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Lung cancer is the leading cause of cancer death and includes two major types: non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), accounting for 85% and 15% of cases, respectively. Non-small-cell lung cancer harboring actionable driver mutations is generally treated with tyrosine kinase inhibitors (TKIs) molecularly targeting individual oncogenes. Although TKIs have greatly contributed to better clinical outcomes, acquired resistance to them inevitably occurs. Histologic or lineage transformation is a rare but well-documented off-target mechanism associated with acquired resistance, and has been identified in settings following treatment with multiple different TKIs and other drugs. It includes neuroendocrine transformation, squamous cell transformation, and epithelial-to-mesenchymal transition. Here, we review the clinicopathologic features of transformed tumors and current understanding of the key genetic alterations and biologic mechanism of lineage transformation in NSCLC, particularly TKI-triggered transformation.
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Carcinoma Pulmonar de Células não Pequenas , Transformação Celular Neoplásica , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares , Inibidores de Proteínas Quinases , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Transformação Celular Neoplásica/genética , Transição Epitelial-Mesenquimal/genética , Mutação , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/genéticaRESUMO
Overexpression of OCIAD2 in lung adenocarcinoma has already been reported in several research articles, but the molecular mechanism involved remains unknown. Promoter CpG methylation is a representative form of epigenetic gene regulation, and a considerable number of tumor suppressor genes show hypermethylation in many cancers. In contrast, promoter CpG hypomethylation causes oncogene overexpression, resulting in carcinogenesis and malignant progression. In the present study, we investigated the CpG methylation and expression status of OCIAD2 using tumor tissues and adjacent normal tissues from seven cases of lung adenocarcinoma. We also examined the relationship between CpG methylation status and outcome in 58 patients with adenocarcinoma. Pyrosequencing showed that CpG sites in OCIAD2 promoter regions were more frequently demethylated in tumor tissues than in adjacent normal tissues, and reverse transcription-quantitative polymerase chain reaction revealed overexpression of OCIAD2 in lung adenocarcinoma. There was a correlation between OCIAD2 CpG demethylation and the level of mRNA expression, and statistical analysis showed that CpG hypomethylation of OCIAD2 was associated with poor outcomes. Our results suggest that overexpression of OCIAD2 might be caused mainly by CpG hypomethylation and that OCIAD2 methylation status might be a useful prognostic indicator in lung adenocarcinoma.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/genética , Ilhas de CpG/genética , Metilação de DNA , Desmetilação , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Proteínas de Neoplasias/genética , RNA MensageiroRESUMO
Patient-derived xenograft (PDX) murine models are employed for preclinical research on cancers, including non-small cell lung cancers (NSCLCs). Even though lung squamous cell carcinomas (LUSCs) show the highest engraftment rate among NSCLCs, half of them nevertheless show PDX failure in immunodeficient mice. Here, using immunohistochemistry and RNA sequencing, we evaluated the distinct immunohistochemical and gene expression profiles of resected LUSCs that showed successful engraftment. Among various LUSCs, including the basal, classical, secretory, and primitive subtypes, those in the non-engrafting (NEG) group showed gene expression profiles similar to the pure secretory subtype with positivity for CK7, whereas those in the engrafting (EG) group were similar to the mixed secretory subtype with positivity for p63. Pathway analysis of 295 genes that demonstrated significant differences in expression between NEG and EG tumors revealed that the former had enriched expression of genes related to the immune system, whereas the latter had enriched expression of genes related to the cell cycle and DNA replication. Interestingly, NEG tumors showed higher infiltration of B cells (CD19+) and follicular dendritic cells (CD23+) in lymph follicles than EG tumors. Taken together, these findings suggest that the PDX cancer model of LUSC represents only a certain population of LUSCs and that CD19- and CD23-positive tumor-infiltrating immune cells in the original tumors may negatively influence PDX engraftment in immunodeficient mice.
