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Secondary osteosarcoma is a rare complication of primary malignancies and benign bone lesions. There are various types of diseases that cause secondary osteosarcoma. A 15-year-old male presented at our medical center complaining of pain and redness in the right lower leg. He had been diagnosed with osteofibrous dysplasia in the right tibia when he was 2 years old and since then had been followed up. Although he had a pathological fracture of the right tibia at the age of 7, his fracture healed with a plaster cast and did not require surgery. At the time of the patient's last visit, a radiograph revealed a periosteal reaction as well as erosion of the bone cortex. Magnetic resonance imaging revealed an infiltrative area in the soft tissue surrounding the osteofibrous dysplasia lesion in the tibia. Consequent to pathological examination (through bone biopsy), the patient was diagnosed with secondary osteosarcoma. The patient underwent chemotherapy and extensive resection with liquid nitrogen. He has been progressing satisfactorily after the operation. The present case is the first report of secondary osteosarcoma associated with osteofibrous dysplasia. During the long-term follow-up of osteofibrous dysplasia, oncologists should be aware of the possibility of secondary osteosarcoma.
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Doenças do Desenvolvimento Ósseo , Neoplasias Ósseas , Displasia Fibrosa Óssea , Segunda Neoplasia Primária , Osteossarcoma , Masculino , Humanos , Adolescente , Pré-Escolar , Neoplasias Ósseas/complicações , Neoplasias Ósseas/diagnóstico por imagem , Doenças do Desenvolvimento Ósseo/patologia , Tíbia/cirurgia , Osteossarcoma/complicações , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/cirurgia , Displasia Fibrosa Óssea/complicações , Displasia Fibrosa Óssea/diagnóstico por imagemRESUMO
BACKGROUND: Granulomatosis with polyangiitis (GPA) is characterized by granulomatous inflammation, vasculitis, and elevated levels of serum proteinase 3 (PR3)-anti-neutrophil cytoplasmic antibody (PR3-ANCA). OBJECTIVE: We tried to characterize immune cells accumulated into the lung lesions of a GPA patient exhibiting spontaneous regression. METHODS: Transbronchial lung biopsy (TBLB) samples were subjected to immunohistochemical analyses. RESULTS: Multiple lung nodules were detected by CT. TBLB showed granulomatous inflammation and small vessel vasculitis. This case was diagnosed as GPA based on pathological findings and elevation of PR-3 ANCA levels. Spontaneous disappearance of multiple lung nodules was observed in CT. CD3+ T cells and CD20+ B cells accumulated in the inflammatory lesions surrounding the vessels whereas granulomatous inflammation was mainly comprised of CD3+ T cells and CD68+ macrophages, but not B cells or myeloperoxidase+ neutrophils. CONCLUSIONS: We characterized immune cell compositions of the lung lesions of a patient with GPA exhibiting spontaneous regression.
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Therapies targeted to human epidermal growth factor receptor 2 (HER2) have proven effective against tumors positive for HER2 amplification, but there is an unmet clinical need for the treatment of tumors that express HER2 protein in the absence of HER2 amplification. [fam-] trastuzumab deruxtecan (DS-8201a) is a novel antibody-drug conjugate composed of the anti-HER2 antibody and the topoisomerase I inhibitor, an exatecan derivative. It has shown efficacy against tumors that express HER2 and is currently under evaluation in clinical trials. We here show that the antitumor activity of [fam-] trastuzumab deruxtecan is dependent on the expression level of HER2 protein in colorectal cancer (CRC) cell lines negative for HER2 amplification. We established isogenic CRC cell lines that express various levels of HER2 protein in the absence of HER2 amplification, and we found that cells that express HER2 at a high level were sensitive to [fam-] trastuzumab deruxtecan but not to conventional HER2-targeted therapies. Furthermore, [fam-] trastuzumab deruxtecan manifested a bystander killing effect both in vitro and in vivo, with cells essentially negative for HER2 expression also being killed in the presence of HER2-expressing cells, an effect that has the potential to overcome heterogeneity of HER2 expression in CRC tumors. Our results thus suggest that [fam-] trastuzumab deruxtecan warrants further study as a potential treatment for CRC tumors that express HER2 protein in the absence of HER2 amplification.
