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1.
Exp Dermatol ; 32(6): 831-839, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37017196

RESUMO

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the two most common skin cancer and impose a huge medical burden on society. Histopathological examination based on whole-slide images (WSIs) remains to be the confirmatory diagnostic method for skin tumors. Accurate segmentation of tumor tissue in WSIs by deep-learning (DL) models can reduce the workload of pathologists and help surgeons ensure the complete removal of tumors. To accurately segment the tumor areas in WSIs of BCC, SCC and squamous cell papilloma (SCP, homologous to SCC) with robust models. We established a data set (ZJU-NMSC) containing 151 WSIs of BCC, SCC and SCP in total. Seven models were utilized to segment WSIs, including the state-of-the-art model, models proposed by us and other models. Dice score, intersection over union, accuracy, sensitivity and specificity were used to evaluate and compare the performance of different models. Heatmaps and tumor tissue masks were generated to reflect the results of the segmentation. The processing times of models are also recorded and compared. While the dice score of most models is higher than 0.85, deeplab v3+ has the best performance and the corresponding tumor tissue mask is more consistent with the ground truth tumor areas even with complex and small lobular lesions. This study broadens the use of DL-based segmentation models in WSIs of skin tumors in terms of tumor types and computational approaches. Segmenting tumor areas can simplify the process of histopathological inspection and benefit the diagnosis and following management of the diseases in practice.


Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Aprendizado Profundo , Neoplasias Cutâneas , Humanos , Semântica , Neoplasias Cutâneas/diagnóstico por imagem , Carcinoma Basocelular/diagnóstico por imagem , Carcinoma de Células Escamosas/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos
2.
BMC Cancer ; 23(1): 841, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37684569

RESUMO

BACKGROUND: Breast cancers with 1-10% cell staining for estrogen receptor (ER) present particular clinical features. The clinical data of estrogen receptor expression level and treatment effect are limited, particularly regarding chemotherapy benefit. We evaluated the pathologic response to neoadjuvant chemotherapy (NAC) in ER low positive tumors (ER staining 1-10%) and compared it with ER > 10% positive tumors (ER staining > 10%) and ER-negative tumors. We further explored the differences in recurrence and survival with respect to the ER expression level. METHOD: Patients with stages II and III HER2-negative primary breast cancer who received neoadjuvant chemotherapy followed by definitive surgery were categorized according to their ER percentages into three groups: ER-negative, ER low positive, and ER > 10% positive. Logistic regression models were used to assess the association between each variable and pathologic complete response (pCR). Kaplan‒Meier analysis was used to estimate survival outcomes. Cox models were used to adjust for patient and tumor characteristics. RESULTS: A total of 241 patients were analyzed. Of all patients included, 22 (9.1%) had ER low positive tumors, 159 (66.0%) had ER > 10% positive tumors, and 60 (24.9%) were ER-negative. Low ER positivity was significantly associated with a higher pCR rate than ER > 10% positivity (OR, 0.249; 95% CI, 0.067-0.923; P = 0.038). After a median follow-up time of 32 months, the disease-free survival (DFS) and overall survival (OS) of the patients with ER low positive tumors were significantly worse than those of the patients with ER > 10% positive tumors but similar to those with ER-negative tumors. After adjustment for covariates, ER low positive tumors were significantly associated with worse DFS than ER > 10% positive tumors. CONCLUSION: Our results indicated that ER low positive breast cancer presents a better response to neoadjuvant chemotherapy and significantly worse prognosis for patients than those with ER > 10% positive tumors, but similar to the ER-negative group. These data support that this category of patients behaves clinically like patients with ER-negative breast cancer and should be treated differently from patients with ER > 10% positive tumors. Further prospective study is needed.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Receptores de Estrogênio , Terapia Neoadjuvante , Prognóstico , Intervalo Livre de Doença
3.
World J Surg Oncol ; 21(1): 342, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37884941

