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Endocervical adenocarcinomas (EACs) are a group of malignant neoplasms associated with diverse pathogenesis, morphology, and clinical behavior. As a component of the International Society of Gynecological Pathologists International Endocervical Adenocarcinoma Project, a large international retrospective cohort of EACs was generated in an effort to study potential clinicopathological features with prognostic significance that may guide treatment in these patients. In this study, we endeavored to develop a robust human papillomavirus (HPV)-associated EAC prognostic model for surgically treated International Federation of Gynecology and Obstetrics (FIGO) stage IA2 to IB3 adenocarcinomas incorporating patient age, lymphovascular space invasion (LVSI) status, FIGO stage, and pattern of invasion according to the Silva system (traditionally a 3-tier system). Recently, a 2-tier/binary Silva pattern of invasion system has been proposed whereby adenocarcinomas are classified into low-risk (pattern A/pattern B without LVSI) and high-risk (pattern B with LVSI/pattern C) categories. Our cohort comprised 792 patients with HPV-associated EAC. Multivariate analysis showed that a binary Silva pattern of invasion classification was associated with recurrence-free and disease-specific survival (P < 0.05) whereas FIGO 2018 stage I substages were not. Evaluation of the current 3-tiered system showed that disease-specific survival for those patients with pattern B tumors did not significantly differ from that for those patients with pattern C tumors, in contrast to that for those patients with pattern A tumors. These findings underscore the need for prospective studies to further investigate the prognostic significance of stage I HPV-associated EAC substaging and the inclusion of the binary Silva pattern of invasion classification (which includes LVSI status) as a component of treatment recommendations.
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Adenocarcinoma , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/classificação , Estudos Retrospectivos , Adenocarcinoma/patologia , Adenocarcinoma/virologia , Adenocarcinoma/classificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/diagnóstico , Pessoa de Meia-Idade , Adulto , Prognóstico , Idoso , Papillomaviridae/isolamento & purificação , Patologistas , Estadiamento de Neoplasias , Ginecologia , Papillomavirus HumanoRESUMO
OBJECTIVES: A focal intimal disruption (FID) is a risk factor for adverse aorta-related events in patients with acute type B intramural haematoma. This study evaluated the impact of FIDs on overall survival with a selective intervention strategy for large or growing FIDs. Additionally, this study evaluated the risk factors associated with the growth of FIDs. METHODS: This retrospective study included all consecutive patients admitted for acute type B intramural haematomas between November 2004 and April 2021. The primary outcome was overall survival. The secondary outcome was the cumulative incidence of composite aortic events and the growth of FIDs. The latter was calculated on centreline-reconstructed computed tomography images. RESULTS: A total of 105 patients were included. A total of 106 FIDs were identified in 73 patients (73/105, 69.5%). The 1- and 5-year cumulative incidence rates of composite aortic events were 36.2% and 39.2%, respectively. The 1- and 5-year overall survival was 93.3% and 81.5%, respectively. Initial maximal aortic diameter and large FIDs during acute phase were significant risk factors for composite aortic events, but not risk factors for overall survival. The early appearance interval of an FID was a significant risk factor for growth of an FID. CONCLUSIONS: With a selective intervention strategy for large or growing FIDs, the presence of large FIDs during the acute phase does not affect overall survival. The early appearance interval was associated with the growth of FIDs.
