Contents

Search

adenocarcinoma of the lung

Etiology: - see non-small cell lung carcinoma Epidemiology: 1) most common histological subtype of lung cancer* [11] - 50% of non-small cell lung cancer 2) age > 50 years 3) most common form of lung cancer in non-smokers - 15% of patients with NSCLC are never-smokers [17] - incidence of NSCLC among never-smokers increased from 8% in 1990 to 15% in 2013 [17] - increased incidence largely, if not exclusively, due to increased incidence of lung adenocarcinoma in never-smokers * lung cancer is the most cause of cancer-related mortality Pathology: 1) most arise in the peripheral lung fields & remain undetected until they have spread locally or distally 2) six cytological categories: a) bronchial surface cell type b) goblet cell type c) bronchial gland cell type d) Clara cell type e) type II alveolar epithelial cell type f) mixed cell type 3) brain metastases (25%) Genetics: - epidermal growth factor receptor (EGFR)-activating mutations in some patients [4]; (14%) [6] - prevalent in females, never smokers, & Asians [10] - abnormalities in the anaplastic lymphoma kinase (ALK) protein in some patients [4] - activating mutations in KRAS (30%) [6] - RET fusion gene (1-2%) - ROS1 gene mutation (5%) [12] - inv(2)(p21:q23) resulting in EML4-ALK fusion gene [5] - from The Cancer Genome Atlas [6] - TTN (titin) (57%) - TP53 (54%) - MUC16 (48%) - RYR2 (45%) - CSMD3 (44%) - MALAT1 transcript associated with metastasis ? - other implicated genes: - SPECC1, RNF43, BIRC5, USP4 - ABCA13 ADAMTS12 ADAMTS20 ADCY2 AFF2 AHNAK AHNAK2 ANK2 ANKRD30A APOB ASPM ASTN1 ASTN2 ASXL3 BAGE2 BAI3 C1ORF173 CACNA1C CACNA1E CDH10 CDH12 CDH9 CNTNAP2 CNTNAP5 COL11A1 COL22A1 COL3A1 COL6A3 CPS1 CRB1 CSMD1 CSMD2 CTNNA2 CTNND2 CUBN DCAF4L2 DCDC1 DCHS2 DMD DNAH11 DNAH3 DNAH5 DNAH7 DNAH8 DNAH9 DOCK2 DSCAM DST EPHA5 FAM135B FAM47A FAM47C FAM5C FAT1 FAT3 FAT4 FBN2 FLG FLG2 FMN2 FRG1B GPR112 GPR158 GPR98 GRIN2B HCN1 HERC2 HMCN1 HRNR HSD17B7P2 HYDIN KEAP1 KIAA1109 KIF2B KMT2C LAMA2 LL22NC03-80A10.6 LPHN3 LRP1B LRP2 LRRC7 MAGEC1 MGAM MUC17 MUC5B MXRA5 MYH1 MYH2 MYH7 MYH8 MYO18B NALCN NAV3 NBPF10 NCKAP5 NEB NF1 NLRP3 NPAP1 NRXN1 OBSCN PAPPA2 PCDH10 PCDH11X PCDH15 PCDH17 PCLO PDE4DIP PEG3 PKHD1 PKHD1L1 PLEC PLXNA4 PRDM9 PRUNE2 PTPRB PTPRD PTPRT PTPRZ1 PXDNL RELN RIMS2 RP1L1 RYR1 RYR3 SALL1 SETBP1 SI SLC8A1 SLITRK2 SNHG14 SNTG1 SORCS1 SPTA1 SSPO STK11 SYNE1 SYNE2 TENM1 TENM2 TEX15 TG TIAM1 TLR4 TNN TNR TP53 TPTE TRPS1 TSHZ3 UNC79 USH2A VCAN XIRP2 ZAN ZFHX4 ZFPM2 ZNF208 ZNF536 ZNF804A ZNF831 ZP4 [6] Clinical manifestations: 1) symptoms generally indicate advanced disease 2) clubbing 3) hypertrophic pulmonary osteoarthropathy 4) SIADH (uncommon) 5) acanthosis nigricans (uncommon) 6) hypercalcemia uncommon (see Laboratory:) Laboratory: 1) sputum cytology has low diagnostic yield 2) serum calcium: hypercalcemia (3%) 3) serum calcitonin: increased secretion of calcitonin (70%) 4) increased secretion of hCG, LH & FSH may occur - serum chorionic gonadotropin - serum luteinizing hormone - serum follicle-stimulating hormone 5) immunohistochemistry: - CD66E: + - CEAD-14: - - AE1/AE3: + - CK5: - - CK6: - - CK7: + - TTF1: +/- 6) EGFR gene mutation