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1.
Neuropathology ; 2023 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-37953487

RESUMEN

Meningiomas are the most diagnosed primary central nervous system tumor. Currently, 15 different subtypes of meningioma exist with various characteristics. One extremely rare subtype is myxoid meningioma, which is a World Health Organization grade 1 benign meningioma. These specific meningiomas have only been reported 12 times in the literature. In this representative case, we present a 46-year-old female patient with a left frontal myxoid meningioma, describe the findings on imaging, and provide the histopathological features that are needed for diagnosis. Furthermore, this report discusses the other existing myxoid meningioma case reports found throughout the literature.

2.
Clin Neuropathol ; 40(4): 201-208, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33835015

RESUMEN

Few cases of malignant transformation of supposedly low-grade gliomas were described in patients with neurofibromatosis type 1 (NF1). A 27-year-old man with NF1 presented with weakness of his lower extremities and was radiologically found to have a spinal intramedullary tumor primarily involving the Th11 level. The tumor histologically demonstrated features diagnosed as a low-grade astrocytoma, subtype indeterminate (WHO grade II). Immunohistochemically, GFAP was positive, and IDH1 R132H and BRAF V600E were negative. ATRX immunoreactivity was retained. Five years after the surgery, the intramedullary tumor extended to the levels from Th8 to L1 and was partially resected. It showed histologic features similar to those of the first tumor. Two years after the second surgery, the residual spinal cord tumor was found to widely involve the levels from Th5 to L3. Spinal cordectomy was subsequently undertaken and revealed anaplastic glial cells infiltrating diffusely into the spinal cord parenchyma, with prominent subarachnoid spreading and nerve root involvement. Both necrosis and microvascular proliferation were observed. This recurrent tumor was histologically indistinguishable from glioblastoma. Loss of ATRX was noted in the second and third surgical specimens. This is the first histologically proven case of malignant transformation of NF1-associated astrocytoma with ATRX loss during the course.


Asunto(s)
Astrocitoma/patología , Neurofibromatosis 1 , Neoplasias de la Médula Espinal/patología , Proteína Nuclear Ligada al Cromosoma X/metabolismo , Adulto , Astrocitoma/metabolismo , Transformación Celular Neoplásica , Humanos , Masculino , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Neoplasias de la Médula Espinal/metabolismo
3.
Int J Colorectal Dis ; 35(10): 1967-1972, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32504335

RESUMEN

INTRODUCTION: Familial adenomatous polyposis (FAP) is typically characterized by more than hundred adenomatous polyps in the colorectum, caused by germline APC mutation. A small proportion of the polyps progress to colorectal adenocarcinoma via adenoma-carcinoma sequence. Serrated lesions and polyps, characterized by a serrated architecture of the epithelium, are noted for two types of genetic pathways in colorectal carcinogenesis. BRAF and KRAS mutations are observed in the serrated pathway. CASE REPORT: We report a young FAP patient with rectal serrated adenomas that were removed by colonoscopic procedures. The histological features with villiform projections and slit-like serration indicated traditional serrated adenoma. A genetic examination with next-generation sequencing showed a somatic BRAF mutation in the serrated adenoma and APC mutations in the tubular adenomas. His germline mutation was found at APC p.Q1928fs*. CONCLUSION: Serrated adenomas with dual genetic alterations in a FAP patient may be associated with colorectal carcinogenesis and should be considered a target lesion for treatment. The present study demonstrated the malignant potential of serrated adenoma in a FAP patient.


Asunto(s)
Adenoma , Poliposis Adenomatosa del Colon , Pólipos del Colon , Neoplasias Colorrectales , Adenoma/genética , Poliposis Adenomatosa del Colon/genética , Neoplasias Colorrectales/genética , Humanos , Mutación/genética , Proteínas Proto-Oncogénicas B-raf/genética
4.
J Transl Med ; 17(1): 207, 2019 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-31221178

