Squamous cell carcinoma of the ear arising in patients after radiotherapy for nasopharyngeal carcinoma.

Radiation-induced malignancies are a rare but serious complication arising in patients receiving radiotherapy for nasopharyngeal carcinoma (NPC). To characterize patients who develop post-irradiation squamous cell carcinoma (PISCC) of the ear after radiotherapy for NPC and to compare their outcomes with patients who have de novo squamous cell carcinoma (SCC) of the ear. Clinical and pathological characteristics and their outcomes were analysed and compared between post-irradiation and de novo SCC cases. From 2002 to 2011, 25 patients were treated at our institution for SCC of the ear, of which 8 (32%) occurred after prior irradiation. There were no significant differences between the two groups with regards to age, gender, race, smoking status, tumour size, grade, stage and differentiation. Patients in the PISCC group appeared to have inferior overall survival (median survival 71.2 vs. 85.6 months; p = 0.292) and disease-specific survival (mean 59.6 vs. 71.5 months; p = 0.441). PISSC of the ear in long-standing survivors of NPC has a poor prognosis despite advances in medical care. Surgical resection with clear margins seems to offer the best outcomes.

von Hippel-Lindau disease: deafness due to a non-MRI-visible endolymphatic sac tumor despite targeted screening.

OBJECTIVE: Endolymphatic sac tumours (ELSTs) of the inner ear occur in 16% of patients with the hereditary tumor syndrome von Hippel-Lindau disease (vHL). ELSTs of all sizes can cause irreversible hearing loss which can, however, be prevented through early diagnosis and treatment. We aim to emphasize the challenges of prophylactic ELST screening and to explore the role of audiometry in pre-symptomatic ELST screening. DESIGN: For a period of 17 years our patient was screened for ELSTs with inner-ear MRI (magnetic resonance imaging), audiometry, and clinical interviews. STUDY SAMPLE: A male vHL patient who became deaf in one ear due to a radiologically undetectable ELST. RESULTS: Despite annual MRIs, the ELST was not visible until four months after onset of deafness when it appeared as a 1.4 × 1.4 mm tumor mass. Although his hearing was objectively within normal limits for the first 14 years, a distinct pattern of low-frequency hearing loss could retrospectively be seen at all audiometries. CONCLUSIONS: Audiometry is a candidate screening tool for detection of non-symptomatic pre-MRI-visible ELSTs, and we have initiated an international collaborative study to further determine its application. At present, we suggest an ELST screening protocol of yearly audiological assessment and inner ear MRI.

[Multidisciplinary approach to the endolymphatic sac tumour]. / Abordaje multidisciplinar al tumor de saco endolinfático.

INTRODUCTION: Papilar adenocarcinoma of endolymphatic sac is related with Von Hippel Lindau disease at 15% of cases, has a slow growing with a high local aggressiveness, and doesn't metastasize. It causes symptoms of Meniere's syndrome due to the compression that produces at endolymphatic duct. When it presents with hearing loss is usually sudden and irreversible manner. The diagnostic is made with image tests and analysis of its structure with immunohistochemical tests. The elective treatment is surgical remove, and its main complication the perioperative bleeding it can be avoided with preoperative embolization or stereotactic radiation. CASE REPORT: A case of endolymphatic sac tumour is presented, in a 17-years-old male with unilateral deafness and crisis of rotate vertigo, with family history of Von Hippel-Lindau disease. Perceptive deafness and right vestibular arreflexia are detected at technical exploration. In a petrous bone computer tomography appears a mass at vestibular aqueduct. We performed a petrosectomy with presigmoidal approach and saving of inner ear. Pathological analysis revealed an endolymphatic sac tumour. DISCUSSION: In patients with a family history of Von Hippel Lindau disease and clinical symptoms of vertigo and normal hearing or with slight hearing loss we should suspect the presence of endolymphatic sac tumor. The clinical presentation of hearing loss can be sudden and irreversible even with negative or inconclusive images. Therefore, a quick action is important for the preservation of this function.

Effectiveness of chemoradiotherapy for radiation-induced bilateral external auditory canal cancer: A case report and literature review.

