Mini ReviewOpen Access

Spectrum of Lung and Cardiovascular Diseases in Association with Pulmonary Interstitial Glycogenosis

Rose Chami*

Division of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada


“Pulmonary Interstitial Glycogenosis (PIG) associated with a spectrum of neonatal pulmonary disorders”, reported by Cutz et al represents one of the largest series published to date. The report included twenty-eight cases of lung or cardiac disorders with coincident diffuse, patchy, or focal PIG reviewed in Division of Pathology, The Hospital for Sick Children. The authors focused on reporting a spectrum of disorders associated with PIG and described four clinicopathological subgroups including imaging, ultrastructural findings, and clinical outcome. The present paper highlights the main findings reported by Cutz et al, and a review of literature is also presented.


PIG is a rare interstitial lung disease of infancy that is placed in the category of “specific conditions of undefined etiology” in the childhood interstitial lung disease (ChILD) classification (1). PIG has been reported mainly in either pre-term or full-term babies younger than six months of age (2, 3). Infants with PIG usually present with persistent tachypnea and hypoxemia shortly after birth or in the first few weeks of life (3, 4, 5). The reported PIG cases have been described in otherwise normal lungs (isolated/diffuse or patchy pattern) (3, 5) or often in conjunction with other cardiovascular or pulmonary abnormalities (2, 3, 6, 7). To the best of my knowledge, approximately 78 cases of patients with PIG (not including the cases published by Cutz et al) have been reported in the literature with variable information regarding the clinical presentation, comorbidities, imaging, histopathology, and outcome were published. The described findings are summarized in Table 1.

PIG was first described in 2002 by Canakis et al (4). The definitive diagnosis is made by histologic examination. Histologic features on lung biopsy are characterized by expansion of pulmonary interstitium by round to ovoid-shaped mesenchymal cells with pale cytoplasm (fig. 1A & 1B) due to glycogen accumulation demonstrable by periodic acid-Schiff positivity (diastase sensitive) on light microscopy. However, the presence of glycogen is best identified on electron microscopy (EM). The ultrastructural examination showed poorly differentiated interstitial mesenchymal cells with vesicular nuclei and cytoplasm containing sparse organelles and abundant monoparticulate glycogen (fig. 1C & 1D). Some PIG cells showed features of differentiation toward the fibroblast lineage differentiation (2).

