Introduction: With advancements in the understanding of lung cancer biology, targeted therapy has become the rule rather than the exception. Patients with ALK rearrangements are amenable to therapy with Alectinib and other ALK inhibitors, which has been associated with better patient outcomes. While ALK rearrangement should be routinely tested in non-squamous non-small cell lung cancer (NSCLC), the cost and availability of this test is a prohibitive factor, particularly in the Philippine setting. Objectives: This study aimed (1) to determine the prevalence of ALK-rearranged NSCLC among adult Filipino lung cancer patients in St. Luke’s Medical Center (SLMC) from 2016 to 2018 and (2) to determine the clinico-pathologic features of adult Filipinos with ALK-rearranged NSCLC. Methodology: This is a retrospective cross-sectional descriptive study wherein the prevalence of ALK-rearranged NSCLC, detected using fluorescence in-situ hybridization (FISH) or immunohistochemistry (IHC), was determined. Clinical data of patients for whom ALK testing was performed were collected. Hematoxylin and Eosin (H&E) slides were retrieved and reviewed for the presence of certain morphologic features. Patients whose H&E slides cannot be retrieved were excluded from the study. Results: ALK rearrangement was seen in 7.8% (8/103) of tumors submitted for ALK testing. Patients with ALK-rearranged tumors were generally young, light smokers, and presented with advanced clinical stage. Clear cell features and solid pattern were noted in one case and three cases, respectively. However, due to small sample size, further statistical analysis could not be performed to analyze the association of these features with the presence of ALK rearrangement. Conclusion Despite a small sample size, the prevalence and clinical profile of ALK-rearranged NSCLC in our institution are congruent with those previously described in Western populations. The association of clinical profile and morphologic features with the presence of ALK rearrangement can be further explored in future studies.
Lung Neoplasms ; Anaplastic Lymphoma Kinase

Humans ; Lymphoma, Large-Cell, Anaplastic ; Receptor Protein-Tyrosine Kinases ; Anaplastic Lymphoma Kinase ; Soft Tissue Neoplasms

Humans ; Anaplastic Lymphoma Kinase ; Histiocytosis, Langerhans-Cell ; Receptor Protein-Tyrosine Kinases ; Lymphoma, Large-Cell, Anaplastic/pathology*

Humans ; Lymphoma, Large-Cell, Anaplastic/pathology* ; Receptor Protein-Tyrosine Kinases ; Anaplastic Lymphoma Kinase ; Central Nervous System/pathology*

Objective: To investigate the clinicpathological characteristics of ALK-positive anaplastic large cell lymphoma (ALCL) of the gastrointestinal tract, and to discuss its diagnosis and differential diagnosis. Methods: Five cases of gastrointestinal ALK-positive ALCL diagnosed and treated in Xijing Hospital of the Fourth Military Medical University, between 2011 and 2019 were collected. There were three male and two female patients, aged 5-42 years (mean 25 years). These patients clinically presented with fever and night sweats, weight loss, abdominal pain, abdominal mass, ulcers, bleeding, or intestinal obstruction, and underwent surgical resection of the tumors or endoscopic biopsy. The clinical manifestations, auxiliary examinations, histopathological characteristics, immunophenotypes and genetic alterations were analyzed. Results: In this cohort, one case was common type, two cases were monomorphic variant of common type, and two cases were small cell variant. The tumor cells in all cases expressed ALK, CD30, and one or more T lymphocyte markers, while all the markers of B lymphocyte and plasmacyte were negative. Clonality analysis showed that two cases had clonal T cell receptor (TCR) and immunoglobulin (Ig) gene rearrangement, one case had no clonal TCR but Ig gene rearrangement, and one case had no clonal TCR and Ig gene rearrangements. During the 4 to 67 months' follow-up, two patients died of the disease, two were alive with free of disease and one had a relapse. Conclusions: ALK-positive ALCL of the gastrointestinal tract is extremely rare, and has poor prognosis. Lymphoma originating from this site with CD30 and ALK-positive phenotypes may be considered to be ALCL; however differentiation from other tumors that had anaplastic features, expressed CD30 and or ALK, in particular, ALK positive large B-cell lymphoma is necessary.
Male ; Female ; Humans ; Lymphoma, Large-Cell, Anaplastic/pathology* ; Receptor Protein-Tyrosine Kinases/genetics* ; Anaplastic Lymphoma Kinase ; Gastrointestinal Tract/pathology* ; Lymphoma, Large B-Cell, Diffuse/genetics*

Anaplastic Lymphoma Kinase ; Humans ; Lung/pathology* ; Lung Neoplasms/pathology* ; Mesothelioma/surgery* ; Mesothelioma, Malignant ; Pleural Neoplasms/surgery*

