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Soft tissue sarcomas harboring EWSR1::PATZ1 are a recently recognized entity with variable morphology and a heterogeneous immunohistochemical profile. We studied 17 such tumors. The tumors occurred in 12 men and 5 women (median age, 50 years; range, 15-71 years), involved the thoracoabdominal soft tissues (14 cases; 82%), lower extremities (2 cases; 12%), and tongue (1 case; 6%), and ranged from 0.7 to 11.3 cm (median, 4.7 cm). All but 1 patient received complete surgical resection; 7 were also treated with neoadjuvant chemo/radiotherapy. All cases showed typical features of EWSR1::PATZ1 sarcoma, including uniform round to spindled cells, fibromyxoid matrix, fibrous bands, hyalinized vessels, and pseudoalveolar/microcystic spaces. Unusual features, seen in a subset of cases, included degenerative-appearing nuclear atypia, epithelioid cytomorphology, mature fat, abundant rhabdomyoblasts, high mitotic activity, and foci with increased cellularity and nuclear atypia. Positive immunohistochemical results were desmin (16/17, 94%), MyoD1 (13/14, 93%), myogenin (6/14, 43%), GFAP (10/10, 100%), S100 protein (15/17, 88%), SOX10 (7/13, 54%), keratin (10/17, 59%), CD99 (4/11, 36%), H3K27me3 (retained expression 9/9, 100%), p16 (absent expression 1/4, 25%), and p53 (wild type 3/3, 100%). Fusion events included EWSR1 exon 8::PATZ1 exon 1 (14/17, 82%), EWSR1 exon 9::PATZ1 exon 1 (2/17, 12%), and EWSR1 exon 7::PATZ1 exon 1 (1/17, 6%). No evaluated tumor had alterations of CDKN2A/B and/or TP53, or MDM2 amplification. Clinical follow-up (16 patients: median, 13.5 months; range, 1-77 months) showed distant metastases in 3 patients (1/3 at time of presentation) and no local recurrences. At the time of last follow-up, 14 patients were disease free, 1 was alive with disease, 1 was dead of disease (at 13 months), and 1 had an indeterminant pulmonary nodule. We conclude that the morphologic spectrum of EWSR1::PATZ1 is broader than has been previously appreciated. Although more long-term follow-up is needed, the prognosis of these very rare sarcomas may be more favorable than previously reported.
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Sarcoma , Neoplasias de Tecidos Moles , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Sarcoma/genética , Sarcoma/terapia , Sarcoma/patologia , Fatores de Transcrição , Proteína EWS de Ligação a RNA/genética , Proteínas S100 , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/terapia , Neoplasias de Tecidos Moles/patologia , Prognóstico , Biomarcadores Tumorais/genética , Proteínas Repressoras/genética , Fatores de Transcrição Kruppel-LikeRESUMO
BACKGROUND: Atypical intradermal smooth muscle neoplasm, also commonly termed cutaneous leiomyosarcoma, is a soft tissue tumor with a low risk of aggressive behavior. These lesions arise in the dermis with possible superficial subcutaneous extension, demonstrate cytologic atypia, and often show mitotic activity. METHODS: A retrospective review of patient demographics, tumor characteristics, and treatment methods was conducted in a consecutive series of patients presenting to MD Anderson Cancer Center (MDACC) from 2002 to 2021 (n = 95). All pathology was reviewed by MDACC pathologists and determined to be atypical intradermal smooth muscle neoplasm. RESULTS: Median age at diagnosis was 58 years (range 22-86), and 74% were male. Ninety-five percent (n = 90) of patients identified as White, non-Hispanic. Most tumors were slow-growing, solitary, and painless nodules. Tumors were in the lower extremities (44.2%), followed by the upper extremity (28.4%), trunk (22.1%), and head and neck (5.2%). All patients (n = 44, 46.3%) who had a punch/incisional biopsy for diagnostic purposes had a subsequent tumor excision. Unplanned excision or excisional biopsy was performed on the remaining 46 (48%) patients. Of this subset, 41 of the 46 aforementioned patients (89%) had positive margins and underwent re-excision. Final pathology in 25/38 (66%) re-excision specimens was negative for residual tumor despite an initial positive margin. Two patients in the cohort had local recurrence 2 and 3 years after initial surgery. Both patients had positive margins, underwent excision of the recurrent tumor, and remain free of disease. After median follow-up of 6.9 years (range 1 day-18 years), 5-year recurrence-free survival was 96% and overall survival (OS) of the entire cohort was 78%. CONCLUSION: In this study of consecutive patients presenting with atypical intradermal smooth muscle neoplasm, we found good OS and local control after definitive surgical excision with negative margins, including excisional biopsy with close margins. Atypical intradermal smooth muscle neoplasm is unlikely to metastasize and has an excellent prognosis. Guidelines to determine optimal surveillance strategies for these patients should be revisited.