Table 1. Reported Cases of PIG
Authors N. of patients GA at birth, preterm or term Sex Age at presentation CHD PHN Other comorbidities Lung histopathology (main findings) Chest HRCT (main findings) Outcome at time of last follow-up
Liptzin et al, 2018 (6) 24 Late preterm/term (N=18) M (N=15)
F (N=9)
Range 0.3-6 months 63 % of patients [including HLHS, PVS, ASD, VSD], PDA, TF, mitral stenosis, coarctation of aorta) 38% of patients (N=9) Cleft lip/palate (N=2)
Autism (N=1)
Unilateral kidney (N=1)
Neurologic deficits (N=4)
Hypotonia (N=1)
Seizure (N=1)
Hypothyroidism (N=1)
Airway malacia (N=3)
Aspiration (N=1)
Urinary retention (N=1)
Connective tissue disease (N=1)
22q deletion (N=1)
Diffuse PIG (45.8%; N=11)
Patchy PIG (45.8%, N=11)
Alveolar simplification (79%, N=19)
PAH (79%, N=19)
GGO (N=19)
Cysts (N=11)
Linear reticular opacities (N=3/22)
Off all respiratory support (N=12)
Supplemental oxygen (N=8)
Mechanical ventilation (N=2)
Lung transplantation (N=1)
Died (N=1)
Weinman et al, 2018 (10) 15 39 weeks M Birth PFO, DTV Yes - Diffuse PIG, PAH GGO, cysts Oxygen at rest
40 weeks M 3 months PFO, PDA Yes Aspiration, autism, airway malacia Patchy PIG, PAH, Alveolar simplification Architectural distortion, atelectasis Off respiratory support
34 weeks F Birth PFO, PVS Yes Seizures Diffuse PIG, PAH, PH Alveolar simplification GGO, cysts, interlobular septal thickening Lung transplantation and oxygen at rest
40 weeks F 3 months Absent No - Patchy PIG, PAH GGO, cysts Oxygen with sleep
32 weeks F Birth Absent Yes Airway malacia Diffuse PIG, PAH, Alveolar simplification GGO, cysts, architectural distortion Off respiratory support
29 weeks F Birth PDA No Airway malacia Patchy PIG, PAH, PN Alveolar simplification Cysts, GGO, interlobular septal thickening Mechanical ventilation
39 weeks M Birth Absent Yes Airway malacia Diffuse PIG, PAH, PH, Alveolar simplification Air trapping, GGO Off respiratory support
36 weeks M Birth ASD No - Patchy PIG, PAH, PN, PH, alveolar simplification Cysts, GGO, architectural distortion Oxygen at rest
29 weeks M Birth PDA No - Patchy PIG, PAH, CMV, alveolar simplification Cysts, GGO, architectural distortion Off respiratory support
36 weeks M Birth TF Yes Aspiration, septo-optic dysplasia Patchy PIG, pleural thickening, alveolar simplification GGO, atelectasis, PIE Off respiratory support
37 weeks M Birth Absent Yes CDH Diffuse PIG, PAH, PH, Alveolar simplification GGO, cysts, interlobular thickening Died
30 weeks M Birth ASD, PDA Yes - Diffuse PIG, PAH, Alveolar simplification Cysts, GGO, interlobular thickening Off respiratory support
40 weeks F Birth ASD, PDA Yes Single kidney Patchy PIG, PAH, Alveolar simplification GGO, architectural distortion, atelectasis Oxygen at rest
27 weeks M Birth PDA No - NA GGO, cysts, interlobular thickening Off respiratory support
40 weeks F 1 month ASD, PDA, ascending aortic dilation Yes CTD ACTA2 mutation, Airway malacia NA Cysts, GGO, architectural distortion Off respiratory support
Seidl et al, 2018 (7) 11 Term F Birth No Yes Mucopolysaccharidosis NA Consolidation, linear opacities, bronchiectasis Reduced, but persistent respiratory symptoms, no oxygen demand, ±
Term M Birth PDA Yes Mucopolysaccharidosis Diffuse PIG, mild reduced alveolarization GGO, consolidation, septal thickening Reduced, but persistent respiratory symptoms, no oxygen demand, ±
Term M Birth VSD, PFO Yes Brain (divided plexus) Diffuse PIG, moderate reduced alveolarization Linear opacities, consolidation Asymptomatic
Term M Birth Absent Yes - Diffuse PIG, moderate reduced alveolarization GGO, mosaic attenuation, linear opacity, consolidation, architectural distortion Died
34 weeks M Birth Absent No Encephalopathy, hepatic cysts Diffuse PIG, mild reduced alveolarization Hyperinflated 2ndary lobule, septal thickening Reduced, but persistent respiratory symptoms, no oxygen demand, ±±
Term F Birth Absent Yes - Diffuse PIG, mild reduced alveolarization GGO, consolidation, mosaic attenuation, linear opacities Asymptomatic
30 weeks M Birth PDA No Hypoglycemia NA GGO, septal thickening, crazy paving pattern, linear opacity, hyperinflated secondary lobule Reduced, but persistent respiratory symptoms, no oxygen demand
Term F Birth Absent Yes - Diffuse PIG, severe reduced alveolarization GGO, linear opacity, bronchial wall thickening Asymptomatic
Term M 7 weeks AVSD Yes - Patchy PIG, moderate reduced alveolarization GGO, mosaic attenuation, septal thickening, emphysema Asymptomatic