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Carcinoma de Células Escamosas/metabolismo , Neoplasias Pulmonares/metabolismo , Transplante de Neoplasias , Animais , Antígenos CD19/metabolismo , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Perfilação da Expressão Gênica , Pulmão/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Camundongos SCID , Neoplasias Experimentais , Receptores de IgE/metabolismoRESUMO
BACKGROUND: Anal canal cancer occasionally accompanies extramammary Paget disease. Although most of them are squamous cell carcinoma, anal canal adenocarcinoma with neuroendocrine features accompanying secondary extramammary Paget disease has never been reported. CASE PRESENTATION: Here, we report a 76-year-old man presented with pruritus in the perianal area. Investigation revealed a fist-sized perianal erythema, diffuse liver tumors, and right inguinal lymph node swelling. Pathological examination of biopsies from the erythema suggested secondary extramammary Paget disease with positive cytokeratin-7 and -20 expressions and negative GCDFP-15 expression. The anal canal tumor was confirmed by digital examination and endoscopy. Biopsies from the anal canal tumor, swollen lymph node, and Paget lesion all showed poorly differentiated adenocarcinoma with neuroendocrine features expressing synaptophysin and chromogranin A. Serum CEA and NSE levels were high, 809.4 ng/ml and 85.8 ng/ml, respectively. After chemotherapy with modified FOLFOX6 for 2 months, the Paget lesion disappeared, and the primary anal canal tumor and liver metastases shrunk remarkably. Serum CEA and NSE levels decreased promptly to within normal ranges. CONCLUSIONS: This is a clinically significant case, as it reveals novel pathological features about anal canal cancer with secondary Paget disease and successfully treated with modified FOLFOX6. Careful pathological investigation and appropriate treatment choice are needed for this rare cancer.
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Adenocarcinoma/tratamento farmacológico , Canal Anal/efeitos dos fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/tratamento farmacológico , Doença de Paget Extramamária/tratamento farmacológico , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Idoso , Canal Anal/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Ânus/complicações , Neoplasias do Ânus/patologia , Carcinoma Neuroendócrino/complicações , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/patologia , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Compostos Organoplatínicos/administração & dosagem , Doença de Paget Extramamária/etiologia , Doença de Paget Extramamária/patologia , Resultado do TratamentoRESUMO
Sclerosing pneumocytoma is a rare tumor of the lung, commonly affecting middle-aged women, and is mostly isolated. Although this tumor is thought to be derived from primitive respiratory epithelial cells, the characteristics of the precursor cells are still unknown. A 19-year-old woman presented with multiple nodules in the right lung. Partial resection of the right middle lobe was performed, and seven sclerosing pneumocytomas, including four that were microscopic, were detected. The latter showed a simple papillary pattern, and three of them consisted of only round cell-like cells (single population). Interestingly, these round cell-like cells were positive for both p63 and TTF-1, but totally negative for SP-A. On the other hand, the tumor cells of the other four sclerosing pneumocytomas showing a papillary pattern with a dual population, were diffusely positive for TTF-1 and focally positive for SP-A (only in surface cells), but negative or very focally positive for p63. It has been reported that p63-positive stem cell-like cells are present in the distal airway and have potential to differentiate into type II pneumocytes. The immunohistochemical features of these multiple microscopic lesions suggest that the p63-TTF-1 double-positive cells are candidate precursor cells of sclerosing pneumocytoma.
