Case report: Clinical management of recurrent small cell lung cancer transformation complicated with lung cancer-induced acute pancreatitis after lung adenocarcinoma surgery
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ABSTRACT:
SUBMITTER: Zhang S
PROVIDER: S-EPMC10644230 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:Small cell transformation was one mechanism by which EGFR-mutation NSCLC acquired resistance after tyrosine kinase inhibitors (TKIs) treatment. A few reports of small cell transformation occurred in other oncogene-driven lung cancers. We found the first case of transformation of a RET-rearranged lung adenocarcinoma to SCLC after selpercatinib, a novel highly selective RET TKIs. Whole-exome sequencing (WES) was used to explore alteration in gene expression in tumor tissue at initial diagnosis and after transformation into small cell carcinoma. We found that transformed into SCLC tumor tissue had inactivation of RB1 and TP53, with RET fusion was still present. In addition, the APOBEC family of cytidine deaminases appeared amplification. Although RET rearrangement still existed, using another RET TKIs was ineffective, and etoposide plus platinum might be an effective rescue treatment.
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Project description:IntroductionTransformation from lung adenocarcinoma (LUAD) to small cell lung cancer (SCLC) is one of the mechanisms responsible for acquired EGFR-TKIs resistance. Although it rarely happens this event determines a rapid disease deterioration and needs specific treatment.Patient and methodWe report a case of 75-year-old LUAD female with a p.L858R mutation in Epidermal Growth Factor Receptor (EGFR) who presented with SCLC transformation after responding to first line osimertinib treatment for only 6 months. To understand the underlying molecular mechanism, we retrospectively sequenced the first (LUAD) and the second (SCLC) biopsy using a 56 multi-gene panel. Immunohistochemistry (IHC) staining and Fluorescence In Situ Hybridization (FISH) was applied to confirm the genetic aberrations identified.ResultsEGFR p.E709A and p.L858R, Tumor Protein p53 (TP53) p.A159D and Retinoblastoma 1 (RB1) c.365-1G>A were detected in both the diagnostic LUAD and transformed SCLC samples. A high copy number gain for Proto-Oncogene C-Myc (MYC) and a Phosphoinositide 3-Kinase Alpha (PIK3CA) p.E545K mutation were found in the transformed sample specifically. Strong TP53 staining and negative RB1 staining were observed in both LUAD and SCLC samples, but FISH only identified MYC amplification in SCLC tissue.ConclusionWe consider the combined presence of MYC amplification with mutations in TP53 and RB1 as drivers of SCLC transformation. Our results highlight the need to systematically evaluate TP53 and RB1 status in LUAD patients to offer a different therapeutic strategy.
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Project description:Transformation to small cell lung cancer (SCLC) is one of the mechanisms of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, it is uncertain how it works and there is no standard treatment after the transformation. In this study, 7 patients with transformation of SCLC from advanced lung adenocarcinoma (ADC) were analyzed retrospectively and the clinical pathology, imaging characteristics and treatment were analyzed.We identified 7 patients with primary lung ADC that showed transformation to SCLC on second biopsy during a 6-year period. Clinicopathologic information was analyzed and EGFR mutation results were performed in initial biopsy samples.Seven patients showed transformation from ADC to SCLC, of which 6 patients were 19 del EGFR mutation, only 1 patient is L858R mutations. The imaging forms did not have the typical imaging features of primary SCLC. All patients underwent etoposide and carboplatin (EC) regimen chemotherapy after pathological transformation. However, the response rate of EC was less than primary small cell lung cancer. One of the patients was receiving EC for 4 cycles. After chemotherapy the patients performed radiation therapy and finally with erlotinib maintains treatment, the progress free survival (PFS) was more than 12 months.NSCLC can acquire a neuroendocrine phenotype with EGFR-TKI treatment. The transmutation is more common in 19del mutation patients. A comprehensive treatment based on EC regimen chemotherapy and the maintenance with EGFR-TKI is likely to be the appropriate treatment for these patients.
