Endolymphatic sac tumor: single-institution series of seven cases with updated review of literature.

BACKGROUND: Endolymphatic sac tumour (ELST) is a rare low-grade locally aggressive neoplasm arising from the endolymphatic duct or sac. It presents mostly with vestibulo-cochlear symptoms either sporadically or as part of von Hippel-Lindau (VHL) syndrome. Micro-neurosurgical excision remains the cornerstone of therapy with the role of radiotherapy (RT) being controversial. This is a clinico-pathological analysis of consecutive ELST patients presenting to a single-institution in India. METHODS: Neuropathology database of a tertiary-care comprehensive cancer centre was searched electronically to identify consecutive patients with histopathological diagnosis of ELST registered at the institute over last one decade. Data regarding demographic profile, clinical presentation, histopathological features, treatment details and outcomes were retrieved from electronic medical records for this retrospective analysis. RESULTS: Electronic search identified seven unique patients with biopsy-proven ELST registered at the institute between 2009 and 2020. Median age of the study cohort was 39 years (range 24-65 years) with strong male predilection (5:2 ratio) and left-sided preponderance (71%). Most common presenting symptoms were hearing loss (86%) and earache (71%) on affected side followed by headache (43%). All patients underwent maximal safe resection at initial diagnosis and were followed-up closely with periodic surveillance imaging. Two patients underwent salvage RT using high-precision conformal techniques at recurrence/progression. CONCLUSION: ELST is a rare low-grade locally aggressive neoplasm that arises generally as part of VHL syndrome or sometimes sporadically. Gross total resection provides the best chance of cure with RT being reserved for unresectable disease, large residue, medical inoperability, or as salvage therapy for recurrent/progressive tumor.

Radiotherapy for a rare phosphaturic mesenchymal tumor in the middle ear presenting with oncogenic osteomalacia: A case report.

RATIONALE: Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm causing oncogenic osteomalacia. Surgery remains the definitive treatment for PMT, and radiotherapy is seldom employed. However, surgery for PMT involving the head and neck is often difficult due to the local invasion and complicated anatomy. We report the first case of PMT, which was successfully treated with the combination of radiotherapy and supplementation of activated vitamin D. PATIENT CONCERNS: A 55-year-old woman suffered from pain in the hip and bilateral femur. Serum phosphate and calcium decreased to abnormal levels. Serum alkaline phosphatase and fibroblast growth factor 23 increased to abnormal levels. The hearing loss of the right ear had continued and a middle ear tumor was revealed. DIAGNOSES: Subsequent biopsy provided the diagnosis of PMT that caused oncogenic osteomalacia. These clinical and pathological characteristics were consistent with and provided the final diagnosis of benign PMT. INTERVENTIONS: Surgery of the PMT was difficult and the patient underwent radiotherapy. The prescribed dose was 36 Gy in 10 fractions. Simultaneously, the patient started supplementation of 1,25-dihydroxyvitamin D3 (1-2 µg/day) and continued for 2 years. OUTCOMES: Near-complete resolution of the symptoms was achieved and abnormal laboratory values recovered. At 5 years of follow-up, the irradiated tumor showed no regrowth. Severe hearing loss of the right ear was not observed. LESSONS: Radiotherapy was effective for the PMT and could be an important treatment option for inoperable cases.

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.

Effects of ErbB2 signaling on the response of vestibular schwannoma cells to gamma-irradiation.

