Namratha Ravishankar

What is a cystic lesion in the lung?

Pathology

A cyst is a round circumscribed space surrounded by an epithelial or fibrous wall of variable thickness.

Hansell DM, Bankier AA, MacMahon H, et al. Fleischner Society: Glossary of terms for thoracic imaging. Radiology 2008;246(3):697-722.

Namratha R

CYSTIC LESIONS OF THE LUNG

Radiology

A cyst appears as a round parenchymal lucency or low attenuating area with a well defined interface with normal lung. The wall thickness is usually <4mm

No associated pulmonary emphysema

Usually contain air but may contain fluid or solid material

Hansell DM, Bankier AA, MacMahon H, et al. Fleischner Society: Glossary of terms for thoracic imaging. Radiology 2008;246(3):697-722. Accessed via Pubmed.com

Cyst-Radiology

Also used to describe enlarged thin walled air spaces in lymphangioleiyomyomatosis and Langhan’s cell histiocytosis

Thick walled honeycomb lungs seen in end stage fibrosis

Entity Imaging characteristics

Lung cyst Well-circumscribed, rounded, thin-walled air-filled structure within the lung parenchyma. Wall thickness of ≤3mm.

Cavity Air-filled space within the pulmonary parenchyma with thicker walls (>4 mm).

Emphysema Polygonal-shaped lucent area without definable walls.

Bronchiectasis Air-filled space within the lung parenchyma that branches and connects with the airway. Associated airway abnormalities including air trapping, bronchial wall thickening, and bronchiolar impactions.

Honeycombing Clustered subpleural airspaces with variable size and wall thickness. Other signs of pulmonary fibrosis: architectural distortion, traction bronchiectasis, and reticular opacities.

Mechanisms of cyst formation They include bronchiolar check-valve mechanism, vascular

occlusion or ischaemia necrosis, and dilation of the bronchioles

Degradation of the connective matrix, especially by metalloproteinases, may play a further role particularly in LAM and PLCH

1. Kuhlman JE, Reyes BL, Hruban RH, et al. Abnormal air-filled spaces in the lung. Radiographics 1993; 13: 47–75.

2. Ichikawa Y, Kinoshita M, Koga T, et al. Lung cyst formation in lymphocytic interstitial pneumonia: CT features. J Comput Assist Tomogr 1994; 18: 745–748. 331.

3. Worthy SA, Brown MJ, Muller NL. Technical report: cystic air spaces in the lung: change in size on expiratory high-resolution CT in 23 patients. Clin Radiol 1998; 53: 515–519. 332

4. Lee KN, Yoon SK, Choi SJ, et al. Cystic lung disease: a comparison of cystic size, as seen on expiratory and

5. inspiratory HRCT scans. Korean J Radiol 2000; 1: 84–90.

CHECK VALVE MECHANISM

The valve mechanism had been defined by BROOKE as ‘‘one in which the entrance from a bronchus into a lung cavity become obstructed in a valve-like manner, presumably with a piece of necrotic tissue, and thus allows the ingress of air during inspiration but prevents the egress during expiration’’.

Brooke B. Excessive spontaneous inflation of a lung cavity. Lancet 1931; 2: 240–241.

Etiology

Focal or multifocal cystic lung diseaseCongenital Bronchogenic cysts Pulmonary sequestration Congenital cystic adenomatoid malformations

(CCAM)Infectious Pulmonary tuberculosis Coccidioidomycosis Pneumocystis carinii pneumonia Echinococcus granulosus or E multilocularisLymphocytic interstitial pneumonia (LIP)Desquamative interstitial pneumonia (DIP)

Etiology

Diffuse cystic lung diseasePulmonary Langerhans’ cell histiocytosis (PLCH)Lymphangioleiomyomatosis (LAM)Honeycomb cystic lung disease Asbestosis Idiopathic pulmonary fibrosis Collagen vascular disease Hypersensitivity pneumonitis SarcoidosisMiscellaneous Cystic lung disease in Down’s syndrome118 119 Birt-Hogg Dube syndrome120–122 Trauma

Cystic focal and multifocal disease

Diffuse cystic lung disease

Paediatric-Developmental

Bronchogenic cyst Pulmonary sequestration Congenital cystic adenomatoid

malformation Lobar emphysema Bronchial atresia Lymphangiectasia Plueropulmonary blastoma

Non developmental

Pneumatocoele

Others Lymphatic cysts Enteric cysts Mesothelial cysts Simple parenchymal cysts

Bronchogenic cyst

 Shanti and Klein (2008) studied a series of 236 patients undergoing pulmonary resection for cystic lung lesions.

Bronchogenic cysts constituted 20% of this group. Of these 47 cases, 20 involved a lobar location, which required lobectomy, and 27 cases were extralobar and were treated with resection of the cyst.

Shanti CM, Klein MD. Cystic lung disease. Semin Pediatr Surg. Feb 2008;17(1):2-8. 

Bronchogenic cyst

Bronchogenic cysts are supernumery foregut buds disconnected and separated from the tracheobronchial tree to form a cystic mass during embryogenesis (between 4th - 6th weeks)

Most common site is middle mediastinum (65-90%)

 Remote locations, including the interatrial septum, neck, abdomen, and retroperitoneal space.

CLINICAL FEATURES

Most bronchogenic cysts are found incidentally.

