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1.
JAMA Otolaryngol Head Neck Surg ; 148(1): 70-79, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-34792560

RESUMEN

Importance: Human papillomavirus (HPV)-positive status in patients with oropharyngeal squamous cell carcinoma (OPSCC) is associated with improved survival compared with HPV-negative status. However, it remains controversial whether HPV is associated with improved survival among patients with nonoropharyngeal and cervical squamous cell tumors. Objective: To investigate differences in the immunogenomic landscapes of HPV-associated tumors across anatomical sites (the head and neck and the cervix) and their association with survival. Design, Setting, and Participants: This cohort study used genomic and transcriptomic data from the Cancer Genome Atlas (TCGA) for 79 patients with OPSCC, 435 with nonoropharyngeal head and neck squamous cell carcinoma (non-OP HNSCC), and 254 with cervical squamous cell carcinoma and/or endocervical adenocarcinoma (CESC) along with matched clinical data from TCGA. The data were analyzed from November 2020 to March 2021. Main Outcomes and Measures: Positivity for HPV was classified by RNA-sequencing reads aligned with the HPV reference genome. Gene expression profiles, immune cell phenotypes, cytolytic activity scores, and overall survival were compared by HPV tumor status across multiple anatomical sites. Results: The study comprised 768 patients, including 514 (66.9%) with HNSCC (380 male [73.9%]; mean [SD] age, 59.5 [10.8] years) and 254 (33.1%) with CESC (mean [SD] age, 48.7 [14.1] years). Human papillomavirus positivity was associated with a statistically significant improvement in overall survival for patients with OPSCC (adjusted hazard ratio [aHR], 0.06; 95% CI, 0.02-0.17; P < .001) but not for those with non-OP HNSCC (aHR, 0.64; 95% CI, 0.31-1.27; P = .20) or CESC (aHR, 0.50; 95% CI, 0.15-1.67; P = .30). The HPV-positive OPSCCs had increased tumor immune infiltration and immunomodulatory receptor expression compared with HPV-negative OPSCCs. Compared with HPV-positive non-OP HNSCCs, HPV-positive OPSCCs showed greater expression of immune-related metrics including B cells, T cells, CD8+ T cells, T-cell receptor diversity, B-cell receptor diversity, and cytolytic activity scores, independent of tumor variant burden. The immune-related metrics were similar when comparing HPV-positive non-OP HNSCCs and HPV-positive CESCs with their HPV-negative counterparts. The 2-year overall survival rate was significantly higher for patients with HPV-positive OPSCC compared with patients with HPV-negative OPSCC (92.0% [95% CI, 84.8%-99.9%] vs 45.8% [95% CI, 28.3%-74.1%]; HR, 0.10 [95% CI, 0.03-0.30]; P = .009). Conclusions and Relevance: In this cohort study, tumor site was associated with the immune landscape and survival among patients with HPV-related tumors despite presumed similar biologic characteristics. These tumor site-related findings provide insight on possible outcomes of HPV positivity for tumors in oropharyngeal and nonoropharyngeal sites and a rationale for the stratification of HPV-associated tumors by site and the subsequent development of strategies targeting immune exclusion in HPV-positive nonoropharyngeal cancer.


Asunto(s)
Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/inmunología , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/inmunología , Neoplasias de la Columna Vertebral/genética , Neoplasias de la Columna Vertebral/inmunología , Adulto , Anciano , Alphapapillomavirus , Vértebras Cervicales/patología , Estudios de Cohortes , Femenino , Genómica , Neoplasias de Cabeza y Cuello/virología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias de la Columna Vertebral/virología , Tasa de Supervivencia
2.
Clin Transl Oncol ; 22(12): 2324-2332, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32504188

RESUMEN

PURPOSE: Chordoma is a rare tumor of the skeletal system that is characterized by a high recurrence rate and treatment resistance. Given the common finding of immune dysregulation in chordoma, immunotherapy has emerged as potential treatment option. As an important immune checkpoint regulator, we evaluated cytotoxic T-lymphocyte antigen-4 (CTLA-4) expression and its prognostic significance for patients with chordoma of the spine. METHODS: CTLA-4 expression was analyzed immunohistochemically in 32 chordoma tissues and 14 nucleus pulposus tissues to examine the specificity of CTLA-4 expression in chordoma. Univariate log-rank analysis was used to evaluate the association of CTLA-4 expression in tumor cells and tumor-infiltrating lymphocytes (TILs) with survival. Cox multivariate analysis was used to identify independent factors of survival. RESULTS: Positive CTLA-4 expression was observed in all of the TILs and tumor cell cytoplasm, and partial in the membrane or in both the membrane and nucleus, with a markedly higher positivity rate than that observed in normal nucleus tissues. Higher CTLA-4 expression in the tumor but not in TILs was significantly associated with shorter continuous disease-free survival (CDFS) and overall survival (OS). CTLA-4 expression in tumor cells and TILs were independent predictors for CDFS, whereas only tumor cell expression was a significant predictor of OS. Furthermore, the combination of CTLA-4 expression in the tumor and TILs had higher prognostic value. CONCLUSIONS: Targeting CTLA-4 may be a potential novel therapeutic strategy for chordoma patients.