RESUMEN

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) originates from squamous epithelium of the upper aerodigestive tract and is the most common malignancy in the head and neck region. Among HNSCCs, oropharynx squamous cell carcinoma (OSCC) has a unique profile and is associated with human papillomavirus infection. Recently, anti-programmed cell death-1 monoclonal antibody has yielded good clinical responses in recurrent and/or metastatic HNSCC patients. Therefore, programmed death-ligand 1 (PD-L1) may be a favorable target molecule for cancer immunotherapy. Although PD-L1-expressing malignant cells could be targeted by PD-L1-specific CD8+ cytotoxic T lymphocytes, it remains unclear whether CD4+ helper T lymphocytes (HTLs) recognize and kill tumor cells in a PD-L1-specific manner. METHODS: The expression levels of PD-L1 and HLA-DR were evaluated using immunohistochemical analyses. MHC class II-binding peptides for PD-L1 were designed based on computer algorithm analyses and added into in vitro culture of HTLs with antigen-presenting cells to evaluate their stimulatory activity. RESULTS: We found that seven of 24 cases of OSCC showed positive for both PD-L1 and HLA-DR and that PD-L1241-265 peptide efficiently activates HTLs, which showed not only cytokine production but also cytotoxicity against tumor cells in a PD-L1-dependent manner. Also, an adoptive transfer of the PD-L1-specific HTLs significantly inhibited growth of PD-L1-expressing human tumor cell lines in an immunodeficient mouse model. Importantly, T cell responses specific for the PD-L1241-265 peptide were detected in the HNSCC patients. CONCLUSIONS: The cancer immunotherapy targeting PD-L1 as a helper T-cell antigen would be a rational strategy for HNSCC patients.


Asunto(s)
Antígeno B7-H1/metabolismo , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/terapia , Inmunoterapia/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Linfocitos T Colaboradores-Inductores/fisiología , Animales , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/genética , Línea Celular Tumoral , Células Cultivadas , Citotoxicidad Inmunológica/genética , Citotoxicidad Inmunológica/inmunología , Epítopos de Linfocito T/química , Epítopos de Linfocito T/uso terapéutico , Femenino , Técnicas de Silenciamiento del Gen , Neoplasias de Cabeza y Cuello/patología , Humanos , Inmunoterapia/tendencias , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Fragmentos de Péptidos/inmunología , Fragmentos de Péptidos/uso terapéutico , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Linfocitos T Colaboradores-Inductores/metabolismo
5.
J Surg Res ; 228: 147-153, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29907205

RESUMEN

BACKGROUND: Edaravone is a powerful free radical scavenger that is in clinical use. However, data concerning its dose-response relationship against multiple free radicals remain sparse. The purpose of the present study was to demonstrate the dose-dependency of direct scavenging activity of edaravone against multiple free radical species. MATERIALS AND METHODS: Free radical-scavenging activities of edaravone against six free radical species were evaluated by electron spin resonance spectroscopy using spin-trapping method. RESULTS: Edaravone scavenged the following free radicals in dose-dependent manners with reaction rate constants (kedaravone) or 50% inhibitory concentration (IC50) as indicated: hydroxyl radical (kedaravone = 5.2 × 1010 M-1 s-1), superoxide anion (kedaravone/kG-CYPMPO = 0.63), tert-butyl peroxyl radical (kedaravone/kG-CYPMPO = 8.8), ascorbyl free radical (IC50 = 0.17 ± 0.06 mM), 2,2-diphenyl-1-picrylhydrazyl (DPPH, IC50 = 4.7 ± 0.3 µM), and nitric oxide (kedaravone = 7.0 × 103 M-1 s-1). CONCLUSIONS: The dose-dependent scavenging activities of edaravone against multiple free radical species were clearly illustrated. It is speculated that edaravone acts as antioxidant by dose-dependently scavenging multiple free radical species along the chain reactions of oxidative stress in surgery.


Asunto(s)
Edaravona/farmacología , Depuradores de Radicales Libres/farmacología , Radicales Libres/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Edaravona/uso terapéutico , Espectroscopía de Resonancia por Spin del Electrón , Depuradores de Radicales Libres/uso terapéutico , Radicales Libres/química , Humanos , Estrés Oxidativo/efectos de los fármacos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Daño por Reperfusión/etiología , Daño por Reperfusión/prevención & control , Procedimientos Quirúrgicos Operativos/efectos adversos
6.
Cancer Immunol Immunother ; 66(7): 877-890, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28349165

