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- 2. Overview Very Important • Fundamentals of Histopathology • Liver • Diseases of the Gallbladder and Pancreas • Upper GI Disease • Lower GI Disease • Connective Tissue Disease Quite Important • Breast Pathology • Endocrine Disease • Gynaecological Pathology • Renal Disease • Skin Pathology • Urological Pathology • Respiratory Pathology Worth Learning • Bone Disease • Vascular and Cardiovascular Pathology • Cytopathology • Neuro-oncology • Cerebrovascular Disease • Neurodegeneration
- 3. Overview Very Important • Fundamentals of Histopathology • Liver • Diseases of the Gallbladder and Pancreas • Upper GI Disease • Lower GI Disease • Connective Tissue Disease Quite Important • Breast Pathology • Endocrine Disease • Gynaecological Pathology • Renal Disease • Skin Pathology • Urological Pathology • Respiratory Pathology Worth Learning • Bone Disease • Vascular and Cardiovascular Pathology • Cytopathology • Neuro-oncology • Cerebrovascular Disease • Neurodegeneration
- 5. Basics Cell Appearance Significance Neutrophil Multilobed nuclei with granules Acute inflammation Lymphocyte Little cytoplasm with big nucleus Chronic inflammation, lymphoma Eosinophil Bi-lobed nucleus with red granules Allergic, parasites, Hodgkin lymphoma Mast Cell Large and heavily granular Allergy (e.g. urticaria) Macrophage Large with lots of cytoplasm Late acute inflammation, chronic inflammation (inc granuloma)
- 6. Basics Type of Cancer Histological Features Sites Squamous Cell Carcinoma Keratin production Intercellular bridges Lung, skin, oesophagus Adenocarcinoma Mucin production Glands Lung, breast, colon, pancreas, cervix, stomach Transitional Cell Carcinoma - Bladder, ureter, urethra Sarcoma Arises from mesenchymal cells Bone, cartilage, fat, vascular
- 7. Basics Stains Chemical reaction between stain and tissue Antibodies bind to specific antigen Examples H&E: everyday stain Prussian Blue: iron Congo Red: amyloid Examples Cytokeratin antibody: epithelial cells CD45: lymphoid marker Immunohistochemical Histochemical
- 8. Upper & Lower GI Pathology
- 9. Question 1 A 45-year-old man presents to his GP with a 3-month history of worsening dysphagia. He is now unable to comfortably swallow solid foods. He has never suffered from heartburn and takes no regular medications. He has a 20 pack year smoking history and drinks in moderation. A barium swallow identifies an apple core lesion in the middle third of the oesophagus. This is followed by an OGD and biopsy which reveals abnormal keratinised cells with intercellular bridges that have invaded the basement membrane. What is the most likely diagnosis? A Barrett’s oesophagus B Transitional cell carcinoma C Oesophageal lymphoma D Adenocarcinoma E Squamous cell carcinoma
- 10. Question 2 A 16-year-old girl has suffered from diarrhoea for the past 6 months. She describes the diarrhoea as foul-smelling and has lost 5 kg over this time period. An endoscopy and biopsy reveals increased intraepithelial lymphocytes with a 2:1 villous to crypt ratio. What is the most likely diagnosis? A Lymphocytic duodenitis B Coeliac disease C Crohn’s disease D Duodenal MALToma E Linitis plastica
- 11. Oesophagus and Stomach Histology Oesophagus • Contains submucosal glands • Transitions from squamous to columnar epithelium at the z-line Body and Fundus • Columnar lining • Produce acid and intrinsic factor Pylorus and Antrum • Columnar lining • Produce gastrin Duodenum • Columnar epithelium with goblet cells • 2:1 villous: crypt ratio
- 12. Oesophageal Cancer Adenocarcinoma Squamous Cell Carcinoma Associated with Barrett’s oesophagus Associated with GORD Lower 1/3 of oesophagus Associated with smoking and alcohol Lower 2/3 of oesophagus Histology: keratinised cells with intercellular bridges Histology: glandular epithelium
