Sandbox lung cancer differential

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  • Differentiation of primary and secondary lung tumors is difficult due to overlapping histologic features.
  • Topography, size and form of pulmonary growth pattern are important aspects for the differential diagnosis.
  • The following table summarizes the differentiation of various lung tumors based on histological and topographical features:[1]
Abrevations:

HPV: human papillomavirus; CEA: Carcino embryogenic antigen; TTF1: Thyroid transcription factor-1; EMA: Epithelial membrane antigen; CK: Cyto keratin; CD: Cluster differentiation; NCAM: Neural Cell Differentiation Molecule;

MMP's: Mettaloprotineases matrix ; GFAP: Glial fibrocilliary acid protein

Benign Lung Tumors[2]
Benign lung tumor Risk/Epidemiology Pleuripotent cells Topography Gross Histology Immunohistochemistry Imaging Metastasis
Papilloma[3] Squamous cell papilloma
  • HPV 6 and 11
  • Men
  • Median age of diagnosis is 54 years
  • Endobronchial
  • Cauliflower-like lesions
  • Tan-white soft to semifirm protrutions
  • Loose fibrovascular core
  • Stratified squamous epithelium
  • Acanthosis
  • Binucleate forms and perinuclear halos
  • Koilocytosis
  • N/A
  • Well circumscribed
  • Homogenous
  • Non-calcified
  • Solitary mass
  • N/A
Glandular papilloma
  • Rare
  • Mean age of diagnosis is 68 years
  • Endobronchial
  • White to tan endobronchial polyps that measure from 0.7-1.5 cm
  • N/A
  • Well circumscribed
  • Homogenous
  • Non-calcified
  • Solitary mass
  • N/A
Adenoma[4] Alveolar adenoma
  • Mean age of diagnosis is 53 years
  • Female predominance
  • All lung lobes
  • Lower lobes
  • Hilar
  • 0.7-6.0 cm
  • Well demarcated smooth
  • Lobulated, multicystic
  • Soft to firm
  • Pale yellow to tan cut surfaces
  • Well circumscribed
  • Homogenous
  • Non-calcified
  • Solitary mass
  • N/A
Papillary adenoma[5]
  • Mean age of diagnosis is 32 years
  • Male predominance
  • Bronchioloalveolar cell
  • No lobar predilection
  • Involves alveolar parenchyma
  • Well defined
  • Encapsulated
  • Soft, spongy to firm mass
  • Granular gray white/ brown
  • 1.0- 4.0 cm
  • Incidental finding
  • N/A
Mucinous cystadenoma
  • No sex predilection
  • Mean age of diagnosis is 52 years
  • Central
  • White-pink to tan
  • Smooth and shiny tumors
  • Gelatinous mucoid solid core
  • 0.7-7.5 cm
  • Numerous mucin-filled cystic spaces
  • Non-dilated microacini, glands, tubules and papillae
  • Coin lesion
  • Air-meniscus sign
  • N/A
Malignant Lung Tumors[6]
Variants of lung carcinoma Risk Factors/Epidemiology Pleuripotent cell Topography Gross Histology Immunohistochemistry Imaging Metastasis
Squamous cell carcinoma (SCC)[7] Papillary
  • Epithelial cells
  • Central
  • Exophytic
  • Intra-epithelial
  • Without invasion
Clear cell
Basaloid
  • Peripheral palisading of nuclei.
  • Poor differentiation
Small cell carcinoma[8]
  • Bronchial precursor cell