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Intraoperative delineation of tumor margins is critical for effective pancreatic cancer surgery. Yet, intraoperative frozen section analysis of tumor margins is a time-consuming and often challenging procedure that can yield confounding results due to histologic heterogeneity and tissue-processing artifacts. We have previously described the development of the MasSpec Pen technology as a handheld mass spectrometry-based device for nondestructive tissue analysis. Here, we evaluated the usefulness of the MasSpec Pen for intraoperative diagnosis of pancreatic ductal adenocarcinoma based on alterations in the metabolite and lipid profiles in in vivo and ex vivo tissues. We used the MasSpec Pen to analyze 157 banked human tissues, including pancreatic ductal adenocarcinoma, pancreatic, and bile duct tissues. Classification models generated from the molecular data yielded an overall agreement with pathology of 91.5%, sensitivity of 95.5%, and specificity of 89.7% for discriminating normal pancreas from cancer. We built a second classifier to distinguish bile duct from pancreatic cancer, achieving an overall accuracy of 95%, sensitivity of 92%, and specificity of 100%. We then translated the MasSpec Pen to the operative room and predicted on in vivo and ex vivo data acquired during 18 pancreatic surgeries, achieving 93.8% overall agreement with final postoperative pathology reports. Notably, when integrating banked tissue data with intraoperative data, an improved agreement of 100% was achieved. The result obtained demonstrate that the MasSpec Pen provides high predictive performance for tissue diagnosis and compatibility for intraoperative use, suggesting that the technology may be useful to guide surgical decision-making during pancreatic cancer surgeries.
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Tecnologia Biomédica , Margens de Excisão , Espectrometria de Massas , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Idoso , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Ducto Colédoco/patologia , Ducto Colédoco/cirurgia , Feminino , Humanos , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Pâncreas/patologia , Pâncreas/cirurgia , Neoplasias Pancreáticas/patologia , Estatística como AssuntoRESUMO
Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia characterized by granulomatous lesions containing pathological CD207+ dendritic cells (DCs) with persistent MAPK pathway activation. Standard-of-care chemotherapies are inadequate for most patients with multisystem disease, and optimal strategies for relapsed and refractory disease are not defined. The mechanisms underlying development of inflammation in LCH lesions, the role of inflammation in pathogenesis, and the potential for immunotherapy are unknown. Analysis of the immune infiltrate in LCH lesions identified the most prominent immune cells as T lymphocytes. Both CD8+ and CD4+ T cells exhibited "exhausted" phenotypes with high expression of the immune checkpoint receptors. LCH DCs showed robust expression of ligands to checkpoint receptors. Intralesional CD8+ T cells showed blunted expression of Tc1/Tc2 cytokines and impaired effector function. In contrast, intralesional regulatory T cells demonstrated intact suppressive activity. Treatment of BRAFV600ECD11c LCH mice with anti-PD-1 or MAPK inhibitor reduced lesion size, but with distinct responses. Whereas MAPK inhibitor treatment resulted in reduction of the myeloid compartment, anti-PD-1 treatment was associated with reduction in the lymphoid compartment. Notably, combined treatment with MAPK inhibitor and anti-PD-1 significantly decreased both CD8+ T cells and myeloid LCH cells in a synergistic fashion. These results are consistent with a model that MAPK hyperactivation in myeloid LCH cells drives recruitment of functionally exhausted T cells within the LCH microenvironment, and they highlight combined MAPK and checkpoint inhibition as a potential therapeutic strategy.
