RESUMO
BACKGROUND: Invasive lobular carcinoma (ILC) is distinct from invasive ductal carcinoma (IDC) in terms of their hormonal microenvironments that may require different therapeutic strategies. We previously reported that selective estrogen receptor modulator (SERM) function requires F-box protein 22 (Fbxo22). Here, we investigated the role of Fbxo22 as a potential biomarker contributing to the resistance to endocrine therapy in ILC. METHODS: A total of 302 breast cancer (BC) patients including 150 ILC were recruited in the study. Fbxo22 expression and clinical information were analyzed to elucidate whether Fbxo22 negativity could be a prognostic factor or there were any correlations among clinical variables and SERM efficacy. RESULTS: Fbxo22 negativity was significantly higher in ILC compared with IDC (58.0% vs. 27.0%, P < 0.001) and higher in postmenopausal patients than premenopausal patients (64.1% vs. 48.2%, P = 0.041). In the ILC cohort, Fbxo22-negative patients had poorer overall survival (OS) than Fbxo22-positive patients, with 10-year OS rates of 77.4% vs. 93.6% (P = 0.055). All patients treated with SERMs, Fbxo22 negativity resulted in a poorer outcome, with 10-year OS rates of 81.3% vs. 92.3% (P = 0.032). In multivariate analysis regarding recurrence-free survival (RFS) in ILC patients, Fbxo22 status was independently predictive of survival as well as lymph node metastasis. CONCLUSION: Fbxo22 negativity significantly impacts on survival in BC patients with IDC and ILC, and the disadvantage was enhanced among ILC postmenopausal women or patients treated with SERMs. The findings suggest that different therapeutic strategies might be needed according to the different histopathological types when considering adjuvant endocrine therapy.
Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Carcinoma Lobular/patologia , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Carcinoma Ductal de Mama/patologia , Resultado do Tratamento , Microambiente TumoralRESUMO
BRCA1/2 mutation carriers are at high risk for type II ovarian, fallopian tube or peritoneal cancer. Although risk-reducing salpingo-oophorectomy plays an important role in the prevention of these BRCA1/2-associated gynecological cancers, occult ovarian, fallopian tube, or peritoneal cancer is discovered upon risk-reducing salpingo-oophorectomy in 1-4% of BRCA1/2 mutation carriers. Notably, around 30% of BRCA1/2 mutation carriers who undergo risk-reducing salpingo-oophorectomy have undergone adjuvant chemotherapy for breast cancer. We describe the discovery and treatment of occult cancer at the edge of the left fimbria in a BRCA1 mutation carrier who had, just a short time previously, undergone neoadjuvant paclitaxel plus carboplatin (TC) chemotherapy for triple-negative breast cancer. During subsequent risk-reducing salpingo-oophorectomy, a 5.5-mm nodule was observed at the edge of the left fimbria. Microscopic examination of the tumour tissue revealed high-grade serous carcinoma with degenerate tumour cells and fibrosis. Peritoneal fluid was negative for cancer cells. Two months later, hysterectomy, omentectomy and retroperitoneal lymphadenectomy were performed. The final diagnosis was stage FIGO IA fallopian tube cancer. Adjuvant chemotherapy (TC administered every 3 weeks) was applied, and there has been no evidence of recurrence for 5 years. In applying gynecologic surgery and adjuvant chemotherapy, we followed the general recommendation for stage IA fallopian tube cancer. There is no standard strategy for the treatment of occult fallopian tube cancer detected after chemotherapy for BRCA1-associated triple-negative breast cancer. According to our experience in this case, we believe the clinical value of staging laparotomy in cases of a small occult BRCA1/2-associated gynecological cancer should be further investigated.
Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias das Tubas Uterinas/patologia , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/patologia , Salpingo-Ooforectomia , Carboplatina/uso terapêutico , Quimioterapia Adjuvante , Tubas Uterinas/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/uso terapêuticoRESUMO
BACKGROUND: Primary epithelial ovarian cancer is divided into several subtypes. The relationships between apparent diffusion coefficient (ADC) values and their subtypes have not yet been established. PURPOSE: To investigate whether ADC values of epithelial ovarian cancer vary according to histologic tumor cellularity and evaluate the difference of clear cell carcinoma (CCC), high-grade serous carcinoma (HGSC), and endometrioid carcinoma (EC). MATERIAL AND METHODS: This retrospective study included 51 cases of epithelial ovarian cancer (17 CCC, 20 HGSC, and 14 EC) identified by magnetic resonance imaging with pathological confirmation. All patients underwent diffusion-weighted imaging and the ADC values of lesions were measured. We counted the tumor cells in three high-power fields and calculated the average for each case. The Spearman's correlation coefficient test was used to analyze correlation between ADC values and tumor cellularity. The ADC values of HGSC, EC, and CCC were compared using the Steel-Dwass test. RESULTS: The ADC values of all cases were significantly inversely correlated with tumor cellularity (rs = -0.761; P < 0.001). The mean ± SD ADC values (×10-3 mm2/s) of CCC, HGSC, and EC were 1.24 ± 0.17 (range 0.98--1.65), 0.84 ± 0.10 (range 0.67--1.06), and 0.84 ± 0.10 (range 0.67--1.07). The mean ± SD tumor cellularity of CCC, HGSC, and EC was 162.88 ± 63.28 (range 90.33--305.67), 440.60 ± 119.86 (range 204.67--655.67), and 461.02 ± 81.86 (range 333.33--602.33). CONCLUSION: There is a significant inverse correlation between ADC values and tumor cellularity in epithelial ovarian cancer. The mean ADC value of CCC was higher than those of HGSC and EC, seemingly due to the low cellularity of CCC.
Assuntos
Adenocarcinoma de Células Claras/diagnóstico por imagem , Carcinoma Endometrioide/diagnóstico por imagem , Cistadenocarcinoma Seroso/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Ovarianas/diagnóstico por imagem , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/patologia , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Ovarianas/patologia , Estudos RetrospectivosRESUMO
Here, cases of a 68- (Case 1) and a 44-year-old (Case 2) female are presented. They had an abnormality in the breast, and came to our hospital for further examination and treatment. Radiologically, malignancy could not completely excluded so breast excision was performed. Histologically, both cases revealed papillary neoplastic lesions lined by fibrovascular core and nuclear inverse polarity without atypia. Loss of myoepithelial cells was observed by HE, p63, and calponin. Previous report indicate CK5/6, ER, p63 and MUC3 are important for distinguishing between papillary lesions according to the differential index (based on Allred score) of ([ER total score] + [MUC3 total score])/([CK5/6 total score] + [p63 total score] + 1). Based on this analysis, our two cases had benign lesions. However, based on immunopositivity for cell-cycle marker Cyclin-D1, Case 1 was negative, and Case 2 was about 70% positive. Additionally, the Ki-67 index was <1% in both cases, and no evidence of disease was observed after a maximum 62 months of follow-up in both cases, despite lack of additional treatment. Thus, we propose that lack of myoepithelial cells in papillary lesions do not necessarily indicate malignancy and are thought to be, at the most, uncertain malignant potential.
Assuntos
Neoplasias da Mama/patologia , Papiloma/patologia , Adulto , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Feminino , HumanosRESUMO
PURPOSE: The purpose of this study was to evaluate the possible clinical application of optical coherence tomography for assessing ovarian reserve in individual specimens of human ovarian tissue for fertility preservation. METHODS: Ovarian tissue examination by optical coherence tomography was performed before ovarian tissue cryopreservation. Three of the four subjects had hematological disease or cancer, and they faced a threat to their fertility due to impending chemotherapy. One patient underwent ovarian tissue extraction for in vitro activation of dormant follicles as fertility treatment. RESULTS: The current full-field optical coherence tomography technique can detect primordial follicles in non-fixed and non-embedded human ovarian tissue. These images are well correlated with histological evaluation and the ovarian reserve test, including follicle counts. CONCLUSION: It was demonstrated that optical coherence tomography could assess localization of primordial follicles and ovarian reserve in specimens of non-fixed human ovarian cortex, although optimization for examination of human ovarian tissue is needed for clinical application. Additionally, this technique holds the possibility of assessing the ovarian reserve of patients with unevaluable ovarian reserve. TRIAL REGISTRATION NUMBER: UMIN000023141.
