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New therapies are being developed for breast cancer, and in this process, some "old" biomarkers are reutilized and given a new purpose. It is not always recognized that by changing a biomarker's intended use, a new biomarker assay is created. The Ki-67 biomarker is typically assessed by immunohistochemistry (IHC) to provide a proliferative index in breast cancer. Canadian laboratories assessed the analytical performance and diagnostic accuracy of their Ki-67 IHC laboratory-developed tests (LDTs) of relevance for the LDTs' clinical utility. Canadian clinical IHC laboratories enrolled in the Canadian Biomarker Quality Assurance Pilot Run for Ki-67 in breast cancer by invitation. The Dako Ki-67 IHC pharmDx assay was employed as a study reference assay. The Dako central laboratory was the reference laboratory. Participants received unstained slides of breast cancer tissue microarrays with 32 cases and performed their in-house Ki-67 assays. The results were assessed using QuPath, an open-source software application for bioimage analysis. Positive percent agreement (PPA, sensitivity) and negative percent agreement (NPA, specificity) were calculated against the Dako Ki-67 IHC pharmDx assay for 5%, 10%, 20%, and 30% cutoffs. Overall, PPA and NPA varied depending on the selected cutoff; participants were more successful with 5% and 10%, than with 20% and 30% cutoffs. Only 4 of 16 laboratories had robust IHC protocols with acceptable PPA for all cutoffs. The lowest PPA for the 5% cutoff was 85%, for 10% was 63%, for 20% was 14%, and for 30% was 13%. The lowest NPA for the 5% cutoff was 50%, for 10% was 33%, for 20% was 50%, and for 30% was 57%. Despite many years of international efforts to standardize IHC testing for Ki-67 in breast cancer, our results indicate that Canadian clinical LDTs have a wide analytical sensitivity range and poor agreement for 20% and 30% cutoffs. The poor agreement was not due to the readout but rather due to IHC protocol conditions. International Ki-67 in Breast Cancer Working Group (IKWG) recommendations related to Ki-67 IHC standardization cannot take full effect without reliable fit-for-purpose reference materials that are required for the initial assay calibration, assay performance monitoring, and proficiency testing.
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Neoplasias da Mama , Imuno-Histoquímica , Antígeno Ki-67 , Humanos , Antígeno Ki-67/metabolismo , Antígeno Ki-67/análise , Neoplasias da Mama/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Feminino , Imuno-Histoquímica/métodos , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Canadá , Sensibilidade e Especificidade , Análise Serial de Tecidos/métodosRESUMO
Synovial sarcomas are malignant soft-tissue tumors that typically affect young patients. They can arise from nearly anywhere in the body, most commonly the extremities, head and neck, and thorax. The imaging features are highly variable and depend on the anatomic origin. Most lesions present as large aggressive heterogeneous masses containing hemorrhagic and cystic foci, often with calcification. However, up to one-third of lesions have commonly benign features and can appear homogeneously solid or cystic. Especially in these cases, their innocuous imaging and clinical presentation can lead to delayed diagnosis. Therefore, knowledge of the imaging spectrum is crucial to ensuring adequate follow-up or timely pathologic sampling. We reviewed 30 pathologically proven cases in various anatomic sites from our institution to illustrate these characteristics.
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Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Imageamento por Ressonância Magnética , Sarcoma Sinovial/diagnóstico por imagem , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias Torácicas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Ultrassonografia Doppler em Cores , Adolescente , Adulto , Idoso , Dorso , Extremidades , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço , PrognósticoRESUMO
BACKGROUND: Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches. METHODS: This is a multicenter phase II study randomizing one hundred and forty patients with T1-2 N0-2 HPV+ OPC in a 1:1 ratio between de-escalated primary radiotherapy (60 Gy) ± concomitant chemotherapy and TOS ± de-escalated adjuvant radiotherapy (50-60 Gy based on risk factors). Patients will be stratified based on smoking status (< 10 vs. ≥ 10 pack-years). The primary endpoint is OS of each arm compared to historical control; we hypothesize that a 2-year OS of 85% or greater will be achieved. Secondary endpoints include progression free survival, QOL and toxicity. DISCUSSION: This study will provide an assessment of two de-escalation approaches to the treatment of HPV+ OPC on oncologic outcomes, QOL and toxicity. Results will inform the design of future definitive phase III trials. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03210103. Date of registration: July 6, 2017, Current version: 1.3 on March 15, 2019.
