Classification of different patterns of pulmonary adenocarcinomas

Abstract

The epidemic increase of adenocarcinoma histology accounting for more than 50% of primary lung malignancies and the advent of effective molecular targeted-therapies against specific gene alterations characterizing this tumor type have led to the reconsideration of the pathologic classification of lung cancer. The new 2015 WHO classification provided the basis for a multidisciplinary approach emphasizing the close correlation among clinical, radiologic and molecular characteristics and histopathologic pattern of lung adenocarcinoma. The terms ‘bronchioloalveolar carcinoma’ and ‘mixed adenocarcinoma’ have been eliminated, introducing the concepts of ‘adenocarcinoma in situ’, ‘minimally invasive adenocarcinoma’ and the use of descriptive predominant patterns in invasive adenocarcinomas (lepidic, acinar, papillary, solid and micropapillary patterns). ‘Invasive mucinous adenocarcinoma’ is the new definition for mucinous bronchioloalveolar carcinoma, and some variants of invasive adenocarcinoma have been included, namely colloid, enteric and fetal-type adenocarcinomas. A concise update of the immunomorphologic, radiological and molecular characteristics of the different histologic patterns of lung adenocarcinoma is reported here.

Keywords:

• adenocarcinoma
• epidermal growth factor receptor
• ground-glass
• immunohistochemistry
• in-situ
• lung
• mucinous
• pattern
• thyroid transcription factor 1
• v-ki-ras2 kirsten rat sarcoma viral oncogene homolog

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Adenocarcinoma displaced the other histological types of lung cancer, and its incidence is increasing among young people, nonsmokers and women.

• The new 2015 WHO classification of invasive lung adenocarcinoma is based on the predominant patterns of growth (e.g., lepidic, acinar, papillary, micropapillary and solid) and some variants (e.g., colloid, mucinous, enteric and fetal).

• The term ‘bronchioloalveolar carcinoma’ has been eliminated, and new tumor entities have been introduced, namely adenocarcinoma in situ as preinvasive lesion, and minimally invasive adenocarcinoma.

• The proposed definitions require the examination of a surgically resected sample, while cytology and small biopsies may reliably recognize only few patterns (e.g., lepidic) or variants (e.g., mucinous).

• A precise recognition of lung adenocarcinoma on cytology and small biopsies requires a close integration of morphologic and radiologic features when the maximum tumor dimeter is less than 3 cm.

• The patterns and variants of adenocarcinoma may be associated with peculiar characteristics at CT-based imaging (ground-glass opacities in preinvasive, minimally invasive and lepidic types) and molecular level (occurrence of EGFR mutations in papillary and micropapillary patterns or KRAS mutations in solid pattern and mucinous variant).

• The WHO classification seems to have a prognostic value when analyzing overall survival in early-stage tumors and a good reproducibility among pathologists.

• Immunohistochemistry demonstrates expression of markers of pneumocytic differentiation in the majority of patterns (lepidic, acinar, papillary, micropapillary) and fetal-type variant, while variable staining with antibodies of intestinal differentiation characterizes the remaining variants (colloid, mucinous and enteric).