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In 1977, the American Joint Committee on Cancer (AJCC) introduced the inaugural Cancer Staging Manual, which implemented the T (tumor extent), N (regional lymph node status), and M (presence or absence of distant metastasis) staging system. This systematic approach aimed to convey the extent of disease across various cancer types, providing clinicians with a practical framework to plan treatment strategies, predict prognosis, and assess outcomes. The AJCC 8th edition, effective from January 1, 2018, continues this tradition. However, certain shortcomings persist in the AJCC 8th edition, as identified through clinical experience. Specifically, challenges arise in accurately assessing depth of invasion in unique histological variants of oral squamous cell carcinoma (e.g., Oral verrucous carcinoma, Carcinoma cuniculatum, and Papillary squamous cell carcinoma) and minor salivary gland tumors. Additionally, discrepancies exist in the perception of bone invasion patterns and in reporting practices. There is also a need for staging guidelines for malignant odontogenic tumors and multifocal tumors of the oral cavity, supplemented by diagrammatic representations. Lastly, there is a call for comprehensive staging criteria for carcinomas of the ear, external auditory canal, and temporal bone. We advocate for the inclusion of these considerations in future editions of the AJCC Cancer Staging Manual.
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Neoplasias de los Labios , Neoplasias de la Boca , Estadificación de Neoplasias , Humanos , Neoplasias de la Boca/patología , Estadificación de Neoplasias/normas , Estadificación de Neoplasias/métodos , Neoplasias de los Labios/patologíaRESUMEN
BACKGROUND/AIM: Cancer-associated fibroblasts (CAFs) have recently been suggested as critical cellular components of bone invasion in oral squamous cell carcinoma (OSCC). However, the underlying molecular mechanisms and subtypes related to their bone-invasive function are unclear. This study investigated the implications of thymidine phosphorylase (TP)-positive CAFs (TP+CAFs) in OSCC bone invasion. MATERIALS AND METHODS: TP expression was determined in 116 patients with OSCC using immunohistochemistry. The influence of TP expression on the biological behavior of CAFs was investigated in vitro. The possible impact of TP+CAFs on bone invasion in OSCC was further evaluated using patient-derived xenograft (PDX) mouse models. RESULTS: In bone-invasive OSCC tissues, TP+CAFs were mainly distributed on the surface of resorbed bone tissue rather than on the tumor side. High levels of TP+CAFs were significantly associated with higher T-stage, bone invasion, and worse overall survival and recurrence-free survival in our study cohort. Recombinant human TP promoted the proliferative and invasive abilities of CAFs and increased matrix metalloproteinase-9 mRNA expression in vitro, related to bone resorption. In the PDX mouse models, TP+CAFs were found in early bone resorption on the surface of resorbed bony tissues. Bone resorption occurred more frequently in the PDX models with TP+CAFs than in those without. CONCLUSION: TP+CAFs were significantly associated with bone invasion and the prognosis of OSCC. This study provides insights into cellular and molecular targets for the early diagnosis and treatment of bone-invasive OSCC.
