Lung adenocarcinoma

From patholines.org
Jump to navigation Jump to search

Author: Mikael Häggström [note 1]

Comprehensiveness

On this resource, the following formatting is used for comprehensiveness:

  • Minimal depth
  • (Moderate depth)
  • ((Comprehensive))

Presentation

Microscopic examination

Adenocarcinoma diagnosis

The major differential diagnosis of squamous-cell carcinoma of the lung.
Small-cell carcinoma, another differential, with typical findings shown.[1]

Lepidic and/or acinar patterns (see below) strongly support the adenocarcinoma diagnosis, otherwise also consider other kinds of lung tumor. For more solid patterns, mainly consider the differential diagnosis of squamous-cell carcinoma (SCC) of the lung. If uncertain, the most useful immunostains are:

Invasiveness

  • An adenocarcinoma in situ is defined as a tumour of ≤ 3 cm with pure lepidic pattern but no lymphatic, vascular or pleural invasion and no tumor necrosis.[3]
  • Minimally invasive adenocarcinoma: a small (≤3 cm), solitary tumour with predominant alveolar epithelial appearance (lepidic growth), as in situ adenocarcinoma of the lung, with a zone of focal invasion of the stroma with a size inferior to 5 mm.[3] It has no lymphatic, vascular or pleural invasion and no tumor necrosis.
  • Invasive adenocarcinoma: Tumor of larger size or focus of invasion, or with lymphatic, vascular, pleural invasion or tumor necrosis.

Predominant pattern

For invasive adenocarcinomas, generally specify the pattern (mainly lepidic, acinar, papillary, micropapillary, solid predominant or "predominant subtype cannot be determined).

Degree of differentiation

Histopathology of poorly differentiated lung adenocarcinoma, showing solid pattern and pleomorphic nuclei. A nucleus near top left shows an atypical (triangular) mitosis.[image 1]

Lung adenocarcinomas may be classified as follows:[4]

Well differentiated Solid pattern< 90% and mild/moderate atypia
Moderately differentiated
  • Solid pattern ≥ 90% and mild/moderate atypia
  • Solid pattern< 90% and severe atypia
Poorly differentiated Solid pattern ≥ 90% and severe atypia

Staging

Specify:

Tumor size

If the tumor has both lepidic and invasive components, specify the maximum dimension of each.

Growth into adjacent structures

Notable adjacent structures possibly involved are:[5]

  • Parietal pleura
  • Main bronchus
  • Hilar soft tissues
  • Organs of the mediastinum (specify where possible)

Classification

Staging of non-small-cell lung cancers (AJCC, 8th Ed.):[6] edit

T category T criteria
TX Primary tumor cannot be assessed, or tumor proven by the presence of malignant cells in sputum or bronchial washings, but not visualized by imaging or bronchoscopy.
T0 No evidence of primary tumor
Tis Carcinoma in situ
Squamous cell carcinoma in situ (SCIS)
Adenocarcinoma in situ (AIS): Adenocarcinoma with pure lepidic pattern, ≤3 cm in greatest dimension
T1 Tumor ≤ in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic invasion more proximal than the lobar bronchus (i.e., not in the main bronchus).
  T1mi Minimally invasive adenocarcinoma: Adenocarcinoma (≤3 cm in greatest dimension) with a predominantly lepidic pattern and ≤5 mm invasion in greatest dimension.
  T1a Tumor ≤1 cm in greatest dimension. It also includes a superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus (but these are uncommon)
  T1b Tumor >1 cm but ≤2 cm in greatest dimension
  T1c Tumor >2 cm but ≤3 cm in greatest dimension
T2 Tumor >3 cm but ≤5 cm or having any of the following features:
  • Involves the main bronchus regardless of distance to the carina, but without involvement of the carina.
  • Invades visceral pleura (PL1 or PL2)
  • Associated with atelectasis or obstructive pneumonitis that extends to the hilar region, involving part or all of the lung.

T2 tumors with these features are classified as T2a if ≤4 cm or if the size cannot be determined and T2b if >4 cm but ≤5 cm.

  T2a Tumor >3 cm but ≤4 cm in greatest dimension
  T2b Tumor >4 cm but ≤5 cm in greatest dimension
T3 Tumor >5 cm but <7 cm in greatest dimension or directly invading any of the following: Parietal pleura (PL3), chest wall (including superior sulcus tumors), phrenic nerve, parietal pericardium; or separate tumor nodule(s) in the same lobe as the primary.
T4 Tumor >7 cm or tumor of any size invading one or more of the following: Diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina. Separate tumor nodule(s) in an ipsilateral lobe different from that of the primary.
N category N criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension.
N2 Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s)
N3 Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph nodes(s)
M category M criteria
M0 No distant metastasis
M1 Distant metastasis
 M1a Separate tumor nodule(s) in a contralateral lobe; tumor with pleural or pericardial nodes or malignant pleural or pericardial effusion (but note that in a few patients, effusions are negative for tumor in multiple microscopic examinations, and the fluid is non-bloody and is not an exudate, and in such cases the effusion should be excluded as a staging descriptor).
  M1b Single extrathoracic metastasis in a single organ (including involvement of a single nonregional node)
  M1c Multiple extrathroracic metastases in a single organ or in multiple organs.
When T is... And N is... And M is... Then the stage group is...
TX N0 M0 Occult carcinoma
Tis N0 M0 0
T1mi N0 M0 1A1
T1a N0 M0
T1a N1 M0 IIB
T1a N2 M0 IIIA
T1a N3 M0 IIIB
T1b N0 M0 IA2
T1b N1 M0 IIB
T1b N2 M0 IIIA
T1b N3 M0 IIIB
T1c N0 M0 IA3
T1c N1 M0 IIB
T1c N2 M0 IIIa
T1c N3 M0 IIIB
T2a N0 M0 IB
T2a N1 M0 IIB
T2a N2 M0 IIIA
T2a N3 M0 IIIB
T2b N0 M0 IIA
T2b N1 M0 IIB
T2b N2 M0 IIIA
T2b N3 M0 IIIB
T3 N0 M0 IIB
T3 N1 M0 IIIA
T3 N2 M0 IIIB
T3 N3 M0 IIIC
T4 N0 M0 IIIA
T4 N1 M0 IIIA
T4 N2 M0 IIIB
T4 N3 M0 IIIC
Any T Any N M1a IVA
Any T Any N M1b IVA
Any T Any N M1c IVB