Assuntos
Preservação da Fertilidade , Infertilidade Feminina/terapia , Folículo Ovariano/citologia , Ovário/citologia , Ovário/transplante , Tomografia de Coerência Óptica/métodos , Adolescente , Adulto , Neoplasias do Ânus/fisiopatologia , Criança , Feminino , Humanos , Pessoa de Meia-Idade , Reserva OvarianaRESUMO
Several reports have demonstrated the use of whole-slide imaging (WSI) for primary pathological diagnosis, but no such studies have been published from Asia. We retrospectively collected 1070 WSI specimens from 900 biopsies and small surgeries conducted in nine hospitals. Nine pathologists, who participated in this study, trained for the College of American Pathologists guidelines, reviewed the specimens and made diagnoses based on digitized, 20× or 40× optically magnified images with a WSI scanner. After a washout interval of over 2 weeks, the same observers reviewed conventional glass slides and diagnosed them by light microscopy. Discrepancies between microscopy- and WSI-based diagnoses were evaluated at the individual institutes, and discrepant cases were further reviewed by all pathologists. Nine diagnoses (0.9%) showed major discrepancies with significant clinical differences between the WSI- and microscopy-based diagnoses, and 37 (3.5%) minor discrepancies occurred without a clinical difference. Eight out of nine diagnoses with a major discrepancy were considered concordant with the microscopy-based diagnoses. No association was observed between the level of discrepancy and the organ type, collection method, or digitized optical magnification. Our results indicate the availability of WSI-based primary diagnosis of biopsies and small surgeries in routine daily practice.
Assuntos
Neoplasias Gastrointestinais/diagnóstico , Interpretação de Imagem Assistida por Computador/métodos , Humanos , Japão , Variações Dependentes do Observador , Patologia Clínica/métodos , Patologia Cirúrgica/métodos , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
The differential diagnosis of epithelial proliferative disease using core needle biopsy (CNB) is problematic because it is difficult to differentiate between intraductal papilloma, ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma. Many studies have reported that breast cancer lesions are positive for neuroendocrine (NE) markers, whereas only a small number of studies have reported immunopositivity for NE markers in normal mammary tissues or benign lesions. We asked whether NE factors could be used as markers of breast cancer. We determined the immunopositivity rate of synaptophysin, an NE marker, in 204 lesions excised from the breast using CNB in patients who visited a university-affiliated comprehensive medical facility and examined whether synaptophysin is a marker of breast cancer. The specimens were classified as synaptophysin-negative cases (56 benign, 99 malignant); equivocal cases (<1 %: 2 benign, 15 malignant); and synaptophysin-positive cases (1 benign, 31 malignant). The sensitivity, specificity, positive predictive value, and negative predictive value for malignancy of the lesions classified as synaptophysin positive were 23.3 %, 98.2 %, 96.9 %, and 36.1 %, respectively. The respective values for lesions classified as equivocal were 11.6 %, 96.6 %, 88.2 %, and 36.1 %. Synaptophysin may provide a marker of breast cancer diagnosed by CNB.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Sinaptofisina/metabolismo , Biomarcadores Tumorais/normas , Biópsia com Agulha de Grande Calibre , Mama/patologia , Feminino , Humanos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) are widely used for detecting uterine endometrial cancer. The relationships between ADC values and pathological features of endometrial cancer have not yet been established. PURPOSE: To investigate whether ADC values of endometrial cancer vary according to histologic tumor cellularity and tumor grade. MATERIAL AND METHODS: We retrospectively reviewed 30 pathologically confirmed endometrial cancers. All patients underwent conventional non-enhanced magnetic resonance imaging (MRI) and DWI procedures, and ADC values were calculated. Tumor cellularity was evaluated by counting cancer cells in three high-power ( × 400) fields. The correlation between ADC values and tumor cellularity was assessed using Pearson's correlation coefficient test for statistical analysis. RESULTS: The mean ± standard deviation (SD) ADC value ( ×10(-3) mm(2)/s) of endometrial cancer was 0.85 ± 0.22 (range, 0.55-1.71). The mean ± SD tumor cellularity was 528.36 ± 16.89 (range, 298.0-763.6). ADC values were significantly inversely correlated with tumor cellularity. No significant relationship was observed between ADC values and tumor grade (mean ADC values: G1, 0.88 ± 0.265 × 10(-3) mm(2)/s; G2, 0.80 ± 0.178 × 10(-3) mm(2)/s; G3, 0.81 ± 0.117 × 10(-3) mm(2)/s). CONCLUSION: There is a significant inverse relationship between ADC values and tumor cellularity in endometrial cancer. No significant differences in average ADC value were observed between G1, G2, and G3 tumors. However, the lower the tumor grade, the wider the SD.
Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estudos RetrospectivosRESUMO
Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) comprise lymphoid proliferations or lymphomas that arise in patients treated with immunosuppressive drugs for autoimmune diseases, especially rheumatoid arthritis (RA) treated with methotrexate (MTX). MTX has been increasingly administered to patients with RA, resulting in methotrexate-associated lymphoproliferative disorder (MTX-LPD) in patients. We report herein on four cases of patients with RA, who diagnosed with head and neck region. In two cases (one case MTX and another case tacrolimus) drug therapy was discontinued, when the patients were diagnosed as having OIIA-LPD in only a few local findings. These patients have followed good clinical courses for 24 months. In the other two cases, consultations were performed for cervical lymphadenopathy by the Division of Rheumatology. In one case drug therapy was discontinued and a good clinical course was followed. In case of the other patient, however, who had undergone tacrolimus therapy after MTX therapy was discontinued, she relapsed and died. In the case of patients with an autoimmune disease such as RA who are taking MTX, tacrolimus, or anti TNF-α therapy, when cervical lymphadenopathy and extranodal disease are detected, OIIA-LPD should be suspected. We should cooperate with a hematologist-oncologist, a rheumatologist, and pathologist in such a case.
Assuntos
Doença Iatrogênica , Transtornos Linfoproliferativos/etiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Cabeça/patologia , Humanos , Transtornos Linfoproliferativos/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pescoço/patologia , Resultado do TratamentoRESUMO
BRCA1 and 53BP1 antagonistically regulate homology-directed repair (HDR) and non-homologous end-joining (NHEJ) of DNA double-strand breaks (DSB). The histone deacetylase (HDAC) inhibitor trichostatin A directly inhibits the retention of 53BP1 at DSB sites by acetylating histone H4 (H4ac), which interferes with 53BP1 binding to dimethylated histone H4 Lys20 (H4K20me2). Conversely, we recently found that the retention of the BRCA1/BARD1 complex is also affected by another methylated histone residue, H3K9me2, which can be suppressed by the histone lysine methyltransferase (HKMT) inhibitor UNC0638. Here, we investigate the effects of the class I HDAC inhibitors MS-275 and FK228 compared to UNC0638 on histone modifications and the DNA damage response. In addition to H4ac, the HDAC inhibitors induce H3K9ac and inhibit H3K9me2 at doses that do not affect the expression levels of DNA repair genes. By contrast, UNC0638 selectively inhibits H3K9me2 without affecting the levels of H3K9ac, H3K56ac or H4ac. Reflecting their effects on histone modifications, the HDAC inhibitors inhibit ionizing radiation-induced foci (IRIF) formation of BRCA1 and BARD1 as well as 53BP1 and RIF1, whereas UNC0638 suppresses IRIF formation of BRCA1 and BARD1 but not 53BP1 and RIF1. Although HDAC inhibitors suppressed HDR, they did not cooperate with the poly(ADP-ribose) polymerase inhibitor olaparib to block cancer cell growth, possibly due to simultaneous suppression of NHEJ pathway components. Collectively, these results suggest the mechanism by that HDAC inhibitors inhibit both the HDR and NHEJ pathways, whereas HKMT inhibitor inhibits only the HDR pathway; this finding may affect the chemosensitizing effects of the inhibitors.
