RESUMO
BACKGROUND: Ovarian pseudomyxoma peritonei (OPMP) are rare, without well-defined therapeutic guidelines. We aimed to evaluate cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) to treat OPMP. METHODS: Patients from the French National Network for Rare Peritoneal Tumors (RENAPE) database with proven OPMP treated by CRS/HIPEC and with histologically normal appendix and digestive endoscopy were retrospectively included. Clinical and follow-up data were collected. Histopathological and immunohistochemical features were reviewed. RESULTS: Fifteen patients with a median age of 56 years were included. The median Peritoneal Cancer Index was 16. Following CRS, the completeness of cytoreduction (CC) score was CC-0 for 9/15 (60%) patients, CC-1 for 5/15 (33.3%) patients, and CC-2 for 1/15 (6.7%) patients. The median tumor size was 22.5 cm. After pathological review and immunohistochemical studies, tumors were classified as Group 1 (mucinous ovarian epithelial neoplasms) in 3/15 (20%) patients; Group 2 (mucinous neoplasm in ovarian teratoma) in 4/15 (26.7%) patients; Group 3 (mucinous neoplasm probably arising in ovarian teratoma) in 5/15 (33.3%) patients; and Group 4 (non-specific group) in 3/15 (20%) patients. Peritoneal lesions were OPMP pM1a/acellular, pM1b/grade 1 (hypocellular) and pM1b/grade 3 (signet-ring cells) in 13/15 (86.7%), 1/15 (6.7%) and 1/15 (6.7%) patients, respectively. Disease-free survival analysis showed a difference (p = 0.0463) between OPMP with teratoma/likely-teratoma origin (groups 2 and 3; 100% at 1, 5, and 10 years), and other groups (groups 1 and 4; 100%, 66.6%, and 50% at 1, 5, and 10 years, respectively). CONCLUSION: These results suggested that a primary therapeutic strategy using complete CRS/HIPEC for patients with OPMP led to favorable long-term outcomes.
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Neoplasias do Apêndice , Hipertermia Induzida , Neoplasias Císticas, Mucinosas e Serosas , Pseudomixoma Peritoneal , Teratoma , Feminino , Humanos , Pessoa de Meia-Idade , Pseudomixoma Peritoneal/patologia , Quimioterapia Intraperitoneal Hipertérmica , Procedimentos Cirúrgicos de Citorredução/métodos , Estudos Retrospectivos , Hipertermia Induzida/métodos , Neoplasias do Apêndice/terapia , Neoplasias do Apêndice/patologia , Terapia Combinada , Taxa de SobrevidaRESUMO
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma most reported in Asia. We performed a comprehensive clinical, pathological and genomic study of 71 European MEITL patients (36 males, 35 females, median age 67 years). The majority presented with gastrointestinal involvement and had emergency surgery, and 40% had stage IV disease. The tumors were morphologically classified into two groups: typical (58%) and atypical (i.e., non-monomorphic or with necrosis, angiotropism or starry-sky pattern) (42%), sharing a homogeneous immunophenotypic profile (CD3+ [98%] CD4- [94%] CD5- [97%] CD7+ [97%] CD8+ [90%] CD56+ [86%] CD103+ [80%] cytotoxic marker+ [98%]) with more frequent expression of TCRgd (50%) than TCRab (32%). MYC expression (30% of cases) partly reflecting MYC gene locus alterations, correlated with non-monomorphic cytology. Almost all cases (97%) harbored deleterious mutation(s) and/or deletion of the SETD2 gene and 90% had defective H3K36 trimethylation. Other frequently mutated genes were STAT5B (57%), JAK3 (50%), TP53 (35%), JAK1 (12.5%), BCOR and ATM (11%). Both TP53 mutations and MYC expression correlated with atypical morphology. The median overall survival (OS) of 63 patients (43/63 only received chemotherapy after initial surgery) was 7.8 months. Multivariate analysis found a strong negative impact on outcome of MYC expression, TP53 mutation, STAT5B mutation and poor performance status while aberrant B-cell marker expression (20% of cases) correlated with better survival. In conclusion, MEITL is an aggressive disease with resistance to conventional therapy, predominantly characterized by driver gene alterations deregulating histone methylation and JAK/STAT signaling and encompasses genetic and morphologic variants associated with very high clinical risk.
