FRCPath exam and GI pathology • look at the information proffered – age, sex & clinical details • look at the slide – five seconds of holding up to the light
• context • if the case is ‘easy’ – give extra information to demonstrate your knowledge, look for a second (or third or more) diagnosis!! • if the case is difficult, give extra information to demonstrate how you would further investigate and what you would then do (second opinion, MDTM discussion, further clinical data, further biopsy, bigger (EMR/ER) biopsy, expert opinion)
Gloucestershire Cellular Pathology Laboratory
Case 1
Gloucestershire Cellular Pathology Laboratory
Clinical history 72F. Discrete erosion in upper oesophagus. Oesophageal biopsies.
Gloucestershire Cellular Pathology Laboratory
Case 1: Diagnosis Gastric heterotopia (so-called ''inlet patch'')
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5
3.0
Correct diagnosis with clinical correlation and relevance/prognosis
2.5
Good description, give differential diagnosis
2.0
Mediocre description, miss point of case (call it Barrett’s oesophagus, etc)
1.5
Don’t call it dysplasia (very unusual in gastric heterotopia)
1.0
Case 2
Gloucestershire Cellular Pathology Laboratory
Clinical history 18M. Oesophageal trachealisation. Oesophageal biopsies.
Gloucestershire Cellular Pathology Laboratory
Case 2: Diagnosis ‘In keeping with eosinophilic oesophagitis’
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5
3.0
Differential diagnosis. Comment on endoscopic findings. Knowledge of other tests
2.5
Suggest differential diagnosis.
2.0
Too dogmatic about diagnosis of EE….
1.5
Miss eosinophils.
1.0
Causes of intra-epithelial eosinophils in the oesophagus •
reflux (either acid or alkaline)
•
‘eosinophilic gastroenteritis’
•
‘eosinophilic oesophagitis’
•
drug/pill-induced oesophagitis
•
infections
•
achalasia
•
leiomyomatosis
•
inflammatory polyps including inflammatory fibroid polyp
•
tumours – secondary to obstructing tumours at OGJ Kaye et al, 2007
•
eradication therapy (PDT, laser, ABC, etc) and neo-adjuvant chemoradiotherapy (especially in muscularis propria)
Gloucestershire Cellular Pathology Laboratory
Eosinophilic oesophagitis •
male patients with history of allergy/atopy
•
children or adults
•
chronic dysphagia in 63%, often since childhood - food sticking common
•
no evidence of GORD on pH monitoring
•
may be peripheral blood eosinophilia
•
responds to steroids, allergen exclusion, anti-IL5
Gloucestershire Cellular Pathology Laboratory
Eosinophilic oesophagitis
Endoscopic appearance of corrugated or ringed oesophagus (trachealisation)
Linear furrows (feline oesophagus) observed on endoscopy
Gloucestershire Cellular Pathology Laboratory
Case 3
Gloucestershire Cellular Pathology Laboratory
Clinical history 42M. Island of Barrett's epithelium within lower oesophagus. Abnormal-appearing mucosa of gastro-oesophageal junction. Mild duodenitis within bulb.
Gloucestershire Cellular Pathology Laboratory
Case 3: Diagnosis
Corroborative of Barrett’s oesophagus & CMV oesophagitis
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5
3.0
Consider implications of CMV infection. Good description of difficulties of CLO vs OGJ mucosa
2.5
Suggest CMV. Competent interpretation of glandular appearances.
2.0
Miss CMV connection but describe abnormal cells.
1.5 1.0
Case 4
Gloucestershire Cellular Pathology Laboratory
Clinical history 70 year old male. Barrett's oesophagus. EMR of oesophagus.
Gloucestershire Cellular Pathology Laboratory
Gloucestershire Cellular Pathology Laboratory
Case 3
Case 4: Diagnosis High grade dysplasia +/- intramucosal adenocarcinoma in CLO
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5
3.0
Talk about management options. MDT discussion.
2.5
Good description. Correct diagnosis. Confirmed by second pathologist.
2.0
Incomplete description. Misgrade dysplasia.
1.5
Overcall as invasive adenocarcinoma.