Assuntos
Proteína BRCA1/metabolismo , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Reparo do DNA por Junção de Extremidades/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Western Blotting , Células HeLa , Humanos , Microscopia de Fluorescência , Neoplasias/metabolismo , Quinazolinas/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína 1 de Ligação à Proteína Supressora de Tumor p53RESUMO
Dysregulation of homologous recombination (HR) DNA repair has been implicated in breast carcinogenesis and chemosensitivity. Here, we investigated the methylation status of sixteen HR genes and analyzed their association with tumor subtypes and responses to neoadjuvant chemotherapy. Core specimens were obtained before neoadjuvant chemotherapy from sixty cases of primary breast cancer of the following four subgroups: luminal breast cancer (LBC) with pathological complete response (pCR), LBC with stable disease, triple-negative breast cancer (TNBC) with pCR and TNBC with poor response. The aberrant DNA methylation status of the following HR related-genes was analyzed using bisulfite-pyrosequencing: BRCA1, BRCA2, BARD1, MDC1, RNF8, RNF168, UBC13, ABRA1, PALB2, RAD50, RAD51, RAD51C, MRE11, NBS1, CtIP and ATM. Among the genes analyzed, only the incidence of BRCA1 and RNF8 methylation was significantly higher in TNBC than that in LBC. Whereas the incidence of BRCA1 methylation was tended to be higher in pCR cases than in poor-response cases in TNBC, that of RNF8 was significantly lower in pCR cases than in poor-response cases. Our results indicate that the methylation status of HR genes was not generally associated with TNBC subtype or chemosensitivity although hypermethylation of BRCA1 is associated with TNBC subtype and may impact chemosensitivity.
Assuntos
Neoplasias da Mama/genética , Metilação de DNA , Reparo do DNA/genética , Terapia Neoadjuvante , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Ilhas de CpG , Ciclofosfamida/administração & dosagem , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Recombinação Homóloga , Humanos , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Taxoides/administração & dosagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológicoRESUMO
Patients with Crohn's disease are at higher risk of opportunistic infection, especially if treated with immunosuppressive therapy. Cytomegalovirus has been reported to cause ulcerated lesions mainly in the lower gastrointestinal tract of inflammatory bowel disease patients. We herein report a rare case of Crohn's disease complicated with cytomegalovirus esophagitis, which was difficult to distinguish from exacerbation of Crohn's disease. Diagnostic values of clinical course, blood tests, endoscopic and histological examinations are limited but the present case was therapeutically diagnosed by antiviral therapy in combination with histological evidence of cytomegalovirus.
Assuntos
Doença de Crohn , Infecções por Citomegalovirus , Esofagite , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/complicações , Esofagite/virologia , Esofagite/diagnóstico , Esofagite/tratamento farmacológico , Diagnóstico Diferencial , Antivirais/uso terapêutico , Masculino , Feminino , Adulto , Progressão da DoençaRESUMO
Peritoneal washing cytology (CY) in patients with pancreatic cancer is mainly used for staging; however, it may also be used to evaluate the intraperitoneal status to predict a more accurate prognosis. Here, we investigated the potential of deep learning of CY specimen images for predicting the 1-year prognosis of pancreatic cancer in CY-positive patients. CY specimens from 88 patients with prognostic information were retrospectively analyzed. CY specimens scanned by the whole slide imaging device were segmented and subjected to deep learning with a Vision Transformer (ViT) and a Convolutional Neural Network (CNN). The results indicated that ViT and CNN predicted the 1-year prognosis from scanned images with accuracies of 0.8056 and 0.8009 in the area under the curve of the receiver operating characteristic curves, respectively. Patients predicted to survive 1 year or more by ViT showed significantly longer survivals by Kaplan-Meier analyses. The cell nuclei found to have a negative prognostic impact by ViT appeared to be neutrophils. Our results indicate that AI-mediated analysis of CY specimens can successfully predict the 1-year prognosis of patients with pancreatic cancer positive for CY. Intraperitoneal neutrophils may be a novel prognostic marker and therapeutic target for CY-positive patients with pancreatic cancer.