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Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos/farmacologia , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Imunoconjugados/farmacologia , Receptor ErbB-2/genética , Animais , Camptotecina/farmacologia , Linhagem Celular Tumoral , Feminino , Células HCT116 , Células HT29 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Trastuzumab , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
A fungal ball of a maxillary sinus sometimes includes dental treatment-related foreign material because the sinus is close to the root of the upper teeth. We present a case of right maxillary sinus fungal ball with a gutta-percha point, a dental root canal filler. X-ray analysis of the foreign material in the paraffin section of the fungal ball successfully detected zinc, sulfur, and barium, all of which were constituents of the gutta-percha point. The gutta-percha point might have facilitated the formation of the fungal ball through disruption of the sinus-clearing mechanism. Another interesting histological feature of the fungal ball was the finding of calcium oxalate crystals and non-hyphal fungal elements such as cleistothecia, Hülle cells, and conidial heads. This is the first report of such a combination being found in a specimen of human fungal disease. Although fungal culture was not available in the present case, molecular analysis of the formalin-fixed paraffin-embedded tissue of the fungal ball succeeded in revealing only DNA sequences of Aspergillus nidulans and some other environmental Aspergillus spp.
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Cavidade Pulpar/patologia , Maxila/patologia , Seio Maxilar/microbiologia , Seio Maxilar/patologia , Aspergillus nidulans/patogenicidade , Cavidade Pulpar/microbiologia , Proteínas Fúngicas/metabolismo , Guta-Percha , Humanos , Masculino , Maxila/microbiologia , Pessoa de Meia-Idade , Micoses/diagnóstico , Micoses/patologia , Dente/microbiologia , Dente/patologiaRESUMO
Anti-HER2 therapies are beneficial for patients with HER2-positive breast or gastric cancer. T-DM1 is a HER2-targeting antibody-drug conjugate (ADC) comprising the antibody trastuzumab, a linker, and the tubulin inhibitor DM1. Although effective in treating advanced breast cancer, all patients eventually develop T-DM1 resistance. DS-8201a is a new ADC incorporating an anti-HER2 antibody, a newly developed, enzymatically cleavable peptide linker, and a novel, potent, exatecan-derivative topoisomerase I inhibitor (DXd). DS-8201a has a drug-to-antibody-ratio (DAR) of 8, which is higher than that of T-DM1 (3.5). Owing to these unique characteristics and unlike T-DM1, DS-8201a is effective against cancers with low-HER2 expression. In the present work, T-DM1-resistant cells (N87-TDMR), established using the HER2-positive gastric cancer line NCI-N87 and continuous T-DM1 exposure, were shown to be susceptible to DS-8201a. The ATP-binding cassette (ABC) transporters ABCC2 and ABCG2 were upregulated in N87-TDMR cells, but HER2 overexpression was retained. Furthermore, inhibition of ABCC2 and ABCG2 by MK571 restored T-DM1 sensitivity. Therefore, resistance to T-DM1 is caused by efflux of its payload DM1, due to aberrant expression of ABC transporters. In contrast to DM1, DXd payload of DS-8201a inhibited the growth of N87-TDMR cells in vitro. This suggests that either DXd may be a poor substrate of ABCC2 and ABCG2 in comparison to DM1, or the high DAR of DS-8201a relative to T-DM1 compensates for increased efflux. Notably, N87-TDMR xenograft tumor growth was prevented by DS-8201a. In conclusion, the efficacy of DS-8201a as a treatment for patients with T-DM1-resistant breast or gastric cancer merits investigation.