Asunto(s)
Antígeno CTLA-4/metabolismo , Cordoma/metabolismo , Linfocitos Infiltrantes de Tumor/metabolismo , Neoplasias de la Columna Vertebral/metabolismo , Adolescente , Adulto , Anciano , Niño , Cordoma/inmunología , Cordoma/mortalidad , Cordoma/terapia , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunoterapia , Masculino , Persona de Mediana Edad , Núcleo Pulposo/metabolismo , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias de la Columna Vertebral/inmunología , Neoplasias de la Columna Vertebral/mortalidad , Neoplasias de la Columna Vertebral/terapia , Adulto Joven
3.
Semin Cancer Biol ; 64: 36-50, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-31254615

RESUMEN

Sarcomas, especially spine sarcomas, are rare yet debilitating and are underestimated types of cancer. Treatment options for spine sarcomas are limited to chemotherapy, radiotherapy and surgical intervention. Accumulating evidence suggests a complex course associated with the treatment of spine sarcomas as compared to other soft tissue sarcomas in the extremities since adjuvant therapy adds limited success to the oncological outcome. Likewise, the limitations of surgical interventions imposed by the proximity and high sensitivity of the spinal cord, leads to an increased recurrence and mortality rates associated with spine sarcomas. Finding novel treatment options to spine sarcomas as such is inevitable, necessitating a more thorough understanding of the different mechanisms of the underlying etiologies of these tumors. In this review, we discuss the most recent studies tackling the involvement of the immune system; a key player in the emergence of the different types of spine sarcomas and the promising immune-mediated targeted therapy that can be applied in these kind of rare cancers.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Sistema Inmunológico/inmunología , Sarcoma/patología , Neoplasias de la Columna Vertebral/patología , Animales , Humanos , Sarcoma/tratamiento farmacológico , Sarcoma/inmunología , Neoplasias de la Columna Vertebral/tratamiento farmacológico , Neoplasias de la Columna Vertebral/inmunología
4.
Semin Cancer Biol ; 64: 83-92, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-31152785

RESUMEN

At the dawn of the third millennium, cancer has become the bane of twenty-first century man, and remains a predominant public health burden, affecting welfare and life expectancy globally. Spinal osteogenic sarcoma, a primary spinal malignant tumor, is a rare and challenging neoplastic disease to treat. After the conventional therapeutic modalities of chemotherapy, radiation and surgery have been exhausted, there is currently no available alternative therapy in managing cases of spinal osteosarcoma. The defining signatures of tumor survival are characterised by cancer cell ability to stonewall immunogenic attrition and apoptosis by various means. Some of these biomarkers, namely immune-checkpoints, have recently been exploited as druggable targets in osteosarcoma and many other different cancers. These promising strides made by the use of reinvigorated immunotherapeutic approaches may lead to significant reduction in spinal osteosarcoma disease burden and corresponding reciprocity in increase of survival rates. In this review, we provide the background to spinal osteosarcoma, and proceed to elaborate on contribution of the complex ecology within tumor microenvironment giving arise to cancerous immune escape, which is currently receiving considerable attention. We follow this section on the tumor microenvironment by a brief history of cancer immunity. Also, we draw on the current knowledge of treatment gained from incidences of osteosarcoma at other locations of the skeleton (long bones of the extremities in close proximity to the metaphyseal growth plates) to make a case for application of immunity-based tools, such as immune-checkpoint inhibitors and vaccines, and draw attention to adverse upshots of immune-checkpoint blockers as well. Finally, we describe the novel biotechnique of CRISPR/Cas9 that will assist in treatment approaches for personalized medication.