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Fibroblastos Asociados al Cáncer , Carcinoma de Células Escamosas , Neoplasias de la Boca , Invasividad Neoplásica , Timidina Fosforilasa , Humanos , Animales , Neoplasias de la Boca/patología , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/genética , Femenino , Masculino , Ratones , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Timidina Fosforilasa/metabolismo , Timidina Fosforilasa/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/genética , Persona de Mediana Edad , Neoplasias Óseas/patología , Neoplasias Óseas/metabolismo , Neoplasias Óseas/genética , Línea Celular Tumoral , Anciano , Proliferación Celular , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Pronóstico , Ensayos Antitumor por Modelo de Xenoinjerto , Resorción Ósea/patología , Resorción Ósea/metabolismoRESUMEN
OBJECTIVES: Radiomics, a recently developed image-processing technology, holds potential in medical diagnostics. This study aimed to propose a machine-learning (ML) model and evaluate its effectiveness in detecting oral squamous cell carcinoma (OSCC) and predicting bone metastasis using magnetic resonance imaging (MRI). MATERIALS-METHODS: MRI radiomic features were extracted and analyzed to identify malignant lesions. A total of 86 patients (44 with benign lesions without bone invasion and 42 with malignant lesions with bone invasion) were included. Data and clinical information were managed using the RadCloud Platform (Huiying Medical Technology Co., Ltd., Beijing, China). The study employed a hand-crafted radiomics model, with the dataset randomly split into training and validation sets in an 8:2 ratio using 815 random seeds. RESULTS: The results revealed that the ML method support vector machine (SVM) performed best for detecting bone invasion (AUC = 0.999) in the test set. Radiomics tumor features derived from MRI are useful to predicting bone invasion from oral squamous cell carcinoma with high accuracy. CONCLUSIONS: This study introduces an ML model utilizing SVM and radiomics to predict bone invasion in OSCC. Despite the promising results, the small sample size necessitates larger multicenter studies to validate and expand these findings.
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Bone invasion by head and neck squamous cell carcinoma (HNSCC) significantly impacts tumor staging, treatment choice, prognosis, and quality of life. While HNSCC is known to cause osteolytic bone invasion, we found that specific HNSCC subtypes can induce osteogenic bone destruction at the tumor-bone interface. This destruction mode significantly correlated with reduced patient survival rates and increased neck lymph node metastasis. Further in vivo and in vitro experiments indicated that HNSCC cells triggered abnormal phenotypic changes in osteoblasts to remodel the tumor-bone microenvironment, facilitating tumor lymphatic metastasis. Through transcriptome analysis, we identified three genes-osteopontin (SPP1), chemokine (C-X-C motif) ligand 1 (CXCL1), and matrix metalloprotein (MMP)9 (MMP9) linked to a poorer prognosis. We discovered osteoblasts with abnormal phenotypes at the tumor-bone interface exhibiting high SPP1, MMP9, and CXCL1 expressions. Based on these characteristics, we identified this osteoblast subpopulation as "cancer-associated osteoblasts (CAOs)." HNSCC cells activated the TNF-α/NF-κB signaling pathway in osteoblasts, transforming them into "CAOs." These CAOs significantly contributed to the progression of tumor-induced bone invasion, facilitating cancer growth and metastasis. We first provided clinical data and in vivo and in vitro evidence that HNSCC cells can promote tumor progression by manipulating osteoblasts into "CAOs" in the bone invasion.
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Neoplasias de Cabeza y Cuello , Osteoblastos , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Osteoblastos/metabolismo , Osteoblastos/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Animales , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/metabolismo , Ratones , Línea Celular Tumoral , Masculino , Progresión de la Enfermedad , Femenino , Microambiente Tumoral , Transducción de Señal , Regulación Neoplásica de la Expresión Génica , Metaloproteinasa 9 de la Matriz/metabolismo , FN-kappa B/metabolismo , Persona de Mediana Edad , Metástasis Linfática/patología , Osteopontina/metabolismo , Osteopontina/genéticaRESUMEN
Oral carcinoma cuniculatum (CC) is a rare distinct variant of oral squamous cell carcinoma (OSCC) displaying unique clinical and histopathological features. CC is a locally aggressive malignancy with lower metastatic potential and has a tendency to invade the underlying bone yielding nonspecific clinical presentation resembling fungal/bacterial infections or osteomyelitis. Seven rare cases of gingival CC are reported with special emphasis on immunohistochemistry and special stains. Clinical and demographic profile were analysed and all cases were subjected to Ki-67 and p53 immunostaining and Ayoub-Shklar histochemical staining. For comparison, age and gender matched seven cases of conventional OSCC with bony involvement were recruited. IBM SPSS statistics software version 26 (IBM Analytics, Armonk, New York, U.S.) was used to analyse the data. All cases of CC lacked p53 expression in contrast to OSCC and demonstrated intermediate to high proliferation index in stroma also. The keratin staining and cytokeratin profile in OSCC and CC were also found to be statistically different. CC is a rare well differentiated variant of OSCC with different pathways involved in the pathogenesis. Local aggressive and invasive nature could be the result of unique interaction between epithelium and stromal elements. Oral health care provider must be familiar with this uncommon variant of OSCC.