In infants- compression of the trachea or bronchi and esophagus-wheezing, stridor, dyspnea, and dysphagia.

Intraparenchymal cysts may manifest with recurrent infection.

Thin walled spherical unilocular masses –fluid filled, air filled or with air fluid levelsCalcification of cyst wall

Bronchogenic cysts

Lined by secretory respiratory epithelium (cuboid or columnar ciliated epithelium) 

Wall-cartilage, elastic tissues, mucous glands and smooth muscle 

They do not usually communicate with the bronchial tree, and are therefore typically not air filled.  

Contain fluid (water), variable amounts of proteinaceous material, blood products, and calcium oxalate 

DifferentialsMIMICS

Enteric cyst Posterior mediastinumGastric epithelium

Oesophageal cyst Squamous liningDouble muscle layer

Pericardial cyst Unilocular, Mesothelial lining

Bronchogenic cyst

ComplicationsFistula formationUlceration of cyst wallSuperimposed infectionHaemorrhage

Pulmonary sequestration

It is characterized by a portion of lung

that does not connect to the tracheobronchial tree and has a systemic arterial supply,usually from the thoracic or abdominal aorta

Newman B. Congenital bronchopulmonary foregut malformations: concepts and controversies.

Pediatr Radiol 2006;36(8):773–791.

Sequestered lung

Two types of sequestration have been described: intralobar and extralobar.

The extralobar form has its own pleural investment and systemic venous drainage,

The intralobar form shares the pleural investment with the normal lung and usually (but not invariably) drains into the pulmonary venous system

CLINICAL FEATURES

Intralobar sequestrationEarly childhood or adolesence with

recurrence lower lobe pneumoniaExtralobarUsually asymptomaticMay have cyanosis and feeding

difficultiesAssociated with diaphragmatic hernias,

cardiac malformations and foregut anomalies

Pulmonary Sequestration Usually seen in the left lower lobe CT-homogenous soft tissue mass, cysts

containing air or fluid, focal emphysema or hypervascular focus of lung parenchyma

Lung tissue is poorly developed and cystically dilated

Cysts lined by columnar to cuboidal epithelium

GROSS PATHOLOGY

Pleura thickened with adhesions Parenchyma-cysts upto 5cm in dia

with mucinous or purulent material and fibrosis.

MICROSCOPY

Loose, spongy tissue with numerous small cystic spaces containing clear, mucoid fluid.

Dilated bronchi with mucous or purulent material Alveoli filled with foamy macrophages Thick walled vessels reflecting systemic vascular

drainage with elastic stains

1. DeParedes CG, Pierce WS, Johnson DG, Waldhausen JA. Pulmonary sequestration in infants and children: a 20-year experience and review of the literature. J Pediatr Surg. Apr 1970;5(2):136-47.

2. AFIP, Non neoplastic disorders of lower respiratory tract

Congenital pulmonary airways malformation (CPAM) 

A congenital pulmonary airways malformation (CPAM) (until recently described as a congenital cystic adenomatoid malformation (CCAM)) refers to a multi-cystic mass of segmental lung tissue with abnormal bronchial proliferation.

It is considered part of the spectrum of bronchopulmonary foregut malformations

Berrocal T, Madrid C, Novo S et-al. Congenital anomalies of the tracheobronchial tree, lung, and mediastinum: embryology, radiology, and pathology. Radiographics. 24 (1): e17.

PATHOPHYSIOLOGY

Failure of normal broncho-alveolar development with hamartomatous proliferation of terminal respiratory units in a gland-like pattern (adenomatoid) without proper alveolar formation.

These lesions have intracystic communications and, unlike bronchogenic cysts, can also have a connection to the tracheobronchial tree

Pathophysiology

The term congenital adenomatoid malformation of the lung was first used by Ch’in and Tang in 1949

Incidence of about 1 in 25,000 live births

Stocker described 3 types which were expanded to 5 types in 2005

Type 0 (Tracheobronchial) to type 4 (Alveolar)

Congenital pulmonary airway malformation, type 0

CPAM, type 0, also known as acinar dysplasia or agenesis, is a rarely occurring and infrequently described malformation that is largely incompatible with life.

It is seen in term and premature infants who are cyanotic at birth and survive only a few hours

Associated with cardiovascular abnormalities and dermal hypoplasia

Histology

Bronchial type airways with cartilage, smooth muscle and glands separated by abundant loosely vascularised mesenchyme

Ciliated pseudostratified cells with goblet cells

Mucous cells and cartilage in all cases

CPAM, type 1-most common

CPAM, type 1, the large or predominant cyst type

First week to month of life, can be seen in older children and even young adults.

65% of cases ,amenable to surgery with a good prognosis.

CT scan shows multiple large cysts (>2cm) involving the lower lobe of left lung. The cysts are air-filled, expand the lower lobe, cause mediastinal shift and hypoplasia of right lung

Histology

Boundary between lesion and adjacent lobe sharply delineated

Cysts(2-10cm in diameter) lined by pseudostratified cilated columnar epithelium interspersed with rows of mucous cells(in 1/3rd of cases)

Polypoid or papillary appearance due to elastic tissue beneath the epithelium

Interspersed alveolar ducts,saccules and alveolae

Absent cartilage and inflammation

BAL in CCAM type 1

Type 1 congenital cystic adenomatoid malformation (CCAM), the most frequent malformation of the lung, is the only type to present intracystic mucinous cell clusters, which may form beyond the cysts, extracystic mucinous proliferation resembling mucinous bronchioloalveolar carcinomas (BACs).