Asunto(s)
Biomarcadores de Tumor/antagonistas & inhibidores , Vacunas contra el Cáncer/administración & dosificación , Inmunoterapia/métodos , Osteosarcoma/terapia , Neoplasias de la Columna Vertebral/terapia , Animales , Biomarcadores de Tumor/inmunología , Humanos , Osteosarcoma/inmunología , Osteosarcoma/patología , Neoplasias de la Columna Vertebral/inmunología , Neoplasias de la Columna Vertebral/patología , Microambiente Tumoral
5.
World Neurosurg ; 135: 192-196, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31809898

RESUMEN

BACKGROUND: Epstein-Barr virus-associated smooth muscle tumors (SMTs) are rare neoplasms that have been found to develop in immunocompromised patients. Three distinct groups of affected patients have been described: (1) human immunodeficiency virus-infected patients, (2) post-transplant patients, and (3) patients with congenital immunodeficiency. The tumors can develop anywhere in the body, with 17 reported cases occurring in the spinal canal, all in patients with human immunodeficiency virus infection. CASE DESCRIPTION: We report the first case of Epstein-Barr virus-associated SMT affecting the spinal canal in a post-bone marrow transplant adult patient. Interestingly, unlike other reported cases, the patient described here had not been receiving immunosuppressive therapy in the 2 years prior to diagnosis of the tumor. CONCLUSIONS: Despite the growing number of case reports, this diagnosis presents a challenge, as the pathophysiology and optimal treatment regimens are not well understood. Results of a literature review of Epstein-Barr virus-associated SMT of the spine as well as a discussion of the presentation, management, and prognosis of this condition is presented here.


Asunto(s)
Infecciones por Virus de Epstein-Barr/inmunología , Huésped Inmunocomprometido , Tumor de Músculo Liso/diagnóstico por imagen , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Descompresión Quirúrgica , Trasplante de Células Madre Hematopoyéticas , Humanos , Inmunosupresores/efectos adversos , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Neuritis Óptica/tratamiento farmacológico , Tumor de Músculo Liso/inmunología , Tumor de Músculo Liso/cirugía , Tumor de Músculo Liso/virología , Fusión Vertebral , Neoplasias de la Columna Vertebral/inmunología , Neoplasias de la Columna Vertebral/cirugía , Neoplasias de la Columna Vertebral/virología , Vértebras Torácicas
6.
Neurosurgery ; 85(6): E1095-E1110, 2019 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-31501892

RESUMEN

BACKGROUND: Currently, little is known about the clinical relevance of tumor-stroma ratio (TSR) in chordoma and data discussing the relationship between TSR and immune status of chordoma are lacking. OBJECTIVE: To characterize TSR distribution in spinal chordoma, and investigated its correlation with clinicopathologic or immunological features of patients and outcome. METHODS: TSR was assessed visually on hematoxylin and eosin-stained sections from 54 tumor specimens by 2 independent pathologists. Multiplex immunofluorescence was used to quantify the expression levels of microvessel density, Ki-67, Brachyury, and tumor as well as stromal PD-L1. Tumor immunity status including the Immunoscore and densities of tumor-infiltrating lymphocytes (TILs) subtypes were obtained from our published data and reanalyzed. RESULTS: Bland-Altman plot showed no difference between mean TSR derived from the two observers. TSR was positively associated with stromal PD-L1 expression, the Immunoscore and CD3+ as well as CD4+ TILs density, but negatively correlated with tumor microvessel density, Ki-67 index, surrounding muscle invasion by tumor and number of Foxp3+ and PD-1+ TILs. Low TSR independently predicted poor local recurrence-free survival and overall survival. Moreover, patients with low TSR and low Immunoscore chordoma phenotype were associated with the worst survival. More importantly, combined TSR and Immunoscore accurately reflected prognosis and enhanced the ability of TSR or Immunoscore alone for outcome prediction. CONCLUSION: These data reveal the significant impact of TSR on tumor progression and immunological response of patients. Subsequent use of agents targeting the stroma compartment may be an effective strategy to treat chordoma especially in combination with immune-based drugs.


Asunto(s)
Cordoma/inmunología , Cordoma/mortalidad , Neoplasias de la Columna Vertebral/inmunología , Neoplasias de la Columna Vertebral/mortalidad , Microambiente Tumoral/inmunología , Anciano , Cordoma/diagnóstico por imagen , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Tasa de Supervivencia/tendencias
7.
Neurosurgery ; 84(6): E318-E333, 2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-30032257