1.0
Case 5
Gloucestershire Cellular Pathology Laboratory
Clinical history
55M. Oesophageal polyp.
Gloucestershire Cellular Pathology Laboratory
Gloucestershire Cellular Pathology Laboratory
Gloucestershire Cellular Pathology Laboratory
Case 5: Diagnosis
Granular cell tumour
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5
3.0
Clinical significance. Remove with EMR. Majority benign and small. Histogenesis and CD68 positive
2.5
Appropriate description and diagnosis
2.0
Miss diagnosis or lack conviction
1.5 1.0
Case 6
Gloucestershire Cellular Pathology Laboratory
Clinical history 50 year old female with EMR of oesophageal nodule.
Gloucestershire Cellular Pathology Laboratory
Gloucestershire Cellular Pathology Laboratory
Case 6: Diagnosis Smooth muscle tumour
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5
3.0
Less likely to be GIST at this site. Emphasise unpredictable nature but this one small and circumscribed and likely to have a favourable natural history
2.5
Suggest correct diagnosis and nomenclature. Suitable corroborative tests.
2.0
Poor description; calling it leiomyoma………
1.5 1.0
Case 7
Gloucestershire Cellular Pathology Laboratory
Clinical history 53F. Nausea, vomiting and weight loss.
Gloucestershire Cellular Pathology Laboratory
Call it
Case 7: Diagnosis Chemical/reactive gastritis, now known as reactive gastropathy. The presence of stainable iron indicates that this may be due to, at least in part, oral iron therapy.
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5
3.0
Spot iron. Description of iron erosion disease in oesophagus, stomach and duodenum. History of ‘reactive gastropathy’.
2.5
Good description. Give causes of reactive gastropathy.
2.0
Describe and yet miss significance findings
1.5
Call it dysplasia……
1.0
Case 8
Gloucestershire Cellular Pathology Laboratory
Clinical history 77M. Microcytic anaemia. Adenomatous pedunculated polyps in fundus. Gastritis anterior lower body. “Gastric fundal polyp“.
Gloucestershire Cellular Pathology Laboratory
Case 8: Diagnosis Xanthelasma or xanthoma of the stomach
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5
3.0
Description of the possible cause
2.5
Description and additional tests.
2.0
Describe but no diagnosis
1.5 1.0
Call it signet ring cell carcinoma or other neoplasm…..
Case 9
Gloucestershire Cellular Pathology Laboratory
Clinical history 77F. Gastric antral biopsy.
Gloucestershire Cellular Pathology Laboratory
Case 9: Diagnosis
Gastric antral vascular ectasia (GAVE)
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5
3.0
Full CPC discussion of GAVE.
2.5
Reactive gastropathy and suggest additional diagnosis.
2.0
Sound description only.
1.5
Call it dysplasia….
1.0
Case 10
Gloucestershire Cellular Pathology Laboratory
Clinical history 69M. Anaemia. Gastric polyp. Gastric biopsies.
Gloucestershire Cellular Pathology Laboratory
Gloucestershire Cellular Pathology Laboratory
Case 10: Diagnosis High grade lymphoma. If you want to be really clever: DLBCL; centroblastic variant with an activated phenotype (WHO)
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5
3.0
Good suggestions for immunophenotyping and molecular testing. Good description of types of primary gastric lymphoma and their management.
2.5
Lymphoma with reasonable adjunctive tests. Favour DLBCL.
2.0
Suggest differential diagnosis but lack direction.
1.5
Dogmatic wrong diagnosis (eg benign; carcinoma, etc).
1.0
Case 11
Gloucestershire Cellular Pathology Laboratory
Clinical history 48F. Wedge resection of gastric tumour.
