The Respiratory Tract

Bronchobiliary and bronchoesophageal fistulae

disease

Bronchiectasis

tussis

Immotile cilia syndrome

sis, male subfertility ●● EM: Absence of both inner and outer dynein

arms, radial spoke defect, compound cilia

Cystic fibrosis

Williams-Campbell syndrome

main stem bronchus

Bronchogenic cyst

●● Extrapulmonary mass, midline, located in subcutaneous tissue (anywhere from supra sternum to diaphragm)

cuboidal epithelium

●● Fibrous wall contains mucinous glands and cartilage

by squamous epithelium, have skeletal muscle), enteric cysts (lined by mucus secreting columnar epithelium, have gastric glands in the wall)

Plastic bronchitis

●● Bronchial casts made up of fibrin, mucin, inflammatory cells

LUNG

Pulmonary agenesis

●● Unilateral, compatible with long-term survival

Sequestrations

Extralobar

●● Masses of pulmonary parenchyma outside visceral pleura, usually inside thorax

●● Develop from outpouching of foregut/not connected to tracheobronchial tree

neonatal period ●● CPAM-type 2 associated with sequestra-

tion ●● Associated anomalies: Bronchogenic cysts,

cardiovascular malformations, diaphragmatic hernia

●● Well-circumscribed discrete lesion, variable size

●● Blood supply by direct branch of thoracic/ abdominal aorta (systemic vessels)

like structures seen (as in CPAM type 2) ●● Prominent lymphatics around broncho-

vascular structures ●● Rhabdomyomatous dysplasia associated

Intralobar

●● Portion of pulmonary parenchyma, within the pleura

●● Sequestered from rest of trachea-bronchial tree

pulmonary infection ●● Children after 5 years of age, not congeni-

tal, not associated with other congenital abnormalities

●● Pulmonary parenchyma shows multiple distorted cysts, chronic inflammation, and fibrosis

Hypoplasia

ber/size of alveoli (normal radial alveolar count = 5-6)

●● Extrathoracic compression; restriction of space for lung growth (renal agenesis → oligohydramnios → decreased uterine space), enlarged kidneys

●● Intrathoracic compression (diaphragmatic hernia, extralobar sequestration, thoracic neuroblastoma)

●● Musculoskeletal abnormalities (thanatophoric dwarfism)

Infantile (congenital) lobar emphysema (ILE)

●● Overdistension/hyperplasia of pulmonary lobe (due to partial/complete obstruction of bronchus) by extrinsic/intrinsic factors

●● Etiology: Bronchial atresia, bronchial stenosis, abnormal origin of bronchus, aspirated meconium, mucus plug, foreign body

Hyperinflated lung

●● Classic form: Alveolar ducts/alveoli dilated up to 3-10 times normal size but otherwise unremarkable

●● Hyperplastic form: Not overinflated, complex acinar formation, large number of alveoli (↑RAC)

Congenital pulmonary lymphangiectasis

●● Rare, fatal disorder, within a few hours of birth

●● Primary disorder/associated with other congenital cardiovascular malformations

●● Infants with “total anomalous pulmonary venous return” show enormously dilated lymphatics

Congenital pulmonary airway malformation (CPAM)

●● Most frequent cystic lung disease in children

anomalies

CPAM type 0

CPAM type 1

cysts, compressed normal parenchyma ●● Cysts lined by ciliated pseudostratified

columnar/cuboidal epithelium ●● Mucus-producing cells (potential to pro-

duce bronchioloalveolar carcinoma) may be interspersed in between

CPAM type 2

anomalies ●● Back-to-back bronchiole-like structures

lined by cuboidal/columnar cells ●● Associated rhabdomyomatous dysplasia ●● Similar morphological features seen in

extralobar sequestration

CPAM type 3

shift

●● Resembles immature lung, bronchiole-like structures, adenomatoid appearance

CPAM type 4

●● Large air-filled cysts at the periphery of lung

toma ●● Respiratory distress/pneumothorax (PT)

Congenital alveolar capillary dysplasia

●● Progressive hypoxemia in newborn/ uniformly fatal

CHD, asplenia ●● Failed formation and ingrowth of alveolar

capillaries ●● Large centrally placed capillaries within

alveolar septal wall ●● Misalignment of veins: Ectatic veins within

bronchovascular bundles

Peripheral cysts of the lung

●● Down syndrome, pulmonary infarction/ spontaneous PT

Subpleural cysts

●● Air-filled, vascular fibrous connective tissue lined by alveolar lining cells, 0.2-1 cm

