RESUMO
Malignant mesothelioma is strongly associated with prior asbestos exposure. Recently there has been interest in the role of talc exposure in the pathogenesis of mesothelioma. We have analyzed lung tissue samples from a large series of malignant mesothelioma patients. Asbestos bodies were counted by light microscopy and mineral fiber concentrations for fibers 5 µm or greater in length were determined by scanning electron microscopy equipped with an energy dispersive spectrometer. The values were compared with 20 previously published controls. Among 609 patients with mesothelioma, talc fibers were detected in 375 (62%) and exceeded our control values in 65 (11%). Elevated talc levels were found in 48/524 men (9.2%) and 17/85 women (20%). Parietal pleural plaques were identified in 30/51 informative cases (59%) and asbestosis in 5/62 informative cases (8%). Commercial amphiboles (amosite and/or crocidolite) were elevated in 52/65 (80%) and noncommercial amphiboles (tremolite, actinolite or anthophyllite) in 41/65 (63%). Both were elevated in 34/65 (52%). Asbestos body counts by light microscopy were elevated in 53/64 informative cases (83%). A history of working in industries associated with asbestos exposure and increased mesothelioma risk was identified in 36/48 cases in men, and a history of exposure as household contacts of an occupationally exposed individual was identified in 12/17 cases in women. We conclude that among patients with mesothelioma, the vast majority have talc levels indistinguishable from background. Of the remaining 11% with elevated talc levels, the vast majority (80%) have elevated levels of commercial amphibole fibers.
Assuntos
Mesotelioma Maligno/química , Fibras Minerais/análise , Neoplasias Peritoneais/química , Neoplasias Pleurais/química , Talco/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Amianto/efeitos adversos , Amianto/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Minerais/efeitos adversos , Talco/efeitos adversosRESUMO
BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a treatment option for peritoneal surface malignancies. The ability to detect microscopic foci of peritoneal metastasis intraoperatively may ensure the completeness of cytoreduction. In this study, we evaluated the suitability of a hand-held cathepsin-based fluorescent imaging system for intraoperative detection of appendiceal and colorectal peritoneal metastasis. METHODS: Peritoneal tumors and normal peritoneal tissues were collected from patients with appendiceal and colorectal peritoneal metastasis. Expression of different cathepsins (CTS-B, -D, -F, -G, -K, -L, -O, and -S) was determined by quantitative RT-PCR and immunohistochemistry. The hand-held cathepsin-based fluorescent imaging system was used to detect peritoneal xenografts derived from human colon cancer cells (HT29, LoVo and HCT116) in nu/nu mice. RESULTS: While the expression levels of CTS-B, -D, -L, and -S could be higher in peritoneal tumors than normal peritoneum with a median (range) of 6.1 (2.9-25.8), 2.0 (1.0-15.8), 1.4 (0.8-7.0), and 2.1 (1.6-13.9) folds by quantitative RT-PCR, respectively, CTS-B was consistently the major contributor of the overall cathepsin expression in appendiceal and colonic peritoneal tumors, including adenocarcinomas and low-grade appendiceal mucinous neoplasms. Using peritoneal xenograft mouse models, small barely visible colonic peritoneal tumors (<2.5 mm in maximum diameter) could be detected by the hand-held cathepsin-based fluorescent imaging system. CONCLUSIONS: Because cathepsin expression is higher in peritoneal tumors than underlying peritoneum, the hand-held cathepsin-based fluorescent imaging system could be useful for intraoperative detection of microscopic peritoneal metastasis during CRS-HIPEC and clinical trial is warranted.
