PDX models closely recapitulate primary tumor biology and clinical outcome. They may serve as important laboratory models to investigate mechanisms of resistance to targeted therapies, and for preclinical testing of novel treatment strategies.

In the era of personalised cancer therapy, the demand for molecular profiling of the patient's tumour is steadily increasing. In advanced nonsmall cell lung cancer (NSCLC) patients, testing for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements has become an essential component of clinical practice to select patients who are most likely to benefit from EGFR and ALK tyrosine kinase inhibitors, respectively. Furthermore, obtaining tissue specimens from recurrent or metastatic tumours or from patients who develop resistance to initial effective therapies are essential for our understanding of the molecular basis of tumour progression and development of drug resistance. Therefore, the sampling of tumour tissue that is representative and is adequate in quantity and quality for pathological diagnosis and genomic profiling is crucial. In this review, we will discuss factors that should be considered in obtaining and processing biopsy specimens to enable routine molecular analysis in NSCLC patients. @ERSpublications Personalised therapy: adequate tumour tissue sampling for pathological diagnosis and molecular profiling is critical

Availability of lung cancer models that closely mimic human tumors remains a significant gap in cancer research, as tumor cell lines and mouse models may not recapitulate the spectrum of lung cancer heterogeneity seen in patients. We aimed to establish a patient‐derived tumor xenograft (PDX) resource from surgically resected non‐small cell lung cancer (NSCLC). Fresh tumor tissue from surgical resection was implanted and grown in the subcutaneous pocket of non‐obese severe combined immune deficient (NOD SCID) gamma mice. Subsequent passages were in NOD SCID mice. A subset of matched patient and PDX tumors and non‐neoplastic lung tissues were profiled by whole exome sequencing, single nucleotide polymorphism (SNP) and methylation arrays, and phosphotyrosine (pY)‐proteome by mass spectrometry. The data were compared to published NSCLC datasets of NSCLC primary and cell lines. 127 stable PDXs were established from 441 lung carcinomas representing all major histological subtypes: 52 adenocarcinomas, 62 squamous cell carcinomas, one adeno‐squamous carcinoma, five sarcomatoid carcinomas, five large cell neuroendocrine carcinomas, and two small cell lung cancers. Somatic mutations, gene copy number and expression profiles, and pY‐proteome landscape of 36 PDXs showed greater similarity with patient tumors than with established cell lines. Novel somatic mutations on cancer associated genes were identified but only in PDXs, likely due to selective clonal growth in the PDXs that allows detection of these low allelic frequency mutations. The results provide the strongest evidence yet that PDXs established from lung cancers closely mimic the characteristics of patient primary tumors.

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Objective: To evaluate the effectiveness of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) and to analyze the causes of unclear diagnoses following BSRTC adoption. Study Design: According to the BSRTC, we reclassified cytologic samples originally diagnosed as ‘indeterminate’ with sequential surgical resection. Then, we analyzed the causes of cases, which were recategorized as ‘atypia undetermined significance/follicular lesion of undetermined significance (AUS/FLUS)’. Results: According to the BSRTC, 154 ‘indeterminate’ cases were reclassified as follows: unsatisfactory, n = 5 (3.2%); benign, n = 43 (27.9%); AUS/FLUS, n = 77 (50.0%); suspicious for a follicular neoplasm, n = 7 (7.1%); suspicious for a Hürthle cell neoplasm, n = 4 (2.6%); suspicious for malignancy, n = 15 (9.7%), and malignancy, n = 3 (1.9%). Then, the AUS/FLUS group was analyzed according to the scenarios proposed by the BSRTC. Fifty-nine (58.9%) cases of AUS/FLUS were due to suboptimal preparation. In addition, papillary microcarcinoma and coexisting Hashimoto’s thyroiditis caused inconclusive diagnoses. Conclusion: The BSRTC can be easily applied to thyroid fine-needle aspiration. We were able to reclassify indeterminate thyroid nodules into more detailed categories and thus reduce the number of cases classified as indeterminate. However, suboptimal preparation, papillary microcarcinoma, and coexisting Hashimoto’s thyroiditis precluded cytopathologists from making definitive diagnoses.

Lung cancer rarely occurs in young patients. Recent studies have demonstrated that epidemiologic data are closely correlated to some molecular characteristics. We investigated the clinicopathologic characteristics of lung adenocarcinoma in young patients and evaluated immunohistochemically detected epidermal growth factor receptor (EGFR) mutation status and anaplastic lymphoma kinase (ALK) positivity. Among lung adenocarcinoma patients, 31 cases were of the ≤ 40 yr-old group and 261 cases of > 50 yr-old group. Young patients were more likely to be females (67.7% vs 40.2%), and nonsmokers (58.1% vs 45.2%) and more often had high TNM stage (stage IV was 80.6% vs 52.1%) and had a high rate of distant metastasis (51.6% vs 28.0%) compared with older patients. The signet ring cell feature was more common (25.8% vs 11.5%) and lepidic growth pattern was rarely present (3.2% vs 16.5%) in the adenocarcinoma of young patients. There was no significant survival difference between the two age groups. The rate of EGFR mutation status and ALK positivity did not show a statistical difference between two groups. In conclusion, lung adenocarcinoma of young patients demonstrates distinct pathologic features with frequent presence of a signet ring cell feature and rare occurrence of lepidic growth pattern. Further investigation for other genetic abnormalities would be needed.

Mutations of the epidermal growth factor receptor (EGFR) are the strongest predictive factor for response to EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. EGFR TKIs are approved in Korea as a first-line treatment for lung cancer patients with mutated EGFR. Rapid and accurate EGFR mutation testing is essential for patient selection and establishing targeted therapies with EGFR TKIs. Thus, a standard set of guideline recommendations for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of guideline recommendations for EGFR mutation testing that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.

Henoch-Schönlein purpura (HSP) is an IgA-mediated small vessel vasculitis with a predominant cutaneous involvement. We assessed adult patients with HSP to identify the clinical and histopathological features and evaluate predictive factors of relapse. We reviewed the records of 29 adult patients with HSP who presented at our department between 2002 and 2009. Adult HSP was confirmed by skin biopsy showing leukocytoclastic vasculitis and direct immunofluorescence showing IgA deposit. Among the 29 patients (15 men, 14 women; mean age 36.2 years old), renal involvement was initially found in 22 patients (75.9%). They were divided into 2 groups according to the presence or absence of relapse. We compared clinical and histopathologic differences between 15 patients with relapse and 14 patients without relapse. By univariate analysis, older age at onset, persistent rash, abdominal pain, hematuria, and underlying disease at the onset of HSP are significantly related to relapse. Among the histopathological variables, severity of leukocytoclasis and absence of IgM deposit on the vessel walls are significantly associated to relapsing disease (P < 0.05). Our results are significant, because, they may help to understand the predictive factors related to relapses of HSP in adults. Further studies are necessary to identify whether more aggressive treatment in adults with HSP with these predictive factors can prevent relapse and severe renal sequelae.