Lung tumor

Author: Negar Rassaei, M.D. (see Authors page)

Revised: 26 August 2015, last major update August 2015

Copyright: (c) 2003-2015,, Inc.

PubMed Search: Adenocarcinoma classification [title] lung
Definition / General
  • Lung carcinomas are mainly divided into two groups: non small cell (NSCLC) and small cell carcinoma (SCLC)
  • Adenocarcinoma is a type of NSCLC arising from the bronchi, bronchioles and alveolar cells, with or without mucin production (WHO: Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart, 2004)
  • Clinical Features
  • Most common type of lung cancer in females, nonsmokers and younger males
  • Patients typically present with fatigue, weight loss, cough, dyspnea, hemoptysis, chest pain
  • 5 year survival (American Cancer Society - Survival Rates) by stage:
    • 49% for stage IA
    • 45% for stage IB
    • 30% for stage IIA
    • 31% for stage IIB
    • 14% for stage IIIA
    • 5% for stage IIIB
    • 1% for stage IV
  • Gross Description
  • Single or multiple, solid, firm, yellow-white nodule or mass which may invade into the pleura and cause pleural retraction/puckering
  • Unlike squamous cell carcinoma, usually does not form a cavitary lesion
  • May present as diffuse pleural thickening resembling malignant mesothelioma
  • Micro Description
  • In 2011, the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) revised the classification of lung adenocarcinoma and proposed new morphological criteria to provide a uniform diagnostic terminology for multidisciplinary patient management
  • This classification delivers a comprehensive histologic subtyping based on pattern recognition and a semi-quantitative assessment of each pattern in 5% increments to evaluate a single, predominant pattern in invasive adenocarcinomas (Proc Am Thorac Soc 2011;8:381)
  • Different histologic subtypes in lung adenocarcinomas include lepidic, acinar, papillary, micropapillary, and solid subtypes:
    • Lepidic pattern is defined as a tumor composed of neoplastic cells lining the alveolar lining with no architectural disruption/complexity, and no lymphovascular and/or pleural invasion
    • Acinar pattern is characterized by glandular formation
    • Papillary pattern displays true fibrovascular cores lined by tumor cells replacing the alveolar lining
    • Micropapillary is composed of ill-defined projection/tufting with no fibrovascular cores
    • Solid pattern is defined as solid sheets and nests of tumor
  • Most lung adenocarcinomas demonstrate a mixture of different histologic patterns
  • Different histologic subtypes have prognostic significance, with lepidic subtype harboring the best course, and micropapillary and solid patterns having a more aggressive behavior
  • Based on this classification, adenocarcinomas measuring 3 cm or less in greatest dimension and pure lepidic pattern with no features of invasion are classified as "adenocarcinoma in-situ" and the term "bronchioloalveolar carcinoma" is no longer used
  • Solitary tumors measuring 3 cm or less with a predominantly lepidic pattern and 5 mm or less invasion in any greatest dimension in any one focus are classified as "minimally invasive adenocarcinoma"
  • Tumors are classified as invasive if they present any of the following features:
    • Histologic patterns other than lepidic
    • Infiltrating tumor with desmoplatic reaction
    • Presence of lymphovascular or pleural invasion
    • Necrosis
  • Based on this classification, adenocarcinomas should be classified by the predominant pattern of growth
  • Based on the new classification, invasive adenocarcinomas with multiple different patterns should no longer be classified as "mixed adenocarcinoma", and each subtype has to be assessed and reported semi-quantitatively (in 5% increments)
  • Micro Images
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    Acinic cell carcinoma

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    Lepidic growth pattern

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    Papillary pattern

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    Solid pattern

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    TTF1, Napsin A and CK7

    Positive Stains
  • Has CK7 (+) CK20 (-) immunoprofile
  • Typically immunoreactive with TTF1 (nuclear positivity) and Napsin A (cytoplasmic positivity)
  • TTF1 and Napsin A have sensitivity/specificity of 84.5%/96.4%, and 92.0%/100% respectively (Clin Transl Med 2015;4:16)
  • None of these markers are entirely specific for lung adenocarcinoma; thus, correlation with clinical data is helpful
  • Molecular / Cytogenetics Description
  • Due to targeted therapy, molecular testing is routine
  • Epidermal growth factor receptor (EGFR) mutations:
    • 10-15% of lung adenocarcinoma
    • More common in never smokers, females
    • Tumors with EGFR mutation are responsive to treatment with tyrosine kinase inhibitors (Science 2004;304:1497)
  • Kras mutation found in 15-25%
    • More common in smokers
    • Patients with Kras mutation have a poorer prognosis and are resistant to EGFR-tyrosine kinase inhibitors (Proc Am Thorac Soc 2009;6:201)
  • Fusion between echinoderm microtubule-associated protein like 4 (EML4) and ALK:
    • Present in 2-7%
    • More common in nonsmokers or light smokers
    • Patients with ALK rearrangement benefit from treatment with ALK inhibitors
  • EGFR, Kras and ALK mutations are mutually exclusive
  • Met is a heterodimere receptor tyrosine kinase involved in organogenesis
    • Met amplification is associated with poor prognosis and EGFR acquired resistance
    • Several Met inhibitors have demonstrated beneficial effect in treatment of NSCLC (Transl Lung Cancer Res 2013;2(1))
  • Differential Diagnosis
  • In some cases, definitive tumor classification is difficult based on H&E
  • Adenocarcinoma with predominant solid pattern: resembles other non small cell carcinomas of lung
  • Neuroendocrine tumors: positive for synaptophysin, chromogranin and CD56
  • Mesothelioma: use calretinin, D2-40, CK5/6, and WT1 to differentiate
  • In some cases the differential may include sarcoma, melanoma or lymphoma