This document describes several cystic lung diseases including pulmonary Langerhans cell histiocytosis (PLCH), lymphangioleiomyomatosis (LAM), and lymphoid interstitial pneumonia (LIP). PLCH presents with irregularly shaped cysts predominantly in the upper lobes sparing the costophrenic angles. LAM features uniformly distributed cysts throughout the lungs. LIP involves fewer uniformly shaped cysts with abnormal lung surrounding the cysts, often associated with conditions like Sjogren's syndrome or AIDS.

1. Cystic lung diseases

3. •Round parenchymal lucencies or low-attenuation areas with well-defined interfaces with normal
lung.
•Thin-walled structures with walls less than 3-4 mm in size, usually containing air, although
occasionally containing fluid or solid material

4. Cystic mimics Cystic lung diseases Cystic lung diseases(Rare)
Emphysema (e.g., bullae)
Cystic bronchiectasis
Honeycombing
PLCH
LAM (isolated LAM or
associated with the TSC)
LIP
Follicular bronchiolitis
BHD syndrome
Amyloidosis and LCDD
Cysts associated with DIP
Benign metastasizing
leiomyoma
Cystic pulmonary
metastases
Tracheobronchial
papillomatosis
Proteus syndrome
Neurofibromatosis

6. PULMONARY LANGERHANS CELL HISTIOCYTOSIS
young adults
heavy smokers
peribronchiolar location of lesions
Dyspnea/nonproductive cough
Pleuritic chest pain
Spontaneous pneumothorax

7. Radiographic Findings
reticular, nodular, and reticulonodular patterns, and honeycombing, often in combination
bilateral, predominantly the middle and upper lung zones, with relative sparing of the costophrenic
angles
Lung volumes normal or increased.
Nodules when present have irregular borders and vary from 1 to 10 mm in size.
With progression, PLCH results in a predominantly reticulonodular pattern, with subsequent
development of cystic lung disease.
Pneumothoraces occur and are frequently the initial presentation of recurrent disease.
Additional findings include mediastinal adenopathy, pulmonary consolidation, and a SPN

9. HRCT
Nodules
◦ Early stage
◦ Few to innumerable( activity of disease)
◦ 1-10mm diameter
◦ Centrilobular distribution,peribrochial or peribronchiolar
◦ Irregular margins
◦ May be cavitatory nodules with thick walls ,later cysts
◦ Intervening normal lung parenchyma

10. Cysts
◦ Later stage
◦ <10mm diameter
◦ Upto 2-3cm size
◦ Extreme bases preserved
◦ Usually thin walled,upto few mm thick
◦ distinct walls (differentiate from areas
of emphysema, which can also be
seen in some patients.)
◦ Bizarre shapes d/t confluence of cysts or
cysts sometimes represent ectatic
and thick-walled bronchi
◦ Bilobed
◦ Cloverleaf
◦ Branching
◦ Internal septation

12. Other findings
GG0,Reticular opacities-DIP like change
Mosaic attenuation
Interlobular septal thickening
Emphysema
LATE STAGES: coalescent cysts
fibrosis
honeycombing

15. Complications
Cyst rupture
◦ Spontaneous pneumothorax
◦ Pneumomediastinum
Interstitial fibrosis
◦ PAH & cor pulmonale
◦ ESPF & Respiratory failure

16. D/D
Early stage:
Granulomatous disease
◦ Granulomatosis with polyangiitis
◦ Sarcoidosis
Mets
Miliary TB

17. LAM
◦ Diffuse distribution
◦ Regular shaped & sized cysts
Cystic bronchiectasis
◦ Central distribution, signet ring sign
◦ Mucus plugging
Centrilobular emphysema
◦ Lack of visible cyst wall
PCP
IPF
◦ Basal & subpleural distribution
◦ Reduced lung volumes

18. Lymphocytic interstitial pneumonitis(LIP)
◦ Smooth walled simple cysts
◦ a/w autoimmune disease
HRCT may be valuable in directing lung biopsy to areas showing lung nodules

19. LYMPHANGIOMYOMATOSIS AND TUBEROUS SCLEROSIS
COMPLEX
Low grade destructive metastasizing PEComatous tumor
LAM cell proliferation in lung, kidney & axial lymphatics
Mutation of TSC2/1 genes
Women (premenopausal)
Young men if a/w Tsc

