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• W1991495073 abstract "A 68-year-old white non-smoker woman was admitted to our department for the symptomless radiological evidence of two bilateral pulmonary lesions detected during the routine follow-up for a breast cancer diagnosed and cured in 2001. A computed tomography (CT)-scan revealed a round irregularly shaped lesion in the left upper lobe (LUL), 1.8 cm in the major axis (Figure 1A) and a synchronous pseudonodular contralateral lesion in the right upper lobe (RUL), measuring 1.4 cm (Figure 1E. The positron emission tomography (PET)-CT scan (18F-FDG/PET-CT) characterized the LUL lesion with a SUV of 7.3 (Figure 1B) and the RUL one of 1.7 (Figure 1D). According to the oncological history, a resection of the left nodule was chosen as first step and a wedge resection was performed. Intraoperative histology was strongly suggestive for lung adenocarcinoma, so the patient underwent a left apico-dorsal segmentectomy plus systematic mediastinal lymphadenectomy. Final pathology confirmed a G3 adenocarcinoma with a G2 component, pT1aN0 (AJCC 2010) (Figure 2A–D). One month later, cytology obtained by a fine-needle aspiration biopsy of the RUL nodule was suggestive of adenocarcinoma. A right upper segmentectomy was performed and final pathology confirmed a G2 adenocarcinoma of very probable lung origin (Figure 2E–F). To definitely confirm the primary nature of the two lung nodules with respect to the previous breast cancer and to further differentiate the two lesions, we performed a epidermal growth factor receptor (EGFR) mutational analysis to establish clonality. We identified an EGFR exon 19 microdeletion (ΔE746–A750) in the LUL adenocarcinoma (Figure 3A) and an exon 21 mutation (L858R) in the RUL one (Figure 3B). Based on this finding that confirmed different DNA profiles, a certain diagnosis of synchronous primary non–small cell lung cancer (NSCLC) was achieved.FIGURE 2(A) Moderately differentiated component of the left upper lobe (LUL) adenocarcinoma composed of papillary structures with a central fibrovascular core lined by columnar cells with moderate cyto-nuclear atypia; neoplastic cells exhibit a diffuse nuclear immunoreactivity for TTF-a (B), (A) Haematoxylin and eosin (B) haematoxylin counterstaining; original magnification ×200, (C) Poorly differentiated component of the LUL adenocarcinoma with a solid grow pattern, composed of sheets of polygonal cells sometimes markedly anaplastic with a high mitotic count and a weak and focal nuclear positivity for TTF-1 (D), (C) Haematoxylin and eosin (D) haematoxylin counterstaining, original magnification ×200, (E) The right upper lobe neoplasm is a moderately differentiated adenocarcinoma showing the same morphological and immunohystochemical features of the first, with papillary structures lined by columnar cells diffusely stained for TTF-1 in a nuclear pattern (F), (E) Haematoxylin and eosin, (F) haematoxylin counterstaining, original magnification × 200.View Large Image Figure ViewerDownload (PPT)FIGURE 3Partial nucleotide sequence of (A) exon 19 and (B) exon 21 of the EGFR gene. The exon 19 shows a heterozygous deletion of five amino-acids from 746 to 750 position (ΔE746–A750) as shown by the arrow indicating the starting point of frame shift. The exon 21 shows a heterozygous mutation at code 858 (CTG > CGG) with a substitution of arginine for leucine at position 858 (L858R); the arrow indicates the point mutation (T > G).View Large Image Figure ViewerDownload (PPT) The Martini and Melamed criteria1Martini N Melamed MR Multiple primary lung cancers.J Thorac Cardiovasc Surg. 1975; 70: 606-612PubMed Google Scholar are still widely used for the management of multiple primary lung cancers (MPLCs), although a comprehensive histologic assessment allows a more accurate diagnosis.2Girard N Deshpande C Lau C et al.Comprehensive histologic assessment helps to differentiate multiple lung primary nonsmall cell carcinomas from metastases.Am J Surg Pathol. 2009; 33: 1752-1764Crossref PubMed Scopus (190) Google Scholar Clinically, the distinction of clonality in patients with synchronous primary cancers is relevant therapeutically and prognostically. Nowadays, detection of EGFR alterations can improve the clonality assessment because of the frequently mutated exons on EGFR genes (exons 18–22) in NSCLC.3Chang YL Wu CT Lin SC Hsiao CF Jou YS Lee YC Clonality and prognostic implications of p53 and epidermal growth factor receptor somatic aberrations in multiple primary lung cancers.Clin Cancer Res. 2007; 13: 52-58Crossref PubMed Scopus (90) Google Scholar In the case we report, the assessment of the primary or secondary nature of the two nodules was pivotal for the therapeutic strategy: in brief, ruling out the metastatic nature of the lung lesions (with respect to the previously cured breast cancer or to lung neoplasm) allowed us to plan for a radical surgery with curative intent. According to the different prognosis related to metastatic and early-stage NSCLCs, the different EGFR mutational profiles as detected in both lesions allowed a precise diagnosis and staging. A radical surgery, considered to be the treatment of choice for synchronous MPLCs,4Finley DJ Yoshizawa A Travis W et al.Predictors of outcomes after surgical treatment of synchronous primary lung cancers.J Thorac Oncol. 2010; 5: 197-205Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar is further justified by the evidence that onco-developmentally independent (lung) adenocarcinomas have a better prognosis if compared to tumors with the same EGFR profile.3Chang YL Wu CT Lin SC Hsiao CF Jou YS Lee YC Clonality and prognostic implications of p53 and epidermal growth factor receptor somatic aberrations in multiple primary lung cancers.Clin Cancer Res. 2007; 13: 52-58Crossref PubMed Scopus (90) Google Scholar Interestingly, the case we report supports the recently reported findings that there is a significant correlation of the 18F-FDG/PET-CT SUV (< 9.2) and NSCLC-patients harboring EGFR mutations.5Na II Byun BH Kim KM et al.18F-FDG uptake and EGFR mutations in patients with non-small cell lung cancer: a single-institution retrospective analysis.Lung Cancer. 2010; 67: 76-80Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar Further investigation is needed to understand the predictive potential of this correlation. In conclusion, we advocate that the EGFR mutational analysis should be routinely performed in NSCLCs, either for planning targeted therapy, either in case of MPLCs, to help discriminating the primary or secondary nature of the synchronous lesions." @default.
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• W1991495073 date "2012-05-01" @default.
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• W1991495073 title "Difference in Clonality as a Tool for Differential Diagnosis of Primary Versus Secondary Lung Neoplasms" @default.
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