- 13. Chronic Gastritis Histology Abundance of lymphocytes Gastritis, Ulcers and Cancer Causes of Gastritis • Autoimmune • H. pylori • Chemical (alcohol, NSAIDs) Mucosa-Associated Lymphoid Tissue • Chronic gastritis induces lymphoid tissue in the stomach • Strongly associated with H. pylori • Increased risk of lymphoma
- 14. Gastric Ulcers and Cancer Gastric Ulcer Definition: the depth of loss of tissue goes beyond the mucosa (i.e. into the submucosa) Chronic ulcers are characterised by scarring and fibrosis IMPORTANT: ALL ulcers should be biopsied to exclude malignancy Gastric Adenocarcinoma Intestinal: well-differentiated, mucin-containing glands Diffuse: poorly differentiated, composed of single cells, no gland formation Linitis plastica Signet ring cell carcinoma Types Niche Gastric Cancer (5%) Squamous cell carcinoma Lymphoma Gastrointestinal stromal tumour Neuroendocrine tumour
- 15. Malabsorption due to Partial Villous Atrophy Villous atrophy Crypt hyperplasia Increased intraepithelial lymphocytes
- 16. Malabsorption due to Partial Villous Atrophy Lymphocytic Duodenitis: inflammatory changes without architectural changes i.e. increased intraepithelial lymphocytes but no villous atrophy/crypt hyperplasia Coeliac Disease: inflammatory and architectural changes Many will go on to develop coeliac disease Investigations Antibodies: tissue transglutaminase and endomysial Duodenal Biopsy: showing villous atrophy whilst ingesting gluten Tropical Sprue: form of malabsorption with similar histology to coeliac disease
- 17. Lower GI Pathology Colitis Congenital • Hirschsprung Disease absence of myenteric plexus ganglion cells Px: constipation, abdo distension, vomiting Ix: full thickness rectal biopsy Rx: resection of affected section (anorectal pull- through) Diverticular Disease • Outpouchings • Low-fibre diet • Complications: pain, diverticulitis, bleeding Acute Pseudomembranous Chronic Infection, drugs, chemo/radio Crohn’s, UC and TB
- 18. Pseudomembranous Colitis Px: explosive watery diarrhoea, usually after a course of antibiotics Ix: C. difficile stool toxin assay Rx: Metronidazole Vancomycin Fidaxomicin Faecal Transplant
- 19. Ischaemic Colitis Definition: inflammation and injury of the large intestine caused by an inadequate blood supply Watershed: area between the supply of the SMA and IMA Causes Arterial (e.g. thrombus) Venous (e.g. hypercoagulable) Small vessel disease (e.g. DM) Low flow (e.g. shock) Obstruction (e.g. hernia)
- 20. Polyps and Adenomas Polyp Neoplastic Non-Neoplastic Tubular adenoma Tubulovillous adenoma Villous adenoma Hyperplastic Inflammatory (pseudopolyp) Hamartomatous FAP Autosomal dominant APC tumour suppressor gene Large numbers of polyps, pretty much everyone gets cancer Gardner Syndrome Same features as FAP Extra-intestinal manifestations: Osteomas Desmoid tumours Dental caries Supernumerary teeth HNPCC Autosomal dominant DNA mismatch repair genes High risk of cancer, no polyps
- 21. Answer 1 A 45-year-old man presents to his GP with a 3-month history of worsening dysphagia. He is now unable to comfortably swallow solid foods. He has never suffered from heartburn and takes no regular medications. He has a 20 pack year smoking history and drinks in moderation. A barium swallow identifies an apple core lesion in the middle third of the oesophagus. This is followed by an OGD and biopsy which reveals abnormal keratinised cells with intercellular bridges that have invaded the basement membrane. What is the most likely diagnosis? A Barrett’s oesophagus B Transitional cell carcinoma C Oesophageal lymphoma D Adenocarcinoma E Squamous cell carcinoma
- 22. Answer 2 A 16-year-old girl has suffered from diarrhoea for the past 6 months. She describes the diarrhoea as foul-smelling and has lost 5 kg over this time period. An endoscopy and biopsy reveals increased intraepithelial lymphocytes with a 2:1 villous to crypt ratio. What is the most likely diagnosis? A Lymphocytic duodenitis B Coeliac disease C Crohn’s disease D Duodenal MALToma E Linitis plastica