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Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Histiocitose de Células de Langerhans/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Modelos Animais de Doenças , Sinergismo Farmacológico , Histiocitose de Células de Langerhans/patologia , Humanos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidoresRESUMO
AIMS: NUTM1-rearranged sarcoma is an emerging entity that differs from NUT carcinoma at the molecular level, with most of the former tumours harbouring fusions involving genes in the MYC-associated factor X dimerization (MAD) transcription family (MXD1, MXD4, MXI1 [or MXD2], and MGA). MGA::NUTM1 is one of the most recently described novel gene fusions associated with NUTM1-rearranged sarcoma. Herein we describe the clinicopathologic features of three sarcomas with an MGA::NUTM1 fusion. METHODS AND RESULTS: The three study patients were male, with an age range of 10-28 years. The tumour sites were deep soft tissue of the thigh, the chest wall, and the pelvis. All three tumours were aggressive, with multiple recurrences and metastases. Histologically, the tumours were composed of monotonous spindle, round, or epithelioid cells in variably hyalinized stroma and prominent aggregates of amianthoid fibre-like collagen or collagen rosettes. Mitotic activity was relatively low (5-12 mitotic figures per 10 hhpf). All tumours tested expressed NUT, with one tumour having S100 protein expression and two tumours having CD99 and CD56 expression. The genetic breakpoints were MGA exon 21, MGA exon 22, and NUTM1 exon 3. CONCLUSION: MGA::NUTM1 sarcoma often exhibits hyalinized stroma with amianthoid fibre-like collagen or collagen rosettes in the presence of monotonous round, epithelioid, or spindle cell morphology. NUT immunohistochemistry and molecular testing can help confirm the diagnosis.
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Sarcoma , Neoplasias de Tecidos Moles , Humanos , Masculino , Criança , Adolescente , Adulto Jovem , Adulto , Feminino , Proteínas de Neoplasias/genética , Fatores de Transcrição/genética , Sarcoma/genética , Sarcoma/patologia , Fusão Gênica , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Colágeno , Proteínas de Fusão Oncogênica/genética , Proteínas Repressoras/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genéticaRESUMO
Oropharyngeal squamous cell carcinoma (OPSCC), largely fueled by the human papillomavirus (HPV), has a complex biological and immunologic phenotype. Although HPV/p16 status can be used to stratify OPSCC patients as a function of survival, it remains unclear what drives an improved treatment response in HPV-associated OPSCC and whether targetable biomarkers exist that can inform a precision oncology approach. We analyzed OPSCC patients treated between 2000 and 2016 and correlated locoregional control (LRC), disease-free survival (DFS) and overall survival (OS) with conventional clinical parameters, risk parameters generated using deep-learning algorithms trained to quantify tumor-infiltrating lymphocytes (TILs) (OP-TIL) and multinucleated tumor cells (MuNI) and targeted transcriptomics. P16 was a dominant determinant of LRC, DFS and OS, but tobacco exposure, OP-TIL and MuNI risk features correlated with clinical outcomes independent of p16 status and the combination of p16, OP-TIL and MuNI generated a better stratification of OPSCC risk compared to individual parameters. Differential gene expression (DEG) analysis demonstrated overlap between MuNI and OP-TIL and identified genes involved in DNA repair, oxidative stress response and tumor immunity as the most prominent correlates with survival. Alteration of inflammatory/immune pathways correlated strongly with all risk features and oncologic outcomes. This suggests that development of OPSCC consists of an intersection between multiple required and permissive oncogenic and immunologic events which may be mechanistically linked. The strong relationship between tumor immunity and oncologic outcomes in OPSCC regardless of HPV status may provide opportunities for further biomarker development and precision oncology approaches incorporating immune checkpoint inhibitors for maximal anti-tumor efficacy.
