Best practices in epidermal growth factor receptor T790M testing for advanced non-small-cell lung cancer in Hong Kong.

The T790M mutation in the epidermal growth factor receptor gene causes most acquired resistance to firstor second-line epidermal growth factor receptor-tyrosine kinase inhibitors in advanced non-small-cell lung cancer. The results of T790M testing can guide subsequent treatment. Despite the availability of guidelines from international organisations, T790M testing practices in Hong Kong must be streamlined and adapted to the Hospital Authority setting. To address this issue, a panel of experts in oncology and pathology met for discussion of key topics regarding T790M testing practices in Hong Kong, including the appropriate timing of testing and re-testing, as well as optimal testing methods. All panel members voted on the results of the discussion to achieve consensus. Items supported by a majority vote were adopted as consensus statements regarding current best practices for T790M testing in Hong Kong. Among the topics discussed, the panel agreed that T790M testing should be initiated upon radiological progression, including symptomatic disease progression or central nervous system-only progression. The experts also preferred initial testing with liquid biopsy, using the widely available digital polymerase chain reaction platform. This document provides the final consensus statements, as well as a testing and treatment workflow, for clinicians in Hong Kong to use as guidance in T790M testing.

Comparison of fluorescence in-situ hybridisation with dual-colour in-situ hybridisation for assessment of HER2 gene amplification of breast cancer in Hong Kong.

OBJECTIVES: To compare the PathVysion fluorescence in-situ hybridisation assay with the INFORM HER2 Dual in-situ hybridisation assay on 104 invasive breast cancers with a broad spectrum of immunohistochemistry scores. METHODS: This case series involved consecutive patients diagnosed with invasive breast carcinoma with equivocal immunohistochemistry score and referred for further HER2 assessment from the departments of Surgery and/or Clinical Oncology of the two hospitals between January 2013 and February 2014. An additional 10 cases with negative HER2 immunohistochemistry and 11 cases with positive HER2 immunohistochemistry were further included. RESULTS: The results of both fluorescence in-situ hybridisation and dual in-situ hybridisation were available in 99 of 104 cases, respectively. Student'st test showed no statistically significant difference in the mean number of HER2 count, CEP17 copies, or HER2/CEP17 ratio between that obtained by fluorescence in-situ hybridisation and that obtained by dual in-situ hybridisation. Pearson's correlation of results for the two assays was strong for HER2/CEP17 signal ratio (R=0.963, P<0.001) and mean HER2 copies per nucleus (R=0.897, P<0.001). Overall agreement was 96.0% (95 out of 99 cases, ĸ0.882). Three of the four discordant cases were equivocal for either fluorescence in-situ hybridisation or dual in-situ hybridisation. The results of immunohistochemistry 0/1+ and 3+ cases showed 100% concordance between the two assays. The failure rate was 0.96% for fluorescence in-situ hybridisation and 3.85% for dual in-situ hybridisation. Cases that failed for fluorescence in-situ hybridisation were successful for dual in-situ hybridisation and vice versa. CONCLUSIONS: Our study showed that dual in-situ hybridisation is a reliable and useful option for HER2 testing in breast cancer.

HER2 overexpression of breast cancers in Hong Kong: prevalence and concordance between immunohistochemistry and in-situ hybridisation assays.

OBJECTIVES: To evaluate the prevalence of human epidermal growth factor receptor 2 (HER2) gene overexpression in breast cancer patients encountered in Hong Kong and the concordance of HER2 findings from primary immunohistochemistry assays and confirmatory in-situ hybridisation assays. DESIGN: Retrospective study. SETTING: Department of Clinical Oncology in a public hospital in Hong Kong. PATIENTS: All patient referrals between July 2006 and June 2007 with newly diagnosed invasive breast cancer (for prevalence evaluation), and all patients treated at our unit with confirmatory in-situ hybridisation tests performed within the study period (for concordance evaluation). RESULTS: There were 272 consecutive breast cancer patients eligible for prevalence evaluation. The distribution for immunohistochemistry staining in 249 cases for scores 0, 1+, 2+, and 3+ were 99 (40%), 40 (16%), 58 (23%), and 52 (21%) respectively. In the remaining 23 patients, four and 19 breast cancers were unscored and reported by immunohistochemistry to be HER2-positive and -negative, respectively. The overall HER2 overexpression rate (3+ or reported as positive) was 21%. HER2 overexpression was associated with grade 3 histology (P<0.001) and negative hormonal receptor status (P<0.001). However, it was not associated with age (P=0.525), T-classification (P=0.740), N-classification (P=0.691), nor group stages (P=0.433). Of the 37 patients with confirmatory in-situ hybridisation tests performed, 10 (71%) of 14 with immunohistochemistry staining of 3+ and 1 (4%) of 23 with immunohistochemistry staining of 2+ were found to have HER2 gene amplification. CONCLUSIONS: More than 25% of HER2 overexpression identified by immunohistochemistry assays in this Hong Kong cohort could not be verified by confirmatory in-situ hybridisation assays. Compliance with the latest guidelines for HER2 testing should improve the future accuracy and concordance.

