Non infective & infective granulomas

1. Non infective & infective granulomas Soheir Mahfouz

2. SARCOIDOSIS Like TB granuloma without the caseation Chapter 7 p102-103

3. Sarcoidosis • Definition A non infective granuloma characterized by tubercle –like lesions • Aetiology ? Sarcoidosis is not contagious.

4. Pathology of sarcoidosis • Multisystem affection by multiple lesions • Skin lesions • LNs • Spleen • Lung • Bones • eyes

5. Microscopic picture sarcoidosis • Tubercles with no caseation surrounded by FT • Epitheloid cells-lymphocytes and giant cells • 2 types of GC + crystalline inclusions • asteroid bodies • Schauman bodies

6. How is sarcoidosis diagnosed? There is no single way to diagnose sarcoidosis, since all the symptoms and laboratory results can occur in other diseases. The main tools your doctor will use to diagnose sarcoidosis include: • Chest x-rays--to look for cloudiness (pulmonary infiltrates) or swollen lymph glands (lymphadenopathy) • CT scan--to provide an even more detailed look at the lungs and lymph glands than provided by a chest x-ray • Pulmonary function (breathing) tests--to measure how well the lungs are working • Bronchoscopy-The purpose of this test is to inspect the bronchial tubes and to extract a biopsy (a small tissue sample) to look for granulomas and to obtain material to rule out infection. • Keviem test

7. What can happen as the disease progresses?Course of the disease • In many people with sarcoidosis, the disease appears briefly and then disappears without the person even knowing they have the disease. • Twenty to 30 percent of people have some permanent lung damage. • For 10 to 15 percent, sarcoidosis is a chronic condition resulting in the deterioration of the affected organ. • Sarcoidosis can be fatal in 5 to 10 percent of patients.

8. LEPROSYChapter 7 p103-104

9. LEPROSY DEFINITION: Infective granuloma caused by Mycobacterium leprae ETIOLOGY & PATHOGENESIS Organism: Mycobacterium leprae Acid-alcohol fast bacillus Source: prolonged close contact Site: skin and nerves

10. 1)Tuberculoid (mild) Maculo-anaesthetic leprosy Good immunity 2)Lepromatous (severe) Nodular leprosy—leonine facies Low immunity MANIFESTATIONS ACCORDING TO TYPE

11. 2)Lepromatous (severe) Nodules or erythematous macules + nerve Inflammation (Thick, cord-like) 1)Tuberculoid (mild) Macules (flat hypopigmented patches) + nerve Inflammation (thickening) GROSS

12. 2)Lepromatous (severe) Granuloma + many organisms 1)Tuberculoid (mild) Granuloma (leproma) + few organisms MICROSCOPIC Lymphocytes + plasma cells +Giant cells+ foamy macrophages (clear cells or foam cells) called lepra cells

13. MICROSCOPIC

14. 1)Tuberculoid (mild) loss of sensation & sweating Trophic changes (ulcers) Deformities and loss of parts of limbs due to loss of sensation & low blood supply) 2)Lepromatous (severe) Loss of sensation severe trophic changes Deformities and loss of parts limbs severe leonine facial disfigurement Clinical Picture

15. SYPHILIS Chapter 7 p104-112

16. SYPHILIS DEFINITION: Venereal Infective spirochetal granulomatous disease caused by Treponema pallidum

17. AETIOLOGY & PATHOGENESIS • Organism: spirochete Treponema pallidum Diagnosed by: Silver stains -Immunofluorescence-Dark field illumination microscopy • Route & Site of entry: • Skin by intimate contact (venereal) : genital organs (male-female) – extragenital sites: lips-breasts etc…. • Non- venereal (transplacental: spirochetes spread via placenta to fetus).