RESUMEN

Nasal natural killer/T-cell lymphoma (NNKTL) is an aggressive neoplasm with poor therapeutic responses and prognosis. The programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway plays an important role in immune evasion of tumor cells through T-cell exhaustion. The aim of the present study was to examine the expression of PD-L1 and PD-1 molecules in NNKTL. We detected the expression of PD-L1 in biopsy samples from all of the NNKTL patients studied. PD-L1 was found on both malignant cells and tumor-infiltrating macrophages, while PD-1-positive mononuclear cells infiltrated the tumor tissues in 36% of patients. Most significantly, soluble PD-L1 (sPD-L1) was present in sera of NNKTL patients at higher levels as compared to healthy individuals and the levels of serum sPD-L1 in patients positively correlated with the expression of PD-L1 in lymphoma cells of tumor tissues. In addition, the high-sPD-L1 group of patients showed significantly worse prognosis than the low-sPD-L1 group. Furthermore, we confirmed that membrane and soluble PD-L1 was expressed on the surface and in the culture supernatant, respectively, of NNKTL cell lines. The expression of PD-L1 was observed in tumor tissues and sera from a murine xenograft model inoculated with an NNKTL cell line. Our results suggest that sPD-L1 could be a prognostic predictor for NNKTL and open up the possibility of immunotherapy of this lymphoma using PD-1/PD-L1 axis inhibitors.


Asunto(s)
Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Inmunoterapia/métodos , Linfoma Extranodal de Células NK-T/terapia , Neoplasias Nasales/terapia , Receptor de Muerte Celular Programada 1/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Biopsia , Línea Celular Tumoral , Supervivencia sin Enfermedad , Femenino , Xenoinjertos , Humanos , Estimación de Kaplan-Meier , Linfoma Extranodal de Células NK-T/metabolismo , Linfoma Extranodal de Células NK-T/mortalidad , Linfoma Extranodal de Células NK-T/patología , Masculino , Ratones , Persona de Mediana Edad , Neoplasias Nasales/metabolismo , Neoplasias Nasales/mortalidad , Neoplasias Nasales/patología , Pronóstico
7.
Neuropathology ; 36(4): 354-64, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26991787

RESUMEN

The histologic expression of epithelial and organ-related immunohistochemical markers in primary sellar region tumors has received little attention to date. This lack of empirical data may lead to mistaken assumptions in the evaluation of sellar region neoplasms. To address this issue, the frequency and specificity of epithelial (cytokeratin 7(CK7), CK20) and organ-related differentiation markers (gross cystic disease fluid protein-15 (GCDFP-15), thyroid transcription factor-1 (TTF-1), Napsin A, paired box 8 (PAX-8), hepatocyte paraffin 1 (HepPar1) and estrogen receptor (ER)) were studied in 40 patients with adenomas comprising five hormonal sub-types. Non-parametric statistical procedures were used to examine associations between marker expression and tumor sub-type. CK7 and CK20 immunoreactivity were seen in 48% and 8% of tumors, respectively, although never in a diffuse pattern. CK20 expression was nearly exclusive to corticotrophs, whereas CK7 frequently highlighted cells with dendritic-type morphology. The specificity of organ-related differentiation markers was 100% (monoclonal Napsin A, GCDFP-15 and TTF-1), 97% (HepPar1 and PAX-8), 90% (polyclonal Napsin A) and 72% (ER); no tumors demonstrated significant co-expression of these organ-related markers with either CK7 or CK20. The first major conclusion of this study is that CK7 staining in adenoma is more frequent than has been previously than has been previously described. CK7 immunoreactive cells often displayed a dendritic-type morphology, including within large macroadenomas, which raises the question as to whether these represent tumor cells with folliculo-stellate cell-type differentiation, as these also have dendritic cell-type morphology and express CK7 in non-neoplastic glands. The second major conclusion, which confirms earlier findings, is that CK20 staining is a very infrequent immunohistochemical finding in adenomas that is virtually limited to corticotrophs and thus is helpful in diagnostic confirmation of that sub-type. The final conclusion is in regard to those features that separate adenomas from sellar region metastases: adenomas do not demonstrate significant expression of TTF-1, monoclonal Napsin A, PAX-8, HepPar1 or GCDFP-15, nor do they exhibit diffuse expression of CK7 and CK20.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Hipofisarias/metabolismo , Adolescente , Adulto , Anciano , Antígenos de Neoplasias/metabolismo , Ácido Aspártico Endopeptidasas/metabolismo , Proteínas Portadoras/metabolismo , Diferenciación Celular , Femenino , Glicoproteínas/metabolismo , Humanos , Queratina-20/metabolismo , Queratina-7/metabolismo , Masculino , Proteínas de Transporte de Membrana , Persona de Mediana Edad , Proteínas Nucleares/metabolismo , Factor de Transcripción PAX8/metabolismo , Neoplasias Hipofisarias/patología , Receptores de Estrógenos/metabolismo , Factor Nuclear Tiroideo 1 , Factores de Transcripción/metabolismo , Adulto Joven
8.
Eur Spine J ; 25 Suppl 1: 239-44, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-27015688