Assuntos
Neoplasias do Apêndice/patologia , Catepsinas/análise , Neoplasias Colorretais/patologia , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Imagem Óptica/instrumentação , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/terapia , Adulto , Idoso , Animais , Catepsina B/análise , Catepsinas/genética , Feminino , Fluorescência , Células HCT116 , Células HT29 , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Pessoa de Meia-Idade , Transplante de Neoplasias , Imagem Óptica/métodos , Neoplasias Peritoneais/química , Neoplasias Peritoneais/secundário , Período Pré-Operatório , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: Indoleamine 2,3-dioxygenase-1 (IDO1) is a key regulator of immune tolerance in ovarian cancer. This study investigated efficacy and safety of the IDO1 enzyme inhibitor epacadostat versus tamoxifen in patients with biochemical-only recurrence (CA-125 elevation) following complete remission after first-line chemotherapy for advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer. METHODS: In this open-label, phase 2 study (NCT01685255), patients were randomised 1:1 to epacadostat 600mg or tamoxifen 20mg twice daily for successive 28-day cycles and stratified by time since completion of first-line chemotherapy to first CA-125 elevation (3 to <12 or ≥12months). The primary endpoint was investigator-assessed progression-free survival (PFS; RECIST v1.1). Secondary endpoints included CA-125 response (Gynecologic Cancer InterGroup criteria), overall survival, safety, and tolerability. RESULTS: The study was terminated primarily due to slow accrual and lack of evidence of superiority. Median PFS was 3.75months for epacadostat (n=22) versus 5.56months for tamoxifen (n=20; HR, 1.34 [95% CI, 0.58-3.14]; P=0.54). Of evaluable patients, 1 (5.0%) epacadostat and 3 (15.8%) tamoxifen patients had confirmed CA-125 responses. The most common treatment-emergent adverse event was fatigue (epacadostat, 36.4%; tamoxifen, 40.0%). Immune-related adverse events, observed with epacadostat only, were primarily rash (18.2%) and pruritus (9.1%). Epacadostat pharmacokinetics/pharmacodynamics were consistent with its known mechanism of action. IDO1 expression was observed in 94% of archival tumour samples. CONCLUSIONS: This first report of immunotherapy evaluation in biochemical-only relapse ovarian cancer and of IDO1 inhibitor monotherapy in ovarian cancer found no significant difference in efficacy between epacadostat and tamoxifen. Epacadostat was generally well tolerated.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Oximas/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Sulfonamidas/uso terapêutico , Tamoxifeno/uso terapêutico , Adulto , Idoso , Antineoplásicos Hormonais/efeitos adversos , Antígeno Ca-125/sangue , Carcinoma Epitelial do Ovário , Intervalo Livre de Doença , Toxidermias/etiologia , Término Precoce de Ensaios Clínicos , Exantema/induzido quimicamente , Neoplasias das Tubas Uterinas/sangue , Neoplasias das Tubas Uterinas/química , Fadiga/induzido quimicamente , Feminino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/análise , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/sangue , Neoplasias Epiteliais e Glandulares/química , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/química , Oximas/efeitos adversos , Oximas/farmacocinética , Neoplasias Peritoneais/sangue , Neoplasias Peritoneais/química , Prurido/induzido quimicamente , Recidiva , Critérios de Avaliação de Resposta em Tumores Sólidos , Sulfonamidas/efeitos adversos , Sulfonamidas/farmacocinética , Taxa de Sobrevida , Tamoxifeno/efeitos adversosRESUMO
Objective: To investigate the morphological features, diagnosis and differential diagnosis of extrapleural sarcomatoid malignant mesothelioma (SMM). Methods: Six cases of extrapleural SMM were evaluated for their clinical, histological, immunohistochemical features, and prognosis. Results: Patients included 3 men and 3 women, with a median age of 60 years (range 41-75 years). All patients had no asbestos exposure in history and no pleural lesions. The tumors involved peritoneum (3 cases), bone (2 cases), and neck soft tissue (1 case). Histologically, the tumors were mainly composed of slender to plump spindle cells with occasional polymorphic cells, arranged in fascicular to storiform pattern or haphazardly organized, closely resembling those of fibromatosis, fibrosarcoma or malignant fibrous histiocytoma. The tumor cells were imunohistochemically positive for cytokeratin (pan, 6/6), calretinin (5/6), podoplanin (6/6), D2-40 (4/6), vimentin (6/6), WT1 (4/6), CD10 (3/6), SMA (4/6), and variably positive for CK7, and CK8/18, but were negative for other linage-specific markers. The Ki-67 proliferation indexes ranged from 25% to 55%, consistent with the diagnosis of malignant mesothelioma of the sarcomatous type. Ultrastructurally, the tumor cells possessed discontinuous external lamina, cytoplasmic processes, microfilaments and desmosomal intercellular junctions. Local recurrence or metastasis was seen in 1 case and 4 cases, respectively, after surgery, and all the patients died of the disease within 9 months. Conclusions: Extrapleural SMM, although rare, should be considered as a differential diagnosis among other benign or malignant sarcomatoid tumors and sarcomas. Along with clinical and radiological presentation, the combination of broad-spectrum cytokeratin, vimentin, and a series of mesothelial markers are useful for diagnosis of SMM.