18. AETIOLOGY & PATHOGENESIS Types: • Congenital syphilis: baby born to syphilitic mother with lesions • Venereal type: • Primary (1ry) lesion at time of first contact • Secondary (2ry) lesions all over body due to blood spread • Tertiary (3ry) lesions due to hypersensitivity

19. AETIOLOGY & PATHOGENESIS Mechanism: Spirochete enters (by intimate contact) → IP 2wks → 1ry proliferative lesion (granuloma) 33%cases undergo healing Rest of cases spread by blood & lymphatics & after 2 months → 2ry lesions 33%cases undergo healing3ry lesions (gumma) 2- 10 years later

20. GROSS Nodule (early) Ulcer (hard sore/chancre) edges punched out & straight floor clean smooth base: syphilitic GT Regional lymphadenitis MORPHOLOGYBasic reaction 1ry

21. 1ry Microscopic ( syphilitic GT) • plasma cells > lymphocyte • macrophages & FT • early endarteritis obliterans + gummatous necrosis central

22. Gross Rash in mucous membranes & skin -macular rash -papular rash +/- Ulcerations Generalized lymphadenopathy Microscopic syphilitic GT MORPHOLOGYBasic reaction 2ry

23. MORPHOLOGYBasic reaction 3ry Hepar lobatum Gross a-GummaHypersensitivity type IV firm –yellow-rubbery surrounded by FT. It occurs in: heart septum-liver – bone-brain b-Diffuse inflammation Aorta & meninges bones, testis & tongue *

24. MORPHOLOGYBasic reaction 3ry Microscopic a-Gummais a localized area of necrosissurrounded by syphilitic GT b-Diffuse inflammation • Chronic diffuse inflammation +fibrosis (syphilitic GT) • Hypersensitivity necrosis

25. Heart Gumma of septum Diffuse syphilitic myocarditis Diffuse Syphilitic pericarditis BV Syphilitic arteritis Syphilitic aortitis Cvs syphilis

26. gross Intima: Proliferation of CT opposite media lesions Atherosclerotic plaques Wrinkling of intima Media: mononuclears & end arteritis obliterans VV necrosis of musculoelastic tissue FIBROSIS Adventitia mononuclears & end arteritis obliterans VV and fibrosis Syphilitic aortitis Microscopic

27. Syphilitic aortitis gross • Aortic cusps thick and rolled up • Dilated aorta (ascending) • Raised atheroscl plaques • TV wrinklings (furrrows) • Media thin white (fibrotic • Adventitia thickened by FT • Coronary ostia narrowed

28. Syphilitic aortitis complications • Aortic incompetence • Stretched aortic ring (dilatation of aorta • Shrunken cusps with incomplete closure Resulting in LHF • Aortic aneurysm: weak fibrotic wall • Stenosis of coronary artery • Gradual ischemia: Myocardial fibrosis & angina • Sudden ischemia : sudden death VF / infarction

29. Syphilis of bones • Gumma • Worm eaten skull • Saddle nose perforated septum • Gumma of hard palate perforated palate • Diffuse osteomyelitis NB syphilitic osteitis causes osteosclerosis NO PATHOLOGIC FRACTURE

30. neurosyphilis • Meningovascular • Gumma or diffuse syphilitic meningitis • Syphilitic arteritis • Parenchymatous a. General paralysis of the insane (dementia paralytica) infl + necrosis of frontal lobes with flattening of convolutions b. Tabes dorsalis producing Charcot joint & chronic ulcers due to: posterior column nerve demyelination meningitis followed by gliosis

31. Congenital syphilis Transplacental spread→abortion or still birth. If fetus survives: EARLY MANIFESTATIONS (during 1st 2years of life)(like 2ry syphilis) • Skin condylomata: papillary skin projections-desquamation-macules • Mucous patches • Generalized lymphadenopathy • Rhagades: radiating scars at the angle of the mouth