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Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Inibidor p16 de Quinase Dependente de Ciclina/análise , Humanos , Neoplasias Orofaríngeas/patologia , Papillomaviridae , Infecções por Papillomavirus/patologia , Medicina de Precisão , Prognóstico , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
Thyroid neoplasia is common and requires appropriate clinical workup with imaging and fine-needle aspiration (FNA) biopsy to evaluate for cancer. Yet, up to 20% of thyroid nodule FNA biopsies will be indeterminate in diagnosis based on cytological evaluation. Genomic approaches to characterize the malignant potential of nodules showed initial promise but have provided only modest improvement in diagnosis. Here, we describe a method using metabolic analysis by desorption electrospray ionization mass spectrometry (DESI-MS) imaging for direct analysis and diagnosis of follicular cell-derived neoplasia tissues and FNA biopsies. DESI-MS was used to analyze 178 tissue samples to determine the molecular signatures of normal, benign follicular adenoma (FTA), and malignant follicular carcinoma (FTC) and papillary carcinoma (PTC) thyroid tissues. Statistical classifiers, including benign thyroid versus PTC and benign thyroid versus FTC, were built and validated with 114,125 mass spectra, with accuracy assessed in correlation with clinical pathology. Clinical FNA smears were prospectively collected and analyzed using DESI-MS imaging, and the performance of the statistical classifiers was tested with 69 prospectively collected clinical FNA smears. High performance was achieved for both models when predicting on the FNA test set, which included 24 nodules with indeterminate preoperative cytology, with accuracies of 93% and 89%. Our results strongly suggest that DESI-MS imaging is a valuable technology for identification of malignant potential of thyroid nodules.
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Espectrometria de Massas por Ionização por Electrospray/métodos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/metabolismo , Biópsia por Agulha Fina , Feminino , Humanos , Masculino , Estudos Prospectivos , Neoplasias da Glândula Tireoide/metabolismo , Nódulo da Glândula Tireoide/química , Nódulo da Glândula Tireoide/diagnóstico por imagemRESUMO
BACKGROUND: Intraoperative tissue analysis and identification are critical to guide surgical procedures and improve patient outcomes. Here, we describe the clinical translation and evaluation of the MasSpec Pen technology for molecular analysis of in vivo and freshly excised tissues in the operating room (OR). METHODS: An Orbitrap mass spectrometer equipped with a MasSpec Pen interface was installed in an OR. A "dual-path" MasSpec Pen interface was designed and programmed for the clinical studies with 2 parallel systems that facilitated the operation of the MasSpec Pen. The MasSpec Pen devices were autoclaved before each surgical procedure and were used by surgeons and surgical staff during 100 surgeries over a 12-month period. RESULTS: Detection of mass spectral profiles from 715 in vivo and ex vivo analyses performed on thyroid, parathyroid, lymph node, breast, pancreatic, and bile duct tissues during parathyroidectomies, thyroidectomies, breast, and pancreatic neoplasia surgeries was achieved. The MasSpec Pen enabled gentle extraction and sensitive detection of various molecular species including small metabolites and lipids using a droplet of sterile water without causing apparent tissue damage. Notably, effective molecular analysis was achieved while no limitations to sequential histologic tissue analysis were identified and no device-related complications were reported for any of the patients. CONCLUSIONS: This study shows that the MasSpec Pen system can be successfully incorporated into the OR, allowing direct detection of rich molecular profiles from tissues with a seconds-long turnaround time that could be used to inform surgical and clinical decisions without disrupting tissue analysis workflows.