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Hematoma , Humanos , Masculino , Estudos Retrospectivos , Feminino , Hematoma/epidemiologia , Hematoma/etiologia , Idoso , Pessoa de Meia-Idade , Fatores de Risco , Túnica Íntima/patologia , Túnica Íntima/diagnóstico por imagem , Doença Aguda , Tomografia Computadorizada por Raios X , Idoso de 80 Anos ou mais , Doenças da Aorta/epidemiologiaRESUMO
BACKGROUND: Reports of intravascular thrombosis and cardiac complications have raised concerns about the safety of COVID-19 vaccinations, particularly in patients with high cardiovascular risk. Herein, we aimed to analyze the impact of preoperative COVID-19 vaccination on outcomes after coronary artery bypass grafting (CABG). METHODS AND RESULTS: Among 520 patients who underwent isolated CABG from 2020 to 2022, 481 patients (mean±SD age: 67±11 years, 86 women) whose COVID-19 vaccination status could be confirmed were included. A total of 249 patients who had not received any COVID-19 vaccine before CABG (never vaccinated group) and 214 patients who had completed primary vaccination (fully vaccinated group) were subjected to 1:1 propensity score matching, and 156 pairs of patients were matched. There was no significant difference in early mortality between the 2 groups after matching. After matching, overall survival (P=0.930) and major adverse cardiovascular and cerebrovascular event-free survival (P=0.636) did not differ between the 2 groups. One-year graft patency also did not differ significantly between the 2 groups; all patent grafts in 85/104 patients (82%) and 62/73 patients (85%) in the never vaccinated and fully vaccinated groups, respectively (P=0.685). Subgroup analysis showed equivalent overall and major adverse cardiovascular and cerebrovascular event-free survival among AstraZeneca and Pfizer vaccine recipients and between those with ≤30 days versus >30 days from vaccination to CABG. CONCLUSIONS: Despite the very high cardiovascular risk for patients undergoing CABG, COVID-19 vaccination did not affect major outcomes after CABG. Therefore, there is no reason for patients with coronary artery disease requiring CABG to avoid preoperative COVID-19 vaccination.
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COVID-19 , Doença da Artéria Coronariana , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Ponte de Artéria Coronária , Doença da Artéria Coronariana/complicações , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/complicações , Vacinas contra COVID-19/administração & dosagem , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento , VacinaçãoRESUMO
Background: Sutureless valves are widely used in aortic valve replacement surgery, with Perceval valves and Intuity valves being particularly prominent. However, concerns have been raised about postoperative thrombocytopenia with Perceval valves (Corcym, UK). We conducted a comparative analysis with the Intuity valve (Edwards Lifesciences, USA), and assessed how thrombocytopenia affected patient and transfusion outcomes. Methods: Among 595 patients who underwent aortic valve replacement from June 2016 to March 2023, sutureless valves were used in 53 (Perceval: n=23; Intuity: n=30). Platelet counts were monitored during hospitalization and outpatient visits. Daily platelet count changes were compared between groups, and the results from patients who underwent procedures using Carpentier Edwards Perimount Magna valves were used as a reference group. Results: Compared to the Intuity group, the Perceval group showed a significantly higher amount of platelet transfusion (5.48±1.64 packs vs. 0.60±0.44 packs, p=0.008). During the postoperative period, severe thrombocytopenia (<50,000/µL) was significantly more prevalent in the Perceval group (56.5%, n=13) than in the Intuity group (6.7%, n=2). After initial postoperative depletion, daily platelet counts increased, with significant differences observed in the extent of improvement between the Perceval and Intuity groups (p<0.001). However, there was no significant difference in early mortality or the incidence of neurological complications between the 2 groups. Conclusion: The severity of postoperative thrombocytopenia differed significantly between the Perceval and Intuity valves. The Perceval group showed a significantly higher prevalence of severe thrombocytopenia and higher platelet transfusion volumes. However, thrombocytopenia gradually recovered during the postoperative period in both groups, and the early outcomes were similar in both groups.
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Recurrent gene fusions have been observed in epithelioid and myxoid variants of uterine leiomyosarcoma. PGR::NR4A3 fusions were recently described in a subset of epithelioid leiomyosarcomas exhibiting rhabdoid morphology. In this study, we sought to expand the clinical, morphologic, immunohistochemical, and genetic features of gynecologic leiomyosarcomas harboring NR4A3 rearrangements with PGR and novel fusion partners. We identified 9 gynecologic leiomyosarcomas harboring PGR::NR4A3, CARMN::NR4A3, ACTB::NR4A3, and possible SLCO5A1::NR4A3 fusions by targeted RNA sequencing. Tumors frequently affected premenopausal women, involving the uterine corpus, uterine cervix, or pelvis. All were similarly characterized by lobules of monomorphic epithelioid and/or spindled cells arranged in sheets, cords, trabeculae, and micro- and macrocysts associated with abundant myxoid matrix and hemorrhage, creating labyrinth-like or pulmonary edema-like architecture. Myogenic differentiation with frequent estrogen receptor and progesterone receptor staining and no CD10 expression characterized all tumors. All cases showed high NR4A3 RNA expression levels and NOR1 (NR4A3) nuclear staining similar to salivary gland acinic cell carcinomas and a subset of extraskeletal myxoid chondrosarcomas harboring NR4A3 rearrangements. NOR1 (NR4A3) immunohistochemistry may serve as a useful diagnostic marker of NR4A3 fusion-positive gynecologic leiomyosarcomas.