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Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/terapia , Protocolos Clínicos , Procedimentos Cirúrgicos Bucais , Neoplasias Orofaríngeas/etiologia , Neoplasias Orofaríngeas/terapia , Infecções por Papillomavirus/complicações , Radioterapia Adjuvante , Carcinoma de Células Escamosas/diagnóstico , Terapia Combinada , Feminino , Humanos , Masculino , Procedimentos Cirúrgicos Bucais/métodos , Neoplasias Orofaríngeas/diagnóstico , Infecções por Papillomavirus/virologia , Radioterapia Adjuvante/métodos , Projetos de PesquisaRESUMO
BACKGROUND: Transoral robotic surgery (TORS) with concurrent neck dissection has supplanted radiotherapy in the USA as the most common treatment for oropharyngeal squamous cell carcinoma (OPSCC), yet no randomised trials have compared these modalities. We aimed to evaluate differences in quality of life (QOL) 1 year after treatment. METHODS: The ORATOR trial was an investigator-initiated, multicentre, international, open-label, parallel-group, phase 2, randomised study. Patients were enrolled at six hospitals in Canada and Australia. We randomly assigned (1:1) patients aged 18 years or older, with Eastern Cooperative Oncology Group scores of 0-2, and with T1-T2, N0-2 (≤4 cm) OPSCC tumour types to radiotherapy (70 Gy, with chemotherapy if N1-2) or TORS plus neck dissection (with or without adjuvant chemoradiotherapy, based on pathology). Following stratification by p16 status, patients were randomly assigned using a computer-generated randomisation list with permuted blocks of four. The primary endpoint was swallowing-related QOL at 1 year as established using the MD Anderson Dysphagia Inventory (MDADI) score, powered to detect a 10-point improvement (a clinically meaningful change) in the TORS plus neck dissection group. All analyses were done by intention to treat. This study is registered with ClinicalTrials.gov (NCT01590355) and is active, but not currently recruiting. FINDINGS: 68 patients were randomly assigned (34 per group) between Aug 10, 2012, and June 9, 2017. Median follow-up was 25 months (IQR 20-33) for the radiotherapy group and 29 months (23-43) for the TORS plus neck dissection group. MDADI total scores at 1 year were mean 86·9 (SD 11·4) in the radiotherapy group versus 80·1 (13·0) in the TORS plus neck dissection group (p=0·042). There were more cases of neutropenia (six [18%] of 34 patients vs none of 34), hearing loss (13 [38%] vs five [15%]), and tinnitus (12 [35%] vs two [6%]) reported in the radiotherapy group than in the TORS plus neck dissection group, and more cases of trismus in the TORS plus neck dissection group (nine [26%] vs one [3%]). The most common adverse events in the radiotherapy group were dysphagia (n=6), hearing loss (n=6), and mucositis (n=4), all grade 3, and in the TORS plus neck dissection group, dysphagia (n=9, all grade 3) and there was one death caused by bleeding after TORS. INTERPRETATION: Patients treated with radiotherapy showed superior swallowing-related QOL scores 1 year after treatment, although the difference did not represent a clinically meaningful change. Toxicity patterns differed between the groups. Patients with OPSCC should be informed about both treatment options. FUNDING: Canadian Cancer Society Research Institute Grant (#701842), Ontario Institute for Cancer Research Clinician-Scientist research grant, and the Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers grant.