OBJECTIVE: For vestibular schwannomas (VSs) that require treatment, options are limited to microsurgery or irradiation (IR). Development of alternative therapies that augment or replace microsurgery or IR would benefit patients not suitable for current therapies. This study explored the ability of ErbB2 inhibitors to modulate the effects of IR on VS cells. STUDY DESIGN: Prospective study using primary cultures derived from human VSs. METHODS: Primary cultures of VS cells were derived from acutely resected tumors. Cultures received single escalating doses (15-40 Gy) of gamma-irradiation from a Cs gamma-irradiation source. Cell proliferation was determined by BrdU uptake and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Trastuzumab (Herceptin) and PD158780 were independently used to inhibit ErbB2 signaling while neuregulin-1beta (NRG-1) was used to activate ErbB2. RESULTS: IR induces VS cell cycle arrest and apoptosis in doses greater than 20 Gy, demonstrating that VS cells are relatively radioresistant. This radioresistance likely arises from their low proliferative capacity as a sublethal dose of IR (10 Gy) strongly induces deoxyribonucleic acid (DNA) damage evidenced by histone H2AX phosphorylation. Inhibition of ErbB2, which decreases VS cell proliferation, protects VS cells from radiation-induced apoptosis, while NRG-1, an ErbB2 ligand and VS cell mitogen, increases radiation-induced VS cell apoptosis. CONCLUSIONS: Compared with many neoplastic conditions, VS cells are relatively radioresistant. The radio-protective effect of ErbB2 inhibitors implies that the sensitivity of VS cells to IR depends on their proliferative capacity. These results hold important implications for current and future treatment strategies.

[The outcome of treatments for carcinoma of the external auditory canal]. / Résultats des traitements des tumeurs malignes du conduit auditif externe.

OBJECTIVE: A retrospective analysis of management and survival of patients treated for temporal bone carcinoma. PATIENTS AND METHODS: Thirty patients underwent treatment for carcinoma of the temporal bone. Twenty-five squamous cell carcinomas, 1 melanoma, 2 basocellular carcinomas and 2 adenoid cystic carcinomas were treated. Thirteen patients were treated before for the same disease. RESULTS: Staging revealed 12 T1 and T2, 6 T3 and 12 T4 tumours. The mean follow up was 5 years (2-276 months). The Kaplan Meier survival curves showed survival rates at 2 years of 82%, 67% and 32%, and at 5 years of 82%, 67% and 17%, respectively for the stages T1 or T2, T3 and T4. At the end of follow up at 9 years the survival rates were 66%, 66% and 17% for the stages T1 or T2, T3 and T4 respectively. Overall stages a complete remission was found in 65% and 23%, and deceased was 35% and 77%, respectively for the primary treatment group and the salvage surgery group. CONCLUSION: Long-term prognosis of the carcinoma of the external auditory canal mainly depends on the stage and primary treatment. Surgery (lateral temporal bone or subtotal temporal bone resection, both in combination with a neck dissection and a parotidectomy) and adjuvant radiotherapy is the treatment of choice for part of stage T1 and all T2 and T3 tumours. The improved survival (65%) of patients treated de novo compared with those treated with salvage surgery (23%) suggests that early referral and aggressive primary surgical treatment with postoperative radiotherapy offer the greatest chance of cure.

Bipolar radiofrequency induced thermotherapeutic volumetric reduction of VX2 metastases in an animal model.

BACKGROUND: Radiofrequency-induced thermotherapy has shown promising results in the palliative treatment of various tumor entities. The purpose of this study was to investigate the effectiveness of bipolar radiofrequency volumetric tissue reduction (VTR) on lymph node (LN) metastases in the VX2 SCC model. MATERIALS AND METHODS: Six male New Zealand white rabbits, with palpable metastatic disease within the parotid lymph nodes, were treated using the Celon-ProSurge probe, needle length 10 mm, diameter of 2.3 mm. The animals were sacrificed on the 4th, 8th, 11th, 14th, 18th and 22nd postoperative days respectively. RESULTS AND CONCLUSION: Bipolar radiofrequency VTR could prevent progression of local metastatic disease in one-third of the animals compared to the control group of untreated VX2 carcinoma rabbits. These results encourage further studies, directed at whether this treatment modality could play a role in the palliative therapy of metastatic LN. Future studies should concentrate on the refinement of the treatment parameters and optimization of the treatment duration.

Preservation of tap vestibular evoked myogenic potentials despite resection of the inferior vestibular nerve.