BACKGROUND: Radiation-induced bilateral external auditory canal cancer is an extremely rare disease that has yet to be fully characterized in the clinical literature. METHODS: Herein, we present a case study of a 75-year-old man with radiation-induced bilateral external auditory canal cancer. The patient's medical history included left maxillary cancer that had been treated with chemoradiation 19 years earlier and local recurrence with total maxillectomy 10 years earlier. Intracavitary radiation was delivered to the site of postoperative recurrence 8 years before the current presentation. The patient declined radical surgery for the external auditory canal cancer at this time, and a customized combined modality regimen was thus administered. RESULTS: There was no recurrence of cancer for 22 months, to date, after completing chemoradiotherapy. CONCLUSIONS: Our finding that radiotherapy can be successfully used for radiation-induced cancer indicates that chemoradiotherapy may be a useful strategy for treating this type of malignancy.

CAIX and pax-8 Commonly Immunoreactive in Endolymphatic Sac Tumors: A Clinicopathologic Study of 26 Cases with Differential Considerations for Metastatic Renal Cell Carcinoma in von Hippel-Lindau Patients.

Endolymphatic sac tumors (ELSTs) are rare, slowly growing temporal bone neoplasms which show a high association with von Hippel-Lindau (VHL) syndrome. The immunohistochemistry evaluation of these papillary-cystic neoplasms frequently raises the differential diagnosis with renal cell carcinoma, among other metastatic neoplasms, whether in VHL patients or not. A cohort of 26 patients with ELSTs were evaluated for histologic features, immunohistochemistry findings, and association with VHL. Standard immunohistochemistry evaluation was performed. Sixteen females and 10 males ranging in age from 10 to 69 years (mean 44; VHL mean: 32) at initial presentation, comprised the cohort of patients. Most (86%) experienced hearing changes or inner ear symptoms (vertigo, dizziness), with an average duration of symptoms for 39 months (range 2-240 months). The tumors were an average of 2.9 cm (range 0.4-8 cm), with 14 left, 11 right sided and one bilateral tumor. Nine patients had documented VHL, with 3 patients having a concurrent or subsequent clear cell renal cell carcinoma. Patients were followed an average of 6.2 years (available in 24 patients): 19 alive without disease, 7.5 years; 2 dead without disease, 1.2 years; and 3 alive with disease, 3.1 years. The neoplastic cells show the following immunohistochemistry findings: AE1/AE3, EMA, CK7, CAIX, GLUT1, VEGF: 100% of cases tested were positive; pax-8: 85% of cases positive; CD10 and RCC: 0% of cases reactive. Based on this cohort of 26 patients with ELST, 9 of whom had VHL, the strong pax-8 and CAIX should be used in conjunction with negative CD10 and RCC to help exclude a metastatic renal cell carcinoma. As CAIX is an enzyme overexpressed in hypoxia and hypoxia inducible factor is what VHL protein regulates, this is an expected, although previously unreported finding. Whether part of VHL or not, VHL mutations may be a somatic rather than germline finding in the tumors, a possible further explanation for the CAIX reaction.

Bilateral radiation-induced squamous cell carcinomas of the external auditory canal 30 years after radiotherapy for a pituitary adenoma: a case report.

INTRODUCTION: The most important long-term effect of radiotherapy is induction of secondary cancers. A rare radiation-induced tumor is a squamous cell carcinoma of the external auditory canal. Case reports have been described in Asian patients after radiotherapy for nasopharyngeal cancer. CASE DESCRIPTION: We describe an unusual case report of a 53-year-old Caucasian man who developed squamous cell carcinomas of the right and left external auditory canal, respectively 29 and 30 years after radiotherapy for a pituitary adenoma. CONCLUSION: In young patients with benign tumors, we should always evaluate whether the benefits of radiotherapy outweigh the risks and side effects. After radiotherapy, screening programs should be developed since early detection improves salvage treatment of these secondary and often morbid tumors.

The vestibular aqueduct: site of origin of endolymphatic sac tumors.

OBJECT: Although endolymphatic sac tumors (ELSTs) frequently destroy the posterior petrous bone and cause hearing loss, the anatomical origin of these neoplasms is unknown. To determine the precise topographic origin of ELSTs, the authors analyzed the imaging, operative, and pathological findings in patients with von Hippel-Lindau disease (VHL) and ELSTs. METHODS: Consecutive VHL patients with small (

Traumatic neuroma of the tympanic (Jacobson's) nerve as a possible cause of otalgia.