RESUMEN

BACKGROUND: Currently, clinical implications of immune system cells in chordoma remain to be elucidated. OBJECTIVE: To characterize in situ immune cell infiltrates, the Immunoscore, and investigate their correlation with clinicopathologic data of spinal chordoma patients and outcome. METHODS: Tumor-infiltrating lymphocytes (TILs) subtypes were assessed in 54 tumor specimens using immunohistochemistry for CD3, CD4, CD8, CD20, Foxp3, PD-1, and PD-L1. RESULTS: Overall, immune cell infiltrates were present in all samples and there was low or moderate correlation among several TILs subsets. PD-1+ TILs density, CD3+, and CD8+ TILs densities in the tumor interior (TI) subarea were associated with surrounding muscle invasion by tumor, whereas PD-L1+ TILs showed inverse association with tumor pathological grade and stage. The density of PD-1+ TILs, PD-L1+ TILs, CD4+ TILs, and CD3+ TILs both in the TI and combined tumor regions (TI and invasion margin) were significantly associated with local recurrence-free survival and overall survival (OS). However, Foxp3+ TILs (P = .024) and CD8+ TILs evaluated in the TI (P < .001) only correlated with OS. The Immunoscore predicted less aggressive clinical features and favorable outcomes. Patients with an Immunoscore of 4 had a median OS of 128 mo, while I0 (Immunoscore of 0) patients survived only 27 mo. Multivariate analysis demonstrated that the Immunoscore was an independent favorable prognostic factor of both local recurrence-free survival (P = .026) and OS (P = .046). CONCLUSION: Our data suggest a clinically relevant role of the immune microenvironment in spinal chordoma and identify the Immunoscore as promising prognostic marker.


Asunto(s)
Cordoma/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Neoplasias de la Columna Vertebral/inmunología , Microambiente Tumoral/inmunología , Adulto , Anciano , Cordoma/patología , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Neoplasias de la Columna Vertebral/patología , Linfocitos T/inmunología , Adulto Joven
8.
World Neurosurg ; 120: e617-e627, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30165212

RESUMEN

BACKGROUND: Schwannoma comprises approximately 25% of all spinal tumors, but there is little information published in the literature regarding this subject. Our aim in this study was to discuss diagnostic and prognostic factors for spinal schwannoma. METHODS: A retrospective study was performed to analyze the clinical and immunohistochemical data of patients with spinal schwannoma surgically treated in our center between 2005 and 2013. RESULTS: A total of 524 patients with spinal schwannoma were included in the study. The mean follow-up period was 58.3 months. Forty-eight patients developed recurrence, and 26 died. Findings from the statistical analyses suggested duration of preoperative symptoms, Sridhar classification, tumor size, bone damage, Ki67 labeling index, and S100 expression were different between benign schwannoma and the malignant subtype. Recurrence was associated with resection mode, segments of involvement, pathology grade, CD57 expression, Ki67 labeling index, and S100 expression. The overall survival was closely related with recurrence, location in sacrum, pathology grade, Ki67 labeling index, and P53 expression. CONCLUSIONS: Compared with the benign subtype, malignant schwannoma has a shorter duration of preoperative symptoms, larger tumor size, greater Sridhar classification, and poorer prognosis. Total resection can significantly reduce recurrence but not guarantee a better survival, which is associated location and pathology grade. A Ki67 labeling index >5% was not only an index for malignant subtype but also a prognostic indicator for recurrence and poor survival. Moreover, S100-negative was a prognostic indicator for recurrence, whereas P53-positive was associated with a poor prognosis.


Asunto(s)
Neoplasias de la Vaina del Nervio/inmunología , Neoplasias de la Vaina del Nervio/cirugía , Neurilemoma/inmunología , Neurilemoma/cirugía , Neoplasias de la Columna Vertebral/inmunología , Neoplasias de la Columna Vertebral/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Antígeno Ki-67/análisis , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/análisis , Adulto Joven
9.
Cancer Immunol Immunother ; 67(2): 209-224, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29051990

RESUMEN

Currently, little is known about the interactions between microRNAs (miRNAs) and the PD-1/PD-L1 signaling pathway in chordoma, and data discussing the role of the immune milieu in chordoma prognosis are limited. We aimed to analyze the relationship between PD-L1, miR-574-3p, microenvironmental tumor-infiltrating lymphocytes (TILs) and clinicopathological features of spinal chordoma patients. PD-L1 expression and TILs (including Foxp3+, CD8+, PD-1+ and PD-L1+) were assessed by immunohistochemistry in tumor specimens of 54 spinal chordoma patients. MiRNAs microarray and bioinformatical analysis were used to identify miRNAs potentially regulating PD-L1 expression, which were further validated by quantitative RT-PCR. miR-574-3p was identified to potentially regulate PD-L1 expression in chordoma, which inversely correlated with PD-L1. Positive PD-L1 expression on tumor cells was associated with advanced stages (P = 0.041) and TILs infiltration (P = 0.005), whereas decreased miR-574-3p level correlated with higher muscle invasion (P = 0.012), more severe tumor necrosis (P = 0.022) and poor patient survival. Importantly, a patient subgroup with PD-L1+/miR-574-3plow chordoma phenotype was significantly associated with worse local recurrence-free survival (LRFS) (P = 0.026). PD-1+ TILs density was associated with surrounding muscle invasion (P = 0.014), and independently portended poor LRFS (P = 0.040), while PD-L1+ TILs showed tendencies of less aggressive clinical outcomes. Multivariate analysis of OS only found CD8+/Foxp3+ ratio to be independent prognostic factor (P = 0.022). These findings may be useful to stratify patients into prognostic groups and provide a rationale for the use of checkpoint blockade therapy, possibly by administering miR-574-3p mimics, in spinal chordoma.