RESUMO

INTRODUCTION: Primary breast lymphoma (PBL) is rare, and most cases occur in female patients, with few reported cases in male patients. The clinical presentation is similar to that of breast cancer, but the condition needs to be well understood, as treatment options and clinical course vary. Hence, we provide a relatively rare case of primary breast diffuse large B cell lymphoma (PB-DLBCL) in a male, including its complete clinicopathological features, radiological findings, genomic mutational profiles, and clinical course. CASE PRESENTATION: A 45-year-old male presented with a lump in his right breast for 1 week and was pathologically diagnosed with breast malignancy after a breast puncture biopsy at the local hospital. He came to our hospital for further treatment and underwent breast ultrasound and systemic positron emission tomography/computed tomography (PET/CT) imaging, followed by right mastectomy and sentinel lymph node biopsy. Histomorphology showed diffuse hyperplasia of tumor cells with clear boundaries and surrounding normal breast ducts. The adhesion of tumor cells was poor with obvious atypia. Immunohistochemical results showed that the tumor cells were positive for CD20, Bcl6, and MUM-1 but negative for CK (AE1/AE3), ER, PR, CD3, and CD10. Forty percent of the tumor cells were positive for c-Myc, and 80% of tumor cells were positive for Bcl2. The Ki-67 proliferation index was up to 80%. The tumor cells were negative for MYC and BCL2 rearrangements but positive for BCL6 rearrangement by fluorescent in situ hybridization. No abnormality was found in the pathological examination of bone marrow aspiration. Therefore, the male was diagnosed with PB-DLBCL, nongerminal center (non-GCB) phenotype, dual-expression type. The sample were sequenced by a target panel of 121 genes related to lymphoma. Next-generation sequencing revealed six tumor-specific mutated genes (IGH/BCL6, TNFAIP3, PRDM1, CREBBP, DTX1, and FOXO1). The patient was given six cycles of orelabrutinib plus R-CHOP chemotherapy and two cycles of intrathecal injection of cytarabine. The last follow-up was on April 13, 2023 (17 months). No recurrence or metastasis was found in laboratory and imaging examinations. CONCLUSION: We reported a relatively rare PB-DLBCL in a male, non-GBC phenotype, dual-expression type. It is worth mentioning that this case had IgH/BCL6 fusion, nonsense mutations in TNFAIP3, frameshift mutations in PRDM1, and missense mutations in CREBBP, DTX1, and FOXO1. To the best of our knowledge, this case is the first report of genomic mutational profiles of PB-DLBCL in males.


Assuntos
Neoplasias da Mama , Linfoma Difuso de Grandes Células B , Humanos , Masculino , Pessoa de Meia-Idade , Progressão da Doença , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Mastectomia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Proteínas Proto-Oncogênicas c-bcl-2/genética
5.
Tumour Biol ; 37(1): 115-25, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26563372

RESUMO

Inflammatory cells and mediators form a major part of the tumor microenvironment and play important roles in the regulation of cancer initiation, tumor cell proliferation, and metastasis. MicroRNAs (miRNAs) play important roles in several physiological and pathological processes, including the regulation of the inflammatory microenvironment in cancer. Transforming growth factor-ß (TGF-ß) is an inflammation-related cytokine that functions in both tumor suppression and promotion; however, its underlying molecular mechanisms remain unclear. Recent evidence indicates an association between miRNAs and TGF-ß signaling, providing new insight into the nature of the inflammatory microenvironment in cancer. The present review is an overview of the interaction between miRNAs and inflammatory cytokines, with emphasis on the cross talk between TGF-ß signaling and miRNAs and their influence on cancer cell behavior. The emerging roles of miRNAs in cancer-related inflammation and the potential to target miRNA signaling pathways for cancer therapy are also discussed.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Neoplasias/genética , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral , Animais , Citocinas/metabolismo , Humanos , Inflamação , Camundongos , Neoplasias/imunologia , Neoplasias/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transdução de Sinais , Proteínas Smad/metabolismo , Regulação para Cima
6.
Pancreas ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38904669