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Anticorpos Monoclonais Humanizados/farmacologia , Camptotecina/análogos & derivados , Imunoconjugados/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Inibidores da Topoisomerase I/farmacologia , Ado-Trastuzumab Emtansina , Animais , Anticorpos Monoclonais Humanizados/química , Camptotecina/química , Camptotecina/farmacologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imunoconjugados/química , Maitansina/análogos & derivados , Maitansina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína 2 Associada à Farmacorresistência Múltipla , Distribuição Aleatória , Receptor ErbB-2/biossíntese , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/imunologia , Inibidores da Topoisomerase I/química , TrastuzumabRESUMO
Purpose To assess the clinical accuracy and reproducibility of liver fat quantification with the multimaterial decomposition (MMD) algorithm, comparing the performance of MMD with that of magnetic resonance (MR) spectroscopy by using liver biopsy as the reference standard. Materials and Methods This prospective study was approved by the institutional ethics committee, and patients provided written informed consent. Thirty-three patients suspected of having hepatic steatosis underwent non-contrast material-enhanced and triple-phase dynamic contrast-enhanced dual-energy computed tomography (CT) (80 and 140 kVp) and single-voxel proton MR spectroscopy within 30 days before liver biopsy. Percentage fat volume fraction (FVF) images were generated by using the MMD algorithm on dual-energy CT data to measure hepatic fat content. FVFs determined by using dual-energy CT and percentage fat fractions (FFs) determined by using MR spectroscopy were compared with histologic steatosis grade (0-3, as defined by the nonalcoholic fatty liver disease activity score system) by using Jonckheere-Terpstra trend tests and were compared with each other by using Bland-Altman analysis. Real non-contrast-enhanced FVFs were compared with triple-phase contrast-enhanced FVFs to determine the reproducibility of MMD by using Bland-Altman analyses. Results Both dual-energy CT FVF and MR spectroscopy FF increased with increasing histologic steatosis grade (trend test, P < .001 for each). The Bland-Altman plot of dual-energy CT FVF and MR spectroscopy FF revealed a proportional bias, as indicated by the significant positive slope of the line regressing the difference on the average (P < .001). The 95% limits of agreement for the differences between real non-contrast-enhanced and contrast-enhanced FVFs were not greater than about 2%. Conclusion The MMD algorithm quantifying hepatic fat in dual-energy CT images is accurate and reproducible across imaging phases. © RSNA, 2017 Online supplemental material is available for this article.
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Fígado Gorduroso/diagnóstico por imagem , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Algoritmos , Biópsia , Fígado Gorduroso/patologia , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
NEW FINDINGS: What is the central question of this study? An inverse correlation between circulating adiponectin and many diseases has been reported, but some studies have found no correlation. To evaluate this controversy, we investigated the relationship between heart-bound adiponectin and hypertension or cardiac hypertrophy, compared with serum adiponectin. What is the main finding and its importance? Using hypertensive and normotensive rats, we found that heart-bound adiponectin was inversely correlated with cardiac hypertrophy, suggesting that heart-bound adiponectin has a more important function in preventing cardiac hypertrophy than circulating adiponectin. Our study provides new insights regarding the role of adiponectin in diseases. The inverse correlation between circulating adiponectin concentration and hypertension or cardiac hypertrophy is still controversial. In addition to circulating adiponectin, adiponectin is also bound to tissues such as the heart and skeletal muscle. In this study, we investigated the relationship of serum adiponectin and heart-bound adiponectin with hypertension and cardiac hypertrophy. Four types of hypertensive rats presenting different blood pressure levels were used at different ages, as follows: normotensive Wistar-Kyoto rats (WKYs); two sub-strains (strains C and B2, having low and high blood pressure, respectively) of spontaneously hypertensive rats (SHRs); and stroke-prone SHRs (SHRSPs). Blood pressure, heart-to-body weight ratio, serum adiponectin and heart-bound adiponectin were determined. Histopathological analysis of the heart was carried out to evaluate the relationship with heart-bound adiponectin. Serum adiponectin concentration was not inversely correlated with blood pressure or heart-to-body weight ratio. In contrast, heart-bound adiponectin levels were significantly lower in SHRSPs than in other strains at respective ages. This resulted from a decrease in T-cadherin expression, which induced adiponectin binding to tissues. No significant difference in heart-bound adiponectin among WKYs and SHRs (C and B2) was detected, indicating that heart-bound adiponectin is not related to hypertension. In addition, differences in heart-bound adiponectin did not affect AMP-activated protein kinase in the traditional adiponectin activation cascade. Histopathological analysis revealed that heart-bound adiponectin was inversely correlated with cardiomyocyte hypertrophy and left ventricular wall thickness and, in part, with cardiac fibrosis. These results suggest that the decreased level of heart-bound adiponectin in SHRSPs is more related to their cardiac hypertrophy than circulating adiponectin.
