Cryptococcosis Systemic infection involving Lungs CNS Skin Lymph nodes Usually an opportunistic infection in immunocompromised host Cryptococcal lymph

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9 Cryptococcosis Systemic infection involving Lungs CNS Skin Lymph nodes Usually an opportunistic infection in immunocompromised host Cryptococcal lymphadenitis is a rare AIDS defining illness Incidence of infection increasing since 1980s 1 million new cases per year, mortality 20-70% Western countries: 10-15% of AIDS patients Zimbabwe: 88% of AIDS patients

10 Crptococcus neoformans First described by a German pathologist, Otto Busse, in 1894 Isolated from a tibia of a 31 year old female In 1895, a surgeon, Abraham Buschke, isolated the same organisms from the same patient Isolated from fermented peach juice in 1895 by an Italian scientist (Sanfelice) Synonyms: Torulosis Europoean blastomycosis Busse-Buschke disease

11 Crptococcus neoformans 37 species: var neoformans var gattii Northern hemisphere: var neoformans Found in pigeon droppings Australia: var gattii Found in eucalyptus trees Causes pneumonia in immunocompetent 8 per million per year

12 Pulmonary cryptococcosis Majority are asymptomatic or present with cough, fever, sputum, chest pain (similar to other causes of pneumonia) Round thin walled yeast forms, 2-20 µm, with wide clear polysaccharide capsule Narrow necked budding Stain with Alcian blue, mucicarmine, cresyl violet, Masson- Fontana, GMS, PAS/D Host response depends on immune status Immunodefficient: numerous confluent aggregates of organisms fill alveolar spaces, septa and capillaries with little host response Immunocompetent: granulomatous inflammation with caseation and fibrosis

13 Lung disease with granulomas Sarcoid Mycobacterial/fungal/parasitic infections Wegener s granulomatosis, Churg Strauss Extrinsic allergic alveolitis Rheumatoid arthritis Aspiration Bronchocentric granulomatosis Necrotising sarcoid angiitis Berylliosis Talc pneumoconiosis/intravenous talcosis

14 Case year old male. Died from stabbing. History of alcohol abuse.

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26 Aspiration Causes Drunkenness General anaesthesia CVA Drug overdose Coma Dysphagia

27 Aspiration pneumonia Dependent parts of lung Prone: apical segment of lower lobe Side: lateral portion of anterior and posterior portions of upper lobe Necrotising bronchopneumonia Pulse granuloma Often leguminous material (resistant cellulose capsules) Can use PAS and silver stains

28 Case 5 28 year old male. Died from stabbing

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34 S100

35 CD1a

36 Pulmonary Langerhans cell histiocytosis

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38 Pulmonary Langerhans cell histiocytosis Normal lung alternates with stellate nodular interstitial lesions Central cystic degeneration Adjacent to bronchioles Histiocytes, eosinophils, plasma cells, lymphocytes Langerhan s cells: Folded, indented, vesicular nuclei Abundant eosinophilic cytoplasm with indistinct borders Older lesions: stellate fibrosis, few LCs

39 Pulmonary Langerhans cell histiocytosis +/- DIP-like reaction +/- RBILD IHC: S100 +ve (must be in clusters) CD1a +ve EM: Birbeck granules

40 Pulmonary Langerhans cell histiocytosis Differential diagnosis Eosinophilic pleuritis Eosinophilic pneumonia DIP

41 Pulmonary Langerhans cell histiocytosis Alternative terms: Histiocytosis X Letterer-Siwe disease (acute generalised) Hand-Schuller-Christian disease (chronic generalised) Eosinophilic granuloma (localised) Majority smokers M>F 15% have extrapulmonary involvement

42 Langerhans cell histiocytosis Non specific symptoms Spontaneous pneumothoraces No peripheral eosinophilia Aetiology: Abnormal immune reaction (possibly to cigarette smoke)? Some clonal (particularly extra-pulmonary)

43 Pulmonary Langerhans cell histiocytosis Prognosis: Most resolve spontaneously May relapse and remit Rarely irreversible fibrosis Treatment: Stop smoking Steroids? Bone marrow transplant? Lung transplant?

44 Case 11 9 year old male. Acute shortness of breath then died.

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50 Asthma status asthmaticus Mucus plugging (concentric/spiral pattern) Oedema Smooth muscle hypertrophy Subepithelial collagen thickened Desquamation of bronchial epithelial cells Eosinophils Goblet cell hyperplasia Enlarged submucosal glands Involves bronchi and bronchioles

51 Effects of inhaled steroids on pathology of asthma Reduced numbers of eosinophils, mast cells and lymphocytes (within 2 weeks) Persistent tissue eosinophilia Decrease in basement membrane thickness shown in long term studies Improved epithelial integrity Decreased vascularity

52 Lung disease with prominent eosinophils Langerhans cell histiocytosis Asthma Fungal/parasitic infection Drugs ABPA Mucoid impaction of bronchi Bronchocentric granulomatosis Eosinophilic pleuritis Eosinophilic pneumonia Simple (Loffler s syndrome) Acute Chronic

53 Case year old male. Died in nursing home suffering from pressure sores, S. aureus sepsis, dehydration and renal failure. Medical history of caecal carcinoma, hypertension, congestive cardiac failure and type 2 diabetes. At autopsy extensive tumour found in liver and lungs. Prostate cancer and multiple skin cancers also found at autopsy

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59 AE1/3 S100 HSA Glypican 3

60 Glutamine synthetase

61 Metastatic hepatocellular carcinoma Markers of hepatocellular differentiation HSA (HepPar-1, OCH1) AFP pcea & CD10 stain bile canaliculi CD34 stains sinusoids Arginase-1 Glypican-3 (benign vs malignant) Glutamine synthetase (benign vs malignant) A panel is advised

62 Case 7 84 year old female. Collapsed at home and died shortly after admission to hospital where she was found to be profoundly hypotensive.

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