RESUMO

INTRODUCTION: Epidermoid cyst in an intra-pancreatic accessory spleen (ECIPAS) is an exceedingly rare pancreatic lesion that is always mistakenly suspected of malignancy preoperatively. CASE SUMMARY: A 25-year-old male incidentally found a giant mass in the left upper abdomen neighboring the hilum of the spleen. The patient denied any obvious discomfort. Except for a slightly elevated carbohydrate antigen 19-9 (CA19-9, 43.5 U/ml), no abnormal laboratory test results were found. Contrast-enhanced computed tomography (CT), conventional ultrasound (US), and magnetic resonance imaging (MRI) were performed. The patient received a laparoscopic distal pancreatectomy. The final pathology showed ECIPAS. The postoperative course was uneventful and no signs of recurrence during 2 years of follow-up. DISCUSSION: For an incidental pancreatic cystic lesion (PCL), ECIPAS should be considered in the differential diagnosis. ECIPAS may mimic pancreatic cystadenoma. Imaging follow-up or surgical removal may be useful for the exclusion of malignant risks in ECIPAS.

7.
Diagn Pathol ; 19(1): 8, 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38184586

RESUMO

BACKGROUND: Cutaneous Melanocytic Tumor with CRTC1::TRIM11 Fusion (CMTCT) represents a novel and rare entity in the realm of dermatological oncology, characterized by distinct melanocytic differentiation. This particular tumor type has yet to be officially recognized by the World Health Organization (WHO). CMTCT is generally perceived as a tumor with a relatively indolent nature; however, it is not devoid of metastatic potential. Therefore, ensuring complete surgical excision of the tumor, coupled with rigorous long-term follow-up, is paramount for patient management. In this context, we report the case of an 18-year-old female patient who presented with a dull red nodule on her left leg. Initial surgical intervention led to a pathological diagnosis of CMTCT, but it was determined that the tumor had not been fully excised. Consequently, a second surgical procedure was undertaken to achieve complete removal of the tumor. During a follow-up period of six months post-surgery, the patient showed no signs of local recurrence or metastasis, indicating a successful outcome. CASE PRESENTATION: An 18-year-old female patient noticed a dull red nodule on her left leg three years ago, which exhibited slow growth over time. She underwent a subcutaneous tumor resection. Histological examination under high-power magnification revealed that the neoplasm consisted of epithelioid cells arranged in nests, fascicles, bundles, or sheets. The tumor cells had round or ovoid nuclei with prominent nucleoli and visible mitotic figures. Notably, areas resembling nevus cell clusters were observed. Immunohistochemical analysis confirmed melanocytic differentiation. Next-generation sequencing (NGS) identified a CRTC1::TRIM11 fusion, and fluorescence in situ hybridization (FISH) for CRTC1 confirmed rearrangement. Consequently, a diagnosis of cutaneous melanocytic tumor with CRTC1::TRIM11 fusion was established. CONCLUSIONS: CMTCT is a rare tumor characterized by melanocytic differentiation. In this case, the tumor predominantly comprised epithelioid cells with localized nevus cell clusters. The expression of melanocyte markers could easily lead to a misdiagnosis as cutaneous melanoma. However, several distinguishing features were noted: the tumor was not connected to the epidermis, exhibited low cellular heterogeneity and proliferation index, and showed minimal cellular atypia. Additionally, tests for EWSR1 rearrangement (FISH) and BRAF V600E mutation (PCR-ARMS) were negative.This case underscores the importance of a comprehensive diagnostic approach when clinical, microscopic, immunohistochemical, and molecular findings do not align. The presence of nevus cell clusters morphology in the tumor cells enhances our understanding of this disease's histological spectrum and aids in avoiding misdiagnosis or missed diagnosis.


