Squamous cell carcinoma of the lung differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]

Overview

Squamous cell carcinoma of the lung must be differentiated from other diseases that cause chronic cough, weight loss, hemoptysis, and dyspnea among adults such as pulmonary tuberculosis, sarcoidosis, pneumonia, pulmonary fungal infection, and secondary metastases.

Differentiating Squamous Cell Carcinoma of the Lung from other Diseases

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
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
Organ system Diseases Clinical manifestations Diagnosis Other features
Symptoms Physical exam
Onset Duration Productive cough Hemoptysis Weight lost Fever Dyspnea Ascultation Lab findings Imaging PFT Gold standard
Respiratory Parenchyma Lung cancer[20][21] Chronic
  • Years
+ + + +/− + The following investigations may be helpful:
  • Not specific
Interstitial lung disease[22][23] Chronic
  • Variable
+ + + The following investigations may be helpful:
  • Lung biopsy when lab, imaging, and PFT has indeterminate result
Tuberculosis (TB)[24][25] Chronic
  • More than 2 or 3 weeks
+ + + + +
Cardiac Pulmonary hypertension[26][27] Chronic
  • More than 2 years
+ + + The following investigations may be helpful:
Organ system Diseases Clinical manifestations Diagnosis Other features
Symptoms Physical exam
Onset Duration Productive cough Hemoptysis Weight lost Fever Dyspnea Ascultation Lab findings Imaging PFT Gold standard
Autoimmune Wegener's disease (GPA) [28][29] Chronic
  • Months
+ + + + + The following investigations may be helpful:
Microscopic polyangitis (MPA)[30] Chronic
  • Variable
+ + + + + The following investigations may be helpful:
Churg−Strauss[31][32] Chronic
  • Variable
+ + + + +
  • Infiltrates in chest X−Ray
  • Ground glass opacities, tree−in−bud sign and small nodules in chest CT