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AIMS: A bone-invasive pituitary adenoma exhibits aggressive behavior, leading to a worse prognosis. We have found that TNF-α promotes bone invasion by facilitating the differentiation of osteoclasts, however, before bone-invasive pituitary adenoma invades bone tissue, it needs to penetrate the dura mater, and this mechanism is not yet clear. METHODS: We performed transcriptome microarrays on specimens of bone-invasive pituitary adenomas (BIPAs) and noninvasive pituitary adenomas (NIPAs) and conducted differential expressed gene analysis and enrichment analysis. We altered the expression of TNF-α through plasmids, then validated the effects of TNF-α on GH3 cells and verified the efficacy of the TNF-α inhibitor SPD304. Finally, the effects of TNF-α were validated in in vivo experiments. RESULTS: Pathway act work showed that the MAPK pathway was significantly implicated in the pathway network. The expression of TNF-α, MMP9, and p-p38 is higher in BIPAs than in NIPAs. Overexpression of TNF-α elevated the expression of MAPK pathway proteins and MMP9 in GH3 cells, as well as promoted proliferation, migration, and invasion of GH3 cells. Flow cytometry indicated that TNF-α overexpression increased the G2 phase ratio in GH3 cells and inhibited apoptosis. The expression of MMP9 was reduced after blocking the P38 MAPK pathway; overexpression of MMP9 promoted invasion of GH3 cells. In vivo experiments confirm that the TNF-α overexpression group has larger tumor volumes. SPD304 was able to suppress the effects caused by TNF-α overexpression. CONCLUSION: Bone-invasive pituitary adenoma secretes higher levels of TNF-α, which then acts on itself in an autocrine manner, activating the MAPK pathway and promoting the expression of MMP9, thereby accelerating the membrane invasion process. SPD304 significantly inhibits the effect of TNF-α and may be applied in the clinical treatment of bone-invasive pituitary adenoma.
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Adenoma , Sistema de Señalización de MAP Quinasas , Metaloproteinasa 9 de la Matriz , Invasividad Neoplásica , Neoplasias Hipofisarias , Factor de Necrosis Tumoral alfa , Factor de Necrosis Tumoral alfa/metabolismo , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/patología , Humanos , Adenoma/patología , Adenoma/metabolismo , Animales , Metaloproteinasa 9 de la Matriz/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Línea Celular Tumoral , Femenino , Ratones , Ratones Desnudos , Comunicación Autocrina/fisiología , Comunicación Autocrina/efectos de los fármacos , Persona de Mediana Edad , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Adulto , Ratas , Movimiento Celular/efectos de los fármacos , Movimiento Celular/fisiología , Transducción de Señal/fisiología , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVES: This study aimed to evaluate the diagnostic accuracy of contrast-enhanced computed tomography (CT) in detecting bone invasion in oral squamous cell carcinoma (OSCC) patients and to explore clinicopathological factors associated with its reliability. MATERIALS AND METHODS: 417 patients underwent preoperative contrast-enhanced CT followed by radical surgery. The presence or absence of bone invasion served as the outcome variable, with histopathologic examination of the resection specimen considered the gold standard. Statistical analyses, comprising correlation analyses and the determination of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were conducted. RESULTS: CT exhibited 76.85% sensitivity, 82.20% specificity, 47.14% PPV, and 89.67% NPV. False-positive and false-negative rates were 11.27% and 5.99%, respectively. Artifacts affected assessment in 44 patients, but not in those with bone invasion. Tumor size, depth of invasion (DOI), tumor localization at the upper jaw, lymphatic invasion, and perineural invasion correlated with incorrect identification of bone invasion (Chi-square, p < 0.05). CONCLUSIONS: Despite utilizing thin-section CT, notable false-positive and false-negative results persisted. Patients with T3 tumors, DOI ≥ 10 mm, or upper jaw tumors are at higher risk for misidentification of bone invasion. Combining multiple methods may enhance diagnostic accuracy, and the integration of artificial intelligence or tracking electrolyte disturbances by tumor depth profiling shows promise for further assessment of bone invasion before histopathology. CLINICAL RELEVANCE: Surgeons should consider these insights when planning tumor resection. Supplementary imaging may be warranted in cases with high risk factors for misidentification. Further methodological advancements are crucial for enhancing diagnostic precision.