32. Congenital syphilisEARLY MANIFESTATIONS contin • Syphilitic osteochondritis: epiphysial line appears yellow , broad & irregular due to infiltration by Syphilitic GT resulting in growth retardation • Syphilitic inflammation of organs • Pneumonia alba • Syphilitic cirrhosis (monocellular cirrhosis)

33. Congenital syphilisLate MANIFESTATIONS (2-30 years) • Hutchinson’s teeth: The permanent central incisors are notched & widely separated. • Deafness due to 8th cranial nerve affection • Eye: keratitis • Saber tibia: thickening and bending of tibia (sword like i.e. curved) diffuse periosteitis • Gumma of palate with perforation • Gumma nasal septum→saddle nose • Effusion large joints

34. ACTINOMYCOSIS Chapter 7 p112-123

35. ACTINOMYOCOSIS DEFINITION: Infective suppurative granulomatous disease caused by the filamentous bacteria, Actinomyces Israeli.

36. ETIOLOGY & PATHOGENESIS • Organism: filamentous anaerobic gram+ve organism. It is a Commensal found in oral cavity & intestines. Long blue filaments, having red nobby tips. The filaments branch. • Sites: Cervico-oral (jaw)- intestine (ileocoecal) , lungs (pulmonary) & less commonly skin

37. GROSS Multiple pus containing cavities surrounded by FT multiple sinuses opening onto skin releasing granular yellow material (sulfur granules) which is pus containing organism MANIFESTATIONS

38. MICROSCOPIC Central zone of pus + irregular blue clump of organism with a red periphery PNLs & macrophage Outer zone of lymphocytes-plasma cells-macrophages endarteritis obliterans & FT (chronic inflammation)

39. LECTURE RESOURCES • BOOKS & Lecture notes •  Textbook : Basic Pathology by Kumar, Cotran & Robbins - •  General & systemic pathology J.C.E Underwood 3d edition Livingstone- •  Gamal Nada's General Pathology •  Gamal Nada's General Museum of Pathology •  Soheir Mahfouz's Guidlelines in General Pathology • WEBSITES • Important web sites from which many images or text were taken. • NB. Those not mentioned may be found on web searches: google , Yahoo & ask.com • http://www.pathmax.com/ • http://www-medlib.med.utah.edu/WebPath/LABS/LABMENU.html#2 • http://www.med.uiuc.edu/PathAtlasf/titlePage.html • http://www.medscape.com/pathologyhome • http://www.gwumc.edu/dept/path/2F.HTM • http://ampat.amu.edu.pl/czasopis/contents.htm • http://www.urmc.rochester.edu/smd/pathres/long.html • http://www.medscape.com/pathology/cme

40. LECTURE RESOURCES • http://www.medscape.com/pathology/cme • http://www.mic.ki.se/Diseases/C23.html • http://dir.yahoo.com/Health/medicine/pathology/ • http://www.iaphomepage.org/ • http://search.msn.com/results.aspx?q=Pathology+lectures+on+line&FORM=QBRE2 • http://dpalm.med.uth.tmc.edu/faculty/bios/hunter/pathlinks.htm • http://www.pathmax.com/main.html • http://www.pathguy.com • http://www.emedicine.com/oncology/ • http://www.thedoctorsdoctor.com/diseases/liposarcoma.htm#histo • http://www.humpath.com/article.php3?id_article=3532 • http://www.ec.upstate.edu/path/ • http://peir.net/ • http://medstat.med.utah.edu/WebPath/webpath.html • ATLAS • http://www.emedicine.com/asp/image_search.asp?query=actinomycosis&offset=12 • http://erl.pathology.iupui.edu/C604/INDEX.HTM • http://www.path.uiowa.edu/virtualslidebox/ • http://www.mic.ki.se/MEDIMAGES.html#G02.403.776.600 • http://www.palms.med.usyd.edu.au/pathology_museum/ • http://www.med.uiuc.edu/PathAtlasf/titlePage.html