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Linfoma de Células T Associado a Enteropatia , Masculino , Feminino , Humanos , Idoso , Linfoma de Células T Associado a Enteropatia/genética , Linfoma de Células T Associado a Enteropatia/metabolismo , Linfoma de Células T Associado a Enteropatia/patologia , Genômica , Mutação , Transdução de SinaisRESUMO
Rosai-Dorfman-Destombes disease is a rare non-Langerhansian cell histiocytosis characterized by the accumulation of large activated histiocytes in the affected tissues with images of emperipolesis. The diagnosis is not really problematic in the classical forms, with a lymph node presentation, whose histology is very suggestive. However, it can be much more difficult in the extra-nodal forms, which are misleading in both their clinical and histological presentation. We report here a case illustrating this diagnostic difficulty. Firstly, clinically, the disease was revealed by an unusual laryngeal location, responsible for acute obstructive respiratory distress and requiring urgent surgical management. Secondly, histologically, the diagnosis was not evoked in the first instance by analysis of the laryngeal lesion. Indeed, there was a not specific appearing polymorphic infiltrate, associating small lymphocytes, plasma cells and numerous histiocytes, without evidence for a lymphoma after immunohistochemistry and lymphocyte clonality analysis. However, after re-examination of the slides, the histiocytes sometimes appeared large or xanthomised and have a PS100+, CD1a-, langerhine- phenotype, with rare images of emperipolesis. These aspects finally suggested the diagnosis of Rosai-Dorfman-Destombes disease, then confirmed by a cervical lymph node biopsy showing characteristic histological features. Simultaneously, NGS analysis of the laryngeal lesion showed a mutation in the MAP2K1 gene, in accordance with the diagnosis. The patient was treated with revlimid and dexamethasone for 6 months, with complete remission, and is currently undergoing maintenance treatment with revlimid.
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Histiocitose Sinusal , Humanos , Lenalidomida/uso terapêutico , Histiocitose Sinusal/diagnóstico , Histiocitose Sinusal/patologia , Histiócitos/patologia , Plasmócitos/patologia , Dexametasona/uso terapêuticoRESUMO
As the impact of targeted next-generation sequencing (TNGS) on daily diagnosis has not been evaluated, we performed TNGS (46 genes) on lymphomas of unclear subtype following expert haematopathological review. The potential impact on patient care and modifications of final diagnosis were divided into major and minor changes according to the European Society of Medical Oncology (ESMO) guidelines. Among 229 patients [19 primary central nervous system lymphomas (PCNSL), 48 large B-cell lymphomas (LBCLs), 89 small BCLs (SBCLs), seven Hodgkin lymphomas (HL), 66 T-cell lymphomas], the overall concordance rate of histological and TNGS diagnosis was 89·5%. TNGS confirmed the histological diagnosis in 144 cases (62·9%), changed the diagnosis in 24 cases (10·5%) and did not help to clarify diagnosis in 61 cases (26·7%). Modifications to the final diagnosis had a clinical impact on patient care in 8·3% of cases. Diagnostic modifications occurred in all types of lymphoma except in PCNSL and HL; the modification rate was 14·6% in SBCL and 12·5% in LBCL. While comparing informative and uninformative cases, no differences were found in terms of DNA amplification, quality or depth of sequencing and biopsy type. The present study highlights that TNGS may directly contribute to a more accurate diagnosis in difficult-to-diagnose lymphomas, thus improving the clinical management in routine practice.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Linfoma , Sistema de Registros , Idoso , Feminino , França , Humanos , Linfoma/diagnóstico , Linfoma/genética , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Adenomatoid tumors are benign tumors from mesothelial origin, usually occurring in the genital tract. Extragenital locations, especially in the adrenal gland are extremely rare. Here we are reporting two cases of a 28-year-old and 50-year-old men with an adenomatoid tumor of the right adrenal gland. Usual morphological aspects join scattered and microcystic pattern with epithelioid or signet-ring cells. According to the morphological features, main differential diagnoses are adenocarcinoma metastasis, vascular tumors or mesotheliomas. Immunohistochemistry provides precious help to confirm the mesothelial origin thanks to positivity of epithelial markers (CK7, AE1-AE3, CK5/6) coupled to mesothelial markers (D2-40, Calretinin, WT1). On the other hand, there is no loss of BAP1 by immunohistochemistry and usually a surexpression of P16. Adrenal gland adenomatoid tumor is a benign tumor, which can be promoted by iatrogenous or constitutive immunodepression.