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Carcinoma de Células Escamosas , Medios de Contraste , Neoplasias de la Boca , Invasividad Neoplásica , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X , Humanos , Femenino , Masculino , Neoplasias de la Boca/diagnóstico por imagen , Neoplasias de la Boca/patología , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Anciano , Adulto , Reproducibilidad de los Resultados , Valor Predictivo de las Pruebas , Anciano de 80 o más Años , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Neoplasias Óseas/patologíaRESUMEN
BACKGROUND: As per AJCC 8th edition TNM staging system, bone invasion is a poor prognostic marker that upstages oral cavity squamous carcinoma (OSCC) to pT4a. Cortical erosion alone of bone or tooth socket by a gingival primary is not sufficient to upstage a tumour. The differentiation of cortical erosion from invasion through the cortical bone into the medulla is often challenging, limiting accurate staging. This review aims to assess the difficulties in differentiating cortical erosion from medullary invasion and evaluate the prognostic significance of different patterns of bone involvement. METHODS: A retrospective review of OSCC with primary curative surgery and bone resection treated at a single-center over 10 years, was performed to assess the prognostic significance of bone invasion. Hematoxylin-eosin stained slides of a subset of cases were re-reviewed in a planned manner to assess difficulties in precise categorization (no invasion/erosion/cortical invasion and medullary invasion), evaluate interobserver agreement, and correlate with clinical outcome. RESULTS: Five hundred and ninety patients were included, with a median follow-up of 28 months. On univariate analysis, the 3-year local, nodal and distant metastasis control were not significantly different in the 3 groups of no invasion, erosion, and invasion (p = 0.43, 0.47, and 0.47, respectively). Overall survival (OS) at 3 years was 78.1% and disease-free-survival(DFS) was 63.7% in the entire cohort. On univariate analysis, there was significant difference in OS and DFS based on these groups. This did not translate into independent prognostic benefit on multivariable analysis (p = 0.75 and 0.19, respectively). The independent prognostic factors were margin positivity, tumor differentiation, perineural invasion and pathological nodal involvement. Planned re-review of a subset of 202 cases resulted in a change in bone involvement category in 26/202 cases, which was mainly due to difficulty in assessing cortico-medullary junction near the tooth socket and bone fragmentation. The assessment showed moderate to near complete agreement (kappa 0.59-0.82) between 2 observers. CONCLUSION: Our study shows that bone involvement is not an independent prognostic marker and there is no specific correlation of medullary invasion with outcome over those that showed cortical erosion. Several factors contribute to difficulties and interobserver variability in assessing bone involvement.
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Neoplasias de la Boca , Invasividad Neoplásica , Humanos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Neoplasias de la Boca/patología , Neoplasias de la Boca/mortalidad , Anciano , Adulto , Anciano de 80 o más Años , Neoplasias Óseas/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas/patologíaRESUMEN
It is important for surgeons performing sarcoma surgery to know that bone resection and tumor prosthesis applications in soft tissue sarcomas (STS) have unique features in terms of indication, surgical approach and follow-up, in terms of the management of these cases. Some STS are associated with bone and major neurovascular structures. Bone-associated STS are generally relatively large and relatively deep-seated. Additionally, the tendency for metastasis is high. In some cases, the decision about which structures to resect is difficult. These cases are often accompanied by poor oncological and surgical outcomes. Management of cases should be done by a multidisciplinary team in advanced centers specialized in this field. The surgical team must have sufficient knowledge and experience in the field of limb-sparing surgery. Preoperative evaluation and especially good planning of bone and soft tissue reconstruction are vital.