Assuntos
Neoplasias Ósseas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Mesotelioma/patologia , Neoplasias Peritoneais/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Neoplasias Ósseas/química , Calbindina 2/análise , Diagnóstico Diferencial , Feminino , Fibrossarcoma/patologia , Neoplasias de Cabeça e Pescoço/química , Humanos , Imuno-Histoquímica , Queratinas/análise , Masculino , Mesotelioma/química , Mesotelioma/diagnóstico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Peritoneais/química , Prognóstico , Sarcoma/patologia , Vimentina/análiseRESUMO
Peritoneal malignant mesothelioma is a rare and extremely aggressive tumor that is sometimes difficult to diagnose. We report two cases of metastatic malignant peritoneal mesothelioma. In one case, malignant metastatic cells were identified in cervical lymph nodes while in the other case, the cells were found in the liver. In both cases, metastases were identified before discovering the primary tumor. This led to the misdiagnosis of carcinoma of unknown origin. Nevertheless, the histological and immuno-histochemical patterns were typical of malignant mesothelioma. Regarding metastasis of unknown origin, a differentiation of epithelioid peritoneal malignant mesothelioma and adenocarcinoma proved to be difficult. Therefore, we discuss the diagnostic usefulness of immuno-histochemical mesothelioma markers.
Assuntos
Erros de Diagnóstico , Neoplasias Pulmonares/secundário , Metástase Linfática , Mesotelioma/secundário , Neoplasias Peritoneais/diagnóstico , Adenocarcinoma/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais , Calbindina 2/análise , Feminino , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/química , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/diagnóstico por imagem , Mesotelioma/química , Mesotelioma/diagnóstico , Mesotelioma/diagnóstico por imagem , Mesotelioma Maligno , Militares , Neoplasias Primárias Desconhecidas/diagnóstico , Exposição Ocupacional , Omento/patologia , Doenças Peritoneais/diagnóstico , Neoplasias Peritoneais/química , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/patologia , Tomografia Computadorizada por Raios XRESUMO
A comprehensive pathological report is essential for optimal patient management, cancer staging and prognostication. In many countries, proforma reports are used but these vary in their content. The International Collaboration on Cancer Reporting (ICCR) is an alliance formed by the Royal College of Pathologists of Australasia, the Royal College of Pathologists of the United Kingdom, the College of American Pathologists, the Canadian Partnership Against Cancer and the European Society of Pathology, with the aim of developing an evidence-based reporting data set for each cancer site. This will reduce the global burden of cancer data set development and reduplication of effort by different international institutions that commission, publish and maintain standardised cancer reporting data sets. The resultant standardisation of cancer reporting will benefit not only those countries directly involved in the collaboration but also others not in a position to develop their own data sets. We describe the development of a cancer data set by the ICCR expert panel for the reporting of primary ovarian, fallopian tube and peritoneal carcinoma and present the 'required' and 'recommended' elements to be included in the report with an explanatory commentary. This data set encompasses the recent International Federation of Obstetricians and Gynaecologists staging system for these neoplasms and the updated World Health Organisation Classification of Tumours of the Female Reproductive Organs. The data set also addresses issues about site assignment of the primary tumour in high-grade serous carcinomas and proposes a scoring system for the assessment of tumour response to neoadjuvant chemotherapy. The widespread implementation of this data set will facilitate consistent and accurate data collection, comparison of epidemiological and pathological parameters between different populations, facilitate research and hopefully will result in improved patient management.
Assuntos
Carcinoma/patologia , Neoplasias das Tubas Uterinas/patologia , Neoplasias Ovarianas/patologia , Patologia Clínica/normas , Neoplasias Peritoneais/patologia , Projetos de Pesquisa/normas , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia/normas , Carcinoma/química , Carcinoma/tratamento farmacológico , Carcinoma/genética , Carcinoma/cirurgia , Quimioterapia Adjuvante , Diagnóstico Diferencial , Neoplasias das Tubas Uterinas/química , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/cirurgia , Feminino , Humanos , Imuno-Histoquímica/normas , Técnicas de Diagnóstico Molecular/normas , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/química , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/química , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/cirurgia , Valor Preditivo dos TestesRESUMO
BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare locoregional disease characterized by disseminated intraperitoneal mucinous tumors. However, little is known about PMP from urachal neoplasm as a result of its rarity. METHODS: A total of 9 patients with PMP of urachal origin were treated by cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in our institution. All specimens of surgeries were submitted for pathologic examination. Representative slides of tumors and normal urachus were submitted for immunohistochemical staining. RESULTS: Four patients were men; the median age was 48 years (range 27-65 years). Initial radiologic examination of all patients showed a cystic tumor located between posterior aspect of umbilicus and the dome of urinary bladder, with or without leaking mucin. Complete CRS and HIPEC were performed in all patients. Until the latest follow-up, local recurrence occurred in 1 patient. Other 8 patients had a median disease-free survival of 27.5 months. Primary urachal tumors of 9 cases were all mucinous adenocarcinoma. Six patients had low-grade mucinous carcinoma peritonei, and 3 patients had high-grade mucinous carcinoma peritonei. Signet ring cells were noted in 4 patients. All tumor specimens of 9 patients were diffuse positive for CK-20, CDX-2, MUC-2, and MUC-5AC, and were variant positive for CK-7. CONCLUSIONS: PMP arising from urachus comes from neoplastic cells with development of intestinal-type mucinous neoplasm. It shares a similar pathophysiology as PMP from appendix. CRS including total urethrectomy, partial cystectomy, and peritonectomy plus HIPEC can be considered as a new option of treatment for PMP originating from urachus.
