Complete response with talimogene laherparepvec in recurrent melanoma of the ear: A case report.

The current standard of care for cutaneous melanoma of the ear is surgical excision. This approach may result in unfavorable functional and cosmetic outcomes. We report here a case of recurrent melanoma of the ear that achieved complete response with talimogene laherparepvec treatment after the patient declined surgical resection.

Clinical response to pazopanib in a patient with endolymphatic sac tumor not associated with von Hippel-Lindau syndrome.

Endolymphatic sac tumors (ELSTs) are rare, locally invasive, vascular tumors of the temporal bone. These lesions are associated with von Hippel-Lindau syndrome but may arise sporadically. Early surgical intervention is recommended to prevent permanent neurologic deficits; however, many ELSTs are unresectable or are subtotally resected due to neurovascular compromise. Chemotherapeutic salvage therapy in trials of neoplasms of associated syndromes has targeted angiogenesis with variable response. We present the case of a sporadic ELST, previously minimally responsive to bevacizumab, treated with pazopanib, a multi-kinase inhibitor and antiangiogenic, with good response. Cases such as our patient may demonstrate the utility of novel antiangiogenics in the treatment of these rare neoplasms, particularly when the tumor is unresectable or necessitates subtotal resection.

CD20-negative primary middle ear diffuse large B-cell lymphoma coexpressing MYC and BCL-2 secondary to acute lymphoblastic leukemia: A case report.

RATIONALE: Second diffuse large B-cell lymphoma (DLBCL) after treatment of acute lymphoblastic leukemia (ALL) is uncommon. To our knowledge, primary middle ear DLBCL which presents CD20-negative and coexpression of MYC and BCL-2 has not been reported yet. PATIENT CONCERNS: A 20-year-old Chinese man complained fever and weakness for 2 months. Subsequently bone marrow morphology and flow cytometry immunophenotype suggested ALL. Administrated with 9 cycles of multiagent combined chemotherapy, he felt right ear progressive hearing loss, otalgia, aural fullness. Otoendoscopic examination revealed a pitchy mass obstructing the right external auditory canal. Then the mass resection was performed for biopsy and immunohistochemistry examination. DIAGNOSIS: The mass was diagnosed as DLBCL which was negative for CD20 and double expression of MYC and BCL-2. INTERVENTIONS: Chemotherapy. OUTCOMES: The patient eventually gave up and died of severe infection. LESSONS: Although intensive chemotherapy has markedly improved the survival of ALL, more and more secondary cancers have been reported. In addition, primary middle ear lymphoma is much rare; hence, it is easy to be misdiagnosed. Furthermore, DLBCL with negative CD20 and double expression of MYC and BCL-2 is aggressive, which is characterized by chemotherapy resistance and inferior survival rates. We discuss this case aiming at raising awareness of tumors secondary to ALL and exploring the appropriate treatment options for the rare DLBCL.

Unusual presentation for small lymphocytic lymphoma: Case report of a man with bilateral ear involvement and review of the literature.

INTRODUCTION: Ear involvement by non-Hodgkin lymphoma is quite rare and can be mistaken for other common lesions encountered in otolaryngology. The literature on this subject is also limited. CASE SUMMARY: A 45-year-old man with bilateral ear nodules that progressed over two years. Biopsy of the right ear revealed a B-cell small lymphocytic lymphoma (SLL). The patient responded to radiotherapy well. He received an additional dose two months after the initial treatment because of a remaining nodularity on the right earlobe. After several months, he presented a new lesion on his nasal tip, for which a biopsy confirmed a lymphoma relapse. The patient was managed with oral prednisone and low-dose radiation with a favourable response. DISCUSSION: This case highlights the importance of including lymphoma in the differential diagnosis of ear lesions from an otolaryngology perspective. A biopsy of any lesion or nodule with an atypical course should be considered for appropriate diagnosis and management.