Hyaline membrane disease (HMD)

homogenous pink) membranes along terminal/respiratory bronchioles/alveolar ducts

●● Premature infants, pulmonary surfactant deficiency

●● Surfactant replacement therapy-decreased incidence of HMD

Bronchopulmonary dysplasia

●● Also known as chronic lung disease of prematurity

tion, poor bronchial drainage

necrotic/hyaline membranes): Distal acinus protected from toxic effects of oxygen therapy/mechanical ventilation

●● In the bronchi that are fully patent/ incompletely obstructed: Distal acini exposed to oxygen toxicity/barotrauma

●● Acinar atrophy, pleural fissures, alveolar septal fibrosis

BPD in a child who has received surfactant therapy

much complexity (acinar simplification), thin septa

Congenital surfactant deficiency

immediately after birth ●● Lung transplant may be necessary ●● Surfactant protein B deficiency most

frequent = caused by deficiency of adenosine triphosphate-binding cassette protein (most frequently ABCA3)

material admixed with macrophages and desquamated epithelial cells

septal fibrosis

Interstitial pulmonary emphysema

●● Dissection of air along bronchovascular bundles, intralobular septa and through pleura

dium

Acute

septa and pleura

Persistent (PIPE)

lobular septa ●● Cysts are air filled/lined by smooth

membrane, compression of pulmonary parenchyma

●● Cyst wall made up of fibrous connective tissue, lined by foreign body type giant cells

Aspiration

monitis (meconium or gastric contents aspiration)

●● Post-term infants: Amniotic fluid aspiration fills up alveoli/ducts, by squames

●● Aspiration of maternal blood during delivery, milk, and other chemicals and solid objects; symptomatic and dangerous

Meconium aspiration syndrome (MAS)

●● Alveoli filled with amorphous debris/ neutrophils

●● Serious condition, may require ECMO/ surfactant lavage

Extracorporeal membrane oxygenation (ECMO)

●● Indications: MAS, CHD, ACD, diaphragmatic hernia, severe infections

●● Intrapulmonary changes: Alveolar hemorrhage, alveolar cell hyperplasia, interstitial fibrosis, mucinous/squamous cell metaplasia hyperinflation, airway obstruction

●● Extrapulmonary changes: Cerebral infarcts, hemorrhages, periventricular leukomalacia

Pulmonary hemorrhage

●● Etiology: HMD, BPD, DIC, Goodpasture syndrome, erythroblastosis, congestive heart failure, congenital malformations

●● Differentiated from aspirated maternal blood (by identification of fetal erythrocytes)

Pulmonary veno-occlusive disease

tric intimal fibrosis/thrombi, arterialized veins

Pulmonary alveolar microlithiasis

●● May cause pulmonary hypertension and respiratory failure

(bronchoalveolar lavage/lung biopsy)

Pulmonary hemosiderosis

●● Indicative of previous hemorrhage/aspiration in lungs

Idiopathic pulmonary hemorrhage

●● Hemoptysis, iron deficiency anemia, diffuse parenchymal infiltrates

Secondary pulmonary hemorrhage

●● Immunologically mediated renal or vascular disease

RESPIRATORY SYNCYTIAL VIRUS

●● Most common respiratory pathogen of childhood

ADENOVIRUS

●● Severe necrotizing bronchitis, bronchiolitis, and alveolitis

●● Intranuclear smudged inclusions basophilic/eosinophilic, bronchiolar/alveolar epithelial cells

LEGIONELLA PNEUMONIA

EOSINOPHILIC PNEUMONIA

blood ●● Drugs, parasites, other infectious agents

INTERSTITIAL LUNG DISEASES

●● Interstitium includes alveolar walls, interlobular septa, and connective tissue around bronchovascular bundles

Chronic lung disease of infancy

●● Idiopathic, progressive respiratory insufficiency several days to weeks after birth

●● Mild chronic interstitial inflammation, minimal interstitial fibrosis, reactive type 2 pneumocytes

●● Possible nutritional deficiencies/postinfectious

Neuroendocrine hyperplasia of infancy

Pulmonary interstitial glycogenosis

cells containing abundant glycogen (PAS positive and diastase labile)