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Leiomiossarcoma , Receptores dos Hormônios Tireóideos , Humanos , Feminino , Leiomiossarcoma/genética , Leiomiossarcoma/patologia , Pessoa de Meia-Idade , Adulto , Receptores dos Hormônios Tireóideos/genética , Receptores de Esteroides/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Proteínas de Ligação a DNA/genética , Idoso , Neoplasias dos Genitais Femininos/genética , Neoplasias dos Genitais Femininos/patologia , Receptores de Progesterona/metabolismo , Receptores de Progesterona/genética , Proteínas de Fusão Oncogênica/genética , Fusão GênicaRESUMO
OBJECTIVES: The clinical characteristics and early outcomes of surgical repair in octogenarians with acute type A aortic dissection were compared with those in nonoctogenarians. METHODS: All patients who underwent emergency surgical repair for acute type A aortic dissection in our institution between 2003 and 2022 were included in this study. The patients were divided into an octogenarian group and a nonoctogenarian group. The patients in the 2 groups were propensity score matched at a ratio of 1:1. Before matching, the baseline characteristics were compared between 2 groups. The major complication and 30-day mortality rates were compared in the matched population. RESULTS: A total of 495 patients were screened, and 471 were included in the analysis, with 48 in the octogenarian group and 423 in the nonoctogenarian group. Before matching, DeBakey type II dissection was significantly more prevalent in the octogenarians (42% vs 14% in the octogenarians and nonoctogenarians, respectively, P < 0.001). Additionally, intramural haematomas (39.6% vs 14.4%, P < 0.001) were more prevalent in the octogenarians. However, severe aortic regurgitation (4.2% vs 15.4%, P = 0.046) and root enlargement (0% vs 13.7%, P = 0.009) were less prevalent in the octogenarians. After matching (36 pairs), the incidence of postoperative delirium was higher in the octogenarians (56% vs 25%, P = 0.027). However, there were no significant differences in 30-day and in-hospital mortality rates, intensive care unit stay or major complications, including stroke, paraplegia, respiratory complications, mediastinitis and haemodialysis. CONCLUSIONS: The octogenarians with acute type A aortic dissection had higher incidences of DeBakey type II dissection and intramural haematomas and lower incidences of severe aortic regurgitation and aortic root enlargement than the nonoctogenarians. Being an octogenarian was not associated with an increased risk of early major complications or mortality after surgery for acute type A aortic dissection.
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OBJECTIVES: Mesonephric (MA) and mesonephric-like (MLA) adenocarcinomas are rare cancers, and data on clinical behavior and response to therapy are limited. We sought to report molecular features, treatment, and outcomes of MA/MLA from a single institution. METHODS: Patients with MA (cervix) or MLA (uterus, ovary, other) treated at Memorial Sloan Kettering Cancer Center (MSK) from 1/2008-12/2021 underwent pathologic re-review. For patients with initial treatment at MSK, progression-free survival (PFS1) was calculated as time from initial surgery to progression or death; second PFS (PFS2) was calculated as time from start of treatment for recurrence to subsequent progression or death. Overall survival (OS) was calculated for all patients. Images were retrospectively reviewed to determine treatment response. Somatic genetic alterations were assessed by clinical tumor-normal sequencing (MSK-Integrated Mutation Profiling of Actionable Cancer Targets [MSK-IMPACT]). RESULTS: Of 81 patients with confirmed gynecologic MA/MLA, 36 received initial treatment at MSK. Sites of origin included cervix (n = 9, 11%), uterus (n = 42, 52%), ovary (n = 28, 35%), and other (n = 2, 2%). Of the 36 patients who received initial treatment at MSK, 20 (56%) recurred; median PFS1 was 33 months (95% CI: 17-not evaluable), median PFS2 was 8.3 months (95% CI: 6.9-14), and median OS was 87 months (95% CI: 58.2-not evaluable). Twenty-six of the 36 patients underwent MSK-IMPACT testing, and 25 (96%) harbored MAPK pathway alterations. CONCLUSION: Most patients diagnosed with early-stage disease ultimately recurred. Somatic MAPK signaling pathway mutations appear to be highly prevalent in MA/MLA, and therapeutics that target this pathway are worthy of further study.