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Adiponectina/sangue , Hipertensão/sangue , Hipertrofia Ventricular Esquerda/sangue , Miocárdio/metabolismo , Acidente Vascular Cerebral/etiologia , Proteínas Quinases Ativadas por AMP/metabolismo , Acetil-CoA Carboxilase/metabolismo , Adiponectina/genética , Fatores Etários , Animais , Biomarcadores/sangue , Pressão Sanguínea , Caderinas/metabolismo , Modelos Animais de Doenças , Fibrose , Hipertensão/complicações , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Esquerda/prevenção & controle , Gordura Intra-Abdominal/metabolismo , Masculino , Miocárdio/patologia , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Função Ventricular Esquerda , Remodelação VentricularRESUMO
BACKGROUND: Although pleomorphic adenomas account for over 90% of all benign submandibular gland tumors, the imaging features of submandibular pleomorphic adenomas have not been reported in a large number of cases. PURPOSE: To assess the conventional magnetic resonance imaging (MRI) findings for predicting the submandibular pleomorphic adenoma. MATERIAL AND METHODS: MR studies of 42 pleomorphic adenomas and 28 other types of tumor were reviewed. MR images were assessed for the presence of hyperintense areas on T2-weighted images (first sign), a well-defined margin (second sign), and presence of crescent-shaped compression of the ipsilateral normal submandibular gland (third sign). RESULTS: For identifying submandibular pleomorphic adenoma, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 97.6%, 50.0%, 74.5%, 93.3%, and 78.6% for the first sign, 95.2%, 46.4% 72.7%, 86.7%, and 75.7% for the second sign, and 23.8%, 100%, 86.7%, 46.7%, and 54.3% for the third sign, respectively. Combining the first and second findings achieved to 85.7% specificity and 90.9% accuracy. CONCLUSION: Although non-specific, submandibular pleomorphic adenomas usually have hyperintense areas on T2-weighted images and well-defined margins. In addition, crescent-shaped compression of the ipsilateral normal gland seems to represent a highly specific sign.
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Adenoma Pleomorfo/diagnóstico , Imageamento por Ressonância Magnética/métodos , Neoplasias da Glândula Submandibular/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Introduction: The histological types of urethral cancer are mainly squamous cell or transitional cell carcinoma. Neuroendocrine tumor is extremely a rare type of urethral cancer. Case presentation: A 72-year-old man visited with an erythema at the external urethral meatus. After 3 months, a 1-cm reddish solid tumor was found on the external urethral meatus. He had a history of bladder cancer (pTa with carcinoma in situ), including the prostatic urethra, and underwent radical cystectomy with urethrectomy and ileal conduit construction 11 years ago. After 3 months, a 1-cm reddish solid tumor was found on the external urethral meatus. The pathological diagnosis was a neuroendocrine tumor. Partial penectomy was performed. Conclusion: Small cell neuroendocrine tumor could occur on urethral remnant after radical cystectomy with urethrectomy for urothelial cancer. Inspection of the penis and urethral meatus is important during regular follow-up of patients after radical cystectomy.
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Hyphae are usually the only fungal elements found in tissue of mucormycosis, and other fungal elements are quite rarely encountered. We found chlamydospores in bronchial lumina in autopsied tissue of pulmonary mucormycosis of a diabetic patient. Chlamydospores are thick-walled, asexually produced spores arising from the modification of a hyphal segment. This is the first histologic demonstration of chlamydospores in mucormycosis in which the causative fungus is culturally identified to species level. Rhizopus microsporus var. rhizopodiformis was isolated from the present autopsied pulmonary tissue. A literature review of human infection by this fungus found 27 cases with histopathologic evidence.
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Pneumopatias/microbiologia , Mucormicose/microbiologia , Rhizopus/isolamento & purificação , Adulto , Idoso , Autopsia , Evolução Fatal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rhizopus/genética , Rhizopus/fisiologia , Adulto JovemRESUMO
We report the case of a 4-year-old boy with coarctation of the aorta resulting from persistent fifth aortic arch, a rare abnormality, along with an interrupted fourth aortic arch. When he visited a general practitioner with an upper respiratory infection, a heart murmur was noted. Computed tomography findings led to the diagnosis of persistent fifth aortic arch with an interrupted fourth aortic arch. He underwent aortic arch repair, excision of the fifth aortic arch, and anastomosis of the original arch with the descending aorta. Pathologically, the tissue of the fifth aortic arch was different from that of the normal aortic arch.