As mucinous BACs are increasingly described in the literature in young patients with CCAM, we hypothesized that type 1 CCAM mucinous cells could represent BAC precursors. 

Mucinous Cells in Type 1 Pulmonary Congenital Cystic Adenomatoid Malformation as Mucinous Bronchioloalveolar Carcinoma Precursors

Lantuejoul, Sylvie MD, PhD; Nicholson, Andrew G. MD†; Sartori, Giuliana PhD; Piolat, Christian MD; Danel, Claire MD, PhD∥; Brabencova, Eva MD; Goldstraw, Peter MD; Brambilla, Elisabeth MD, PhD*; Rossi, Giulio MD

AJSP, June 2007 - Volume 31 - Issue 6 - pp 961-969 doi: 10.1097/01.pas.0000249444.90594.27

MALIGNANCY

CCAM-Maturation defects at various points during organogenesis and maturation

Focal atypical goblet cell hyperplasia in 33% Bronchioloalveolar carcinoma in 1%. Mean age -26 years All mucinous in character Sheffield et al described premalignant

changes in type 1 CCAM Epithelial hyperplasia and malignant

change in congenital lung cysts Clin pathol 1987;40.61-14

Bronchioalveolar carcinoma Mucous cell proliferation-hyperplasia Extension into adjacent alveoli- lepidic

growth pattern-Brochioloalveolar cell carcinoma

IHC:IL-3,IL4 and MUC-2 nuclear staining in atypical goblet cells and cytoplasmic and nuclear staining in adjacent epithelium

Chromosomal aberrations in the mucous cells similar to those in adenocarcinoma in non smokers

Good prognosis with exceptional metastasis

PROGNOSIS

BAC in CCAM less aggressive disease than BAC in a structurally normal lung

Douglas West et al, Dept of histopathology and

cardiothorasic surgery,Glasgow uk The society of thorasic surgeons

Congenital pulmonary airway malformation (CPAM), type 2.

CPAM, type 2, the medium cyst type, accounts for 10% to 15% of cases.

Seen within the first year of life Poorer outcome Grossly, cysts rarely more than

1.5 cm in diameter that tend to blend with the normal adjacent parenchyma.

Areas of low attenuation consist of clusters of multiple, small and evenly spaced air cysts

Histology

Multiple small cysts(0.5-2cm) Small relatively uniform cysts

resembling bronchioles separated by normal alveoli.

Cysts are lined by cuboid-to-columnar epithelium and have a thin fibromuscular wall.

No mucous cells or cartilage Solid pale tumor-like tissue with

striated muscle in 5%

Congenital pulmonary airway malformation (CPAM), type 3.

First days to month of life Male predominance, and owing to its

large size Maternal polyhydramnios and fetal

anasarca, high mortality rate Grossly, the lesion is “noncystic”

and appears more like dense pulmonary parenchyma

GROSS

Grossly a solid mass without obvious cyst formation

Histology

Solid appearance Excess of bronchiolar structure

separated by small air spaces, with cuboidal lining resembling late fetal lung

Microscopic adenomatoid cysts

CPAM, type 4

The peripheral acinar cyst type, appears to be a

hamartomatous malformation of the distal acinus.

This variant is seen equally in boys and girls, with an age range of newborn to 4 years and accounts for 10% to 15% of cases.

type 4 lesions may present with mild respiratory distress, sudden respiratory distress from tension pneumothorax, pneumonia.

Grossly, large thin-walled cysts are present at the “periphery” of the lobe and appear to be lined by a smooth membrane.

Histology type 4

Cysts(upto 10 cm) are lined by flattened epithelial cells (type I and II alveolar lining cells) over most of wall, with occasional low cuboidal epithelium seen.

The wall of the cyst is composed of loose mesenchymal tissue with prominent arteries and arterioles.

Loose mesenchyme must not be confused with similar features seen in the cystic type of PPB.

MICROSCOPY

 Focal stromal hypercellularity (50%)

Focal immature cartilage Associated pleuropulmonary

blastoma (bilateral type 4 CCAM with stromal cellularity) 

Pleuropulmonary blastoma Low-grade cystic PPB has been confused with large

cyst type 1 CCAM/CPAM and type 4 CPAM, and likely accounts for many, if not all, reports of malignancy arising in large cyst CCAM.

Low-grade cystic PPB can be distinguished histopathologically on the basis of the presence of a thin layer of primitive mesenchymal cells beneath the cyst wall

Hill DA, Jarzembowski JA, Priest JR, Williams G, Schoettler P, Dehner LP. Type I pleuropulmonary blastoma: pathology and biology study of 51 cases from the international pleuropulmonary blastoma registry. Am J Surg Pathol 2008;32(2):282–295.

Associations

Type 2 CPAM has been noted in nearly 50% of cases of extralobar sequestrations.

CCAM and PPB

Type I or purely cystic PPB is usually associated with larger cysts, more typical of type 4 CCAM.