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Tumor Adenomatoide , Neoplasias das Glândulas Suprarrenais , Mesotelioma , Tumor Adenomatoide/diagnóstico , Neoplasias das Glândulas Suprarrenais/diagnóstico , Glândulas Suprarrenais , Adulto , Biomarcadores Tumorais , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Masculino , Mesotelioma/diagnóstico , Proteínas Supressoras de Tumor , Ubiquitina TiolesteraseRESUMO
Composite and sequential lymphomas involving both classical Hodgkin lymphoma (CHL) and primary mediastinal B-cell lymphoma (PMBCL) are rare phenomena. Beyond the relevant biological interest raised by these cases, treatments and outcome data are poorly covered in the recent literature. This retrospective analysis describes the pathological and clinical characteristics of 10 composite and 15 sequential cases included after a central pathological review. At diagnosis, 70% of the composite lymphomas presented a disseminated and extranodal disease. Among the 15 sequential lymphomas, 12 were CHL at first occurrence and three were PMBCL. Based on their clinical evolution, these sequential lymphomas could be divided into early (i.e., diagnosis of second lymphoma within a year) and late [(i.e., a second lymphoma occurrence occurring after a long period of complete remission]). All composite cases were alive in complete remission after a median follow-up of 34 months. If the early sequential lymphoma presented a particularly poor outcome with a median overall survival shorter than one year, the late cases were efficiently salvaged. Further molecular studies are needed to describe the underlying biology of these rare diseases, possibly representing the extreme of tumour cell plasticity found in grey-zone lymphoma.
Assuntos
Doença de Hodgkin/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
AIMS: The peritoneal regression grading score (PRGS) and peritoneal cytology (PC) assess response to chemotherapy in peritoneal metastasis (PM) in a setting of palliative treatment by pressurized intraperitoneal aerosol chemotherapy (PIPAC). Progression has been defined as an increase of PRGS between first and third PIPAC procedures (iPRGS). iPRGSand positive peritoneal cytology were not associated with prognostic impact. These results may be explained by a lack of statistical power. Also, it is not known whether the mean or the highest PRGS among taken peritoneal biopsies bears the highest clinical value. We therefore conducted the largest prospective study to investigate the prognostic impact of PGRS, PC, and their combination, designated as combined progression index (CPI). METHODS AND RESULTS: Patients with PM who underwent >3 PIPAC (n = 112) between December 2016 and February 2019 were prospectively included. A significant difference in OS and PFS according to CPI (used highest value of PRGS) was found (OS: CPI-, 83.3, 95% CI [49.8; NA] vs. CPI+, 48.1, 95% CI [38.5; 66.4] months; and PFS (respectively, 59.7, 95% CI [43.0; 96.0] vs. 33.7, 95% CI [30.4; 44.2] months). PRGS or PC had no independent prognostic impact. CPI+ was an independent predictor of worse prognosis, in OS (HR = 5.24, 95% CI [2.07; 13.26]), and PFS (HR = 4.41, 95% CI [1.40; 13.88]). CONCLUSIONS: The CPI based on highest PRGS and PC was found to be independently associated with a worse prognosis for OS and for PFS in the setting of peritoneal metastasis. These results indicate that it should be of interest to systematically take peritoneal fluid for cytological examination and to implement the CPI in the therapeutic decision-making process in the context of PIPAC.