References

  1. Erasmus JJ, Connolly JE, McAdams HP, Roggli VL (2000). "Solitary pulmonary nodules: Part I. Morphologic evaluation for differentiation of benign and malignant lesions". Radiographics. 20 (1): 43–58. doi:10.1148/radiographics.20.1.g00ja0343. PMID 10682770.
  2. Gümüştaş S, Inan N, Akansel G, Ciftçi E, Demirci A, Ozkara SK (June 2012). "Differentiation of malignant and benign lung lesions with diffusion-weighted MR imaging". Radiol Oncol. 46 (2): 106–13. doi:10.2478/v10019-012-0021-3. PMC 3472932. PMID 23077446.
  3. Maxwell RJ, Gibbons JR, O'Hara MD (January 1985). "Solitary squamous papilloma of the bronchus". Thorax. 40 (1): 68–71. PMC 459982. PMID 3969658.
  4. Shiota Y, Matsumoto H, Sasaki N, Taniyama K, Hashimoto S, Sueishi K (1998). "Solitary bronchioloalveolar adenoma of the lung". Respiration. 65 (6): 483–5. doi:10.1159/000029319. PMID 9817965.
  5. Kanchustambham V, Saladi S, Patolia S, Mahmoud Assaf S, Stoeckel D (March 2017). "A Rare Case of a Benign Primary Pleomorphic Adenoma of the Lung". Cureus. 9 (3): e1069. doi:10.7759/cureus.1069. PMC 5375953. PMID 28409070.
  6. Kelley LC, Puette M, Langheinrich KA, King B (November 1994). "Bovine pulmonary blastomas: histomorphologic description and immunohistochemistry". Vet. Pathol. 31 (6): 658–62. doi:10.1177/030098589403100605. PMID 7863581.
  7. Roth E, Smidt D (January 1970). "[Studies on early ejaculate collection using electroejaculation in German improved land-swines and Goettinger miniature pigs]". Berl. Munch. Tierarztl. Wochenschr. (in German). 83 (1): 7–11. PMID 5528918.
  8. Jackman DM, Johnson BE (2005). "Small-cell lung cancer". Lancet. 366 (9494): 1385–96. doi:10.1016/S0140-6736(05)67569-1. PMID 16226617.
  9. Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. "Chapter 13, box on morphology of adenocarcinoma". Robbins Basic Pathology (8th ed.). Philadelphia: Saunders. ISBN 1-4160-2973-7.
  10. Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S; et al. (2007). "Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer". Nature. 448 (7153): 561–6. doi:10.1038/nature05945. PMID 17625570.
  11. Adenocarcinoma of the lung. Librepathology 2015. http://librepathology.org/wiki/index.php/File:Adenocarcinoma_%283950819000%29.jpg
  12. Rossi G, Mengoli MC, Cavazza A, Nicoli D, Barbareschi M, Cantaloni C, Papotti M, Tironi A, Graziano P, Paci M, Stefani A, Migaldi M, Sartori G, Pelosi G (January 2014). "Large cell carcinoma of the lung: clinically oriented classification integrating immunohistochemistry and molecular biology". Virchows Arch. 464 (1): 61–8. doi:10.1007/s00428-013-1501-6. PMID 24221342.
  13. Huang SY, Shen SJ, Li XY (October 2013). "Pulmonary sarcomatoid carcinoma: a clinicopathologic study and prognostic analysis of 51 cases". World J Surg Oncol. 11: 252. doi:10.1186/1477-7819-11-252. PMC 3850921. PMID 24088577.
  14. Dahabreh J, Stathopoulos GP, Koutantos J, Rigatos S (March 2009). "Lung carcinoid tumor biology: treatment and survival". Oncol. Rep. 21 (3): 757–60. PMID 19212636.
  15. Elnayal A, Moran CA, Fox PS, Mawlawi O, Swisher SG, Marom EM (July 2013). "Primary salivary gland-type lung cancer: imaging and clinical predictors of outcome". AJR Am J Roentgenol. 201 (1): W57–63. doi:10.2214/AJR.12.9579. PMC 3767141. PMID 23789697.
  16. Greenberg AK, Yee H, Rom WN (2002). "Preneoplastic lesions of the lung". Respir. Res. 3: 20. PMC 107849. PMID 11980589.
  17. Koenigkam-Santos M, Sommer G, Puderbach M, Safi S, Schnabel PA, Kauczor HU, Heussel CP (April 2014). "Primary intrathoracic malignant mesenchymal tumours: computed tomography features of a rare group of chest neoplasms". Insights Imaging. 5 (2): 237–44. doi:10.1007/s13244-013-0306-0. PMC 3999366. PMID 24407922.
  18. Bhatt M, Kant S, Bhaskar R (2012). "Pulmonary tuberculosis as differential diagnosis of lung cancer". South Asian J Cancer. 1 (1): 36–42. doi:10.4103/2278-330X.96507. PMC 3876596. PMID 24455507.
  19. Kamiya K, Yoshizu A, Misumi Y, Hida N, Okamoto H, Yoshida S (2011). "[Lung abscess which needed to be distinguished from lung cancer; report of a case]". Kyobu Geka. 64 (13): 1204–7. PMID 22242302.
  20. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011). "Global cancer statistics". CA Cancer J Clin. 61 (2): 69–90. doi:10.3322/caac.20107. PMID 21296855.
  21. Ost DE, Jim Yeung SC, Tanoue LT, Gould MK (2013). "Clinical and organizational factors in the initial evaluation of patients with lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines". Chest. 143 (5 Suppl): e121S–e141S. doi:10.1378/chest.12-2352. PMC 4694609. PMID 23649435.
  22. Lama VN, Martinez FJ (2004). "Resting and exercise physiology in interstitial lung diseases". Clin. Chest Med. 25 (3): 435–53, v. doi:10.1016/j.ccm.2004.05.005. PMID 15331185.
  23. Chetta A, Marangio E, Olivieri D (2004). "Pulmonary function testing in interstitial lung diseases". Respiration. 71 (3): 209–13. doi:10.1159/000077416. PMID 15133338.
  24. Perlman DC, el-Sadr WM, Nelson ET, Matts JP, Telzak EE, Salomon N, Chirgwin K, Hafner R (1997). "Variation of chest radiographic patterns in pulmonary tuberculosis by degree of human immunodeficiency virus-related immunosuppression. The Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). The AIDS Clinical Trials Group (ACTG)". Clin. Infect. Dis. 25 (2): 242–6. PMID 9332519.
  25. Barnes PF, Verdegem TD, Vachon LA, Leedom JM, Overturf GD (1988). "Chest roentgenogram in pulmonary tuberculosis. New data on an old test". Chest. 94 (2): 316–20. PMID 2456183.
  26. Brown LM, Chen H, Halpern S, Taichman D, McGoon MD, Farber HW, Frost AE, Liou TG, Turner M, Feldkircher K, Miller DP, Elliott CG (2011). "Delay in recognition of pulmonary arterial hypertension: factors identified from the REVEAL Registry". Chest. 140 (1): 19–26. doi:10.1378/chest.10-1166. PMC 3198486. PMID 21393391.
  27. Sun XG, Hansen JE, Oudiz RJ, Wasserman K (2003). "Pulmonary function in primary pulmonary hypertension". J Am Coll Cardiol. 41 (6): 1028–35. PMID 12651053.
  28. Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, Rottem M, Fauci AS (1992). "Wegener granulomatosis: an analysis of 158 patients". Ann. Intern. Med. 116 (6): 488–98. PMID 1739240.
  29. Falk RJ, Gross WL, Guillevin L, Hoffman GS, Jayne DR, Jennette JC, Kallenberg CG, Luqmani R, Mahr AD, Matteson EL, Merkel PA, Specks U, Watts RA (2011). "Granulomatosis with polyangiitis (Wegener's): an alternative name for Wegener's granulomatosis". Arthritis Rheum. 63 (4): 863–4. doi:10.1002/art.30286. PMID 21374588.
  30. Jennette, J. Charles; Falk, Ronald J. (1997). "Small-Vessel Vasculitis". New England Journal of Medicine. 337 (21): 1512–1523. doi:10.1056/NEJM199711203372106. ISSN 0028-4793.
  31. Vaglio A, Buzio C, Zwerina J (2013). "Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): state of the art". Allergy. 68 (3): 261–73. doi:10.1111/all.12088. PMID 23330816.
  32. Lanham JG, Elkon KB, Pusey CD, Hughes GR (1984). "Systemic vasculitis with asthma and eosinophilia: a clinical approach to the Churg-Strauss syndrome". Medicine (Baltimore). 63 (2): 65–81. PMID 6366453.