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Proteínas de Ligação a DNA/genética , Histiocitoma Fibroso Benigno/patologia , Neoplasias Pulmonares/patologia , Pulmão/patologia , Fatores de Transcrição/genética , Biomarcadores Tumorais , Feminino , Histiocitoma Fibroso Benigno/genética , Humanos , Imuno-Histoquímica/métodos , Neoplasias Pulmonares/genética , Esclerose Múltipla/patologia , Adulto JovemRESUMO
Hirschsprung disease (HSCR) is a congenital disease resulting from failure of neural crest-derived ganglion cells to colonize the colon. Conventional diagnostic methods are insufficient for evaluating the 'functional' prognosis of HSCR. In order to elucidate the maturation of ganglion cells, 17 immunohistochemical markers were examined. We examined the digestive tracts of 2 human early delivery patients, 2 miniature swine fetuses, 4 little infants, 3 infants, 3 children, 6 adults, and 3 aged individuals. With increasing age, the labeling index (LI) for both calretinin and tyrosine hydroxylase (TH) increased, whereas that for SOX10 decreased. We then examined the 'transitional zone' of HSCR in 21 affected patients and 18 controls for these three markers. The LI of calretinin and TH were significantly lower than in the controls (median: 3.7 in HSCR and 8.2 in controls, P < 0.001, median: 27.9 in HSCR and 44.4 in controls, P < 0.001, respectively). In contrast, the LI for SOX10 showed no significant difference (median: 33.7 in HSCR and 29.2 in controls, P = 0.666) however, hierarchical cluster analysis was able to divide HSCR patients into two groups. These results suggest that immature ganglion cells are present in the transitional zone of HSCR, and that HSCR may have two different pathophysiological processes.
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Calbindina 2/metabolismo , Sistema Nervoso Entérico/patologia , Gânglios Autônomos/patologia , Doença de Hirschsprung/metabolismo , Fatores de Transcrição SOXE/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Adolescente , Adulto , Idoso , Anticorpos , Biomarcadores/metabolismo , Calbindina 2/imunologia , Criança , Pré-Escolar , Sistema Nervoso Entérico/metabolismo , Feminino , Gânglios Autônomos/metabolismo , Trato Gastrointestinal/patologia , Doença de Hirschsprung/patologia , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Masculino , Fatores de Transcrição SOXE/imunologia , Coloração e Rotulagem , Tirosina 3-Mono-Oxigenase/imunologiaRESUMO
INTRODUCTION: HNF4α expression and SMARCA4 loss were thought to be features of non-terminal respiratory unit (TRU)-type lung adenocarcinomas, but their relationships remained unclear. MATERIALS AND METHODS: HNF4α-positive cases among 241 lung adenocarcinomas were stratified based on TTF-1 and SMARCA4 expressions, histological subtypes, and driver mutations. Immunohistochemical analysis was performed using xenograft tumors of lung adenocarcinoma cell lines with high HNF4A expression. RESULT: HNF4α-positive adenocarcinomas(n = 33) were divided into two groups: the variant group(15 mucinous, 2 enteric, and 1 colloid), where SMARCA4 was retained in all cases, and the conventional non-mucinous group(6 papillary, 5 solid, and 4 acinar), where SMARCA4 was lost in 3/15 cases(20%). All variant cases were negative for TTF-1 and showed wild-type EGFR and frequent KRAS mutations(10/18, 56%). The non-mucinous group was further divided into two groups: TRU-type(n = 7), which was positive for TTF-1 and showed predominantly papillary histology(6/7, 86%) and EGFR mutations(3/7, 43%), and non-TRU-type(n = 8), which was negative for TTF-1, showed frequent loss of SMARCA4(2/8, 25%) and predominantly solid histology(4/8, 50%), and never harbored EGFR mutations. Survival analysis of 230 cases based on histological grading and HNF4α expression revealed that HNF4α-positive poorly differentiated (grade 3) adenocarcinoma showed the worst prognosis. Among 39 cell lines, A549 showed the highest level of HNF4A, immunohistochemically HNF4α expression positive and SMARCA4 lost, and exhibited non-mucinous, high-grade morphology in xenograft tumors. CONCLUSION: HNF4α-positive non-mucinous adenocarcinomas included TRU-type and non-TRU-type cases; the latter tended to exhibit the high-grade phenotype with frequent loss of SMARCA4, and A549 was a representative cell line.
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A 38-year-old woman was admitted to our university hospital with loss of muscle strength. She was diagnosed with dermatomyositis and underwent contrast-enhanced computed tomography of the entire body to check for malignant tumors. Computed tomography revealed multiple enhanced hepatic nodules and an extrahepatic portosystemic shunt. Although a needle biopsy of the nodule could not diagnose definitive hepatocellular carcinoma, some nodules increased in size after three months. Because of the inconclusive results of the second biopsy, we performed shunt embolization using a vascular plug. After another three months, the hepatic nodules shrank markedly, as expected.