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Antineoplásicos/administração & dosagem , Citodiagnóstico/métodos , Metástase Neoplásica/diagnóstico , Metástase Neoplásica/tratamento farmacológico , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Aerossóis , Idoso , Idoso de 80 Anos ou mais , Biópsia , Quimioterapia Adjuvante/métodos , Progressão da Doença , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Prognóstico , Intervalo Livre de Progressão , Estudos ProspectivosRESUMO
Syphilis is a resurging sexually transmitted infection linked to Treponema Pallidum. Syphilitic lymphadenitis can be present during the 3 stages of the disease. Its histological diagnosis remains challenging for the pathologist given its possible misleading aspect and its ability to mimic as well as reactional as tumoral conditions. We report the case of an HIV-infected young patient referred for suspicion of an aggressive lymphoma. Histological and immunohistochemical analysis of cervical lymphadenopathy revealed secondary syphilis.
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Patologistas , Sífilis/diagnóstico , Adulto , Biópsia , Diagnóstico Diferencial , Infecções por HIV/complicações , Humanos , Linfonodos/patologia , Masculino , Papel do Médico , Pseudolinfoma/diagnóstico , Pele/patologia , Sífilis/complicações , Sífilis/microbiologia , Sífilis/patologia , Sorodiagnóstico da Sífilis , Treponema pallidum/imunologia , Treponema pallidum/isolamento & purificaçãoRESUMO
AIM: This novel multiparameter Phase I study aimed to optimize doses/dosing schedules of everolimus and sorafenib drug combination, based on modeling/simulation (NCT01932177). PATIENTS & METHODS: About 26 patients with solid tumors were treated in four different dosing schedules. Everolimus once daily + sorafenib twice daily were given continuously in arms A and B, and intermittently in arms C (alternating every other week) and D (everolimus continuous and sorafenib 3 days on/4 days off). RESULTS: Continuous schedules exhibited higher toxicity risks than intermittent schedules (64.1 vs 35.9%; p < 0.0001), and trends for lower disease control rates (80 vs 100%). No significant pharmacokinetic interaction was identified. CONCLUSION: Feasibility of EVESOR trial is demonstrated. Intermittent schedules might provide better tolerance and efficacy than continuous schedules.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Esquema de Medicação , Everolimo/administração & dosagem , Everolimo/farmacocinética , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Niacinamida/administração & dosagem , Niacinamida/análogos & derivados , Niacinamida/farmacocinética , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/farmacocinética , Inibidores de Proteínas Quinases/administração & dosagem , Sorafenibe , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Kasabach-Merritt phenomenon (KMP) is a rare life-threatening vascular condition of infancy. Prognosis factors and long-term follow-up data are lacking. We retrospectively analysed the records of 24 infants (10 females, 14 males) treated for KMP in the Department of Dermatology of Necker-Enfants Malades Hospital, Paris, France, from 1984 to 2012. Mean duration of thrombocytopaenia (2,000-38,000 platelets/mm3, mean 10,500/µl) was 8.8 months (range 3 days-84 months), which correlated with tumour infiltration depth on imaging. D-dimer levels were always elevated, even before KMP onset. Each patient received a mean of 4.8 different treatments (range 1-10). Median follow-up was 6.5 years (range 2 months-22 years). All infants had residual cutaneous lesions, along with inflammatory manifestations (n = 9), elevated D-dimer (n = 5) and orthopaedic sequelae (n = 5). The permanent coagulopathy (elevated D-dimer) even after resolution of KMP suggests the presence of chronic low-grade platelet trapping, with possible sudden worsening, and raises the possibility of prophylactic anti-platelet therapy.