RESUMEN

PURPOSE: Symptoms of cauda equina syndrome due to ependymoma in the conus medullaris or filum terminale develop slowly. However, hemorrhagic change inside spinal tumors can induce acute neurologic decline. Here, we report a case of posttraumatic hemorrhage inside a filum terminale myxopapillary ependymoma presenting as acute neurologic decline, which had a positive prognosis after surgical resection. METHODS: A 28-year-old man presented with buttock pain, sensory disturbance, and motor weakness of bilateral lower extremities after falling on ice during smelt fishing. Magnetic resonance imaging demonstrated a mixed-intensity hemorrhagic intradural mass extending from L1 to L2. RESULTS: The patient underwent emergent surgical decompression and resection. Pathologic examination revealed a myxopapillary ependymoma with intratumoral hemorrhage. After surgery, the patient demonstrated gradual improvement in neurologic deficits and no tumor recurrence. CONCLUSIONS: This is the first case of a filum terminale myxopapillary ependymoma with an acute neurologic decline after injury. Early diagnosis and treatment are associated with favorable outcomes.


Asunto(s)
Ependimoma/complicaciones , Hemorragia/etiología , Polirradiculopatía/etiología , Neoplasias de la Médula Espinal/complicaciones , Accidentes por Caídas , Adulto , Cauda Equina/cirugía , Descompresión Quirúrgica/métodos , Ependimoma/patología , Ependimoma/cirugía , Hemorragia/patología , Hemorragia/cirugía , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Polirradiculopatía/cirugía , Neoplasias de la Médula Espinal/patología , Neoplasias de la Médula Espinal/cirugía
9.
Pathol Int ; 65(8): 438-42, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26059172

RESUMEN

Subependymoma is a rare subtype of benign ependymal neoplasm with distinct histological features. Anaplastic transformation has not yet been reported in this tumor to date. We present here a very unusual case of a 62-year-old woman with recurrent subependymoma of the fourth ventricle with multiple atypical histological features. Histologically, the resected recurrent tumor showed characteristic small cell clusters and nests of ependymal cells with an interspersed gliofibrillary matrix as seen in a classic subependymoma. In addition, there were very unusual histological features, including multiple areas of necrosis, microvascular proliferation, thrombosed blood vessels, and scattered mitotic figures. No coexisting ependymoma component of higher World Health Organization (WHO) grade was present. Immunohistochemically, MIB-1 labeling index was high, with up to 15% in the highest areas. Review of this patient's initial tumor, which was resected 6 years prior to recurrence, demonstrated features of a typical classic subependymoma without atypical features or a secondary tumor component. Subependymomas are known to be low-grade tumors and are usually cured if completely excised. The tumor presented here is unique in that several atypical pathological features were found in an otherwise typical subependymoma. Our case may represent anaplastic transformation of subependymoma, although no such examples have been reported to date.


Asunto(s)
Neoplasias del Ventrículo Cerebral/patología , Cuarto Ventrículo/patología , Glioma Subependimario/patología , Recurrencia Local de Neoplasia/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad
11.
Neuropathology ; 35(5): 456-61, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25923831

RESUMEN

Central nervous system (CNS) involvement by metastatic cancer is well-recognized and typically presents with multifocal solid tumors within the brain parenchyma or leptomeningeal dissemination. We describe herein a histologically very rare case of CNS metastasis in a 52-year-old woman who presented with mental status changes. Post mortem examination revealed extensive CNS involvement by metastatic inflammatory breast carcinoma, characterized by the presence of single tumor cells diffusely present within capillaries without parenchymal or perivascular invasion, and acute ischemic changes/infarcts bilaterally involving multiple areas. The cancer cells were found predominantly in the cerebral cortices and deep gray matter structures. Pre-mortem magnetic resonance and CT imaging of the brain did not identify metastatic cancer; however, widespread ischemic changes (i.e. brain infarcts) were identified. Inflammatory breast carcinoma is well-known to have a predilection for spread through lymphovascular spaces. Post mortem examination revealed tumor involvement of bilateral lungs, heart and bladder, with sinusoidal spread in the liver and lymph nodes and prominent involvement of the splenic red pulp in addition to extensive vascular involvement of the brain and spinal cord without a discrete mass, despite the presence of widely metastatic disease. The tumor cells in the CNS were strongly immunoreactive for pancytokeratin, E-cadherin, cytokeratin-7, epithelial membrane antigen and CAM 5.2. This unique histologic pattern of tumor spread is considered to represent "intravascular carcinomatosis" in the CNS, and most likely the cause of the patient's widespread ischemic injuries.