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Neoplasias Pancreáticas , Humanos , Espectrometria de Massas , Paratireoidectomia , Glândula TireoideRESUMO
Extramammary Paget disease of the vulva accounts for 1%2% of the neoplasms of the anogenital area. Very rarely, extramammary Paget disease of the vulva has been associated with an underlying mammary-like carcinoma, usually ductal, extremely rarely mixed ductal and lobular. We report the case of a 60-year-old female with a recurrent extramammary Paget disease of the vulva. Pathological examination of the wide excision of the vulva revealed an extramammary Paget disease with an underlying invasive carcinoma composed of medium size cells organized in single files, a morphology similar to that of an invasive lobular breast carcinoma. Immunohistochemical staining showed a comparable profile in the Paget cells and in the invasive tumoral cells: CEA and CK7 positivity; GCDFP-15, ER focal positivity. E-cadherin and HER2 were diffusely positive. S100 and CK20 were negative. HER2-CISH was amplified. The diagnosis of extramammary Paget disease of the vulva with an underlying mammary-like lobular carcinoma was made. Despite the characteristic lobular features, the immunohistochemical profile differs from the typical profile of a lobular carcinoma of the breast. The implications in term of prognostic and therapeutic significance need to be further studied.
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Neoplasias da Mama , Carcinoma Lobular/patologia , Coristoma/patologia , Glândulas Mamárias Humanas , Doença de Paget Extramamária/patologia , Neoplasias Vulvares/patologia , Animais , Biomarcadores Tumorais/análise , Biópsia , Carcinoma Lobular/química , Coristoma/metabolismo , Coristoma/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Doença de Paget Extramamária/química , Doença de Paget Extramamária/cirurgia , Neoplasias Vulvares/química , Neoplasias Vulvares/cirurgiaRESUMO
INTRODUCTION: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was introduced in 2018 to standardize cytology reporting and guide patient treatment. We aimed to evaluate the utility of this system applied to patients at our cancer center. MATERIALS AND METHODS: We retrospectively reviewed cases of salivary gland fine-needle aspirations (FNAs) performed in our institution (2019-2022). All were performed by radiologists and immediately assessed for specimen adequacy. The cytologic findings were classified into the MSRSGC except for non-mucinous cystic contents (NMCC) where the lesion was radiologically consistent with a cyst and totally collapsed after FNA. Such lesions were categorized as non-neoplastic (NN) instead of non-diagnostic (ND). The cytologic findings were compared to corresponding histologic findings (212 available cases), and the risk of malignancy was calculated. RESULTS: Five hundred five FNAs were categorized as: 25 (4.95%) ND; 86 (17.03%) NN, of which 39 were NMCC; 9 (1.78%) atypia of undetermined significance; 138 (27.33%) benign neoplasms; 57 (11.29%) salivary gland neoplasm of undetermined malignant potential; 16 (3.17%) suspicious for malignancy; and 174 (34.46%) malignant. The risk of malignancy rates for the following categories were: ND, 40%; NN, 25%; atypia of undetermined significance, 0%; benign neoplasms, 1%; salivary gland neoplasm of undetermined malignant potential, 54.54%; suspicious for malignancy, 90.9%; and malignant, 100%. Thirty-one NMCC with available follow-up resolved/remained stable. CONCLUSIONS: Our results validate the reproducibility of the MSRSGC applied in our cancer center. Based on the benign course of cysts with NMCC, we propose that such cases be categorized as NN, provided the cyst is totally resolved after FNA.