Asunto(s)
Antígeno B7-H1/inmunología , Linfocitos T CD8-positivos/inmunología , Cordoma/inmunología , Factores de Transcripción Forkhead/inmunología , MicroARNs/inmunología , Neoplasias de la Columna Vertebral/inmunología , Adulto , Anciano , Antígeno B7-H1/biosíntesis , Antígeno B7-H1/genética , Estudios de Casos y Controles , Cordoma/genética , Cordoma/patología , Femenino , Humanos , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , MicroARNs/biosíntesis , MicroARNs/genética , Persona de Mediana Edad , Pronóstico , Neoplasias de la Columna Vertebral/genética , Neoplasias de la Columna Vertebral/patología , Microambiente Tumoral/inmunología , Adulto Joven
11.
Spine J ; 14(8): 1567-71, 2014 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-24314768

RESUMEN

BACKGROUND CONTEXT: Total en bloc spondylectomy (TES) is a surgery designed to achieve complete resection of a malignant spinal tumor, such as spinal metastasis. Although this procedure decreases the rate of local recurrence, it is questionable whether local control prolongs a patient's survival. In cryosurgery, antitumor immunity is activated after percutaneous cryoablation of tumors. We applied this tumor-induced cryoimmunology to TES surgery and developed a "second-generation TES" that brings about TES enhancing antitumor immunity to prolong a patient's survival. PURPOSE: To present a second-generation TES applied tumor-induced cryoimmunology and assess the immunity-enhancing effect after implementing this surgery. STUDY DESIGN: This is a retrospective review of prospectively collected data. PATIENT SAMPLE: The sample consisted of 65 consecutive patients who underwent second-generation TES. OUTCOME MEASURES: Interferon gamma (IFN-γ) and interleukin-12 (IL-12) before surgery and at both 1 and 3 months after surgery was used to assess the immunity-enhancing effect. METHODS: In second-generation TES, instead of harvesting autograft from the ilium or fibula, the resected lamina and vertebral body from TES are frozen using liquid nitrogen and used as grafted bone for spinal reconstruction. In the most recent 33 of the 65 cases, in addition to the TES procedure, a small amount of the tumor tissue from the resected tumor-bearing vertebra was also placed into liquid nitrogen. This small amount of tumor tissue was then implanted subcutaneously on one side of the axilla at the end of the TES surgery. In 60 of 65 cases, measurement of IFN-γ and IL-12 was performed. RESULTS: IFN-γ increased after surgery in 45 (75%) of 60 cases. The mean IFN-γ relative concentrations at both 1 and 3 months after surgery, as compared with before surgery, were significantly higher (284%±596% and 275%±354%: p<.05). IL-12 increased after surgery in 44 (73.3%) of 60 cases. The mean IL-12 relative concentrations at both 1 and 3 months after surgery, as compared with before surgery, were significantly higher (277%±385% and 486%±1032%: p>.05 and p<.01) at 3 months. At final follow-up, 13 of the 65 patients died due to progression of metastases (mean 12.6 months after TES), 15 remained free from disease, and 36 patients were alive with disease. CONCLUSIONS: The second-generation TES using frozen tumor-bearing autograft inside a cage affords three benefits: (1) no pain at the bone harvest site, (2) shortening of operation time, and (3) decrease of blood loss. Moreover, our results show that second-generation TES provides not only a local radical cure but also a systemic immunological enhancement.


