Leslie Case 4. Prac%cal Approach to Granulomatous Lung Disease. PRE-TEST Which of these images is more likely to have organisms on special stains?

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1 Leslie Case 4 Prac%cal pproach to Granulomatous Lung Disease Kevin O. Leslie, MD Professor and Consultant Mayo Clinic rizona PRE-TEST have organisms on special stains? PRE-TEST represent infection? PRE-TEST Which of these granulomas is LEST likely to have organisms? Case Study 50 year old Caucasian woman was in her usual state of good health when she developed a mild upper respiratory tract infection. During the recovery phase of that illness, she was bothered by persistent bronchitis with a mildly productive cough.

2 Case Study (cont.) On advise from her physician husband, she began self treatment with hot moisturized air, while using an indoor hot water soaking tub ( Hot tub of Jacuzzi ). Daily, she would place a towel over her head, and breathe in deeply while seated in the tub. Over the next few weeks, her cough persisted and was progressively accompanied by shortness of breath. Eventually she was seen by a pulmonary specialist and a CT scan was performed ronchoscopy was nondiagnostic and a surgical lung biopsy was performed

3 Diagnosis Diffuse granulomatous pneumonitis resulting from bioaerosol inhalation of M. vium (so-called Hot Tub Lung ) The Wide Spectrum of M. vium-ssociated Lung Disease 1. Fibrocaseous disease similar to MTb 2. Disseminated infection in the immunocompromised host 3. Localized/patchy nodular disease complicating bronchiectasis and other chronic lung disease. 4. Diffuse interstitial/nodular disease in normal hosts (so-called hot tub lung ) 5. Eosinophilic pneumonia (very rare)

4 pproach to granulomatous lung disease In the patient with diffuse lung disease, the differential diagnosis ranges from: Conditions with classic sarcoid-like granulomas (with or without necrosis). Conditions in which granulomas are poorly formed or represented only isolated clusters of giant cells. Simply identifying granulomas in a surgical specimen is inadequate for a final diagnosis. It is always important to attempt to characterize: 1. The distribution and qualitative features of the granulomas 2. ny other accompanying findings and results of special stains. pproach to granulomatous lung disease Common diffuse granulomatous diseases: 1. s - Mycobacteria - Fungi (including pneumocystis) Hypersensitivity pneumonitis 4. spiration Uncommon causes of granulomatous lung disease ronchiectasis erylliosis and other pneumoconioses Drug reactions Collagen vascular diseases (e.g. Sjogren syndrome) Intravenous durg abuse with crushed tablets Vasculitis (rarely) Eosinophilic pneumonia Immunoglobulin deficiency Diffuse lymphoid hyperplasia (regardless of cause) Giant cell interstitial pneumonia (hard metal disease) Diffuse neoplasms (lymphoma, leukemia, other) Inflammatory bowel disease Incidental granuloma

5 LUNG MICRONTOMY natomic Distribution of Granulomas Image courtesy of T. Colby ad M. Smith irway-centered granulomas Granulomas along lymphatic routes ngiocentric granulomas Scattered (random ) granulomas Inhalational: -s -Dust disease -spiration s IV drugs Miliary infections Critical questions regarding granulomas re the granulomas well formed? re the granulomas loose aggregations of epithelioid histiocytes? re the granulomas identifiable only as giant cells, singly or in groups? re the granulomas necrotizing, and what is the appearance of the necrosis? spiration Hypersensitivity Lympho-prolif. diseases Drug toxicity Hypersensitivity Hard metal disease Granulomatosis with polyangiitis Critical questions regarding granulomas Granulomas scattered and single? Granulomas coalescent? irefringent material and secondary structures associated with the granulomas? Extensive fibrous tissue around the granulomas? Is there a mononuclear cell infiltrate associated with the granulomas? spiration { nonspecific, Chronic aspiration, Hypersensitivity Lymphoprolif.

6 POST-TEST have organisms on special stains? Take Home Lessons Even the town policeman can recognize granulomas natomical location and appearance of granulomas provide key clues to accurate diagnosis! POST-TEST represent infection? POST-TEST Which of these granulomas is LEST likely to have organisms? C D Key References Khoor, Leslie KO, Tazelaar HD, Helmers R, Colby TV: Diffuse pulmonary disease caused by non-tubeculous mycobacteria in immunocompetent people (Hot tub lung). m J Clin Pathol 2001; 115: Cheung OY, Muhm JR, Helmers R, ubry MC, Tazelaar HD, Khoor, Leslie KO, and Colby TV: Surgical pathology of granulomatous interstitial pneumonia. nn Diag Pathol 7(2): , 2003 Hutton Klein JR, Tazelaar HD, Leslie KO, Colby TV: One hundred consecutive granulomas in a pulmonary pathology consultation practice. m J Surg Pathol Oct;34(10): NECROSIS IS THE KEY!