Lung tumor

Topic Completed: 1 December 2015

Revised: 16 April 2019

Revised: 31 January 2019, last major update October 2015

Copyright: (c) 2003-2018,, Inc.

PubMed Search: Adenocarcinoma [title] lung

Page views in 2018: 30,028
Page views in 2019 to date: 11,630
Cite this page: Rassaei N. Adenocarcinoma-general. website. Accessed April 25th, 2019.
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
Case reports
  • A middle aged woman with a history of lung carcinoma presented with a single cerebellar mass (Case of the Week #425)
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

Images hosted on other servers:
Missing Image

Peripheral tumor

Microscopic (histologic) 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
Microscopic (histologic) images

Images hosted on PathOut server:

Contributed by Andrey Bychkov, M.D., Ph.D.

High PDL1

Negative PDL1

Contributed by Dr. Ankur Sangoi, California

Case of the Week #425, metastatic lung adenocarcinoma, ALK rearranged

Case of the Week #425, metastatic lung adenocarcinoma, ALK rearranged

COW #425, NapsinA

COW #425, TTF1

COW #425, ALK break apart FISH images (ALK gene in RED)

Contributed by Dr. Fulvio Lonardo, Michigan
Missing Image

High grade cytological features

Missing Image


Missing Image

Micropapillary pattern

Missing Image Missing Image Missing Image Missing Image Missing Image

Fibrovascular cores

Missing Image Missing Image Missing Image Missing Image Missing Image Missing Image

Various images

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)
Molecular / cytogenetics images

Images hosted on PathOut server:

Images kindly provided by LeicaBiosystems Amsterdam:

ALK / EML4 t(2;2); inv(2)

ALK (2p23)

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
Back to top