Subtyping Non-Small Cell Lung Cancer: Relevant Issues and Operative Recommendations for the Best Pathology Practice.

Int J Surg Pathol. 2013 Jun 5;

Authors: Rossi G, Pelosi G, Barbareschi M, Graziano P, Cavazza A, Papotti M

Abstract
Morphology still remains the cornerstone in lung cancer classification and cytology and small biopsy samples should be interpreted by morphology, whenever feasible, according to shared and widely agreed-upon diagnostic schemes. However, as novel therapy strategies are being offered on the basis of the diverse tumor characteristics, pathologists are now challenged by the need to offer clinicians more detailed typing of non-small cell lung cancer, not otherwise specified (NSCLC-NOS), especially when dealing with limited diagnostic material or poorly differentiated tumors. Close integration of morphology, immunohistochemistry, and clinical data is highly warranted according to a multidisciplinary approach to limit the category of NSCLC-NOS as much as possible or exclude unsuspected metastases, so rendering more definite and clinically useful diagnoses. Among the many proposed immunohistochemical markers, which as a whole are more practical and diagnostically useful than cumbersome and expensive molecular assays, a 2-hit model including thyroid transcription factor-1 (TTF-1) and p40 (the latter more specific for squamous differentiation than p63) seems to be the most effective to basically highlight adenocarcinoma (positivity for TTF-1 regardless of p63) and squamous (always strongly and diffusely positive for p40 or p63 and negative for TTF-1) differentiation. This minimalist 2-hit diagnostic approach paves the way to novel perspectives in clinical trials on lung cancer, and it is also in keeping with the need of strategically preserving diagnostic material for molecular assays that are essential for personalizing therapies.

PMID: 23740564 [PubMed - as supplied by publisher]

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Epidermal growth factor receptor mutation in a patient with squamous cell carcinoma of the lung: who should be tested?

Case Rep Oncol. 2013 May;6(2):263-8

Authors: Schwitter M, Rodriguez R, Schneider T, Kluckert T, Brutsche M, Früh M

Abstract
We report the case of a 64-year-old ex-smoker with metastatic poorly differentiated squamous cell carcinoma (SCC) of the lung and an epidermal growth factor receptor (EGFR) mutation in exon 21 (p.L858R) who achieved prolonged clinical benefit from treatment with an EGFR tyrosine kinase inhibitor (TKI). The initial diagnosis of SCC of the lung obtained by bronchoscopic biopsy was based on immunohistochemical staining only with positivity for cytokeratin (CK) 5/6 and p63 because morphological diagnosis was not possible. Patients with non-small cell lung cancer (NSCLC), not otherwise specified (NOS) favouring SCC are usually not tested for the presence of EGFR mutations, and therefore may not receive EGFR TKI therapy. A bronchoscopic rebiopsy showed small nests of undifferentiated tumour cells with weak immunoreactivity of some tumour cells for CK5/6, p63 and no positivity of some tumour cells for thyroid transcription factor-1. These findings suggested a mixed squamous/glandular immunophenotype that has been missed at the initial biopsy. Our clinical case illustrates the problem of tumour heterogeneity encountered in small bronchoscopic biopsies and the difficulties of evaluating the histological subtype in poorly differentiated carcinomas. Initial bronchoscopy should be performed by an experienced pulmonologist who attempts to obtain sufficient material from different areas of the tumour. In the era of targeted therapy, a remote smoking history in a patient with NOS favouring SCC should also lead to EGFR mutation testing to allow highly effective therapy to be offered to mutation-positive patients.

PMID: 23741221 [PubMed]

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Prognostic significance of the extent of lymph node involvement in stage II-N1 non-small cell lung cancer.

