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Successful human pregnancy needs several highly controlled steps to guarantee an oocyte's fertilization, the embryo's pre-implantation development, and its subsequent implantation into the uterine wall. The subsequent placenta development ensures adequate fetal nutrition and oxygenation, with the trophoblast being the first cell lineage to differentiate during this process. The placenta sustains the growth of the fetus by providing it with oxygen and nutrients and removing waste products. It is not surprising that issues with the early development of the placenta can lead to common pregnancy disorders, such as recurrent miscarriage, fetal growth restriction, pre-eclampsia, and stillbirth. Understanding the normal development of the human placenta is essential for recognizing and contextualizing any pathological aberrations that may occur. The effects of these issues may not become apparent until later in pregnancy, during the mid or advanced stages. This review discusses the process of the embryo implantation phase, the molecular mechanisms involved, and the abnormalities in those mechanisms that are thought to contribute to the development of pre-eclampsia. The review also covers the histological hallmarks of pre-eclampsia as found during the examination of placental tissue from pre-eclampsia patients.
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Placenta , Placentación , Preeclampsia , Humanos , Preeclampsia/metabolismo , Preeclampsia/patología , Embarazo , Femenino , Placenta/patología , Placenta/metabolismo , Implantación del Embrión , Trofoblastos/metabolismo , Trofoblastos/patologíaRESUMEN
Fumarate hydratase (FH)-deficient renal cell carcinomas are rare neoplasms characterized by wide morphologic heterogeneity and pathogenetic mutations in the FH gene. They often show aggressive behavior with rapid diffusion to distant organs, so novel therapeutic scenarios have been explored, including EGFR inhibitors and PD-L1 expression for targeted immunotherapy. Herein, we investigated a series of 11 primary FH-deficient renal cell carcinomas and 7 distant metastases to evaluate tumor heterogeneity even in metastatic sites and estimate the specific spread rates to various organs. Furthermore, the tumors were tested for immunohistochemical PD-L1 expression and EGFR mutations. Most metastatic cases involved the abdominal lymph nodes (4/7; 57%), followed by the peritoneum (3/7; 42%), the liver (2/7; 29%), and the lungs (1/7; 14%). Six metastatic localizations were histologically documented, revealing a morphologic heterogeneous architecture often differing from that of the corresponding primary renal tumor. Peritoneal involvement morphologically resembled a benign reactive mesothelial process or primary peritoneal mesothelioma, thus advocating to perform an accurate immunohistochemical panel, including PAX8 and FH, to reach a proper diagnosis. A pure low-grade succinate dehydrogenase-looking primary FH-deficient renal cell carcinoma was also recorded. As for therapy, significant PD-L1 labeling was found in 60% of primary renal tumors, whereas none of them carried pathogenetic EGFR mutations. Our data show that FH-deficient renal cell carcinoma may be morphologically heterogeneous in metastases as well, which involve the lymph nodes, the liver, and the peritoneum more frequently than other renal tumors. Due to the high frequency of this latter (42%), pathologists should always be concerned about ruling out mesothelial-derived mimickers, and the occurrence of rarer, primary, low-grade-looking types. Finally, contrary to EGFR mutations, PD-L1 expression could be a possible predictive biomarker for the therapy of these tumors.
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OBJECTIVE: To compare the accuracy of available classification systems (Folpe, modified Folpe, Bennet, and Schoolmester) in predicting the behavior of uterine Perivascular Epithelioid Cell tumors (PEComas). METHODS: We reviewed the pathology registry to identify all uterine PEComas treated at our center. We conducted a systematic literature review searching electronic databases from inception to November 2023. We included all references reporting at least one case of uterine PEComa; cases associated with tuberous sclerosis complex were excluded. Patient-level data were extracted by identified records. Survival analysis was used to assess the accuracy of all proposed classification systems to classify uterine PEComas as malignant versus non-malignant. RESULTS: Six uterine PEComas were treated at our center. The literature search identified 101 uterine PEComas from 32 studies. Eighty-five out of 107 PEComas (28 studies and our series) reported enough follow-up data and details to apply all four classifications. The modified Folpe classification demonstrated the highest hazard ratio (HR) for relapse (HR:8.63; 95% confidence interval [CI] 2.06-36.1) and death due to PEComa (HR:6.8, 95%CI:0.89-51.6) for malignant versus non-malignant PEComas. Changing the cut-off of PEComa size to ≥8 cm and mitotic figures per 50 high power fields to ≥5, the HR for recurrence lowered (HR:6.26; 95% CI 2.20-17.80), but HR for death increased (HR:10.3; 95% CI 1.35-77.80). CONCLUSIONS: The modified Folpe classification was the most accurate in predicting the PEComa behavior. Changing the cut-off of PEComa size and number of mitotic figures may improve the accuracy in predicting death due to disease.