Assuntos
Melanoma , Nevo Pigmentado , Nevo , Neoplasias Cutâneas , Feminino , Humanos , Adolescente , Neoplasias Cutâneas/genética , Melanoma/genética , Hibridização in Situ Fluorescente , Fatores de Transcrição/genética , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases
8.
Diagnostics (Basel) ; 14(7)2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38611678

RESUMO

Bone metastasis has been reported in up to 70% of patients with advanced breast cancer. A total of 55.76% of skeletal metastases in women were derived from breast cancer. However, patients with bone metastasis from an occult primary breast cancer are a rare subset of patients. Here, we present the case of a 38-year-old woman who had sternum pain for 4 months. A whole-body PET-CT scan revealed that the FDG uptake of both the sternum and internal mammary node was significantly increased. The final diagnosis of occult breast cancer was established by immunohistochemical (IHC) staining, which is of great significance for identifying the origin of a metastatic tumor despite no visualized lesions of mammary glands.

9.
Clin Breast Cancer ; 24(3): 191-198, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38368247

RESUMO

PURPOSE: This study was a retrospective and nonrandomized study to assess the safety and reliability of identifying the surgical margin in breast cancer breast-conserving surgery (BCS) by using intraoperative ultrasonic location and specimen mammography instead of traditional intraoperative frozen pathological section. METHODS: Among the patients who underwent BCS from May 2019 to October 2021, according to the different methods of evaluating the intraoperative margin, 104 breast cancer patients were included in the frozen edge group, 53 breast cancer patients were included in the freeze-free group, and the surgeon judged whether extended resection was needed based on the results of pathological section or evaluation of intraoperative ultrasound and mammography. The surgical margins of the two groups were judged by postoperative pathological results as the gold standard. RESULTS: The median waiting pathology results time in the frozen edge group was 64 minutes, while the waiting time in the freeze-free group was 30 minutes, and the difference was statistically significant (P < .0001). The postoperative pathological results showed that the positive rate of the surgical margin in the frozen edge group was 0.96%. The coincidence rate of intraoperative frozen and postoperative pathological results was 99.04%. The coincidence rate between intraoperative mammography and postoperative pathological results was 100%. CONCLUSIONS: In BCS, the method of using intraoperative staining markers combined with mammography to evaluate the resection margin is highly accurate, reliable, economical and convenient, and at the same time reduces the waiting time of the operator during the operation. However, this was not a randomized controlled study, and there was patient selection bias, and its safety needs to be confirmed by long-term follow-up. In the future, it is expected to become the mainstream means of evaluating.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Mastectomia Segmentar/métodos , Secções Congeladas/métodos , Estudos Retrospectivos , Margens de Excisão , Reprodutibilidade dos Testes
10.
Diagn Pathol ; 18(1): 60, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37161448

RESUMO

OBJECTIVES: Cancer metastasis to the kidney is a rare event. We retrospectively analyzed clinicopathologic characteristics in 6 cases of diagnosed renal metastases from primary lung cancer. We also provide clinical follow-up data and brief review of the literature. METHODS: Immunohistochemistry was used to evaluate the expression of TTF-1, NapsinA, CK7, CK(AE1/AE3), P63, P40, CgA, PAX-8, GATA3 and Ki-67 in primary tumor and metastases. Additionally, the clinical characteristics, imaging features, diagnosis, and treatment were analyzed. RESULTS: With the help of immunohistochemistry and combined clinical history, we found four cases were lung adenocarcinomas, one case was lung squamous cell carcinoma, and the other case was lung small cell carcinoma metastases to the kidney.The patients were all male by gender and had a mean age of 62 years, and metastasis to the left kidney were more universal. Most of the tumors histological grade originating from the lung were poorly-moderately differentiated, and the time to metastasis to the kidney was relatively short for squamous lung cancer and small cell lung cancer, while the time to metastasis for lung adenocarcinoma was related to its degree of differentiation. Overall, we found the prognosis of lung cancer patients with renal metastases were poor especially with multi-site metastases. CONCLUSIONS: Distinguishing primary and secondary tumors of the kidney is essential to guide treatment and prevent unnecessary surgery, so clinical information, radiology, histological correlation of the primary tumor, and immunohistochemical findings help the pathologist determine correct diagnosis.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Renais , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rim
11.
Front Immunol ; 14: 1199465, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37469520