Asunto(s)
Neoplasias Encefálicas/secundario , Carcinoma/secundario , Neoplasias Inflamatorias de la Mama/patología , Resultado Fatal , Femenino , Humanos , Persona de Mediana Edad
12.
Neuromodulation ; 17(5): 405-18; discussion 418, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24947418

RESUMEN

OBJECTIVES: Despite the widespread use of deep brain stimulation (DBS) in the treatment of neurologic disorders for over a quarter of a century, there has not been a systematic review and analyses of cases in which long-term postmortem clinic-pathologic data have been collected demonstrating the effects of chronically implanted electrodes and electrical stimulation on human brain tissue. Our objective is to provide a comprehensive systematic review of the literature on clinicopathologic findings of DBS tissue-electrode interface (TEI) and to determine types and prevalences of neuropathological findings among electrode materials and stimulation parameters and to augment this with previously unpublished histopathological data, images, and analyses from a DBS case implanted for 12 years, providing the longest duration histopathological follow-up. MATERIALS AND METHODS: A Medline literature review identified DBS cases upon which postmortem clinicopathologic follow-up was performed with adequate characterization of TEI. Direct follow-up with authors augmented this with unpublished data and neuropathological details. RESULTS: We identified 40 cases, mean age 59.1 ± 13.0 (range: 21-88) years, involving 58 implanted DBS electrodes. The mean postmortem histopathological follow-up of the implanted DBS electrodes was 22.2 ± 29.2 (range: 0.067-146) months, including our case with a 12-year follow-up. The following histological changes were identified: fibrous sheaths (5-25 µm thickness) surrounding the electrode (94%), fibrillary gliosis (73%), reactive astrocytes (78%), multinucleated giant cells (75%), mononuclear leukocytes (92%), and macrophages (91%). Microglial activation (60%), axonal spheroids (64%), and neuronal loss (60%) were less common and absent at 12-year follow-up in the index case. This is seventh case reporting T cell presence at the TEI. CONCLUSIONS: Neuropathological findings from published cases and our 12-year follow-up index case confirm the long-term safety of neuromodulation and stimulation thresholds and demonstrate persistence of T cells and occasional subclinical focal tissue injury.


Asunto(s)
Estimulación Encefálica Profunda/efectos adversos , Electrodos Implantados/efectos adversos , Enfermedades del Sistema Nervioso/patología , Enfermedades del Sistema Nervioso/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , MEDLINE/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Adulto Joven
13.
Pathol Int ; 63(6): 326-32, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23782335

RESUMEN

Metachronous bilateral renal cell carcinomas (RCCs) are rare but well known. We present a case of metachronous bilateral RCCs with a ureter orifice metastasis, for which the pathological diagnosis was confirmed with single nucleotide polymorphism microarray (SNP-M) and gene expression assay (GEA). A 53-year-old man presented with a right ureteral obstruction. A cystoscopy showed a large pedunculated tumor emanating from the right ureteral orifice, consistent with a drop metastasis, which was biopsied. He had a history of a clear cell RCC (ccRCC) 1.5 years prior and a right renal pelvic mass found 8 months later. Histologically, the biopsied right ureteral tumor demonstrated sheets of poorly differentiated cancer cells composed of a mixture of spindled and focal clear cell components. The main differential diagnosis was metastatic RCC versus urothelial carcinoma, but the immunohistochemical profile was not contributory. SNP-M revealed a genomic profile consistent with a metastatic ccRCC with loss of chromosome 3p. GEA showed a gene expression pattern consistent with kidney origin. The cytogenomic array also identified chromosome copy number patterns that were shared between both kidney tumors. This finding suggests that both tumors had a common origin, and thus, the metachronous ccRCC in the contralateral kidney represents a metastasis.