Sound and skull-tap induced vestibular evoked myogenic potentials (VEMP) were studied in a 43-year-old man following inferior vestibular neurectomy. Surgery was performed because of a small acoustic neuroma. Postoperative caloric testing suggested sparing of superior vestibular nerve function on the operated side. In response to sound stimulation there were no VEMP on the operated side, irrespective of whether sounds were presented by air- or bone-conduction. This suggests sound-induced VEMP to be critically dependent on inferior vestibular nerve function and this is in agreement with present knowledge. However, VEMP were obtained in response to forehead skull taps, i.e. positive-negative VEMP not only on the healthy side but also on the operated side. This suggests remnant vestibular function on the operated side of importance for forehead skull tap VEMP, because with complete unilateral vestibular loss there are no (positive-negative) VEMP on the lesioned side. Thus, forehead skull-tap VEMP depend, at least partly, on the superior vestibular nerve function.

Invasive fungal and bacterial infections of the temporal bone.

OBJECTIVES/HYPOTHESIS: Objectives were to highlight the importance of surgical therapy in treating invasive polymicrobial infections of the temporal bone, to discuss the importance of antifungal therapy, and to review the differential diagnosis of ear canal granulomatous disorders. STUDY DESIGN: Retrospective case review at a tertiary care medical center. METHODS: A retrospective chart review of all patients diagnosed with invasive polymicrobial temporal bone infections was performed. Four patients were identified. All patients required surgical therapy for definitive management. All patients were followed for at least 1 year or until death. RESULTS: Three of four patients had invasive fungi as pathogens. One patient had an occult squamous cell carcinoma. At the time of writing, one patient was free of disease, two were dead of disease, and one was alive with disease. CONCLUSION: Invasive polymicrobial temporal bone infections can occur in immunocompromised patients and can possibly harbor an occult malignancy. Surgical debridement may be necessary to arrive at a correct diagnosis. Modified radical mastoidectomy with parenteral antibiotic therapy and other adjunctive measures may be necessary for disease resolution.

Basal cell carcinoma of the earlobe after auricular acupuncture.

The genesis of familial and sporadic basal cell carcinomas involves activation of the Sonic hedgehog signal transduction pathway. Other known factors for the development of basal cell carcinoma are ultraviolet exposure, X-rays, race, age, gender and decreased DNA repair capacity. We here report the case of a right earlobe sporadic basal cell carcinoma in a 65-year-old woman. This case is unusual because of its earlobe localization and its association with multiple auricular acupuncture treatments. This observation suggests a connection between local traumas, which occur in the course of acupuncture treatment and ear piercing, and the genesis of basal cell carcinoma. The incidence of minor adverse events associated with acupuncture is high, but serious events are uncommon. Acupuncture is not known to date for promoting the development of tumors. This connection remains to be elucidated.

Auricular exostoses among the prehistoric population of different islands of the Canary archipelago.

It is generally believed that auricular exostoses are due to prolonged exposure to cold water, so their existence in ancient remains may inform us about economic activities in the past. This study was performed to analyze the prevalence of auricular exostoses among 150 pre-Hispanic individuals of different islands of the Canary archipelago. Individuals from Gran Canaria (6/26), Fuerteventura (1/15), and Tenerife (2/64), but not from El Hierro (0/45), showed auricular exostoses, thus supporting the hypothesis of a greater reliance on fishing and shellfishing in the former 3 islands.

[Extramedullary relapse in the external auditory canal in a patient with acute promyelocytic leukemia treated with all-trans retinoic acid and autologous peripheral blood stem cell transplantation].

