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. 2021 Feb 18;21(1):176.
doi: 10.1186/s12885-021-07892-8.

Morphological and genetic heterogeneity of synchronous multifocal lung adenocarcinoma in a Chinese cohort

Donglin Zhu  1 , Dan Cao  2 , Minghong Shen  2 , Jinghuan Lv  3
Affiliations

Morphological and genetic heterogeneity of synchronous multifocal lung adenocarcinoma in a Chinese cohort

Donglin Zhu et al. BMC Cancer. .

Abstract

Background: Synchronous multifocal lung cancer (SMLC) is diagnosed with increasing frequency in clinical practice globally. Due to innate variation in clinical management and outcome, it is vital to properly distinguish between synchronous multifocal primary lung cancer (SMPLC) and intrapulmonary metastasis (IM). The pathologic features and principal classification criteria of multifocal lung cancer remain unclear. Our objective was to evaluate the diagnostic value of histological morphologic features and driver gene mutations in SMLC classification.

Methods: We collected a unique cohort of Chinese patients with SMLC, and fully explored the morphologic, immunohistochemical, and molecular features of the disease. Twenty-one SMLC patients with a total of 50 tumours were included in our study. The pathological features that were presented by these patients were analysed, including the tumours location, tumours size, pathological types, predominant pattern of adenocarcinoma, and immunohistochemical staining. We conducted molecular testing of nine driver oncogenes that are associated with lung cancer, namely, EGER, KRAS, BRAF, NRAS, ALK, ROS1, RET, HER2, and PIK3CA.

Results: According to the Martini-Melamed classification and refined standard, 8 and 17 patients, respectively, were considered to have SMPLCs. Gene mutations were identified in 18 tumours (36%). Twelve patients had different gene mutations.

Conclusions: We demonstrate that conventional morphological assessment is not sufficient to clearly establish the clonal relationship of SMPLCs. Instead, the evaluation of histological subtypes, including nonmucinous adherent components, is required. Multiplex genotypic analysis may also prove to be a useful additional tool.

Keywords: Morphological assessment; Multiplex genotypic analysis; Synchronous multifocal lung cancer (SMLC); Synchronous multifocal primary lung cancer (SMPLC).

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Classification of a case of SMPLC accordomg to the Martini and Melamed criteria. Normal lung tissue (a, HE), an adenocarcinoma in the left upper lobe (b, HE; d, TTF-1; g, ki-67) and an adenosquamous carcinoma in the right upper lobe (c, HE; e, CK5/6; f, TTF-1; h, ki-67) of case 1
Fig. 2
Fig. 2
Classification of a case of SMPLC according to the Martini and Melamed criteria. Normal lung tissue (a, HE; d, ki-67), an adenocarcinoma in the right upper lobe (b, HE; e, ki-67) and a mucinous adenocarcinoma in the right lower lobe (c, HE; f, ki-67) of case 8
Fig. 3
Fig. 3
Classification of a case of SMPLC according to the Martini and Melamed criteria. Normal lung tissue (a, HE; d, ki-67) and two separate adenocarcinoma foci in situ in the left lower lobe (b, and c, HE; e, and f, ki-67) of case 2
Fig. 4
Fig. 4
Classification if a case of SMPLC according to the refined standard. Normal lung tissue (a, HE; d, ki-67), an AIS (b, HE; e, ki-67) and a lepidic predominant adenocarcinoma lesion (c, HE; f, ki-67) in the right lower lobe of case 11
Fig. 5
Fig. 5
Mutation analyses of 50 tumours from 21 patients. a shows the genetic mutation status of each tumour. The red columns indicate the presence of mutations. Gene mutations were identified in 18 tumours (36%). b and c compare the tumour sizes between driver mutation-positive and driver mutation-negative lesions
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