Term F Birth VSD, ASD hypoplastic pulmonary arterial system Yes Renal failure, megaureter (left) Diffuse PIG, severe reduced alveolarization NA Asymptomatic
Term M Birth ASD, VSD, coarctation Yes Heterotaxy syndrome (heart, lung, abdomen) Diffuse PIG, severe reduced alveolarization GGO, consolidation Reduced, but persistent respiratory symptoms, no oxygen demand, ±±
Still et al, 2018 (17) 1 Term F Birth Absent Yes - Patchy PIG, Alveolar simplification (moderate), PAH Diffuse mosaic attenuation, right pulmonary artery enlargement On low flow oxygen, multidrug regimen for persistent pulmonary hypertension
Demirel et al, 2018 (18) 1 Term F Shortly after birth PDA (large), secundum ASD* Yes Filamin A protein deficiency, Bronchomalacia (LLL) Patchy PIG (mild), moderate alveolar simplification and hyperinflation Findings most consistent with Filamin A deficiency ** Supplemental oxygen, multidrug regimen for pulmonary hypertension, steroids
Deutsch et al, 2016 (19) 5 38 M Birth Absent NA - PIG (pattern distribution NA), lung growth abnormality NA Persistent tachypnea, cough
37 M Birth Absent NA Severe chylothorax PIG (pattern distribution NA), lung growth abnormality NA Asymptomatic
41 F Birth Total anomalous pulmonary venous return/vein stenosis Yes - PIG (pattern NA), lymphangiectasia, PAH NA Died
35 F Birth Double outlet right ventricle Yes VACTERL PIG (pattern NA), lung growth abnormality, PAH NA ntermittent asthma
36 M Birth Absent Yes - PIG (pattern NA), lung growth abnormality, PAH NA Asymptomatic
Sanchez-de-Toledo et al, 2015 (20) 1 Term NA Birth D-transposition of great arteries with intact ventricular septum Yes - PIG NA Successful corrective surgery, Asymptomatic
Simons et al, 2014 (21) 1 NA F 1 month ASD, massive window duct with right ventricular hypertrophy and pulmonary trunk dilation NA Aniridia PIG, alveolar simplification NA Successful corrective surgery, Asymptomatic
Ehsan et al, 2014 (22) 1 Term M Birth Absent NA - Diffuse PIG Alveolar simplification (diffuse) GGO (diffuse) Asymptomatic, no oxygen demand, although FVC remained significantly reduced compared to healthy control patients
Ross et al, 2014 (23) 1 34 M Birth Pulmonary valve abnormalities No Noonan syndrome (positive test for heterozygous G60A mutation in PTPN11) Diffuse PIG, Alveolar growth abnormality/simplification, Mild acute inflammation Septal thickening, Extensive dependent airspace opacities, Small pleural effusions On nocturnal supplemental oxygen
Alkhorayyef et al, 2013 (16) 1 Term M Birth Severe hypertrophic cardiomyopathy, PFO Yes - Diffuse PIG CT none done Chest X-ray: bilateral GGO Died
Radman et al, 2012 (14) 2 Term F Birth D-transposition of great arteries with intact ventricular septum, PFO, and large PDA Yes - Patchy PIG, PAH NA Asymptomatic
Term M Birth Heterotaxy with complex cardiovascular abnormalities Yes - Diffuse PIG, PAH (minimal) NA On supplemental oxygen
King et al, 2011 915) 1 Term M Birth Large PDA, PFO Yes - Patchy PIG, severe lung growth abnormality, PAH (mild) NA Died
Smets et al, 2011 (23) & 2004 (24) 1 Term   Birth Absent Yes Hunter syndrome (mucopolysaccharidosis type II) Diffuse PIG Architectural distortion, linear opacities, areas of hyperinflation and GGO Frequent upper respiratory infections, Lung function tests: severe combined obstructive/restrictive pattern
Castillo et al, 2010 (12) 1 37 M Birth Absent NA - Patchy PIG, Severe alveolar growth abnormality, Mild pleural thickening GGO (diffuse), prominent interstitial opacities, multiple scattered cystic spaces Asymptomatic
Lanfranchi et al, 2010 (26) 1 31 M 18 days of life Absent NA - Diffuse PIG Diffuse coarse reticular opacities Asymptomatic
Orlando et al, 2005 (27) 2 31 M Birth Absent No - Diffuse PIG GGO, septal thickening Asymptomatic
31 M Birth Absent No - Diffuse PIG GGO, septal thickening Asymptomatic
Canakis et al, 2002 (4) 7 33 M 5 days Absent NA - Diffuse PIG Not done at initial presentation Mild intermittent bronchospasm
38 M 1 day Absent NA - Diffuse PIG GGO, patchy (performed at 7 months age) Mild intermittent bronchospasm
40 M 4 weeks Absent NA - Diffuse PIG GGO, patchy (performed at 2 years of age) Asymptomatic
33 M 1 day Absent NA - Diffuse PIG NA On supplemental oxygen
29 F 1 day Absent NA - Diffuse PIG NA Asymptomatic
40 M 1 day Absent NA - Diffuse PIG NA Asymptomatic
25 M 1 day Absent NA - Diffuse PIG NA Died (cor pulmonale)