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Esvaziamento Cervical/efeitos adversos , Qualidade de Vida , Radioterapia de Intensidade Modulada/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Neoplasias da Língua/terapia , Neoplasias Tonsilares/terapia , Idoso , Quimiorradioterapia Adjuvante , Deglutição , Transtornos de Deglutição/etiologia , Feminino , Perda Auditiva/etiologia , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Procedimentos Cirúrgicos Robóticos/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/complicações , Estomatite/etiologia , Inquéritos e Questionários , Zumbido/etiologia , Neoplasias da Língua/complicações , Neoplasias Tonsilares/complicações , Trismo/etiologiaAssuntos
Olho/irrigação sanguínea , Arterite de Células Gigantes/diagnóstico , Isquemia/etiologia , Pseudotumor Cerebral/complicações , Base do Crânio/diagnóstico por imagem , Idoso , Biópsia , Diagnóstico Diferencial , Humanos , Isquemia/diagnóstico , Imageamento por Ressonância Magnética/métodos , Masculino , Pseudotumor Cerebral/diagnóstico , SíndromeRESUMO
Members of Rho family GTPases including Cdc42 are known to play pivotal roles in cell migration. Cell migration is also known to be regulated by many protein kinases. Kinetworks KPSS 11.0 phospho-site screening of Cdc42-silenced Hs578T breast cancer cells revealed most dramatic change in ERK5 MAP kinase. In the present study, we set out to determine the relationship between Cdc42 and ERK5 and its significance in breast cancer cell migration and invasion. Specific siRNAs were used for knocking down Cdc42 or ERK5 in breast cancer cells. Increased ERK5 phosphorylation in breast cancer cells was achieved by infection of constitutively active MEK5 adenovirus. The cells were then subjected to cell migration or invasion assay without the presence of serum or any growth factor. We found that Cdc42 negatively regulated phosphorylation of ERK5, which in turn exhibited an inverse relationship with migration and invasiveness of breast cancer cells. To find out some in vivo relevance of the results of our in vitro experiments we also examined the expression of ERK5 in the breast cancer tissues and their adjacent normal control tissues by real-time RT-PCR and immunocytochemistry. ERK5 expression was found to be reduced in breast cancer tissues as compared with their adjacent uninvolved mammary tissues. Therefore, Cdc42 may promote breast cancer cell migration and invasion by inhibiting ERK5 phosphorylation and ERK5 expression may be inversely correlated with the progression of some breast tumors.
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Neoplasias da Mama/metabolismo , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , Proteína cdc42 de Ligação ao GTP/metabolismo , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Movimento Celular/fisiologia , Feminino , Humanos , Proteína Quinase 7 Ativada por Mitógeno/genética , Fosforilação/genética , Fosforilação/fisiologia , Proteína cdc42 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP/genética , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
Intraductal carcinoma has been described in the salivary glands as a relatively benign tumour with low-grade histopathologic features. To our knowledge, this tumour has not previously been reported in the lacrimal gland. We report the first case of low-grade intraductal carcinoma occurring in the lacrimal gland. This tumour was discovered incidentally on neuro-imaging in an asymptomatic 65-year-old patient. Incisional biopsy revealed uniform, polygonal cells with eosinophilic cytoplasm and minimal nuclear atypia, arranged in solid, cribiform and micropapillary nests. The patient underwent complete surgical excision with no evidence of recurrence at 8 months of follow-up.