Assuntos
Adenocarcinoma Mucinoso/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Neoplasias Peritoneais/terapia , Pseudomixoma Peritoneal/terapia , Úraco , Adenocarcinoma Mucinoso/química , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Fator de Transcrição CDX2 , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Feminino , Proteínas de Homeodomínio/análise , Humanos , Infusões Parenterais , Queratina-20/análise , Queratina-7/análise , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Mucina-5AC/análise , Mucina-2/análise , Neoplasias Peritoneais/química , Neoplasias Peritoneais/patologia , Pseudomixoma Peritoneal/metabolismo , Pseudomixoma Peritoneal/patologia , Transativadores/análiseAssuntos
Sarcoma Histiocítico/diagnóstico , Neoplasias Peritoneais/diagnóstico , Ascite/etiologia , Biomarcadores Tumorais , Erros de Diagnóstico , Evolução Fatal , Hemorragia Gastrointestinal/etiologia , Hepatite C Crônica/complicações , Histiócitos/patologia , Sarcoma Histiocítico/complicações , Sarcoma Histiocítico/metabolismo , Sarcoma Histiocítico/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/química , Neoplasias Peritoneais/complicações , Neoplasias Peritoneais/patologia , Peritonite/diagnósticoRESUMO
AIM: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and locally aggressive tumor with poor prognosis, related in most cases to asbestos exposure. It is increasing in frequency, but currently no standard therapy is available. The biology of this disease is still poorly understood. Several highly specialized centers have recently reported improved survival by means of an innovative local-regional approach. The purpose of this article is to evaluate the survival benefit and the morbidity rate of patients affected by DMPM treated at our institution by cytoreductive surgery (CRS) associated with hyperthermic intraperitoneal perioperative chemotherapy (HIPEC). METHODS: This study includes 42 patients affected by DMPM treated by an uniform approach consisting of cytoreductive surgery associated with HIPEC using cisplatin and doxorubicin. The primary end point was overall survival and morbidity rate. The secondary end point was evaluation of prognostic variables for overall survival. RESULTS: The median follow-up period was 72 months (range 1-235 months). Thirty-five patients (83.3%) presented epithelial tumors and 7 were affected by multicystic mesothelioma. The mean peritoneal cancer index (PCI) was 13. Thirty-eight patients (90.4%) had complete cytoreduction (CC-0/1). The overall morbidity rate was 35.7% associated to a perioperative mortality of 7.1%. Median overall survival rate was 65 months with a 1- and 5-year survival rates of 63% and 44%, respectively. CONCLUSION: The treatment of DMPM by CRS+HIPEC in selected patients is a feasible technique that allows to achieve encouraging results in terms of overall survival rate, with an acceptable morbidity rate. Further investigations are needed to clarify the role and the timing of this promising technique.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Laparotomia , Neoplasias Pulmonares/cirurgia , Mesotelioma/cirurgia , Neoplasias Peritoneais/cirurgia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/análise , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Terapia Combinada , Doxorrubicina/administração & dosagem , Feminino , Humanos , Hipertermia Induzida , Infusões Parenterais , Estimativa de Kaplan-Meier , Antígeno Ki-67/análise , Laparoscopia , Neoplasias Pulmonares/química , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Mesotelioma/química , Mesotelioma/diagnóstico , Mesotelioma/tratamento farmacológico , Mesotelioma Maligno , Pessoa de Meia-Idade , Seleção de Pacientes , Neoplasias Peritoneais/química , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/tratamento farmacológico , Cuidados Pré-Operatórios , Resultado do Tratamento , Adulto JovemRESUMO
Wolffian tumor and its nosologic relative, the recently defined STK11 adnexal tumor are rare neoplasms thought to arise from mesonephric remnants. These tumors typically arise in the broad ligament, fallopian tube, and ovarian hilum and although most are associated with a good prognosis, up to 50% of STK11 adnexal tumors demonstrate aggressive clinical behavior. The chief differential diagnoses include endometrioid adenocarcinoma and sex cord stromal tumors. However, the morphologic and immunohistochemical features of these tumors exhibit considerable overlap with peritoneal mesothelioma. To fully characterize their immunophenotypic signature, we examined a total of 21 cases (18 Wolffian and 3 STK11 adnexal tumors) with standard markers used in the diagnosis of mesothelioma. Morphologic and immunohistochemical (IHC) features were reviewed and additional IHC performed for cases with available material. Patient age ranged from 25 to 73 (mean: 51) years. Sites included adnexa/broad