Asunto(s)
Interferón gamma/sangre , Interleucina-12/sangre , Procedimientos de Cirugía Plástica/métodos , Neoplasias de la Columna Vertebral/cirugía , Columna Vertebral/cirugía , Adolescente , Adulto , Anciano , Autoinjertos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prótesis e Implantes , Estudios Retrospectivos , Neoplasias de la Columna Vertebral/sangre , Neoplasias de la Columna Vertebral/inmunología , Neoplasias de la Columna Vertebral/patología , Columna Vertebral/patología , Resultado del Tratamiento , Adulto Joven
12.
Eur Spine J ; 23 Suppl 2: 222-7, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24097232

RESUMEN

PURPOSE: Distant metastases from thyroid carcinoma are successfully cured if they take up radioiodine ((131)I), are of small size, and located in the lungs. Bone metastases have the worst prognosis because (131)I therapy and external beam radiotherapy are less effective. Our propose here is to report a patient with solitary spinal metastasis and multiple lung metastases from thyroid carcinoma, whose spinal metastasis was treated by total en bloc spondylectomy (TES) enhancing antitumor immunity using frozen tumor-bearing bone for spinal reconstruction. METHODS: The patient was a 37-year-old male who had solitary spinal metastasis at T4 and multiple lung metastases from thyroid carcinoma. (131)I therapy for the multiple lung metastases resulted in no effect because the apparent (131)I uptake was observed only in T4 metastasis. We performed a TES of T4 with cryotreatment. After en bloc excision of T4, the excised tumor-bearing vertebra was frozen by liquid nitrogen. In spinal reconstruction, the frozen vertebra was used in a mesh cage inserted into the anterior defect. RESULTS: After surgery, the thyroglobulin level decreased without any other adjuvant therapy and the serum levels of INF-γ and IL-12 increased. This indicates antitumor immunity was activated. Then, (131)I therapy became effective to the lung metastases causing the tumors to decrease in size and number. Three years after surgery, progression in the lung metastases, other metastasis, and local recurrence have not been observed. CONCLUSIONS: TES with cryotreatment as presented is a novel surgery which can enhance antitumor immunity against other visible or non-visible metastases.


Asunto(s)
Carcinoma Papilar/secundario , Criocirugía , Procedimientos Neuroquirúrgicos/métodos , Neoplasias de la Columna Vertebral/secundario , Neoplasias de la Columna Vertebral/cirugía , Vértebras Torácicas/cirugía , Adulto , Carcinoma Papilar/inmunología , Carcinoma Papilar/cirugía , Humanos , Interferón gamma/sangre , Interleucina-12/sangre , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Masculino , Nitrógeno , Prótesis e Implantes , Neoplasias de la Columna Vertebral/inmunología , Neoplasias de la Tiroides/inmunología , Neoplasias de la Tiroides/patología
13.
Spine (Phila Pa 1976) ; 33(24): E929-32, 2008 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-19011534

RESUMEN

STUDY DESIGN: A natural killer/T-cell lymphoma originating in the spine of a 60-year-old man is first reported, along with a brief review of the literature on the topic. OBJECTIVE: To describe the presentation and diagnosis of this disorder along with an emphasis on the importance of this type of rare tumor, needing early and accurate immunophenotypic profiling to make a right diagnosis. SUMMARY OF BACKGROUND DATA: Natural killer (NK)/T-cell lymphomas represent a rare type of lymphoma derived from either activated NK cell or rarely cytotoxic T cells. It usually originates in the nasal cavity/nasopharynx and invades the surrounding tissues, which is aggressive and, usually, a delay in diagnosis could result in a fatal outcome. METHODS: A 60-year-old man presented with severe pain in his chest and back for 3 weeks and developed paralysis soon. After we got a negative result of lymphomatous from a bone marrow biopsy, we took a piecemeal excision of the 10th thoracic vertebra. Titanium mesh with bone cement filling-in and mass screw internal fixation system were used for reconstructing the stability of the spine. The histopathology was consistent with NK/T-cell lymphomas. RESULT: The condition of the patient became worse suddenly after he regained some strength in his both lower limbs a week after the operation. He was not suitable for any aggressive chemotherapy or radiation therapy because of his poor condition and died 20 days later. CONCLUSION: NK/T-cell lymphomas originated at other sites but nasal cavity/nasopharynx do not present typical clinical features and symptoms in the absence of lymphadenopathy. There are possibilities for misdiagnosis of NK/T-cell lymphoma that originates at other sites. The unfavorable prognosis of this tumor emphasized the need for novel molecular targets and more effective therapies.


