RESUMO
BACKGROUND AND PURPOSE: Intraplaque neovessels (INVs) have been recognized as a major cause of intraplaque hemorrhage and subsequent vulnerability of the carotid plaque. However, the exact mechanisms by which INVs cause intraplaque hemorrhage remain unclear. Various sizes of INVs coexist in carotid plaques pathologically, and we hypothesized that the size of INVs would be associated with carotid plaque histology, particularly in terms of intraplaque hemorrhage. Detection method of INV is important when determining whether carotid plaques are vulnerable, and contrast-enhanced ultrasonography (CEUS) is one of the most useful methods to detect them. The purpose of this study was to examine the relationship between findings from CEUS and vascular pathology obtained by carotid endarterectomy (CEA). We focused on associations between small and large INVs evaluated by CEUS and histologically defined intraplaque hemorrhage. METHODS: Participants comprised 115 patients (mean age, 73.0 ± 7.2 years; 96 men) who underwent preoperative CEUS and underwent CEA. CEUS findings were evaluated as vascular grade at 0 min (Vas-G0) and 10 min (Vas-G10) after contrast injection. Plaques were histologically evaluated quantitatively for the total area of intraplaque hemorrhage, cholesterol, and calcification and the thinnest fibrous cap. Immunohistochemical studies were conducted using anti-CD-34 antibody as a marker for endothelial cells. INVs were divided into two groups depending on diameter: small INVs, <50 µm; and large INVs, ≥50 µm. The numbers of small and large blood vessels in the plaque were quantified histologically. Associations of small and large INVs with CEUS, plaque histology, and clinical findings were assessed by uni- and multivariable analyses. RESULTS: Multivariable analyses indicated that CEUS Vas-G0 was associated with the 4th quartile of the number of small INVs compared with other quartiles, and Vas-G10 was associated with the 4th quartile of the number of large INVs. Histologically, the presence and area of intraplaque hemorrhage were associated with the number of small INVs, while the increased number of large INVs was associated with infrequent plaque disruption and thicker fibrous cap. CONCLUSIONS: Our study showed that early phase enhancement in the CEUS can help identify plaque vulnerability by predicting a larger number of small INVs. This information can also help determine treatment strategies for carotid plaque.
Assuntos
Estenose das Carótidas , Endarterectomia das Carótidas , Placa Aterosclerótica , Masculino , Humanos , Idoso , Idoso de 80 Anos ou mais , Estenose das Carótidas/complicações , Células Endoteliais , Meios de Contraste , Artérias Carótidas/patologia , Ultrassonografia , Placa Aterosclerótica/complicações , Hemorragia/etiologia , Hemorragia/complicações , Neovascularização Patológica/diagnóstico por imagem , Neovascularização Patológica/complicações , Neovascularização Patológica/patologiaRESUMO
As more than 80% of pleural mesothelioma (PM) cases start with pleural effusions, diagnosis with effusion smear cytology or pleural biopsy is important. For diagnosing PM, a three-step approach is used: (1) detecting atypical cells; (2) verifying their mesothelial origin using immunohistochemistry (IHC); and (3) discriminating PM from benign mesothelial proliferations (BMP). The third step is critical for diagnosing early lesions. In small biopsy or cytologic specimens in which tumor cell fat invasion cannot be assessed, genomic-based assays, including IHC-detected BAP1 loss and fluorescence in situ hybridization (FISH)-detected homozygous deletion (HD) of CDKN2A/p16, are effective for differentiation. Both BAP1 IHC and CDKN2A FISH can equally be applied to histologic and cytologic specimens, with 100% specificity in discriminating PM from BMP. We found that methylthioadenosine phosphorylase (MTAP) loss as detected by IHC could serve as a feasible alternative in tissue and cytologic preparations for CDKN2A FISH. However, a combination including FISH was still most effective: the addition of NF2 FISH to CDKN2A FISH and BAP1 IHC yielded a greater sensitivity of close to 100% in diagnosing PM tissues. Although IHC is more feasible than FISH, owing to remaining challenges in data interpretation, caution and familiarity are warranted when diagnosing PM.
Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Biomarcadores Tumorais/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Genômica , Homozigoto , Humanos , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/patologia , Mesotelioma/diagnóstico , Mesotelioma/genética , Mesotelioma/patologia , Mesotelioma Maligno/diagnóstico , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/genética , Neoplasias Pleurais/patologia , Deleção de Sequência , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genéticaRESUMO
A 71-year-old woman presenting with headache and nausea was admitted to hospital. Magnetic resonance imaging revealed a tumorous lesion that surrounded the sella turcica and infiltrated the sphenoid sinus with bone destruction. The tumor was removed by nasal endoscopy. The histology was consistent with pituitary adenoma; immunohistochemistry indicated silent corticotroph adenoma with melanocyte proliferation. The possibility that melanocytes were incorporated into the tumor mass in the sphenoid sinus and underwent proliferation was evaluated by investigating the mechanisms of melanocyte proliferation associated with basic fibroblast growth factor (bFGF) and α melanocyte-stimulating hormone (αMSH). In the normal tissue, the pars intermedia and adrenocorticotropic hormone (ACTH)-producing cells were positive for αMSH. None of the control adenoma tissues were positive for bFGF or αMSH by immunostaining. In the present case, bFGF-positive cells and αMSHpositive cells were observed, suggesting that both may have been involved in melanocyte proliferation. The expression of bFGF has been linked to aggressive disease. Pituitary adenoma with melanocyte proliferation has not been previously reported. Careful follow-up is deemed necessary in the future.
Assuntos
Adenoma , Neoplasias dos Seios Paranasais , Neoplasias Hipofisárias , Adenoma/patologia , Idoso , Proliferação de Células , Feminino , Humanos , Imageamento por Ressonância Magnética , Melanócitos/patologia , Neoplasias dos Seios Paranasais/patologia , Neoplasias Hipofisárias/patologia , Seio Esfenoidal/metabolismo , Seio Esfenoidal/patologiaRESUMO
AIM: Genomic-based ancillary assays including immunohistochemistry (IHC) for BRCA-1 associated protein-1 (BAP1) and methylthioadenosine phosphorylase (MTAP), and fluorescence in situ hybridization (FISH) for CDKN2A are effective for differentiating pleural mesothelioma (PM) from reactive mesothelial proliferations. We previously reported a combination of MTAP and BAP1 IHC effectively distinguishes sarcomatoid PM from fibrous pleuritis (FP). Nevertheless, cases of sarcomatoid PM with desmoplastic features (desmoPM) are encountered where the IHC assessment is unclear. METHODS AND RESULTS: We evaluated assessment of MTAP IHC, BAP1 IHC, and CDKN2A FISH in 20 desmoPM compared to 24 FP. MTAP and BAP1 IHC could not be assessed in 11 (55 %) and 10 (50 %) cases, respectively, due to loss or faint immunoreactivity of internal positive control cells, while CDKN2A FISH could be evaluated in all cases. The sensitivities for MTAP loss, BAP1 loss, and CDKN2A homozygous deletion in desmoPM were 40 %, 10 %, and 100 %. A combination of MTAP loss and BAP1 loss yielded 45 % of sensitivity. CONCLUSIONS: MTAP IHC is a useful surrogate diagnostic marker in differentiating ordinary sarcomatoid PM from FP, but its effectiveness is limited in desmoPM. CDKN2A FISH is the most effective diagnostic assays with 100 % sensitivity and specificity in discriminating desmoPM from FP in the facilities where the FISH assay is available.
Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Sarcoma , Neoplasias de Tecidos Moles , Biomarcadores Tumorais , Inibidor p16 de Quinase Dependente de Ciclina/genética , Homozigoto , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Mesotelioma/diagnóstico , Mesotelioma/genética , Mesotelioma Maligno/diagnóstico , Neoplasias Pleurais/diagnóstico , Purina-Núcleosídeo Fosforilase , Deleção de Sequência , Ubiquitina Tiolesterase/genéticaRESUMO
Malignant peritoneal mesothelioma historically carried a grim prognosis, but outcomes have improved substantially in recent decades. The prognostic significance of clinical, morphologic, and immunophenotypic features remains ill-defined. This multi-institutional cohort comprises 225 malignant peritoneal mesotheliomas, which were assessed for 21 clinical, morphologic, and immunohistochemical parameters. For epithelioid mesotheliomas, combining nuclear pleomorphism and mitotic index yielded a composite nuclear grade, using a previously standardized grading system. Correlation of clinical, morphologic, and immunohistochemical parameters with overall and disease-free survival was examined by univariate and multivariate analyses. On univariate analysis, longer overall survival was significantly associated with diagnosis after 2000 (P = 0.0001), age <60 years (P = 0.0001), ECOG performance status 0 or 1 (P = 0.01), absence of radiographic lymph-node metastasis (P = 0.04), cytoreduction surgery (P < 0.0001), hyperthermic intraperitoneal chemotherapy (P = 0.0001), peritoneal carcinomatosis index <27 (P = 0.01), absence of necrosis (P = 0.007), and epithelioid histotype (P < 0.0001). Among epithelioid malignant mesotheliomas only, longer overall survival was further associated with female sex (P = 0.03), tubulopapillary architecture (P = 0.005), low nuclear pleomorphism (P < 0.0001), low mitotic index (P = 0.0007), and low composite nuclear grade (P < 0.0001). On multivariate analyses, the low composite nuclear grade was independently associated with longer overall and disease-free survival (P < 0.0001). Our data further clarify the interactions of clinical and pathologic features in peritoneal mesothelioma prognosis and validate the prognostic significance of a standardized nuclear-grading system in epithelioid malignant mesothelioma of the peritoneum.