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BACKGROUND: Oral squamous carcinoma (OSCC) is often diagnosed at late stages and bone erosion or invasion of the jawbone is frequently present. Computed tomography (CT) and magnetic resonance imaging (MRI) are known to have high diagnostic sensitivities, specificities, and accuracies in detecting these bone affections in patients suffering from OSCC. To date, the existing data regarding the impact of cone-beam computed tomography (CBCT) have been weak. Therefore, this study aimed to investigate whether CBCT is a suitable tool to detect bone erosion or invasion in patients with OSCC. METHODS: We investigated in a prospective trial the impact of CBCT in the diagnosis of bone erosion or invasion in patients with OSCC who underwent surgery. Every participant received a CBCT, CT, and MRI scan during staging. Imaging modalities were evaluated by two specialists in oral and maxillofacial surgery (CBCT) and two specialists in radiology (CT and MRI) in a blinded way, to determine whether a bone affection was present or not. Reporting used the following 3-point system: no bony destruction ("0"), cortical bone erosion ("1"), or medullary bone invasion ("2"). Histological examination or a follow-up served to calculate the sensitivities, specificities, and accuracies of the imaging modalities. RESULTS: Our results revealed high diagnostic sensitivities (95.6%, 84.4%, and 88.9%), specificities (87.0%, 91.7%, and 91.7%), and accuracies (89.5%, 89.5%, and 90.8%) for CBCT, CT, and MRI. A pairwise comparison found no statistical difference between CBCT, CT, and MRI. CONCLUSION: Our data support the routine use of CBCT in the diagnosis of bone erosion and invasion in patients with OSCC as diagnostic accuracy is equal to CT and MRI, the procedure is cost-effective, and it can be performed during initial contact with the patient.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Tomografía Computarizada de Haz Cónico Espiral , Humanos , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Tomografía Computarizada de Haz Cónico , Células Epiteliales , Imagen por Resonancia Magnética , Neoplasias de la Boca/diagnóstico por imagen , Neoplasias de la Boca/patología , Estudios Prospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello , Tomografía Computarizada por Rayos XRESUMEN
Background: Pediatric glioblastoma multiforme (p-GBM) is an exceptionally rare and aggressive brain tumor, with even fewer reported cases with radiographic and intraoperative characteristics that mimic those of extra-axial lesions, often posing a diagnostic challenge. Despite advancements in imaging technologies, the diagnosis of GBM can still be intricate, relying primarily on histopathological confirmation. Case Description: We present a unique case of a 15-year-old female who presented to our hospital with a new-onset focal-to-bilateral tonic-clonic seizure described as clonic movements of her left hemicorps; on clinical examination, a subcutaneous mass was evident in the right parietal region. Magnetic resonance imaging of the brain revealed a sizable extra-axial enhancing mass measuring 9 cm, located in the right parieto-occipital region with notable bone invasion. Moreover, the intraoperative findings revealed an extra-axial mass attached to the dura. Total en bloc resection was achieved. The histopathological analysis confirmed the diagnosis of glioblastoma multiforme. Subsequently, the patient underwent adjuvant radiotherapy in conjunction with temozolomide chemotherapy. Postoperatively, she exhibited clinical improvement and remained stable throughout the 6-month follow-up period. Conclusion: We present the first case of extra-axial p-GBM in a young patient, which remarkably led to the destruction of the bone and finally resulted in a sizable parietal subcutaneous lesion in the absence of prior surgery or radiation.