ligament (6, 28%), paratubal (5, 24%), ovary/paraovarian (5, 24%), tubal (intraluminal) (2, 9.5%), pelvis (2, 9.5%), and liver (1, 5%). The mean tumor size was 9.3 cm (range: 0.2 to 22 cm). The histomorphology in most cases (14/21, 66%) consisted of tubular to solid sheets of neoplastic cells lined by columnar to cuboidal cells containing uniform round to oval nuclei. Compressed tubules with slit-like lumens and sieve-like pattern were also seen in at least 7 (33%) cases. Three cases demonstrated interanastomosing cords and trabeculae of epithelioid cells with cribriform and microacinar patterns growing within prominent myxoid stroma as described in STK11 adnexal tumors. In the cases with available IHC for 3 mesothelial markers (calretinin, WT1, D2-40), 55.5% (5 of 9) showed reactivity with all 3 markers. In cases with at least 2 available mesothelial markers, 69% (11/16) were positive for 2 markers (mostly calretinin and WT1). Claudin-4, MOC31, and BER-EP4 were negative in most cases tested (78% [7/9], 71.4% [5/7], and 100% [6/6], respectively). Given the resemblance to mesothelioma, there was initial strong consideration and/or actual misdiagnosis of mesothelioma in 3 cases (14%). In summary, the morphologic and immunohistochemical features of Wolffian tumor and its recently defined relative, STK11 adnexal tumor, can lead to misdiagnosis of mesothelioma, particularly when encountered in the disseminated or metastatic setting. Wolffian tumor and STK11 adnexal tumor should be considered in the differential diagnosis of all pelvic and peritoneal mesotheliomas.
Assuntos
Biomarcadores Tumorais , Imuno-Histoquímica , Mesotelioma , Neoplasias Peritoneais , Humanos , Feminino , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/química , Neoplasias Peritoneais/diagnóstico , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Pessoa de Meia-Idade , Idoso , Adulto , Mesotelioma/patologia , Mesotelioma/diagnóstico , Mesotelioma/química , Valor Preditivo dos Testes , Quinases Proteína-Quinases Ativadas por AMP , Adenoma , Doenças dos AnexosRESUMO
OBJECTIVE: Well-differentiated papillary mesothelioma is an uncommon subtype of mesothelioma with a frequently indolent course, although it occasionally manifests in a more aggressive form. To establish a treatment strategy for this rare disease, we report the clinical characteristics and outcomes of 15 patients with well-differentiated papillary mesothelioma. METHODS: All pathologically diagnosed well-differentiated papillary mesothelioma cases were reviewed between 1998 and 2012. RESULTS: Of the 15 cases, 8 and 7 presented with single and multiple lesions, respectively. All cases with single lesions were asymptomatic, while 4 out of the 7 cases with multiple lesions were symptomatic. After tumor excision, none of the eight single-lesion cases experienced tumor recurrence. Among the other seven cases with multiple lesions, only one patient with disseminated lesions died due to disease burden. Five patients with multiple lesions received cisplatin-based intravenous or intraperitoneal chemotherapy, with a mix of complete (n= 2) and partial (n= 2) responses observed. Of particular note, one patient receiving cisplatin and pemetrexed combination chemotherapy experienced complete tumor resolution without any serious toxicity. CONCLUSIONS: We recommend different treatment strategies based on the disease status. If the tumor is completely resectable, an excisional biopsy seems to be sufficient. If complete resection is unavailable for the asymptomatic patient with a localized tumor extent, close follow-up is an appropriate option. When the tumor is extensive or accompanied by symptoms, chemotherapy should be strongly considered.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Mesotelioma/diagnóstico , Mesotelioma/terapia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/terapia , Adulto , Idoso , Anticorpos Monoclonais Murinos/análise , Calbindina 2 , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Feminino , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Imuno-Histoquímica , Infusões Intravenosas , Infusões Parenterais , Masculino , Mesotelioma/química , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Mesotelioma/cirurgia , Pessoa de Meia-Idade , Imagem Multimodal , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/terapia , Pemetrexede , Neoplasias Peritoneais/química , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Tomografia por Emissão de Pósitrons , Prognóstico , Fatores de Risco , Proteína G de Ligação ao Cálcio S100/análise , Tomografia Computadorizada por Raios X , Resultado do TratamentoAssuntos
Adenocarcinoma/secundário , Neoplasias Primárias Desconhecidas/patologia , Neoplasias Peritoneais/secundário , Adenocarcinoma/química , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Idoso de 80 Anos ou mais , Algoritmos , Biomarcadores Tumorais , Feminino , Humanos , Proteínas de Neoplasias/análise , Especificidade de Órgãos , Neoplasias Peritoneais/química , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/patologiaRESUMO