Asunto(s)
Carcinoma de Células Renales/patología , Cromosomas Humanos Par 3/genética , Análisis Citogenético/métodos , Neoplasias Renales/patología , Neoplasias Ureterales/secundario , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/secundario , ADN de Neoplasias/química , ADN de Neoplasias/genética , Diagnóstico Diferencial , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/genética , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Polimorfismo de Nucleótido Simple , Neoplasias Ureterales/genética , Neoplasias Ureterales/patología , Obstrucción Ureteral/etiología
14.
Hum Pathol ; 134: 74-84, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36549600

RESUMEN

Human telomerase reverse transcriptase (hTERT) is highly expressed in various cancers, including breast cancer. Although telomere elongation is an essential role for hTERT, the nuclear export after oxdative stress has also been shown in several cancer cell lines and is associated with drug-resistance in vitro. As only a few reports focused on the subcellular localization of hTERT in clinical specimens, we performed immunohistochemistry (IHC) and analyzed the correlation between intracellular hTERT expression and the clinicopathological characteristics to identify the clinical significance of hTERT subcellular expression in breast cancers. 144 invasive breast cancers classified by IHC subtype without primary systemic therapy (PST), were selected from a surgical resection cohort and were immunostained for hTERT, p-STAT3, p-AKT and p-ERK. The nuclear and/or cytoplasmic staining intensity and proportion of hTERT were scored and compared with clinicopathological parameters. The nuclear hTERT expression was significantly correlated with HER2 expression (p = 0.00156), and the scores were significantly correlated with p-STAT3 and p-AKT expression scores (r = 0.532, p = 0.000587 and r = 0.345, p = 0.0339, respectively) in the HER2-immunopositive breast cancer including luminal-HER2 and HER2 subtypes. Furthermore, hTERT was expressed more in cytoplasm in the specimens after PST than those before PST, and the score tended to be negatively correlated with tumor shrinkage rate in HER2 subtype (r = -0.593, p = 0.0705). These results suggest that nuclear and/or cytoplasmic hTERT may play a different role before and after PST including the tumorigenesis and drug-resistance in breast cancer. Suppression of cytoplasmic hTERT expression may lead to more effective strategy for drug-resistant HER2 subtype in breast cancer.


Asunto(s)
Neoplasias de la Mama , Telomerasa , Femenino , Humanos , Neoplasias de la Mama/patología , Núcleo Celular/patología , Transformación Celular Neoplásica , Proteínas Proto-Oncogénicas c-akt/metabolismo
15.
Head Neck Pathol ; 17(1): 265-274, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36303014

RESUMEN

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare translocation-related soft tissue sarcoma, occurring mainly in the limbs and trunk in young adults and adolescents. ASPS is rarely seen in the head and neck and one fourth of those cases described are tongue primary. Given its nonspecific symptoms, clinical findings, and rarity in this location, lingual ASPS (L-ASPS) has been reported to be commonly misdiagnosed as various benign tumors, leading to adverse outcomes. METHODS: We report a case of L-ASPS occurring in the oldest (78 years) female patient published to date and comprehensively review the literature from 1952 to 2022. RESULTS: She presented with a slow-growing (2-year duration) tongue mass, measuring 3.5 cm on palpation. Intraoperative frozen section could not render the definitive diagnosis. The pathological findings of the tumor were characteristic of ASPS with eosinophilic polygonal cells in an organoid/nested pattern, rich sinusoidal capillaries, and TFE3 immunoreactivity, except for the strong diffuse aberrant cytoplasmic CD68 immunoexpression and absence of intracytoplasmic crystalline inclusions on PAS with diastase. After TFE3 gene rearrangement had been identified with fluorescent in-situ hybridization, reflex testing confirmed a rearrangement of TFE3 gene with the known fusion partner ASPSCR1. CONCLUSIONS: ASPS should be included in the differential diagnoses in cases of any slow-growing lingual masses (especially vascular ones) with non-specific clinical pictures, regardless of the patient's age.


Asunto(s)
Sarcoma de Parte Blanda Alveolar , Neoplasias de los Tejidos Blandos , Neoplasias de la Lengua , Adolescente , Adulto Joven , Humanos , Femenino , Anciano , Sarcoma de Parte Blanda Alveolar/diagnóstico , Factores de Transcripción , Neoplasias de los Tejidos Blandos/patología , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética
16.
Mol Clin Oncol ; 18(3): 24, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36844465