The Auricular VX2 Carcinoma Is a Suitable Animal Model for Identifying Biomarkers for HNSCC Therapy Response.

BACKGROUND/AIM: The rabbit auricular VX2 carcinoma is an established animal model for human head and neck squamous cell carcinoma (HNSCC). Previously, we observed that intraperitoneal oxidative (O3/O2) stress induced tumor remission. Our aim was to evaluate candidate genes associated with tumor regression. MATERIALS AND METHODS: For identification of tumor remission-related genes, microarray analysis was performed with subsequent validation by polymerase chain reaction (PCR), in situ hybridization, immunohistochemistry and western blot analysis. RESULTS: Microarray analysis indicated a prominent reduction of epidermal growth factor receptor (Egfr, Erbb1) expression levels in regressing tumors. Quantitative PCR confirmed a significant (p<0.005) down-regulation of Erbb1-3 mRNA in regressing VX2 tumors. Histological localization of Erbb1-3 mRNA transcript and protein indicated reduced Erbb gene expression occurring at the level of individual VX2 tumor cells rather than solely being an effect of tumor shrinkage. This study highlights changes in the Erbb gene signature of regressing VX2 carcinomas as a predictor for therapy response. The VX2 carcinoma animal model, therefore, appears suitable for the identification and evaluation of new diagnostic, prognostic and therapeutic biomarkers prior to their application in patients with HNSCC.

Complete remission and long-term survival of a patient with melanoma metastases treated with high-dose fever-inducing Viscum album extract: A case report.

INTRODUCTION: Metastatic malignant cutaneous melanoma (MCM)-a highly immunogenic cancer-typically has a poor prognosis. Viscum album extracts (VAEs) have strong immune-stimulating, apoptogenic, and cytotoxic effects. CASE PRESENTATION: A 66-year-old MCM patient with newly diagnosed lymph node metastases opted for sole VAE treatment. VAEs were initially applied subcutaneously, and then later in exceptionally high, fever-inducing doses, both intravenously and intralesionally. The metastases shrunk over the following months, and after 2 years, all lesions had completely remitted (regional and hilar lymph nodes). The patient has been tumor free for 3.5 years at the time of publication (and for 5 years since initiation of intensified VAE treatment). Besides fever and flu-like symptoms, no side effects occurred. DISCUSSION: We presume that VAE triggered an increased release of tumor-associated antigens, enhanced immunologic recognition, and increased immune response against the tumor tissue and induced tumor remission.

Comparing the sensitivity of linear and volumetric MRI measurements to detect changes in the size of vestibular schwannomas in patients with neurofibromatosis type 2 on bevacizumab treatment.

OBJECTIVE: To compare the sensitivity of linear and volumetric measurements on MRI in detecting schwannoma progression in patients with neurofibromatosis type 2 on bevacizumab treatment as well as the extent to which this depends on the size of the tumour. METHODS: We compared retrospectively, changes in linear tumour dimensions at a range of thresholds to volumetric tumour measurements performed using Brainlab iPlan(®) software (Feldkirchen, Germany) and classified for tumour progression according to the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) criteria. RESULTS: Assessment of 61 schwannomas in 46 patients with a median follow-up of 20 months (range 3-43 months) was performed. There was a mean of 7 time points per tumour (range 2-12 time points). Using the volumetric REiNS criteria as the gold standard, a sensitivity of 86% was achieved for linear measurement using a 2-mm threshold to define progression. CONCLUSION: We propose that a change in linear measurement by 2 mm (particularly in tumours with starting diameters 20-30 mm, the majority of this cohort) could be used as a filter to identify cases of possible progression requiring volumetric analysis. This pragmatic approach can be used if stabilization of a previously growing schwannoma is sufficient for a patient to continue treatment in such a circumstance. ADVANCES IN KNOWLEDGE: We demonstrate the real-world limitations of linear vs volumetric measurement in tumour response assessment and identify limited circumstances where linear measurements can be used to determine which patients require the more resource-intensive volumetric measurements.