- 24. Question 5 A 36-year-old woman who was identified as having an abnormal cervical smear, underwent a cervical excision biopsy which reveals cervical glandular intraepithelial neoplasia. Which type of cancer would this have progressed to if left untreated? A Adenocarcinoma B Krukenberg tumour C Squamous cell carcinoma D Transitional cell carcinoma E Serous carcinoma
- 25. Cervical Cancer Risk Factors • HPV 16 and 18 • Multiple sexual partners • Smoking • Immunosuppression Tumorigenesis HPV 16 and 18 encode two proteins that inactivate tumour suppressor genes E6 – p53 E7 – retinoblastoma Squamous Columnar Transformation
- 26. Cervical Cancer Cervical Intraepithelial Neoplasia (CIN) Dysplastic changes within the epithelium with an intact basement membrane. Squamous cell carcinoma Progresses to Histological classification CGIN: cervical glandular intraepithelial neoplasia progresses to adenocarcinoma (20%)
- 27. Endometrial Cancer Risk Factors • OESTROGEN • Nulliparity • Obesity • Diabetes mellitus • COCP • Tamoxifen • HRT • Early menarche • Late menopause Type 1 (85%) Type 2 (15%) Endometrioid Mucinous Secretory Types Serous Clear cell Types Younger patients Oestrogen-dependent Associated with atypical endometrial hyperplasia Usually low grade Features Older patients Less oestrogen-dependent Arises from atrophic endometrium Higher grade, deeper invasion Features
- 28. Gestational Trophoblastic Disease (Molar Pregnancy) Gestational Trophoblastic Disease: a spectrum of tumours and tumour-like conditions characterised by proliferation of pregnancy-associated trophoblastic tissue. Complete Empty 23X 23X OR 23X 46XX Partial 23X 23X OR 46XY 23X 69XXY
- 29. Ovarian Tumours Ovary Germ Cells Stroma Epithelium Type 1 Type 2 Low-grade serous Endometrioid Mucinous Clear cell Mostly serous Granulosa cell tumour Fibroma Thecoma Sertoli-Leydig cell Dysgerminoma Choriocarcinoma Teratoma Endodermal sinus tumour
- 30. Epithelial Ovarian Tumours Type Features Serous MOST COMMON Arise from bland epithelium May be benign, borderline or malignant Mucinous Mucin-secreting epithelium Endometrioid 10-20% associated with endometriosis Co-existence of endometrial carcinoma is common Better prognosis than mucinous/serous Clear cell STRONG association with endometriosis
- 31. Sex Cord Stromal Tumours Type Features Fibroma Benign No endocrine production Granulosa cell tumour Variable behaviour May produce oestrogen Thecoma Benign May produce oestrogen Rarely produces androgens Sertoli-Leydig cell tumour Variable behaviour May be androgenic
- 32. Germ Cell Tumours and Secondary Tumours Secondary Tumours Krukenberg Tumour • Bilateral metastases • Mucin-producing signet- ring cells • Usually from gastric or breast cancer Metastatic Colorectal Cancer
- 33. Question 5 A 36-year-old woman who was identified as having an abnormal cervical smear, underwent a cervical excision biopsy which reveals cervical glandular intraepithelial neoplasia. Which type of cancer would this have progressed to if left untreated? A Adenocarcinoma B Krukenberg tumour C Squamous cell carcinoma D Transitional cell carcinoma E Serous carcinoma
- 34. Skin Pathology
- 35. Question 6 A 55-year-old woman has been referred to the dermatology outpatient clinic by her GP after developing multiple blisters on her face. On examination, the blisters are flaccid and extend across her face and shoulders. A biopsy is taken, and immunofluorescence analysis reveals of IgG deposition across the middle of the epidermis. What is the most likely diagnosis? A Pemphigus Vulgaris B Pemphigus Foliaceus C Bullous Pemphigoid D Erythroderma E Epidermolysis Bullosa
- 36. What they show you.