RESUMEN

A 60-year-old woman presented with a 3-year history of a slow-growing, painless mass in their left parotid gland. Ultrasonography revealed a well-circumscribed, lobulated, hypoechoic mass measuring 19x12x10 mm in the left parotid gland. Computed tomography revealed a well-circumscribed, solid mass with homogeneous enhancement. Fluorodeoxyglucose-positron emission tomography revealed uptake by the tumor but no uptake in other organs, including the nasopharynx. The patient underwent superficial parotidectomy with adequate safety margins and selective neck dissection followed by radiotherapy. No facial paralysis or recurrence of the tumor had been observed as of 20 months post-operation. Histologically, the tumor was composed of sheets of syncytial cancer cells with prominent nucleoli in a dense lymphoplasmacytic background. Epstein-Barr virus (EBV)-encoded RNA in situ hybridization was diffusely positive in the tumor cells. These findings indicated that the tumor was an EBV-associated lymphoepithelial carcinoma. Metastasis, especially from the nasopharynx, was excluded endoscopically and radiologically. Targeted next-generation sequencing of 160 cancer-related genes using the surgical specimen revealed no mutations, including known significant mutations detected in EBV-associated nasopharyngeal carcinoma.

17.
Head Neck Pathol ; 16(4): 980-990, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35507302

RESUMEN

Polymorphous adenocarcinoma (PAC) is a rare variant of minor salivary gland tumors. Because of its architectural diversity, histological diagnosis of PAC can be difficult especially for small biopsies, and immunohistochemistry is of great help in differentiating it from its histologic mimics. The aim of this study is to conduct a systematic literature review to identify reliable immunohistochemical markers for PAC. We conducted an electronic literature search of the MEDLINE, ScienceDirect, SpringerLink, and Wiley Online Library databases, covering the literature published in the period between 1988 and 2021. The eligibility criteria included case reports and retrospective studies of PAC cases with details of immunohistochemical markers. Following the search and selection process, 32 studies with 409 cases were included in this systematic review. Overall, > 90% positivity was observed for pan-cytokeratin (CK) (97.3%), CK7 (96.8%), CK7/8 (97.4%), E-cadherin (90.0%), Vimentin (92.5%), S100 (97.0%), p63 (91.7%), and SOX10 (100%), while little to no positivity was observed for CK20 (0.0%), p40 (0.0%), and GFAP (5.0%). The average MIB-1 labeling index was 3.78%. The results of this systematic review indicate that CK7+/CK20-, p63+/p40-, S100+, Vimentin+, and GFAP- immunophenotype have diagnostic value for PAC. In addition, the use of S100, MSA, p40, and c-Kit provide additional layers of information helpful to differentiate PAC from adenoid cystic carcinoma, one of challenging differential diagnoses.


Asunto(s)
Glándulas Salivales Menores , Humanos , Estudios Retrospectivos
18.
BMC Biomed Eng ; 4(1): 2, 2022 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-35287761

RESUMEN

BACKGROUND: The COVID-19 pandemic revealed a substantial and unmet need for low-cost, easily accessible mechanical ventilation strategies for use in medical resource-challenged areas. Internationally, several groups developed non-conventional COVID-19 era emergency ventilator strategies as a stopgap measure when conventional ventilators were unavailable. Here, we compared our FALCON emergency ventilator in a rabbit model and compared its safety and functionality to conventional mechanical ventilation. METHODS: New Zealand white rabbits (n = 5) received mechanical ventilation from both the FALCON and a conventional mechanical ventilator (Engström Carestation™) for 1 h each. Airflow and pressure, blood O2 saturation, end tidal CO2, and arterial blood gas measurements were measured. Additionally, gross and histological lung samples were compared to spontaneously breathing rabbits (n = 3) to assess signs of ventilator induced lung injury. RESULTS: All rabbits were successfully ventilated with the FALCON. At identical ventilator settings, tidal volumes, pressures, and respiratory rates were similar between both ventilators, but the inspiratory to expiratory ratio was lower using the FALCON. End tidal CO2 was significantly higher on the FALCON, and arterial blood gas measurements demonstrated lower arterial partial pressure of O2 at 30 min and higher arterial partial pressure of CO2 at 30 and 60 min using the FALCON. However, when ventilated at higher respiratory rates, we observed a stepwise decrease in end tidal CO2. Poincaré plot analysis demonstrated small but significant increases in short-term and long-term variation of peak inspiratory pressure generation from the FALCON. Wet to dry lung weight and lung injury scoring between the mechanically ventilated and spontaneously breathing rabbits were similar. CONCLUSIONS: Although conventional ventilators are always preferable outside of emergency use, the FALCON ventilator safely and effectively ventilated healthy rabbits without lung injury. Emergency ventilation using accessible and inexpensive strategies like the FALCON may be useful for communities with low access to medical resources and as a backup form of emergency ventilation.