Dabrafenib in an elderly patient with metastatic melanoma and BRAF V600R mutation: a case report.

BACKGROUND: Approximately 50 % of malignant melanomas harbor activating point mutations in the BRAF gene. Typically, these mutations result in the substitution of the amino acid valine at codon 600 of the gene, and 90-95 % of mutations are either BRAF (V600E) or BRAF (V600K). Specific BRAF inhibitors such as dabrafenib and vemurafenib are the mainstays of treatment in patients with metastatic BRAF-mutant malignant melanomas. The third most common BRAF mutation is V600R, which also leads to increased BRAF signaling. Although evidence exists about the activity of dabrafenib and vemurafenib in patients with the BRAF (V600R) mutation, these patients have been systematically excluded from recent trials with targeted therapies. CASE PRESENTATION: Here, we report the positive results in terms of survival and quality of life obtained with dabrafenib in an 80-year-old Caucasian male patient with a Charlson Comorbidity Index of 8 diagnosed with metastatic malignant melanoma harboring the BRAF (V600R) mutation. Our patient was treated with dabrafenib for 7 months with minimal toxicity. We also report exploratory analyses of circulating tumor DNA during targeted treatment. Interestingly, the mutation was not detected after starting treatment and became detectable before radiological disease progression. CONCLUSIONS: Our report suggests that (1) a relevant benefit can be obtained with a BRAF inhibitor in real-world patients with a malignant melanoma harboring a BRAF (V600R) mutation, and that (2) circulating tumor DNA detection might be of help in assessing tumor burden in everyday clinical practice. The results reported here should encourage the inclusion of patients with BRAF (V600R)-mutated malignant melanomas in future prospective clinical trials with BRAF inhibitors.

Carcinoma espinocelular del oído externo con extensión parotídea: a propósito de un caso / Squamous cell carcinoma of the external ear with parotid extension: case report

El pabellón auricular y el conducto auditivo externo constituyen una región anatómica que puede ser asiento de múltiples patologías, entre ellas procesos inflamatorios, infecciosos y neoplásicos, tanto benignos como malignos. Con respecto a los tumores, los diversos tipos suelen presentarse con síntomas y signos similares y en general es difícil inferir la variedad histológica del tumor a través del examen físico, por lo cual es necesario el estudio histopatológico para determinar el diagnóstico. La mayoría de los tumores del oído externo son carcinomas; entre ellos se destacan el carcinoma basocelular, el más frecuente, y el carcinoma espinocelular. Menos frecuentemente se encuentran otros tipos de tumores como los melanomas, adenocarcinomas, carcinomas de glándulas ceruminosas, carcinomas mucoepidermoides, sarcomas, procesos linfoproliferativos, etc. Suelen ocurrir en la edad media y avanzada (50-70 años) y con mayor periodicidad en el sexo masculino. En el presente trabajo se describe un caso clínico de carcinoma espinocelular del oído externo, tratado exitosamente mediante cirugía y radioterapia, así como también se describen las características clínicas de esta enfermedad, con especial atención al compromiso del oído externo por ella.

The pinna and the ear canal are an anatomical region that can be affected by many diseases, including inflammatory, infectious and benign and malignant neoplastic processes. With regard to tumors, various types usually present with similar symptoms and usually is very difficult to know the histological type through physical examination, so histopathological examination is necessary in order to determine the diagnosis. Most tumors are carcinomas; they can be basal cell carcinoma (more frequently), or squamous carcinoma. Less frequently are other types of tumors such as melanomas, adenocarcinomas, ceruminous glands carcinomas, mucoepidermoid carcinomas, sarcomas, lymphoproliferative disorders, etc. They usually present in middle and advanced age people (50-70 years) and are more frequently in men. In this article we present a case of squamous cell carcinoma of the external ear with extention to parotid gland, successfully treated with surgery and radiotherapy, as well as we describe the clinical characteristics of this disease, with special attention to the compromise of the external ear. (AU)