  • Peripheral
  • White-tan, soft, friable perihilar masses
  • Extensive necrosis
  • 5% peripheral coin lesions
  • Sheet-like growth
  • Nesting
  • Trabeculae
  • Peripheral palisading
  • Rosette formation
  • High mitotic rate
  • Bone marrow
  • Liver
Variants of lung carcinoma Risk Factors/Epidemiology Pleuripotent cell Topography Gross Histology Immunohistochemistry Imaging Metastasis
Adenocarcinoma[9][10][11] Acinar adenocarcinoma
  • Columnar cells of bronchioles
  • Peripheral
  • Single or multiple lesions
  • Different in size
  • Peripheral distribution
  • Gray-white central fibrosis
  • Pleural puckering
  • Anthracotic pigmentation
  • Lobulated or ill defined edges
  • Irregular-shaped glands
  • Malignant cells:
    • Hyperchromatic nuclei
    • Fibroblastic stroma
  • Peripheral nodules under 4.0 cm in size
  • Central location as a hilar or perihilar mass
  • Rarely show cavitations.
  • Hilar adenopathy
  • Adenocarcinomas account for the majority of small peripheral cancers identified radiologically.
Aerogenous spread is characteristic
  • Brain
  • Bone
  • Adrenal glands
  • Liver
  • Kidney
  • Gastrointestinal Tract
Papillary adenocarcinoma
Bronchio-alveolar carcinoma Non-mucinous
Mucinous
  • Low grade differentiation
  • Composed of:
    • Tall columnar cells
    • Basal nuclei
    • Pale cytoplasm resembling goblet cells
    • Varying amounts of cytoplasmic mucin
  • Cytologic atypia
Mixed non-mucinous and mucinous or indeterminate
  • Mixed type of cells
  • Low to high grade differentiated cells.
Solid adenocarcinoma with mucin production Fetal adenocarcinoma
Mucinous (“colloid”) carcinoma
Mucinous cystadenocarcinoma
Signet ring adenocarcinoma
  • Focal
  • Cells with nuclei displaced to sides
  • Components of other cells are present.
Clear cell adenocarcinoma
  • Clear cells with no nuclei
Variants of lung carcinoma Risk Factors/Epidemiology Pleuripotent cell Topography Gross Histology Immunohistochemistry Imaging Metastasis
Large cell carcinoma[12] Basaloid large cell carcinoma of the lung
  • Approximately 10% of lung cancers
  • Smoking
  • Soft, pink-tan tumor
  • Invasive growth pattern
  • Peripheral palisading
  • Small, monomorphic, cuboidal fusiform
  • Large, peripheral masses
Clear cell carcinoma of the lung
Lymphoepithelioma-like carcinoma of the lung
Large-cell lung carcinoma with rhabdoid phenotype
Mixed type
Variants of lung carcinoma Risk Factors/Epidemiology Pleuripotent cell Topography Gross Histology Immunohistochemistry Imaging Metastasis
Sarcomatoid carcinoma[13] Carcinosarcoma
  • Central or peripheral
  • Upper lobes
  • No specific imaging features 
Spindle cell carcinoma
  • Only spindle shaped tumor cells
  • Lymphoplasmacytic infiltrates
Giant cell carcinoma
Pleomorphic carcinoma
Pulmonary blastoma
Variants of lung carcinoma Risk Factors/Epidemiology Pleuripotent cell Topography Gross Histology Immunohistochemistry Imaging Metastasis
Carcinoid tumor[14] Typical carcinoid