20. C/F
TSc LAM-childhood-Developmental delay, seizures, skin lesions/tumors
sLAM-late teens/adults-lymphatic /lung disease
Cystic lung disease & renal AML-in both
Pneumothorax-recurrent,B/L
Progressive dyspnea
Haemoptysis
Acute abdominal pain & shock(hemorrhagic renal AML)

22. Plain Radiograph
•large volume lungs with abnormal architecture mimicking emphysema in advanced disease
•chylothorax
•Pneumothorax

23. HRCT
•large lungs containing scattered thin-walled rounded empty cysts
• in early disease, the cysts are few and small with normal intervening lung parenchyma
• the cysts progressively enlarge and become more numerous until there is little normal lung remaining
•transient areas of increased lung opacity due to hemorrhage
•small lung nodules representing multifocal micronodular pneumocyte hyperplasia
(MMPH) especially in tuberous sclerosis
•pneumothorax
•chylous effusions: pleural, pericardial
•lymphadenopathy
•dilated thoracic duct
•myocardial fatty foci in tuberous sclerosis

25. Abdominal findings
Best delineated by CT or MRI:
•single or multiple renal AMLs containing a mixture of fat and soft tissue
• >90% incidence in TSC cases which have larger and more numerous AMLs compared with
about 30% incidence in s-LAM
•hepatic, adrenal or retroperitoneal AMLs
•chylous ascites
•lymphangioleiomyomas: soft cystic/solid masses which can insinuate between normal structures
without compressing them
•lymphadenopathy

27. Skeletal findings
multiple osteoblastic bone lesions in tuberous sclerosis, similar in appearance to enostoses

28. Complications
•respiratory failure
•recurrent pneumothorax (B/L as well)
•hemorrhagic AML, potentially fatal
•sirolimus or everolimus toxicity, including organizing pneumonia, cryptogenic organizing
pneumonia, interstitial pneumonitis, focal fibrosis or alveolar hemorrhage, Pneumocystis
jirovecii pneumonia, cardiac failure
•sudden death due to obstructing SEGCA in TSC
•Osteoporosis may occur in immobile patients

29. D/D
•lymphocytic interstitial pneumonitis (LIP)
• in women of child-bearing age, LIP is usually
associated with connective tissue disease,
especially Sjögren syndrome
• a smaller number of lower zone
predominant perivascular cysts, some with
internal soft-tissue may coexist with
nodules, ground-glass opacity, tree-in-bud
opacities, lymphoma or amyloid deposits
• lung changes may pre-date typical
serological abnormalities, delaying diagnosis

30. •emphysema
• advanced emphysema can appear similar to advanced cystic lung disease in LAM
• fibrosis may mimic cyst walls
• emphysema distribution depends on etiology
• LAM will have typical cysts separated by normal parenchyma in the least affected areas

31. •Pulmonary LCH
• upper zone predominant and bronchocentric cavitating nodules, branching or irregular
cysts
• spares costophrenic and costomediastinal angles
• typically a disease of young adult smokers, especially men
•Birt-Hogg-Dubé syndrome
• fewer cysts with characteristic subpleural distribution and characteristic cyst shapes
• AD inheritance
• family h/o pneumothorax or renal tumors
• characteristic skin lesions
• folliculin gene mutation

32. LYMPHOID INTERSTITIAL PNEUMONIA
Benign lymphoproliferative disorder characterized by lymphocyte predominant infiltration of the
lungs.
Subtype of ILD.
It also falls under the umbrella of non-lymphomatous pulmonary lymphoid disorders

33. Associations
•Sjögren syndrome:
• M. C. lung pathology in these patients
• can occur in up to 25% of those with LIP
•AIDS: particularly if it occurs in the young
•autoimmune thyroid disease
•SLE
•Castleman disease
•common variable immune deficiency
•RA
•pulmonary amyloidosis

34. gradual onset of dyspnea and cough.
Less frequently, systemic symptoms -fever, night sweats, arthralgia, and weight loss.
If the disease progresses to end-stage respiratory failure- cyanosis and clubbing
Hypertrophy of the salivary glands (in 20% of patients)
Complication-5% cases transform into lymphoma

35. Radiograph
Features can be non-specific, but may include:
•lower-zone predominant B/L reticular opacification
•chronic bilateral airspace opacification