Asunto(s)
Células Asesinas Naturales/patología , Linfoma de Células T Periférico/patología , Neoplasias de la Columna Vertebral/patología , Linfocitos T Citotóxicos/patología , Vértebras Torácicas/patología , Dolor de Espalda/etiología , Dolor de Espalda/patología , Dolor en el Pecho/etiología , Dolor en el Pecho/patología , Resultado Fatal , Humanos , Inmunofenotipificación , Inestabilidad de la Articulación/etiología , Inestabilidad de la Articulación/patología , Células Asesinas Naturales/inmunología , Linfoma de Células T Periférico/complicaciones , Linfoma de Células T Periférico/inmunología , Linfoma de Células T Periférico/cirugía , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/patología , Parálisis/etiología , Índice de Severidad de la Enfermedad , Compresión de la Médula Espinal/etiología , Compresión de la Médula Espinal/patología , Fracturas de la Columna Vertebral/etiología , Fracturas de la Columna Vertebral/patología , Fusión Vertebral , Neoplasias de la Columna Vertebral/complicaciones , Neoplasias de la Columna Vertebral/inmunología , Neoplasias de la Columna Vertebral/cirugía , Linfocitos T Citotóxicos/inmunología , Vértebras Torácicas/inmunología , Vértebras Torácicas/cirugía , Tomografía Computarizada por Rayos X
15.
Zhonghua Bing Li Xue Za Zhi ; 25(3): 142-4, 1996 Jun.
Artículo en Chino | MEDLINE | ID: mdl-9275666

RESUMEN

UNLABELLED: In order to investigate the clinicopathological and immunohistochemical features of chordomas, 34 chordomas, with 5 chondrosarcomas for comparison, were studied by clinicopathological and immunohistochemical methods. RESULTS: Based on the presence or absence of cartilaginous areas, chordomas are classified into two subtypes: chondroid chordoma (14 cases) and classic chordoma (20 cases). Chondroid chordoma occurred in a younger age group (mean age 40.9 years) than classic chordoma (mean age 51.1 years). 7/14 (50%) of chondroid chordomas occurred in the sacrococcygeal region, 4/ 14 (28.6%) occurred in the spheno-occipital region. Immunohistochemical staining showed that all chordomas were positive for cytokeratin, and 16 (47.1%) chordomas were also positive for EMA. In contrast, 5 chondrosarcomas were immunonegative for both cytokeratin and EMA. Vimentin and S-100 protein were positive in the majority of chordomas (29 & 24 respectively) and in the 5 chondrosarcomas. The present study confirms the dual features of chordoma-epithelial and mesenchymal, and also the utility of immunohistochemical staining in the differential diagnosis of chordoma and chondrosarcoma. The pathologic diagnosis of chondroid chordoma and other issues were also discussed in the study.


Asunto(s)
Cordoma/patología , Neoplasias de la Base del Cráneo/patología , Neoplasias de la Columna Vertebral/patología , Adolescente , Adulto , Niño , Preescolar , Condrosarcoma/inmunología , Condrosarcoma/patología , Cordoma/inmunología , Femenino , Humanos , Inmunohistoquímica , Lactante , Queratinas/análisis , Masculino , Persona de Mediana Edad , Mucina-1/análisis , Región Sacrococcígea , Neoplasias de la Base del Cráneo/inmunología , Neoplasias de la Columna Vertebral/inmunología
17.
Acta Neurochir (Wien) ; 135(3-4): 122-5, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-8748800

RESUMEN

The authors report a retrospective study of 15 patients with solitary vertebral plasmacytoma. 15 patients were considered in this study on the basis of the following characteristics: 1) histologically confirmed plasmacytoma following surgical removal; 2) existence of a single vertebral lesion, documented by skeletal and MRI scan; 3) no signs, at diagnosis of disseminated disease by blood laboratory test, urine analysis, sternal puncture, iliac bone marrow biopsy, a total-body CT scan. The clinical course of the patients has been analysed on the basis of the following factors: age, sex, length of clinical history before diagnosis, site, presence/absence of the M component. The M component is an electrophoretically homogeneous immunoglobin. The most significant factors for predicting development of multiple myeloma proved to be the presence /absence of the M component at diagnosis and, to a lesser degree, the age of the patient. In the light of other reports too, it would seem that the presence of the M component at diagnosis is a reflection of aggressive biological and clinical tumour behaviour.