Assuntos
Mesotelioma Maligno/patologia , Gradação de Tumores/métodos , Neoplasias Peritoneais/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Núcleo Celular/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Prognóstico , Adulto JovemRESUMO
Squamous cell carcinoma of the external auditory canal (SCC-EAC) is rare and has a poor prognosis. The SCC-EAC cases with high-grade tumor budding (TB) or poorly differentiated clusters (PDCs) are associated with shorter survival than those with low-grade TB or PDCs. Extracellular matrix metalloproteinase inducer (emmprin) is a protein expressed in tumor cells that stimulates the production of MMP-2 by stromal fibroblasts to facilitate tumor invasion. Recently, we reported that emmprin forms a complex with CD73 to regulate MMP-2 production from fibroblasts in vitro. Here, we examined the association of emmprin and CD73 expression with TB or PDCs as well as with survival in 34 biopsy specimens of SCC-EAC patients. High tumoral emmprin expression was associated with high-grade TB, whereas high stromal CD73 expression was associated with high-grade PDCs. Furthermore, concurrent elevated expression of tumoral emmprin and stromal CD73 was determined to be an independent poor prognostic factor. In immunoprecipitation analyses, complex formation between emmprin and CD73 was demonstrated in vitro. Production of MMP-2 from fibroblasts was more abundant when cocultured with tumor cells than from fibroblasts cultured alone. Furthermore, MMP-2 production was reduced by the transfection of CD73 siRNA in fibroblasts cocultured with tumor cells. The colocalization of emmprin and CD73 was enhanced in not only the peripheral cells of the tumor cell clusters that interact with fibroblasts but also in the cells of intratumor clusters. Overall, this study provides novel insights into the roles of emmprin, CD73, and MMP-2 in tumor invasiveness.
Assuntos
5'-Nucleotidase/metabolismo , Basigina/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/mortalidade , Meato Acústico Externo/patologia , Neoplasias da Orelha/mortalidade , 5'-Nucleotidase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Basigina/genética , Biomarcadores Tumorais/genética , Biópsia , Fibroblastos Associados a Câncer/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Técnicas de Cocultura , Intervalo Livre de Doença , Neoplasias da Orelha/genética , Neoplasias da Orelha/patologia , Feminino , Seguimentos , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica/patologia , Prognóstico , RNA Interferente Pequeno/metabolismo , Estudos Retrospectivos , Microambiente TumoralRESUMO
Neurofibromatosis type 2 (NF2) gene, a tumor suppressor gene located on chromosome 22q12.2, is frequently abnormal in mesothelioma. Recent studies have revealed the effectiveness of diagnostic assays for differentiating malignant pleural mesothelioma from reactive mesothelial hyperplasia. These include detection of homozygous deletion of the 9p21 locus by fluorescence in situ hybridization (FISH) (9p21 FISH), loss of expression of BAP1 as detected by immunohistochemistry, and loss of expression of methylthioadenosine phosphorylase (MTAP) as detected by immunohistochemistry. However, the application of FISH detection of NF2 gene deletion (NF2 FISH) in differentiation of malignant pleural mesothelioma from reactive mesothelial hyperplasia has not been fully evaluated. In this study, we investigated whether NF2 FISH, either alone or in a combination with other diagnostic assays (9p21 FISH, MTAP immunohistochemistry, and BAP1 immunohistochemistry), is effective for distinguishing malignant pleural mesothelioma from reactive mesothelial hyperplasia. This study cohort included malignant pleural mesothelioma (n = 47) and reactive mesothelial hyperplasia cases (n = 27) from a period between 2001 and 2017. We used FISH to examine deletion status of NF2 and 9p21 and immunohistochemistry to examine expression of MTAP and BAP1 in malignant pleural mesothelioma and in reactive mesothelial hyperplasia. Hemizygous NF2 loss (chromosome 22 monosomy or hemizygous deletion) was detected in 25 of 47 (53.2%) mesothelioma cases. None of the mesothelioma cases showed homozygous NF2 deletion. Hemizygous NF2 loss showed 53.2% sensitivity and 100% specificity in differentiating malignant pleural mesothelioma from reactive mesothelial hyperplasia. A combination of NF2 FISH, 9p21 FISH, and BAP1 immunohistochemistry yielded greater sensitivity (100%) than that detected for either diagnostic assay alone (53.2% for NF2 FISH, 78.7% for 9p21 FISH, 70.2% for MTAP immunohistochemistry, or 57.4% for BAP1 immunohistochemistry). Thus, NF2 FISH in combination with other diagnostic assays is effective for distinguishing malignant pleural mesothelioma from reactive mesothelial hyperplasia.