RESUMO

Introduction: Lipid metabolic reprogramming is gaining attention as a hallmark of cancers. Recent mounting evidence indicates that the malignant behavior of breast cancer (BC) is closely related to lipid metabolism. Here, we focus on the estrogen receptor-positive (ER+) subtype, the most common subgroup of BC, to explore immunometabolism landscapes and prognostic significance according to lipid metabolism-related genes (LMRGs). Methods: Samples from The Cancer Genome Atlas (TCGA) database were used as training cohort, and samples from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), Gene Expression Omnibus (GEO) datasets and our cohort were applied for external validation. The survival-related LMRG molecular pattern and signature were constructed by unsupervised consensus clustering and least absolute shrinkage and selection operator (LASSO) analysis. A lipid metabolism-related clinicopathologic nomogram was established. Gene enrichment and pathway analysis were performed to explore the underlying mechanism. Immune landscapes, immunotherapy and chemotherapy response were further explored. Moreover, the relationship between gene expression and clinicopathological features was assessed by immunohistochemistry. Results: Two LMRG molecular patterns were identified and associated with distinct prognoses and immune cell infiltration. Next, a prognostic signature based on nine survival-related LMRGs was established and validated. The signature was confirmed to be an independent prognostic factor and an optimal nomogram incorporating age and T stage (AUC of 5-year overall survival: 0.778). Pathway enrichment analysis revealed differences in immune activities, lipid biosynthesis and drug metabolism by comparing groups with low- and high-risk scores. Further exploration verified different immune microenvironment profiles, immune checkpoint expression, and sensitivity to immunotherapy and chemotherapy between the two groups. Finally, arachidonate 15-lipoxygenase (ALOX15) was selected as the most prominent differentially expressed gene between the two groups. Its expression was positively related to larger tumor size, more advanced tumor stage and vascular invasion in our cohort (n = 149). Discussion: This is the first lipid metabolism-based signature with value for prognosis prediction and immunotherapy or chemotherapy guidance for ER+ BC.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Metabolismo dos Lipídeos , Prognóstico , Nomogramas , Lipídeos , Microambiente Tumoral
12.
J Zhejiang Univ Sci B ; 24(8): 711-722, 2023 Aug 15.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-37551557

RESUMO

Composite lymphoma (CL) involving B-cell lymphoma and T-cell lymphoma is extremely rare. Herein, we report three such cases using immunohistochemistry, flow cytometry, and the next-generation sequencing (NGS) to identify the pathological and molecular characteristics of CL. In the first case, the patient was admitted to hospital for generalized pruritic maculopapular rash over the whole body. An excisional biopsy of the skin lesions showed T-cell lymphoma. At the same time, the staging bone marrow (BM) biopsy revealed a diffuse large B-cell lymphoma (DLBCL). After R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapies, the patient produced a good response with substantial dissipation of the rashes and relief of skin. The other two patients were admitted to hospital due to lymphadenopathy and were diagnosed with DLBCL and follicular lymphoma (FL) after core needle biopsy of lymph nodes, BM biopsy, BM aspiration, and flow cytometry. Following R-CHOP and R-COP (rituximab, cyclophosphamide, vincristine, and prednisone) therapies, they achieved complete remission unconfirmed (CRu) and complete remission (CR). However, one or two years later, they suffered a relapse of lymphadenopathy. The shocking fact was that re-biopsy of lymphadenopathy revealed peripheral T-cell lymphoma (PTCL) and angioimmunoblastic T-cell lymphoma (AITL). NGS findings identified DNA methyltransferase 3a (DNMT3a), isocitrate dehydrogenase 2 (IDH2), Ras homolog gene family, member A (RHOA), splicing factor 3B subunit 1 (SF3B1), and tumor protein p53 (TP53) mutations. After immunochemotherapy, these patients achieved CRu and CR again. Nevertheless, they suffered a second relapse of T-cell lymphoma. Finally, they died due to progression of disease. We found that the occurrence of CL is associated with Epstein-Barr virus infection and DNMT3a, IDH2, and TP53 mutations, and the prognosis of the disease is closely related to the T-cell lymphoma components.