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Localized jawbone invasion is a milestone in the progression of oral squamous cell carcinoma (OSCC). The factors that promote this process are not well understood. Sclerostin is known to be involved in bone metabolism and there are preliminary reports of its involvement in bone tumors and bone metastasis. To identify a possible involvement of sclerostin in the bone invasion process of OSCC, sclerostin expression was analyzed in vitro in two different human OSCC tumor cell lines by quantitative real-time polymerase chain reaction (qRT-PCR), and the effect of recombinant human (rh)-sclerostin treatment on tumor cell capabilities was evaluated using proliferation, migration, and invasion assays. Undifferentiated human mesenchymal stem cells (hMSCs) were osteogenically differentiated and co-cultured with OSCC tumor cells to demonstrate potential interactions and migration characteristics. Sclerostin expression was evaluated in clinical cases by immunohistochemistry at the OSCC-jawbone interface in a cohort of 15 patients. Sclerostin expression was detected in both OSCC tumor cell lines in vitro and was also detected at the OSCC-jawbone interface in clinical cases. Tumor cell proliferation rate, migration and invasion ability were increased by rh-sclerostin treatment. The migration rate of tumor cells co-cultured with osteogenically differentiated hMSCs was increased. The results presented are the first data suggesting a possible involvement of sclerostin in the bone invasion process of OSCC, which deserves further investigation and may be a potential approach for drug-based tumor therapy.
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Carcinoma de Células Escamosas , Neoplasias de la Boca , Humanos , Bioensayo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismoRESUMEN
Oral squamous cell carcinoma (OSCC) accounts for nearly 90% of oral and oropharyngeal cancer cases and is characterized by high mortality and poor prognosis. RNA-based gene therapies have been developed as an emerging option for cancer treatment, but it has not been widely explored in OSCC. In this work, we developed an efficient siRNA cationic micelle DOTAP-mPEG-PCL (DMP) by self-assembling the cationic lipid DOTAP and monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) polymer. We tested the characteristics and transformation efficiency of this micelle and combined DMP with siRNA targeting STAT3 and TGF-ß to evaluate the antitumor effect and bone invasion interfering in vitro and in vivo. The average size of the DMP was 28.27 ± 1.62 nm with an average zeta potential of 54.60 ± 0.29 mV. The DMP/siRNA complex showed high delivery efficiency, with rates of 97.47 ± 0.42% for HSC-3. In vitro, the DMP/siSTAT3 complex exhibited an obvious cell growth inhibition effect detected by MTT assay (an average cell viability of 25.1%) and clonogenic assay (an average inhibition rate of 51.9%). Besides, the supernatant from HSC-3 transfected by DMP/siTGF-ß complexes was found to interfere with osteoclast differentiation in vitro. Irrespective of local or systemic administration, DMP/siSTAT3+siTGF-ß showed antitumor effects and bone invasion inhibition in the OSCC mice mandibular invasion model according to tumor volume assays and Micro-CT scanning. The complex constructed by DMP cationic micelles and siSTAT3+siTGF-ß represents a potential RNA-based gene therapy delivery system for OSCC.
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Carcinoma de Células Escamosas , Ácidos Grasos Monoinsaturados , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Compuestos de Amonio Cuaternario , Ratones , Animales , Micelas , ARN Interferente Pequeño/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello , Neoplasias de la Boca/genética , Neoplasias de la Boca/terapia , Polietilenglicoles , Poliésteres , Línea Celular TumoralRESUMEN
Background Oral squamous cell carcinoma (OSCC) is considered to be the most common epithelial malignant neoplasm of the oral cavity. Despite advancements in diagnosis and therapeutics the clinical outcome of the disease has not improved much which may be attributed to tumor biology and heterogeneity. Bone invasion by cancer cells is currently staged as a moderately advanced disease. However, many low-grade carcinomas such as verrucous carcinoma and carcinoma cuniculatum show body invasion but less nodal metastases and better overall survival. The present study was orchestrated to analyze if bone invasion in OSCC has any impact on regional nodal metastases and survival. Materials and methods A total of 122 cases of OSCC who underwent excision and neck dissection were retrieved and included. These cases were then divided into two study groups. Group I comprised 56 OSCC cases with bone involvement and 66 cases with no bony involvement. The bone invasion was correlated with nodal metastases, survival and pattern of invasion. Statistical analysis was done using SPSS software (IBM Corp., Armonk, NY, USA). Results There was no statistically significant correlation between bone invasion with either nodal metastases or pattern of invasion, however, the worst pattern of invasion (WPOI)-4,5 showed a statistically higher incidence of nodal involvement in OSCC. No statistical difference was noted in overall survival between the two groups. Conclusion The worst pattern of invasion and not bone involvement, depicts nodal metastases in OSCC and thus, deserves consideration while staging and treatment planning.