Assuntos
Biomarcadores Tumorais/genética , Deleção de Genes , Hibridização in Situ Fluorescente , Mesotelioma Maligno/genética , Neurofibromina 2/genética , Neoplasias Pleurais/genética , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 9 , Feminino , Predisposição Genética para Doença , Hemizigoto , Humanos , Hiperplasia , Imuno-Histoquímica , Masculino , Mesotelioma Maligno/química , Mesotelioma Maligno/mortalidade , Mesotelioma Maligno/patologia , Pessoa de Meia-Idade , Fenótipo , Neoplasias Pleurais/química , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/patologia , Valor Preditivo dos Testes , Prognóstico , Purina-Núcleosídeo Fosforilase/análise , Reprodutibilidade dos Testes , Estudos Retrospectivos , Proteínas Supressoras de Tumor/análise , Ubiquitina Tiolesterase/análiseRESUMO
Ancillary studies facilitate accurate diagnosis of morphologically challenging mesothelial proliferations. The current diagnostic algorithm proceeds from BAP1 immunohistochemistry to CDKN2A fluorescence in situ hybridization. While MTAP immunohistochemistry has recently shown promise as a surrogate for CDKN2A fluorescence in situ hybridization, it has been examined in only a few single-institution studies. Furthermore, there are no published reports on interobserver agreement or interlaboratory reproducibility for MTAP immunohistochemistry. We performed MTAP immunohistochemistry on 20 benign mesothelial lesions and 99 malignant mesotheliomas from five mesothelioma centers in four countries, and each MTAP stain was independently interpreted by four pathologists. CDKN2A fluorescence in situ hybridization data were available for a subset of cases, and a subset of cases was subjected in MTAP immunohistochemistry in multiple laboratories to assess interlaboratory reproducibility. Interobserver agreement in MTAP immunostain interpretation was excellent for all mesothelial lesions (kappa: 0.85) and for malignant mesothelioma cases only (kappa: 0.82). Interlaboratory reproducibility was also excellent (kappa values for paired protocols: 0.77-0.89). MTAP loss by immunohistochemistry was 78% sensitive and 96% specific for CDKN2A homozygous deletion. MTAP immunohistochemistry is a reliable surrogate for CDKN2A fluorescence in situ hybridization in diagnosis of malignant mesothelioma. Interobserver agreement is excellent for interpretation of MTAP staining, and protocols performed in different laboratories yield concordant MTAP staining results. Rare cases with immunohistochemical MTAP loss may retain normal CDKN2A copy number, and the MTAP staining results should be correlated with clinicopathologic findings and other ancillary studies.
Assuntos
Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Mesotelioma Maligno/enzimologia , Mesotelioma Maligno/genética , Neoplasias Pleurais/enzimologia , Neoplasias Pleurais/genética , Purina-Núcleosídeo Fosforilase/análise , França , Humanos , Mesotelioma Maligno/patologia , América do Norte , Variações Dependentes do Observador , Neoplasias Pleurais/patologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , TóquioRESUMO
AIMS: Laminin (Ln)-γ 2, one of the chains of Ln-332, is a marker of invasive tumours and is frequently expressed as a monomer in malignant tumours. Desmoplastic trichoepithelioma (DTE), some types of basal cell carcinoma (BCC) (infiltrating and morphoeic BCC) and microcystic adnexal carcinoma (MAC) belong to a group of tumours known as sclerosing adnexal neoplasms (SAN) that are frequently difficult to differentiate and often require immunohistochemistry for diagnosis. The aim of this study was to assess the usefulness of Ln-γ 2 expression in the differential diagnosis of DTE, infiltrating/morphoeic BCC, MAC and syringoma. METHODS AND RESULTS: In this study, we compared the expression of Ln-γ 2 in infiltrating/morphoeic BCC (n = 28), DTE (n = 26), MAC (n = 10) and syringoma (n = 20). Immunohistochemically, Ln-γ 2 positivity was noted in 96% (27 cases) of infiltrating/morphoeic BCC and 90% (nine cases) of MAC, while all DTE and syringoma cases were negative. Furthermore, Ln-γ 2 expression pattern in infiltrating/morphoeic BCC was different from that in MAC. Ln-γ 2 expression was found in the cytoplasm of tumour cells in infiltrating/morphoeic BCC tumour cells, while in MAC linear expression was noted both along tumour nests and in the cytoplasm. CONCLUSION: Ln-γ 2 is a helpful adjunct in the differential diagnosis of SAN.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Basocelular/diagnóstico , Moléculas de Adesão Celular/metabolismo , Neoplasias de Anexos e de Apêndices Cutâneos/diagnóstico , Neoplasias Cutâneas/diagnóstico , Neoplasias das Glândulas Sudoríparas/diagnóstico , Siringoma/diagnóstico , Carcinoma Basocelular/patologia , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Japão , Queratina-20/metabolismo , Neoplasias , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Esclerose , Neoplasias Cutâneas/patologia , Neoplasias das Glândulas Sudoríparas/patologia , Siringoma/patologia , CalininaRESUMO
OBJECTIVE. The purpose of this article is to review the appearance of various abnormalities that affect the lumbar intervertebral disk and diskovertebral segment through anatomic-pathologic correlation in cadavers. CONCLUSION. Familiarity with the pathologic conditions in and around the intervertebral disk is important in recognizing such conditions as a potential source of symptoms. We revisit the principal role of MRI in evaluating these abnormalities and excluding other sources of significant clinical manifestations.