Deciduoid mesothelioma is a rare variant of epithelioid mesothelioma that was initially considered to occur exclusively in the peritoneum of young women who had no history of asbestos exposure and to be characterized by an aggressive clinical course, but it was later demonstrated that this tumor could also occur in the pleura of older men and women who had been exposed to asbestos. Some subsequent studies have also indicated that the clinical course is no different from that of conventional epithelioid mesothelioma. Herein are reported 21 cases of deciduoid mesothelioma that were investigated using a large panel of immunohistochemical markers, 9 of which were also studied by electron microscopy. Fifteen of the patients were male and 6 were female (mean age, 60 years). Seventeen of the cases originated in the pleura and four in the peritoneum. Histologically, all of the cases were composed of large, polygonal or ovoid cells with well-defined cell borders, dense eosinophilic cytoplasm, and single or multiple nuclei. In some cases, the cells exhibited a wide variation in their size and shape, frequent loss of cell cohesion, marked nuclear atypia, and high mitotic activity (>5 per 10 HPF); whereas, in others, the cells were more cohesive, less pleomorphic, and the mitotic activity low. As the survival of patients in the first group of cases was shorter (mean, 7 months), when compared with that of the latter (mean, 23 months), it is concluded that the differences in prognosis reported in deciduoid mesothelioma are due to the existence of a high-grade subgroup that presents highly aggressive clinical behavior. Therefore, when a high-grade deciduoid mesothelioma is present, it should be reported as it can significantly affect prognosis and treatment. The use of immunohistochemistry and electron microscopy in assisting in the differential diagnosis of deciduoid mesothelioma is also discussed.
Assuntos
Células Epitelioides , Mesotelioma , Neoplasias Peritoneais , Neoplasias Pleurais , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/análise , Forma Celular , Tamanho Celular , Diagnóstico Diferencial , Células Epitelioides/química , Células Epitelioides/ultraestrutura , Feminino , Humanos , Imuno-Histoquímica , Masculino , Mesotelioma/química , Mesotelioma/mortalidade , Mesotelioma/terapia , Mesotelioma/ultraestrutura , Microscopia Eletrônica , Pessoa de Meia-Idade , Índice Mitótico , Gradação de Tumores , Neoplasias Peritoneais/química , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/terapia , Neoplasias Peritoneais/ultraestrutura , Neoplasias Pleurais/química , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/terapia , Neoplasias Pleurais/ultraestrutura , Valor Preditivo dos Testes , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Intraperitoneal accumulation of mucinous ascites in pseudomyxoma peritonei (PMP) promotes an inflammatory/fibrotic reaction that progresses to bowel obstruction and eventual patient demise. Cytokines and inflammation-associated transcription factor binding sites, such as glucocorticoid response elements and COX-2, regulate secretory mucin, specifically MUC2, production. We hypothesized that anti-inflammatory drugs targeting inflammation-associated pathways may reduce mucin production and subsequent disease morbidity in PMP. METHODS: The effects of dexamethasone and Celebrex were assessed in mucin-secreting human colon cancer LS174T cells in vitro and murine xenograft models of LS174T and human appendiceal PMP in vivo by serial parametric measurements, MUC2 transcripts via real-time RT-PCR, and MUC2 protein expression via immunofluorescence assays. RESULTS: Dexamethasone significantly inhibited basal MUC2 mRNA levels in LS174T cells, inhibited mucinous tumor accumulation in an intraperitoneal PMP xenograft model, and prolonged survival in a subcutaneous LS174T xenograft model. Celebrex significantly inhibited sodium butyrate-stimulated MUC2 mRNA levels in LS174T cells and demonstrated a statistically nonsignificant trend toward reduced mucinous tumor growth and prolonged survival in the xenograft models. MUC2 protein analysis by immunofluorescence demonstrated a dual effect of dexamethasone on mucin production and tumor cell count. CONCLUSIONS: Inflammatory mediators are known to regulate mucin production and may promote overexpression of MUC2 by neoplastic cells with goblet cell phenotype in PMP. Anti-inflammatory drugs, dexamethasone and Celebrex, could inhibit extracellular mucin production in PMP by targeting inflammatory cascades and, therefore, may decrease compressive symptoms, increase the disease-free interval, and reduce the extent or frequency of morbid cytoreductive surgeries.