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Carcinoma Ductal/patologia , Neoplasias Oculares/patologia , Doenças do Aparelho Lacrimal/patologia , Idoso , Biomarcadores Tumorais/metabolismo , Biópsia , Carcinoma Ductal/diagnóstico por imagem , Carcinoma Ductal/metabolismo , Carcinoma Ductal/cirurgia , Neoplasias Oculares/diagnóstico por imagem , Neoplasias Oculares/metabolismo , Neoplasias Oculares/cirurgia , Feminino , Humanos , Doenças do Aparelho Lacrimal/diagnóstico por imagem , Doenças do Aparelho Lacrimal/metabolismo , Doenças do Aparelho Lacrimal/cirurgia , Tomografia Computadorizada por Raios XRESUMO
Idiopathic avascular necrosis of the scaphoid bone, Preiser's disease, was originally described as a deteriorative pathology whereby the osseous structure necroses due to loss of blood supply. It may present with multifactorial etiology, which is still largely not well understood. We describe a case of Preiser's disease in a 70-year-old female, with worsening pain and loss of range of motion in her right wrist over a two-year period. Past medical history was significant for Sjogren's disease, fibromyalgia, and dystonia. Pain began several months following traumatic right dorsal wrist injury. Diagnosis of traumatic scaphoid fracture was originally suspected. Conservative treatment was unsuccessful. Radiographs did not demonstrate evidence of primary fracture. CT scan and MRI demonstrated osteonecrosis of the proximal pole of the scaphoid, but no evidence of fracture, either residual or healing, was found. Proximal row carpectomy was performed for avascular necrosis of the scaphoid. Histology confirmed diagnosis and verified absence of fracture. Postoperatively, the patient's pain and range of motion improved. This report combines histological findings of Preiser's disease with radiographic images which may ameliorate understanding of the clinical pathophysiology. We describe an unusual manifestation of Preiser's disease whereby a single traumatic event, in the absence of fracture, led to idiopathic scaphoid avascular necrosis, which may have been associated with Sjogren's syndrome and fibromyalgia. These conditions may have negatively impacted microvasculature and decreased bone mineral density, inversely correlated with the production of fatty marrow, facilitating the onset of osteonecrosis in the scaphoid.
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Vascular leiomyomas are infrequent benign soft tissue neoplasms arising from vascular wall. These lesions are more frequent in females, predominantly seen in lower extremities presenting as slowly enlarging freely mobile palpable soft tissue lesions, often painful. The role of imaging in small peripheral soft tissue masses is often limited to preoperative mapping with a long list of potential differentials. We are presenting 2 case studies of palpable masses with similar pathology, soft tissue vascular leiomyomas where its MR features can be helpful in inclusion of this entity not only in differential diagnosis of enhancing small peripheral soft tissue masses but can suggest a diagnosis in appropriate clinical scenario.
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Background: There are a number of nerve grafting options for facial reanimation and the ansa hypoglossi (AH) may be considered in select situations. Objective: To compare axonal density, area, and diameter of AH with other nerves more usually used for facial reanimation. Methods: AH specimens from patients undergoing neck dissections were submitted in formalin. Proximal to distal cross sections, nerve diameters, and the number of axons per nerve, proximally and distally, were measured and counted. Results: Eighteen nerve specimens were analyzed. The average manual axon count for the distal and proximal nerve sections was 1378 ± 333 and 1506 ± 306, respectively. The average QuPath counts for the proximal and distal nerve sections were 1381 ± 325 and 1470 ± 334, respectively. The mean nerve area of the proximal and distal nerve sections was 0.206 ± 0.01 and 0.22 ± 0.064 mm2, respectively. The mean nerve diameter for the proximal and distal nerve sections were 0.498 ± 0.121 and 0.526 ± 0.75 mm, respectively. Conclusion: The histological characteristics of the AH support clinical examination of outcomes as a promising option in facial reanimation.
Assuntos
Paralisia Facial , Humanos , Paralisia Facial/cirurgia , Paralisia Facial/patologia , Nervo Facial/cirurgia , Axônios/patologia , Face , Procedimentos NeurocirúrgicosRESUMO
BACKGROUND: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has markedly increased over the last three decades due to newly found associations with human papillomavirus (HPV) infection. Primary radiotherapy (RT) is the treatment of choice for OPSCC at most centers, and over the last decade, the addition of concurrent chemotherapy has led to a significant improvement in survival, but at the cost of increased acute and late toxicity. Transoral robotic surgery (TORS) has emerged as a promising alternative treatment, with preliminary case series demonstrating encouraging oncologic, functional, and quality of life (QOL) outcomes. However, comparisons of TORS and RT in a non-randomized fashion are susceptible to bias. The goal of this randomized phase II study is to compare QOL, functional outcomes, toxicity profiles, and survival following primary RT (± chemotherapy) vs. TORS (± adjuvant [chemo] RT) in patients with OPSCC. METHODS/DESIGN: The target patient population comprises OPSCC patients who would be unlikely to require chemotherapy post-resection: Tumor stage T1-T2 with likely negative margins at surgery; Nodal stage N0-2, ≤3 cm in size, with no evidence of extranodal extension on imaging. Participants will be randomized in a 1:1 ratio between Arm 1 (RT ± chemotherapy) and Arm 2 (TORS ± adjuvant [chemo] RT). In Arm 1, patients with N0 disease will receive RT alone, whereas N1-2 patients will receive concurrent chemoradiation. In Arm 2, patients will undergo TORS along with selective neck dissections, which may be staged. Pathologic high-risk features will be used to determine the requirement for adjuvant radiotherapy +/- chemotherapy. The primary endpoint is QOL score using the M.D. Anderson Dysphagia Inventory (MDADI), with secondary endpoints including survival, toxicity, other QOL outcomes, and swallowing function. A sample of 68 patients is required. DISCUSSION: This study, if successful, will provide a much-needed randomized comparison of the conventional strategy of primary RT vs. the novel strategy of primary TORS. The trial is designed to provide a definitive QOL comparison between the two arms, and to inform the design of an eventual phase III trial for survival outcomes. TRIAL REGISTRATION: NCT01590355.