Abbreviations: PIG= pulmonary interstitial glycogenosis, N= number of patients, GA=gestational age, CHD=congenital heart disease, PHN=pulmonary arterial hypertension, HRCT= high-resolution computed tomography, HLHS=hypoplastic left heart syndrome, PVS= pulmonary vein stenosis, ASD=atrial septal defect, VSD=ventricular septal defects, PDA=patent ductus arteriosus, TF=Tetralogy of Fallot, NA=not available, PAH= pulmonary artery hypertrophy, GGO=ground glass opacities, PFO=patent foramen ovale, DTV=dysplastic tricuspid valve, PH=pulmonary hemorrhage, PN=pneumonia, CMV=cytomegalovirus, CDH=congenital diaphragmatic hernia, CTD=connective tissue disease, AVSD= atrial-ventricular septal defects, LLL=left lower lobe, VACTERL= vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities, FVC=forced vital capacity.

* large patent PDA, secundum atrial septal defect with left to right shunting, associated left atrial, right atrial and right ventricular enlargement, and pulmonary insufficiency with right ventricular hypertrophy. Moderate to severe pulmonary arterial hypertension.

**diffuse pulmonary hyperinflation, pruning of the peripheral pulmonary vasculature, and patchy areas of atelectasis.

± recurrent respiratory infections, reduced exercise tolerance

±± tachypnea at rest

rarediseases-17-1170-Fig1

Figure 1: (A) Abnormal enlarged alveoli (stars) with diffuse interstitial thickening (double head arrows) with mesenchymal cells [H&E stain]; (B) Interstitial mesenchymal cells with pale cytoplasm (H&E stain); (C) Mesenchymal cells with rare organelles and abundant monoparticulate glycogen in cytoplasm (white X) and pneumocytes type II (black Asterix) [Transmission EM]; (D) Close-up view of PIG cells with pools of glycogen (white X) [Transmission EM].

Additionally, 28 cases of PIG in association with a spectrum of lung or cardiac disorders have been reported recently by Cutz et al. In this paper, we described four clinicopathologic subgroups including comorbidities, imaging and outcome (summarized in Table 2). As previously reported (3, 6, 8), we found that PIG is most commonly associated with lung/alveolar growth abnormality, with or without pulmonary arterial hypertension. The mean age at time of biopsy was 10.3 weeks (range 16 days-6 months). This group of patients presented with respiratory distress in the first weeks of life. Most patients in our series had pulmonary hypertension. Chest imaging studies revealed variable changes such as diffuse lung interstitial thickening and ground-glass opacities. The lung biopsies showed patchy or diffuse PIG changes, and abnormal alveolarization manifested by alveolar enlargement and simplification. This group of patients had a high mortality rate with 6 of the 9 infants dying of respiratory failure within few weeks of presentation despite conventional treatment. Most infants in this group developed refractory pulmonary hypertension.