Assuntos
Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/patologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Imageamento por Ressonância Magnética , Cadáver , Humanos , Dor Lombar/diagnóstico por imagem , Dor Lombar/patologiaRESUMO
Mesothelioma in situ (MIS) has recently been investigated as a distinct phase of mesothelioma carcinogenesis. The diagnostic criteria proposed for MIS include a loss of BRCA1-associated protein 1 (BAP1) expression detected by immunohistochemistry (IHC). However, the length of time that MIS typically remains an in situ lesion before progression to invasive disease is still unclear. Herein, we report a case of a Japanese woman in her early seventies who had suffered from recurrent pleural effusions for 15 years, during which MIS developed and progressed to invasive mesothelioma. Retrospective diagnosis of partial MIS, fully developed MIS, and invasive disease was made using BAP1 IHC on three biopsy specimens and via clinical observations with radiological images. MIS and invasive lesions revealed BAP1 loss. The interval from partial or full MIS to invasive disease was 14 and 7 years, respectively. These results support a diagnostic strategy combining histomorphology with genomic-based assays including BAP1 IHC in biopsy tissues from a patient with recurrent pleural effusions.
Assuntos
Mesotelioma , Derrame Pleural/complicações , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Biópsia , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Mesotelioma/diagnóstico , Mesotelioma/patologia , Mesotelioma Maligno/diagnóstico , Mesotelioma Maligno/patologia , Derrame Pleural/patologia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/patologia , Prognóstico , Estudos RetrospectivosRESUMO
There are several reports of pleural adenomatoid (microcystic) mesothelioma, but peritoneal adenomatoid mesothelioma is extremely rare. A 64-year-old Japanese woman presented with no symptoms and no asbestos exposure history. An abdominal computed tomography scan revealed multiple hypervascular masses on the liver surface, pelvic cavity and anterior peritoneum. Over 10 pieces of the multiple resected tumors showed numerous microcysts composed of a bland mesothelial cell background with rich capillary vessels. Focally, atypical cells with bizarre nuclei with prominent nucleoli were observed. Adenomatoid mesothelioma was suspected based on histochemical, immunohistochemical and fluorescence in situ hybridization findings. The tumors relapsed 4 years later and metastasized to the lung, but the patient remains alive 7 years after the first tumor resection surgery. Although the prognosis of adenomatoid mesothelioma of pleural origin is poor, the progression of this peritoneal case is slow.
Assuntos
Tumor Adenomatoide/patologia , Mesotelioma/patologia , Neoplasias Peritoneais/patologia , Peritônio/patologia , Feminino , Humanos , Hibridização in Situ Fluorescente/métodos , Mesotelioma Maligno/diagnóstico , Mesotelioma Maligno/patologia , Pessoa de Meia-Idade , Neoplasias Peritoneais/diagnóstico , PrognósticoRESUMO
BRCA1-associated protein 1 (BAP1) or methylthioadenosine phosphorylase (MTAP) immunohistochemistry (IHC) or 9p21 fluorescence in situ hybridization (FISH) are useful for the diagnosis of malignant pleural mesothelioma (MPM). However, the effect of these assays on the diagnostic yield of effusion cytology in MPM cases with suspicious cytomorphology or the diagnostic challenges in BAP1 or MTAP IHC have not been fully elucidated. Two cohorts of cytologic preparations obtained from pleural effusions were examined: MPM cases in cohort 1 were used to evaluate whether BAP1 or MTAP IHC or 9p21 FISH increase the diagnostic yield of effusion cytology; cohort 2 included cases suspicious for MPM, to which BAP1 or MTAP IHC was applied to clarify the challenges in the clinical assessment of these assays. In cohort 1 (n = 28), either assay elevated 62.5% of class II or III cases to class V. In cohort 2 (n = 139), 21.7% of BAP1 immunocytochemistry in smears and 10.6% of BAP1 IHC and 9.4% of MTAP IHC in cell blocks, were identified to be challenging. The application of genomic-based assays increased the diagnostic yield of effusion cytology in the diagnosis of MPM. However, diagnostic challenges limit the application of these assays in some cases.