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Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/cirurgia , Carcinoma de Células Escamosas/patologia , Protocolos Clínicos , Humanos , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/patologiaRESUMO
We present a unique case of a 6 cm, incidental, ureteral myopericytoma which was initially believed to be an ovarian tumor with mass effect, causing hydroureteronephrosis. A 75-year-old woman presented with a three-month history of postprandial cramps and heartburn. A right distal ureterectomy with en-bloc resection of the mass was performed. Histologically, a well-circumscribed, cellular proliferation of uniform, cytologically bland, spindle cells was identified that had a multilayered, concentric growth pattern around numerous blood vessels. Immunohistochemically, the spindle lesional cells stained strongly and diffusely with antibodies against smooth muscle actin and failed to stain for pancytokeratin and S100 protein.
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PURPOSE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has risen rapidly, because of an epidemic of human papillomavirus infection. The optimal management of early-stage OPSCC with surgery or radiation continues to be a clinical controversy. Long-term randomized data comparing these paradigms are lacking. METHODS: We randomly assigned patients with T1-T2, N0-2 (≤ 4 cm) OPSCC to radiotherapy (RT) (with chemotherapy if N1-2) versus transoral robotic surgery plus neck dissection (TORS + ND) (with or without adjuvant therapy). The primary end point was swallowing quality of life (QOL) at 1-year using the MD Anderson Dysphagia Inventory. Secondary end points included adverse events, other QOL outcomes, overall survival, and progression-free survival. All analyses were intention-to-treat. Herein, we present long-term outcomes from the trial. RESULTS: Sixty-eight patients were randomly assigned (n = 34 per arm) between August 10, 2012, and June 9, 2017. Median follow-up was 45 months. Longitudinal MD Anderson Dysphagia Inventory analyses demonstrated statistical superiority of RT arm over time (P = .049), although the differences beyond 1 year were of smaller magnitude than at the 1-year timepoint (year 2: 86.0 ± 13.5 in the RT arm v 84.8 ± 12.5 in the TORS + ND arm, P = .74; year 3: 88.9 ± 11.3 v 83.3 ± 13.9, P = .12). These differences did not meet the threshold to qualify as a clinically meaningful change at any timepoint. Certain differences in QOL concerns including more pain and dental concerns in the TORS + ND arm seen at 1 year resolved at 2 and 3 years; however, TORS patients started to use more nutritional supplements at 3 years (P = .015). Dry mouth scores were higher in RT patients over time (P = .041). CONCLUSION: On longitudinal analysis, the swallowing QOL difference between primary RT and TORS + ND approaches persists but decreases over time. Patients with OPSCC should be informed about the pros and cons of both treatment options (ClinicalTrials.gov identifier: NCT01590355).
