Case Report: Recurrence of Testicular Myofibroblastic Tumor After Surgery

Inflammatory myofibroblastic tumour (IMT), also known as plasma cell granuloma (PCG) or inflammatory pseudotumour (IPT), is a distinctive, rarely metastasizing neoplasm composed of myofibroblastic and fibroblastic spindle cells accompanied by inflammatory infiltration of plasma cells, lymphocytes and/or eosinophils. IMT predominantly affects children and young adults, and the age at presentation ranges from 3 to 89 years. We present a very rare case of recurrent testicular IMT without ALK rearrangement. This case highlights the clinical characteristics and diagnostic factors associated with primary and recurrent foci of this rare tumour, along with key therapeutic approaches.

Case Report: A Novel Non-Reciprocal ALK Fusion: ALK-GCA and EML4-ALK Were Identified in Lung Adenocarcinoma, Which May Respond to Alectinib Adjuvant-Targeted Therapy

Anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancers (NSCLCs) have favorable and impressive response to ALK tyrosine kinase inhibitors (TKIs). However, ALK rearrangement had approximately 90 distinct fusion partners. Patients with different ALK fusions might have distinct responses to different-generation ALK-TKIs. In this case report, we identified a novel non-reciprocal ALK fusion: ALK-grancalcin (GCA) (A19: intragenic) and EML4-ALK (E20: A20) by next-generation sequencing (NGS) in a male lung adenocarcinoma patient who was staged as IIIB-N2 after surgery. After a multidisciplinary discussion, the patient received alectinib adjuvant targeted therapy and postoperative radiotherapy (PORT). He is currently in good condition, and disease-free survival (DFS) has been 20 months so far, which has been longer than the median survival time of IIIB NSCLC patients. Our study extended the spectrum of ALK fusion partners in ALK + NSCLC, and we reported a new ALK fusion: ALK-GCA and EML4-ALK and its sensitivity to alectinib firstly in lung cancer. It is vital for clinicians to detect fusion mutations of patients and report timely the newfound fusions and their response to guide treatment.

Demographics, Risk Factors and Survival Analysis of Lung Cancer in Young Adults (<30 Years) in China-A Retrospective Cohort Study

Background Lung cancer in very young adults in China aged <30 is on the rise and the clinicopathological characteristics of this unique population are incomplete and are yet to be elucidated. Our study aims to explore the characteristics, trends and distinctive features of lung cancer this age group to provide more information that can aid in developing optimal treatment regimens and improve prognosis for this exclusive age group. Method A retrospective review of 141 lung cancer patients admitted at our hospital from August 2011 to October 2021 was performed. The focused age group in our study was 18-30 years old. The data collected included demographics, tumor pathology, gene mutations, and treatment. Overall survival and prognosis were systematically analyzed. Results From a total of 141 of young lung cancer patients, 139 were included in final analysis. The gender distribution in our series favored female(65.5%), and only 7.2% of the study cohort had a history of smoking. Adenocarcinoma was the most common histological type in our study, presenting 93.5% of all patients. The most common stages at diagnosis was stage I(61.2%) and stage IV(30.2%). Genetic testing was performed in only 24.5% (34/139) of the patients. From the 23/34 patients in our study who tested positive for a genetic mutation, 19 (82.3%) were stage IV. The most common gene mutation was Anaplastic Lymphoma kinase(ALK) rearrangement observed in 13/23 (56.5%) gene mutation positive patients. Among stage IV NSCLC, OS was longer in patients who received targeted therapy, compared to the patients not receiving target therapy: 88 months vs 24 months (95% CI: 0.15-1.0, p=0.0282). Conclusion Lung cancer in the young adult population has particular characteristics (Common in female, non-smoker and adenocarcinoma patients). Higher stages of disease were observed in those with a gene mutation (notably ALK rearrangement). Although the sample size was small, the current data suggests a higher mutation rate in the younger population. These findings have fundamental implications for practice and we propose that all patients under 30 diagnosed with lung cancer should undergo genetic testing so they can receive personalized treatment and therefore achieve better outcomes.

Management of Oligoprogression in Patients with Metastatic NSCLC Harboring ALK Rearrangements

Personalized treatment based on driver molecular alterations, such as ALK rearrangement, has revolutionized the therapeutic management of advanced oncogene addicted NSCLC patients. Multiple effective ALK tyrosine kinase inhibitors (TKIs), with the amelioration of the activity at central nervous system level, are now available, leading to substantial prognosis improvement. The exposure to TKIs triggers resistance mechanisms and the sequential administration of other TKIs and chemotherapy is, for the most part, not targeted. In this context, extending the benefit deriving from precision medicine is paramount, above all when disease progression occurs in a limited number of sites. Retrospective data indicate that, in oligoprogressive disease, targeted therapy beyond progression combined with definitive local treatment of the progressing site(s) is an effective alternative. In these cases, multidisciplinary approach becomes essential for an integrated treatment strategy, depending on the site of disease progression, in order to improve not only survival, but also quality of life. In this review we provide an updated and comprehensive overview of the main treatment strategies in case of ALK rearranged oligoprogression, including systemic treatment as well as local therapy, and report real-world clinical stories, with the final aim of identifying the most promising management for this subset of patients.