SARCOIDOSIS

verting enzyme levels ●● More common in black individuals ●● Bilateral hilar lymphadenopathy ●● Non-caseating granulomas: Central core of

epithelioid cells, multinucleated giant cells, peripheral rim of lymphocytes

●● Asteroid bodies/Schaumann bodies in giant cells

CYSTIC FIBROSIS

●● AR disorder, CFTR gene located on chromosome 7, delta F508

●● Highly viscous mucoid secretions in lungs, liver, GIT, pancreas

●● Mucus plugging and secondary changes in these organs

●● Bronchiectasis is common: Massively ectatic bronchi filled with viscid mucus, inflammation

●● Secondary infections by Pseudomonas aeruginosa, aspergillosis, candidiasis common

ASTHMA

sal glands ●● Thickening of muscular wall and basement

membrane underlying mucosal epithelial cells

●● Bronchus infiltrated by lymphocytes, plasma cells, and eosinophils

●● Curschmann spirals, creola bodies, Charcot-Leyden crystals in sputum

DIAPHRAGMATIC HERNIA

thoracic cavity ●● Hypoplasia of lungs ●● Associated anomalies: Trisomy 18 and

21, TEF, CPAM, pulmonary hypoplasia, extralobar sequestration, TOF, ectopia cordis

DIAPHRAGMATIC EVENTRATION

●● Thorax markedly reduced in size due to elevation of diaphragm (abdominal contents protruded upward)

●● Aplasia/hypoplasia of muscle between diaphragm leaflets

●● Diaphragm consists of thin thoracic/ abdominal mesothelium with few strands of muscle in between

BENIGN TUMORS

Inflammatory pseudotumor/myofibroblastic tumor

●● Circumscribed, interlacing fascicles of spindle-shaped myofibroblasts separated by plasma cells/lymphocytes

desmin) positive

Chondromatous hamartoma

●● Irregular lobules of cartilage, vascularized adipose tissue, fibrous tissue

●● May be part of Carney triad (pulmonary chondroma, GIST, extra-adrenal paraganglioma)

Juvenile laryngotracheal papillomatosis

koilocytic changes ●● HPV6+, HPV11+

Sclerosing hemangioma

●● Peripheral solitary tumor composed of surface cells (lining papillae) and round cells (within papillary cores)

Granular cell myoblastoma

cytoplasm ●● Positive for S100

MALIGNANT TUMORS

●● Most common are metastatic tumors, especially metastatic osteosarcoma

Bronchial carcinoid

●● Most common pulmonary malignant tumor in children

with round nuclei, finely granular cytoplasm, separated into discrete bundles by delicate vascular septa

Bronchial mucoepidermoid carcinoma

●● Arises from bronchial minor salivary glands

●● Epidermoid/intermediate cells admixed with mucinous cells, arranged in sheets/ glands

Adenoid cystic carcinoma

●● Arises from bronchial minor salivary glands

●● Accumulation of mucin/hyaline material in tumor cell clusters, cribriform pattern

Bronchioloalveolar carcinoma

ters of tumor cells ●● Alveolar septa lined by columnar epithe-

lial cells, irregular basal nuclei, and apical mucin

Bronchogenic carcinoma

●● Adenocarcinoma and undifferentiated carcinoma

●● Primary or second tumors after treatment of Hodgkin lymphoma/Ewing sarcoma

Sarcomas

(MPNST), leiomyosarcoma, fibrosarcoma

Synovial sarcoma

CD34, translocation ●● t(X;18)

Embryonal/alveolar rhabdomyosarcoma

●● Muscle markers desmin+, myogenin+ myoglobin+, MyoD1+

Pleuropulmonary blastoma

common ●● Germline loss of function of DICER1 muta-

tions in familial pleuropulmonary blastoma syndrome

Type I (cystic)

●● Large air-filled cyst resembling type 4-CPAM

●● Cyst wall lined by interrupted cuboidal/ columnar epithelial cells, overlying fibromuscular stroma

●● Dense cambium layer of malignant rhabdomyoblasts (tumor cells beneath epithelial lining)

●● Positive for MyoD1, myogenin, myoglobin, and desmin

Type II (both solid/cystic)

primitive mesenchymal cells of RMS, chondrosarcoma/undifferentiated sarcomas

Type III (solid)

Midline poorly differentiated carcinoma

ANGIOFIBROMA

fibrous background with stellate fibroblasts

●● Cells are positive for beta-catenin (nuclear) and CD117 (cytoplasmic)

NASOPHARYNGEAL CARCINOMA

●● Adolescent males, common in southern China

●● Malignant neoplasm that metastasizes to unilateral lymph nodes

dispersed) surrounded by a diffuse infiltrate of reactive lymphocytes