Chest. 2013 Jun 6;

Authors: Li ZM, Ding ZP, Luo QQ, Wu CX, Liao ML, Zhen Y, Chen ZW, Lu S

Abstract
BACKGROUND: The non-small-cell lung cancer (NSCLC) staging system published in the 7th edition of the Union for International Cancer Control (UICC) and American Joint Commission on Cancer (AJCC) cancer staging manuals in 2009 did not include any changes to current N descriptors for NSCLC. However the prognostic significance of the extent of lymph node (LN) involvement, including the lymph node zones involved (hilar/interlobar or peripheral), cancer-involved lymph node ratios (LNR), and the number of involved lymph nodes remain unknown. The aim of this report is to evaluate the extent of lymph node involvement and other prognostic factors in predicting outcome after definitive surgery among Chinese stage II-N1 NSCLC patients. METHODS: We retrospectively reviewed the clinicopathological characteristics of 206 stage II (T1a-T2bN1M0) NSCLC patients who had undergone complete surgical resection at Shanghai Chest Hospital from June 1999 to June 2009. Overall survival (OS) and disease-free survival (DFS) were compared using Kaplan-Meier statistical analysis. Stratified and Cox regression analyses were used to evaluate the relationship between the lymph node involvement and survival. RESULTS: Peripheral zone lymph node involvement, cancer-involved lymph node ratio, smaller tumor size, and squamous cell carcinoma were shown to be statistically significant indicators of higher OS and DFS by univariate analyses. Visceral pleural involvement was also shown to share a statistically significant relationship with DFS by univariate analyses. Multivariate analyses showed tumor size and zone of lymph node involvement were to be significant predictors of OS. CONCLUSION: Zone of N1 lymph node, LNR and tumor size were both found to provide independent prognostic information in patients with stage II NSCLC. This information may be used to stratify patients into groups by risk for recurrence.

PMID: 23744276 [PubMed - as supplied by publisher]

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The increment in standardized uptake value determined using dual-phase (18)F-FDG PET is a promising prognostic factor in non-small-cell lung cancer.

Eur J Nucl Med Mol Imaging. 2013 Jun 7;

Authors: Chen HH, Lee BF, Su WC, Lai YH, Chen HY, Guo HR, Yao WJ, Chiu NT

Abstract
PURPOSE: We aimed to determine whether the increment in the maximal standardized uptake value (SUVmax) of the primary lung tumour between the initial and delayed imaging by dual-phase (18)F-FDG PET has prognostic value in patients with non-small-cell lung cancer (NSCLC). METHODS: We reviewed the records of patients with NSCLC who underwent pretreatment dual-phase (18)F-FDG PET/CT scans acquired at 1 h and 2 h after injection. The SUVmax increment (SUVinc) of the primary lung tumour was the 2-h SUVmax minus the 1-h SUVmax. Univariate and multivariate analyses were used to assess the prognostic significance of SUVinc, retention index, whole-body total metabolic tumour volume, whole-body total lesion glycolysis (TLGwb), 1-h SUVmax, 2-h SUVmax, gender, age, performance status, histological subtype, T stage, N stage and clinical stage. RESULTS: The records of 187 consecutive patients were reviewed. The median follow-up time was 3.9 years. The estimated median progression-free survival (PFS) and overall survival (OS) were 1.3 years and 4.4 years, respectively. An SUVinc cut-off value of >1 had the best discriminative yield for PFS. The 3-year PFS and OS were 61.6 % and 87.8 % in patients with SUVinc ≤1 versus 21.1 % and 46.2 % in patients with SUVinc >1 (all P < 0.01). Using the forward stepwise multivariate Cox proportional hazards model, SUVinc, TLGwb, and clinical stage were significant factors for PFS (all P < 0.01). A subgroup analysis of 117 patients treated with surgery showed that SUVinc (P = 0.02) and clinical stage (P < 0.01) were significant prognostic factors for PFS. Furthermore, in stage I patients treated with surgery alone, SUVinc was the only significant prognostic factor (HR 28.07; 95 % CI 2.42 - 326.41). CONCLUSION: SUVinc determined from dual-phase (18)F-FDG PET is a promising prognostic factor for NSCLC. It adds to the value of dual-phase (18)F-FDG PET.

PMID: 23744342 [PubMed - as supplied by publisher]