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Project description:IntroductionAcute pancreatitis (AP) is a serious inflammatory condition of the pancreas. Hypertriglyceridemia (HTG) is considered an uncommon cause of AP. The current study aims to present a unique case of recurrent seasonal severe HTG-induced AP (HTG-AP); treated with insulin and heparin.Case reportA 36-year-old male presented with recurrent attacks of severe upper abdominal pain that was radiating to the back and associated with repeated vomiting. The condition has being occurring every autumn-winter for the last three years. He had thalassemia minor and had a history of HTG-AP. His TG levels were relatively normal from February to August; however, from September to February, his TG levels highly elevated which has resulted in HTG-AP every year for the past three years. The condition was confirmed via a contrast-enhanced computerized tomography scan of the abdomen. To prevent the next HTG-AP, his TG level was monitored monthly. When TG levels spiked again, the patient was put on an insulin infusion with heparin, glucose, and potassium to rapidly reduce TG level. After two days, serum TG was dramatically reduced (<500 mg/dL).DiscussionDespite multiple theories being proposed, the pathogenesis of HTG-AP is yet to be understood. Usually, HTG-AP is a single episodic, and recurrent HTG-AP is considered uncommon finding. Previous reports are contradictory regarding TG level and seasonal variation. There is currently no standard management approach to treat HTG-AP cases.ConclusionHTG-AP rarely reoccurs on an annual basis, and seasonal variation seems to play a major role in its onset. The condition can be managed with insulin, heparin, and glucose infusions.
| S-EPMC8977940 | biostudies-literature
Project description:Introduction: Small cell lung cancer (SCLC) transformation represents a mechanism of resistance to osimertinib in EGFR-mutated lung adenocarcinoma, which dramatically impacts patients' prognosis due to high refractoriness to conventional treatments. Case Description: We present the case of a patient who developed a SCLC phenotypic transformation as resistance mechanism to second-line osimertinib for T790M-positive EGFR-mutated NSCLC. Our patient received platinum-etoposide doublet following SCLC switch and achieved a modest clinical benefit which lasted 4 months. NGS and IHC analyses for p53 and Rb were performed on subsequent liver biopsies, revealing baseline TP53 mutation and complete absence of p53 and Rb expression. Primary cell cultures were established following a liver biopsy at the time of SCLC transformation, and drug sensitivity assays showed meaningful cell growth inhibition when osimertinib was added to platinum-etoposide compared with control (p < 0.05). A review of the current literature regarding SCLC transformation after failure of osimertinib was performed. Conclusions: Based on retrospective data available to date, platinum-etoposide chemotherapy is the preferred treatment choice in the occurrence of SCLC transformation after osimertinib failure. The extension of osimertinib in combination with chemotherapy in the occurrence of SCLC transformation as resistance mechanism to osimertinib is a matter of debate. The combination of osimertinib and platinum-etoposide was effective in inhibiting cell growth in our primary cell cultures. Clinical studies are needed to further explore this combination in the occurrence of SCLC transformation as a resistance mechanism to osimertinib.
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Project description:First-generation epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have markedly improved the treatment of non-small cell lung cancer (non-SCLC) with EGFR-sensitive mutations. However, acquired resistance to these drugs was inevitable. The transformation of lung adenocarcinoma to SCLC following treatment with EGFR-TKIs is a rare phenomenon that contributes to resistance to EGFR-TKIs. The present case concerns a 74-year-old man previously diagnosed with and treated for pneumonia; however, this was later pathologically confirmed as lung adenocarcinoma by transbronchial lung biopsy. Deletion of exon 19 of EGFR was identified by next-generation sequencing technology. The patient improved markedly when treated with gefitinib, but relapsed after 1 year, with markedly increased serum levels of neuron-specific enolase (NSE). Transformation to SCLC was detected by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) re-biopsy, which was negative for the deletion of exon 19 of EGFR. The patient was positive for vimentin expression and refractory to etoposide and cisplatin chemotherapy, and succumbed to the disease 18 months after diagnosis. Transformation of the disease from adenocarcinoma to SCLC may have been due to cancer heterogeneity. Re-biopsy is therefore important in EGFR-TKI-resistant patients for genetic and histological re-evaluation. NSE serum levels may also be useful for detecting early SCLC transformation.