36. HRCT
• diffuse with mid to lower lobe predominance
•thickening of bronchovascular bundles
•interstitial thickening along lymph channels
•small but variable-sized pulmonary nodules (can be centrilobular or subpleural, and are
often ill-defined)
•ground-glass changes
•scattered thin-walled cysts
• usually deep within the lung parenchyma
• typically abut vessels (i.e. perivascular or subpleural)
• size range between 1-30 mm (useful for differentiation from lymphoma of the lung )
• Mediastinal LAP

38. MIP minIP

40. D/D
•pneumocystis pneumonia (PCP)
• cystic changes (pneumatoceles) seen in advanced disease
• can be difficult to differentiate particularly in those with AIDS
•LAM
• younger females
• cysts - uniformly distributed throughout the lungs
•LCH
• smokers
• bizarre cysts - spare the costophrenic angles
• upper lung zone predominant

41. BIRT-HOGG-DUBÉ SYNDROME
Birt-Hogg-Dubé syndrome (BHDS), also known as folliculin gene-associated syndrome, is a multi-system
disease characterized by:
•cutaneous manifestations- fibrofolliculomas
•multiple lung cysts and spontaneous pneumothoraces
•increased risk of renal tumors, typically chromophobe oncocytomas and/or chromophobe carcinomas
• Men =women AD disorder.
• family h/o pneumothorax.

42. Diagnosis
One major criterion:
•5 adult-onset fibrofolliculomas
•pathogenic FLCN germline mutation
Two minor criteria:
•typical lung cysts with no other explanation
•multifocal/bilateral renal cancer < 50 years
•renal cancer of mixed chromophobe and oncocytic histology
•1st-degree relative with Birt-Hogg-Dubé syndrome

43. C/F
•skin lesions
• develop in ͠ 80% and manifest in 3rd and 4th decades and progress over time
• Fibrofolliculomas- characteristic lesion, typically in the midface
• Others- trichodiscomas and acrochordons (skin tags)
•renal cancer
• 7-fold increased risk of malignancy
• less usual histological forms - search for other features of Birt-Hogg-Dubé syndrome (most often
chromophobe oncocytomas and/or chromophobe ca)
• chromophobe oncocytomas (50%), chromophobe carcinomas (34%), clear cell
carcinomas (9%), oncocytomas (5%), papillary Rcc (2%)
• frequently bilateral, multifocal, and slow-growing

44. •lung cysts
• early or mid-adulthood, predating renal cancer
• asymptomatic , 50-fold increase in pneumothorax
• ​pneumothorax - recurrent and even bilateral, risk increases with cyst volume and volume changes
associated with activities such as flying and diving​

45. HRCT
Lung cysts typically develop in early adulthood and have the following characteristics:
•multiple lower zone predominant and B/L
•predilection for subpleural lung including paramediastinal and perifissural location
•adjacent to interlobular septa, arteries and veins
•thin-walled, variable in size, round or elongated, sometimes multilobulated or multiseptate
•​cysts adjoining the pleura may have a relatively narrow pleural base
•cyst rupture-pneumothorax, pneumomediastinum or pneumopericardium

48. D/D
Other causes of cystic lung disease or focal hyperlucencies:
•lymphangioleiomyomatosis (LAM)
• scattered distribution, i.e. no spared areas
• absence of sub-pleural cysts along fissures
• underlying TSC gene mutations occur in both TSC and sporadic LAM (cysts develop in women during
their child-bearing years)
• +/- renal angiomyolipomas and other features related to either TSC or sLAM
•pulmonary Langerhans cell histiocytosis
• upper zone predominant and bronchocentric cavitating nodules, branching or irregular cysts
• spares costophrenic and costomediastinal angles
• typically a disease of young adult smokers, especially men

49. •lymphocytic interstitial pneumonitis
• lower zone predominant perivascular cysts which may contain internal structures
• other features of the underlying disease e.g. nodules, ground-glass opacity, lymphoproliferative
disease or amyloid in Sjögren syndrome, features of AIDS
•light chain deposition disease
• cysts, nodules and lymphadenopathy
• older adult with a plasma cell dyscrasia (e.g. multiple myeloma) and renal failure

50. LCH LAM LIP
Variable shaped cysts Uniform shaped cysts Uniform shaped cysts(few)
Upper lobe predominance with
costophrenic sparing
Evenly distributed Evenly distributed
Normal intervening lung
parenchyma
Normal intervening lung
parenchyma
Abnormal surrounding lung
Smoking ++ No a/w smoking
female
TSc Sjogrens,AIDS