Asunto(s)
Inmunoglobulina M/sangre , Mieloma Múltiple/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Plasmacitoma/diagnóstico , Neoplasias de la Columna Vertebral/diagnóstico , Adulto , Terapia Combinada , Femenino , Humanos , Laminectomía , Masculino , Persona de Mediana Edad , Mieloma Múltiple/inmunología , Mieloma Múltiple/radioterapia , Mieloma Múltiple/cirugía , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Plasmacitoma/inmunología , Plasmacitoma/radioterapia , Plasmacitoma/cirugía , Pronóstico , Dosificación Radioterapéutica , Radioterapia Adyuvante , Estudios Retrospectivos , Neoplasias de la Columna Vertebral/inmunología , Neoplasias de la Columna Vertebral/radioterapia , Neoplasias de la Columna Vertebral/cirugía , Tomografía Computarizada por Rayos X
18.
Clin Oncol (R Coll Radiol) ; 5(1): 65-6, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8424919

RESUMEN

Localized sympathetic over-activity is a rare manifestation of intrathoracic malignancy. We report the case of a 62-year-old woman who presented with a right-sided hyperhidrosis limited to the face, trunk and upper extremities; this revealed a left paraspinal intrathoracic IgD lambda myelomatous tumour. The episodes of sweating were abolished by local radiotherapy, concomitant with the disappearance of the tumour.


Asunto(s)
Hiperhidrosis/etiología , Mieloma Múltiple/complicaciones , Neoplasias de la Columna Vertebral/complicaciones , Vértebras Torácicas , Femenino , Humanos , Inmunoglobulina D/análisis , Cadenas lambda de Inmunoglobulina/análisis , Persona de Mediana Edad , Mieloma Múltiple/inmunología , Mieloma Múltiple/radioterapia , Neoplasias de la Columna Vertebral/inmunología , Neoplasias de la Columna Vertebral/radioterapia
19.
Rinsho Ketsueki ; 33(1): 75-81, 1992 Jan.
Artículo en Japonés | MEDLINE | ID: mdl-1545518

RESUMEN

A 60-year-old man born in Miyazaki prefecture was admitted to our hospital complaining of skin rash in December 1989. On hematological examinations, leukocyte count was 14,200/microliters with 49% of abnormal lymphocytes showing lobulated nuclei. The surface marker study revealed their phenotype as CD4+8-. Anti human T cell leukemia virus type I (HTLV-I) antibody and monoclonal integration of proviral DNA were positive. From the above results, he was diagnosed as adult T-cell leukemia (ATL). Abnormal lymphocytes gradually decreased without treatment after the first admission. In January, 1990, he began to complain of neck pain. Two months later he was readmitted because of paresis of extremities and disturbance of urination. Vertebral bone mass and a compressed spinal cord in the 4th cervic level were confirmed by MR imaging. He received a resection of tumor and an anterior fusion of vertebrae. The bone tumor was histologically diagnosed as malignant lymphoma, diffuse medium-size cell type and the infiltrating cells had their phenotype as CD4+8+. He was postoperatively treated with combination chemotherapies, but neurological abnormalities did not improve. He died of pneumonia on 35 days after the operation. A postmortem examination revealed extradural tumor formation with ATL cells. This case is considered to be rare in respect of both the disappearance of most peripheral abnormal lymphocytes without any treatments and the cervical bone tumor showing immunophenotypic change.


Asunto(s)
Vértebras Cervicales , Leucemia-Linfoma de Células T del Adulto/inmunología , Neoplasias de la Columna Vertebral/inmunología , Antígenos CD4/metabolismo , Antígenos CD8/metabolismo , Humanos , Inmunofenotipificación , Linfoma no Hodgkin/inmunología , Masculino , Persona de Mediana Edad
20.
Chest ; 100(3): 860-1, 1991 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-1889288

RESUMEN

A young man undergoing chemotherapy for Ewing's sarcoma presented with fever, neutropenia, anemia, thrombocytopenia, and a new infiltrate on the chest roentgenogram. Routine cultures and cytopathologic examination of bronchoalveolar lavage fluid provided no evidence for an etiology; however, special cultures of the BAL fluid demonstrated heavy growth of Mycoplasma pneumoniae. We recommend that evaluation of pneumonia in the immuno-compromised host include appropriate cultures of BAL fluid for M pneumoniae, particularly when the patient is 5 to 25 years old, the age of high incidence of mycoplasmal pneumonia.


Asunto(s)
Tolerancia Inmunológica , Neumonía por Mycoplasma/diagnóstico , Adulto , Líquido del Lavado Bronquioalveolar , Diagnóstico Diferencial , Humanos , Pulmón/diagnóstico por imagen , Masculino , Neumonía por Mycoplasma/diagnóstico por imagen , Neumonía por Mycoplasma/inmunología , Radiografía , Sarcoma de Ewing/inmunología , Sarcoma de Ewing/terapia , Neoplasias de la Columna Vertebral/inmunología , Neoplasias de la Columna Vertebral/terapia
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