Limits...
Comparative genetic analysis of a rare synchronous collision tumor composed of malignant pleural mesothelioma and primary pulmonary adenocarcinoma.

Naka T, Hatanaka Y, Marukawa K, Okada H, Hatanaka KC, Sakakibara-Konishi J, Oizumi S, Hida Y, Kaga K, Mitsuhashi T, Matsuno Y - Diagn Pathol (2016)

Bottom Line: We experienced a rare synchronous collision tumor composed of malignant pleural mesothelioma (MPM) and primary pulmonary adenocarcinoma (PAC) in a 77-year-old man with a history of long-term smoking and asbestos exposure, and compared the DNA copy number alteration (CNA) and somatic mutation in these two independent tumors.PAC did not harbor CNAs that have been identified in asbestos-associated lung cancer, but did harbor some of the CNAs associated with smoking.In this particular case, asbestos exposure may not have played a primary role in PAC carcinogenesis, but cigarette smoking may have contributed more to the occurrence of CN gains in PAC.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgical Pathology, Hokkaido University Hospital, Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan.

ABSTRACT

Background: Although asbestos acts as a potent carcinogen in pleural mesothelial and pulmonary epithelial cells, it still remains unclear whether asbestos causes specific and characteristic gene alterations in these different kinds of target cells, because direct comparison in an identical patient is not feasible. We experienced a rare synchronous collision tumor composed of malignant pleural mesothelioma (MPM) and primary pulmonary adenocarcinoma (PAC) in a 77-year-old man with a history of long-term smoking and asbestos exposure, and compared the DNA copy number alteration (CNA) and somatic mutation in these two independent tumors.

Methods: Formalin-fixed paraffin-embedded (FFPE) tissues of MPM and PAC lesions from the surgically resected specimen were used. Each of these MPM and PAC lesions exhibited a typical histology and immunophenotype. CNA analysis using SNP array was performed using the Illumina Human Omni Express-12_FFPE (Illumina, San Diego, CA, USA) with DNA extracts from each lesion. Somatic mutation analysis using next-generation sequencing was performed using the TruSeq Amplicon Cancer Panel (Illumina).

Results: The CNA analysis demonstrated a marked difference in the frequency of gain and loss between MPM and PAC. In PAC, copy number (CN) gain was detected more frequently and widely than CN loss, whereas in MPM there was no such obvious difference. PAC did not harbor CNAs that have been identified in asbestos-associated lung cancer, but did harbor some of the CNAs associated with smoking. MPM exhibited CN loss at 9p21.2-3, which is the most common genetic alteration in mesothelioma.

Conclusion: In this particular case, asbestos exposure may not have played a primary role in PAC carcinogenesis, but cigarette smoking may have contributed more to the occurrence of CN gains in PAC. This comparative genetic analysis of two different lesions with same amount of asbestos exposure and cigarette smoke exposure has provided information on differences in the cancer genome related to carcinogenesis.

No MeSH data available.


Related in: MedlinePlus

Histology and immunohistochemistry of the two lesions of the synchronous collision tumor. Representative histologic features of the diffuse pleural thickening (a), epithelioid-type MPM, and the intrapulmonary tumor (b), PAC. c and d show the area of collision, PAC being distributed on the upper left, and MPM on the lower right. d Is the magnified images of the rectangle area in (c). MPM and PAC exhibit typical immunohistochemical staining for TTF-1 (e) and calretinin (f), respectively
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4836188&req=5

Fig2: Histology and immunohistochemistry of the two lesions of the synchronous collision tumor. Representative histologic features of the diffuse pleural thickening (a), epithelioid-type MPM, and the intrapulmonary tumor (b), PAC. c and d show the area of collision, PAC being distributed on the upper left, and MPM on the lower right. d Is the magnified images of the rectangle area in (c). MPM and PAC exhibit typical immunohistochemical staining for TTF-1 (e) and calretinin (f), respectively

Mentions: Histologically, these two tumors showed distinct features. The pleural tumor was composed of neoplastic cells growing in a tubulopapillary pattern, or in solid sheets or nests in some areas (Fig. 2a). Most of the papillae were covered by a single layer of cuboidal tumor cells, and the pseudoglands were lined by similar cells, often with a solid growth pattern. These histologic findings were conclusive of MPM, epithelioid type. On the other hand, the intrapulmonary tumor was composed of neoplastic cells showing lepidic growth in the peripheral portion, and papillary or acinar invasive growth patterns in the central portion (Fig. 2b). Its stroma varied from fibrous to desmoplastic. These findings suggested a diagnosis of PAC, which is invasive adenocarcinoma, lepidic predominant (lepidic 60 %, papillary 30 %, acinar 10 %) according to Sica’s classification [11]. The two tumors, MPM and PAC, collided within the same lower lobe of the left lung (Fig. 2c, d). Asbestos bodies were detected rather easily in HE-stained sections of the subpleural or peribronchial non-tumorous lung parenchyma.Fig. 2


Comparative genetic analysis of a rare synchronous collision tumor composed of malignant pleural mesothelioma and primary pulmonary adenocarcinoma.