Objective: To investigate the expressions of growth arrest-specific protein (GAS1), IL-1 receptor accessory protein (IL-1RAP) and perforin (PRF1) in patients with anaplastic lymphoma kinase positive, anaplastic large cell lymphoma (ALK⁺ ALCL) and their relationships with clinical significances and the prognoses of ALK⁺ ALCL. Methods: Twenty-six formalin-fixed paraffin-embedded (FFPE) samples of ALK⁺ ALCL patients who were diagnosed from January 2011 to September 2016 were collected. Twelve FFPE samples of patients with ALK⁺ALCL, 13 FFPE samples of patients with peripheral T cell lymphoma (not otherwise specified) (PTCL-NOS) and 8 FFPE samples of patients with angioimmunoblastic T-cell lymphoma (AITL) were used as control groups. RQ-PCR and immunohisto-chemical staining were used to detect the mRNA and protein expressions of GAS1, IL-1RAP and PRF1. The clinical data were analyzed. Results: ①The expression levels of GAS1, IL-1RAP and PRF1 gene and protein in ALK⁺ ALCL group were higher than those of the control groups (P<0.05), but the expression levels had no statistically significant differences between the control groups (P>0.05). ②Patients with elevated lactate dehydrogenase (LDH) (0.77 vs 1.38, z=-3.292, P=0.001) or International prognostic index (IPI)≥3(0.62 vs 1.29, z=-2.495, P=0.013) had lower expression level of GAS1. Patients with stage Ⅲ/Ⅳ disease (0.89 vs 1.18, z=-2.212, P=0.027) or IPI≥3 (0.48 vs 1.13, z=-2.008, P=0.045) had lower expression level of PRF1. IL-1RAP expression level was not associated with clinical features. ③ALK⁺ ALCL patients in complete remission (CR) group had higher expression levels of GAS1 and PRF1 than patients in non-remission (NR) group (P values were 0.016 and 0.009). ④Kaplan-Meier survival analysis showed that patients with high expression levels of GAS1 and PRF1 had longer median overall survival and progression-free survival than patients with low expression levels of GAS1 and PRF1. Conclusion: GAS1, IL-1RAP and PRF1 could be molecular markers for ALK⁺ ALCL patients. They have potential diagnostic value and can be used for differential diagnosis in some difficult cases. ALK⁺ ALCL patients with high expression levels of GAS1 or PRF1 have better curative effects and prognoses.
Anaplastic Lymphoma Kinase ; Cell Cycle Proteins ; GPI-Linked Proteins ; Humans ; Lymphoma, Large-Cell, Anaplastic ; Perforin ; Protein-Tyrosine Kinases ; Receptor Protein-Tyrosine Kinases ; Receptors, Interleukin-1

Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/pathology* ; Anaplastic Lymphoma Kinase ; Neoadjuvant Therapy ; Protein Kinase Inhibitors

Lung cancer is the most common in incidence and mortality worldwide. With the development of next generation sequencing (NGS) detection technology, more and more patients with rare anaplastic lymphoma kinase (ALK) fusion mutations were detected. A case of advanced lung adenocarcinoma with rare COX7A2L-ALK (C2:A20) fusion detected by NGS was reported in Peking Union Medical College Hospital, and all cases with rare ALK fusion mutations were searched from medical datebase from January 1, 2014 to March 31, 2021, to investigate the treatment of rare ALK fusion mutations with ALK inhibitors. The best response of the patient was assessed as partial response (PR) with Ceritinib treatment. By literature review, 22 cases of rare ALK fusion were reported in 19 articles. Combined with this case, 23 cases were analyzed. The objective response rate (ORR) was 82.6% (19/23) and disease control rate (DCR) was 95.7% (22/23) for rare ALK fusions patients treated with ALK inhibitors. Lung adenocarcinoma patients with rare ALK fusion could benefit from ALK inhibitors.
.
Humans ; Anaplastic Lymphoma Kinase/genetics* ; Lung Neoplasms/diagnosis* ; Crizotinib ; Adenocarcinoma of Lung/genetics* ; Protein Kinase Inhibitors/pharmacology* ; Oncogene Proteins, Fusion/genetics*

Objective: To analyze the clinical features and prognostic factors of primary systemic anaplastic large cell lymphoma (ALCL) . Methods: 40 ALCL cases treated in the First Affiliated Hospital of Zhejiang University from January 2013 to December 2018 were retrospectively analyzed. Results: ① With a median age of 41 (14-67) years, there were 29 males and 11 females, 36 patients (90.0%) had Ann Arbor stage Ⅲ-Ⅳ tumors, 23 patients (57.5%) were in high-intermediate or high international prognostic index (IPI) risk group. 25 patients (62.5%) had B symptoms, such as fever, emaciation and night sweat.38 patients (95.0%) had extranodal invasion, 25 patients (62.5%) had higher LDH level, and 25 patients (62.5%) had high expression of Ki-67 (80% or more) . With 22 ALK(+) patients (55.0%) and 18 ALK(-) patients (45.0%) , there was a significantly difference in the median age of the two groups [29 (14-67) years old vs 51.5 (19-67) years old, P=0.003]. ② All patients received chemotherapy, 18 cases were treated with CHOP (cyclophosphamide, doxorubicin, vindesine, prednisone) , 12 cases with ECHOP (cyclophosphamide, doxorubicin, vindesine, prednisone, etoposide) , 10 cases with other treatments and 26 patients (65.0%) obtained complete remission (CR) . ALK(-) (P=0.029, OR=13.458) and Ki-67 expression of 80% or more (P=0.04, OR=14.453) were independent factors of CR rate, the CR rate of ECHOP chemotherapy was higher than CHOP chemotherapy (P=0.026) . ③ LDH level, IPI score, ALK expression and chemotherapy regimen had significantly effect on progression free survival (PFS) and overall survival (OS) (P<0.05) . Conclusion: The study shows that primary systemic ALCL usually occurs in males, the average age of ALK(+) patients were younger than ALK(-) patients. Most patients are in stage Ⅲ-Ⅳ with extranodal invasion, more than half of the patients have B symptoms, elevated LDH, and high expression of Ki-67. The expression level of Ki-67, ALK expression, and chemotherapy regimen have prognostic value for CR rate, the LDH level, IPI score, ALK expression and chemotherapy regimen for PFS and OS. ECHOP is a better choice with improved prognosis.
Adolescent ; Adult ; Aged ; Anaplastic Lymphoma Kinase ; Antineoplastic Combined Chemotherapy Protocols ; Cyclophosphamide ; Doxorubicin ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse ; Lymphoma, Large-Cell, Anaplastic ; Male ; Middle Aged ; Prednisone ; Prognosis ; Receptor Protein-Tyrosine Kinases ; Retrospective Studies ; Vincristine ; Young Adult