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Adenocarcinoma , Humanos , Feminino , Estudos Retrospectivos , Adenocarcinoma/genética , Adenocarcinoma/terapia , Adenocarcinoma/patologia , Mutação , Ovário/patologia , Colo do Útero/patologiaAssuntos
Adenocarcinoma Mucinoso , Proteínas de Ligação a DNA , Mutação , Infecções por Papillomavirus , Proteína Smad4 , Fatores de Transcrição , Neoplasias do Colo do Útero , Humanos , Feminino , Proteína Smad4/genética , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/virologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/genética , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/virologia , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Colo do Útero/patologia , Colo do Útero/virologia , Pessoa de Meia-Idade , Papillomavirus HumanoRESUMO
In general, endometrioid-defining features such as squamoid morular metaplasia are not thought to be associated with mesonephric adenocarcinoma (MA) and mesonephric-like adenocarcinoma (MLA). Here, we report a case of FGFR2-mutated ovarian MLA with squamoid morular metaplasia accompanied by aberrant nuclear and cytoplasmic ß-catenin expression and CTNNB1 mutation. Histologically, the tumor showed classical MLA histology, including well-formed glands with intraluminal eosinophilic secretions and cells with papillary thyroid carcinoma-like nuclei. Squamoid morular metaplasia was intimately associated with the tumor. Glandular epithelial elements, including those immediately associated with the squamoid morules, were negative for ER, but positive for both GATA3 and PAX8; aberrant ß-catenin expression was limited to the squamoid morules. This case illustrates the ability of mesonephric neoplasia to exhibit histological features previously thought to be restricted to an endometrioid phenotype.
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Adenocarcinoma , Ovário , Feminino , Humanos , Ovário/patologia , beta Catenina/genética , beta Catenina/metabolismo , Adenocarcinoma/patologia , Metaplasia , Mutação , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismoAssuntos
Adenofibroma , Carcinoma Endometrioide , Neoplasias Ovarianas , Feminino , Humanos , Carcinoma Endometrioide/patologia , Tubas Uterinas/patologia , Cateninas/metabolismo , Carcinoma Epitelial do Ovário/patologia , Neoplasias Ovarianas/patologia , Adenofibroma/patologia , Células-Tronco/metabolismo , Células-Tronco/patologia , Fator de Transcrição PAX8/genética , Fator de Transcrição PAX8/metabolismo , Fator de Transcrição CDX2/metabolismo , Fator 1 de Ligação ao Facilitador Linfoide/metabolismoRESUMO
AIMS: Ovarian Wilms tumour (WT)/nephroblastoma is an extremely rare neoplasm that has been reported to occur in pure form or as a component of a teratomatous neoplasm. We hypothesized that teratoma-associated and pure ovarian WT may represent different tumour types with diverging molecular backgrounds. To test this hypothesis, we comprehensively characterized a series of five tumours originally diagnosed as ovarian WT. METHODS AND RESULTS: The five cases comprised three teratoma-associated (two mature and one immature) and two pure WTs. Two of the teratoma-associated WTs consisted of small nodular arrangements of "glandular"/epithelial structures, while the third consisted of both an epithelial and a diffuse spindle cell/blastemal component. The pure WTs consisted of "glandular" structures, which were positive for sex cord markers (including inhibin and SF1) together with a rhabdomyosarcomatous component. The two pure WTs harboured DICER1 pathogenic variants (PVs), while the three associated with teratomas were DICER1 wildtype. Panel-based DNA sequencing of four of the cases did not identify PVs in the other genes investigated. Analysis of the HA19/IGF2 imprinting region showed retention of imprinting in the pure WTs but loss of heterozygosity with hypomethylation of the ICR1 region in two of three teratoma-associated WTs. Furthermore, copy number variation and clustering-based whole-genome DNA methylation analyses identified divergent molecular profiles for pure and teratoma-associated WTs. CONCLUSION: Based on the morphological features, immunophenotype, and molecular findings (DICER1 PVs, copy number, and DNA methylation profiles), we suggest that the two cases diagnosed as pure primary ovarian WT represent moderately to poorly differentiated Sertoli Leydig cell tumours (SLCTs), while the tumours arising in teratomas represent true WTs. It is possible that at least some prior cases reported as pure primary ovarian WT represent SLCTs.