 Controversy exists as to whether the tumor develops within a CCAM or whether the cystic lesion represents PPB from the onset

 In a report of 50 cases from the PPB registry, the authors propose that CCAM could be a precursor to PPB just as nephrogenic rests and nephroblastomatosis are to Wilms tumor

J.R. Priest, M.B. McDermott, S. Bhatia et al. Pleuropulmonary blastoma,A clinicopathologic study of 50 cases Cancer, 80 (1997), pp. 147–161

D.A. Hill, L.P. Dehner, L.V. Ackerman A cautionary note about congenital cystic adenomatoid

malformation (CCAM) type 4 Am J Surg Pathol, 28 (2004), pp. 554–555

Pleuropulmonary blastoma Pulmonary blastomas are a relatively rare group

of primary lung neoplasms that are composed of immature malignant epithelial and/or mesenchymal tissues whose features may resemble early embryological lung tissues.

First described by Barnard in 1952.

Koss M, Travis W, Moran C. Pulmonary sarcomas,blastomas, carcinosarcomas and Teratomas. Spencer’sHistopathology of the Lung (5th edn). New York, NY:McGraw Hill, 1996:1092–100. Barnard WG. Embryoma of lung. Thorax 1952;7:299

RADIOLOGY

 Solid, mixed and cystic heterogeneous low attenuation, pleural effusion , contralateral mediastinal shift, and lack of chest wall

invasion .

MICROSCOPY

Type 1-Multicystic Cysts separated by fibrovascular

septae lined with benign respiratory epithelium

Stroma-small round to spindle cells condensing to form a continuous cambium layer beneath the epithelium

Rhabdomyoblastic differentiation

Congenital lobar emphysema

Congenital lobar emphysema (CLE) refers to an over inflation of one or more lung lobes presumably due to various factors including a possible obstructive check valve mechanism at a bronchial level .

Berrocal T, Madrid C, Novo S et-al. Congenital anomalies of the tracheobronchial tree, lung, and mediastinum: embryology, radiology, and pathology. Radiographics. 24 (1): e17.doi:10.1148/rg.e17

Congenital lobar emphysema

Neonatal period or infancy Males>females Left upper lobe and right middle lobe

Congenital lobar emphysema

Congenital lobar overinflation-Normal architecture with overdistention of the alveoli

No true emphysematous changes Emphysema: Permanent

distention of the airspaces distal to the terminal bronchiole with destruction of their walls

Etiology

Etiology Not found in up to 50% Bronchial obstruction found in ~25% Allows collapse on exhalation (ball-

valve mechanism) Air trapping leads to alveolar

overinflation

Etiology

1. Intrinsic obstruction (more common) Intramural: Defect in the bronchial wallDefective quantity or quality of cartilage Intraluminal: Lesion in the lumen of the

bronchus Redundant bronchial folds, mucous plugs1. Extrinsic obstruction Compression of the bronchus from a lesion

outside the bronchial wall Cardiovascular: PDA, vascular sling Mass: Lymph node, bronchogenic cyst, oncologic

mass

Involvement

Upper lobes are predominantly involved

LUL: 42%RML: 35%RUL: 21%Lower lobes: <1%Bilateral involvement: ~20%

CLINICAL FEATURES

Symptoms (in order of decreasing frequency)

1. Moderate respiratory distress (most)

2. Cyanosis (half)3. Mild respiratory distress (less than

half)4. Asymptomatic (infrequent)5. Severe life-threatening distress

(least common)

Massive distention of alveolar spaces, but no tissue destruction

CLE

It is necessary for pediatricians to evaluate associated anomalies because 14% of the cases of CLE have coexistent congenital heart disease

Bronchial atresia (BA)

Bronchial atresia (BA) is a developmental anomaly characterised by focal obliteration of the proximal segment of a bronchus. 

The bronchi distal to the atresia become filled with mucus and may form a mucocoele

The lung distal to the atretic bronchus develops normally but is overinflated due to collateral air drift with air trapping.

Most commonly occurs at the apico-posterior segment of the left upper lobe

The bronchioles plugged by mucus and the surrounding alveoli are dilated. Many neutrophils and macrophages were found within the bronchi and surrounding lung parenchyma, indicating acute or chronic infection. Alveoli were enlarged, with a loss of alveolar walls.

Primary pulmonary lymphangiectasia (PPL)

Primary pulmonary lymphangiectasia (PPL) is a rare disorder of unknown aetiology characterised by dilatation of the pulmonary lymphatics

Primary pulmonary lymphangiectasia in infancy and childhood

P.M. Barker, C.R. Esther Jr, L.A. Fordha, S.J. Maygarden, W.K. Funkhouser

European respiratory journal

Lymphangiectasia

Full term infants with respiratory distress, pleural effusion(chylous)/generalised oedema

Pleural effusions with diffuse interstitial infiltrates

Diffuse thickening of the interstitium, both of the peribronchovascular interstitium and the septa surrounding the lobules

Dilated lymphatic spaces in the sub-pleural connective tissue, along thickened interlobar septa, and around bronchovascular axes

Differential Diagnosis of Cystic Lung Disease

Developmental cystsNon-infectious: Blebs and bullae Pulmonary Langerhans’ cell histiocytosis (PLCH) Lymphangioleiomyomatosis (LAM) Honeycomb lungInfectious: Pneumatocoele Pneumocystis carinii pneumonia (PCP) Tuberculosis Hydatid cyst Coccidiodomycosis

TUMOURS

Pleuropulmonary blastoma Cystic teratoma Multicystic mesothelioma Cystic mesenchymal hamartoma Metastases