Assuntos
Dexametasona/administração & dosagem , Mucina-2/biossíntese , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/metabolismo , Pseudomixoma Peritoneal/tratamento farmacológico , Pseudomixoma Peritoneal/metabolismo , Pirazóis/administração & dosagem , Sulfonamidas/administração & dosagem , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Neoplasias do Apêndice/química , Neoplasias do Apêndice/tratamento farmacológico , Neoplasias do Apêndice/metabolismo , Neoplasias do Apêndice/patologia , Celecoxib , Neoplasias do Colo/química , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esquema de Medicação , Humanos , Camundongos , Camundongos Nus , Mucina-2/efeitos dos fármacos , Mucina-2/isolamento & purificação , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Peritoneais/química , Neoplasias Peritoneais/patologia , Pseudomixoma Peritoneal/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoAssuntos
Carcinossarcoma/patologia , Falência Renal Crônica/terapia , Diálise Peritoneal , Neoplasias Peritoneais/patologia , Diálise Renal , Idoso , Biomarcadores Tumorais/análise , Biópsia , Carcinossarcoma/química , Carcinossarcoma/diagnóstico por imagem , Evolução Fatal , Humanos , Imuno-Histoquímica , Queratinas/análise , Falência Renal Crônica/diagnóstico , Masculino , Neoplasias Peritoneais/química , Neoplasias Peritoneais/diagnóstico por imagemAssuntos
Neoplasias da Próstata/patologia , Sarcoma/patologia , Humanos , Antígeno Ki-67/análise , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Neoplasias Peritoneais/química , Neoplasias Peritoneais/secundário , Prostatectomia , Hiperplasia Prostática/cirurgia , Neoplasias da Próstata/química , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/cirurgia , Receptores de Progesterona/análise , Sarcoma/química , Sarcoma/diagnóstico , Sarcoma/cirurgia , Ressecção Transuretral da Próstata , Vimentina/análiseRESUMO
Benign papillary mesothelioma of the peritoneum is an uncommon lesion that is usually discovered by chance during a surgical procedure. This lesion resembles metastatic carcinoma in gross appearance; therefore, intraoperative diagnosis can be difficult. This report presents a case of benign papillary mesothelioma concurrent with gastric cancer. The tumor was located on the hepatogastric ligament and resembled a metastatic peritoneal implant. A pathological review confirmed the diagnosis to be benign papillary mesothelioma.
Assuntos
Adenocarcinoma/patologia , Mesotelioma/patologia , Neoplasias Primárias Múltiplas , Neoplasias Peritoneais/patologia , Neoplasias Gástricas/patologia , Adenocarcinoma/química , Adenocarcinoma/cirurgia , Biomarcadores Tumorais/análise , Biópsia , Gastrectomia , Humanos , Imuno-Histoquímica , Masculino , Mesotelioma/química , Mesotelioma/cirurgia , Pessoa de Meia-Idade , Neoplasias Peritoneais/química , Neoplasias Peritoneais/cirurgia , Valor Preditivo dos Testes , Neoplasias Gástricas/química , Neoplasias Gástricas/cirurgia , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the significance of expression of epidermal growth factor receptor (EGFR), telomerase and topoisomerase IIα (topo IIα) in cells of malignant effusions of patients under chemotherapy. METHODS: We studied the expression of EGFR, telomerase and topo IIα in malignant effusion smears of 95 cancer patients before and after chemotherapy. Immunocytochemical and in situ hybridization techniques were applied. RESULTS: Positive expression before chemotherapy of telomerase, topo IIα and EGFR was found in 64.2, 63.2 and 69.5% of the cases, respectively; the expression of these markers following chemotherapy was 43.6, 28.2 and 53.8%, respectively. The stronger prognostic factor affecting survival before chemotherapy was telomerase (p=0.0002), whereas after chemotherapy the strongest factor was EGFR (p<0.0001). A positivity for all three markers following chemotherapy was associated with shorter survival compared with positivity for only 1 or 2 markers (p<0.0001) or with a negative expression. CONCLUSION: It seems that expression of EGFR, telomerase and topo IIα in malignant effusion smears is adversely affecting prognosis and survival.