Un simulador clásico de vasculitis sistémica / A classic mimicker of systemic vasculitis

Fundamento y objetivo. Las manifestaciones embolígenas y constitucionales de los tumores cardíacos intracavitarios se engloban dentro de los mimetizadores clásicos de las vasculitis sistémicas, sobre todo en aquellas ocasiones donde no se presentan manifestaciones cardiológicas. Se describe un caso de mixoma auricular con clínica exclusivamente sistémica, cuya orientación diagnóstica inicial fue de vasculitis. Se revisan los casos descritos en la literatura. Paciente y método. Se describe un caso de mixoma auricular con presentación en forma de manifestaciones sistémicas sin sintomatología cardiológica acompañante. Se expone el caso clínico y se compara con 11 casos de seudovasculitis por mixoma auricular descritos en la literatura, haciendo énfasis en las similitudes y divergencias. Discusión. Los síntomas constitucionales junto con las manifestaciones cutáneas fueron los más frecuentes. La mayoría de los casos presentaban respuesta parcial al tratamiento glucocorticoideo, reforzando la teoría del componente inflamatorio en su patogenia. La demora media en el diagnóstico fue de 12,27 meses. Conclusión. El mixoma auricular es un simulador de vasculitis sistémica y es de difícil diagnóstico cuando no presenta manifestaciones cardíacas. La demora diagnóstica puede conllevar complicaciones graves (AU)

Background and objective. Embolic and constitutional manifestations of intracavitary cardiac tumors are included within the classic mimickers of systemic vasculitis, especially in those in which there are no cardiac manifestations. We present a case report of atrial myxoma in which the patient only presented systemic symptoms and in whom an initial diagnostic approach of systemic vasculitis was made. We also performed a literature search of the cases described. Patient and method. A case report of atrial myxoma with atypical presentation manifested as a systemic disease with no concomitant cardiac symptoms is described. The case report is discussed and 11 cases of atrial myxoma pseudovasculitis described in the literature are reviewed, emphasizing their similarities and differences. Discussion. Constitutional symptoms and cutaneous manifestations were the most common. Most of the cases showed partial response to glucococorticosteroid treatment, reinforcing the theory of the inflammatory role in its pathogenesis. Mean delayed time to diagnosis was 12.27 months. Conclusion. Atrial myxoma is a systemic vasculitis mimicker, this being difficult to diagnose in the absence of cardiac manifestations. This delay in diagnosis entails serious complications (AU)

Primary T-cell lymphoblastic lymphoma in the middle ear.

T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive lymphoma characterized by precursor T-cell malignancy and lymphadenopathy or mediastinal involvement. We present the case of an 11-year-old boy with a diagnosis of middle ear T-LBL, which manifested as a headache, hearing loss and peripheral facial paralysis. The child was given intensive chemotherapy and had a complete response. To our knowledge, this is the first case reported in the literature of T-LBL originating in the middle ear. This case aims to help clinicians to be vigilant about the possibility of primary lesions at atypical sites in some special diseases.

Transdermal drug targeting and functional imaging of tumor blood vessels in the mouse auricle.

Subcutaneously growing tumors are widely utilized to study tumor angiogenesis and the efficacy of antiangiogenic therapies in mice. To additionally assess functional and morphologic alterations of the vasculature in the periphery of a growing tumor, we exploited the easily accessible and hierarchically organized vasculature of the mouse auricle. By site-specific subcutaneous implantation of a defined preformed mouse B16/F0 melanoma aggregate, a solid tumor nodule developed within 14 d. Growth of the tumor nodule was accompanied by a 4-fold increase in its perfusion as well as a 2- to 4-fold elevated diameter and perfusion of peripheral blood vessels that had connected to the tumor capillary microvasculature. By transdermal application of the anticancer drug bortezomib, tumor growth was significantly diminished by about 50% without provoking side effects. Moreover, perfusion and tumor microvessel diameter as well as growth and perfusion of arterial or venous blood vessels supplying or draining the tumor microvasculature were decreased under these conditions by up to 80%. Collectively, we observed that the progressive tumor growth is accompanied by the enlargement of supplying and draining extratumoral blood vessels. This process was effectively suppressed by bortezomib, thereby restricting the perfusion capacity of both extra and intratumoral blood vessels.