Assuntos
Infecções por Vírus Epstein-Barr , Linfadenopatia , Linfoma Difuso de Grandes Células B , Linfoma de Células T , Humanos , Rituximab/uso terapêutico , Vincristina/uso terapêutico , Prednisona/uso terapêutico , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Herpesvirus Humano 4 , Recidiva Local de Neoplasia , Linfoma de Células T/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Doxorrubicina/uso terapêutico , Linfadenopatia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
13.
Nat Commun ; 14(1): 3469, 2023 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-37328469

RESUMO

Fibroadenomas (FAs) are the most common breast tumors in women. No pharmacological agents are currently approved for FA intervention owing to its unclear mechanisms and a shortage of reproducible human models. Here, using single-cell RNA sequencing of human FAs and normal breast tissues, we observe distinct cellular composition and epithelial structural changes in FAs. Interestingly, epithelial cells exhibit hormone-responsive functional signatures and synchronous activation of estrogen-sensitive and hormone-resistant mechanisms (ERBB2, BCL2 and CCND1 pathways). We develop a human expandable FA organoid system and observe that most organoids seem to be resistant to tamoxifen. Individualized combinations of tamoxifen with ERBB2, BCL2 or CCND1 inhibitors could significantly suppress the viability of tamoxifen-resistant organoids. Thus, our study presents an overview of human FA at single-cell resolution that outlines the structural and functional differences between FA and normal breast epithelium and, in particular, provides a potential therapeutic strategy for breast FAs.


Assuntos
Neoplasias da Mama , Fibroadenoma , Feminino , Humanos , Fibroadenoma/tratamento farmacológico , Fibroadenoma/genética , Fibroadenoma/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Estrogênios , Células Epiteliais/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2
15.
J Clin Med ; 11(19)2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36233802

RESUMO

PURPOSE: This study sought to characterize the tumor immune microenvironment (TIME) of lung adenocarcinomas with ALK rearrangements (ALK+ LUAD), which responds poorly to immune checkpoint inhibitors (ICIs) therapy. MATERIALS AND METHODS: Immune score evaluation and immunohistochemical (IHC) validation of B cells, cytotoxic, helper, regulatory T cells, dendritic cells, and tumor-associated macrophages were performed on the TCGA cohort and the whole tissue sections of our matched surgical samples, respectively, between ALK+ and ALK- LUAD. The formation and spatial organization of TLS, intra- and extra-TLS immune cell features, and tumor PD-L1 expression were analyzed independently. RESULTS: Immune scores and TLS-signature gene levels were found to be lower in ALK+ TCGA LUAD. Quantitative IHC comparison confirmed the lower densities of TLS (0.10/mm2 vs. 0.34/mm2, p = 0.026) and intra-TLS immune cells (CD4+ helper T cells: 57.65/mm2 vs. 274.82/mm2, p = 0.026; CD8+ cytotoxic T cells: 22.46/mm2 vs. 172.83/mm2, p = 0.018; and CD20+ B cells: 36.08/mm2 vs. 207.29/mm2, p = 0.012) in ALK+ surgical samples. The TLS formation was negatively correlated with tumor progression in ALK+ tumors. The proportion of intra-TLS CD8+ cytotoxic T cells was the independent protective factors of node metastasis (HR: 0.599, 95% CI: 0.414-0.868, p = 0.007), and the density of intra-TLS CD20+ B cells was the independent protective factor of pStage (HR: 0.641, 95% CI: 0.446-0.922, p = 0.016). Tumors with intratumoral TLS showed significantly higher expression of PD-L1 (p = 0.029). CONCLUSION: ALK+ LUAD harbored a cold TIME featured by decreased TLS formation, which closely correlated to tumor progression and might contribute to the poor efficiency of ICIs.

