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lepidic growth pattern in pulmonary adenocarcinoma

Monday 26 March 2012

Adenocarcinoma with bronchioloalveolar growth pattern; adenocarcinoma with lepidic pattern; pulmonary adenocarcinoma with prominent lepidic spread

Definition: In the 2004, WHO classification, the term "bronchioloalveolar carcinoma" (BAC) is restricted to tumors in which the characteristic lepidic growth pattern (growth along intact alveolar septae) comprises the entire tumor.


- pulmonary AIS : pulmonary adenocarcinoma in situ
- pulmonary MIA : pulmonary minimally invasive adenocarcinoma in situ
- lepidic predominant invasive adenocarcinoma

BAC therefore lacks any stromal, pleural, or lymphatic invasion, although fibrous tissue or a chronic inflammatory cell infiltrate may thicken the alveolar septa. Both mucinous and non-mucinous subtypes are recognized. In the 2011 classification scheme, these tumors have been renamed as " pulmonary adenocarcinoma in situ " or " lepdidic adenocarcinoma ".

Historically, pulmonary adenocarcinomas with lepidic growth (growth along alveolar septa) have been termed bronchioloalveolar carcinoma (BAC), a term coined by Dr Averill Liebow in 1960. He noted that BAC had an indolent clinical course compared to other aggressive types of lung cancer.

The definition of BAC was made more stringent over the years and was eventually defined as a tumor showing " entirely lepidic growth without any tumoral invasion of the stroma or chorion ".

Minimal invasion or limited invasion

Subsequent studies focused on small lepidic-predominant tumors with limited areas of invasion, which have shown that the size of invasion or scarring may be more prognostic than gross tumor size.

Tumors with less than or equal to 5 mm of invasion are associated with excellent survival and have been termed minimally invasive adenocarcinoma (MIA).

A consensus classification was proposed by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society in 2011, which has been adopted by the 2015 World Health Organization (WHO) classification of pulmonary adenocarcinoma.

Invasive component

This classification abandons the term BAC in favor of adenocarcinoma in situ (AIS) and formally introduces MIA as a diagnostic category, whereas tumors with greater than 5 mm invasion are classified as invasive adenocarcinoma (IA).

AIS and MIA are limited to tumors less than or equal to 3 cm because data on larger tumors are very limited.

Studies have shown that solid and micropapillary tumors are more aggressive, whereas lepidic tumors have better survival, so it is also recommended that IAs be subclassified according to the predominant histologic pattern.

Approximately one third of lung adenocarcinomas have significant lepidic spread, and of these, nearly one third are minimally invasive.

Measurement of the invasive component may be difficult without elastotic desmoplasia.

Lymph node and distant metastases occurred only in those with complex invasive patterns, but lung recurrence occurred in all subtypes, including MIAs.

The morphological features of these tumors are similar irrespective of solitary, disseminated, or diffuse growth.

The macroscopic findings of this tumor are those of a solitary pulmonary nodule that cannot measure more than 3 cm in greatest dimension.

Histologically, the tumor is characterized by growth along the alveolar walls, which can be partially or completely replaced by a low cuboidal or cylindrical epithelium. The cells have oval or round nuclei, which may show inconspicuous or prominent nucleoli.

Even though mitotic activity is not prominent, rare mitotic figures can be seen in some cases. By definition, the tumor should not show any stromal, pleural, lymphatic, or nodal invasion.

See also

- lepidic growth pattern
- invasive growth pattern

  • invasive papillary growth pattern
  • invasive acinar growth pattern

- foci of tumoral invasion / focus of tumoral invasion

- thickening of the alveolar walls

  • fibrosis of the alveolar walls

Paywall References

- Comprehensive study of mutational and clinicopathologic characteristics of adenocarcinoma with lepidic pattern in surgical resected lung adenocarcinoma.
Xu Y, Zhu C, Qian W, Zheng M.
J Cancer Res Clin Oncol. 2017 Jan;143(1):181-186. doi : 10.1007/s00432-016-2255-8
PMID: 27738759

- The role of extent of surgical resection and lymph node assessment for clinical stage I pulmonary lepidic adenocarcinoma: An analysis of 1,991 patients.
Cox ML, Yang CJ, Speicher PJ, Anderson KL, Fitch ZW, Gu L, Davis RP, Wang X, D’Amico TA, Hartwig MG, Harpole DH Jr, Berry MF.
J Thorac Oncol. 2017 Jan 7. pii: S1556-0864(17)30004-7. doi : 10.1016/j.jtho.2017.01.003
PMID: 28082103

- Adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive pulmonary adenocarcinoma—analysis of interobserver agreement, survival, radiographic characteristics, and gross pathology in 296 nodules.
Boland JM, Froemming AT, Wampfler JA, Maldonado F, Peikert T, Hyland C, de Andrade M, Aubry MC, Yang P, Yi ES.
Hum Pathol. 2016 May;51:41-50. doi : 10.1016/j.humpath.2015.12.010
PMID: 27067781

- Adenocarcinomas with prominent lepidic spread: retrospective review applying new classification of the American Thoracic Society. Xu L, Tavora F, Battafarano R, Burke A. Am J Surg Pathol. 2012 Feb;36(2):273-82. PMID: 22198010

- A.C. Borczuk, F. Qian, A. Kazeros, et al. Invasive size is an independent predictor of survival in pulmonary adenocarcinoma Am J Surg Pathol, 33 (2009), pp. 462–469

- H. Terasaki, T. Niki, Y. Matsuno, et al. Lung adenocarcinoma with mixed bronchioloalveolar and invasive components: clinicopathological features, subclassification by extent of invasive foci, and immunohistochemical characterization. Am J Surg Pathol, 27 (2003), pp. 937–951