A 41-year-old man was given a diagnosis with of acute promyelocytic leukemia (APL) in August 1994. A chromosome analysis showed 46, XY, t(15; 17) and 47, XY, idem, +8 at that time. Because initial induction chemotherapy (BHAC-DMP) has not been successful, the patient was given 45 mg/m2 of all-trans retinoic acid (ATRA) and achieved complete remission (CR) after 26 days on this regimen. Following intensified chemotherapy, he received an autologous peripheral blood stem cell transplant (PBSCT) with high-dose busulfan and cyclophosphamide in April 1995. Competitive RT-PCR for PML-RAR alpha mRNA did not find any of APL cells in the collected stem-cell fraction. Although the patient remained in CR without therapy, a myeloblastoma was found in his left external auditory canal in August 1996. Recurrence in bone marrow, moreover, was discovered the following month. A chromosome analysis of bone marrow cells showed 47, XY, t(15; 17), +8 at this time. Thus, the extramedullary relapse developed after autologous PBSCT. This case provides information linking ATRA to the development of extramedullary relapse in patients with APL.

Contralateral suppression of transiently evoked otoacoustic emissions and neuro-otology.

Transiently evoked otoacoustic emissions can be suppressed with simultaneous contralateral sound stimulation. This is considered to be effected via the efferent pathway from the superior olivary complex (SOC) to the contralateral cochlea. This study examined this effect in patients with extrinsic and intrinsic lesions of the brainstem which may affect the efferent pathway either within the vestibular nerve which carries the efferent bundle to the cochlea or within the brainstem at the level of the SOC. Suppression is reduced or absent in these patients and the site and size of the lesion determines whether the suppression is affected unilaterally or bilaterally. Lesions affecting the auditory afferent pathway without significant alteration in hearing appear to affect the efferent pathway too.

Squamous cell carcinoma of the pinna: a 6-year study.

Over a 6-year period, 54 sequential lesions of squamous cell carcinoma of the pinna were studied in 44 patients with regard to the side, clinical features and their duration, TNM clinicopathological classification, treatment and follow-up. Treatment delay, types of surgical procedures, anaesthesia and postoperative complications were all analysed. The overall incidence of residual and recurrent cancer was 25.92%. The regional lymph node recurrence was 9.26%, though only 5.56% had clinically persistent cancer. Six patients subsequently died; two of these deaths were due to the cancer.

[Simultaneous occurrence of an acoustic neurinoma and a glomus tympanicum tumor in a patient. An unusual constellation and problematic surgical task]. / Gleichzeitiges Vorkommen eines Akustikusneurinoms und eines Glomus-tympanicum-Tumors bei einem Patienten. Eine ungewöhnliche Konstellation und problematische chirurgische Aufgabe.

We present the case of a 65-year-old woman who was found to have a concurrent ipsilateral acoustic neuroma and glomus tympanicum tumor. Both tumors were removed in one operation. The acoustic neuroma was removed via the translabyrinthine approach because of preoperative deafness while the glomus tumor was found only during the operation to remove the neuroma. A preoperative biopsy was not associated with significant bleeding while microscopic examination of the biopsy tissue indicated only chronic infection.

Effects of aminothiols in 2-acetylaminofluorene-treated rats. I. Damage and repair of liver DNA, hyperplastic foci, and Zymbal gland tumors.

One hundred and seventy-nine male Wistar rats were divided into 6 groups and fed with a standard diet supplemented with 0.05% 2-acetylaminofluorene (2AAF) and/or 0.1% glutathione (GSH) or N-acetyl-L-cysteine (NAC). Each treatment cycle lasted for 3 weeks, followed by 1 week of standard meal. After 4 cycles, survival was 100% in the 3 control groups, and 86.0, 100 and 91.7%, in the groups receiving 2AAF, 2AAF plus GSH, and 2AAF plus NAC, respectively. After an additional 4-8 weeks, all the 5 surviving rats fed with 2AAF exhibited deforming ear tumors, which on histological examination were classified as sebaceous squamocellular carcinomas of Zymbal glands. No such tumors were detectable in control groups, nor in the 16 surviving rats fed with 2AAF plus GSH or NAC. In the liver, 2AAF produced significant DNA damage at the 3rd week of each cycle, which was partially repaired during the week of standard meal feeding. Moreover, 2AAF determined the appearance of gamma-glutamyl transpeptidase-positive foci, which tended to increase with time both in number and in size. GSH and NAC exerted similar protective effects on these phenomena, but only at early stages of the experimental model used.