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Carcinoma de Células Escamosas , Transtornos de Deglutição , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Procedimentos Cirúrgicos Robóticos , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Transtornos de Deglutição/etiologia , Humanos , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/cirurgia , Qualidade de Vida , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
Importance: The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown. Objective: To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC. Design, Setting, and Participants: This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up. Interventions: Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings). Main Outcomes and Measures: The primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects. Results: Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively). Conclusions and Relevance: In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes. Trial Registration: Clinicaltrials.gov Identifier: NCT03210103.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/cirurgia , Infecções por Papillomavirus/complicações , Qualidade de Vida , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapiaRESUMO
PURPOSE: To investigate the role of intra-lesional interleukin-2 (IL-2) injection for treatment of in-transit melanoma metastases. METHODS: Consecutive patients with in-transit metastases were treated with intra-lesional IL-2 injections. Two independent observers evaluated response to treatment using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. A blinded pathologist confirmed clinical response with post-treatment biopsies. RESULTS: Thirty-nine patients were included. Patients received biweekly IL-2 injections. At each treatment session, a mean of 2.08 ml (5 µ/ml) of IL-2 were distributed amongst a mean of 12 (range 1-57) in-transit lesions. Patients were followed for an average of 30.4 months (range 2.2-66.6 months). The overall patient response rate was 82%. A complete response was obtained in 20 patients (51%), a partial response in 12 (31%), and no response in seven (18%). Of the 629 in-transit metastases, 479 (76%) completely resolved. Complete responders had a significant in transit-free (P = 0.0005) and an overall (P = 0.012) survival advantage compared with partial responders. CONCLUSIONS: The treatment of in-transit metastatic melanoma with intra-lesional IL-2 resulted in a 76% percent clearance of lesions. Complete response is associated with superior in transit-free and overall survival when compared with partial response.
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Antineoplásicos/administração & dosagem , Interleucina-2/administração & dosagem , Melanoma/tratamento farmacológico , Melanoma/secundário , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Feminino , Humanos , Injeções Intralesionais , Interleucina-2/efeitos adversos , Metástase Linfática , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Estudos Prospectivos , Terapia de Salvação , Neoplasias Cutâneas/patologia , Análise de SobrevidaRESUMO
Primary intraoral angiosarcoma is an exceptionally rare malignancy of vascular origin which can be challenging to diagnose due to microscopic and immunohistochemical variability. A histopathologically challenging case of primary intraoral angiosarcoma, occurring in a pediatric patient is presented. A comprehensive review of the literature reveals that primary intraoral angiosarcomas occur with nearly equal frequency in males and females, affect the gingiva and the tongue most commonly and are treated primarily with surgery. As with angiosarcoma in other sites, primary intraoral angiosarcoma behaves aggressively with the majority of patients succumbing to their disease.
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Hemangiossarcoma/patologia , Neoplasias Bucais/patologia , Adolescente , Humanos , MasculinoRESUMO
The WHO Classification of Tumors of Soft Tissue and Bone divides rhabdomyosarcoma (RMS) into alveolar, embryonal, pleomorphic, and spindle cell/sclerosing types. Advances in molecular diagnostics have allowed for further refinement of RMS classification including the identification of new subtypes. Very rare RMS with epithelioid and spindle cell morphology, female predominance, marked osseous predilection, ALK expression, EWSR1/FUS-TFCP2 gene fusions, and highly aggressive clinical behavior have recently been recognized with only 23 cases reported in the English language literature. Herein, we report two additional cases with detailed clinicopathologic description and molecular confirmation. In brief, two young women presented each with a primary bone tumor-one with a frontal bone tumor and another with an osseous pelvic tumor. Both tumors showed epithelioid to spindle cell morphology, ALK expression, and EWSR1/FUS-TFCP2 gene fusions. Both patients died of disease less than 17 months from diagnosis despite administration of multiple lines of aggressive treatment. In addition, we review the literature and discuss differential diagnostic and potential treatment considerations.