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Cistos , Neoplasias das Glândulas Salivares , Humanos , Estudos Retrospectivos , Reprodutibilidade dos Testes , Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/patologia , Cistos/patologiaRESUMO
Sclerosing epithelioid fibrosarcoma (SEF) is a distinctive sarcoma that may arise in nearly any soft tissue site or bone. While there has been past controversy as to whether it is related to low-grade fibromyxoid sarcoma (LGFMS), it has been shown to behave far more aggressively than LGFMS. SEF has a propensity to metastasize to the lungs and bone and arise within the abdominal cavity. Histologically, it is characterized by uniform nuclei embedded in a densely collagenous stroma simulating osteoid. By immunohistochemistry, it is often strongly positive for MUC4. The majority (75%) have EWSR1 gene rearrangement, most commonly with CREB3L1 as a fusion partner, although a variety of FUS/EWSR1 and CREB3L1/CREB3L2/CREB3L3 fusions have been described in addition to others. SEF is currently recalcitrant to nearly all chemotherapy and radiation therapy.
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Fibrossarcoma , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Fibrossarcoma/diagnóstico , Fibrossarcoma/genética , Fibrossarcoma/patologia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Biomarcadores Tumorais/genéticaRESUMO
Urban green space (UGS) was widely regarded as an effective nature-based solution to mitigate the urban heat island (UHI) effect, therefore, developing landscape strategies to enhance its cooling intensity (CI) is crucial. However, two main problems prevent the application of results to practical actions: one is the inconsistency of relationships between influencing factors of landscape and the thermal environment; another is the unfeasibility of some common conclusions such as simply increasing the amount of vegetation cover in highly-urbanized areas. This study compared the CIs of UGSs, investigated the influencing factors of CI and identified the absolute threshold of cooling (ToCabs) of the influencing factors in four Chinese cities with very different climatic backgrounds (Hohhot, Beijing, Shanghai and Haikou). Results demonstrate that local climate condition affects the cooling effect of UGS. The CI of UGS is weaker in cities with humid and hot summer than in cities with dry and hot summer. Patch characteristics (area and shape), the percentage of water bodies within the UGS (Pland_w) and neighboring greenspace (NGP), vegetation abundance (NDVI) and planting structure together can explain a significant proportion (R2 = 0.403-0.672, p < 0.001) of the CI variations of UGS. The inclusion of water bodies can ensure effective cooling of UGS, except in the tropical city. Besides, ToCabs of area (Hohhot, 2.6 ha; Beijing, 5.9 ha; Shanghai, 4.0 and Haikou, 5.3 ha), and NGP (Hohhot, 8.5 %; Beijing, 21.6 %; and Shanghai, 23.5 %), NDVI (Hohhot, 0.31; Beijing, 0.33; and Shanghai, 0.39) were identified and related landscape strategies of cooling were proposed. The identification of ToCabs values can provide easy-to-use landscape recommendations to UHI mitigation.
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Temperatura Alta , Parques Recreativos , Cidades , China , ÁguaRESUMO
Importance: Intraoperative identification of tissues through gross inspection during thyroid and parathyroid surgery is challenging yet essential for preserving healthy tissue and improving outcomes for patients. Objective: To evaluate the performance and clinical applicability of the MasSpec Pen (MSPen) technology for discriminating thyroid, parathyroid, and lymph node tissues intraoperatively. Design, Setting, and Participants: In this diagnostic/prognostic study, the MSPen was used to analyze 184 fresh-frozen thyroid, parathyroid, and lymph node tissues in the laboratory and translated to the operating room to enable in vivo and ex vivo tissue analysis by endocrine surgeons in 102 patients undergoing thyroidectomy and parathyroidectomy procedures. This diagnostic study was conducted between August 2017 and March 2020. Fresh-frozen tissues were analyzed in a laboratory. Clinical analyses occurred in an operating room at an academic medical center. Of the analyses performed on 184 fresh-frozen tissues, 131 were included based on sufficient signal and postanalysis pathologic diagnosis. From clinical tests, 102 patients undergoing surgery were included. A total of 1015 intraoperative analyses were performed, with 269 analyses subject to statistical classification. Statistical classifiers for discriminating thyroid, parathyroid, and lymph node tissues were generated using training sets comprising both laboratory and intraoperative data and evaluated on an independent test set of intraoperative data. Data were analyzed from July to December 2022. Main Outcomes and Measures: Accuracy for each tissue type was measured for classification models discriminating