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AIMS: Oral squamous cell carcinoma (OSCC) frequently invades the jaw. The exact mechanism of bone invasion remains unclear. This study investigates (premature) osteoclasts and the expression of its differentiation regulating proteins RANKL, OPG and RANK in patients with OSCC. METHODS: Resection specimens from OSCC patients were divided into NI group (No Invasion), E group (Erosion) or I group (bone Invasion). Tissue sections were stained with Cathepsin K (osteoclast-counting), RANKL, OPG and RANK. The staining intensity was scored on different regions of the tumor: front, center, back and normal mucosa. Immunohistochemistry and qPCR for RANKL/OPG/RANK were performed on five head and neck squamous cell carcinoma (HNSCC) organoids. RESULTS: The mean number of osteoclasts (I group) and premature osteoclasts (E group) was significantly higher compared to the NI group (p = 0.003, p = 0.036). RANKL expression was significantly higher in the tumor front and tumor center compared to normal mucosa (all groups). In the I group, RANKL and RANK expression was significantly higher in the tumor front compared to the tumor back and there was a trend of higher RANKL expression in the tumor front compared to the E group and NI group. qPCR showed a 20-43 times higher RANKL mRNA expression in three out of five tumor organoids compared to a normal squamous cell organoid line. There was no correlation between protein and mRNA expression in the HNSCC organoids. CONCLUSIONS: These findings suggest that OSCCs induce bone invasion by stimulating osteoclast activation by regulating the production of RANKL and RANK proteins.
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PURPOSE: Microscopic tumor spread beyond the macroscopically visible tumor mass in bone represents a major risk in surgical oncology, where the spatial complexity of bony resection margins cannot be countered with rapid bone analysis techniques. Laser-induced breakdown spectroscopy (LIBS) has recently been introduced as a promising option for rapid bone analysis. The present study aimed to use LIBS-based depth profiling based on electrolyte disturbance tracking to evaluate the detection of microscopic tumor spread in bone. METHODS: After en bloc resection, the tumor-infiltrated mandible section of a patient's segmental mandibulectomy specimen was natively investigated using LIBS. Spectral and electrolytic depth profiles were analyzed across 30 laser shots per laser spot position in healthy bone and at the tumor border. For the histological validation of the lasered positions, the mandibular section was marked with a thin separating disc. RESULTS: Solid calcium (Ca) from hydroxyapatite and soluble Ca from dissolved Ca can be reliably differentiated using LIBS and reflect the natural heterogeneity of healthy bone. Increased potassium (K) emission values in otherwise typically healthy bone spectra are the first spectral signs of tumorous bone invasion. LIBS-based depth profiles at the tumor border region can be used to track tumor-associated changes within the bone with shot accuracy based on the distribution of K. CONCLUSION: Depth profiling using LIBS might enable the detection of microscopic tumor spread in bone. In the future, direct electrolyte tracking using LIBS should be applied to other intraoperative challenges in surgical oncology to advance rapid bone analysis by spectroscopic-optical techniques.