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Summary: Unawareness of postprandial hypoglycemia for 5 years was identified in a 66-year-old man at a local clinic. The patient was referred to our hospital because of this first awareness of hypoglycemia (i.e. lightheadedness and impaired consciousness) developing after lunch. In a 75 g oral glucose tolerance test, the plasma glucose concentration was decreased to 32 mg/dL (1.8 mmol/L) at 150 min with relatively high concentrations of insulin (8.1 µU/mL), proinsulin (70.3 pmol/L), and C-peptide (4.63 ng/mL). In a prolonged fasting test, the plasma glucose concentration was decreased to 43 mg/dL (2.4 mmol/L) at 66 h with an insulin concentration of 1.4 µU/mL and a C-peptide concentration of 0.49 ng/mL. Computed tomography showed an 18 mm hyperenhancing tumor in the uncinate process of the pancreas. A selective arterial calcium stimulation test showed an elevated serum insulin concentration in the superior mesenteric artery. The patient was then diagnosed with insulinoma and received pancreaticoduodenectomy. Continuous glucose monitoring (CGM) using the Dexcom G6 system showed unawareness of hypoglycemia mainly during the daytime before surgery. When the sensor glucose value was reduced to 55 mg/dL (3.1 mmol/L), the Dexcom G6 system emitted an urgent low glucose alarm to the patient four times for 10 days. Two months after surgery, an overall increase in daily blood glucose concentrations and resolution of hypoglycemia were shown by CGM. We report a case of insulinoma with unawareness of postprandial hypoglycemia in the patient. The Dexcom G6 system was helpful for assessing preoperative hypoglycemia and for evaluating outcomes of treatment by surgery. Learning points: Insulinoma occasionally leads to postprandial hypoglycemia. The CGM system is useful for revealing the presence of unnoticed hypoglycemia and for evaluating treatment outcomes after surgical resection. The Dexcom G6 system has an urgent low glucose alarm, making it particularly suitable for patients who are unaware of hypoglycemia.
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BACKGROUND: A gastrocolic fistula is an unusual communication between the colon and the stomach. Although colon cancer is the most common malignant cause of gastrocolic fistula in the Western world, the incidence of gastrocolic fistula due to colon cancer is 0.3% in operated cases. CASE PRESENTATION: A 68-year-old man presented with anorexia, general malaise, weight loss, and vomiting of fecal matter. Investigations revealed that the patient had a large nonmetastatic splenic flexure tumor that was diagnosed as colon cancer and had invaded the stomach and pancreas. An upper gastrointestinal series confirmed a gastrocolic fistula. Left hemicolectomy, distal gastrectomy, distal pancreatectomy, and splenectomy were performed. Histology revealed transverse colon cancer, which was UICC stage (8th edition) pT4bN1bcM0 pStage IIIC. Adjuvant chemotherapy was not performed. There was no recurrence or metastasis one year after surgery. We reviewed 17 cases including our case of a gastrocolic fistula caused by colon cancer. Neoadjuvant chemotherapy was not given to any of the patients, and en bloc resections were conducted in all cases. Adjuvant chemotherapy was given to almost all of the patients. There was no recurrence or metastasis. CONCLUSIONS: For gastrocolic fistula caused by advanced colon cancer, secure en bloc surgical resection was the initial treatment in all 17 reported cases including the present case, and adjuvant chemotherapy may contribute to a better prognosis.
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The mechanism underlying the development of tumors, particularly at early stages, still remains mostly elusive. Here, we report whole-genome long and short read sequencing analysis of 76 lung cancers, focusing on very early-stage lung adenocarcinomas such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma. The obtained data is further integrated with bulk and spatial transcriptomic data and epigenomic data. These analyses reveal key events in lung carcinogenesis. Minimal somatic mutations in pivotal driver mutations and essential proliferative factors are the only detectable somatic mutations in the very early-stage of AIS. These initial events are followed by copy number changes and global DNA hypomethylation. Particularly, drastic changes are initiated at the later AIS stage, i.e., in Noguchi type B tumors, wherein cancer cells are exposed to the surrounding microenvironment. This study sheds light on the pathogenesis of lung adenocarcinoma from integrated pathological and molecular viewpoints.