Table 2. List of Cases of PIG Reported by Cutz et al; Patients’ Gender, Gestational Age, Comorbidities, Histopathology, Imaging Findings, And Clinical Outcome at Last Follow-Up
Category Patient GA, preterm, or term Sex Comorbidity Lung histopathology Chest HRCT findings Outcome
I 1 Term M Pulmonary hypertension AGA, diffuse PIG, PAH NA Died
2 Term F - AGA, patchy PIG NA NA
3 32 weeks M - AGA (severe), Diffuse PIG NA NA
4 Term M Pulmonary hypertension AGA, Diffuse PIG, PAH GGO (diffuse) Died
5 Term M Pulmonary hypertension AGA, Patchy PG, PAH GGO Died
6 33 weeks F Pulmonary lymphangiectasis AGA, Diffuse PIG, lymphangiectasia Diffuse septal thickening, bilateral pleural effusion NA
7 Term M Congenital chylothorax NA NA Died
8 Term F Pulmonary hypertension, arthrogryposis AGA, patchy PIG, PAH NA Died
II 9 Term M PDA, dilated cardiomyopathy, pulmonary hypertension Patchy PIG, PAH (mild) GGO (focal) Died
10 Term F Complex cardiac abnormalities (right atrial isomerism, dextrocardia, AVSD, DORV, hypoplastic RPA), pulmonary hypertension Focal PIG, lymphangiectasis, PAH (moderate) GGO (patchy) Died
11 Term M Hypoplastic left heart syndrome Focal PIG, AGA, PAH (mild) GGO Died
12 36 weeks F Noonan syndrome with hypertrophic cardiomyopathy Patchy PIG, lymphangiectasis, PAH Diffuse septal thickening, bilateral pleural effusion Died
13 Term F ASD, VSD, pulmonary hypertension, aspiration, pneumonia Diffuse PIG, PAH (mild) Diffuse lung interstitial disease Died
14   M TAPVD Diffuse PIG, AGA GGO (diffuse, mild), septal thickening (patchy) Successful corrective surgery
III 15 Term M Pulmonary hypertension Hyperplasia of PNE cells, diffuse PIG, “crazy paving” appearance Off all respiratory support
16 Term M Pulmonary lymphangiectasia Hyperplasia of PNE cells, PIG, AGA, lymphangiectasia, GGO, septal thickening, patchy hyperinflation Off all respiratory support
17 30 weeks M ASD, VSD, airway malacia, autism Hyperplasia of PNE cells, PIG, PAH (mild) GGO, basal hyperinflation Off all respiratory support
18 36 weeks F Pulmonary hypertension Hyperplasia of PNE cells, patchy PIG, PAH (mild) NA NA
19 Term F Pulmonary hypertension Hyperplasia of PNE cells, patchy PIG NA NA
IV 20 Term F - CPAM type I (large cyst type), patchy PIG Multicystic lesion with air-filled, thin-walled spaces of large size in in LLL Asymptomatic after surgical treatment
  21 Term F Chiari malformation CPAM type I (large cyst type), diffuse PIG Multicystic lesion with air-filled, thin-walled spaces of large size in RML & LLL Asymptomatic after surgical treatment
  22 Term F Renal dysplasia CPAM type I with systemic arterial supply (hybrid lesion), focal PIG Large air-filled cystic lesion with systemic vascular supply Asymptomatic after surgical treatment
  23 31 weeks M - CPAM type I with systemic arterial supply (hybrid lesion), focal PIG Fluid and air-filled large cystic lesion with systemic vascular supply Asymptomatic after surgical treatment
  24 Term M - CPAM type I (large cyst-type), focal PIG Large air-filled cystic lesion Asymptomatic after surgical treatment
  25 Term F CHD CLE with focal PIG RML hyperinflation Cardiac complication
  26 Term M - CLE with focal PIG RML hyperinflation Asymptomatic
  27 Term M - CLE with diffuse PIG RUL overinflation Asymptomatic after surgical treatment
  28 Term M - CLE with diffuse PIG LUL hyperinflation Asymptomatic after surgical treatment

Abbreviations: PIG= pulmonary interstitial glycogenosis, GA=gestational age, AGA=alveolar growth abnormality, HRCT= high-resolution computed tomography, ASD=atrial septal defect, VSD=ventricular septal defects, PDA=patent ductus arteriosus, NA=not available, PAH= pulmonary artery hypertrophy, DORV=double outlet right ventricle, hypoplastic RPA=hypoplastic right pulmonary artery, GGO=ground glass opacities, AVSD= atrial-ventricular septal defects, TAPVD=Total Anomalous Pulmonary Venous Drainage, CPAM=congenital pulmonary airway malformation, PNE cells=pulmonary neuroendocrine cells, LLL=left lower lobe, RML=right middle lobe, CHD=congenital heart disease, CLE=congenital lobar emphysema/hyperinflation, RUL=right upper lobe, LUL=left upper lobe.

The second subgroup represented patients with PIG associated with congenital heart diseases (CHD) (including hypoplastic left-heart syndrome, hypertrophic cardiomyopathy in patient with Noonan syndrome). Chest imaging studies showed variable non-specific changes (including ground glass opacity, septal thickening). The mean age at lung biopsy was 2.4 weeks (5 days-6weeks). The PIG changes on light microscopy were focal to patchy. Most infants died of complications despite corrective surgery.