Assuntos
Antígenos de Neoplasias/análise , Líquido Ascítico/química , DNA Topoisomerases Tipo II/análise , Proteínas de Ligação a DNA/análise , Receptores ErbB/análise , Neoplasias Peritoneais/química , Derrame Pleural Maligno/química , Telomerase/análise , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/mortalidade , Derrame Pleural Maligno/tratamento farmacológico , Derrame Pleural Maligno/mortalidade , PrognósticoRESUMO
Primary peritoneal malignant mesothelioma (MM) can demonstrate morphologic overlap with low-grade and high-grade tubo-ovarian serous neoplasms; it is also biologically and prognostically distinct from benign mesothelial proliferations. Currently, there is no single biomarker that can definitively distinguish these neoplasms. Sex-determining region Y box 6 (SOX6) immunohistochemistry has been recently described to differentiate pleural epithelioid MM from lung adenocarcinoma, but it has not been evaluated in the peritoneum. SOX6 immunohistochemistry was performed on 43 peritoneal epithelioid MM, 7 peritoneal biphasic MM, 5 well-differentiated papillary mesotheliomas, 5 serous borderline tumors, 29 low-grade serous carcinomas (LGSCs), 20 high-grade serous carcinomas (HGSCs), and 25 cases of peritoneal reactive mesothelial hyperplasia. Quantitative SOX6 expression in epithelioid MM (median, 100% of tumor cells) was significantly greater than in LGSC/serous borderline tumor (median, 90%; P=0.004) and HGSC (median, 45%; P=0.0001). However, when SOX6 is expression is defined as ≥10% of tumor cells, there was no significant difference in the rate of SOX6 positivity between epithelioid MM (41/43, 95%), LGSC (28/29, 97%; P=1.0), and HGSC (17/20, 85%; P=0.16). Quantitative extent of SOX6 expression in epithelioid MM was significantly greater than in biphasic MM (median, 0%; P=0.0001), well-differentiated papillary mesothelioma (median, 20%; P=0.001), and reactive mesothelial hyperplasia (median, 20%; P=0.0001), but not significantly different from flat quiescent mesothelium (median, 90%; P=0.82). SOX6 immunohistochemistry is 95% sensitive for peritoneal epithelioid MM, but is also consistently expressed in LGSC and HGSC, negating its usefulness in this common differential diagnosis. SOX6 also shows variable expression across the spectrum of reactive, benign neoplastic, and malignant mesothelial lesions of the peritoneum, and does not appear to be diagnostically useful in distinguishing benign from malignant mesothelial proliferations.
Assuntos
Biomarcadores Tumorais/análise , Células Epitelioides/química , Neoplasias das Tubas Uterinas/química , Mesotelioma Maligno/química , Neoplasias Císticas, Mucinosas e Serosas/classificação , Neoplasias Ovarianas/química , Neoplasias Peritoneais/química , Fatores de Transcrição SOXD/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células , Bases de Dados Factuais , Diagnóstico Diferencial , Células Epitelioides/patologia , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Mesotelioma Maligno/patologia , Pessoa de Meia-Idade , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Valor Preditivo dos Testes , Adulto JovemRESUMO
Mesonephric-like adenocarcinomas (MLA) are rare neoplasms arising in the uterine corpus and ovary which have been added to the recent 2020 World Health Organization Classification of Female Genital Tumors. They have similar morphology and immunophenotype and exhibit molecular aberrations similar to cervical mesonephric adenocarcinomas. It is debated as to whether they are of mesonephric or Mullerian origin. We describe the clinical, pathologic, immunohistochemical, and molecular features of 5 cases of extrauterine mesonephric-like proliferations (4 ovary, 1 extraovarian), all with novel and hitherto unreported features. These include an origin of MLA in extraovarian endometriosis, an association of ovarian MLA with high-grade serous carcinoma, mixed germ cell tumor and mature teratoma, and a borderline ovarian endometrioid tumor exhibiting mesonephric differentiation. Four of the cases exhibited a KRAS variant and 3 also a PIK3CA variant. In reporting these cases, we expand on the published tumor types associated with MLA and report for the first time a borderline tumor exhibiting mesonephric differentiation. We show the value of molecular testing in helping to confirm a mesonephric-like lesion and in determining the relationship between the different neoplastic components. We provide further evidence for a Mullerian origin, rather than a true mesonephric origin, in some of these cases. We also speculate that in the 2 cases associated with germ cell neoplasms, the MLA arose out of the germ cell tumor.