Assuntos
Adenocarcinoma in Situ , Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/patologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Pulmão/patologia , Adenocarcinoma in Situ/genética , Mutação , Microambiente TumoralRESUMO
Small cell lung cancer (SCLC) subtype classification, based on high-level expression of key transcriptional regulators; ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1 (SCLC-Y), has recently been proposed. YAP1 (and POU2F3) has attracted attention as an important factor for non-neuroendocrine (non-NE) phenotypic subtyping of SCLC. However, subsequent studies reported that YAP1 expression alone cannot define a single group in primary SCLC, which makes it difficult to understand what SCLC-Y is by focusing only on SCLC. In this review, we concluded that YAP1 is an essential anti-neuroendocrine factor in both SCLC and non-small cell lung cancer (NSCLC) based on previous studies, including our own analysis of the cell lines and primary tumors of SCLC and NSCLC. The classification of SCLC-Y is a concept mainly established from the analysis of cell lines, and SCLC-Y cell lines correspond to "variant type" SCLC cell lines. Primary SCLC and large cell neuroendocrine carcinoma (LCNEC) are typically heterogeneous tumors composed mostly of NE-type cells, but they contain a small number of non-NE-type cells. Importantly, individual cells with NE features exhibit YAP1 loss, whereas the non-NE-type cells exhibit YAP1 expression. Although rare in primary SCLC, some cases of primary LCNEC have many YAP1-positive cells, which is correlated with chemotherapy resistance. YAP1 staining may be useful in the exclusion diagnosis of SCLC or in the selection of treatment for LCNEC.
Assuntos
Carcinoma Neuroendócrino , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/metabolismo , Carcinoma Neuroendócrino/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Proteínas de Sinalização YAPRESUMO
Tumor-induced osteomalacia (TIO) is a rare tumor-associated syndrome in which osteomalacia is induced by a tumor. A 67-year-old male patient presented for the first time with low back pain, weakness of the lower extremities and difficulty in walking. Six years earlier, he had nonspecific symptoms such as low back pain, and blood tests showed high alkaline phosphatase and low phosphorus. In addition, fibroblast growth factor 23 (FGF23) was abnormally high at 454 pg/mL. A diagnosis of FGF23-related hypophosphatemic osteomalacia was made. Somatostatin receptor scintigraphy, venous sampling and MRI were performed to localize and diagnose TIO. The tumor was found to be confined to the right femoral head and hemiarthroplasty was performed. Pathological examination revealed a phosphaturic mesenchymal tumor. Postoperatively, symptoms and blood test data improved. Although resection of the lesion and osteochondral transplantation or total hip arthroplasty were considered, hemiarthroplasty was chosen over concerns about treatment failure due to seeding.
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The purposes of the present study were to establish a noninvasive monitoring assay of fecal progestagen measurement to detect pregnancy and to identify the components of fecal progestagens in early, middle and late pregnancy in cheetahs. Feces were collected from 7 female cheetahs and analyzed from 30 days before the last copulation to parturition in 9 pregnancies. Blood was collected from one cheetah. Fecal progestagen and serum progesterone concentrations were determined by enzyme immunoassay (EIA). The profiles of the fecal progestagen concentrations were similar to the serum progesterone profile. Fecal progestagen and serum progesterone concentrations remained at the baseline until copulation. In the mean fecal progestagen profile during pregnancy (92.8 ± 0.4 days; from the last copulation to parturition), the concentrations increased 3-4 days after the last copulation and remained high until parturition. To investigate changes in the components of progestagen metabolites in the tripartite periods of gestation, fecal progestagens were analyzed by HPLC-EIA. Marked immunoreactive peaks consistent with 5α-pregnan-3α/ß-ol-20-one and 5α-pregnan-3,20-dione and small peaks consistent with 5ß-pregnan-3α/ß-ol-20-one were detected. There were no distinct difference in the components of progestagens among the first, second and third trimesters of pregnancy. The hormone assay, as an indicator of fecal 5α-reduced pregnanes, is useful for detecting pregnancy and monitoring pregnant luteal activity in cheetahs.