Assuntos
Antineoplásicos/uso terapêutico , Hemangioendotelioma/terapia , Síndrome de Kasabach-Merritt/terapia , Inibidores da Agregação Plaquetária/uso terapêutico , Corticosteroides/uso terapêutico , Biomarcadores/sangue , Biópsia , Coagulação Sanguínea , Terapia Combinada , Embolização Terapêutica , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hemangioendotelioma/sangue , Hemangioendotelioma/diagnóstico , Hospitais Pediátricos , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Síndrome de Kasabach-Merritt/sangue , Síndrome de Kasabach-Merritt/diagnóstico , Masculino , Invasividade Neoplásica , Contagem de Plaquetas , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION: Diffuse malignant mesothelioma (MMD) is a rare disease. The diagnosis is difficult and needs an antibody panel. The tumor suppressor gene BRCA1 associated protein 1 (BAP1) is involved in several cancers, including MMD. Loss of BAP1 expression is correlated with BAP1 somatic or constitutional genetic defects. Our work assesses the value of integrating BAP1 in the panel of antibodies used for the diagnosis of MMD. MATERIALS AND METHODS: Immunohistochemical techniques were performed on cytological and histological specimens of MMD and adenocarcinoma pleural metastasis. RESULTS: Of the 26 patients with MMD and the 24 patients with adenocarcinoma pleural metastasis, loss of BAP1 expression was observed in 11 (48%) and one adenocarcinoma (6%) on cytological specimens and in 12 MMD (48%) and in one adenocarcinoma (5%) on biopsy specimens. The concordance between immunocytochemistry and immunohistochemistry was 100%. The specificity of BAP1 was 100% on cytological and biopsy specimen for the diagnosis of malignancy in case of mesothelial proliferation. DISCUSSION AND CONCLUSION: Loss of BAP1 expression is an indicator of MMD in a context of mesothelial proliferation. This immunohistochemistry could be integrated in the panel of immunostaining used for MMD diagnosis, either on histological or cytological samples. Furthermore, loss of BAP1 expression guides the patient to an oncology genetic counseling in order to eliminate a MMD developed as part of a constitutional genetic defect.
Assuntos
Biomarcadores Tumorais/análise , Mesotelioma/química , Proteínas de Neoplasias/análise , Neoplasias Pleurais/química , Proteínas Supressoras de Tumor/análise , Ubiquitina Tiolesterase/análise , Adenocarcinoma/química , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Biópsia , Diagnóstico Diferencial , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Aconselhamento Genético , Humanos , Mesotelioma/diagnóstico , Mesotelioma/genética , Mesotelioma/patologia , Pessoa de Meia-Idade , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/genética , Neoplasias Pleurais/patologia , Sensibilidade e EspecificidadeRESUMO
PURPOSE: The primary objective of this study was to determine the incidence rate of pathological complete responses (pCRs) following neoadjuvant systemic chemotherapy for the treatment of peritoneal carcinomatosis (PC) of colorectal origin. The secondary objective was to evaluate whether pathological response assessments predict survival of patients treated with curative intent by complete cytoreductive surgery (CRS). METHODS: A retrospective review was performed of 115 patients who underwent preoperative irinotecan- or oxaliplatin-based chemotherapy, followed by 124 procedures of complete CRS alone or combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The pathological response was defined as the mean percentage of cancer cells remaining within all specimens. Univariate and multivariate analyses were performed to identify predictors of survival and pathological response outcome. RESULTS: Twelve procedures (9.7 %) resulted in pCRs, defined as no residual cancer cells in all specimens, 25 (20.2 %) resulted in major responses (1 to 49 % residual cancer cells), and 87 (70.1 %) resulted in minor or no responses (>50 % residual cancer cells). The cumulative 5-year survival rates were 75 and 57 % for patients with pCR and major responses, respectively. Using multivariate analysis, pathological response was the only independent predictor of survival (P = 0.01; major response: hazard ratio [HR] = 4.91; minor response: HR = 13.46). No significant predictor of pathological response was identified. CONCLUSIONS: Pathological complete response can be achieved with preoperative systemic chemotherapy for patients with PC of colorectal origin. The degree of pathological response can be assessed and represented as a new outcome for prognosis following treatment with curative intent.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia do Câncer por Perfusão Regional , Neoplasias Colorretais/patologia , Hipertermia Induzida , Terapia Neoadjuvante , Neoplasias Peritoneais/secundário , Adulto , Idoso , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Terapia Combinada , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/terapia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de SobrevidaAssuntos
Antígenos CD19/metabolismo , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/metabolismo , Idoso , Antígenos CD19/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Biópsia , Medula Óssea/patologia , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Análise Mutacional de DNA , Suscetibilidade a Doenças , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/etiologia , Técnicas de Diagnóstico Molecular , Mutação , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêuticoRESUMO
As part of the national 2009-2013 Cancer Plan, and with the support of the National cancer Institute and the French ministry of health, the National network for the treatment of rare peritoneal malignancies (RENAPE) has been organized. Its main objective is to optimize the framework for the healthcare management and treatment of rare peritoneal malignancies. This specific organization covers the whole national territory including clinical expert and specialized structures and should lead to an appropriate treatment based on expertise and proximity. Within the RENAPE network, the RENA-PATH group gathers the pathologists actively involved in the management of rare peritoneal malignancies. The actions of RENA-PATH are focused primarily on the harmonization of pathological diagnostic criteria, reporting of new cases in the RENAPE registry and histology reviewing.