- 37. What it really is. Epidermis Dermis Subcutaneous Fat
- 38. Bullous Pemphigoid Elderly Flexor Surfaces Tense Bullae IgG and C3 attack of basement membrane Eosinophil recruitment Damage anchoring proteins Clinical Pathology
- 39. Pemphigus Vulgaris Flaccid Blisters IgG damage within keratinocyte layer (acantholysis) Clinical Pathology
- 40. Pemphigus Foliaceus Very fragile blisters IgG damage to stratum corneum Clinical Pathology
- 42. Answer 6 A 55-year-old woman has been referred to the dermatology outpatient clinic by her GP after developing multiple blisters on her face. On examination, the blisters are flaccid and extend across her face and shoulders. A biopsy is taken, and immunofluorescence analysis reveals of IgG deposition across the middle of the epidermis. What is the most likely diagnosis? A Pemphigus Vulgaris B Pemphigus Foliaceus C Bullous Pemphigoid D Erythroderma E Epidermolysis Bullosa
- 44. Question 1 A 35-year-old female patient has developed right upper quadrant pain with a fever over the past week. On examination, she is visibly jaundiced with excoriation marks across her arms and torso and hepatomegaly is noted. She has a past medical history of ulcerative colitis and asthma. A biopsy of her liver is taken. What histological features would you expect to see? A Regenerating hepatocytes limited by a fibrous cuff B Bile duct obliterations with surrounding granulomas C Bile duct fibrosis D Ballooning with Mallory Denck bodies E Accumulation of iron-rich macrophages
- 45. Answer 1 A 35-year-old female patient has developed right upper quadrant pain with a fever over the past week. On examination, she is visibly jaundiced with excoriation marks across her arms and torso and hepatomegaly is noted. She has a past medical history of ulcerative colitis and asthma. A biopsy of her liver is taken. What histological features would you expect to see? A Regenerating hepatocytes limited by a fibrous cuff B Bile duct obliterations with surrounding granulomas C Bile duct fibrosis D Ballooning with Mallory Denck bodies E Accumulation of iron-rich macrophages
- 46. Question 2 A 53-year-old woman has recently undergone a cholecystectomy after a long-history of biliary cholic and chronic cholecystitis. Which of the following features would you expect to see on histological analysis of the gallbladder? A Predominance of lymphocytes and macrophages with Rokitansky-Aschoff sinuses B Predominance of neutrophils with fibrosis C Glandular to squamous metaplasia D Cyst formation E Presence of signet ring cells
- 47. Answer 2 A 53-year-old woman has recently undergone a cholecystectomy after a long-history of biliary cholic and chronic cholecystitis. Which of the following features would you expect to see on histological analysis of the gallbladder? A Predominance of lymphocytes and macrophages with Rokitansky-Aschoff sinuses B Predominance of neutrophils with fibrosis C Glandular to squamous metaplasia D Cyst formation E Presence of signet ring cells
- 48. Question 6 A 57-year-old woman was identified as having a suspicious lesion on mammography. A biopsy is taken which identifies a central zone of scarring surrounded by proliferating glandular tissue. What is the most likely diagnosis? A Fibroadenoma B Intraductal papilloma C Phyllodes tumour D Invasive ductal carcinoma E Radial scar
- 49. Question 6 A 57-year-old woman was identified as having a suspicious lesion on mammography. A biopsy is taken which identifies a central zone of scarring surrounded by proliferating glandular tissue. What is the most likely diagnosis? A Fibroadenoma B Intraductal papilloma C Phyllodes tumour D Invasive ductal carcinoma E Radial scar