Assuntos
Mesotelioma Maligno , Neoplasias Pleurais , Purina-Núcleosídeo Fosforilase , Proteínas Supressoras de Tumor , Ubiquitina Tiolesterase , Biomarcadores Tumorais/química , Biomarcadores Tumorais/metabolismo , Citodiagnóstico , Diagnóstico Diferencial , Genoma Humano , Genômica , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mesotelioma/diagnóstico , Mesotelioma/genética , Mesotelioma/patologia , Mesotelioma Maligno/diagnóstico , Mesotelioma Maligno/genética , Mesotelioma Maligno/patologia , Gradação de Tumores , Derrame Pleural/patologia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/genética , Neoplasias Pleurais/patologia , Purina-Núcleosídeo Fosforilase/química , Purina-Núcleosídeo Fosforilase/genética , Purina-Núcleosídeo Fosforilase/metabolismo , Proteínas Supressoras de Tumor/química , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/química , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismoRESUMO
AIMS: Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome that results from tobacco smoking. Emphysema and fibrosis in CPFE patients have been considered to exist separately, with emphysema in the upper lobes and interstitial pneumonia in the lower lobes. The aim of this study was to examine the intrapulmonary distribution of fibrosis and emphysema in clinically diagnosed patients with idiopathic pulmonary fibrosis (IPF) and coexisting emphysema. METHODS AND RESULTS: Among IPF patients (n = 40) who had been autopsied or pneumonectomised for lung transplantation from 1993 to 2018, we retrospectively selected patients with IPF and coexisting emphysema (n = 19) on the basis of the appearance on chest computed tomography (IPF patients with emphysema). We then histologically determined the intrapulmonary distribution of emphysema and fibrosis in the upper lobes and the lower lobes separately. In 15 of the 19 IPF patients with emphysema (79%), fibrosis and emphysema coexisted in the upper lobes and the lower lobes. No patients showed emphysema exclusively in the upper lobes and fibrosis exclusively in the lower lobes. CONCLUSIONS: In the autopsied and pneumonectomised specimens of IPF patients with emphysema, craniocaudal separation of emphysema and fibrosis (emphysema in the upper lobes and interstitial pneumonia in the lower lobes) was histologically rare; coexistence or collision of fibrosis and emphysema in each lobe was common.
Assuntos
Fibrose Pulmonar Idiopática/patologia , Enfisema Pulmonar/patologia , Fumar Tabaco/patologia , Autopsia , Humanos , Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pulmão/patologia , Transplante de Pulmão , Prontuários Médicos , Pneumonectomia , Enfisema Pulmonar/complicações , Enfisema Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Fumar Tabaco/efeitos adversos , Tomografia Computadorizada por Raios XRESUMO
Upper-lobe predominance of elastofibrosis is agreed upon for the diagnosis of clinical pleuroparenchymal fibroelastosis (PPFE). We herein describe a patient with dermatomyositis-related interstitial pneumonia with a histology of lower-lobe predominant PPFE. A 71-year-old woman who had been diagnosed with dermatomyositis-related interstitial pneumonia died of respiratory failure. The computed tomography patterns of the lower lobes showed reticular and ground-glass opacities with traction bronchiectasis. An autopsy revealed that the bilateral lower lobes were sclerotic with decreased air volume. A microscopic examination of the lower lobes showed pleural fibrosis and subpleural elastofibrosis without the structural destruction, indicative of histological PPFE. PPFE histology was also evident in the upper lobes but relatively modest compared to that of the lower lobes. In addition, because the computed tomography images of the patient were suggestive of non-PPFE-type fibrosis, lower-lobe dominant PPFE might be overlooked in daily practice.