Further workup

Metastasis versus primary tumor

If a clearly lepidic pattern is seen in association with a tumor, a primary lung tumor can be reported without immunohistochemistry. Otherwise, (look at any related radiology studies), and look for clues in any differentiation of the tumor. In a single undifferentiated lung adenocarcinoma, and there is no evidence of a primary tumor elsewhere in the body, perform immunohistochemistry for TTF-1, (Napsin A), ((broad spectrum cytokeratin marker such as CK AE1/AE3, CK 7 and CK 20)). The presence of multiple tumors indicates an evaluation as a metastasis. Further information: Metastasis

Molecular workup

edit
For primary lung non-small cell carcinoma (NSCLC) stages IB - IV (such as being more than 3 cm in size), generally perform full next generation sequencing panel (DNA and RNA) with PDL-1 immunostaining. For an advanced stage NSCLC that is not a candidate for biopsy or re-biopsy, a viable alternative is “liquid biopsy” on peripheral blood for circulating tumor DNA.[7]

Notes

  1. p63 can distinguish SCC from adenocarcinoma with 85% sensitivity, 95% specificity, 94.4% PPV, and 86.4% NPV, and distinguish SCC from small-cell carcinoma with 85% sensitivity, 100% specificity, 100% PPV, and 87% NPV. Reference:
    - Jafarian AH, Gharib M, Mohammadian Roshan N, Sherafatnia S, Omidi AA, Bagheri S (2017). "The Diagnostic Value of TTF-1, P63, HMWK, CK7, and CD56 Immunostaining in the Classification of Lung Carcinoma. ". Iran J Pathol 12 (3): 195-201. PMID 29531543. PMC: 5835366. Archived from the original. . 
  1. For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.

Main page

References

  1. Image by Mikael Häggström, MD. Source for findings: Caroline I.M. Underwood, M.D., Carolyn Glass, M.D., Ph.D.. Lung - Small cell carcinoma. Pathology Outlines. Last author update: 20 September 2022}}
  2. Jafarian AH, Gharib M, Mohammadian Roshan N, Sherafatnia S, Omidi AA, Bagheri S (2017). "The Diagnostic Value of TTF-1, P63, HMWK, CK7, and CD56 Immunostaining in the Classification of Lung Carcinoma. ". Iran J Pathol 12 (3): 195-201. PMID 29531543. PMC: 5835366. Archived from the original. . 
  3. 3.0 3.1 Lambe, Gerard; Durand, Michael; Buckley, Anne; Nicholson, Siobhan; McDermott, Ronan (2020). "Adenocarcinoma of the lung: from BAC to the future ". Insights into Imaging 11 (1). doi:10.1186/s13244-020-00875-6. ISSN 1869-4101. 
  4. Barletta, Justine A.; Yeap, Beow Y.; Chirieac, Lucian R. (2010). "Prognostic significance of grading in lung adenocarcinoma ". Cancer 116 (3): 659–669. doi:10.1002/cncr.24831. ISSN 0008543X. 
  5. . Protocol for the Examination of Specimens From Patients With Primary Non-Small Cell Carcinoma, Small Cell Carcinoma, or Carcinoid Tumor of the Lung. Version: Lung 4.0.0.2. Protocol Posting Date: June 2017. College of American Pathologists.
  6. Amin, Mahul (2017). AJCC cancer staging manual (8 ed.). Switzerland: Springer. ISBN 978-3-319-40617-6. OCLC 961218414. 
    - For access, see the Secrets chapter of Patholines.
    - Copyright note: The AJCC, 8th Ed. is published by a company in Switzerland, and the tables presented therein are Public Domain because they consist of tabular information without literary or artistic innovation, and therefore do not fulfil the inclusion criterion of the Swiss Copyright Act (CopA) which applies to "literary and artistic intellectual creations with individual character" (see Federal Act on Copyright and Related Rights (Copyright Act, CopA) of 9 October 1992 (Status as of 1 January 2022)). edit
  7. . National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) - Non-Small Cell Lung Cancer. Version 3.2024. Section: Principles of molecular and biomarker analysis (2024-03-12).

Image sources