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Introduction: The surface protein TROP-2/TACSTD2 and the cell adhesion protein NECTIN-4/NECTIN4 are responsible for the efficacy of anticancer therapies based on antibody-drug conjugates (ADC) targeting intracellular microtubules. In contrast with common histologic subtypes of bladder urothelial carcinoma (BUC), little is known of TROP-2 and NECTIN-4 expression in sarcomatoid and rhabdoid BUC. Aims: In this study, we aimed to analyze TROP-2 and NECTIN-4 expression and additional predictive biomarkers by immunohistochemistry and fluorescence in situ hybridization (FISH) on 35 undifferentiated BUC (28 sarcomatoid and 7 rhabdoid). Wide genomic investigation was also performed on 411 BUC cases of the PanCancer Atlas, focusing on genes related to the microtubule pathways. Results: Seven of 35 (20%) undifferentiated BUC showed expression of TROP-2. NECTIN-4 was expressed in 10 cases (29%). Seven cases (20%) co-expressed TROP-2 and NECTIN-4. HER-2 FISH was amplified in 5 cases (14%) while HER-2 immunoexpression was observed in 14 cases (40%). PD-L1 scored positive for combined proportion score (CPS) in 66% of cases and for tumor proportion score (TPS) in 51% of cases. Pan-NTRK1-2/3 was elevated in 9 cases (26%) and FGFR-2/3 was broken in 7 of 35 cases (20%). Of 28 sarcomatoid BUC, 9 (32%) were negative for all (TROP-2, NECTIN-4, PD-L1, HER-2, FGFR and pan-NTRK) biomarkers and 3 (11%) expressed all five biomarkers. Among cases with rhabdoid dedifferentiation, 1 of 7 (14%) showed activation of all biomarkers, whereas 2 of 7 (28%) showed none. The mRNA analysis identified microtubule-related genes and pathways suitable for combined ADC treatments in BUC. Conclusion: Sarcomatoid and rhabdoid BUC do harbor positive expression of the ADC targets TROP-2 or NECTIN-4 in a relatively modest subset of cases, whereas the majority do not. Different combinations of other positive biomarkers may help the choice of medical therapies. Overall, these findings have important clinical implications for targeted therapy for BUC.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Carcinoma de Células Transicionales/patología , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/genética , Antígeno B7-H1 , Nectinas/genética , Vejiga Urinaria/patología , Hibridación Fluorescente in Situ , Biomarcadores de Tumor/análisisRESUMEN
BACKGROUND: Upfront surgery followed by postoperative treatment is a commonly adopted treatment for resectable pancreatic ductal adenocarcinoma (rPDAC). However, the risk of positive surgical margins, the poor recovery that often impairs postoperative treatments, and the risk of recurrence might limit the outcome of this strategy. This study evaluated the safety and the activity of liposomal irinotecan 50â¯mg/m2 +â¯5-fluorouracil 2400â¯mg/m2 +â¯leucovorin 400â¯mg/m2 +â¯oxaliplatin 60â¯mg/m2 (NALIRIFOX) in the perioperative treatment of patients with rPDAC. METHODS: Eligible patients had a rPDAC with <â¯180° interface with major veins' wall. Patients received 3 cycles before and 3 cycles after resection with NALIRIFOX, days 1 and 15 of a 28-day cycle. The primary endpoint was the proportion of patients undergoing an R0 resection. RESULTS: 107 patients began preoperative treatment. Nine patients discontinued the treatment because of related or unrelated adverse events. Disease-control rate was 92.9%. 87 patients underwent surgical exploration, 11 had intraoperative evidence of metastatic disease, and 1 died for surgical complications. R0 resection rate was 65.3%. 49 patients completed the three postoperative cycles. The most common grade ≥â¯3 adverse events were diarrhea and neutropenia. Median overall survival (OS) of ITT patients was 32.3 months (95% CI 27.8-44.3). Median disease-free and OS from surgery of resected patients were 19.3 (95% CI 12.6-34.1) and 40.3 months (95% CI 29-NA), respectively. CONCLUSION: Perioperative NALIRIFOX was manageable and active, and deserves further investigation in randomized trials comparing it with standard upfront surgery followed by adjuvant therapy.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Fluorouracilo , Irinotecán/efectos adversos , Adenocarcinoma/patología , Leucovorina , Terapia Neoadyuvante/efectos adversosRESUMEN