MIMICS

Cystic bronchiectasis

Hartman TE. CT of cystic diseases of the lung. Radiologic Clinics of North America. 2001;39(6):1231-43

Disease Findings Distribution

Assoc. Findings

IPF Honeycomb cystsSubpleural, basilar predominance

Irregular lines of attenuation, ground-glass

PLCH Thin-walled cysts Random, spares bases

Nodules

LAM Thin-walled cysts Random, diffuse Chylous effusion

Differential diagnosisTS Thin-walled cysts Random, diffuse Angiomyolipomas

of kidneys and liver

LIP Thin-walled cysts Basilar predominance

Ground-glass attenuation

Cystic Bronchiectasis

Cystic structures contiguous with bronchial tre

Diffuse or focal Signet ring sign: each cystic space has an attendant vessel

Adapted from: Hartman TE. CT of cystic diseases of the lung. Radiologic Clinics of North America 2001;39(6):1231-43.

Blebs and bullae

CT Scan: Thin walled cystic air space contiguous with the pleura

Arbitrary distinction between bleb and a bulla is of little clinical significance

Hansell DM, Bankier AA, MacMahon H, et al. Fleischner Society: Glossary of terms for thoracic imaging. Radiology 2008;246(3):697-722.

Bleb

The term bleb usually connotes a subpleural collection of air within the layers of visceral pleura caused by a ruptured alveolus.

The air dissects through the interstitial tissue into the thin, fibrous layer of visceral pleura where it accumulates to form a bleb.

Rupture of a bleb is often associated with the development of a spontaneous pneumothorax

Cystic and Bullous Lung Disease Robert R. Klingman, MD, Vito A. Angelillo, MD, and

Tom R. DeMeester, MD Departments of Surgery and Pulmonary Medicine, Creighton University School of Medicine, Omaha, Nebraska

Ann Tkorac Surg 1991;52:576-80)

Bullae

An air filled space within the lung parenchyma resulting from deterioration of the alveolar tissue.

These lesions have a fibrous wall , trabeculated by the remnants of alveolar septa.

They can develop in a lung that is otherwise normal or in a lung in which the architecture has been destroyed by chronic obstructive disease.

Blebs and Bullae

Bullae can reach substantial size and occupy an entire lobe

Usually seen in chronic obstructive pulmonary disease but also seen in normal young healthy individuals

Chronic obstructive pulmonary disease- no lobar predilection for the bullae

Asymptomatic patients, bullae - in the upper lobes and peripherally

Bullae are large dilated airspaces that bulge out from beneath the pleura

Bulla results from destruction of alveolar walls (paraseptal emphysema). The bleb results from rupture of alveolar air into the pleura

Differences

Bullae in the substance of the lung

Blebs in the visceral pleura outside the inner elastic lamina

Pulmonary Langerhans’ cell histiocytosis (PLCH)

PLCH is typically a disease of young adults which predominately affects the lungs and bones

Very strong association with smoking(90%) Interstitial lung disease Lung affected in isolation or in

association with organ systems

Pulmonary Langerhans’ cell histiocytosis (PLCH)

Pulmonary disease in PLCH is characterized by peribronchiolar 1-10 mm nodules in the early stages

In later stages of PLCH, the major pulmonary finding is cysts (present in 80% of patients) and there may be no nodules present

Lung bases are relatively spared at all disease stages

Cysts in pulmonary LCH

The abnormalities are diffuse and symmetrical.

The cysts in PLCH vary in size and shape, in contrast to the uniform appearance of cysts in lymphangioleiomyomatosis (LAM)

Characteristic combination of diffuse cysts and centrilobular micronodules

Cysts in PLCH

Cysts more pronounced later in the disease usually less than 10mm in diameter may measure up to 2 - 3 centimetres in size

Thin-walled, but on occasion may be up to a few millimetres thick

confluence of 2 or more cysts results in bizarre shapes :  bilobed cloverleaf branching internal septations

GROSS PATHOLOGY

Histopathology

The earliest histologic lesion of PLCH consists of proliferation of Langerhans’ cells along small airways

These early cellular lesions expand to form nodules 1 to 5 mm in diameter.

The characteristic lesion is composed of variable numbers of Langerhans’ cells,eosinophils,plasma cells, lymphocytes, fibroblasts, and pigmented alveolar macrophages, which form a loosely aggregated granulomas

These granulomas are typically centered around distal bronchioles, where they infiltrate and destroy airway walls

Histopathology

It is postulated that as these cellular granulomas evolve, peripheral fibrosis forms resulting in traction on the central bronchiole which becomes cyst-like 

Evolution from nodule, through cavitating nodule and thick walled cysts, to the 'stable' thin-walled cysts

Electron microscopy may reveal characteristic Birbeck granule

Lymphangioleiomyomatosis (LAM)

Lymphangioleiomyomatosis (LAM) is a disorder of smooth muscle proliferation.

Primarily affects women of childbearing age.

It also can present after menopause in women undergoing estrogen hormonal treatment.

This condition is indistinguishable from pulmonary involvement in tuberous sclerosis, which can also occur in men

Pathophysiology

Characterized by the progressive proliferating and infiltrating smooth muscle like cells (lymphangioleiomyomatosis cells)

Cystic destruction of the lung parenchyma; obstruction of airways, blood vessels, and lymphatics

2 main forms:tuberous sclerosis complex (TSC)–associated LAM and sporadic LAM (S-LAM).