OBJECTIVE: To show that traumatic neuroma of the tympanic (Jacobson's) nerve may be a cause of recurrent intractable otalgia in patients following radical mastoidectomies. STUDY DESIGN: Histologic evaluation of four temporal bones from three patients with a history of recurrent otalgia following radical mastoidectomy. SUBJECTS AND METHODS: The medical records of three patients with multiple middle ear surgeries in four ears because of recurrent otalgia were reviewed. Histopathologic studies of the four temporal bones were performed. RESULTS: All four of the temporal bones that underwent multiple surgeries were found to have traumatic neuromas of the tympanic (Jacobson's) nerve. CONCLUSION: Recurrent otalgia in patients after radical middle ear surgery may be caused by a traumatic neuroma of the tympanic (Jacobson's) nerve.

Neurologic manifestations of von Hippel-Lindau disease.

von Hippel-Lindau disease (VHL) is an autosomal-dominant neoplasia syndrome that is the result of a germline mutation of the VHL tumor suppressor gene on the short arm of chromosome 3. Patients with VHL are predisposed to develop lesions of the central nervous system and viscera. Central nervous system lesions include hemangioblastomas (the most common tumor in VHL) and endolymphatic sac tumors (ELSTs). Visceral manifestations include renal carcinomas and cysts, pancreatic neuroendocrine tumors and cysts, pheochromocytomas, and cystadenomas of the reproductive adnexal organs. Despite their benign pathology, hemangioblastomas and ELSTs are a frequent cause of morbidity and mortality in patients with VHL. Recent molecular biologic investigations into these VHL-associated central nervous system lesions provide new insight into their origin and development. Emerging data from serial imaging and clinical surveillance protocols provide insight into the natural history of these lesions. Because of the dissimilar pathobiology and clinical course between hemangioblastomas and ELSTs, the optimal management strategies for these neurologic manifestations of VHL are very different.

Development of solitary plasmacytoma in the internal auditory canal and inner ear after allogeneic hematopoietic stem cell transplantation for plasma cell leukemia.

Here we report the first case of the development of intracranial solitary plasmacytoma in the inner ear after allogeneic stem cell transplantation (allo-SCT) in a 39-year-old Japanese female with primary plasma cell leukemia (PCL). A point to note is that this is not a case on multiple myeloma but on PCL. She was successfully treated with local irradiation and survived more than 6 years from the time of diagnosis and transplantation. This case elucidates the biology of PCL and stresses the need for an individual approach to the clinical management of patients with plasma cell neoplasm undergoing allo-SCT.

Enhanced lymphoma incidence in BALB/c mice after ultraviolet light treatment.

Following UV irradiation of BALB/c mice three times a week for 9 months, lymphatic leukemia or reticulosarcoma developed in 44 (12%) of 378 mice whose backs were shaved and whose ears were intact. Only 11 (5%) of 224 UV-irradiated mice whose backs were shaved and whose ears were removed developed lymphomas. Among 311 unirradiated mice whose backs were shaved, 9 lymphomas (3%) occurred. The diagnosis of leukemia or reticulosarcoma was confirmed by microscopy and transplantation. Among irradiated mice, ear tumors developed in 24% of the mice with intact ear, whereas skin tumors developed on the shaved backs in 4% of the mice whose ears were removed and also in 4% of the mice with intact ears.

Tumorigenesis in athymic nude mouse skin by chemical carcinogens and ultraviolet light.

A variety of established skin tumorigenesis protocols were tested for efficacy on athymic nu/nu mice (BALB/c background) and compared on euthymic nu/+ counterparts. Chemical carcinogens and UV light were applied to the ears of 10 mice of each sex and genotype for each group. Treatments were: 0.5 mg 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6] to each ear; 0.125 mg DMBA to each ear, followed by 0.1 microgram 12-O-tetradecanoylphorbol-13-acetate [(TPA) CAS: 16561-29-8] twice weekly for 56 weeks; 0.2 mg N-nitroso-N-methylurea [(NMU) CAS: 684-93-5; 1% in acetone, 20 microliter] to each ear; 0.1 mg NMU to each ear weekly for 30 weeks; 0.2 mg NMU to each ear, followed by TPA twice weekly for 56 weeks; two ip doses of N-nitroso-N-ethylurea [(NEU) CAS: 759-73-9; 25 mg/kg each], followed by TPA twice weekly topically for 56 weeks; and exposure to sunlamps (250- to 400-nm emission) two or three times per week for 20 weeks, for a total dose of 3.7 X 10(5) J/m2. The chemical treatments caused mainly squamous papillomas and carcinomas, sebaceous adenomas and adenocarcinomas, and basal cell tumors, which appeared both on the skin of the ears and elsewhere. UV light caused squamous tumors, basal cell tumors, and sarcomas. Ear skin of the nu/nu mice developed significantly more squamous tumors than those of nu/+ mice after DMBA-TPA, NMU-TPA, NEU-TPA, repeated NMU, or UV light. Similar results were obtained for the skin of the heads and bodies. Even a single dose of NMU caused a few tumors on the nude, but not the euthymic, mice. A single dose of DMBA caused primarily sebaceous adenomas, distributed at random over the entire bodies. These results show that, contrary to previous reports, nude mice are sensitive to skin tumorigenesis, more so than euthymic nu/+ mice similarly exposed to diverse types of carcinogen and treatment protocols.