Assuntos
Dermatomiosite/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pleurais/diagnóstico por imagem , Fibrose Pulmonar/diagnóstico por imagem , Corticosteroides/uso terapêutico , Idoso , Autopsia , Dermatomiosite/complicações , Dermatomiosite/tratamento farmacológico , Dermatomiosite/patologia , Evolução Fatal , Feminino , Humanos , Imunossupressores/uso terapêutico , Pulmão/diagnóstico por imagem , Pulmão/patologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/patologia , Tecido Parenquimatoso/diagnóstico por imagem , Tecido Parenquimatoso/patologia , Inibidores da Fosfodiesterase 5/uso terapêutico , Pleura/diagnóstico por imagem , Pleura/patologia , Doenças Pleurais/complicações , Doenças Pleurais/tratamento farmacológico , Doenças Pleurais/patologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/patologia , Tadalafila/uso terapêutico , Tomografia Computadorizada por Raios XRESUMO
We previously characterized the morphological characteristics of malignant pleural mesothelioma (MPM) cells with 9p21 homozygous deletion (HD) using a combination of the virtual microscopy and fluorescence in situ hybridization (FISH). In this study, we investigated whether MPM cells with BRCA1-associated protein 1 (BAP1) loss show the same morphological characteristics identified in MPM cells with 9p21 HD. MPM cells with either BAP1 loss detected by immunocytochemistry (ICC) or 9p21 HD detected by FISH were identified via virtual microscopy prior to ICC or FISH, followed by analysis and quantification of their morphological characteristics. MPM cells with BAP1 loss or 9p21 HD exhibited significantly more frequent cell-in-cell engulfment, multinucleation, and larger multicellular clusters composed of more than 10 cells than reactive mesothelial cells. In conclusion, MPM cells with BAP1 loss or 9p21 HD share similar cytological features, indicating that the same morphological criteria can be used to detect MPM cells harboring such genetic aberrations.
Assuntos
Mesotelioma/patologia , Neoplasias Pleurais/patologia , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Deleção Cromossômica , Cromossomos Humanos Par 9 , Feminino , Humanos , Imuno-Histoquímica , Masculino , Mesotelioma/genética , Pessoa de Meia-Idade , Neoplasias Pleurais/genética , Deleção de SequênciaRESUMO
Revision of WHO guidelines in 2016 led to the classification of solitary fibrous tumours(SFTs)and haemangiopericytomas(HPCs)as a single tumor entity characterized by NAB2-STAT6 fusion. Standard-of-care treatment involves surgery, but local recurrence and distant metastasis sometimes occur. The average latency to metastasis after surgery is 99 months. A 38-year-old female patient presented with a complaint of headache. An 8×5×2cm lesion showing Gd-T1 enhancement was detected near the superior sagittal sinus. Pathological assessment following resection revealed proliferating, polymorphic, atypical tumor cells with distinct nucleoli in a "patternless pattern." Cellularity was moderate to high, and mitotic figures were observed in 15/10 high power fields. Immunohistochemically, tumor cells tested positive for STAT6, and RT-PCR revealed a NAB2-STAT6 fusion gene(exons 6 and 17, respectively), supporting a diagnosis of SFT/HPC WHO grade III. Despite postoperative radiotherapy, multiple metastases to the spleen were detected 8 months after surgery, and distal pancreatectomy with splenectomy was performed. The pathology of the splenic tumor was similar to that of the intracranial tumor. Recurrent disease in a lymph node was detected 1 month later, and local radiation therapy was administered. The patient died of cancerous peritonitis 5 months later. In this case, exceedingly rapid metastasis to the spleen occurred, despite the administration of vigorous treatment. Here, we review SFT/HPC incidence, treatment, and outcomes to better understand this rare malignancy.
Assuntos
Hemangiopericitoma , Tumores Fibrosos Solitários , Neoplasias Esplênicas/secundário , Adulto , Feminino , Hemangiopericitoma/secundário , Hemangiopericitoma/cirurgia , Humanos , Recidiva Local de Neoplasia , Proteínas Repressoras , Fator de Transcrição STAT6 , Tumores Fibrosos Solitários/patologia , Tumores Fibrosos Solitários/cirurgiaRESUMO
A recently described nuclear grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The current study was undertaken to validate the grading system and to identify additional prognostic factors. We analyzed cases of epithelioid malignant pleural mesothelioma from 17 institutions across the globe from 1998 to 2014. Nuclear grade was computed combining nuclear atypia and mitotic count into a grade of I-III using the published system. Nuclear grade was assessed by one pathologist for three institutions, the remaining were scored independently. The presence or absence of necrosis and predominant growth pattern were also evaluated. Two additional scoring systems were evaluated, one combining nuclear grade and necrosis and the other mitotic count and necrosis. Median overall survival was the primary endpoint. A total of 776 cases were identified including 301 (39%) nuclear grade I tumors, 354 (45%) grade II tumors and 121 (16%) grade III tumors. The overall survival was 16 months, and correlated independently with age (P=0.006), sex (0.015), necrosis (0.030), mitotic count (0.001), nuclear atypia (0.009), nuclear grade (<0.0001), and mitosis and necrosis score (<0.0001). The addition of necrosis to nuclear grade further stratified overall survival, allowing classification of epithelioid malignant pleural mesothelioma into four distinct prognostic groups: nuclear grade I tumors without necrosis (29 months), nuclear grade I tumors with necrosis and grade II tumors without necrosis (16 months), nuclear grade II tumors with necrosis (10 months) and nuclear grade III tumors (8 months). The mitosis-necrosis score stratified patients by survival, but not as well as the combination of necrosis and nuclear grade. This study confirms that nuclear grade predicts survival in epithelioid malignant pleural mesothelioma, identifies necrosis as factor that further stratifies overall survival, and validates the grading system across multiple institutions and among both biopsy and resection specimens. An alternative scoring system, the mitosis-necrosis score is also proposed.