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Coartação Aórtica , Anastomose Cirúrgica , Aorta/cirurgia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Coartação Aórtica/diagnóstico por imagem , Coartação Aórtica/cirurgia , Pré-Escolar , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: EGFR-tyrosine kinase inhibitor (TKI) is a standard first-line therapy for activated EGFR-mutated non-small cell lung cancer (NSCLC). Treatment options for patients with acquired EGFR-TKI resistance are limited. HER3 mediates EGFR-TKI resistance. Clinical trials of the HER3-targeting antibody-drug conjugate patritumab deruxtecan (HER3-DXd) demonstrated its anticancer activity in EGFR-mutated NSCLC; however, the mechanisms that regulate HER3 expression are unknown. This study was conducted with the aim to clarify the mechanisms underlying HER3 regulation in EGFR-mutated NSCLC tumors and explored the strategy for enhancing the anticancer activity of HER3-DXd in EGFR-mutated NSCLC. EXPERIMENTAL DESIGN: Paired tumor samples were obtained from 48 patients with EGFR-mutated NSCLC treated with EGFR-TKI(s). HER3 expression was immunohistochemically quantified with H-score, and genomic alteration and transcriptomic signature were tested in tumors from pretreatment to post-EGFR-TKI resistance acquisition. The anticancer efficacy of HER3-DXd and osimertinib was evaluated in EGFR-mutated NSCLC cells. RESULTS: We showed augmented HER3 expression in EGFR-mutated tumors with acquired EGFR-TKI resistance compared with paired pretreatment samples. RNA sequencing revealed that repressed PI3K/AKT/mTOR signaling was associated with HER3 augmentation, especially in tumors from patients who received continuous EGFR-TKI therapy. An in vitro study also showed that EGFR-TKI increased HER3 expression, repressed AKT phosphorylation in multiple EGFR-mutated cancers, and enhanced the anticancer activity of HER3-DXd. CONCLUSIONS: Our findings help clarify the mechanisms of HER3 regulation in EGFR-mutated NSCLC tumors and highlight a rationale for combination therapy with HER3-DXd and EGFR-TKI in EGFR-mutated NSCLC.
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Anticorpos Monoclonais Humanizados , Camptotecina , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Receptor ErbB-3 , Anticorpos Monoclonais Humanizados/uso terapêutico , Camptotecina/análogos & derivados , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Fosfatidilinositol 3-Quinases/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/genética , Receptor ErbB-3/antagonistas & inibidores , Receptor ErbB-3/genética , Receptor ErbB-3/metabolismoAssuntos
Adenocarcinoma/secundário , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Ovarianas/patologia , Neoplasias Pancreáticas/secundário , Neoplasias Gástricas/secundário , Adenocarcinoma/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Gástricas/diagnósticoRESUMO
BACKGROUND: Autoimmune hepatitis (AIH) and autoimmune pancreatitis (AIP) share clinical and pathological features such as high serum levels of immunoglobulin (Ig) G and autoantibodies, and lymphoplasmacytic infiltration, suggesting the presence of common immunological abnormalities. However, little is known about the possible involvement of IgG4, a hallmark of AIP, in AIH. AIMS: In this study, we examined whether the IgG4 response contributes to the histopathological and clinical findings in AIH. METHODS: Liver sections from 26 patients with AIH, 10 patients with primary biliary cirrhosis (PBC), three patients with primary sclerosing cholangitis (PSC) and 20 chronic hepatitis patients with hepatitis C virus (HCV) infection were immunostained for IgG4. We investigated the relationship among the histopathology, the responses to steroid therapy and the IgG4 staining. RESULTS: Nine of the 26 liver specimens from patients with AIH showed positive staining for IgG4 whereas none of the 10 samples from patients with PBC, the three samples from patients with PSC or the 20 samples from patients with HCV hepatitis were positive. Patients with IgG4-positive AIH also showed increased serum levels of IgG. The numbers of T cells, B cells and plasma cells were significantly increased in the livers of patients with IgG4-positive AIH as compared with those patients with IgG4-negative AIH. Patients with IgG4-positive AIH also showed a marked response to prednisolone therapy. CONCLUSIONS: AIH may be classified into either an IgG4-associated type or an IgG4 non-associated type with the former showing a marked response to prednisolone treatment.
