Lung tumor

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

Revised: 18 October 2015, last major update October 2015

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

PubMed Search: Adenocarcinoma [title] lung

Definition / General
  • Adenocarcinoma is a malignant neoplasm with glandular differentiation, pneumocyte phenotype or mucin production
  • Lung carcinomas are mainly divided into two groups: nonsmall cell (NSCC) and small cell carcinoma (SCC)
  • Adenocarcinoma is a type of NSCC arising from the bronchi, bronchioles and alveolar cells with or without mucin production
  • Adenocarcinoma represents the most common type of lung cancer in females, nonsmokers and younger males
  • Lung cancer is the leading cause of cancer related death worldwide, with tobacco smoking the major risk factor
  • As described by the 2015 WHO classification of lung tumors, other possible risk factors include second-hand tobacco smoke, asbestos, ionizing radiation such as radon, indoor air pollution and chronic lung disease
  • Lung adenocarcinoma may occur in nonsmokers, and it is the most common type of lung carcinoma among this group
Clinical Features
  • Patients may present with fatigue, weight loss, cough, dyspnea, hemoptysis, and chest pain
  • Some patients may be asymptomatic with incidental radiologic finding of lung tumors
  • The American Cancer Society reports the 5 year survival for different stages as follows:
    • 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
Prognostic Factors
  • 2015 WHO Classification of Lung Tumor describes tumor size of 2.5 cm or more, micropapillary and solid variants, and standardized uptake value of 7 or more as predictors of poor prognosis
Radiology description
  • Imaging usually shows ground-glass opacity, solid nodule (3 cm or less in greatest dimension) or mass lesion
  • Ground-glass opacity and solid components mainly correspond to the lepidic pattern and invasive tumor, respectively
  • While carcinoma may occur anywhere within the lung, it occurs more commonly in the periphery and in upper lobes
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, adenocarcinoma usually does not form a cavitary lesion
  • Adenocarcinoma may present as a diffuse pleural thickening resembling malignant mesothelioma
Gross Images
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Peripheral tumor

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 (J Thorac Oncol 2011;6:244)
  • This classification has been followed by the 2015 WHO Classification of Lung Tumors, which delivers important changes from the 2004 WHO classification
  • Most lung adenocarcinomas demonstrate a mixture of different histologic patterns
  • 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 semiquantitatively (in 5% increments)
  • Adenocarcinomas should be classified by the predominant pattern of growth: for example, tumors displaying largely papillary structures should be classified as "adenocarcinoma papillary predominant" (J Thorac Oncol 2011;6:244, Pathol Int 2005;55:619, Eur J Cardiothorac Surg 2015 Mar 11 [Epub ahead of print])
  • Different histologic subtypes in lung adenocarcinomas include lepidic, acinar, papillary, micropapillary and solid subtypes
  • Lepidic pattern is composed of neoplastic cells lining the alveolar lining with no architectural disruption/complexity, and no lymphovascular 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 pattern is composed of ill defined projection / tufting with no fibrovascular cores
  • Solid pattern is defined as solid sheets and nests of tumor
  • Different histologic subtypes have prognostic significance; lepidic has best prognosis, micropapillary and solid patterns have more aggressive behavior
  • Adenocarcinoma in situ: either (a) 3 cm or less or (b) with pure lepidic pattern but no features of invasion; "bronchioloalveolar carcinoma" is no longer used
  • MInimally invasive adenocarcinoma: solitary tumors measuring 3 cm or less with predominantly lepidic pattern and 5 mm or less invasion in any greatest dimension and in any one focus
  • Tumors are classified as invasive if they have any of the following features:
    • Histologic patterns other than lepidic
    • Infiltrating tumor with desmoplastic reaction
    • Lymphovascular or pleural invasion
    • Necrosis
Micro Images

Images courtesy of Dr. Fulvio Lonardo, Wayne State University, Detroit, MI, USA:

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High grade cytological features

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Micropapillary pattern

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Fibrovascular cores

Positive Stains
  • With the development of targeted therapy for certain subtypes of NSCC, more exact histopathological subtyping is required
  • In the new 2015 WHO classification of Lung Tumors, immunohistochemistry is recommended if classification cannot be made with certainty based on light microscopy
  • Typically, lung adenocarcinoma are (CK7 (+) CK20 (-)
  • TTF1 (nuclear staining, Am J Surg Pathol 2002;26:767) and NapsinA (cytoplasmic staining) are useful markers with reported sensitivity/specificity of 84.5% / 96.4% (TTF1), and 92.0% / 100% (NapsinA) (Clin Transl Med 2015;4:16)
  • Correlation with clinical data is recommended
  • Also commonly used: Mucin, EMA, CEA
  • Also surfactant apoprotein (50%), mesothelin (50%), vimentin (9%), S100 (Langerhans cells), p53, CD57/Leu7 (50% of well/moderately differentiated tumors), calretinin (11%, Am J Surg Pathol 2003;27:150)
  • Also EGFR mutation specific antibodies (variable, Lung Cancer 2012;77:299)
Negative Stains
Electron Microscopy Description
  • Goblet cells, mucus cells, nonciliated bronchiolar cells, Clara cells
Molecular / Cytogenetics Description
  • With development of targeted therapy, molecular testing is now routine
  • Common mutations include EGFR, KRAS and BRAF, translocation of ALK, ROS1 and RET, and amplification of MET and FGFR1 in NSCC
  • EGFR mutation is seen in 10-15% of adenocarcinomas from patients of European origin
    • More common in never smokers, Asians and females
    • These tumors are responsive to treatment with tyrosine kinase inhibitors (Science 2004;304:1497)
  • Fusion between echinoderm microtubule associated protein like 4 (EML4) and ALK fusion is present in 2-7% of adenocarcinomas
    • More common in nonsmokers or light smokers
    • Patients with ALK rearrangement may benefit from treatment with ALK inhibitors
  • KRAS mutation and MET amplification are associated with poor prognosis and EGFR acquired resistance (Proc Am Thorac Soc 2009;6:201, Transl Lung Cancer Res 2013;2:23)
Differential Diagnosis
  • Tumor classification may be difficult based on H&E
  • Adenocarcinoma with predominant solid pattern resembles other nonsmall cell carcinomas of lung; markers typically positive in mimics but negative in adenocarcinoma include:
Additional References