Assuntos
Aprendizado Profundo , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/diagnóstico , Feminino , Masculino , Prognóstico , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Redes Neurais de Computação , Curva ROC , Citodiagnóstico/métodos , Estimativa de Kaplan-Meier , Adulto , Lavagem Peritoneal , Idoso de 80 Anos ou mais , Neutrófilos/patologia , CitologiaRESUMO
INTRODUCTION: Cancer genome analysis using next-generation sequencing requires adequate and high-quality DNA samples. Genomic analyses were conventionally performed using formalin-fixed paraffin-embedded sections rather than cytology samples such as cell block or smear specimens. Specimens collected from liquid-based cytology (LBC) have the potential to be sources of high-quality DNA suitable for genetic analysis even after long-term storage. METHODS: We collected breast tumor/lesion fractions from 92 residual LBC specimens using fine-needle aspiration (FNA) biopsy, including breast carcinoma (1 invasive carcinoma and 4 ductal carcinomas in situ), papillomatous lesion (5 intraductal papillomas), and fibroepithelial lesion (19 phyllodes tumors and 53 fibroadenomas) samples, and others (1 ductal adenoma, 1 hamartoma, 1 fibrocystic disease, and 7 unknown). DNA was extracted from all samples and subjected to DNA integrity number (DIN) score analysis. RESULTS: Average DIN score collected from 92 LBC specimens was significantly higher score. In addition, high-quality DNA with high DIN values (7.39 ± 0.80) was successfully extracted more than 12 months after storage of residual LBC specimens. CONCLUSION: Residual LBC specimens collected from FNA of the breast were verified to carry high-quality DNA and could serve as an alternate source for genetic analysis.
Assuntos
Neoplasias da Mama , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/diagnóstico , Feminino , Biópsia por Agulha Fina/métodos , Biópsia Líquida , DNA de Neoplasias/análise , DNA de Neoplasias/genética , Citodiagnóstico/métodos , Tumor Filoide/patologia , Tumor Filoide/genética , Tumor Filoide/diagnóstico , Fibroadenoma/patologia , Fibroadenoma/genética , Fibroadenoma/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/diagnóstico , Pessoa de Meia-Idade , CitologiaRESUMO
We previously reported on two women with breast lesions in whom radiological examination could not exclude malignancy. In both cases, mastectomy was performed, and histological analyses revealed papillary lesions lined by fibrovascular stroma and nuclear inverse polarity. Hematoxylin-eosin, p63, and calponin staining indicated an absence of myoepithelial cells. However, it was concluded that the lesions had been non-malignant. These women have now been under long-term surveillance (74 months for one case and 62 months for the other) and have had no disease recurrence. Mucin (MUC)1, MUC2, MUC4, MUC5AC, MUC5B, and MUC6 immunostaining has also been performed in these women to investigate further whether their tumors were malignant or benign. In both cases, the tumors were only positive for MUC1 in apical luminal apical cells, as in normal breast tissue. MUC5B immunostaining, even when weak, can detect early breast cancer but was completely negative in our two cases. Therefore, both tumors were considered benign. Our findings in these cases suggest that nuclear inverse polarity papillary lesions lacking myoepithelial cells are benign. This knowledge should decrease the number of unnecessary operations performed for this tumor and their negative impact on patients' quality of life.
