Pulmonary Large Cell Carcinoma Lacking Squamous Differentiation Is Clinicopathologically Indistinguishable From Solid-Subtype Adenocarcinoma

Hwang, David H.; Szeto, David; Perry, Anthony S.; Bruce, Jacqueline L.; Sholl, Lynette M.

doi:10.5858/arpa.2013-0179-oa

Cited by 42 publications

(27 citation statements)

References 41 publications

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“…1 Hirsch et al 4 demonstrated major heterogeneity by light microscopy in 13% of 200 consecutive lung cancers. 26,27 It is noteworthy that no histologic heterogeneity was recorded in biopsies, suggesting that the finding of histologic heterogeneity is more probable if large areas of tumor are available. Cell differentiation at electron microscopy is based on recognition of ultrastructural features on tiny pieces of tumor tissue, and mucin stains and primordial polyclonal antibodies are less specific than novel markers.…”

Section: Discussionmentioning

confidence: 99%

Lung Cancer Histologic and Immunohistochemical Heterogeneity in the Era of Molecular Therapies

Cadioli

Rossi²,

Costantini

et al. 2014

American Journal of Surgical Pathology

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On the basis of seminal studies in the 1980s, appreciable histologic heterogeneity, ranging from 45% to 70% of cases, may be encountered in lung cancer. However, the epidemiologic and histologic landscape of lung cancer in the last 3 decades has radically changed. In this study, 172 consecutive surgically resected primary lung carcinomas evaluated from 2010 to 2012 were entirely sampled and examined according to current histologic classifications. In 129 cases, a positive preoperative biopsy was also available. Major histologic heterogeneity (a single tumor showing at least 2 different histologic types) and minor histologic heterogeneity (a single tumor showing just 1 histologic type but at least 2 different growth patterns) were evaluated in all cases. Immunohistochemical heterogeneity (ie, "aberrant" staining) was also assessed using a panel of markers of adenocarcinoma (TTF-1, napsin, and CK7), squamous cell carcinoma (p63, CK5/6), and neuroendocrine differentiation (chromogranin and synaptophysin), both on positive biopsies and surgical specimens. Overall, major and minor histologic heterogeneity on resections were disclosed in 4% (7 cases) and 50.6% (87 cases), respectively, whereas just 1 case of minor heterogeneity (pleomorphic carcinoma) was observed on biopsies. Minor heterogeneity was limited to adenocarcinomas (82.6%, 81/98 cases) and sarcomatoid carcinomas (6 pleomorphic types among 8 sarcomatoid carcinomas). Immunohistochemical heterogeneity was recorded in 22.6% of the cases, with expression of p63 and CK5/6 in a subset of adenocarcinomas (25 cases, 25.5%), CK7 in 17.4% of squamous cell carcinomas, and synaptophysin in 6 cases of non-neuroendocrine tumors (4%, 6/155). The high rate of adenocarcinomas, accounting for 57% (98 cases) of 172 consecutively resected lung cancers, reflects the new scenario of thoracic oncology and may explain the significant lower rate of major histologic heterogeneity (4%) and the higher frequency of different architectural patterns (minor heterogeneity) that we found in lung cancer compared with previous studies.

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Section: Discussionmentioning

confidence: 99%

Lung Cancer Histologic and Immunohistochemical Heterogeneity in the Era of Molecular Therapies

Cadioli

Rossi²,

Costantini

et al. 2014

American Journal of Surgical Pathology

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“…Antibodies used for whole tissue sections included TTF-1 (8G7G3/1), napsin A (polyclonal), and CK5/6 (D5/16B4), all obtained from Roche Ventana (Tucson, Arizona), and were prediluted. The antibody for p40 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) was diluted to 1:3000 and was obtained from EMB Millipore (Billerica, Massachusetts). Immunostaining of whole tissue sections was performed with an automated stainer (BenchMark Ultra; Roche Ventana) and primary antibody incubation times ranging from 20 to 24 minutes.…”

Section: Reclassification By 2015 Who Criteriamentioning

confidence: 99%

Next-Generation Sequencing of a Cohort of Pulmonary Large Cell Carcinomas Reclassified by World Health Organization 2015 Criteria

Driver¹,

Portier²,

Mody³

et al. 2015

Archives of Pathology &Amp; Laboratory Medicine

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“…The presence of EGFR mutations in these latter 2 entities likely reflects miscategorization of solid subtype ACA, in the case of large cell carcinoma, and possibly undersampling of an adenosquamous carcinoma, in the case of squamous cell carcinomas. [22][23][24] Most large studies 22,25 suggest that EGFR mutations virtually never occur in tumors lacking at least some ACA features. The predictive value of lung cancer subtyping for the presence of an underlying EGFR mutation has driven into relative obsolescence the term non-small cell lung carcinoma and, in fact, current recommendations generally discourage use of this term unless a tumor eludes classification despite histologic and immunophenotypic evaluation.…”

Section: -16mentioning

confidence: 99%

“…Among ACA with solidsubtype histology, the frequency of KRAS mutation is 40%. 23 The most common KRAS alteration in current and former smokers is a codon 12 G.T transversion mutation leading to p.Gly12Cys; transversions reflect the typical DNA-level alterations induced by tobacco carcinogens.…”

Section: Kras Mutationsmentioning

confidence: 99%

Biomarkers in Lung Adenocarcinoma: A Decade of Progress

Sholl

2014

Archives of Pathology &Amp; Laboratory Medicine

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Context The analysis of molecular biomarkers in lung adenocarcinoma (ACA) is now a central component of pathologic diagnosis and oncologic care. The identification of an EGFR mutation or ALK rearrangement in advanced-stage lung ACA will dictate a change in first-line treatment from standard chemotherapy to targeted inhibition of these oncogenic alterations. Viable approaches to therapeutic targeting of KRAS-mutated ACA are now under investigation, raising the possibility that this too will become an important predictive marker in this tumor type. The recognized array of less common oncogenic alterations in lung ACA, including in the ROS1, RET, BRAF, and ERBB2 genes, is growing rapidly. The therapeutic implications of these findings are, in many cases, still under investigation. Objective To focus on the major molecular biomarkers in lung ACA, recommended testing strategies, the implications for targeted therapies, and the mechanisms that drive development of resistance. Data Sources Our current understanding of predictive and prognostic markers in lung ACA is derived from a decade of technical advances, clinical trials, and epidemiologic studies. Many of the newest discoveries have emerged from application of high-throughput next-generation sequencing and gene expression analyses in clinically and pathologically defined cohorts of human lung tumors. Conclusions Best practices require a solid understanding of relevant biomarkers for diagnosis and treatment of patients with lung ACA.

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Pulmonary Large Cell Carcinoma Lacking Squamous Differentiation Is Clinicopathologically Indistinguishable From Solid-Subtype Adenocarcinoma

Cited by 42 publications

References 41 publications

Lung Cancer Histologic and Immunohistochemical Heterogeneity in the Era of Molecular Therapies

Lung Cancer Histologic and Immunohistochemical Heterogeneity in the Era of Molecular Therapies

Next-Generation Sequencing of a Cohort of Pulmonary Large Cell Carcinomas Reclassified by World Health Organization 2015 Criteria

Biomarkers in Lung Adenocarcinoma: A Decade of Progress

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