The third category consisted of a specific group of patients with combined PIG and hyperplasia of pulmonary neuroendocrine cells (PNEC), referred to as neuroendocrine hyperplasia of infancy-like (NEHI-like). Infants of this group were either pre-term or full-term, mostly presented with tachypnea and wheezing between 3 and 10 weeks of age. Chest imaging studies revealed variable changes including “crazy paving” appearance, bilateral ground-glass opacities or basal hyperinflation. Lung biopsies demonstrated patchy to diffuse PIG, and prominent hyperplasia of PNEC (identified with immunohistochemistry studies). The patients of this group were mostly asymptomatic over time with normal lung function or persistent mild obstructive defects. The clear significance and etiology of this combined pathology is unknown. PNEC system has multifaceted roles including lung development, neonatal adaptation as airway oxygen sensors, and postnatal airway homeostasis as guardians of a stem cell niche (9). Hyperplasia of PNEC has been identified in several perinatal pediatric lung disorders including bronchopulmonary dysplasia, neuroendocrine hyperplasia of infancy, central hypoventilation syndrome, Sudden Infant Death Syndrome, and cystic fibrosis (9).

The fourth and final group consisted of cases of congenital lung malformation with coincident PIG. This included 5 patients with CPAM type 1 (large cyst type) and 4 patients with congenital lobar emphysema/hyperinflation (CLE). All patients presented with respiratory distress, soon after birth for CPAM, and between 4 weeks and 8 months of age for CLE cases. Chest imaging studies demonstrated changes related to the underlying diseases; localized cystic lesion in patients with CPAM, and lobar emphysema/hyperinflation in patients with CLE. The mean age at time of biopsy was 8.8 weeks for CPAM (range 3 days – 4 weeks), and 11.6 weeks for CLE (range 4 weeks-8 months). Pathologic examination confirmed the diagnosis of CPAM type 1 or CLE. In addition, it showed patchy PIG changes in both the lesion and adjacent <> areas of pulmonary tissue. All patients underwent lobectomy of the affected lung. Except for one case, who had CLE and congenital heart disease, patient with CPAM and CLE all recovered post-surgery and were asymptomatic on follow-up.

In summary, the spectrum of disorders in association with PIG reported by us (2) is diverse and is quite like that reported by Langston et al (3), Liptzin et al. (6), Dishop M. (8), and Weinman (10). We found that PIG is most commonly seen in association with lung alveolar growth abnormality (alveolar simplification) and / or cardiovascular diseases. We have also described additional cases of PIG associated with persistent pulmonary hypertension with or without CHD, cardiovascular disease, Noonan syndrome (23), and congenital lobular emphysema (28). In addition, we have reported a new association of PIG with other lung disorders including NEHI-like, and CPAM type 1 (large cyst type). Similarly, to previous published studies by Liptzin et al. (6), Weinman et al (10), Deutsch et al. (11), Castillo et al. (12), and Lee E. (13), we noticed that the imaging of PIG is variable, non-specific (including diffuse ground-glass opacities, hyperinflation, and cystic spaces), and is likely affected by the presence of coexisting lung disorders. Based on available literature, PIG is considered to have a favorable prognosis, although clinical outcome is dependent on the severity of any associated lung disorders or other comorbidities. In our series, we found that the mortality rate was high when PIG coincided with life-threatening comorbidities (including severe lung growth abnormality, complex cardiovascular disease). This note was also emphasized by multiple previously published reports (6, 11, 12, 14, 15, 16). In the review by Deutsch et al (16), no mortality occurred among the six cases of diffuse/isolated PIG, although respiratory symptoms persist in most patients. Given no radiographic patterns, genetic findings, or biomarkers were characteristic of PIG, the lung biopsy remains the gold standard for diagnosis.

Finally, the precise nature and clinical significance of PIG is unknown. While the pathology demonstrated poorly differentiated interstitial mesenchymal cells, there is a debate whether PIG is a primary developmental lung disorder or a reactive process to abnormal lung development and injury. Our finding of a close association of PIG with different lung developmental disorders and comorbid cardiac developmental diseases favors a defect in interstitial fibroblast differentiation. Further studies are required to define the precise pathogenesis and significance of PIG and its impact on concurrent disease processes.

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Article Notes

  • Published on: December 17, 2018

Keywords

  • Infants
  • Pulmonary interstitial glycogenosis
  • Congenital pulmonary airway malformation
  • Growth alveolar abnormality
  • Hyperplasia of pulmonary neuroendocrine cells
  • Mesenchymal cells

*Correspondence:

Dr. Rose Chami
Division of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada
Email: rose.chami@sickkids.ca

©2018  Chami R. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License.