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Sistemas Multi-Institucionais , Neoplasias/patologia , Neoplasias/terapia , Patologia Clínica , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , França , Humanos , Doenças RarasRESUMO
Peritoneal malignant mesothelioma is a rare tumor, less common than its pleural counterpart. It develops from the mesothelial cells overlying peritoneum and preferentially occurs in male, with an average age ranging from 47 to 60.5 years. Asbestos whose impact is less strong than in pleural mesothelioma, SV 40 virus, chronic peritonitis could be implicated as factors favoring the development of peritoneal mesothelioma. Clinical symptoms are not specific, and the imagery remains little or not contributive. The 2004 WHO classification recognizes 3 different types, which differ in terms of presentation and prognosis: diffuse epithelioid mesothelioma (the most common), sarcomatoid mesothelioma and biphasic mesothelioma. Many variants are described within these groups. Immunohistochemistry is mandatory to affirm or disprove peritoneal malignant mesothelioma diagnosis, based on a panel of antibodies divided in positive markers and negative markers. Indeed an accurate diagnosis is necessary to define a therapeutic strategy more and more frequently based on the combination of radical surgery and hyperthermic intra peritoneal chemotherapy. Such an approach significantly improves the prognosis of these aggressive diseases.
Assuntos
Neoplasias Pulmonares , Mesotelioma , Neoplasias Peritoneais , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/patologia , Mesotelioma/patologia , Mesotelioma Maligno , Neoplasias Peritoneais/patologiaRESUMO
Since the description of primary mediastinal large B-cell lymphoma (PMBL) as a distinct entity from diffuse large B-cell lymphomas (DLBCL), numerous studies have made it possible to improve their definition. Despite this, this differential diagnosis can be challenging in daily practice. However, in some centers, PMBL may be treated according to a particular regimen, distinct from those used in DLBCL, emphasizing the importance of accurate identification at diagnosis. This study aimed to describe the histological and molecular characteristics of PMBL to improve the accuracy of their diagnosis. Forty-nine cases of PMBL were retrospectively retrieved. The mean age at diagnosis was 39 years (21-83), with a sex ratio of 0.88. All cases presented a fibrous background with diffuse growth of intermediate to large cells with an eosinophil (26/49, 53%) or retracted cytoplasm (23/49, 47%). "Hodgkin-like" cells were observed in 65% of cases (32/49, 65%). The phenotype was: BCL6+ (47/49, 96%), MUM1+ (40/49, 82%), CD30+ (43/49, 88%), and CD23+ (37/49, 75%). Genomic DNAs were tested by next generation sequencing of 33 cases using a custom design panel. Pathogenic variants were found in all cases. The most frequent mutations were: SOCS1 (30/33, 91%), TNFAIP3 (18/33, 54.5%), ITPKB (17/33, 51.5%), GNA13 (16/33, 48.5%), CD58 (12/33, 36.4%), B2M (12/33; 36.4%), STAT6 (11/33, 33.3%) as well as ARID1A (10/33, 30.3%), XPO1 (9/33, 27.3%), CIITA (8/33, 24%), and NFKBIE (8/33, 24%). The present study describes a PMBL cohort on morphological, immunohistochemical, and molecular levels to provide pathologists with daily routine tools. These data also reinforce interest in an integrated histomolecular diagnosis to allow a precision diagnosis as early as possible.
RESUMO
PURPOSE: Everolimus (EVE) and sorafenib (SOR) combination was associated with synergistic activity in preclinical models. However, previous clinical studies were hampered by cumulative toxicities when both were given continuously. The academic EVESOR trial (NCT01932177) was designed to assess alternative doses and intermittent dosing schedules of EVE and SOR combination therapy to improve the benefit-risk ratio for patients with solid tumors. METHODS: EVESOR is a multiparameter dose-escalation phase I trial investigating different doses and dosing schedules, with the final objective of generating data for modeling and simulation. Patients were allocated into continuous (A and B) or intermittent (C and D) schedules to determine the recommended phase II dose (RP2D). The clinical outcomes are presented here. RESULTS: Forty-three patients were included from 2013 to 2019. Most of them had gynecological (25.6%), cholangiocarcinomas (23.2%), colorectal (14.0%), and breast cancers (11.6%). Dose-escalation up to EVE 10 mg QD and SOR 400 mg BID was possible on intermittent schedules. Five dose-limiting toxicities were observed, and dose reductions were required in 39.5% patients, stabilizing at EVE 5 mg and SOR 200 mg BID for 58.1% of them. The overall response rate was 6.3%, and disease control rate was 75.0%. The median progression-free survival (PFS) was 3.6 months. The longest median PFS were observed in cholangiocarcinomas (9.9 months), and gynecological adenocarcinomas (9.2 months). CONCLUSION: Intermittent arms were associated with improved efficacy/toxicity profiles; and EVE 5 mg QD and SOR 200 mg BID was defined a clinically feasible dose. Strong signs of efficacy were found in cholangiocarcinomas and gynecologic carcinomas. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01932177.
Assuntos
Neoplasias da Mama , Colangiocarcinoma , Humanos , Feminino , Sorafenibe , Everolimo/efeitos adversos , Niacinamida , Compostos de Fenilureia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
T-follicular helper (TFH) markers are expressed in the microenvironnement of marginal zone B-cell lymphoma (MZL), and in lymphomas arising from TFH-cells, sometimes making the differential diagnosis difficult. In the skin, the "TFH-spectrum" is poorly defined, going from primary cutaneous lymphoproliferative disorder with small/medium CD4+ T-cells (SMLPD) to cutaneous localizations of systemic angioimmunoblastic T-cell lymphoma (cAITL), and may pass through intermediate forms (primary cutaneous T-follicular helper derived lymphoma, not otherwise specified (PCTFHL,NOS)). We retrospectively analyzed 20 MZL, 13 SMLPD, 5 PCTFHL, and 11 cAITL clinically, histologically, and molecularly, to define tools to differentiate them. Characteristics that might favor the diagnosis of MZL over SMLPD are: multiple skin nodules (p < 0.001), nodular architecture (p < 0.01), residual germinal centers with follicular dendritic cell network (p < 0.001), monotypic plasma cells (p < 0.001), and few staining with PD1 (p = 0.016) or CXCL13 (p = 0.03). PCTFHL and cAITL presented as multiple (p < 0.01) lesions, in older patients (p < 0.01), with systemic symptoms and/or biological alterations (p < 0.01). Immunophenotypic loss of T-cell markers (p < 0.001), BCL6 (p = 0.023) and/or CD10 staining (p = 0.08), and a higher proliferative index (≥ 30%, p = 0.039) favoured these diagnoses over SMLPD. Pathogenic variants were observed by genomic sequencing in 47% of MZL (TNFAIP3 (32%), EP300 (21%), NOTCH2 (16%), KMT2D (16%), CARD11 (10.5%)), 8% of SMLPD (TET2), 40% of PCTFHL (SOCS1 (20%), ARID1A (20%)) and 64% of cAITL (TET2 (63.6%), RHOA (36.4%), NOTCH1 (9%)). This study characterizes the various clinical and histological features between cutaneous lymphomas expressing TFH markers and highlights the value of the interest of screening for genomic mutations in difficult cases.