Gastrointestinal, Endocrine, Bone, Renal, and Liver Diseases-1-9 PDF

Pathology Revision 12 12 113 PATHOLOGY REVISION 12 ----- Active space ----- Gastrointestinal System 00:00:29 Helicobacter pylori : Ro...

Pathology Revision 12 12 113 PATHOLOGY REVISION 12 ----- Active space ----- Gastrointestinal System 00:00:29 Helicobacter pylori : Rod shaped bacillus. Pathogenic factor : Cag A & Vac A. Diagnosed through antral biopsy. On biopsy : Floating over mucus layer as they cannot penetrate it. Intra epithelial neutrophils. Subepithelial plasma cells. Special stain : Warthin starry silver stain (Bacilli stain black). Diseases caused by H. pylori : Chronic gastritis. Gastric adenocarcinoma. Marginal zone lymphoma (Maltoma). Gastric adenocarcinoma (Lauren’s classification) : a. Intestinal b. Diffuse Environmental Familial Gastric atrophy, intestinal metaplasia Blood type A Men > women Women > men Increasing incidence with age Younger age group Poorly differentiated. Gland formation Signet ring cells. Hematogenous spread Transmural/lymphatic spread Microsatellite instability APC gene Decreased E-cadherin p53, p16 inactivation Pathology Revision v1.0 Marrow 6.5 2023  114 12 Pathology ----- Active space ----- Cancers related to CDH1 gene mutation & loss of E-cadherin mutation : Diffuse gastric adenocarcinoma. Lobular carcinoma breast. When gastric adenocarcinoma metastasizes to ovary → Krukenburg’s tumor. On gross examination : Linitis plastica (Diffuse type) : Leather bottle appearance On histopathological examination (HPE) : Intestinal type Diffuse type : Signet ring cells with intracellular mucin Gastrointestinal Stromal Tumor (GIST) : M/c mesenchymal tumor of stomach. Pathology : c-kit mutation. Markers : CD 117. DOG 1 : Most specific marker. CD 34. Spindle & epithelioid cells seen. Pathology Revision v1.0 Marrow 6.5 2023  Pathology Revision 12 12 115 Inflammatory bowel disease (IBD) : ----- Active space ----- Feature Crohn’s disease Ulcerative Colitis Starts from colon, progresses to Site Ileum, caecum rectum HLA HLA DR1 HLA DR2 Risk factor : Causative Protective Smoking Cell CD4 TH1 CD4 TH2 Skip lesions. Pseudopolyps & mucosal Cobblestone bridges present. appearance. Toxic megacolon. Gross Transmural. Submucosal. features Pseudopolyps & mucosal bridges absent. Thick rubbery wall. Microscopy Granuloma present Granuloma absent Cryptitis/ + +++ Crypt abscess + More prominent Ulcer (Deep knife like ulcers). (Superficial broad based ulcers). Strictures, fissures, Complications Less common fistulas, sinuses. Colon cancer Equal risk of colon cancer Radiology String sign of Kantor Lead pipe/hose pipe appearance Anti saccharomyces Antibodies p-ANCA cerevisae Note : Most important cell in granuloma : Epithelioid cell (activated macrophage). Most important cytokine : IFN γ/IL-12. Associated with CD4 TH 1. p-ANCA positive vasculitis : a. Microscopic polyangiitis. b. Churg Strauss disease. Crypt abscess Early onset IBD : Mutation in IL-1 or IL-10 receptor. Pathology Revision v1.0 Marrow 6.5 2023  116 12 Pathology ----- Active space ----- Celiac disease : a.k.a Gluten sensitive enteropathy. Barley, Rye, Oats, Wheat (BROW) cannot be included in diet. Site of biopsy : Duodenal biopsy. MARSH score is used for diagnosis. Histopathological features : Villous atrophy. Crypt hyperplasia. Intraepithelial lymphocytes. Antibodies : Anti gliadin antibody. Anti Tissue Trans Glutaminase (TTG) antibody. Anti endomysial antibody. Increased risk of dermatitis herpetiformis. Enteropathy associated T-cell lymphoma can be seen. Whipple’s disease : Giardiasis : Caused by Tropheryma whipplei. HPE : Foamy histiocytes Containing PAS positive organisms in lamina propria. Giardiasis : Pear shaped organism over mucus layer PAS positive organisms Pathology Revision v1.0 Marrow 6.5 2023  Pathology Revision 12 12 117 Microvillus inclusion disease (A.k.a Davidson disease) : ----- Active space ----- AR, MYO5B gene (vesicular transport of water & ions). Clinical feature : Diarrhea. Biopsy : Tiny eosinophilic inclusions at the apex. IHC : villin, CD 10. EM : Inclusion with microvilli. Peutz Jheger’s syndrome : Eosinophilic inclusions at the apex AD, LKB1/STK11 gene mutation. Multiple hamartomatous polyps. Perioral melanosis/mucosal hyperpigmentation. Increased risk of pancreatic, breast, thyroid & colon cancer. HPE : Arborizing pattern of smooth muscle mixed with lamina propria → Christmas tree appearance. Christmas tree appearance Perioral melanosis Polyps : 1. Tubular polyp 2. Villous polyp 3. Tubulovillous polyp Most malignant : Villous polyp & sessile polyps. Adenocarcinoma colon : Tumor markers : CEA, CA-19-9. Adenoma-carcinoma sequence : (Mneumonic : AK-53) APC → KRAS → p53 → Telomerase. Pathology Revision v1.0 Marrow 6.5 2023  118 12 Pathology ----- Active space ----- HNPCC : Mismatch repair pathway : Mutation in mismatch repair genes (MLH1, MSH2, MSH6, PMS1, PMS2) → Senile serrated adenoma (Microsatellite instability) → Carcinoma. Neuroendocrine tumours 00:29:04 Pheochromocytoma : HPE : Zell ballen pattern seen. Cells with salt and pepper chromatin seen. IHC : NSE, synaptophysin, chromogranin +. Other tumors with similar IHC profile : Carcinoid syndrome. Medullary carcinoma thyroid. Pheochromocytoma Small cell carcinoma lung. Paraganglionoma. Polycythemia paraganglioma syndrome : Genetic defect in EPAS 1 →increases HIF 2a. Can lead to phaeochromocytoma, paraganglioma & polycythemia. Familial syndromes associated with pheochromocytoma : Syndrome Gene Other features Multiple endocrine neoplasia Medullary thyroid carcinoma RET type 2A (MEN-2A) Parathyroid hyperplasia Medullary thyroid carcinoma Marfanoid habitus MEN-2B RET Mucocutaneous Ganglioneuroma Neurofibromatosis Neurofibromatosis, type 1 NF1 Café-au-lait spots (NF1) Optic nerve glioma Renal cell carcinoma Hemangioblastoma Von Hippel-Lindau(VHL) VHL Pancreatic endocrine neoplasm Paraganglioma (uncommon) Pathology Revision v1.0 Marrow 6.5 2023  Pathology Revision 12 12 119 Neuroblastoma : ----- Active space ----- C/f : Child with abdominal tumor. Gene : N-MYC mutation. HPE : Small round blue cell tumor. Cells arranged in Homer Wright rosettes. Note : Flexner-Wintersteiner rosettes → Retinoblastoma. Neuroblastoma Thyroid gland 00:32:25 Normal HPE : Thyroid follicles are filled with colloid & lined by cuboidal epithelium. Hashimoto’s thyroiditis : Normal thyroid gland HLA associated autoimmune disease. On HPE : Lymphoid follicles/aggregates → Increased risk of lymphoma. Hurthle cells seen : Cells with abundant eosinophilic granular cytoplasm (d/t excess of mitochondria). Can develop papillary carcinoma of thyroid. Hashimoto’s thyroiditis Criteria for adequacy in thyroid FNAC : At least 6 groups of at least 10 follicular cells, preferably on a single slide. 3 exceptions : 1. Abundant inflammatory cells seen → Thyroiditis. 2. Abundant thick colloid seen → Benign colloid nodule (present as the pres- ence of abundant colloid reliably identifies most benign processes). 3. Atypical/malignant cells seen → Atypia or malignancy. Pathology Revision v1.0 Marrow 6.5 2023  120 12 Pathology ----- Active space ----- Overview of thyroid malignancies : Feature Papillary Follicular Medullary Anaplastic Incidence Most common Least common H/o Radiation, Iodine Thyroglossal cyst, deficiency, Risk factor Hashimotos Multinodular goitre, thyroiditis. long standing goitre. Parafollicular Origin Follicular cells. Follicular cells Follicular cells cells (C cells). Metastasis Lymphatic. Hematogenous Both Both K–RAS Genetics BRAF, RET-PTC. RET, MEN II. p53 PI3K Prognosis Best Worst Papillary, HPE Orphan Anne nuclei, Follicles Amyloid Psamomma bodies. Papillary carcinoma thyroid : On HPE : Papillae. Follicles lined with optically clear nuclei (Orphan Annie nuclei). Coffee bean nuclei. Nuclear pseudo inclusions. Psamomma bodies. Papillae Psamomma bodies Orphan annie nuclei Coffee bean nuclei Follicular variant of papillary carcinoma thyroid : Cells arranged in follicles but nuclear features are that of papillary cancer. Pathology Revision v1.0 Marrow 6.5 2023  Pathology Revision 12 12 121 Follicular carcinoma : ----- Active space ----- Cannot be diagnosed by FNAC as FNAC cannot detect capsular & vascular invasion of tumor. Medullary carcinoma thyroid : Follicular carcinoma Gene : RET on chromosome 10. On HPE : Spindle shaped cells & amyloid present (ACal amyloid). Apple green birefringence on polarized microscopy. Tumor markers : Calcitonin. Medullary carcinoma Bone and soft tissue tumors 00:42:22 Overview of bone tumors : Tumor Age Location Genetics Microscopy and gross X-ray : Codman’s triangle Bimodal Metaphysis Gross : Large, tan distribution, of long bones, Osteosaroma RB gene white gritty masses. 10–20 yrs & M/c site : Distal Microscopy : New bone elderly femur formation, lace like pattern. Osteochondroma Metaphysis of EXT1, EXT2 gene Gross : Mushroom (exostosis) long bones defect shaped protrusion Giant cell tumor F > M, Multinucleated Lower end of (osteo- 20 to 50 osteoclast type giant femur clastoma) years cells Axial skeleton, Malignant hyaline, M>F, 40 Chr. 1p Chondrosarcoma pelvis, ribs, myxoid cartilage, years rearrangement sternum pleomorphic cells Small, round, blue cells Diaphysis of with rosettes Ewings sarcoma