Metastatic tumour of the tunica vaginalis testis from carcinoma of the stomach.

A 50-year-old man with advanced inoperable gastric adenocarcinoma and diffuse peritoneal metastasis received six cycles of palliative chemotherapy and responded clinically with weight gain. Two months after the completion of chemotherapy, however, he developed a left hydrocele. Aspiration yielded 70 ml of yellowish hydrocele fluid, which contained metastatic adenocarcinoma cells, consistent with a gastric primary tumour. A diagnosis of malignant hydrocele was made. Two weeks later, he developed a painful recurrent left hydrocele with increasing pain and swelling. Left orchidectomy was performed. Tiny white mural nodules measuring 1 mm in size were noted on the tunica vaginalis. No focal lesion was noted in the testis. On microscopic examination, the tunica vaginalis showed reactive mesothelial hyperplasia and extensive lymphatic permeation by poorly differentiated adenocarcinoma, consistent with a gastric primary tumour.

Nasopharyngeal carcinoma in situ: two cases of an emerging diagnostic entity.

BACKGROUND: The association of Epstein-Barr virus (EBV) with the oncogenesis of nasopharyngeal carcinoma (NPC) is well established. Latent infection by EBV with clonal proliferation has also been demonstrated in preinvasive lesions of NPC. In situ hybridization for EBV-encoded RNA (ISH EBER) now serves as an ancillary test in the definitive diagnosis of these lesions. METHODS: Two cases of nasopharyngeal carcinoma in situ (NPCIS) are presented in this study. Their biopsies were studied by ordinary light microscopy, the ISH EBER technique, and immunostaining for bcl-2. Tissue samples from 100 high risk subjects negative for NPC and NPCIS, who served as controls, were also studied using the ISH EBER technique. RESULTS: NPCIS was characterized by abnormal light microscopic appearance as well as positive staining by the ISH EBER technique; these features were not observed in samples from the 100 high risk subjects. Immunostaining for bcl-2 protein was positive but less specific. Postradiotherapy biopsies of the two patients were negative for NPCIS. CONCLUSIONS: With the help of the ISH EBER technique, the diagnosis of NPCIS is now possible in routine surgical pathology. As this entity is rare, it is necessary to have a high degree of suspicion when evaluating biopsies from high risk individuals. Radiotherapy for patients with NPCIS is justified in view of the risk of cancer progression and the possibility of a coexisting invasive carcinoma.

Histologic variant of the epithelial-myoepithelial carcinoma of the salivary gland: a case report.

BACKGROUND: Epithelial-myoepithelial carcinoma (EMC) of the salivary gland is a low-grade carcinoma. It has been widely accepted as a clinicopathologic entity only in the past decade. Histologically, the classical bimodal differentiation of inner eosinophilic ductal cells and outer layer of clear myoepithelial cells has been well documented by many authors. However, the proportion of each component may vary in different tumors or within the same tumor, and different histologic patterns have been described. The clinicopathologic findings of an epithelial-myoepithelial carcinoma of the parotid gland in a 73-year-old man are presented. METHODS: Light microscopy including immunohistochemistry and ultrastructural studies were done. RESULTS: The various histologic patterns and bimodal differentiation of the tumor were noted. CONCLUSIONS: The present case demonstrates the myriad of histologic patterns that can occur in epithelial-myoepithelial carcinoma. Differentiation from malignant mixed tumor is essential and possible. The importance of the awareness of its histologic variants is emphasized.