16.
Ann Transl Med ; 8(7): 507, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32395551

RESUMO

A 49-year-old female undergoing a periodic health examination at other hospital revealed a mass in the tail of pancreas. The patient denied any personal history of surgery except subtotal hysterectomy because of multiple myomas in uterus 7 years ago, family history of abdominal cancer and trauma. Physical examination and laboratory finding (including tumor marker) were unremarkable. Chest X-ray result was normal. Contrast enhanced ultrasound (CEUS) examination showed a well-defined hypoechoic pancreatic mass which was suggestive of solid pseudopapillary tumor. Contrast enhanced computed tomography (CE-CT) of the abdomen revealed a mass of hypodensity suggestive of intraductal papillary mucinous neoplasm. Because of the risk of bleeding and exclusion of surgical contraindications, patient underwent laparoscopic surgery. Intraoperatively, a solid mass was identified in the tail of pancreas, the intraoperative frozen pathological examination suggested a heterotopic accessary spleen (HAS) with squamous epithelial cyst. Partial pancreatectomy was performed. The uniqueness of this case is that the spleen can be ectopic to the pancreas, what is even more unexpected is that the HAS undergone cystic change. When encountering a pancreatic mass, we need to think about the possibility of HAS. In conclusion, it is important to diagnose HAS with squamous cyst in the pancreatic tail presenting as other pancreatic masses.

17.
Front Oncol ; 10: 603127, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33312957

RESUMO

BACKGROUND: Sclerosing epithelioid fibrosarcoma (SEF) is an extremely rare, aggressive malignant subtype of fibrosarcoma. Only dozens of cases of primary SEF in the bone have been reported so far, without case involving fibula reported in literature to date. Herein we report the first case of primary SEF in the right fibula in a 19-year-old man. In this case report, we firstly give a comprehensive description of fibula SEF, including its complete clinical course and radiological findings. CASE PRESENTATION: A 19-year-old man presented with a half-year history of soreness in the right lower leg. Contrast-enhanced computed tomography (CE-CT) and magnetic resonance imaging (MRI) of the right lower leg were performed. Based on the radiological examinations, a diagnosis of malignant tumor arising in the fibular diaphysis was made. Final diagnosis of primary SEF in the right fibula was confirmed by histopathological and immunohistochemical examinations after surgical resection. The patient had no signs of recurrence or metastasis during a 24-month follow-up. CONCLUSION: We report an exceedingly rare case of primary SEF in the right fibula and its radiological features with CE-CT and MRI.

18.
Am J Clin Pathol ; 152(5): 582-589, 2019 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-31287861

RESUMO

OBJECTIVES: Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TLLGNPPA) is a relatively rare nasopharyngeal tumor. We performed morphological characterization, immunohistochemical profiling, and investigated gene mutations. We also provide clinical follow-up data and brief review of the literature. METHODS: Immunohistochemistry was used to evaluate the expression of TTF-1, CK19, CK7, EMA, TG, Pax-8, CK5/6, S100, and Ki-67. Additionally, in situ hybridization was utilized to identify the presence of EBV. We investigated mutations in hot-spot exons of KRAS/NRAS/BRAF to rule out common mutations seen in thyroid tumors. RESULTS: Histopathologic examination of four cases identified tumors that were mainly occupied by papillary architectures. One case had a predominantly glandular structure. The tumors expressed TTF-1 and CK19, while TG and Pax-8 were negative. S100 was moderately expressed focally in three cases. CONCLUSIONS: While TLLGNPPA displays a morphological resemblance to papillary thyroid carcinoma (PTC), it is vital to differentiate nasopharyngeal metastasis from PTC for appropriate treatment.