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Neoplasias Renais , Neoplasias Ovarianas , Tumores do Estroma Gonadal e dos Cordões Sexuais , Teratoma , Tumor de Wilms , Masculino , Feminino , Humanos , Variações do Número de Cópias de DNA , Tumor de Wilms/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Teratoma/genética , Teratoma/patologia , Neoplasias Renais/genética , Ribonuclease III/genética , RNA Helicases DEAD-box/genéticaAssuntos
Neoplasias Encefálicas , Carcinoma Endometrioide , Neoplasias Colorretais , Neoplasias do Endométrio , Feminino , Humanos , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Neoplasias Colorretais/patologia , Reparo de Erro de Pareamento de DNA , Proteína 1 Homóloga a MutLRESUMO
Background: Although numerous studies have documented the improved clinical outcomes of patients undergoing cardiac surgery following introduction of attending intensivist, most of these studies included heterogeneous patient populations. We aimed to investigate the impact of an attending intensivist on the clinical outcomes of patients admitted to the cardiac surgical intensive care unit (CSICU) following valvular heart surgery. Methods: Patients who underwent valvular heart surgery between January 2007 and December 2012 (control group, n=337) were propensity matched (1:1) between January 2013 and June 2017 (intensivist group, n=407). Results: During the propensity score matching analysis, 285 patients were extracted from each group. Patients in the intensivist group underwent mechanical ventilation for a significantly shorter time than those in the control group (21.8±69.8 vs. 39.2±115.3 hours, P=0.021). More patients were extubated within 6 hours in the intensivist group than in the control group (53.7% vs. 42.8%, P=0.015). The incidence of ventilator-associated pneumonia (1.4% vs. 4.9%, P=0.031), cardiac arrest due to cardiac tamponade associated with post-cardiotomy bleeding (0.4% vs. 3.9%, P=0.002), and acute kidney injury (2.8% vs. 7.7%, P=0.011) in the intensivist group was significantly lower than that in the control group. The 30-day mortality rate of the intensivist group was significantly lower than that of the control group (2.1% vs. 6.7%, P=0.015). Conclusions: Critical care provided in the CSICU staffed by an attending intensivist is associated with a lower 30-day mortality rate and reduced incidence of postoperative complications.
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PURPOSE: Tumor genomic profiling is increasingly used to guide treatment strategy in patients with cancer. We integrated tumor genomic, clinical demographic, and treatment response data to assess how prospective tumor-normal sequencing impacted treatment selection in patients with cervical cancer. EXPERIMENTAL DESIGN: Cervical cancers were prospectively analyzed using the MSK-IMPACT (Memorial Sloan Kettering Cancer Center - Integrated Mutation Profiling of Actionable Cancer Targets) next-generation sequencing panel. Clinical data, including histology, stage at diagnosis, treatment history, clinical trial enrollment and outcomes, date of last follow-up, and survival status were obtained from medical records. RESULTS: A total of 177 patients with cervical cancer (squamous, 69; endocervical adenocarcinoma, 50; gastric type, 22; adenosquamous, 21; and other, 15) underwent MSK-IMPACT testing. The most prevalent genomic alterations were somatic mutations or amplifications in PIK3CA (25%), ERBB2 (12%), KMT2C (10%), and KMT2D (9%). Furthermore, 13% of patients had high tumor mutational burden (TMB >10 mut/Mb), 3 of which were also microsatellite instability-high (MSI-H). Thirty-seven percent of cases had at least one potentially actionable alteration designated as a level 3B mutational event according to the FDA-recognized OncoKB tumor mutation database and treatment classification system. A total of 30 patients (17%) were enrolled on a therapeutic clinical trial, including 18 (10%) who were matched with a study based on their MSK-IMPACT results. Twenty patients (11%) participated in an immune checkpoint inhibition study for metastatic disease; 2 remain progression free at >5 years follow-up. CONCLUSIONS: Tumor genomic profiling can facilitate the selection of targeted/immunotherapies, as well as clinical trial enrollment, for patients with cervical cancer.