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Neoplasias de la Boca , Potasio , Humanos , Potasio/análisis , Proyectos Piloto , Análisis Espectral/métodos , Calcio/análisis , Rayos Láser , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/cirugía , ElectrólitosRESUMEN
Gliosarcoma (GS) is a primary central nervous system tumor. It is an unusual type of glioblastoma multiforme (GBM) and rarely invades the skull base. It has a biomorphic tissue pattern with rapid alternation zones of glial and mesenchymal differentiation. We report the case of a 62-year-old male who presented with a one-month history of unsteady gait associated with dizziness. Brain MRI showed a right temporal mass that invaded the skull base with perilesional edema and a significant mass effect on the right lateral ventricle. The patient underwent a right-sided frontotemporal craniotomy with gross total resection. The pathology confirmed the diagnosis of GS. Postoperatively, the patient had an uneventful recovery with no complications and was discharged two days post-surgery.
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PURPOSE: This study aimed to determine the diagnostic accuracy of CT and MRI in the preoperative detection of bone involvement for non-melanoma skin cancers (NMSCs) located on the scalp. This study further aimed to evaluate the predictive value of these imaging modalities in determining the need for craniectomy and to identify gaps in the existing literature. METHODS: Electronic searches of the MEDLINE, Embase, Cochrane and Google Scholar databases were performed for English language studies of any type. Studies reporting detection or exclusion of histopathologically confirmed bone involvement through preoperative imaging were identified according to PRISMA guidelines. Studies reporting dural involvement, non-scalp tumours, and lacking tumour type(s) or outcome data were excluded. Outcomes were preoperative imaging result and histopathologically confirmed bone invasion. Meta-analysis was performed and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated (excluding case report and MRI data due to insufficient quality and quantity respectively). RESULTS: Four studies with a total of 69 patients were included in the final review, of which two studies totalling 66 patients were included in the meta-analysis. Preoperative CT had a sensitivity of 38%, specificity of 98%, PPV of 90% and NPV of 73%. CONCLUSIONS: The available data suggests that a preoperative CT finding of calvarial involvement by a scalp NMSC is likely to be real, but the absence of such a finding is unreliable. Current evidence suggests that preoperative imaging cannot exclude the necessity for craniectomy and future research is needed, particularly on the role of MRI.
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Cuero Cabelludo , Neoplasias Cutáneas , Humanos , Imagen por Resonancia Magnética , Valor Predictivo de las Pruebas , Cuero Cabelludo/diagnóstico por imagen , Sensibilidad y Especificidad , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/cirugíaRESUMEN
Lipomas are benign masses of fatty tissue, and in the forehead, they may develop in the subcutaneous or deep fat tissue. While subcutaneous lipomas are common, deep forehead lipomas are unusual and rarely invade the underlying bone. Only a few cases have been reported in the literature, and even fewer cases are reported in children. We present a case of a slowly growing frontal mass corresponding to a deep lipoma responsible for frontal bone invasion, resulting in a bony defect reaching the dural space. Through this case, we aim to emphasize forehead lipomas' clinical and surgical characteristics.
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BACKGROUND AND OBJECTIVES: Bone resection and endoprosthetic reconstruction (EPR) in the setting of soft tissue sarcoma (STS) management is rare and incurs unique challenges. We aim to report on the surgical and oncological outcomes of this relatively previously undocumented cohort. METHODS: This is a single-center retrospective review of prospectively collected data for patients who required EPRs following resection of STSs of the lower extremity. Following inclusion criteria, we assessed 29 cases of EPR for primary STS of the lower limb. RESULTS: The mean age was 54 years (range 18-84). Of the 29 patients, there were 6 total femur, 11 proximal femur, 4 intercalary, and 8 distal femur EPRs. Fourteen of 29 patients (48%) underwent re-operations for surgical complications, with 9 relating to infection (31%). When a matched cohort analysis was performed comparing our cohort to STSs that did not necessitate EPR, a reduced rate of overall survival and metastasis-free survival was found in those requiring EPR. CONCLUSION: This series identifies a high rate of complication from EPRs performed for STS. Patients should be cautioned about the high rate of infection, surgical complications, and lower overall survival in this setting.