In tuberous sclerosis, type II pneumocytes form clusters termed multifocal micronodular pneumocyte hyperplasia that are unique to TSC and may occur in the absence of

LAM in these patients

PATHOLOGY

Two phases of proliferation in lymphangiomyomatosis.

The early phase - proliferation of immature muscle cells which cover alveolar walls, bronchioles, pleura and vessels, including lymphatic routes.

Late phase - development of cystic spaces and wider proliferation of muscle cells throughout the lung.

Cyst formation in LLAM

An immunohistochemical study of metalloproteinases (MMP) and their inhibitors suggested that MMP-2 and MMP-9 (both of which can degrade elastin as well as the collagens) are responsible for the connective tissue destruction and cyst formation in LAM

Hayashi T, Fleming MV, Stetler-Stevenson WG, et al. Immunohistochemical study of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in pulmonary lymphangioleiomyomatosis (LAM). Hum Pathol 1997; 28:

1071–1078.

It shows thin-walled cysts of relatively uniform size diffusely distributed throughout all lung fields . The cysts may vary in size from 2 to 40 mm

PATHOLOGY

Small clusters or nests at the edges of the cysts and along the alveolar walls, pulmonary blood vessels, lymphatics, and bronchioles .

Mitotic figures are rarely seen. Loss of alveoli is associated with cyst

formation

LLAM

The proliferating LAM cells are morphologically heterogeneous and can be classified into 2 types: spindle-shaped cells and epithelioid cells.

Spindle-shaped cells are centrally located, whereas the epithelioid cells exist in the peripheral regions of the LAM cell nodules

IHC

Lymphangioleiomyomatosis cells coexpress smooth muscle markers (such as smooth muscle actin and desmin) and melanocytic markers (such as HMB-45, Melan-A/MART-1, and microphthalmia transcription factor)

Coexpression of contractile proteins and melanocytic markers, LAM cells are suggested to be of perivascular epithelioid cell origin

Immunohistochemistry

Demonstration of the presence of estrogen receptor (ER) and progesterone receptor (PR) in the epithelioid LAM cells (50%) who never received hormone treatment.

ER and PR are selectively expressed in epithelioid LAM cells and are down-regulated by hormone therapy

Matsui K, Takeda K, Yu ZX, et al. Downregulation of estrogen and progesterone receptors in the abnormal smooth muscle cells in pulmonary lymphangioleiomyomatosis following therapy: an immunohistochemical study.

Am J Respir Crit Care Med. 2000;161(3, pt 1):1002–1009.

IHC

Recently, CD1a and cathepsin K were found to be positive in both spindle shaped and epithelioid LAM cells

Useful new markers for the diagnosis of pulmonary LAM and renal angioleiomyoma

Chilosi M, Pea M, Martignoni G, et al. Cathepsin-K expression in pulmonar lymphangioleiomyomatosis. Mod Pathol. 2009;22(2):161–166

Adachi Y, Horie Y, Kitamura Y, et al. CD1a expression in PEComas. Pathol Int. 2008;58(3):169–173

Pneumatocoeles

Pneumatocoeles are intrapulmonary air-filled cystic spaces that can have a variety of sizes and appearances.

They may contain air-fluid levels and are usually the result of ventilator-inducted lung injury in neonates or post-pneumonic

ETIOLOGY

Staphylococcus aureus: most common

Pneumocystis carinii Streptococcus pneumoniae Haemophilus influenzae Escherichia coli Group A streptococci Klebsiella pneumoniae Adenovirus Primary tuberculosis

RADIOLOGY

Smooth inner margins Contain little if any fluid Wall (if visible) is thin and regular Persist despite absence of symtpoms

PATHOLOGY

Arise from necrotic foci that develop early in disease, initially have irregular shapes and thick walls.

Exudate disappears, and walls thin. Necrotic material around the pneumatocele. Walls can contain organized inflammatory cells

with focal collections of multinucleated giant cells. In 1972, Boisset reported the presence of air

corridors between the bronchiolar lumen and the interstitial space

Boisset GF. Subpleural emphysema complicating staphylococcal and other pneumonias. J Pediatr. Aug 1972;81(2):259-66.

Infectious cysts

True infectious cysts that persist despite resolution of the primary infection may occur with Pneumocystis carinii pneumonia or Echinococcosis (hydatid disease).

Pnemucystis carinii pneumonia Cysts vary in size, shape, number, wall

thickness– Thin-walled (<3mm), usually air-filled– Usually multiple, bilateral– May be intraparenchymal or subpleural– upper lobe predominance Cystic disease now occurs in 10-34% PCP

cases Cysts in HIV patient are highly suggestive of

PCP

Boiselle, PM, Crans, CA and Kaplan, MA. The Changing Face of Pneumocystis carinii P in AIDS Patients. AJR 1999; 172: 1301-1309.

Lung cysts are usually multiple, thin walled and bilateral, but range in size, shape and distribution

Alveoli which are distended with honey- combed, foamy, brightly eosinophilic material . There is a scanty inflammatory infiltrate composed mainly of monocyte, occasional plasma cells and histiocytes.

Grocott's silver  stain shows black cysts in alveolar wall & exudates. It looks as round or indented  (“new-moon” shape). )

Tuberculosis

Tuberculosis may present with atypical manifestations in one-third of the cases, and multiple thin-walled cysts are one such rare manifestations of tuberculosis

Lee JY, Lee KS, Jung KJ et al. Pulmonary tuberculosis: CT and

pathologic correlation. J Comput Assist Tomogr 2000; 24:691-8.

