Lung cancer is the leading cause of cancer deaths worldwide, with the majority consisting of non-small cell lung cancer (NSCLC). Genetic mutations present an opportunity for targeted therapy, in addition to current mainstay treatments such as chemotherapy and radiotherapy. Overall, 5% of NSCLCs have an anaplastic lymphoma kinase (ALK) mutation, often prevalent in a younger population. Crizotinib is an ALK inhibitor that was approved to treat ALK-mutated advanced NSCLC. While common side effects such as nausea, fatigue, and diarrhea are mostly well tolerated, adverse side effects can lead to treatment discontinuation or adjustment or can be fatal. This systematic review used articles searched on Google Scholar and PubMed which were assessed using the Cochrane risk-of-bias tool and Newcastle-Ottawa Scale. This yielded nine papers consisting of randomized controlled trials and cohort studies. Side effects resulting in cessation of treatment or dose reduction included liver dysfunction, nausea, neutropenia, and QT prolongation. This review showed that crizotinib has a better side effect profile than chemotherapy in ALK-positive NSCLC, even though toxicities leading to treatment withdrawal are present. Adverse effects were tackled by dose reduction, temporary withdrawal from treatment, and close monitoring.

UNASSIGNED: The therapeutic landscape for non-small cell lung cancer (NSCLC) has evolved considerably in the last few years. The targeted drugs and molecular diagnostics have been developed together at a fast pace. This narrative review explores the evolution of anaplastic lymphoma kinase (ALK) targeting therapies from discovering the ALK protein, molecular tests, present clinical trial data and future perspectives. Since the body of evidence on lung cancer is growing daily, most oncologists need time to implement data in their daily practice.
UNASSIGNED: We developed a narrative review to provide up-to-date help in the clinical decision-making of ALK-altered NSCLC patients. In 2022, the authors reviewed PubMed\'s published pivotal randomized Phase 3 trial results.
UNASSIGNED: The development of ALK inhibitors was a revolution that is still ongoing; second and third-generation ALK inhibitors provided more than 30 months of progression-free survival (PFS) and impressive \"brain-control\". Brigatinib provided a survival benefit for patients with baseline brain metastases (HR 0.43, 95% CI: 0.21-0.89), and Lorlatinib demonstrated intracranial response rates of 82%, with 71% of complete intracranial responses. Personalized medicine is the new paradigm, from performing broad genetic panels for diagnosis to individual targeted therapy or combinations of different targeted agents.
UNASSIGNED: In the future, performing broad molecular panels should be the standard of care in the front line and after each progression to detect arising resistance mechanisms. Longer PFS will substantially convert a deadly condition into an almost chronic disease in the following decades. Treatment sequencing will be the cornerstone for patient survival, and liquid biopsies may replace tissue biopsies.

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Background. Anaplastic large-cell lymphoma (ALCL) is an uncommon lymphoma divided into anaplastic lymphoma kinase (ALK) positive, ALK negative, and breast implant-associated (BIA) ALCL. Gastrointestinal tract involvement is very rare and may be difficult to diagnose. Its recognition is crucial as prognostic ramifications are different. Objectives. To describe clinicopathological features of ALCL involving the gastrointestinal tract. Materials and Methods. Slides were reviewed. Diagnosis was confirmed. Histological and immunohistochemical features were described. Results.Twenty-five tumors were diagnosed during the study period. Ages ranged from 14 to 65 years (mean 41 years). Mean age for ALK-negative and ALK-positive patients were 49 and 17 years, respectively. Twenty-one were males and 4 were females. Eighteen involved small intestine. Mean tumor size was 4.2 cm. All showed diffuse sheets of large anaplastic cells with pleomorphic nuclei, abundant pink cytoplasm, and strong positivity for CD30. Epithelial membrane antigen was positive in 17 tumors and keratin was negative in all. Eighteen tumors were ALK negative. Out of 14 patients with follow-up, 12 died within a few months of diagnosis. Seven had stage IE, 5 had stage IIE, and 2 had stage IV disease. Two patients were alive at 35 and 60 months. Twelve received chemotherapy. Conclusion. A marked male predominance was noted. Small intestine was the commonest site of involvement. Majority were ALK negative. ALK-negative tumors occurred in older patients and ALK positive in younger patients. Prognosis was poor. ALCL should be included in the differential diagnosis of anaplastic epithelioid cell neoplasms in the gastrointestinal tract.