In the spectrum of oncocytic renal neoplasms, a subset of tumors with high-grade-appearing histologic features harboring pathogenic mutations in mammalian target of rapamycin (mTOR) and hitherto clinical indolent behavior has been described. Three cases (2F,1 M) with histologically documented metastases (lymph node, skull, and liver) were retrieved and extensively investigated by immunohistochemistry, FISH, and next-generation sequencing. Tumors were composed of eosinophilic cells with prominent nucleoli (G3 by ISUP/WHO) arranged in solid to nested architecture. Additionally, there were larger cells with perinuclear cytoplasmic shrinkage and sparse basophilic Nissl-like granules, superficially resembling the so-called spider cells of cardiac rhabdomyomas. The renal tumors, including the skull and liver metastases, showed immunoexpression PAX8, CK8-18, and cathepsin-K, and negativity for vimentin. NGS identified mTOR genetic alterations in the three cases, including the skull and liver metastases. One patient was then treated with Everolimus (mTOR inhibitors) with clinical response (metastatic tumor shrinkage). We present a distinct renal tumor characterized by high-grade eosinophilic cells, cathepsin-K immunohistochemical expression, and harboring mTOR gene mutations demonstrating a malignant potential and showing responsiveness to mTOR inhibitors.
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Carcinoma de Células Renales , Neoplasias Renales , Neoplasias Hepáticas , Humanos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Cromosomas Humanos Par 1/metabolismo , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Inhibidores mTOR , Mutación , Serina-Treonina Quinasas TOR/genéticaRESUMEN
The new WHO classification of urogenital tumours published in 2022, contains significant revisions upon the previous 2016 version regarding Renal Cell Carcinoma (RCC). While the most common histotype remains almost untouched, some of the main novelties concerns papillary RCC and oncocytic neoplasms. The main change is the introduction of a new category of molecularly-defined RCC, which includes TFE3-rearranged RCC, TFEB-rearranged, and TFEB-amplified RCC, FH-deficient RCC, SDH-deficient RCC, ALK-rearranged RCC, ELOC (formerly TCEB1)-mutated RCC, SMARCB1 (INI1)-deficient RCC. In this paper we analyze the current knowledge on emerging entities and molecularly-defined RCC to assess whether the current pathological classification offers the oncologist the possibility of selecting more specific and personalized treatments, from both those currently available, as well as those that will soon be available.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/patología , Organización Mundial de la SaludRESUMEN
STING is a molecule involved in immune reactions against double-stranded DNA fragments, released in infective and neoplastic diseases, whose role in the interactions between immune and neoplastic cells in clear cell renal cell carcinoma has not been studied yet. We investigated the immunohistochemical expression of STING in a series of 146 clear-cell renal cell carcinomas and correlated it with the main pathological prognostic factors. Furthermore, tumoral inflammatory infiltrate was evaluated and studied for the subpopulations of lymphocytes. Expression of STING was observed in 36% (53/146) of the samples, more frequently in high-grade (G3-G4) tumors (48%,43/90) and recurrent/metastatic ones (75%, 24/32) than in low grade (G1-G2) and indolent neoplasms (16%, 9/55). STING staining correlated with parameters of aggressive behavior, including coagulative granular necrosis (p = 0.001), stage (p < 0.001), and development of metastases (p < 0.001). Among prognostic parameters, STING immune expression reached an independent statistical significance (p = 0.029) in multivariable analysis, along with the stage and the presence of coagulative granular necrosis. About tumor immune-environment, no significant statistical association has been demonstrated between tumor-infiltrating lymphocytes and STING. Our results provide novel insights regarding the role of STING in aggressive clear cell renal cell carcinomas, suggesting its adoption as a prognostic marker and a potentially targetable molecule for specific immunotherapies.