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Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Estudos Prospectivos , Genômica , Mutação , Instabilidade de Microssatélites , Biomarcadores Tumorais/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodosRESUMO
OBJECTIVES: The impacts of elevated troponin I levels after coronary artery bypass grafting (CABG) on long-term outcomes were investigated. METHODS: A total of 996 patients who underwent elective isolated CABG for stable or unstable angina were enrolled. Patients were divided into higher and lower groups based on 80th percentile postoperative peak troponin I (ppTnI) levels. The relationship between ppTnI and long-term clinical outcomes was analysed. RESULTS: The median ppTnI was 1.55 (2.74) ng/ml and was significantly higher in the conventional CABG subgroup than in the beating-heart CABG subgroup: 4.04 (4.71) vs 1.24 (1.99) ng/ml, P < 0.001. The 80th percentile of ppTnI was 3.3 ng/ml in the beating-heart CABG subgroup and 8.9 ng/ml in the conventional CABG subgroup. In the conventional CABG subgroup (n = 150), 10-year overall survival showed no significant difference between the higher (≥8.9 ng/ml) and lower (<8.9 ng/ml) ppTnI groups: 71% (10%) vs 76% (5%), P = 0.316. However, the beating-heart CABG subgroup (n = 846) showed significantly worse 10-year overall survival in the higher ppTnI group (≥3.3 ng/ml) than in the lower ppTnI group (<3.3 ng/ml): 64% (6%) vs 73% (3%), P = 0.010. In the beating-heart CABG subgroup, multivariable analysis showed that ppTnI exceeding the 80th percentile was a risk factor for overall death (hazard ratio: 1.505, 95% confidence interval: 1.019-2.225, P = 0.040). CONCLUSIONS: Higher ppTnI over the 80th percentile was associated with worse long-term survival in beating-heart CABG, but not in conventional CABG.
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Coração , Troponina I , Humanos , Resultado do Tratamento , Ponte de Artéria Coronária/efeitos adversos , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: The pattern-based (Silva) classification of invasive human papilloma virus (HPV)-associated endocervical adenocarcinomas (HPVA) is an established and reproducible method to predict outcomes for this otherwise stage-dependent group of tumours. Previous studies utilising targeted sequencing have shown a correlation between mutational profiles and an invasive pattern. However, such correlation has not been explored using comprehensive molecular testing. DESIGN: Clinicopathologic data including invasive pattern (Silva groups A, B, and C) was collected for a cohort of invasive HPVA, which previously underwent massive parallel sequencing using a panel covering 447 genes. Pathogenic alterations, molecular signatures, tumour mutational burden (TMB), and copy number alterations (CNA) were correlated with pattern of invasion. RESULTS: Forty five HPVA (11 pattern A, 17 pattern B, and 17 pattern C tumours) were included. Patients with pattern A presented at stage I with no involved lymph nodes or evidence of recurrence (in those with >2 months of follow-up). Patterns B and C patients also mostly presented at stage I with negative lymph nodes, but had a greater frequency of recurrence; 3/17 pattern B and 1/17 pattern C HPVAs harboured lymphovascular space invasion (LVI). An APOBEC mutational signature was detected only in Silva pattern C tumours (5/17), and pathogenic PIK3CA changes were detected only in destructively invasive HPVA (patterns B and C). When cases were grouped as low-risk (pattern A and pattern B without LVI) and high-risk (pattern B with LVI and pattern C), high-risk tumours were enriched in mutations in PIK3CA, ATRX, and ERBB2. There was a statistically significant difference in TMB between low-risk and high-risk pattern tumours (P = 0.006), as well as between Pattern C tumours with and without an APOBEC signature (P = 0.002). CNA burden increased from pattern A to C. CONCLUSION: Our findings further indicate that key molecular events in HPVA correlate with the morphologic invasive properties of the tumour and their aggressiveness. Pattern B tumours with LVI clustered with pattern C tumours, whereas pattern B tumours without LVI approached pattern A genotypically. Our study provides a biologic foundation for consolidating the Silva system into low-risk (pattern A + B without LVI) and high-risk (pattern B with LVI and pattern C) categories.