Assuntos
Adenocarcinoma Papilar/patologia , Neoplasias Nasofaríngeas/patologia , Câncer Papilífero da Tireoide , Adenocarcinoma Papilar/genética , Adenocarcinoma Papilar/cirurgia , Adulto , Biomarcadores Tumorais/análise , Proteínas de Ligação a DNA/análise , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Masculino , Mutação/genética , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/cirurgia , Proteínas S100/análise , Tomografia Computadorizada por Raios X , Fatores de Transcrição/análise
19.
Abdom Radiol (NY) ; 44(5): 1850-1857, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30694370

RESUMO

PURPOSE: The aim of this study was to investigate the effectiveness of contrast-enhanced ultrasound (CEUS) in predicting early nephropathy in cynomolgus macaques with spontaneous type 2 diabetes mellitus (T2DM). METHODS: Six cynomolgus macaques with spontaneous T2DM and six normal cynomolgus macaques (Group 1) were included in this study. The time-intensity curve was used to obtain parameters such as peak values, red blood volume (RBV), red blood flow (RBF), time to peak (TTP), and mean transit time (MTT). Biopsy renal tissue samples were assessed histopathologically. Six cynomolgus macaques with spontaneous T2DM were subgrouped into T2DM without nephropathy group (Group 2) and T2DM with nephropathy group (Group 3) based on histopathological findings. RESULTS: Peak value had the largest area under the curve comparing with RBF, RBV, TTP, MTT. The sensitivity and specificity of peak value with cut-off value of 38.65 dB for the diagnosis of DN were 98.3% and 83%, respectively. Peak value, RBV, and RBF in Group 3 was significantly decreased compared with Group 1 and Group 2 (P = 0.000, x2 = 23.99; P = 0.003, x2 = 9.14; P = 0.02, x2 = 5.14). CONCLUSIONS: The perfusion parameter of peak value in CEUS might be useful in predicting early diabetic nephropathy in spontaneous T2DM cynomolgus macaques.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas/diagnóstico por imagem , Ultrassonografia/métodos , Animais , Biomarcadores/sangue , Biomarcadores/urina , Biópsia com Agulha de Grande Calibre , Meios de Contraste , Processamento de Imagem Assistida por Computador , Macaca fascicularis , Masculino , Fosfolipídeos , Sensibilidade e Especificidade , Hexafluoreto de Enxofre
20.
Endokrynol Pol ; 70(6): 463-468, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31529457

RESUMO

INTRODUCTION: The aim of the study is to investigate the usefulness of ultrasound combined with computed tomography (CT) for distinguishing between primary thyroid lymphoma (PTL) and Hashimoto's thyroiditis (HT). MATERIAL AND METHODS: The investigation was conducted retrospectively in 80 patients from January 2000 to July 2018. All patients underwent pathological tests to be classified into one of two groups: PTL group and HT group. The cut-off value of CT density was determined using receiver-operating characteristic (ROC) curve analysis. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of diagnosis for thyroid by CT alone, ultrasound alone, and the combination of CT plus ultrasound were calculated. RESULTS: Of the 80 study patients, 27 patients were PTL and 53 patients were HT. Mean CT density had a sensitivity of 90.6% and a specificity of 88.9% at a cut-off value of 53.5 HU, with area under the curve (AUC) 0.88. Ultrasound combined with CT had the highest specificity, accuracy, and PPV compared with CT alone and ultrasound alone (p value < 0.05). CONCLUSIONS: Features such as extremely hypoechogenicity, enhanced posterior echo, cervical lymphadenopathy in ultrasound image, and linear high-density strand signs, and very low density in CT imaging have high sensitivity and specificity in thyroid lymphoma. Therefore, ultrasound combined with CT may be useful for distinguishing between PTL and HT.


Assuntos
Doença de Hashimoto/diagnóstico , Linfoma/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Tomografia Computadorizada por Raios X , Ultrassonografia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Doença de Hashimoto/diagnóstico por imagem , Humanos , Linfoma/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/diagnóstico por imagem
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