Bevacizumab treatment for vestibular schwannoma in a patient with neurofibromatosis type 2: hearing improvement and tumor shrinkage.

PURPOSE: Neurofibromatosis type 2 (NF2) is a dominantly inherited genetic condition that clinically manifests through the appearance of multiple meningiomas, ependymomas and bilateral vestibular schwannomas (acoustic neuromas) which lead to progressive hearing loss. Neovascularization is necessary for tumor growth and is driven by tumor-produced angiogenic factors such as vascular endothelial growth factor (VEGF). Bevacizumab is a humanized monoclonal antibody that neutralizes the activity of VEGF. Recent data have shown that VEGF is produced by schwannoma tumor cells. Bevacizumab treatment in patients with NF2 who were considered poor candidates for surgery and radiation therapy was found to result in clinically meaningful hearing improvement and tumor volume reduction in previous studies. METHODS: We report the case of a 40-year-old woman with sudden right-sided hearing loss. Magnetic resonance imaging (MRI) revealed multiple meningiomas and neurinomas (C2 and L5 lesions) and a right-sided acoustic neurinoma, confirming the diagnosis of NF2. Bevacizumab was given as infusion every 2 weeks at a dose of 5.0 mg/kg body weight with MRI monitoring every 6 months. RESULTS: After 6 months from the start of therapy the patient reported progressive improvement of hearing response in audiometry, word recognition and face-to-face conversation. MRI evidenced reduction of the volume of the right vestibular schwannoma and the multiple meningiomas as well as attenuation of brain stem compression. CONCLUSIONS: At the time of writing the patient is continuing treatment with bevacizumab without adverse events. She has good functional status and quality of life.

Epidermal growth factor receptor as a novel molecular target for aggressive papillary tumors in the middle ear and temporal bone.

Adenomatous tumors in the middle ear and temporal bone are rare but highly morbid because they are difficult to detect prior to the development of audiovestibular dysfunction. Complete resection is often disfiguring and difficult because of location and the late stage at diagnosis, so identification of molecular targets and effective therapies is needed. Here, we describe a new mouse model of aggressive papillary ear tumor that was serendipitously discovered during the generation of a mouse model for mutant EGFR-driven lung cancer. Although these mice did not develop lung tumors, 43% developed head tilt and circling behavior. Magnetic resonance imaging (MRI) scans showed bilateral ear tumors located in the tympanic cavity. These tumors expressed mutant EGFR as well as active downstream targets such as Akt, mTOR and ERK1/2. EGFR-directed therapies were highly effective in eradicating the tumors and correcting the vestibular defects, suggesting these tumors are addicted to EGFR. EGFR activation was also observed in human ear neoplasms, which provides clinical relevance for this mouse model and rationale to test EGFR-targeted therapies in these rare neoplasms.

Induction Hedgehog pathway inhibition followed by combined-modality radiotherapy for basal cell carcinoma.

Basal cell carcinoma (BCC), the most common cancer in the U.S.A., is treated primarily with local excision. In some cases, lesion size, location or extent prevent complete resection. Locally advanced BCC responds to systemic therapy with the Hedgehog pathway inhibitor vismodegib, but withdrawal of treatment may result in disease relapse. Here we present a case of locally advanced auricular BCC treated with induction vismodegib and radiation, resulting in durable local control and an acceptable level of acute toxicity.