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Acinonyx/fisiologia , Animais de Zoológico , Fezes/química , Prenhez , Progestinas/análise , Animais , Feminino , GravidezRESUMO
Lung metastasis and metachronous double primary lung cancer are both common and often present diagnostic challenges. We present a case of metachronous isolated contralateral lung metastasis from pulmonary adenosquamous carcinoma with EGFR mutation. A 75-yearold woman presented with left lung nodule on a routine follow-up chest radiograph. She had had surgery for pulmonary adenocarcinoma with EGFR Ex21 L858R mutation 6 years ago. She underwent surgical resection, and histologic findings revealed adenosquamous carcinoma with the same EGFR mutation. Re-assessment of the resected specimen of the primary tumor resected 6 years ago revealed the morphologically similarity to the left lung tumor. Based on morphological and genetic identity, final diagnosis was adenosquamous cell carcinoma and metachronous isolated contralateral lung metastasis. The diagnosis of metachronous isolated metastasis is difficult but important for appropriate management and prediction of prognosis. A careful pathological examination and evaluation of genetic abnormality are needed to make the correct diagnosis.
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Carcinoma Adenoescamoso , Neoplasias Pulmonares , Metástase Neoplásica , Segunda Neoplasia Primária , Idoso , Carcinoma Adenoescamoso/genética , Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/cirurgia , Diagnóstico Diferencial , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Mutação , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/patologia , Administração dos Cuidados ao Paciente/métodos , Pneumonectomia/métodosRESUMO
Endobronchial-invasive lung cancers are generally diagnosed at advanced stages and may require emergency treatment for airway obstruction. Stent implantation is a common intervention for such obstructed airways but certain subsets of patients cannot receive adequate treatment without respiratory support. Veno-venous extracorporeal membrane oxygenation (ECMO) is a salvage therapy for respiratory failure but its usefulness in managing patients with advanced lung cancer remains unclear given the poor prognosis. In recent years, molecular targeted agents for patients with driver mutations offer rapid responses and may be administered even while under critical care. In this report, we describe the case of 39-year-old female who presented to our emergency department with severe respiratory distress. A computed tomography scan revealed a large mediastinal tumor invading the tracheal carina causing severe stenosis of the left main bronchus and right main pulmonary artery. ECMO support was required as the respiratory condition remained unstable despite high pressure ventilation. Under ECMO support, the patient underwent bronchial stent implantation and was successfully weaned off ECMO. The tumor was histologically diagnosed as pulmonary adenocarcinoma with anaplastic lymphoma kinase gene rearrangement. Treatment with a tyrosine kinase inhibitor, alectinib, induced a marked tumor reduction within a short period. The patient recovered well and is now in remission one year later. This case indicates that intensive respiratory support with ECMO may become a bridge through the critical period for selected patients with respiratory failure secondary to advanced lung cancer. KEY POINTS: SIGNIFICANT FINDINGS OF THIS STUDY: ECMO was important to maintain oxygenation during airway intervention for acute respiratory failure due to critical lung adenocarcinoma with ALK gene rearrangement. WHAT THIS STUDY ADDS: With the development of targeted therapies and the improvement in therapeutic bronchoscopy, intensive respiratory support with ECMO may be helpful especially in selected lung cancer patients with oncogenic driver mutations.
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Adenocarcinoma de Pulmão/terapia , Obstrução das Vias Respiratórias/terapia , Oxigenação por Membrana Extracorpórea/métodos , Adulto , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
A 70-year-old woman was referred to our department due to a solitary mediastinal tumor which gradually grew near the site of anastomosis for 8 years after radical surgery of esophageal squamous cell carcinoma. It was difficult to distinguish the lymph node recurrence of esophageal cancer from another tumor of unknown primary origin. Endoscopic ultrasound-guided fine-needle aspiration was performed, and the tumor was diagnosed to be neuroendocrine carcinoma. She received concurrent chemoradiotherapy with etoposide plus cisplatin. After the completion of chemoradiotherapy, the tumor disappeared. A solitary growing tumor which develops after radical resection of cancer would be better to be examined histologically in order to make an accurate diagnosis and select the most appropriate treatment.