Mechanisms

Marked caseating necrosis of the bronchial walls cystic bronchiectasis

Granulomatous involvement of the bronchioles may lead to a check-valve mechanism leading to cyst formation

In isolated cases, isoniazid has been implicated

Multiple large cysts (bilateral), thin walled, and involving all zones of the lung

HYDATID CYST

Hydatid cysts may be solitary or multiple, the number depending mainly on the amount of ova ingested and the number of embryos filtered through the liver and lungs.

A centrally located cyst is said to be usually round, but may become oval or polycyclic

Hydatid cyst

Inferior lobes most commonly affected

Intact:ruptured::3:1 The cysts may change shape on

maximum inspiration and expiration, which is known as the Escudero- Nimerov sign, but which is true also of any thin-walled water filled cyst

Calcified unilocular hydatid cyst. Contrast material-enhanced CT scan shows a round lesion with water attenuation and a ringlike pattern of calcification (arrows). This pattern represents calcification of the pericyst and strongly suggests a diagnosis of hydatid cyst

MICROSCOPY

Outer acellular laminated membrane Germinal membrane  Protoscolices, attached and budding

from the membrane

Coccidiodomycosis

When acute, cavities can be thick-walled or surrounded by dense consolidation.

Thin walled grape skin cysts can also be seen with acute infection or as a result of healing of the thick walled lesions

large (up to 80 micron) spherules/sporangia, as shown in this case. These are filled with numerous spherical endospores. The sporangia and endospores can be within giant cells or extracellularly. 

Honeycomb Lung

The original usage was a gross pathological term employed at autopsy to describe lungs with a wormeaten or honeycomb appearance

II. HEPPLESTON, A. G. Pathology of honeycomb `lung. Thorax, 1956, II, 77-94.

HONEYCOMB LUNG

Honeycombing represents destroyed and fibrotic lung parenchyma with numerous cystic airspaces with thick fibrous walls representing the late stages of lung diseases with complete loss of acinar architecture.

Variable wall thickness and lined by metaplastic bronchiolar epithelium

Hansell DM, Bankier AA, MacMahon H, et al. Fleischner Society: Glossary of terms for thoracic imaging. Radiology. 2008;246(3):697-722.

Pathology

Essential change is the obliteration of bronchioles by fibrosis or granulomata and compensatory dilatation of neighboring bronchioles, which forms the honeycomb appearance

Heppleston AG. The pathology of honeycomblung. Thorax 1956; 11:77–93

HONEYCOMBING

“Clustered cystic air spaces, typically of comparable diameters on the order of 3–10 mm but occasionally as large as 2.5 Cm.

Usually subpleural and characterized by welldefined walls”

However, “the cystic air spaces of honeycomb lung tend to share walls”

Hansell DM, Bankier AA, MacMahon H, McLoud TC, Muller NL, Remy J. Fleischner Society: glossary of

terms for thoracic imaging. Radiology 2008; 246:697–722Webb WR, Muller NL, Naidich DP. Standardized terms for

high-resolution computed tomography of the lung: a proposed glossary. J Thorac Imaging 1993; 8:167–175

Idiopathic interstitial pneumonia

Honeycombing was identified in 41–100% of UIP, depending on the reported series .

Nonspecific interstitial pneumonia (NSIP) and desquamative interstitial pneumonia (DIP), which are the chronic interstitial pneumonias of IIP show honeycombing in 0–30% and 4.3–39%, respectively .

In acute interstitial pneumonia, the frequency is lower, ranging from 6% to 14%

IDIOPATHIC PULMONARY FIBROSIS

Honeycomb cysts are a feature of idiopathic pulmonary fibrosis (IPF) and typically have a subpleural location

Walls of the cysts are clearly defined and thickened – a sign of fibrosis

Predominant in posterior and lower lobes This characteristic distribution distinguishes

UIP from other diseases with honeycomb lung.

Diffuse ground glass opacities with cysts (arrow). (B) A high resolutionCT scan from the same patient more clearly shows cysts within ground glassopacities. Traction bronchiectasis is also present, suggesting that the ground glassopacities are secondary to fibrosis rather than an inflammatory process.

Multiple thin-walled cysts occupying most of lobe. Note that some cysts contain mucous material

Idiopathic pulmonary fibrosis showing traction bronchiectasis (white arrows). The adjacent bronchi and vasculature differentiates these structures from true cysts. End-stage lung fibrosis is evident with diffuse honeycombing (black arrow), reticulation and traction bronchiectasis.

MICROSCOPY

Patchwork pattern, which is characterized by alternating zones of abnormal and normal lung side by side without transition zones

Small islands of residual normal or nearly normal lung interspersed among extensively scarred parenchyma

Combination of areas of honeycomb change and scars that replace normal alveoli

Honeycomb areas are characterized by enlarged airspaces lined by bronchiolar epithelium and often filled by mucin and variable numbers of inflammatory cells.

Small areas of active fibrosis (fibroblast foci) are present in the background of collagen deposition

Desquamative interstitial pneumonia

It is a disease that is seen almost exclusively in current or former smokers

Accumulation of pigmented macrophages within the airspaces with a homogenous appearance and limited mononuclear infiltrate within the interstitium.

