1. LGH

2. History  48 y female seen in OPD  2 Months SOBE, Dry cough Wt loss & Fatigue Wt loss & Fatigue  No orthopnea, PND, Chest pain, wheeze  No hemoptysis, fever, night sweating

3. History  Able to walk 2 blocks  No nausea, vomiting, abdominal pain  No joint pain, swelling or skin rash  No contact with sick person

4. History  Smoker 30 pack  PMH : NHL stage IB 1998 cervical LN Chemo & Radiotherapy 1999 Chemo & Radiotherapy 1999 In remission followed in cancer care In remission followed in cancer care Previous IVDU  -ve HIV, HBV & HCV No previous pneuomnia  No pets, occupational exposure

5. History  No medication, travel  PSH : tonsilectomy,tubal ligation  FH unremarkable  Referred by radiation oncology because of symptoms & abnormal CXR

6. Examination  Afebrile RR 14 Sat 95% RA BP 160/70 HR 90 BP 160/70 HR 90  No Lymphadenopathy, clubbing  Chest : Good breath sound No wheeze, crackles No wheeze, crackles

7. Examination  CVS : S1+S2+0  Abd : No splenomegaly  No LL edema  No skin rash, joint swelling

8. Investigation  CBC  Hb 110 MCV N  Coagulation N  BUN, Creat & Electrolyte N  LFT & LDH N  CXR, Chest CT & PFT

9. Work Up  ANA, ANCA, RF & complement N  6MWT distance 480 m Sat 95%  89% Sat 95%  89% HR 70  100 HR 70  100  BAL  -ve culture & cytology  Transbronchial Bx  non specific

10. Work Up OOOOpen lung Bx Langerhans Cell Histiocytosis

11. Langerhans Cell Histiocytosis  Langerhans cell is an antigen presenting cell  Origin  monocyte – macrophage cell linage  Normally found in dermis, reticuloendothelial system, lung, & pleura.

12. Langerhans Cell Histiocytosis  Can be found in association with cigarette smoking in asymptomatic individuals and in other pulmonary disorders, such as IPF  LCH is a spectrum of diseases caused by proliferation & infiltration of LG cells  First described early 1950s

13. Langerhans Cell Histiocytosis  Different presentations with confusing classification.  No genetic, geographic or occupational predisposition  2 unique pathological features Birbeck granules by EM (intracellular structure) Birbeck granules by EM (intracellular structure) CD1a antigen on cell surface Protein s 100 CD1a antigen on cell surface Protein s 100

15. Pulmonary LCH  Unknown true incidence or prevalence  5% of open lung Bx for ILD work up ? Underestimation ? Underestimation  Disease of Caucasian, Smokers  Young age with equal M:F {? Because of increasing smoking in females} {? Because of increasing smoking in females}

16. Presentations  Incidental CXR finding  Fatigue,wt loss  Respiratory : 6 – 12 months SOBE, dry cough, rib pain SOBE, dry cough, rib pain pneumothorax pneumothorax  Extrapulmonary : DI,bone or skin lesions

17. Presentations  Clinical exam : unremarkable unremarkable Core pulmonale in advanced cases Core pulmonale in advanced cases Bony or skin lesions Bony or skin lesions  Laboratory : Non specific Non specific DI picture in serum & urine electrolytes & osmolality & osmolality

18. Diagnosis  Radiological: bilateral symmetrical disease Ill-defined or stellate nodules (2 to 10 mm in size) Ill-defined or stellate nodules (2 to 10 mm in size) Reticulonodular infiltrates Upper zone cysts or honeycombing Preservation of lung volume Costophrenic angle sparing ( different than LAM ) Reticulonodular infiltrates Upper zone cysts or honeycombing Preservation of lung volume Costophrenic angle sparing ( different than LAM )

19. Diagnosis  Radiological: Correlation between radiological & pathological progression Correlation between radiological & pathological progression Cellular infiltrate { Nodules } around small airways  cavitations  replacement by fibroblast {satellite lesions & Cyst formation } Simultaneous presence of nodules & cyst is highly suggestive of PLCH

20. Diagnosis  Radiological: DDx  LAM, Tuberous sclerosis Tuberous sclerosis Hypersensitivity pneumonitis Hypersensitivity pneumonitis Sarciodosis, IPF Sarciodosis, IPF Mycobacterial & Fungal infections Mycobacterial & Fungal infections Malignancy, Wegner vasculitis Malignancy, Wegner vasculitis

21. Diagnosis  PFT & CPET: Variable, sometimes out of proportion to radiological finding Obstructive out of proportion to smoking, unique to PLCH & LAM than other ILD Restrictive or mixed Limited CPET > COPD due presence of primary pulmonary vasculopathy

22. Diagnosis  BAL: Low yeild 10-40%  focal disease DC1a stained cells in BAL > 5% had a good sensitivity ( single study & small number )  Open Lung Bx Gold standard In symptomatic pateints, equivocal radiological finding & possibility of another Dx cant be excluded & possibility of another Dx cant be excluded

23. Treatment  No RCT  Smoking cessation associated with slow progression  Steroid & chemo has been used in few cases  Transplantation  in young who quit smoking with rapid progression with rapid progression ?Recurrence after transplant

24. Prognosis  Variable  Poor prognostic factors : extreme of ages extreme of ages diffuse progressive disease diffuse progressive disease multisystem involvement multisystem involvement  Risk Of lung Ca : ? pure smoking related risk Vs PLCH additive risk ? pure smoking related risk Vs PLCH additive risk