Naka T, Hatanaka Y, Marukawa K, Okada H, Hatanaka KC, Sakakibara-Konishi J, Oizumi S, Hida Y, Kaga K, Mitsuhashi T, Matsuno Y - Diagn Pathol (2016)

Histology and immunohistochemistry of the two lesions of the synchronous collision tumor. Representative histologic features of the diffuse pleural thickening (a), epithelioid-type MPM, and the intrapulmonary tumor (b), PAC. c and d show the area of collision, PAC being distributed on the upper left, and MPM on the lower right. d Is the magnified images of the rectangle area in (c). MPM and PAC exhibit typical immunohistochemical staining for TTF-1 (e) and calretinin (f), respectively
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4836188&req=5

Fig2: Histology and immunohistochemistry of the two lesions of the synchronous collision tumor. Representative histologic features of the diffuse pleural thickening (a), epithelioid-type MPM, and the intrapulmonary tumor (b), PAC. c and d show the area of collision, PAC being distributed on the upper left, and MPM on the lower right. d Is the magnified images of the rectangle area in (c). MPM and PAC exhibit typical immunohistochemical staining for TTF-1 (e) and calretinin (f), respectively
Mentions: Histologically, these two tumors showed distinct features. The pleural tumor was composed of neoplastic cells growing in a tubulopapillary pattern, or in solid sheets or nests in some areas (Fig. 2a). Most of the papillae were covered by a single layer of cuboidal tumor cells, and the pseudoglands were lined by similar cells, often with a solid growth pattern. These histologic findings were conclusive of MPM, epithelioid type. On the other hand, the intrapulmonary tumor was composed of neoplastic cells showing lepidic growth in the peripheral portion, and papillary or acinar invasive growth patterns in the central portion (Fig. 2b). Its stroma varied from fibrous to desmoplastic. These findings suggested a diagnosis of PAC, which is invasive adenocarcinoma, lepidic predominant (lepidic 60 %, papillary 30 %, acinar 10 %) according to Sica’s classification [11]. The two tumors, MPM and PAC, collided within the same lower lobe of the left lung (Fig. 2c, d). Asbestos bodies were detected rather easily in HE-stained sections of the subpleural or peribronchial non-tumorous lung parenchyma.Fig. 2

Bottom Line: We experienced a rare synchronous collision tumor composed of malignant pleural mesothelioma (MPM) and primary pulmonary adenocarcinoma (PAC) in a 77-year-old man with a history of long-term smoking and asbestos exposure, and compared the DNA copy number alteration (CNA) and somatic mutation in these two independent tumors.PAC did not harbor CNAs that have been identified in asbestos-associated lung cancer, but did harbor some of the CNAs associated with smoking.In this particular case, asbestos exposure may not have played a primary role in PAC carcinogenesis, but cigarette smoking may have contributed more to the occurrence of CN gains in PAC.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgical Pathology, Hokkaido University Hospital, Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan.

ABSTRACT

Background: Although asbestos acts as a potent carcinogen in pleural mesothelial and pulmonary epithelial cells, it still remains unclear whether asbestos causes specific and characteristic gene alterations in these different kinds of target cells, because direct comparison in an identical patient is not feasible. We experienced a rare synchronous collision tumor composed of malignant pleural mesothelioma (MPM) and primary pulmonary adenocarcinoma (PAC) in a 77-year-old man with a history of long-term smoking and asbestos exposure, and compared the DNA copy number alteration (CNA) and somatic mutation in these two independent tumors.

Methods: Formalin-fixed paraffin-embedded (FFPE) tissues of MPM and PAC lesions from the surgically resected specimen were used. Each of these MPM and PAC lesions exhibited a typical histology and immunophenotype. CNA analysis using SNP array was performed using the Illumina Human Omni Express-12_FFPE (Illumina, San Diego, CA, USA) with DNA extracts from each lesion. Somatic mutation analysis using next-generation sequencing was performed using the TruSeq Amplicon Cancer Panel (Illumina).

Results: The CNA analysis demonstrated a marked difference in the frequency of gain and loss between MPM and PAC. In PAC, copy number (CN) gain was detected more frequently and widely than CN loss, whereas in MPM there was no such obvious difference. PAC did not harbor CNAs that have been identified in asbestos-associated lung cancer, but did harbor some of the CNAs associated with smoking. MPM exhibited CN loss at 9p21.2-3, which is the most common genetic alteration in mesothelioma.

Conclusion: In this particular case, asbestos exposure may not have played a primary role in PAC carcinogenesis, but cigarette smoking may have contributed more to the occurrence of CN gains in PAC. This comparative genetic analysis of two different lesions with same amount of asbestos exposure and cigarette smoke exposure has provided information on differences in the cancer genome related to carcinogenesis.

No MeSH data available.


Related in: MedlinePlus