41. LECTURE RESOURCES • http://www.med.uiuc.edu/PathAtlasf/titlePage.html • http://images.google.com/imgres?imgurl=http://www.images.md/intermedia/imgagent/mediaget/getwatermarked/ACNCR01-09-55-001&imgrefurl=http://www.images.md/users/explore_chapter.asp%3FID%3DACNCR01-09-55%26colID%3DACNCR01-09%26coltitle%3DBreast%2BCancer&h=80&w=120&sz=11&tbnid=EZu7ubDWDdUUIM:&tbnh=55&tbnw=83&hl=en&start=67&prev=/images%3Fq%3DFine%2BNeedle%2BAspiration%2Bof%2BBreast%26start%3D60%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DN • http://images.google.com/imgres?imgurl=http://www.hopkinsbreastcenter.org/pathology/benign/1j.jpg&imgrefurl=http://www.hopkinsbreastcenter.org/library/educational_information/benign.shtml&h=380&w=492&sz=289&tbnid=NTEcMCp3mRuZbM:&tbnh=98&tbnw=127&hl=en&start=1&prev=/images%3Fq%3DFine%2BNeedle%2BAspiration%2Bof%2BBreast%26svnum%3D10%26hl%3Den%26lr%3D • http://images.google.com/imgres?imgurl=http://www.webpathology.com/slides/thumbnails/Testes_SexCord_GranulosaCellTumor2TN.jpg&imgrefurl=http://www.webpathology.com/case.cfm%3Fcase%3D38&h=76&w=101&sz=6&tbnid=yup1zvPUIS1u3M:&tbnh=58&tbnw=78&hl=en&start=21&prev=/images%3Fq%3Dgranulosa%2Bcell%2Btumour%2Bovary%26start%3D20%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DN • http://screening.iarc.fr/index.php • http://web.med.unsw.edu.au/pathology/Pathmus/pathmus.htm#InteractiveImages • http://www.hopkinsbreastcenter.org/library/educational_information/benign.shtml • http://eulep.anat.cam.ac.uk/Search_Pathbase/index.php?actiontype=search&mpath= • http://www.diesis.com/fabrizio/atlas/ • Dermatopath • http://www.derm.ubc.ca/pathology/micrneurann.htm • http://tray.dermatology.uiowa.edu/DPT/DPTutor.htm • Reproductive • http://images.google.com/imgres?imgurl=http://www.path.sunysb.edu/coursemat/reproimages/thumbs/4thumb.jpg&imgrefurl=http://www.path.sunysb.edu/coursemat/reproslides.htm&h=86&w=120&sz=5&tbnid=aVSQELIjiWfBAM:&tbnh=59&tbnw=83&hl=en&start=25&prev=/images%3Fq%3Dgranulosa%2Bcell%2Btumour%2Bovary%26start%3D20%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DN • Respiratory • http://iris.nyit.edu/~edoran/Course/Resp1lect01.htm#NORMAL%20ANATOMY%20LUNGS

42. LECTURE RESOURCES • Dermatopath • http://www.derm.ubc.ca/pathology/micrneurann.htm • http://tray.dermatology.uiowa.edu/DPT/DPTutor.htm • Reproductive • http://images.google.com/imgres?imgurl=http://www.path.sunysb.edu/coursemat/reproimages/thumbs/4thumb.jpg&imgrefurl=http://www.path.sunysb.edu/coursemat/reproslides.htm&h=86&w=120&sz=5&tbnid=aVSQELIjiWfBAM:&tbnh=59&tbnw=83&hl=en&start=25&prev=/images%3Fq%3Dgranulosa%2Bcell%2Btumour%2Bovary%26start%3D20%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DN • Respiratory • http://iris.nyit.edu/~edoran/Course/Resp1lect01.htm#NORMAL%20ANATOMY%20LUNGS

43. Good bye & good luck

44. Lectures will be available next week on the net http://www.kasralainy.edu.eg/ english/departments/pathology/