Assuntos
Neoplasias Pulmonares/patologia , Mesotelioma/patologia , Necrose/patologia , Gradação de Tumores/métodos , Neoplasias Pleurais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Núcleo Celular/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Mesotelioma/mortalidade , Mesotelioma Maligno , Pessoa de Meia-Idade , Neoplasias Pleurais/mortalidade , PrognósticoRESUMO
AIMS: Some investigators have detected fibrinous exudate or immature organisation in the alveolar spaces prior to the development of subpleural elastofibrosis in patients with pleuroparenchymal fibroelastosis (PPFE). We hypothesised that PPFE progress is associated with an impaired lymphatic drainage system, resulting in the failed resolution of intra-alveolar exudate. The aim of this study is to investigate the pulmonary lymphatic vessels in PPFE, histologically. METHODS AND RESULTS: We retrospectively reviewed our medical records from 1995 to 2017, and selected autopsied or surgically biopsied patients with PPFE (n = 18), pulmonary apical cap (n = 18), and IPF (n = 26). We detected lymphatic endothelial cells by using immunostained specimens, calculating the percentage of lymphatic vessel area in the non-aerated area (lymphatic vessel density) and the number of lymphatic vessels per non-aerated area (per mm2 ) (lymphatic vessel number). These parameters in PPFE were compared with those in apical cap, IPF, and normal lung tissue. The lymphatic vessel density in PPFE patients [2.97%; interquartile range (IQR) 2.61-3.86] was significantly higher than that in normal lung (0.91%; IQR 0.84-1.07), pulmonary apical cap (0.67%; IQR 0.58-0.83), and IPF (0.91%; IQR 0.68-1.25) (P < 0.01 in any comparison). The lymphatic vessel number in PPFE was also significantly higher than that in normal lung, pulmonary apical cap, and IPF. Among PPFE patients, the increase in lymphatic vessel density was found to be correlated with the characteristic physiology of PPFE, such as a flattened chest cage on computed tomography and high residual volume/total lung capacity ratio on spirometry. CONCLUSIONS: Significant increase in the density and number of lymphatic vessels is a supportive characteristic that enables the differentiation of PPFE from IPF and apical cap.
Assuntos
Tecido Elástico/patologia , Pneumonias Intersticiais Idiopáticas/patologia , Vasos Linfáticos/patologia , Fibrose Pulmonar/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
AIMS: We occasionally encounter patients with idiopathic pulmonary fibrosis (IPF) who have similar imaging patterns to those of pleuroparenchymal fibroelastosis (PPFE) in the upper lung fields but are not diagnosed as having PPFE clinically. The aim of this study is to identify the clinicopathological features and intrapulmonary distribution of elastic fibres and collagen fibres in these patients. METHODS AND RESULTS: We retrospectively reviewed the medical records of patients with a clinical diagnosis of IPF, and selected consecutive patients who underwent autopsy or pneumonectomy for lung transplantation. Patients with histologically confirmed PPFE were also reviewed for comparison. We quantified the collagen fibres and elastic fibres in each lobe as a percentage of the non-aerated lung area (collagen fibre score and elastic fibre score, respectively) in histological specimens by using whole-slide image analysis, and compared these scores between IPF and PPFE patients. In a total of 55 patients (IPF, 48; PPFE, 7), there were no significant differences in the collagen fibre scores between IPF and PPFE patients. The elastic fibre scores in the upper lobe in PPFE patients were significantly higher than those in IPF patients (23.5 versus 10.3, P = 0.005). However, it is of note that, in 12 of 48 IPF patients, the elastic fibre scores of the upper lobes were above the first quartile of those in PPFE patients. CONCLUSIONS: IPF occasionally shows intense elastosis in the upper lobes, and such cases are histologically indistinguishable from PPFE. There seem to be histologically borderline cases between PPFE and IPF.