 The alveolar septa are thickened by a sparse inflammatory infiltrate that often includes plasma cells and occasional eosinophils, and they are lined by plump cuboidal pneumocytes.The intraluminal macrophages in DIP frequently contain dusty brown pigment .

Cellular non-specific interstitial pneumonia (NSIP) pattern. On higher power, the septal widening is due to a mild to moderate infiltrate of lymphocytes with scattered plasma cells, with minimal associated fibrosis.

Marked thickening of the alveolar septa due to interstitial edema, inflammatory cell infiltration, fibroblast proliferation (within the interstitium and airspaces), and type II cell hyperplasia, Hyaline membranes in focal areas along alveolar septa, Thrombi in small arteries

Other causes

Honeycomb cystic lung disease Asbestosis Collagen vascular disease Hypersensitivity pneumonitis Sarcoidosis

Bronchiectasis

Bronchiectasis, or the dilatation and distortion of bronchi and bronchioles, may be mistaken for cystic airspace disease when a dilated airway is viewed ‘‘en face’’

Bronchiectasis may be the result of either a chronic suppurative process or accompany lung fibrosis, when it is then referred to as traction bronchiectasis

Challenges in pulmonary fibrosis ? 3: Cystic lung disease

Gregory P Cosgrove, Stephen K Frankel, Kevin K BrownThorax 2007;62:820–829. doi: 10.1136/thx.2004.031013

Bronchiectasis

Cystic bronchiectasis can be differentiated from true cystic lung disease by the continuous relationship of the cystic structure to bronchial tree

Approximately uniform, medium-sized cavities are typical of cystic bronchiectasis.

Valsalva and Mueller maneuvers produce rapid change in the size of cysts, which freely communicate with the airways; this change distinguishes cystic bronchiectasis from other conditions.

Traction Bronchiectasis

Differentiated from cystic lung disease by the presence of an adjacent blood vessel suggesting a bronchovascular unit rather than a cystic air space.

Mesenchymal cystic hamartoma

Mesenchymal cystic hamartoma (MHC) of the lung is a very rare disease with an indolent clinical course and might be easily misdiagnosed as pleuropulmonary blastoma and other uncommon cystic lung lesions

HISTOLOGY

Bilateral multifocal cysts lined by normal or metaplastic respiratory epithelium resting on a cambium layer of mesenchymal cells

● Lesion is initially solid, but becomes cystic when approximately 1 cm in diameter● Slow growing

Cysts were lined with normal respiratory epithelium. Beneath the epithelium were band-like layers of cells composed of primitive mesenchymal-like cells with dark oval nuclei, scanty cytoplasm, and very rare mitoses . Scattered or clustered mature fat cells were present in some areas of the cysts and nodules

Benign multicystic mesothelioma

Rarely described in the pleura Single or multiple thin walled cysts Multiloculated cyst lined by

attenuated or cuboidal cells with atypia

TERATOMA

Intrapulmonary teratomas typically range from 2.8 to 3 cm in diameter, and are cystic and multiloculated but may rarely be predominantly solid

In 42% of the cases, the cysts are in continuity with bronchi, and have an endobronchial component resulting in hemoptysis or expectoration of hair or sebum

MICROSCOPY

Radiographically, lesions are typically cystic masses often with focal calcification.

Microscopically, mesodermal, ectodermal and endodermal elements are seen in varying proportions.

Pulmonary teratomas are mostly composed of mature, cystic somatic tissue

Mature elements often take the form of squamous lined cysts.

Thymic or pancreatic elements may be seen in mature teratomas

CYSTIC LUNG METASTASES

The appearance of cystic lesions in the lung in malignancy is rare and predisposes to spontaneous pneumothoraces.

Multiple cystic lesions occur commonly in bronchus carcinoma and also sarcoma, bladder cancer and, less commonly, lymphoma

Both chemotherapy and immune suppression can induce cavitation in malignant lesions.

Tumour necrosis and tumour infiltration of air-containing spaces with a check-valve mechanism are postulated for causing these cystic lesions

SARCOMAS

Spontaneous pneumothorax complicating sarcoma is associated with most cell types, recurrent in nearly half of the patients

The main cell types consisted of angiosarcoma (39%), leiomyosarcoma (15%) and osteosarcoma (15%)

Hoag JB, Sherman M, Fasihuddin Q, et al. A comprehensive review of spontaneous pneumothorax complicating sarcoma. Chest 2010; 138: 510–518

Squamous cell carcinoma Metastases from the head and neck tended to

cavitate when small and to have thin walls, whereas metastases from squamous cell carcinomas of the bladder and genitalia generally cavitated when they were larger and had thickened walls.

Seminoma, Ewing sarcoma, myxosarcoma, Wilms tumor, osteogenic sarcoma, angiosarcoma, transitional cell carcinoma, teratocarcinoma

Multiple, Thin-Walled Cystic Lesions of the LungJ. David Godwin,w. Richard Webb, Charles J. SavocaGordon Gamsu, Philip C. GoodmanAJR 135:593-604, September 19800361 -803X/80/1 353-0593

Rare cystic lung lesions

Pulmonary thromboembolism Neurofibromatosis Follicular bronchitis Pulmonary spread of laryngeal

papillomatosis Hodgkin’s lymphoma Rheumatoid arthritis with necrobiotic

nodules Birt Hogg syndrome Down’s syndrome