Assuntos
Neoplasias da Mama , Mucinas , Humanos , Feminino , Neoplasias da Mama/patologia , Qualidade de Vida , Mastectomia , Biomarcadores Tumorais/análise , Recidiva Local de Neoplasia , Mucina-1RESUMO
Metaplastic breast cancers (MBCs) [spindle cell carcinoma (SpCC), squamous cell carcinoma (SCC), and matrix-producing carcinoma (MPC)] and invasive carcinomas with central acellular zones (CACs) were analyzed with respect to biological potential by immunohistochemical analyses. Specimens from 40 patients [20 with MBCs (7 with SCC, 6 with SpCC, 5 with MPC, and 2 with mixed type)] and 20 with CACs were analyzed using antibodies to cytokeratin (CK) 8, 5/6, 14, AE1/AE3, 34αE12, involucrin, c-kit, vimentin (VIM), alpha-smooth muscle actin, p63, epidermal growth factor receptor, epithelial cell adhesion molecule, and estrogen receptor (ER)/progesterone receptor (PR)/HER2. Expression of CK5/6, 34ßE12, VIM, nuclear p63, and cytoplasmic p63 was significantly higher with MBCs than CACs (38%/13%, 70%/43%, 85%/33%, 68%/40%, and 48%/18%, respectively). Other markers were expressed at various levels in these tumors, but the difference between them was not significant. Eighteen MBC and 8 CAC cases were triple (ER/PR/HER2) negative; 17 MBCs and 7 CACs were basal-like tumors. Several differences were seen in MBCs and CACs, but they were heterogeneous, differentiating multipotentially into mesenchymal, myoepithelial, basal-like phenotypes with "stem cell-like" features. Thus, CACs are related to MBCs by immunohistochemical analyses as well as according to morphological findings.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Carcinoma/classificação , Carcinoma/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Carcinoma/diagnóstico por imagem , Carcinoma/metabolismo , Carcinoma Basocelular/diagnóstico por imagem , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patologia , Feminino , Humanos , Imuno-Histoquímica , Metaplasia , UltrassonografiaRESUMO
Consultation by subspecialty experts is the most common mode of rendering diagnosis in challenging cases in pathological practice. Our study aimed to highlight the diagnostic benefits of whole-slide image (WSI)-based remote consultation. We obtained diagnostically challenging cases from two institutions from the years 2010 and 2013, with histological diagnoses that contained keywords "probable," "suggestive," "suspicious," "inconclusive," and "uncertain." A total of 270 cases were selected for remote consultation using WSIs scanned at 40 × . The consultation process consisted of three rounds: the first and second rounds each with 12 subspecialty experts and the third round with six multi-expertise senior pathologists. The first consultation yielded 44% concordance, and a change in diagnosis occurred in 56% of cases. The most frequent change was from inconclusive to definite diagnosis (30%), followed by minor discordance (14%), and major discordance (12%). Out of the 70 cases which reached the second round, 31 cases showed discrepancy between the two consultants. For these 31 cases, a consensus diagnosis was provided by six multi-expertise senior pathologists. Combining all WSI-based consultation rounds, the original inconclusive diagnosis was changed in 140 (52%) out of 266 cases. Among these cases, 80 cases (30%) upgraded the inconclusive diagnosis to a definite diagnosis, and 60 cases (22%) changed the diagnosis with major or minor discordance, accounting for 28 cases (10%) and 32 cases (12%), respectively. We observed significant improvement in the pathological diagnosis of difficult cases by remote consultation using WSIs, which can further assist in patient healthcare. A post-study survey highlighted various benefits of WSI-based consults.
Assuntos
Patologia Cirúrgica , Consulta Remota , Telepatologia , Humanos , Microscopia/métodos , Patologia Cirúrgica/métodos , Consulta Remota/métodos , Telepatologia/métodosRESUMO
Preoperative diagnosis with multimodal approaches might lead to overtreatment. Cautious understanding of cytology and dynamic contrast-enhanced magnetic resonance imaging is required when a Kuttner tumor is cited as differential diagnosis.
RESUMO
Chemotherapy for multiple primary malignancies is challenging. We herein report a case of synchronous primary lung adenocarcinoma and hepatocellular carcinoma (HCC). A 72-year-old man was admitted for the evaluation of an abnormal shadow on his lung. Computed tomography revealed a lung nodule in the right upper lobe and multiple liver masses. He was diagnosed with synchronous primary lung adenocarcinoma and HCC. Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) chemotherapy was efficacious for both tumors. ABCP chemotherapy may be a potential treatment option for synchronous primary lung adenocarcinoma and HCC.