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Carcinoma de Células Renales , Neoplasias Renales , Sarcoma , Humanos , Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Pronóstico , NecrosisRESUMEN
BACKGROUND: The aim of this study is to evaluate the impact of major pathological response on overall survival (OS) in borderline resectable and locally advanced pancreatic ductal adenocarcinoma following neoadjuvant treatment, and to identify predictors of major pathological response. METHODS: Patients surgically resected following neoadjuvant treatment between 2010 and 2020 at the Pederzoli Hospital were retrospectively analyzed. Pathologic response was assessed using the College of American Pathologists (CAP) score, and major pathological response was defined as CAP 0-1. OS was estimated and compared using the Kaplan-Meier method and log-rank test. A logistic and Cox regression model were performed to identify predictors of major pathologic response and OS. RESULTS: Overall, 200 patients were included in the study. A major and complete pathological response were observed in 52(26.0%) and 15(7.3%) patients respectively. The 1-, 3-, 5-year OS was 92.7, 67.2, and 41.7%, and 71.0, 37.4, and 20.8% in patients with or without major pathologic response respectively (log-rank test p < 0.001). Major pathologic response was confirmed as independent predictor of OS (OR 0.50 95%CI 0.29-0.88, p = 0.01). Post-treatment CA19-9 normalization (OR 4.20 95%CI 1.14-10.35, p = 0.02) and radiological post-treatment tumor residual size<25 mm (OR 2.71 95%CI 1.27-5.79, p = 0.01) were found to be independent predictors of major pathologic response. CONCLUSION: Patients experienced a major pathological response after neoadjuvant treatment have an increased survival, and major pathologic response is an independent predictor of OS. A normal CA19-9 value and radiological tumor size at restaging are confirmed to be independent predictors of major pathologic response.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Pronóstico , Terapia Neoadyuvante , Estudios Retrospectivos , Antígeno CA-19-9 , Neoplasias Pancreáticas/tratamiento farmacológico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMEN
Neuroendocrine neoplasms of the urinary bladder are uncommon tumors represented by small-cell neuroendocrine carcinoma and by fewer cases of large-cell neuroendocrine carcinomas and well-differentiated neuroendocrine tumors. Less than 30 examples of this latter entity have been published so far and consisted of clinically indolent lesions mainly located in the bladder neck arranged in a pseudo-glandular architecture often associated with reactive urothelial changes like cystitis cystica/glandularis. Due to their infrequency, pathologists may face difficulty to recognize this proliferation considering it as part of cystitis cystica/glandularis or misinterpreting it as nested urothelial carcinoma, paraganglioma, or secondary bladder involvement by prostatic adenocarcinoma. Herein the case of a 51-year-old female diagnosed with a well-differentiated neuroendocrine tumor of the bladder immunohistochemically expressing GATA3 is reported, pointing out either the pitfall in the differential diagnosis with cystitis cystica/glandularis, nested urothelial carcinoma, and paraganglioma or its usefulness in the differential diagnosis with prostatic adenocarcinoma.
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Carcinoma Neuroendocrino , Cistitis , Tumores Neuroendocrinos , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Neuroendocrino/diagnóstico , Cistitis/diagnóstico , Diagnóstico Diferencial , Tumores Neuroendocrinos/diagnóstico , Vejiga Urinaria/patologíaRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is currently the most deadly cancer. Although characterized by 5-20% of neoplastic cells in the highly fibrotic stroma, immunotherapy is not a valid option in PDAC treatment. As CXCR4-CXCL12 regulates tumor invasion and T-cell access and PD-1/PD-L1 controls immune tolerance, 76 PDACs were evaluated for CXCR4-CXCL12-CXCR7 and PD-1/PD-L1 in the epithelial and stromal component. Neoplastic CXCR4 and CXCL12 discriminated PDACs for recurrence-free survival (RFS), while CXCL12 and CXCR7 discriminated patients for cancer-specific survival (CSS). Interestingly, among patients with radical resection (R0), high tumor CXCR4 clustered patients with worse RFS, high CXCL12 identified poor prognostic patients for both RFS and CSS, while stromal lymphocytic-monocytic PD-L1 associated with improved RFS and CSS. PD-1 was only sporadically expressed (<1%) in focal lymphocyte infiltrate and does not impact prognosis. In multivariate analysis, tumoral CXCL12, perineural invasion, and AJCC lymph node status were independent prognostic factors for RFS; tumoral CXCL12, AJCC Stage, and vascular invasion were independent prognostic factors for CSS. CXCL12's poor prognostic meaning was confirmed in an additional perspective-independent 13 fine-needle aspiration cytology advanced stage-PDACs. Thus, CXCR4-CXCL12 evaluation in PDAC identifies prognostic categories and could orient therapeutic approaches.