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Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/radioterapia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Neoplasias do Mediastino/tratamento farmacológico , Neoplasias do Mediastino/radioterapia , Idoso , Carcinoma Neuroendócrino/fisiopatologia , Cisplatino/uso terapêutico , Neoplasias Esofágicas/fisiopatologia , Carcinoma de Células Escamosas do Esôfago/fisiopatologia , Etoposídeo/uso terapêutico , Feminino , Humanos , Linfonodos/fisiopatologia , Neoplasias do Mediastino/fisiopatologia , Recidiva Local de Neoplasia/fisiopatologia , Radioterapia/métodos , Resultado do TratamentoRESUMO
Thrombotic microangiopathy (TMA) is a rare but life-threatening complication of systemic lupus erythematosus (SLE) and is associated with adverse pregnancy outcomes. We herein report a 30-year-old pregnant woman with SLE complicated by TMA. Because her condition was unresponsive to initial corticosteroid and fresh-frozen plasma infusion treatment, we attempted plasma exchange (PE). Although thrombocytopenia and microangiopathic hemolytic anemia gradually improved, fetal death was confirmed at 23 weeks of gestation. This case suggests that PE is an effective therapeutic option but might be insufficient to maintain pregnancy in patients with SLE complicated by TMA.
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Lúpus Eritematoso Sistêmico , Púrpura Trombocitopênica Trombótica , Microangiopatias Trombóticas , Adulto , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/terapia , Troca Plasmática , Gravidez , Resultado da Gravidez , Púrpura Trombocitopênica Trombótica/complicações , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/terapiaRESUMO
OBJECTIVE: Invasive mucinous adenocarcinoma (IMA) is a variant of lung adenocarcinoma. We present one case of IMA with mixed mucinous and non-mucinous components, suggesting stepwise progression within the tumor. MATERIAL AND METHOD: The two different components of IMA were separately examined by immunohistochemistry and performed amplicon sequencing (Ion Ampliseq Cancer Hotspot Panel v2, ilumina, San Diego, CA). RESULT: Macroscopically, the IMA contained a small and well demarcated solid part. Tumor cells in the main part showed abundant intracytoplasmic mucin, whereas those in the solid part showed scant intracytoplasmic mucin and high-grade nuclear atypia. Both parts harbored the same KRAS p.G12 V mutation. The amplicon sequencing of the IMA showed oncogenic TP53 p.P278 L mutation was detected only in the solid part. CONCLUSION: Oncogenetic TP53 mutation might promote stepwise progression of this case of IMA.
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Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma Mucinoso/metabolismo , Idoso de 80 Anos ou mais , Biomarcadores , Biópsia , Progressão da Doença , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Mucinas/genética , Mucinas/metabolismo , Mutação , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: Central nervous system reactions to new quinolones, such as convulsions due to interaction with nonsteroidal anti-inflammatory drugs (NSAIDS), have attracted increased attention in Japan. METHODS: The safety of levofloxacin (LVX) was investigated in Japan by post-marketing surveillance and reviewing spontaneous reports. RESULTS: Post-marketing surveillance was performed in 16,117 patients between 1994 and 1996. The incidence of adverse reactions was 1.3% (203/16,117), being comparable with that for ofloxacin or that shown by phase II/III studies. Among 4,977 patients receiving concomitant NSAID treatment, the overall incidence of adverse reactions and the incidence of neurological reactions (including convulsions) did not significantly differ from those in patients without anti-inflammatory therapy. Review of the spontaneous reports on convulsions showed that patients with nephropathy, patients over 75 years and patients with a history of convulsive diseases were more likely to develop convulsions during LVX therapy. CONCLUSION: LVX should be used cautiously in patients with the above risk factors.