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Biomarcadores Tumorais/genética , Proteínas de Ligação a DNA/genética , Fusão Gênica , Neoplasias Pélvicas/genética , Proteína EWS de Ligação a RNA/genética , Proteína FUS de Ligação a RNA/genética , Rabdomiossarcoma/genética , Neoplasias Cranianas/genética , Fatores de Transcrição/genética , Adulto , Progressão da Doença , Células Epitelioides/patologia , Evolução Fatal , Feminino , Osso Frontal/patologia , Predisposição Genética para Doença , Humanos , Neoplasias Pélvicas/diagnóstico por imagem , Neoplasias Pélvicas/patologia , Neoplasias Pélvicas/terapia , Fenótipo , Rabdomiossarcoma/diagnóstico por imagem , Rabdomiossarcoma/secundário , Rabdomiossarcoma/terapia , Neoplasias Cranianas/diagnóstico por imagem , Neoplasias Cranianas/patologia , Neoplasias Cranianas/terapia , Adulto JovemRESUMO
BACKGROUND: Spindle cell lipomas (SCLs) are benign tumors that are characteristically present on the upper back and neck, but in rare cases present throughout the respiratory mucosa, causing hoarseness, stridor, dyspnea, and obstruction. OBJECTIVE: To highlight the importance of considering SCL in the diagnosis of benign respiratory tract tumors, a literature review identified all published cases of respiratory tract SCLs, including 2 from our institution: one case in the nasopharynx and 1 in the nasal valve. METHODS: All case reports, series and literature reviews from the English literature from 1975 through March 2018 were systematically identified for review in the MEDLINE, EMBASE, and Scopus databases. Two additional cases from our institution were described. RESULTS: In total, 24 cases of SCL in the respiratory tract were identified for review. Two cases from our institution are described here, bringing the total of reported cases to 26. Extensive analyses of oral cavity SCLs already exist, so we excluded this site from our review and focused on sites where SCLs may present with respiratory symptoms. Excluding the oral cavity and oropharynx, the most common location described is the larynx. All 26 cases were treated with excision. One tumor required a second surgery, but there were no other complications nor recurrences. CONCLUSION: Although rare, SCLs may arise from throughout the respiratory tract and cause dyspnea, hoarseness and stridor. Spindle cell lipoma should be considered in the differential diagnosis of a respiratory tract mass. This diagnosis confers a good prognosis and patients may be reassured that surgery is almost always curative.
Assuntos
Dispneia/diagnóstico , Lipoma/diagnóstico , Neoplasias Bucais/diagnóstico , Idoso , Biópsia , Diagnóstico Diferencial , Dispneia/etiologia , Humanos , Lipoma/complicações , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/complicações , Tomografia Computadorizada por Raios XRESUMO
Ectomesenchymal chondromyxoid tumor is a rare and benign neoplasm with a predilection for the anterior dorsal tongue. Despite morphologic heterogeneity, most cases are characterized by a proliferation of bland spindle cells with a distinctive reticular growth pattern and myxoid stroma. The immunophenotype of these neoplasms is likewise variable; most cases express glial fibrillary acid protein and S100 protein, with inconsistent reports of keratin and myoid marker expression. The molecular pathogenesis is poorly understood; however, a subset of cases has been reported to harbor EWSR1 gene rearrangement. Following identification of an RREB1-MKL2 fusion gene by RNA Sequencing in an index patient, a retrospective review of additional cases of ectomesenchymal chondromyxoid tumors was performed to better characterize the clinical, immunohistochemical, and molecular attributes of this neoplasm. A total of 21 cases were included in this series. A marked predisposition for the dorsal tongue was confirmed. Most cases conformed to prior morphologic descriptions; however, hypercellularity, hyalinized stroma, and necrosis were rare attributes not previously emphasized. The neoplastic cells frequently coexpressed glial fibrillary acid protein, S100 protein, keratin, smooth muscle actin, and/or desmin; a single case was found to contain significant myogenin expression. An RREB1-MKL2 fusion product was identified in 19 tumors (90%), a single tumor (5%) had an EWSR1-CREM fusion product, and the remaining case lacked any known fusion gene by RNA Sequencing. The latter 2 cases subtly differed morphologically from many in the cohort. This series illustrates that recurrent RREB1-MKL2 fusions occur in most, perhaps all, cases of ectomesenchymal chondromyxoid tumor.