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Carcinoma Ductal Pancreático , Quimiocina CXCL12 , Neoplasias Pancreáticas , Receptores CXCR , Humanos , Antígeno B7-H1 , Biomarcadores de Tumor , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Pronóstico , Receptor de Muerte Celular Programada 1 , Receptores CXCR4 , Neoplasias PancreáticasRESUMEN
Microphthalmia Transcription Factor (MiT) family aberration-associated renal cell carcinoma is a rare disease, whose true prevalence is unknown, due to the need of molecular confirmation, commonly by Fluorescent In Situ Hybridization (FISH), for its diagnosis. In fact, this tumor is commonly misdiagnosed, often labeled as clear cell RCC, papillary RCC and chromophobe RCC. It is typically observed in young patients, and it can have indolent or aggressive behavior. In the case of aggressive behavior, the disease is rapidly progressive, showing little-to-no response to the drugs commonly used to treat the usual types of RCC. In this review, we focus on the biological and pathological features of this neoplasm, their impact on its clinical manifestations and we analyze the few experiences of treatment reported in the literature.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Hibridación Fluorescente in Situ , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Factores de Transcripción , Translocación GenéticaRESUMEN
A 79-year-old woman underwent surgical resection of a peripheral, solitary, pulmonary lesion that was diagnosed as malignant PEComa. Her clinical history was positive for uterine leiomyosarcoma, excised 20 years before. Re-evaluation of the primary uterine lesion led to the final diagnosis of lung metastasis from uterine PEComa. While long latency between primary tumour and metastasis is a known and characteristic feature of PEComas, a 20-year interval is unprecedented in the literature.
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Neoplasias Pulmonares , Neoplasias de Células Epitelioides Perivasculares , Neoplasias Uterinas , Anciano , Femenino , Humanos , Neoplasias Pulmonares/secundario , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Neoplasias de Células Epitelioides Perivasculares/patología , Neoplasias de Células Epitelioides Perivasculares/cirugía , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/patologíaRESUMEN
Different programmed cell death-ligand 1 (PD-L1) assays and scoring algorithms are being used in the evaluation of PD-L1 expression for the selection of patients for immunotherapy in specific settings of advanced urothelial carcinoma (UC). In this paper, we sought to investigate three approved assays (Ventana SP142 and SP263, and Dako 22C3) in UC with emphasis on implications for patient selection for atezolizumab/pembrolizumab as the first line of treatment. Tumors from 124 patients with invasive UC of the bladder were analyzed using tissue microarrays (TMA). Serial sections were stained with SP263 and SP142 on Ventana Benchmark Ultra and with 22C3 on Dako Autostainer Link 48. Stains were evaluated independently by two observers and scored using the combined positive score (CPS) and tumor infiltrating immune cells (IC) algorithms. Differences in proportions (DP), overall percent agreement (OPA), positive percent agreement (PPA), negative percent agreement (NPA), and Cohen κ were calculated for all comparable cases. Good overall concordance in analytic performance was observed for 22C3 and SP263 with both scoring algorithms; specifically, the highest OPA was observed between 22C3 and SP263 (89.6%) when using CPS. On the other hand, SP142 consistently showed lower positivity rates with high differences in proportions (DP) compared with 22C3 and SP263 with both CPS and IC, and with a low PPA, especially when using the CPS algorithm. In conclusion, 22C3 and SP263 assays show comparable analytical performance while SP142 shows divergent staining results, with important implications for the selection of patients for both pembrolizumab and atezolizumab.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Antígeno B7-H1/metabolismo , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/patología , Humanos , Inmunohistoquímica , Selección de Paciente , Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