Coexistence of ALK rearrangement in lung adenocarcinoma harbouring EGFR mutation: Real-World Data From a Single-Institution Experience

Background Concomitance of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement have been increasingly reported in lung adenocarcinoma (LUAD). However, the biological mechanism, clinicopathological features and optimization of targeted drugs remain unclear. This study aimed to explore the clinicopathological characteristics of coexisting mutations of EGFR and ALK genes in LUAD patients, with hopes of scientifically guiding such patients towards selected, targeted drugs. Methods Two hundred and thirty-seven cases of LUAD were enrolled. Mutations in exons 18, 19, 20 and 21 of the EGFR gene were detected by the amplification refractory mutation system-peptide nucleic acid (ARMS-PNA) technique, while expression of the ALK fusion gene was detected by the 5′/3′ imbalance strategy for reverse transcription, followed by quantitative polymerase chain reaction (RT–qPCR) analysis. The clinicopathological features of patients with coexisting mutations of EGFR and ALK genes were analysed retrospectively, and the follow-up data of these patients were collected. Results There were 6 cases with coexisting mutations of EGFR and ALK genes, which were more common in women, non-smoking and stage IV LUAD with bone metastasis, hence a positive rate of 2.53% (6/237). Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were the first choice for targeted therapy in patients with LUAD harbouring coexisting mutations of EGFR and ALK genes in Gannan region, and the progression-free survival (PFS) was between 2-6 months. Conclusions These results indicated that the positive rate of coexisting mutations of EGFR and ALK genes in LUAD patients in the Gannan region was relatively high; these genes were more common in women, non-smokers and stage IV patients with bone metastasis. EGFR-TKIs were the first choice for targeted therapy in these patients, but the therapeutic effect was limited. EGFR-TKI combined with ALK-TKI dual targeted therapy may be a more effective treatment.

Anaplastic lymphoma kinase rearrangements in non-small cell lung cancer in Jordan

Introduction/Objective ALK rearrangement is an important oncogenic driver in a substantial portion of non-small cell lung cancer (NSCLC) patients ranging from 2-7%. Treatment options such as ALK tyrosine kinase inhibitors (TKI) improve progression-free survival and overall survival. Candidates for such treatment are selected based on the identification of the ALK rearrangement. While fluorescence in situ hybridization (FISH) was considered the gold standard method, the availability of a robust FDA-approved companion diagnostic immunohistochemistry (IHC) assay has led to a paradigm shift in ALK testing. The purpose of this study is to determine the prevalence of ALK rearrangement in Jordanian NSCLC patients along with their clinicopathological characteristics and to compare the results of IHC and FISH methods for detecting ALK rearrangements. Methods/Case Report A retrospective study was conducted on 449 Jordanian King Hussein Cancer Center patients with NSCLC whose biopsy samples were tested for ALK rearrangement using FISH and or IHC (clone D5F3) in the period between 2018 and 2020. Results (if a Case Study enter NA) During the study period, the rate of ALK positivity by either IHC or FISH method was 4 percent (18 ALK positive cases out of 449 cases of non-small cell lung cancer). Seven cases were positive for both IHC and FISH, and nine cases were positive for IHC with no confirmation by FISH method; one case was ALK positive by IHC and negative by FISH with a significant response to ALK TKI; one case was IHC negative but FISH positive, with no ALK TKI therapy. The calculated sensitivity of ALK D5F3 immunostain compared to FISH results in the current study is 87.5% while the specificity is 96%. ALK positive patients were significantly younger than those with negative results (p-value=0.051), and women were three times more likely than men to have the rearrangement (p-value=0.013). Rearrangement was more likely to be found in nonsmokers/light or ex-smokers (p-value= 0.013). All patients had clinical stage IV or III disease at presentation with stage IV found in tow thirds of the patients. Conclusion ALK rearrangement is found in 4% of all NSCLC in Jordan. Patients are more likely to be younger, females and light or nonsmokers with an advanced stage disease at presentation. IHC is an acceptable alternative to FISH for ALK testing with reasonable sensitivity and specificity in addition to its advantages in terms of robustness, turnaround time and cost savings