useful for treatment [12,14,15] 7) anaplastic lymphoma kinase (ALK) gene rearrangement [5,7] - EML4-ALK fusion transcript [5] 8) ROS1 gene mutation [12] 9) RET gene mutation [9] 10) PD-L1 expression 11) prognostic markers a) KRAS gene mutation analysis [12,14] - useful for prognosis but not treatment b) EBAG9 Special laboratory: - lung biopsy: - fiberoptic bronchoscopy may not reach lung periphery - CT-guided percutaneous needle biopsy - mediastinoscopy if metastases not detected [16] - see lung carcinoma Radiology: - chest X-ray a) small peripheral nodule (most common presentation) b) cavitation (uncommon) c) may present as pneumonia - computed tomography of thorax - MRI of brain to rule out brain metastases [16] - positron emission tomography (PET) for staging [8] Complications: - intractable cancer pain associated with metastases [13] Staging: - see staging of lung cancer Management: 1) general guidelines, see non-small cell lung carcinoma (NSCLC) - staging, see staging of lung cancer - treat as non-small cell lung carcinoma [4] - palliative care referral for advanced-stage NSCLC - concurrent chemotherapy & palliative care can increase life expectancy 20% - surgical resection - neoadjuvant chemotherapy with nivolumab 4 weeks before surgery may reduce tumor burden [18] - cisplatin or carboplatin + permetrexed + PDL-1 inhibitor - regardless of PDL-1 status - carboplatin + permetrexed + pembrolizumab (Keytruda) [14] - MKSAP19 treatment of choice for metastatic lung adenocarcinoma - nivolumab (Opdivo) for metastatic disease with progression on or after platinum-based chemotherapy - cisplatin-based regimen shown to be effective [4] - adjuvant cisplatin-based chemotherapy (4 cycles) improves survival in patients after successful resection of stage 2 or 3 NSCLC regardless of histologic type [4] - adjuvant platinum-based doublet chemotherapy after surgical resection [16] - cisplatin-vinorelbine doublet chemotherapy 4 cycles after surgical resection improves 5 year survival for stage II NSCLC 51% vs 43% - supportive therapy - treat cancer pain [13] - prognosis 2) lung adenocarcinoma-specific guidelines - platinum-based chemotherapy combined with pemetrexed - 4-6 cycles [14] - modified carboplatin plus paclitaxel may be better than gemcitabine or vinorelbine alone [3] - pemetrexed is first-line option [4] - bevacizumab (VEGFR Ab) 15 mg/kg every 3 weeks - may be combined with platinum-based chemotherapy - improves survival (12.3 months vs 10.3 months) in patients with metastatic adenocarcinoma of the lung [16] - 1st line atezolizumab + bevacizumab + carboplatin + paclitaxel improves survival [19] 3) mutation-specific guidelines - EGFR-activating mutations: afatinib, erlotinib or gefitinib, osimertib - EGFR exon 20 mutations: erlotinib, amivantamab [21] - ALK gene rearrangement: aletinib (1st line) loratinib, ensartinib [14] - RET fusion gene: vandetanib & cabozantinib may be useful [9] - ROS1 gene rearrangement: aletinib - only switch-maintenance therapy with pemetrexed & erlotinib FDA-approved [16] 4) prognosis - surgery is best hope - survival with inoperable cancer is poor (see NSCLC) - response to radiation & chemotherapy is poor