Inflammatory, proliferative, and neoplastic lesions at the site of metallic identification ear tags in Wistar [Crl:(WI)BR] rats.

During a 2-yr study of carcinogenesis by CdCl2 in male Wistar [Crl:(WI)BR] rats, weekly clinical observations during the last 6 mo of the study revealed many cases of persistent tumor-like masses at the site of the metal identification tags in the ears of the animals. A total of 14 tumors (mostly compound osteosarcomas) was diagnosed in 168 rats. Histologically, almost 90% of the rats in this study (henceforth referred to as Study I) showed some significant lesion at the tag site including various degrees of chronic inflammation, chondrous hyperplasia, and osseous metaplasia of the pinnal cartilage. In marked contrast, only two tumors were detected in 193 animals in a second study (Study II) in the same strain of rats, and only 56% of the rats had lesions at the tag site. A high incidence (greater than 25%) of clinically severe inflammation at the tag site was seen early in Study I and persisted during the first 6 mo of the study, while the incidence of such reactions in Study II was never more than 1%. Elemental analysis of the tags provided no explanation for the differences between the two studies, as tags used in both studies were of the same composition, predominantly nickel and copper. Metallic internal prostheses have induced local malignancies in humans and animals, and the present observations provide further evidence of the hazard posed by such devices at the site of prolonged contact with tissues. These findings suggest that a persistent tissue reaction may be an important factor in tumor development.

CT and MRI findings of radiation-induced external auditory canal carcinoma in patients with nasopharyngeal carcinoma after radiotherapy.

OBJECTIVE: To summarize the radiological and clinical features of radiation-induced external auditory canal carcinomas (RIEACCs) in patients with nasopharyngeal carcinomas (NPCs) after radiation therapy. METHODS: CT, MRI and clinical features in 16 patients with histologically proven RIEACCs were retrospectively reviewed. There were 2 females and 14 males, with a median age of 52.5 years at the time of diagnosis of RIEACC. Imaging parameters including lesion extent, size, margin, shape, bone destruction, adjacent structure invasion, density/signal intensity, and pattern and degree of enhancement were assessed. Clinical features including clinical staging, histological type, treatment and radiation dose (RD) of primary NPC as well as the histological type, staging of radiation-induced tumour and the latent period between NPC and RIT were recorded. RESULTS: All patients had a single RIEACC. The lesions had a size of 3.5 ± 1.4 cm and were localized (n = 7) or extensive (n = 9). Most of the lesions were partially or ill defined with an irregular shape and had an intermediate density/signal pattern and moderate homogeneous enhancement. The latent period of RIEACCs ranged from 10 to 20 years in nine patients with a RD of 68-70 Gy; from 2 to 10 years in five patients with a RD of 68-74 Gy; and more than 20 years in two patients with a RD of 70 or 72 Gy. CONCLUSION: An external auditory canal (EAC) mass with homogeneous, intermediate CT density or signal intensity in patients with NPC after radiotherapy is highly suggestive of RIEACC, which should be included in the routine surveillance for patients with NPC after radiotherapy. ADVANCES IN KNOWLEDGE: RIEACCs could occur as short as 2 years after radiotherapy in patients with NPC and have distinct features from otitis media and sarcomas. This EAC malignancy should be included in routine surveillance for patients with NPC after radiotherapy.

Black light induction of skin tumors in mice.

Albino inbred mice (A/J strain exposed to 40-w black light fluorescent lamps (BLB) for 12 hr a day for up to a year developed inflammatory and hyperplastic responses on hairless ear and tail skin, but not on back skin covered by hair. After 1 year of such exposure, many individuals developed papillomas, carcinomas, and sarcomas on their ears and tails. It may be concluded that black light is a skin carcinogen for A/J mice.