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Project description:The occurrence of endotracheal/endobronchial metastasis (EEM) after complete resection of a primary lung cancer is rare. Here, we report the case of an 86-year-old woman in whom EEM occurred twice over a 20-year period following complete resection of a primary adenocarcinoma localized to the left main bronchus and trachea. The presence of EEM was confirmed by establishing immunohistochemical homology of the metastases with the primary tumor. To the best of our knowledge, this is the first reported case of repetitive EEM of primary lung adenocarcinoma. Lymphatic invasion in the primary lesion suggested that a possible route for EEM was the peripheral lymphatic tract, explaining the slow recurrence rate. We conclude that observation of the trachea/bronchus over a long period post operation could be important in monitoring for EEM, particularly if lymphatic invasion is confirmed in the primary tumor.
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Project description:Introduction and importanceIn children, acute recurrent pancreatitis is attributed to pancreato-biliary anomalies, hereditary pancreatitis and cystic fibrosis. Pancreatic divisum is a common congenital ductal anomaly that leads to recurrence of pancreatitis.Case presentationA 13 years old female presented with clinical features of acute recurrent pancreatitis. After ruling out common causes, magnetic resonance cholangiopancreatography was done which showed pancreatic divisum. Her symptoms resolved following duodenum preserving pancreatic head resection.DiscussionAcute recurrent pancreatitis is attributed to raised intrapancreatic dorsal ductal pressure due to ductal anomalies especially pancreatic divisum (PD). It is the embryological failure in the fusion of the dorsal and ventral ductal system. PD is further classified into a classical subtype where there is complete failure of ductal fusion and an incomplete subtype where there is partial fusion of the ductal system. The diagnosis is commonly done through abdominal imaging with secretin enhanced magnetic resonance cholangiopancreatography being the choice of imaging modality. The initial approach is endoscopic intervention unless patients present with signs of pancreatic fibrosis where a duodenum preserving pancreatic head resection can be carried out.ConclusionA keen suspicion should be given towards anatomical or structural variants in absence of common etiologies. Early identification and management of pancreatic divisum prevents the recurrence of pancreatitis.
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Project description:BACKGROUND:Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is selective for both epidermal growth factor receptor tyrosine kinase inhibitor-sensitizing and T790M resistance mutations. Almost all patients who initially respond to an epidermal growth factor receptor tyrosine kinase inhibitor subsequently report disease progression. Epidermal growth factor receptor-dependent resistance mechanisms, bypass pathway activation, and histological transformation have been reported with osimertinib therapy. CASE PRESENTATION:We report a case of a 64-year-old Asian man with epidermal growth factor receptor T790M-positive adenocarcinoma that transformed to epidermal growth factor receptor T790M-negative large-cell neuroendocrine carcinoma after osimertinib therapy. A prompt rebiopsy revealed a rare mechanism of resistance to epidermal growth factor receptor tyrosine kinase inhibitor, and subsequently treatment with carboplatin and etoposide was effective. CONCLUSIONS:Despite the promising emergence of circulating tumoral DNA testing, this case report emphasizes the importance of rebiopsy of a progressive epidermal growth factor receptor-mutant tumor.
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Project description:Paraneoplastic Cushing's syndrome (PCS) is a rare, but clinically important feature of small cell lung cancer (SCLC) that is associated with even worse prognosis. To identify key considerations in comprehensive management of SCLC patients complicated with PCS, we conducted a systematic review of relevant reports on PubMed and Web of Science, focusing on SCLC with PCS cases. The systematic review analyzed 61 reports published between 1985 and 2022 with a total of 157 SCLC patients included. Out of the 157 patients, 132 (84.1%) patients across 58 (95.1%) reports were diagnosed with ectopic Cushing's syndrome. The immunohistochemical (IHC) staining for adrenocorticotropic hormone (ACTH) was performed on 30 (19.1%) patients across 22 (36.1%) reports and demonstrated encouraging performance. For treatment, chemotherapy and ketoconazole were utilized in 50 (81.97%) and 24 (39.34%) reports, respectively. Regarding cause of death, infection and cancer were equally frequent, each being recorded in 17 (27.87%) reports. To conclude, the majority of PCS cases in SCLC patients were caused by ectopic hormone secretion. In order to make a differential diagnosis, it is recommended to utilize IHC staining for a specific hormone such as ACTH or corticotropin-releasing hormone. In the comprehensive treatment of SCLC with PCS patients, effective management of hypercortisolism and potent safeguarding against infection play two crucial roles. Ultimately, further confirmations are required regarding the specificity and accuracy of IHC staining technique as well as the efficacy and safety of immunotherapy in the treatment of SCLC with PCS patients.
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