thyroid, parathyroid, and lymph node tissues using MSPen data compared to gross analysis and final pathology results. Results: Of the 102 patients in the intraoperative study, 80 were female (78%) and the median (IQR) age was 52 (42-66) years. For discriminating thyroid and parathyroid tissues, an overall accuracy, defined as agreement with pathology, of 92.4% (95% CI, 87.7-95.4) was achieved using MSPen data, with 82.6% (95% CI, 76.5-87.4) accuracy achieved for the independent test set. For distinguishing thyroid from lymph node and parathyroid from lymph node, overall training set accuracies of 97.5% (95% CI, 92.8-99.1) and 96.1% (95% CI, 91.2-98.3), respectively, were achieved. Conclusions and Relevance: In this study, the MSPen showed high performance for discriminating thyroid, parathyroid, and lymph node tissues intraoperatively, suggesting this technology may be useful for providing near real-time feedback on tissue type to aid in surgical decision-making.
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Glândulas Paratireoides , Glândula Tireoide , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Glândulas Paratireoides/cirurgia , Glândula Tireoide/cirurgia , Paratireoidectomia , Tireoidectomia/métodos , PrognósticoRESUMO
Phylogeographic research concerning Central China has been rarely conducted. Population genetic and phylogeography of Ziziphus jujuba var. spinosa (also called sour jujube) were investigated to improve our understanding of plant phylogeographic patterns in Central China. Single-copy nuclear gene markers and complete chloroplast genome data were applied to 328 individuals collected from 21 natural populations of sour jujube in China. Nucleotide variation of sour jujube was relatively high (π = 0.00720, θ w = 0.00925), which resulted from the mating system and complex population dynamics. Analysis of molecular variation analysis revealed that most of the total variation was attributed to variation within populations, and a high level of genetic differentiation among populations was detected (F st = 0.197). Relatively low long-distance dispersal capability and vitality of pollen contributed to high genetic differentiation among populations. Differences in the environmental conditions and long distance among populations further restricted gene flow. Structure clustering analysis uncovered intraspecific divergence between central and marginal populations. Migrate analysis found a high level of gene flow between these two intraspecific groups. Bayesian skyline plot detected population expansion of these two intraspecific groups. Network and phylogeny analysis of chloroplast haplotypes also found intraspecific divergence, and the divergence time was estimated to occur at about 55.86 Ma. Haplotype native to the Loess Plateau was more ancient, and multiple glacial refugia of sour jujube were found to locate at the Loess Plateau, areas adjacent to the Qinling Mountains and Tianmu Mountains. Species distribution model analysis found a typical contraction-expansion model corresponding to the Quaternary climatic oscillations. In the future, the distribution of sour jujube may shift to high-latitude areas. This study provides new insights for phylogeographic research of temperate plant species distributed in Central China and sets a solid foundation for the application of the scientific management strategy of Z. jujuba var. spinosa.
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When a sarcomatous neoplasm is identified in the breast, distinguishing metaplastic carcinoma, malignant phyllodes tumor (MPT), and primary sarcoma is a diagnostic challenge, especially on small biopsies, as all these tumors may have overlapping morphological features, thoroughly grossing with histological examination and immunohistochemical staining being the standard approach to aid in classifying these lesions. Recently, we identified a highly sensitive and specific breast carcinoma marker TRPS1 with high expression in metaplastic breast carcinoma. In the current study, we tested TRPS1 in MPTs and primary sarcoma of the breast. We found TRPS1 was highly expressed (95%) within spindle cell, chondro-osseous, and/or liposarcomatous components of MPTs, in all breast primary chondrosarcomas and extraskeletal osteosarcomas, but not in other sarcomas of the breast. In extramammary sarcomas, TRPS1 was expressed in 28% of conventional chondrosarcomas and 56% of osteosarcomas of bone, but rarely in undifferentiated pleomorphic sarcomas (UPSs), liposarcomas, and angiosarcomas. In summary, MPTs may share similar genetic background with metaplastic carcinoma exhibiting TRPS1 expression, and TRPS1 may play a role in chondro-osseous differentiation because of its expression in chondro-osseous sarcomas from both breast and extramammary sites. Our findings suggest TRPS1 may be clinically useful in distinguishing MPT and metaplastic carcinoma from primary breast sarcoma except for tumors with chondro-osseous differentiation.