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Adenocarcinoma , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Papillomavirus Humano , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Adenocarcinoma/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Biomarcadores Tumorais , Prognóstico , Invasividade NeoplásicaRESUMO
Urinary cytology is indispensable both for the evaluation of gross hematuria and surveillance of patients with urothelial neoplasms. A positive urine cytology usually indicates the presence of urothelial carcinoma somewhere in the urinary tract. However, in women, it may also signal urothelial carcinoma involvement of the lower gynecologic tract or be the presenting sign for a primary cancer of the lower gynecologic tract or rectum. Guidelines for the evaluation of women with a positive cytology and normal urinary tract are lacking. We present a review of the current literature with case scenarios to bring clinicians attention to this diagnostic dilemma.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Sistema Urinário , Neoplasias Urológicas , Humanos , Feminino , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/patologia , Citologia , Sistema Urinário/patologia , Neoplasias Urológicas/diagnóstico , UrinaRESUMO
BACKGROUND: In cervical cancer, presence of lymph-node macrometastases (MAC) is a major prognostic factor and an indication for adjuvant treatment. However, since clinical impact of micrometastases (MIC) and isolated tumor-cells (ITC) remains controversial, we sought to identify a cut-off value for the metastasis size not associated with negative prognosis. METHODS: We analyzed data from 967 cervical cancer patients (T1a1L1-T2b) registered in the SCCAN (Surveillance in Cervical CANcer) database, who underwent primary surgical treatment, including sentinel lymph-node (SLN) biopsy with pathological ultrastaging. The size of SLN metastasis was considered a continuous variable and multiple testing was performed for cut-off values of 0.01-1.0 mm. Disease-free survival (DFS) was compared between N0 and subgroups of N1 patients defined by cut-off ranges. RESULTS: LN metastases were found in 172 (18%) patients, classified as MAC, MIC, and ITC in 79, 54, and 39 patients, respectively. DFS was shorter in patients with MAC (HR 2.20, P = 0.003) and MIC (HR 2.87, P < 0.001), while not differing between MAC/MIC (P = 0.484). DFS in the ITC subgroup was neither different from N0 (P = 0.127) nor from MIC/MAC subgroups (P = 0.449). Cut-off analysis revealed significantly shorter DFS compared to N0 in all subgroups with metastases ≥0.4 mm (HR 2.311, P = 0.04). The significance of metastases <0.4 mm could not be assessed due to limited statistical power (<80%). We did not identify any cut-off for the size of metastasis with significantly better prognosis than the rest of N1 group. CONCLUSIONS: In cervical cancer patients, the presence of LN metastases ≥0.4 mm was associated with a significant negative impact on DFS and no cut-off value for the size of metastasis with better prognosis than N1 was found. Traditional metastasis stratification based on size has no clinical implication.
Assuntos
Neoplasias da Mama , Linfonodo Sentinela , Neoplasias do Colo do Útero , Feminino , Humanos , Metástase Linfática/patologia , Micrometástase de Neoplasia/patologia , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia , Biópsia de Linfonodo Sentinela , Linfonodos/patologia , Estadiamento de Neoplasias , Neoplasias da Mama/patologia , Linfonodo Sentinela/patologiaRESUMO
Villoglandular adenocarcinoma of the cervix is a rare histologic entity that typically develops in young women, characterized by an association with oral contraceptives and excellent prognosis, though this point is controversial. These tumors have not been studied in the context of the International Endocervical Adenocarcinoma Criteria and Classification (IECC) or Silva Pattern Classification. We analyzed 31 cases that met strict diagnostic criteria, including being completely excised with negative margins. These were categorized according to IECC and Silva Pattern Classification and the association with various pathologic parameters analyzed. Most patients were young with a mean age of 41.1 (range 25-79). There were 14 (45.2%) pattern A, 11 (35.5%) pattern B, and 6 (19.3%) pattern C cases. Only 1 of 22 patients (4.5%) presented with lymph node metastasis at the time of diagnosis (pattern C, stage IB1) and 3 (9.7%) had lymphovascular invasion (2 pattern C, 1 pattern B). Overall survival was 100%, while recurrence-free survival was 96.2% for the entire cohort with only 1 case (3.2%) recurring 25 mo after surgery (IB2, pattern B). Kaplan Meier analysis (log rank test) revealed no significant correlation for recurrence-free survival at 5 and 10 yr associated with depth of invasion, tumor size, Silva pattern, FIGO stage, lymphovascular invasion, or lymph node metastasis. Cox univariate analysis demonstrated no independent prognostic factors predicting recurrence-free survival. These results indicate that completely excised villoglandular adenocarcinoma generally has an excellent prognosis and when Silva Pattern Classification is applied, those tumors that potentially have a higher chance for adverse outcomes can be identified.