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Year : 2016  |  Volume : 12  |  Issue : 2  |  Page : 1090-1092

ALK positivity on pleuroscopic pleural biopsy in lung adenocarcinoma

1 Institute of Pulmonology, Medical Research and Development; Lung Care Team, Fortis Hospitals, Mumbai, Maharashtra, India
2 Department of Oncology, Fortis Hospital, Mulund, Mumbai, Maharashtra, India

Date of Web Publication25-Jul-2016

Correspondence Address:
Prashant N Chhajed
Institute of Pulmonology, Medical Research and Development, B/24, Datta Apartments, Ramkrishna Mission Marg, 15th Road, Khar West, Mumbai - 400 052, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.154053

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 > Abstract 

Lung cancer is the leading cause of cancer deaths worldwide, and around 75% to 80% of lung cancers are detected in advanced stage. Multiple genetic mutations are identified and reported in adenocarcinoma of the lung. Various pulmonary samples can be tested for molecular mutations in lung cancer. However, feasibility of molecular profiling of pleuroscopic pleural biopsies in lung adenocarcinoma is not reported. We describe a case of advanced adenocarcinoma of lung with positive anaplastic lymphoma tyrosine kinase mutation on pleuroscopic pleural biopsy and improved with oral crizotinib. The current case highlights the feasibility of pleuroscopy.-guided pleural biopsies in molecular profiling of lung adenocarcinoma.

Keywords: ALK mutation, adenocarcinoma of lung, EGFR mutation, pleuroscopy, pleural biopsy

How to cite this article:
Vaidya PJ, Kate AH, Mehta D, Dhabar BN, Chhajed PN. ALK positivity on pleuroscopic pleural biopsy in lung adenocarcinoma. J Can Res Ther 2016;12:1090-2

How to cite this URL:
Vaidya PJ, Kate AH, Mehta D, Dhabar BN, Chhajed PN. ALK positivity on pleuroscopic pleural biopsy in lung adenocarcinoma. J Can Res Ther [serial online] 2016 [cited 2020 Jul 12];12:1090-2. Available from: http://www.cancerjournal.net/text.asp?2016/12/2/1090/154053

 > Introduction Top

Lung cancer is the leading cause of cancer deaths worldwide.[1] About 75% to 80% of lung cancers are detected in an advanced stage.[2],[3] Molecular testing of non-small cell lung cancer is recommended to offer targeted therapy, which has been shown to improve prognosis.[2] Various pulmonary samples can be tested for molecular mutations in lung cancer.[4] Molecular testing for lung cancer is feasible in malignant pleural effusions.[5] However, feasibility of molecular profiling of pleuroscopic pleural biopsies in lung adenocarcinoma is not reported. The current case highlights the value of pleuroscopy-guided pleural biopsies in molecular profiling of lung adenocarcinoma.

 > Clinical Scenario Top

A 54-year-old diabetic, non-smoker male presented with dyspnea-modified medical research council grade 3, weight loss and recurrent right-sided pleural effusion. Pleural fluid analysis revealed an exudative effusion with normal adenosine deaminase levels and did not show any malignant cells. Computed tomography of the thorax revealed right-sided effusion, lung mass on the right side, mediastinal lymphadenopathy and lesions in the liver and both adrenal glands suggesting an advanced carcinoma of lung. Chest ultrasound revealed moderate pleural effusion with loculations. An ultrasound-guided therapeutic thoracocentesis was done. Pleural fluid cytology/cell block did not show malignant cells. Pleuroscopy was performed on the right side under local anesthesia and sedation and pleuroscopic pleural biopsies were obtained [Figure 1]. Histopathology of the pleural biopsy revealed metastatic adenocarcinoma [Figure 2]. The pleural cells expressed CK-7 and were immunonegative for CK-20, TTF-1, Napsin A, P 63, Calretinin and WT-1. Serum CYFRA 21.1 was positive (66.42 ng/ml) on complete tumor marker screening.[6] Combined full body positron emission tomography and computed tomography revealed brain, liver, both adrenal glands and skeletal metastases. A diagnosis of adenocarcinoma of lung was made. Pleural biopsy cell block on molecular analysis was negative for epidermal growth factor receptor (EGFR) gene mutation and was positive for anaplastic lymphoma tyrosine kinase (ALK) gene mutation [Figure 3] and [Figure 4] (immunohistochemistry using Ventana kit)[7]. Indwelling pleural catheter (PleurX ) was inserted on the right side. Whole brain radiation with external beam radiotherapy using 30 Gray with 6 Megavoltage photons with bilateral portals for brain metastasis was given for 10 days. Patient was started on oral crizotinib. On follow-up for 12 weeks, the Eastern Cooperative Oncology Group (ECOG) performance status scale has improved from a score of 3 at diagnosis to ECOG score 1. A follow-up X-ray chest done shows remarkable improvement and patient joined full-time work 24 weeks after the initiation of therapy [Figure 5] and [Figure 6].
Figure 1: Pleuroscopic image of malignant pleural nodules

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Figure 2: Histopathology (H and E-stained) slide of pleural biopsy

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Figure 3: ALK positivity of pleural biopsy sample by immunohistochemistry (high power)

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Figure 4: ALK testing by immunohistochemistry negative control

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Figure 5: Chest X-ray erect view dated July 2014

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Figure 6: Follow-up chest X-ray erect view Left dated November 2014 and Right dated September 2014