Gloucestershire Cellular Pathology Laboratory
Case 11: Diagnosis Gastrointestinal stromal tumour (GIST), epithelioid type
Gloucestershire Cellular Pathology Laboratory
GIST Immunohistochemistry • c – kit ( CD117 ) • DOG – 1 • CD34 • SMA • Desmin • S100
Mutation Testing • c - kit mutation • PDGFR alpha • BRAF • SDH deficiency
Gloucestershire Cellular Pathology Laboratory
SDH deficient “Wild-Type” GISTs • • • • • • • • • • •
3 – 5 % of all GISTs Commoner in younger age groups ie. children and young adults < 30 May be part of Carneys Triad or CSS Located in Stomach Often multicentric, multinodular or plexiform Epithelioid or occasionally mixed morphology Metastatic to lymph nodes in 10 – 30 % cases Increased risk of distant metastasis Behaviour less easy to predict with AFIP /NIH consensus criteria Indolent behaviour with prolonged survival Less responsive to Imatinib
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5
3.0
Consideration of molecular aspects and treatment.
2.5
Solid description. Sensible immunotesting. Good grasp of dataset content.
2.0
Basic description, wide differential diagnosis.
1.5
Dogmatic wrong tumour diagnosis
1.0
No diagnostic idea…..
Case 12
Gloucestershire Cellular Pathology Laboratory
Clinical history 28F. Strong family history of gastric cancer.
Gloucestershire Cellular Pathology Laboratory
Case 12: Diagnosis Signet ring cell adenocarcinoma
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5
3.0
Discussion about familial gastric cancer, e-cadherin mutation/CDH1, genetic screening and prophylactic treatment.
2.5
Spot cells and suggest additional tests to confirm.
2.0
Spot cells. Unsure about diagnosis.
1.5 1.0
Xanthelasma/xanthoma ……
Case 13
Gloucestershire Cellular Pathology Laboratory
Clinical history 42M. OGD revealed mass with bleeding vessel in antrum.
Gloucestershire Cellular Pathology Laboratory
Gloucestershire Cellular Pathology Laboratory
Case 13: Diagnosis Glomus tumour
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5
3.0
Correct diagnosis. Good immunophenotyping suggestions (ASMA, bcl-2, hcaldesmon but collagen IV best). Dissertation on glomus tumours in the gut.
2.5
Good differential diagnosis and supplementary immunotests. Should consider neuro-endocrine tumour which has a similar immunophenotype (synaptophysin positive).
2.0
Description only with poor differential diagnosis.
1.5
Dogmatic diagnosis of GIST (very different management).
1.0
Dogmatic diagnoses of tumours like adenocarcinoma.
Case 14
Gloucestershire Cellular Pathology Laboratory
Clinical history 19F. Normal upper GI tract at endoscopy.
Gloucestershire Cellular Pathology Laboratory
Case 14: Diagnosis Increased intra-epithelial lymphocytes: ‘Lymphocytic duodenosis’ ‘Intra-epithelial lymphocytosis with a normal villous architecture’
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5
3.0
Give differential diagnosis and causes (lots). 25% have coeliac disease. Correlate with serology and HLA phenotype.
2.5
Spot abnormality and possible significance.
2.0
Describe but no interpretation.
1.5
Call it normal…..
1.0
Case 15
Gloucestershire Cellular Pathology Laboratory
Clinical history
31F. Duodenal biopsies.
Gloucestershire Cellular Pathology Laboratory
Case 15: Diagnosis Giardiasis
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5 3.0
95% of biopsies with giardiasis are otherwise entirely normal. Can see them in stomach and colon. Mention travel. Mention lots of plasma cells. Suggest other infections if immunosuppressed.
2.5
Description and spot organisms.
2.0 1.5 1.0
Miss giardia.
Case 16
Gloucestershire Cellular Pathology Laboratory
Clinical history
35F. Anaemia.
Gloucestershire Cellular Pathology Laboratory
Case 16: Diagnosis ‘In keeping with untreated coeliac disease’
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5
3.0
Talk about Marsh type. Correlate with serology. HLA DQ2 and 8, etc
2.5
Good description. ‘Compatible with untreated coeliac disease’.
2.0
Over-confident (dogmatic coeliac disease).
1.5
Poor description and no summary.
1.0
Case 17
Gloucestershire Cellular Pathology Laboratory
Clinical history 67M. Duodenitis and ? inflammatory polyps.
Gloucestershire Cellular Pathology Laboratory
Case 17: Diagnosis Gastric heterotopia.