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Hepatite Autoimune/imunologia , Hipergamaglobulinemia/patologia , Imunoglobulina G/sangue , Adulto , Idoso , Colangite Esclerosante/imunologia , Colangite Esclerosante/patologia , Feminino , Glucocorticoides/uso terapêutico , Hepatite C Crônica/imunologia , Hepatite C Crônica/patologia , Hepatite Autoimune/tratamento farmacológico , Humanos , Fígado/metabolismo , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Resultado do TratamentoRESUMO
Scedosporium prolificans has been increasingly recognized as an etiological agent of disseminated mycelial infections in profoundly immunocompromised patients. Reported herein is a case of disseminated S. prolificans infection in a patient undergoing anti-neoplastic chemotherapy for acute myeloid leukemia. Antemortem blood culture yielded S. prolificans, which was confirmed on conventional morphological examination and polymerase chain reaction-based DNA sequencing targeting internally transcribed spacer regions. Histopathology of autopsy specimens indicated fungal infection in the heart, lungs, liver, kidneys, spleen, pancreas and gastrointestinal tract, with the development of hemorrhagic and ischemic necrosis. The infecting fungus had developing septate hyphae and was identified as belonging to the genus Scedosporium, on in situ hybridization of tissue. The combination of haphazardly branching hyphae and lemon-shaped conidia appeared to be the most useful distinguishing features to allow differentiation of this fungus from other filamentous fungi in tissue. Three other unique histopathological characteristics of the fungus were noted: (i) parallel hyphae bridged at right angles to produce letter-H patterns; (ii) intravascular conidiation; and (iii) purple conidia in tissue, though these are usually described as brown in most text books. Precise histopathology, in addition to other techniques such as in situ hybridization, can aid in the identification of etiological fungi.
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Micetoma/patologia , Scedosporium , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Micetoma/complicaçõesAssuntos
Aspergilose/complicações , Aspergillus/isolamento & purificação , Coinfecção , Criptococose/complicações , Cryptococcus/isolamento & purificação , Pneumopatias Fúngicas/complicações , Aspergilose/microbiologia , Criptococose/microbiologia , Humanos , Pulmão/microbiologia , Pneumopatias Fúngicas/microbiologia , Masculino , Pessoa de Meia-IdadeRESUMO
Immunotherapy targeting programmed cell death-1 (PD-1) induces durable antitumor efficacy in many types of cancer. However, such clinical benefit is limited because of the insufficient reinvigoration of antitumor immunity with the drug alone; therefore, rational therapeutic combinations are required to improve its efficacy. In our preclinical study, we evaluated the antitumor effect of U3-1402, a human epidermal growth factor receptor 3-targeting (HER3-targeting) antibody-drug conjugate, and its potential synergism with PD-1 inhibition. Using a syngeneic mouse tumor model that is refractory to anti-PD-1 therapy, we found that treatment with U3-1402 exhibited an obvious antitumor effect via direct lysis of tumor cells. Disruption of tumor cells by U3-1402 enhanced the infiltration of innate and adaptive immune cells. Chemotherapy with exatecan derivative (Dxd, the drug payload of U3-1402) revealed that the enhanced antitumor immunity produced by U3-1402 was associated with the induction of alarmins, including high-mobility group box-1 (HMGB-1), via tumor-specific cytotoxicity. Notably, U3-1402 significantly sensitized the tumor to PD-1 blockade, as a combination of U3-1402 and the PD-1 inhibitor significantly enhanced antitumor immunity. Further, clinical analyses indicated that tumor-specific HER3 expression was frequently observed in patients with PD-1 inhibitor-resistant solid tumors. Overall, U3-1402 is a promising candidate as a partner of immunotherapy for such patients.