TFE3/TFEB-rearranged renal cell carcinomas are characterized by translocations involving TFE3 and TFEB genes. Despite the initial description of typical morphology, their histological spectrum is wide, mimicking common subtypes of renal cell tumors. Thus, the diagnosis is challenging requiring the demonstration of the gene rearrangement, usually by FISH. However, this technique is limited in most laboratories and immunohistochemical TFE3/TFEB analysis is inconsistent. We sought to identify a useful immunohistochemical panel using the most common available markers to recognize those tumors. We performed an immunohistochemical panel comparing 27 TFE3-rearranged and 10 TFEB-rearranged renal cell carcinomas to the most common renal cell tumors (150 clear cell, 100 papillary, 50 chromophobe renal cell carcinomas, 18 clear cell papillary renal cell tumors, and 50 oncocytomas). When dealing with neoplasms characterized by cells with clear cytoplasm, CA9 is a helpful marker to exclude clear cell renal cell carcinoma. GATA3, AMACR, and CK7 are useful to rule out clear cell papillary renal cell tumor. CK7 is negative in TFE3/TFEB-rearranged renal cell carcinoma and positive in papillary renal cell carcinoma, being therefore useful in this setting. Parvalbumin and CK7/S100A1 respectively are of paramount importance when TFE3/TFEB-rearranged renal cell carcinoma resembles oncocytoma and chromophobe renal cell carcinoma. Moreover, in TFEB-rearranged renal cell carcinoma, cathepsin K and melanogenesis markers are constantly positive, whereas TFE3-rearranged renal cell carcinoma stains for cathepsin K in roughly half of the cases, HMB45 in 8% and Melan-A in 22%. In conclusion, since TFE3/TFEB-rearranged renal cell carcinoma may mimic several histotypes, an immunohistochemical panel to differentiate them from common renal cell tumors should include cathepsin K, CA9, CK7, and parvalbumin.
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Adenoma Oxifílico , Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Catepsina K , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Inmunohistoquímica , Neoplasias Renales/diagnóstico , Neoplasias Renales/genética , Neoplasias Renales/patología , Translocación Genética , Adenoma Oxifílico/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisisRESUMEN
Renal oncocytoma and chromophobe renal cell carcinoma were accepted as unique renal tumors in the late 1990s. Since their formal description, criteria for diagnosis have evolved and additional distinct tumor subtypes originally considered as one these two entities are now recognized. The last two decades have witnessed unprecedented interest in the spectrum of low grade oncocytic renal neoplasms in three specific areas: (1) histologic characterization of tumors with overlapping morphologic features between oncocytoma and chromophobe renal cell carcinoma; (2) description of potentially unique entities within this spectrum, such as eosinophilic vacuolated tumor and low-grade oncocytic tumor; and (3) better appreciation of the association between a subset of low grade oncocytic tumors and hereditary renal neoplasia. While this important work has been academically rewarding, the proposal of several histologic entities with overlapping morphologic and immunophenotypic features (which may require esoteric adjunctive immunohistochemical and/or molecular techniques for confirmation) has created frustration in the diagnostic pathology and urology community as information evolves regarding classification within this spectrum of renal neoplasia. Pathologists, including genitourinary subspecialists, are often uncertain as to the "best practice" diagnostic approach to such tumors. In this review, we present a practical clinically relevant algorithmic approach to classifying tumors within the low grade oncocytic family of renal neoplasia, including a proposal for compressing terminology for evolving categories where appropriate without sacrificing prognostic relevance.