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5
3.0
‘Gastric heterotopia is the commonest cause of polypoid nodulation in the proximal duodenum’.
2.5
Describe well and suggest diagnosis
2.0
Suggest wrong diagnosis (eg gastric metaplasia) but recognise tissues.
1.5 1.0
Case 18
Gloucestershire Cellular Pathology Laboratory
Clinical history 46 year old male. 20 mm jejunal polyp.
Gloucestershire Cellular Pathology Laboratory
Gloucestershire Cellular Pathology Laboratory
Gloucestershire Cellular Pathology Laboratory
Case 18: Diagnosis Peutz-Jeghers polyp with Epithelial Misplacement.
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5
3.0
Talk about PJ syndrome, AD, polyps & pigment: cancer risk
2.5
Good description with good differential diagnosis. Suggest correct diagnosis.
2.0
Description only.
1.5
Wrong diagnosis such as adenoma.
1.0
Mistaking epithelial misplacement for adenocarcinoma.
Case 19
Gloucestershire Cellular Pathology Laboratory
Clinical history 64M. Duodenal adenocarcinoma. Whipple’s resection.
Gloucestershire Cellular Pathology Laboratory
Case 19: Diagnosis Seminoma
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5
3.0
Suggest correct diagnosis and likely secondary.
2.5
Good description with reasonable differential diagnosis and further tests.
2.0
Lacks direction and logical approach.
1.5
Benign primary tumour.
1.0
Case 20
Gloucestershire Cellular Pathology Laboratory
Clinical history 65M. Pancreatic mass. Whipple’s resection.
Gloucestershire Cellular Pathology Laboratory
Case 20: Diagnosis Clear cell carcinoma, consistent with metastasis from a primary renal (clear) cell carcinoma.
Gloucestershire Cellular Pathology Laboratory
Marking scheme 3.5
3.0
Ask about history, imaging, etc.
2.5
Good approach with good differential diagnosis.
2.0
Differential diagnosis with less confidence.
1.5 1.0
Benign diagnosis, perhaps primary tumour.
Case 21. CLINICAL HISTORY 76 year old male – lesion in fundus of stomach.
Gloucestershire Cellular Pathology Laboratory
Gloucestershire Cellular Pathology Laboratory
Gloucestershire Cellular Pathology Laboratory
Gloucestershire Cellular Pathology Laboratory
Case 21 . Diagnosis Kaposi Sarcoma – HIV positive.
Gloucestershire Cellular Pathology Laboratory
Case 22. 64 year old female – persistent gastric ulcer despite PPI.
Gloucestershire Cellular Pathology Laboratory
Gloucestershire Cellular Pathology Laboratory
Gloucestershire Cellular Pathology Laboratory
Gloucestershire Cellular Pathology Laboratory
Case 22 Diagnosis Erosive Gastritis with reactive epithelial atypia
Gloucestershire Cellular Pathology Laboratory
Reactive Atypia versus Epithelial Dysplasia • Context : Acute inflammation and Ulceration • Degree of cytological & architectural atypia ie. range of nuclear size, pleomorphism, nucleoli, atypical mitotic figures • “monotonous” or “monomorphic” atypia versus “pleomorphic” atypia ( are all cells atypical in the same way ? ) • Maturation towards mucosal surface ( but remember “basal crypt dysplasia” ) • Spectrum of atypia ie. abrupt transition from atypical to reactive or normal epithelium versus gradual merging of atypical cells with reactive epithelium at edges • Immunohistochemistry : p53, ki67 etc. • Second Opinion & “indefinite for dysplasia” ( re-biopsy ) Gloucestershire Cellular Pathology Laboratory
Case 23 57 year old female – thickened gastric wall – gastric biopsy.
Gloucestershire Cellular Pathology Laboratory
Case 23 Diagnosis Metastatic Lobular Carcinoma of Breast ( ER positive )
Gloucestershire Cellular Pathology Laboratory
Gloucestershire Cellular Pathology Laboratory
Gloucestershire Cellular Pathology Laboratory
Any comments or questions?
Gloucestershire Cellular Pathology Laboratory