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Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Imunoconjugados/farmacologia , Neoplasias Experimentais , Receptor de Morte Celular Programada 1 , Receptor ErbB-3/imunologia , Animais , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: The objective of our study was to investigate whether liver parenchymal phase contrast-enhanced sonography can provide additional information for assessing histologic grades of hepatocellular carcinoma (HCC). SUBJECTS AND METHODS: Contrast-enhanced sonography using Levovist of 50 hepatic nodules was performed. The vascular and liver parenchymal perfusion patterns were evaluated. The sensitivity, specificity, and accuracy of the histologic diagnosis of the tumors using vascular phase imaging only and systematically combined vascular phase imaging with liver parenchymal phase imaging were calculated. We also performed histologic examination and immunostaining for the detection of Kupffer cells and calculated the Kupffer cell count in the tumorous tissue relative to that in the nontumorous tissue (Kupffer cell ratio) and quantitatively evaluated the relationship between the Kupffer cell ratio and the perfusion patterns seen on liver parenchymal phase imaging. RESULTS: The specificity and accuracy of contrast-enhanced sonography in the diagnosis of dysplastic nodules and of moderately and poorly differentiated HCCs were improved by adding liver parenchymal phase imaging (dysplastic nodules, 74% and 78% vs 83% and 86%, respectively; moderately and poorly differentiated HCCs, 74% and 86% vs 85% and 92%). The diagnostic accuracy of contrast-enhanced sonography for dysplastic nodules showed a trend of improvement with the addition of liver parenchymal phase imaging (p = 0.07). Kupffer cell ratios for tumors that showed hypoperfusion during the liver parenchymal phase were significantly lower than those for tumors showing isoperfusion (p < 0.05). CONCLUSION: Adding liver parenchymal phase imaging to contrast-enhanced sonography protocols may yield additional information that can be used to assess histologic grades of tumor and that leads to an improvement in the differential diagnosis of nodular lesions associated with the cirrhotic liver. Further case studies are required in larger numbers of patients for a longer follow-up period.
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Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Lesões Pré-Cancerosas/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Distribuição de Qui-Quadrado , Meios de Contraste , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polissacarídeos , Sensibilidade e Especificidade , Estatísticas não Paramétricas , UltrassonografiaRESUMO
OBJECTIVES: To report MRI findings of spontaneous infarction in parotid tumours. METHODS: 14 patients (13 male, 1 female; mean age 73 years) with spontaneously infarcted parotid tumours were reviewed retrospectively. MR images were assessed for the location, the presence of synchronous parotid masses, margin characteristics, signal intensity on T 1 and T 2 weighted images, and internal architecture according to the distribution of T 2 signal hyperintensity. RESULTS: 12 tumours were located in the parotid tail and 2 in the superficial lobe. Synchronous parotid masses were seen in four tumours, three of which were located in the ipsilateral parotid tail and one in the contralateral parotid tail. Seven tumours had well-defined margins and seven had ill-defined margins. The signal intensities on T 1 weighted images were a mixture of high and intermediate in all cases; in 11 tumours, hyperintense areas were dominant. On T 2 weighted images, all tumours also showed a mixture of high and intermediate signal intensities. Internal architectures on T 2 weighted images were mosaic hyperintensity in three tumours, central hyperintensity in five, and multiseparated hyperintensity in six. CONCLUSIONS: Spontaneously infarcted parotid tumours were mostly located in the parotid tail and showed mixed signal intensities with predominant hyperintensity on T 1 weighted images. Half of the tumours had ill-defined margins, and the internal architectures varied.
Assuntos
Infarto , Imageamento por Ressonância Magnética , Neoplasias Parotídeas , Idoso , Feminino , Humanos , Infarto/diagnóstico por imagem , Masculino , Glândula Parótida , Neoplasias Parotídeas/diagnóstico por imagem , Estudos RetrospectivosRESUMO
Intravascular lymphoma (IVL) is a malignant lymphoma that lacks the expression of cell surface adhesion molecules so that cells fluidly migrate within the blood vessels. The patient in the present study had restricted eye movement caused by IVL, mimicking a cavernous sinus tumor. Because the cavernous sinus lumen is divided into multiple compartments by trabeculae and venous channels, IVL tumor cells were trapped in these compartments, thus forming a mass, which subsequently extended into the contralateral cavernous sinus via the anterior and posterior intercavernous sinuses. This is a rare case of IVL forming a mass inside the cavernous sinus.