19.
Head Neck Pathol ; 16(1): 282-287, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34076847

RESUMEN

A 15-year-old old Japanese male with a 2-month history of swelling of his left subauricular area was admitted to our department. A thumb-sized, hard mass with mild tenderness was palpated on the left parotid gland. Ultrasonography revealed a well-circumscribed, hypoechoic mass exhibiting heterogeneity in the left parotid gland measuring 1.7 × 1.5 × 1.3 cm. Computed tomography scan revealed a well-circumscribed, solid mass exhibiting slight peripheral enhancement in the left parotid gland. Magnetic resonance imaging revealed a hypointense mass in the left parotid gland on both T1- and T2-weighted images. Clinicoradiologic findings suggested a benign or low-grade malignant parotid tumor. The patient underwent left superficial parotidectomy with adequate safety margins. The facial nerve was identified and preserved. Neither facial paralysis nor tumor recurrence was observed as of 1 year postoperatively. Histologically, the nodule consisted of a vaguely nodular arrangement of variably sized ducts and acini in a hyalinized fibrous background with focal myxoid changes. The ductal/acinar component exhibited a bilayered arrangement of cuboidal luminal and flattened abluminal cells exhibiting a variety of epithelial proliferative patterns, including micropapillary and cribriform. Areas of oncocyte-like changes with intracellular coarse eosinophilic granules, apocrine-like feature, foamy/vacuolated changes, and clear cells were noted in the proliferating epithelium. Immunohistologically, the luminal cells were positive for gross cystic disease fluid protein-15. The Ki-67 labeling index was 2-3%. The histologic features and immunohistologic profile were consistent with sclerosing polycystic adenosis. Targeted next-generation sequencing of 160 cancer-related genes using the surgical specimen revealed no mutations, including known significant mutations in PTEN, PIK3CA, or PIK3R1.


Asunto(s)
Neoplasias de la Parótida , Fosfatidilinositol 3-Quinasas , Adolescente , Humanos , Hiperplasia/patología , Imagen por Resonancia Magnética , Masculino , Mutación , Glándula Parótida/patología , Glándula Parótida/cirugía , Neoplasias de la Parótida/genética , Neoplasias de la Parótida/patología
20.
Oncol Lett ; 24(1): 207, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35720490

RESUMEN

The aim of the present study was to analyze the clinical characteristics, surgical treatments and clinical outcome of patients with parotid gland tumors and to compare the results with those cited in the literature. A retrospective study was conducted in 140 patients (male, n=77; female, n=63) with parotid gland tumors who underwent parotidectomy at Hokuto Hospital Department of Otolaryngology-Head and Neck Surgery (Obihiro, Japan) between April 2007 and December 2021. Of the 140 patients enrolled, 118 (84.3%) patients had benign tumors, including 63 (45%) patients with pleomorphic adenomas and 43 (30.7%) patients with Warthin tumors, and 22 patients (15.7%) had parotid carcinoma. Comparison of the three groups of patients with parotid gland tumors indicated that pack years as an indicator of smoking status were significantly higher in patients with Warthin tumors than in those with parotid carcinomas (P=0.011) or pleomorphic adenoma (P<0.001). Fine-needle aspiration cytology (FNAC) was non-diagnostic for only 6 (4.3%) of 140 patients. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of FNAC by both conventional smear and liquid-based cytology (LBC) for parotid carcinomas were 70, 99, 93.3, 94.4 and 82.9%, respectively. Among the 22 patients with parotid carcinoma, extended total/total and superficial parotidectomy were performed in 10 (45%) and 11 (50%) cases, respectively. Total and selective neck dissection of the area from level II to I, II and III were performed in 6 (24%) and 7 (32%) patients, respectively. Postoperative radiotherapy (50 Gy) was performed in 15 (68%) patients. The overall survival (OS) and disease-free survival (DFS) rates at 5 years were 51.5 and 76.4%, respectively. Univariate analysis revealed that age >65 years was significantly associated with poorer 5-year OS (P<0.001) and DFS (P<0.001). Multivariate analysis revealed that an age of more than 65 years combined with high-grade histologic malignancy was associated with worse DFS (P=0.02; hazard ratio, 3.628; 95% confidence interval, 1.283-9.514). In conclusion, the clinical characteristics and treatment outcomes of parotid gland tumors were consistent with the results of previous reports. Smoking may be closely related to the pathogenesis of Warthin tumors. LBC potentially provides improved accuracy in FNAC.

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