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 > Discussion Top

Lung cancer remains the most lethal cancer worldwide.[1] Non-small cell lung cancer accounts for 85% of the lung cancers detected worldwide.[2] A majority of them are detected in an advanced stage.[2] Adenocarcinoma is the commonest non-small cell lung cancer seen among non-smokers.[2] As cancer is a disorder of the cell genome, much genetic diversity may describe a cancer. Multiple genetic mutations are identified and reported in adenocarcinoma of the lung.[8] The clinically relevant or those that can be targeted by drugs are EGFR gene, ALK gene, mesenchymal-epithelial transcription factor (MET) gene, Kirsten rat sarcoma (KRAS) gene and ROS-1.[9] The mutations are mutually exclusive.[9]

Platinum-based chemotherapy regimens were the cornerstone of treatment of unresectable non-small cell lung cancer until molecular typing was discovered. Tyrosine kinase (TK) inhibitors improve outcomes compared to platinum-based chemotherapy, in EGFR gene mutation and ALK gene mutation.[10],[11] Molecular typing of adenocarcinoma of lung is recommended globally to offer targeted therapy and improve outcomes.[2] Gefitinib and Erlotinib are the most studied TK inhibitors targeting EGFR mutation and crizotinib for ALK mutation.[9] Personalized treatment regime based on the genetic profile of the non-small cell lung cancer is the way forward.

The echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma tyrosine kinase (EML4-ALK) gene mutation was first discovered in lung cancer in 2007.[12] The EML4-ALK gene is a fusion gene from a chromosome.

Rearrangement between the N-terminal portion of the EML4 gene and the TK domain of the ALK gene, both located on the short arm of chromosome 2, leading to a chimeric oncoprotein with constitutive TK activity and oncogenic transforming activity.[13] In addition to EML4-ALK, other ALK fusions have also been reported in lung cancer, including TFG-ALK, KIF5B-ALK and KLC1-ALK.[13] The incidence of ALK translocation in non-small cell lung cancer is reported to be 3 − 6%.[11],[14] It is more common in younger patients, patients who were light or non-smokers, and patients with adenocarcinoma.[14] At present, the three primary methods of detecting ALK rearrangements are fluorescent in situ hybridization (FISH), immunohistochemistry (IHC) and the reverse transcriptase polymerase chain reaction (RT-PCR).[13] Each of these individual methods has both advantages and disadvantages.[13] FISH has been considered the gold standard method for detecting ALK rearrangements, as it can detect rearrangements irrespective of the EML4-ALK gene fusion variants and other fusion cohorts, but is expensive and requires expertise.[13]

The feasibility of genotyping of various tissue samples in non-small cell lung cancer has been reported.[4] To our knowledge, this is the first report that highlights the feasibility of molecular genotyping of lung cancer from a pleuroscopic pleural biopsy in a case of adenocarcinoma lung.

 > References Top

Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. Cancer Incidence and Mortality Worldwide. Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359-86.  Back to cited text no. 1
Ettinger DS, Akerley W, Borghaei H, Chang AC, Cheney RT, Chirieac LR, et al. Non-small cell lung cancer, version 2.2013. J Natl Compr Cancer Netw 2013;11:645-53.  Back to cited text no. 2
Chhajed PN, Athavale AU, Shah AC. Clinical and pathological profile of 73 patients with lung carcinoma: Is the picture changing? J Assoc Physicians India 1999;5:483-7.  Back to cited text no. 3
Vanderlaan PA, Yamaguchi N, Folch E, Boucher DH, Kent MS, Gangadharan SP, et al. Success and failure rates of tumor genotyping techniques in routine pathological samples with non-small-cell lung cancer. Lung Cancer 2014;1:39-44.  Back to cited text no. 4
Akamatsu H, Koh Y, Kenmotsu H, Naito T, Serizawa M, Kimura M, et al. Multiplexed molecular profiling of lung cancer using pleural effusion. J Thorac Oncol 2014;7:1048-52.  Back to cited text no. 5
Rapellino M, Niklinski J, Pecchio F, Furman M, Baldi S, Chyczewski L, et al. CYFRA 21-1 as a tumour marker for bronchogenic carcinoma. Eur Respir J 1995;3:407-10.  Back to cited text no. 6
Ying J, Guo L, Qiu T, Shan L, Ling Y, Liu X, et al. Diagnostic value of a novel fully automated immunochemistry assay for detection of ALK rearrangement in primary lung adenocarcinoma. Ann Oncol 2013;10:2589-93.  Back to cited text no. 7
Roh MS. Molecular pathology of lung cancer: Current status and future directions. Tuberc Respir Dis (Seoul) 2014;2:49-54.  Back to cited text no. 8
Korpanty GJ, Graham DM, Vincent MD, Leighl NB. Biomarkers that currently affect clinical practice in lung cancer: EGFR, ALK, MET, ROS-1, and KRAS. Front Oncol. 2014;4:204.  Back to cited text no. 9
Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009;10:947-57.  Back to cited text no. 10
Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 2010;18:1693-703.  Back to cited text no. 11
Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007;7153:561-6.  Back to cited text no. 12
Wang J, Dong Y, Cai Y, Zhou L, Wu S, Liu G, et al. Clinicopathologic characteristics of ALK rearrangements in primary lung adenocarcinoma with identified EGFR and KRAS status. J Cancer Res Clin Oncol 2014;3:453-60.  Back to cited text no. 13
Shaw AT, Yeap BY, Mino-Kenudson M, Digumarthy SR, Costa DB, Heist RS, et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol 2009;26:4247-53.  Back to cited text no. 14


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]


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