Atypical carcinoid

  • Most common in males
  • Mean age of diagnosis 45
  • Atypical carcinoid is more commonly peripheral
  • Firm, well demarcated, tan to yellow tumors
  • Uniform polygonal cells
  • Nuclear atypia
  • Pleomorphism
  • The most common patterns are the organoid and trabecular
  • Highly vascularized fibrovascular stroma
  • Focal necrosis
Salivary gland tumors[15] Mucoepidermoid carcinoma
  • Most patients presents in the third and fourth decade
  • Constitutes of less than 1% tumor
  • No association with cigarette smoking or other risk factors
  • Primitive cells of tracheobronchial origin
  • Bronchial glands
  • Ranging in size from 0.5-6 cm
  • Soft, polypoid, and pink-tan in colour
  • High-grade lesions are infiltrative
  • Well-circumscribed oval or lobulated mass
  • Calcifications
  • Post-obstructive pneumonic infiltrates
Adenoid cystic carcinoma
  • Constitutes less than 1% of all lung tumors
  • Most commonly seen in fourth and fifth decades of life
  • Primitive cells of tracheobronchial origin
  • Gray-white or tan polypoid lesions
  • Size ranges from 1–4 cm
  • Infiltrative margins
  • Invades other cell layers
  • Heterogeneous cellularity
  • Cribriform pattern
  • Perineural invasion
  • Well circumscribed
  • Nodule
Epithelial-myoepithelial carcinoma
  • Age ranges from 33 to 71 years
  • No association with smoking
  • Endobronchial
  • Solid to gelatinous in texture
  • White to gray in colour
Variants of lung carcinoma Risk Factors/Epidemiology Pleuripotent cell Topography Gross Histology Immunohistochemistry Imaging Metastasis
Preinvasive lesions[16] Squamous carcinoma in situ
  • Most commonly seen in fifth or sixth decades
  • Mostly seen in women
  • Basal cells of squamous epithelium
  • Focal or multi-focal plaque-like greyish lesions
  • Nonspecific erythema
  • Even nodular or polypoid lesions
  • Micropapillomatosis
  • Cauliflower like
  • Mosaic pattern
Atypical adenomatous hyperplasia
  • Multiple grey to yellow foci
  • 1mm to 10mm in size
  • Typically not visualized on radiographs
  • Small non-solid nodules
  • Ground-glass opacity
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia
  • Endobronchial
  • Early lesions are:
    • Small, gray-white nodules
    • Resembling ‘miliary bodies’
  • Larger carcinoid tumors are:
    • Firm
    • Homogeneous
    • Well-defined
    • Grey or yellow-white masses
  • Mosaic pattern of air trapping
  • Sometimes with nodules
  • Thickened bronchial and bronchiolar walls
Variants of lung carcinoma Risk Factors/Epidemiology Pleuripotent cell Topography Gross Histology Immunohistochemistry Imaging Metastasis
Mesenchymal tumors[17] Epithelioid haemangioendothelioma / Angiosarcoma
  • Caucasian
  • 80% are women
  • Endothelial cells
  • 0.3-2.0 cm circumscribed mass
  • Gray-white or gray-tan firm tissue
  • Yellow flecks
  • Central calcifications
  • Cut surface has a cartilaginous consistency
Pleuropulmonary blastoma
  • Most common in children
  • Median age of diagnosis is 2 years
  • Purely cystic
  • Thin-walled
  • Rarely solid
  • Firm to gelatinous
  • Upto 15 cm
  • Unilateral
  • Localized airfilled cysts
  • Septal thickening or an intracystic mass
Chondroma
  • Young women
  • Capsulated lobules
  • Hypocellular
  • Features of malignancy are absent
  • N/A
  • Multiple
  • Well circumscribed lesions
  • “Pop-corn” calcifications
Congenital peribronchial myofibroblastic tumor
  • Along the bronchi
  • 5-10 cm
  • Well-circumscribed
  • Non-encapsulated
  • Smooth or multinodular surface
  • The cut surface has a tann-grey to yellow-tan fleshy appearance
  • Hemorrhage
  • Necrosis
  • Well circumscribed
  • Opaque hemithorax
  • Heterogeneous mass
  • Rare
Diffuse pulmonary lymphangiomatosis
  • Children
  • Young adults of both sexes
  • Prominence of the bronchovascular bundles along
  • Anastomosing endothelial-lined cells along lymphatic routes
  • Increased interstitial markings
  • Skin
  • Bone
Inflammatory myofibroblastic tumor
  • Localized to bronchi
  • Solitary
  • Round rubbery masses
  • Yellowish-gray discoloration
  • Average size of 3.0 cm
  • Non-encapculated
  • Calcifications
  • No local invasion
  • Solitary mass
  • Regular borders
  • Spiculated appearance
  • Accompanied by
  • Rare
Pulmonary artery sarcoma
  • Mucoid or gelatinous clots filling vascular lumens
  • The cut surface may show
    • Firm fibrotic areas
    • Bony/gritty or chondromyxoid foci
    • Hemorrhage and necrosis are common in high-grade tumors
  • Spindle cells in
    • A myxoid background
    • Collagenized stroma
    • Recanalized thrombi
Pulmonary vein sarcoma
  • Most common in women
  • Mean age of diagnosis is 49
  • Fleshy-tan tumor
  • Can occlude the lumen of the involved vessel
  • 3.0- 20.0 cm
  • Invasion of wall of the vein
  • N/A

Differentiation of lung cancer from other diseases with similar presentation

The following table summarizes the differentiation of lung cancer from other disease entities with similar presentation.[18][19][20][21][22]

Disease Clinical features

Signs & symptoms

Radiological Findings Characterstic feature
Fever Cough Hemoptysis Dyspnea Chest pain Weight loss Night sweats
High-grade Low grade Productive Dry
Acute Lung abscess + - + - - - + - -
  • Air fluid level
Malignancy

(primary lung cancer)

- + - + + - - + +
  • Coin-shaped lesion
  • Thick wall(>15mm)
  • Ground glass opacities 
Pulmonary Tuberculosis + - + - + - - - +
Necrotizing Pneumonia + - + + - + - -
  • Multiple cavitary lesions
Empyema + - + - + + + - -
Bronchiectasis - - + - + - - - -
  • Linear lucencies
  • Tram tracking appearance
  • Clustered cysts
  • CT confirms the diagnosis
Wegners granulomatosis - - + + + - - -
  • Seen mostly in female age group of 40-55 years
  • Traid of Upper , lower respiratory tract and kidney disease
  • Biopsy of involved organ confirms granulomas
Sarcoidosis + - + - + - - + +
Rheumatoid nodule - - - - - + - + -
Langerhans cell Histiocytosis - - - - - + + + -
  • Thin-walled cystic cavities
Bronchiolitis obliterans - - + - + + + - -
  • Ground-glass opacities
  • Biopsy

References

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