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Adenoma Oxifílico , Carcinoma de Células Renales , Neoplasias Renales , Adenoma Oxifílico/diagnóstico , Adenoma Oxifílico/patología , Biomarcadores de Tumor , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Diagnóstico Diferencial , Humanos , Inmunohistoquímica , Riñón/patología , Neoplasias Renales/diagnóstico , Neoplasias Renales/patologíaRESUMEN
Mixed epithelial and stromal tumour of the kidney is a complex benign neoplasm in which malignancy rarely arises. In this study, we report four mixed epithelial and stromal tumours in which sarcoma or carcinoma developed. In the first, a multifocal adenocarcinoma arose and areas of transition from benign to malignant epithelium were observed. Oestrogen and progesterone receptors were diffusely present in the nuclei of the spindle cell stroma of the benign component. The second was a sarcoma in which benign epithelial elements were intermixed. Outside the renal parenchyma, clusters of small benign glands surrounded by oestrogen receptor-positive benign stroma were present, supporting the diagnosis of mixed epithelial and stromal tumour. Fluorescence in situ hybridisation for SYT-SSX translocation and immunohistochemical results, specifically TLE1 -ativity, argued against primary renal synovial sarcoma. The patient died 24 months after surgery. The third tumour consisted of small blue round cells, positive for epithelial membrane antigen, BCL2, CD99, and FLI1. Throughout the tumour, the presence of benign appearing branching tubules in fibromuscular stroma, reactive for smooth muscle actin, desmin and progesterone receptor, supported the diagnosis of mixed epithelial and stromal tumour in which a small round blue cell sarcoma with EWSR1 rearrangement arose. In the fourth tumour, adenocarcinoma with papillary architecture arose in a typical mixed epithelial and stromal tumour. In summary, we present four cases of mixed epithelial and stromal tumour with malignant transformation, two showing carcinomatous and the other two with sarcomatous transformation. Identification of typical benign looking elements and the absence of SYT-SSX translocation are helpful in recognition of this entity.
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Adenocarcinoma , Neoplasias Renales , Sarcoma Sinovial , Neoplasias de los Tejidos Blandos , Actinas , Biomarcadores de Tumor , Transformación Celular Neoplásica/genética , Desmina , Estrógenos , Humanos , Inmunohistoquímica , Neoplasias Renales/diagnóstico , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Mucina-1 , Proteínas Proto-Oncogénicas c-bcl-2 , Receptores de Estrógenos , Receptores de ProgesteronaRESUMEN
Despite intense investigation, the pathogenesis of COVID-19 and the newly defined long COVID-19 syndrome are not fully understood. Increasing evidence has been provided of metabolic alterations characterizing this group of disorders, with particular relevance of an activated tryptophan/kynurenine pathway as described in this review. Recent histological studies have documented that, in COVID-19 patients, indoleamine 2,3-dioxygenase (IDO) enzymes are differentially expressed in the pulmonary blood vessels, i.e., IDO1 prevails in early/mild pneumonia and in lung tissues from patients suffering from long COVID-19, whereas IDO2 is predominant in severe/fatal cases. We hypothesize that IDO1 is necessary for a correct control of the vascular tone of pulmonary vessels, and its deficiency in COVID-19 might be related to the syndrome's evolution toward vascular dysfunction. The complexity of this scenario is discussed in light of possible therapeutic manipulations of the tryptophan/kynurenine pathway in COVID-19 and post-acute COVID-19 syndromes.
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We aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clearRCC). One hundred cases of clearRCC were sampled. First, usual standard sampling was applied (1 block/cm of tumor); second, the whole tumor was sampled, and 0.6 mm cores were taken from each block to construct a tissue microarray; third, the residual tissue, mapped by taking pieces 0.5 × 0.5 cm, reconstructed the entire tumor mass. Precisely, six randomly derived pieces of tissues were placed in each cassette, with the number of cassettes being based on the diameter of the tumor (called multisite 3D fusion). Angiogenic and immune markers were tested. Routine 5231 tissue blocks were obtained. Multisite 3D fusion sections showed pattern A, homogeneous high vascular density (10%), pattern B, homogeneous low vascular density (8%) and pattern C, heterogeneous angiogenic signatures (82%). PD-L1 expression was seen as diffuse (7%), low (33%) and absent (60%). Tumor-infiltrating CD8 scored high in 25% (pattern hot), low in 65% (pattern weak) and zero in 10% of cases (pattern desert). Grading was upgraded in 26% of cases (G3-G4), necrosis and sarcomatoid/rhabdoid characters were observed in, respectively, 11 and 7% of cases after 3D fusion (p = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes (p = 0.03). Again, 22% of cases were set to intermediate to high risk of clinical recurrence due to new morphological findings of all aggressive G4, sarcomatoid/rhabdoid features by using 3D fusion compared to standard methods (p = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity.