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1.
Int J Mol Sci ; 21(23)2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33266349

RESUMO

Conjunctival melanoma (CM) iss a rare and aggressive tumour that is increasing in frequency. The prognostic value of PD-L1 expression, alone or in combination with CD8 and PD-1 expression and the BRAF and NRAS status, has not been determined in CM to date. We evaluated the expression of PD-L1, CD8, PD-1 in CM and investigated whether there was an association between the expression of these markers and the BRAF and NRAS molecular profile as well as some clinico-pathological criteria. A total of sixty-five CM were assessed for PD-L1, PD-1, and CD8 expression by immunohistochemistry (IHC) and for BRAF and NRAS genomic alterations using molecular biology techniques and anti-BRAF and anti-NRAS antibodies. PD-L1 expression in tumour cells (TC) was very low or absent but detected in tumour-infiltrating immune cells (IC). A correlation was observed between the expression of PD-L1, CD8, and PD-1 in IC. No correlation between PD-L1 expression (in tumour and/or immune cells) and BRAF or NRAS mutations was observed. PD-L1 expression in IC correlated with a higher pTNM stage and PD-L1 expression in TC with worse disease-specific survival. PD-L1 expression is a potential prognostic biomarker that correlates with poor prognosis in CM patients.


Assuntos
Antígeno B7-H1/genética , Biomarcadores Tumorais , Neoplasias da Túnica Conjuntiva/genética , Neoplasias da Túnica Conjuntiva/mortalidade , Expressão Gênica , Melanoma/genética , Melanoma/mortalidade , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Neoplasias da Túnica Conjuntiva/patologia , Feminino , Humanos , Imuno-Histoquímica , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Melanoma/patologia , Mutação , Prognóstico
3.
Eur J Cancer ; 163: 211-221, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35090811

RESUMO

PURPOSE: To prospectively assess the impact of expert pathological review of skin adnexal carcinoma diagnosis in France. METHODS: From 2014 to 2019, 2573 samples from patients with newly diagnosed or suspected skin adnexal carcinomas were reviewed prospectively by expert pathologists through the national CARADERM (CAncers RAres DERMatologiques) network. Changes in diagnosis between referral and expert review were analysed regarding their potential impact on patient care or prognosis. RESULTS: The samples comprised 2205 newly diagnosed adnexal carcinomas, 129 benign adnexal tumours, 136 basal cell carcinomas, 74 squamous cell carcinomas, six cutaneous metastases and 13 other malignancies. There were 930 (42%) sweat gland carcinomas, of which porocarcinoma (261; 11.8%), microcystic adnexal carcinoma (125; 5.7%) and hidradenocarcinoma (109; 4.9%) were the most frequent subtypes; 778 (35%) hair follicle carcinomas, 238 (11%) sebaceous carcinomas and 212 (10%) extramammary Paget diseases/mammary-like anogenital gland adenocarcinomas. A diagnostic change between referral and expert review occurred in 503 (21.3%) patients, significantly higher for cases sent with a provisional diagnosis seeking an expert second opinion (45.7%) than for cases sent with a formal diagnosis (2.8%) (p < .0001). Sweat gland carcinomas were more prone to diagnostic discrepancies than other tumours (p < .0001), including 1.8% of patients with sweat gland carcinoma subtype misclassification with predicted clinical impact. Changes between benign and malignant conditions occurred in 117 samples (5% of patients). CONCLUSION: The study provides a unique description of the distribution of skin adnexal carcinomas and highlights the importance of expert review for these rare cancers. Optimal clinical management was impacted in a significant proportion of patients.


Assuntos
Carcinoma , Neoplasias de Anexos e de Apêndices Cutâneos , Neoplasias das Glândulas Sebáceas , Neoplasias Cutâneas , Neoplasias das Glândulas Sudoríparas , Humanos , Neoplasias de Anexos e de Apêndices Cutâneos/diagnóstico , Neoplasias das Glândulas Sebáceas/diagnóstico , Neoplasias das Glândulas Sebáceas/patologia , Pele/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias das Glândulas Sudoríparas/patologia
5.
Pathol Oncol Res ; 15(1): 65-72, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18752046

RESUMO

The purpose of this study was to find histological clues for reliable differentiation between monoclonal gammopathy of undetermined significance (MGUS) and myeloma when clinical parameters are controversial. Differential appearance of dendritic cells and osteoclasts, two cell types developing from the monocytic lineage upon distinct cytokine activation profile, might be a useful approach. Bone and bone-marrow biopsies performed in 105 patients were studied using histomorphometry after identification of osteoclasts (by histochemical identification of tartrate resistant acid phosphatase) and dendritic cells (by immunohistochemical detection of the S-100 protein). Patients were classified by the World Health Organization criteria but histopathological criteria were more adapted to identify MGUS (53 cases), myeloma (46), B-cell lymphoma (six) since six myeloma were not correctly classified. Histomorphometry was compared to 15 control cases. The number of marrow dendritic cell was significantly increased with B-cell lymphoma >MGUS >myeloma > controls. Dendritic cell were often mixed with lymphoma cells. Myeloma had increased bone resorption with a high osteoclast number and moderate increase in dendritic cells. B-cell lymphomas had a considerable increase in dendritic cell but presented mononucleated osteoclasts. These findings can help in the classification of MGUS in the early stages of the disease and could help to propose preventive treatments.


Assuntos
Medula Óssea/patologia , Células Dendríticas/patologia , Osteoclastos/patologia , Paraproteinemias/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/metabolismo , Células Dendríticas/metabolismo , Diagnóstico Diferencial , Feminino , Citometria de Fluxo , Humanos , Linfoma de Células B/metabolismo , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Osteoclastos/metabolismo , Paraproteinemias/metabolismo , Prognóstico
6.
Int J Dermatol ; 56(5): 527-533, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28188628

RESUMO

BACKGROUND: Immune checkpoint blockade therapy (ICBT) for the treatment of melanoma has led to an important improvement of overall survival in advanced stage patients. However, secondary cutaneous maculopapular eruptions (CMPEs) are frequent and remain poorly characterized. METHODS: We performed a retrospective analysis of melanoma patients from our institution who developed CMPEs during ICBT. Clinical information was retrieved, and histopathological and immunohistochemical characterization was performed by two pathologists. For comparison, a group of biopsies from CMPE caused by anti-v-raf murine sarcoma viral oncogene homolog B1 (BRAF) therapy was analyzed. RESULTS: Eleven patients met the inclusion criteria. On clinical grounds, CMPE developed mainly on early onset of immunotherapy and were of low grade. Typical lesions included erythematous papules and macules affecting the trunk and/or extremities with associated pruritus. The histopathological patterns consisted of a superficial perivascular lymphocytic dermatitis (SPLD) with eosinophils followed by a granulomatous dermatitis. Other patterns included lichenoid, spongiotic, and a case of Grover's disease. The inflammatory infiltrate consisted of T lymphocytes (CD3+ ) with a predominance of CD4+ over CD8+ cells; isolated Foxp3+ cells were invariably present, and PD-1 was not expressed. Biopsies from CMPE caused by anti-BRAF therapy showed an SPLD and a similar lymphocytic immunophenotype. CONCLUSIONS: Our study showed the clinical features of a group of melanoma patients with CMPE for ICBT and emphasized the wide spectrum of histological findings as well as their immunohistochemical profile. Differential diagnosis can be difficult with CMPE provoked by other therapies as was seen in our comparison group of anti-BRAF-induced eruptions.


Assuntos
Antineoplásicos/efeitos adversos , Toxidermias/patologia , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Toxidermias/etiologia , Feminino , Humanos , Imuno-Histoquímica , Imunoterapia/efeitos adversos , Ipilimumab/efeitos adversos , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Nivolumabe , Estudos Retrospectivos , Neoplasias Cutâneas/patologia
7.
Diagn Mol Pathol ; 13(2): 97-104, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15167011

RESUMO

Cytogenetic studies in lymphomas classically require fresh or frozen tissue, whereas in many instances only paraffin-embedded biopsies are available. We applied an interphase FISH assay on nuclei extracted from thick paraffin sections to determine accuracy of molecular cytogenetics in such samples. Twenty-three lymphoma samples and 4 reactive lymph nodes were tested with various commercially available DNA probes, and hybridization patterns were compared with those obtained on frozen nuclei counterparts. Successful hybridization with all probes tested was observed for 23/27 (85%) paraffin-embedded tissues and for all (100%) frozen samples, and cut-off levels defining positivity were superimposable for both situations. Chromosome changes were detected in the same way, without any false-positive or false-negative cases. Hybridization signals observed on dewaxed samples were either those classically expected to define the relevant chromosome change or were atypical: all atypical changes could be demonstrated also into nuclei from the frozen counterpart. Moreover, all typical and atypical chromosome changes observed on frozen nuclei were also detected in paraffin-embedded tissues. Our study shows that our interphase FISH assay performed on paraffin-embedded samples is a valuable alternate to conventional methods to ascertain diagnosis of lymphomas as to include patients into therapeutic trials.


Assuntos
Artefatos , DNA de Neoplasias/análise , Técnicas Histológicas , Linfonodos/patologia , Linfoma não Hodgkin/genética , Aberrações Cromossômicas , DNA de Neoplasias/genética , DNA de Neoplasias/isolamento & purificação , Formaldeído , Secções Congeladas , Técnicas Histológicas/métodos , Humanos , Hibridização in Situ Fluorescente , Inclusão em Parafina , Fixação de Tecidos
8.
Endocr Pathol ; 13(3): 227-33, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12446922

RESUMO

We report a case of a 42-yr-old woman with Langerhans cell histiocytosis (LCH) confined to the thyroid and associated with lymphocytic thyroiditis and a papillary microcarcinoma. This patient remains free of symptoms 14 mo after surgery. Thyroid LCH is rare. In children, it usually occurs as part of a multisystemic disease, whereas it is usually exclusive in adults. Isolated thyroid LCH is frequently associated with another thyroid disease, especially lymphocytic thyroiditis, suggesting that it is a reactive process rather than a neoplastic proliferation. The prognosis of isolated thyroid LCH is good. However, because it can rarely precede or reveal a multisystemic disease, additional investigations as well as a prolonged follow-up are justified.


Assuntos
Carcinoma Papilar/patologia , Histiocitose de Células de Langerhans/patologia , Neoplasias da Glândula Tireoide/patologia , Tireoidite Autoimune/patologia , Adulto , Carcinoma Papilar/complicações , Carcinoma Papilar/cirurgia , Feminino , Histiocitose de Células de Langerhans/complicações , Histiocitose de Células de Langerhans/cirurgia , Humanos , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Tireoidite Autoimune/complicações , Tireoidite Autoimune/cirurgia , Resultado do Tratamento
12.
J Mater Sci Mater Med ; 18(2): 287-94, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17323160

RESUMO

Several studies have shown that macro micro porous bioceramics ectopically implanted promote bone tissue formation. This study aims at investigating the inflammatory response towards biphasic calcium phosphate (BCP) ceramic micro particles. BCP composed of hydroxyapatite (HA) and beta-tricalcium phosphate, HA/beta -TCP ratio of 50/50, were prepared by sintering at 1200 degrees C for 5 h. After crushing, 3 fractions of BCP micro particles < 20, 40-80 and 80-200 micro m were sieved. The micro particles were carefully characterized by using X-ray diffraction (XRD), scanning electron microscopy (SEM) and laser scattering. The inflammatory reactions induced by BCP micro particles implanted in quadriceps muscles of rats for 7, 14 and 21 days were studied by histology (n = 8/group). A fibrous tissue encapsulation of the BCP micro particles implanted in muscle tissue was observed and fibrosis was similar for the 3 groups of micro particles. The comparison of the cellular response indicated that the total number of cells was significantly higher for BCP < 20 micro m than for 40-80 and 80-200 micro m (p < 0.0001). The number of macrophages was relatively higher for the smallest than for the intermediate and largest fractions (p < 0.0001). The relative percentage of giant cells was higher for the intermediate and largest size of particles than for the smallest. The number of lymphocytes was comparable for the 3 fractions and after the 3 delays. Therefore, the BCP micro particles < 20 micro m initiated an inflammatory response which might play an important role in osteogenesis.


Assuntos
Fosfatos de Cálcio/efeitos adversos , Fosfatos de Cálcio/química , Implantes Experimentais/efeitos adversos , Inflamação/induzido quimicamente , Inflamação/patologia , Ácidos Polimetacrílicos/efeitos adversos , Ácidos Polimetacrílicos/química , Engenharia Tecidual/métodos , Animais , Materiais Biocompatíveis/efeitos adversos , Materiais Biocompatíveis/química , Técnicas de Cultura de Células/métodos , Inflamação/imunologia , Teste de Materiais , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Propriedades de Superfície
13.
Mod Pathol ; 16(8): 756-63, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12920219

RESUMO

Routine calcitonin (CT) assay programs and genetic testing for RET proto-oncogene mutations have consistently modified the management and understanding of C-cell proliferative disorders. We report a series of 66 consecutive patients with C-cell hyperplasia (CCH) or medullary thyroid carcinoma (MTC) observed in our institution within an 8-year time period. All the patients had a preoperative basal CT assay and an RET proto-oncogene sequencing. Seventeen patients (F-M ratio: 8:9, mean age: 29.7 y) had a multiple endocrine neoplasia Type 2: 3 children <10 years of age had CCH only, and 14 patients had an MTC, with neoplastic CCH in 10/14 cases. Twenty-seven patients (F-M ratio: 18:9, mean age: 56.6 y) had a sporadic MTC, with physiological CCH in 8 and neoplastic CCH in 3 cases. Twenty-two men (mean age: 46.2 y) had CCH only (physiological CCH in 17 men and neoplastic CCH in 5). We conclude that (1) clinical and pathological characteristics (familial MTC, tumor multifocality, neoplastic CCH) usually associated with hereditary MTC may be misleading and that on the contrary, RET sequencing gives no false positive result; (2) sporadic neoplastic CCH accompanies (and probably precedes) a number of sporadic MTC; and (3) women presenting with a sporadic elevated basal CT have a 100% risk of having an MTC (15/15), but this risk is 3-fold less in men (31%), who will most often have CCH only (69%).


Assuntos
Carcinoma Medular/diagnóstico , Neoplasia Endócrina Múltipla/diagnóstico , Glândula Tireoide/citologia , Neoplasias da Glândula Tireoide/diagnóstico , Adolescente , Adulto , Idoso , Carcinoma Medular/genética , Criança , Pré-Escolar , Feminino , Humanos , Hiperplasia/diagnóstico , Hiperplasia/genética , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla/genética , Mutação , Reação em Cadeia da Polimerase , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-ret , Receptores Proteína Tirosina Quinases/genética , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/genética
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