We report a rare case of ALK-positive large B cell lymphoma which initially presented as a circumscribed breast mass in a young woman mimicking fibroadenoma. The lymphoma demonstrated typical immunoblastic morphology with monomorphic round nuclei and prominent central nucleoli. Immunophenotypically, the lymphoma was positive for MUM1,CD138, BOB1, OCT2, PAX5 (focal), CD4, and was negative for CD20, CD79a and all other T cell antigens. Immunostaining for the ALK protein revealed the characteristic granular cytoplasmic staining typical for ALK-positive large B cell lymphoma with an ALK::CTCL fusion confirmed on genomic profiling study. Notably the cells also expressed CD10 and BCL6. Staging revealed disseminated disease with blood, bone marrow and liver involvement. To our knowledge, this is the first report of ALK-positive large B cell lymphoma initially presenting as a breast lesion. Additionally, expression of CD10 and BCL6 suggested a germinal center origin for the lesion.

After acute leukemia and brain and central nervous system tumors, mature lymphomas represent the third most common cancer in pediatric patients. Non-Hodgkin lymphoma accounts for approximately 60% of lymphoma diagnoses in children, with the remainder representing Hodgkin lymphoma. Among non-Hodgkin lymphomas in pediatric patients, aggressive lymphomas, such as Burkitt lymphoma, diffuse large B-cell lymphoma, and anaplastic large cell lymphoma, predominate. This article summarizes the epidemiologic, histopathologic, and molecular features of selected mature systemic B-cell and T-cell lymphomas encountered in this age group.

Non-small cell lung cancer patients with anaplastic lymphoma kinase or c-ros oncogene 1 mutations who are treated with the tyrosine kinase inhibitor crizotinib rarely develop crizotinib-associated renal cysts (CARCs). Here, we present a case report and review of the literature supporting the hypothesis that CARCs may correlate positively with progression-free survival.

Oral inflammatory myofibroblastic tumor (IMT) is extremely rare and its manifestation as generalized gingival enlargement (GGE) has never been reported. We are reporting the case of 50-year-old female patient presenting with recurrent GGE for 4 years. Panoramic radiograph revealed severe bone loss in posterior sextants and root resorption in some teeth. Initial incisional biopsy was suggestive of chronic inflammatory infiltrate with fibrocollagenous tissue. Definitive treatment comprised of surgical excision of the enlarged gingiva with a tapering dose of steroid therapy. Histopathological and immunohistochemical examination from a repeat biopsy of deeper tissues was suggestive IMT. No recurrence was found at 2 years follow up. Recurrent GGE with advanced bone loss and external root resorption should raise the suspicion of a locally aggressive lesion. Dentists should be aware of oral IMT and include it in differential diagnosis of gingival enlargements for comprehensive management to avoid recurrence of the lesion.

Non-Hodgkin lymphomas are rare causes of primary lung neoplasms and most are B-cell in origin. Anaplastic large cell lymphoma is an exceedingly rare type of primary pulmonary lymphoma, with an aggressive clinical course. We present the case of an 85-year old male patient who attended our Emergency Department complaining of respiratory and constitutional symptoms, and who was found to have a bronchial mass causing subtotal atelectasis of the left lung. Histological examination showed an anaplastic large cell lymphoma and further investigation revealed that it was limited to the lung. To our knowledge, very few similar cases have been reported in the literature.
UNASSIGNED: Non-Hodgkin lymphomas are rare causes of pulmonary lung neoplasms, with the majority of cases being marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue or diffuse large B-cell lymphoma.Anaplastic large cell lymphoma (ALCL) usually involves the lymph nodes, skin and soft tissue. It follows an aggressive clinical course and constitutional symptoms are frequent at presentation. Lung involvement may occur as a result of dissemination in up to 12% of cases. Primary ALCL of the lung is extremely rare.Anaplastic lymphoma kinase (ALK) expression is an important prognostic factor, with ALK+ ALCL patients experiencing better outcomes. Adverse prognostic factors also include advanced age, serum lactate dehydrogenase levels and early relapse after therapy.

Small cell transformation is a well-recognized mechanism of resistance to EGFR-TKI therapy in EGFR-mutant NSCLC, yet it remains a poorly-described phenomenon in ALK-rearranged NSCLC.
Chart and literature review.
We report a case of a patient with ALK-rearranged lung cancer progressing on three-lines of ALK-targeted therapies, with development of acquired resistance to lorlatinib, with both transformation to a neuroendocrine carcinoma, and acquisition of ALK 1196 M.
Given the inevitable development of resistance in ALK + NSCLC, if feasible, re-biopsy on progression should be standard over liquid biopsy. Neuroendocrine carcinoma transformation remains an important mechanism of acquired resistance to lorlatinib.