Interactions

disease interactions

Related

hypertrophic pulmonary osteoarthropathy (Bamberger-Marie syndrome) Li-Fraumeni syndrome

Specific

bronchioloalveolar carcinoma (alveolar cell carcinoma) papillary adenocarcinoma, lung

General

adenocarcinoma carcinoma of the lung

References

  1. Diagnostic Surgical Pathology. Sternberg ed. Raven Press 2nd ed. 1994 p 1064
  2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 768
  3. Davidoff AJ et al. Chemotherapy and survival benefit in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol 2010 May 1; 28:2191 PMID: 20351329
  4. ASCO 2010 Report: Lung Cancer GENETIC AND MOLECULAR DRIVERS OF LUNG CANCER Journal Watch: Massachusetts Medical Society http://oncology-hematology.jwatch.org/cgi/content/full/2010/713/5
  5. Soda M et al Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer Nature. 2007 Aug 2;448(7153):561-6 PMID: 17625570 http://www.nature.com/nature/journal/v448/n7153/full/nature05945.html
  6. The Cancer Genome Atlas. June 9, 2014 http://cancergenome.nih.gov
  7. Dacic S. Molecular genetic testing for lung adenocarcinomas: a practical approach to clinically relevant mutations and translocations. J Clin Pathol. 2013 Oct;66(10):870-4 PMID: 23801495
  8. Van Schil PE, Sihoe AD, Travis WD Pathologic classification of adenocarcinoma of lung. J Surg Oncol. 2013 Oct;108(5):320-6 PMID: 24006216
  9. Kohno T, Tsuta K, Tsuchihara K, Nakaoku T, Yoh K, Goto K RET fusion gene: translation to personalized lung cancer therapy. Cancer Sci. 2013 Nov;104(11):1396-400 PMID: 23991695
  10. Liao BC , Lin CC, Yang JC. First-line management of EGFR-mutated advanced lung adenocarcinoma: recent developments. Drugs. 2013 Mar;73(4):357-69 PMID: 23479407
  11. Gaikwad A, Gupta A, Hare S et al Primary adenocarcinoma of lung: a pictorial review of recent updates. Eur J Radiol. 2012 Dec;81(12):4146-55 PMID: 23000187
  12. ARUP Consult: deprecated reference
  13. Kamdar MM, Doyle KP, Sequist LV et al Case 17-2015 - A 44-Year-Old Woman with Intractable Pain Due to Metastatic Lung Cancer. N Engl J Med 2015; 372:2137-2147. May 28, 2015 PMID: 26017825 http://www.nejm.org/doi/full/10.1056/NEJMcpc1404141
  14. Medical Knowledge Self Assessment Program (MKSAP) 17, 18, 19. American College of Physicians, Philadelphia 2015, 2018, 2021.
  15. Rosell R, Carcereny E, Gervais R et al Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46 PMID: 22285168
  16. Lim MY Non-Small Cell Lung Cancer: 5 Management Challenges. Medscape. Nov 30, 2016 http://reference.medscape.com/features/slideshow/non-small-cell-lung-cancer
  17. Pelosof L, Ahn C, Gao A et al Proportion of Never-Smoker Non-Small Cell Lung Cancer Patients at Three Diverse Institutions. J Natl Cancer Inst. 2017 Jan 28;109(7). PMID:28132018
  18. Castellino AM Neoadjuvant Nivolumab Shows Benefit in NSCLC Medscape. Apr 17, 2018. https://www.medscape.com/viewarticle/895274 - Forde PM, Chaft JE, Smith KN et al Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med. 2018 Apr 16. [Epub ahead of print] PMID: 29658848 Free Article
  19. Smith M. NSCLC Survival Rises with Checkpoint Blocker Add-On Atezolizumab plus standard therapy also slows disease progression. MedPage Today. June 04, 2018 https://www.medpagetoday.com/meetingcoverage/asco/73280 - Socinski MA, Jotte RM, Cappuzzo F et al Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018 Jun 4. PMID: 29863955 - Socinski MA et al Overall survival (OS) analysis of IMpower150, a randomized Ph 3 study of atezolizumab (atezo) + chemotherapy (chemo) +/- bevacizumab (bev) vs chemo + bev in 1L nonsquamous (NSQ) NSCLC. American Society of Clinical Oncology (ASCO) 2018; Abstract 9002
  20. Neilan TG, Price MC, Sanborn DY et al Case 33-2018: A 57-Year-Old Man with Confusion, Fever, Malaise, and Weight Loss. N Engl J Med 2018; 379:1658-1669 PMID: 30354952 https://www.nejm.org/doi/full/10.1056/NEJMcpc1802830
  21. Naidoo J, Sima CS, Rodriguez K et al Epidermal growth factor receptor exon 20 insertions in advanced lung adenocarcinomas: Clinical outcomes and response to erlotinib. Cancer. 2015 Sep 15;121(18):3212-3220 PMID: 26096453 PMCID: PMC4807634 Free PMC article
  22. Adenocarcinoma of the Lung Harvard Medical School https://www.health.harvard.edu/cancer/adenocarcinoma-of-the-lung