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Neoplasias Ósseas , Neoplasias da Mama , Carcinoma , Condrossarcoma , Osteossarcoma , Tumor Filoide , Sarcoma , Neoplasias de Tecidos Moles , Neoplasias Ósseas/genética , Neoplasias da Mama/patologia , Carcinoma/patologia , Condrossarcoma/genética , Feminino , Dedos/anormalidades , Doenças do Cabelo , Humanos , Síndrome de Langer-Giedion , Nariz/anormalidades , Tumor Filoide/patologia , Proteínas Repressoras , Sarcoma/patologiaRESUMO
SIGNIFICANCE: Comprehensive single-cell proteomics analyses of lung adenocarcinoma progression reveal the role of tumor-associated macrophages in resistance to PD-1 blockade therapy. See related commentary by Lee et al., p. 2515.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/patologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Macrófagos , Microambiente TumoralAssuntos
Ácido Aspártico/análogos & derivados , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/diagnóstico , Técnicas de Laboratório Clínico/instrumentação , Salas Cirúrgicas/tendências , Espectrometria de Massas por Ionização por Electrospray , Ácido Aspártico/análise , Neoplasias Encefálicas/cirurgia , Técnicas de Laboratório Clínico/tendências , Humanos , Salas Cirúrgicas/organização & administração , Sensibilidade e EspecificidadeRESUMO
This study examines local residents' place attachment (PA) to the city or town they live and investigates how this attachment influences their perceptions and support for tourism development (ST), as well as comparing the differences of these relationships among the city and town residents in a linear World Heritage Site (WHS) setting. Structural equation model was used to analyze samples of 226 city residents and 235 town residents along the Grand Canal Yangzhou Section, China. The findings suggested that residents' PA is positively correlated their ST. Results also suggested that the PA-ST effect is partially mediated by residents' positive perceptions in the city area while fully mediated by residents' positive and negative perceptions in the town areas. This study could help local governments make heritage development and management policies accordingly for cities and towns along the Grand Canal area.
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Turismo , Cidades , Conservação dos Recursos NaturaisRESUMO
BACKGROUND: The purpose of this study is to describe human epidermal growth factor 2 (HER2) overexpression in head and neck squamous cell carcinoma (HNSCC) and re-evaluate its potential as a target for HER2-directed immunotherapies. METHODS: A retrospective cohort of patients with HNSCC receiving curative treatment was identified, and HER2 expression evaluated in archival tissue by immunohistochemistry and correlated with clinicopathological characteristics. HER2 expression data were also determined for HNSCC patients in The Cancer Genome Atlas. RESULTS: Nineteen percent of HNSCC and 39% of oropharyngeal HNSCC (OPSCC) were HER2 positive. HER2 expression positively correlated with nodal metastasis (p = 0.035). Patients with HER2-positive tumors had decreased overall survival (p = 0.012), including within the human papilloma virus-positive OPSCC subgroup (p = 0.007). CONCLUSIONS: A substantial fraction of HNSCC overexpresses HER2 protein, suggesting it may be a suitable target for antigen-directed immunotherapy. HER2 expression and its correlation with survival vary across HNSCC subsites, making it unsuitable as a prognostic marker.