Electrochemotherapy for the palliative management of non-skin-origin head and neck cancer: case series and UK national survey.

OBJECTIVES: Electrochemotherapy uses electric fields to facilitate the influx of chemotherapy into cancer cells, producing a targeted effect. For head and neck cancer, it is mainly used for palliation of non-skin-origin metastases. It is used infrequently in the UK. This paper presents our experience and a UK survey to identify its frequency of use. METHODS: Between 2016 and 2019, a prospective database was created and reviewed. Only patients with non-skin-origin metastatic head and neck cancer, with no other palliative options, were included. Survival length, complications and symptomatic benefit were assessed. The survey was conducted via e-mail. RESULTS: Five patients were included: three with squamous cell carcinoma, one with esthesioneuroblastoma and one with hepatocellular carcinoma. Survival ranged from 1 month to over 20 months. Minor complications were seen. Only 15 out of 69 UK head and neck multidisciplinary teams offer electrochemotherapy. CONCLUSION: Electrochemotherapy is a well-tolerated adjunct to standard palliation of metastatic head and neck cancer, and is offered by a limited number of UK multidisciplinary teams.

Metastatic olfactory neuroblastoma: A small round blue cell puzzle on fine-needle aspiration cytology.

Small round blue cell tumors (SRBCTs) are a heterogeneous group of malignant neoplasms that can be challenging to distinguish on fine-needle aspiration (FNA) cytology. Ancillary tests as well as clinico-radiological correlation are often required to make an accurate diagnosis. FNA is a low-cost, low-infrastructure test, making it a coveted diagnostic tool, especially in low-resource settings. Olfactory neuroblastoma (ONB) is a rare SRBCT encountered in both pediatric and adult patients. Awareness of the cytomorphologic and immunocytochemical features of ONB is important in the workup of a SRBCT. This case report describes the primary diagnosis of metastatic ONB on FNA cytology.

Late Intramedullary Spinal Metastases from Esthesioneuroblastoma: Case Report and Prognostic Implications.

BACKGROUND: Esthesioneuroblastoma (ENB) is an uncommon neuroectodermal tumor that originates from the olfactory mucosa and often recurs locally. Distant metastases of ENB have been described, but there are few reports of intramedullary metastases to the spinal cord. CASE DESCRIPTION: Here we report a case of a patient presenting with a progressive paraparesis and magnetic resonance imaging findings of multiple drop metastases to thoracic and lumbar regions of the spinal cord, 17 years after diagnosis and treatment for an intracranial ENB with subsequent neck nodal metastases. The dorsal symptomatic lesion was treated with resection, radiotherapy, and adjuvant chemotherapy. The implications of spinal metastases for the clinical prognosis of this disease are discussed, with a review of the few reported cases of spinal ENB metastases in the literature. CONCLUSIONS: Through the presentation of this case we hope to further contribute to a better understanding of this rare disease's prognosis.

Occult olfactory neuroblastoma presenting with multiple bone metastases: a case report.

RATIONABLE: Olfactory neuroblastoma (ONB) is a rare malignant tumor of the nasal cavity, the primary local symptoms are usually inconspicuous. Patients are often admitted to various specialties based on different primary symptoms, which may result in delayed diagnosis and even a misdiagnosis. PATIENT CONCERNS: Here we report a case of ONB that presented initially as multiple ostealgia without any local symptoms of the tumor and primarily misdiagnosed as multiple myeloma. The patient was a 47-year-old female with bone pain at multiple sites. The initial diagnosis was considered as multiple myeloma. However, the morphologic examination of bone marrow suggested that the tumor cells originated from the nervous tissues. After the positron emission computed tomography scan, the primary lesion in the nasal cavity was located, and a biopsy was performed. DIAGNOSIS: The final diagnosis of ONB was confirmed by histopathological tests. INTERVENTIONS: The patient was treated with metronomic chemotherapy. OUTCOMES: The symptoms of bone pain were significantly relieved 3 months later. The emission computed tomography scan of the whole body bones and the magnetic resonance imaging of the head showed that the tumor size did not change significantly and proved a progression-free of the disease. LESSONS: It is a reasonable strategy to identify the original latent tumor by a prompt positron emission computed tomography scan when the primary diagnosis indicates a metastatic disease, especially for the occult malignancies like ONB.

Secondary extradural spinal manifestation of esthesioneuroblastoma.

Secondary spinal manifestations of esthesioneuroblastoma are rare. A 67-year-old woman was presented with an extradural spinal manifestation at the vertebra Th7 within 8 weeks after resection of an esthesioneuroblastoma. Subtotal removal of the epidural tumour was achieved combined with dorsal transpedicular stabilization. Early screening for distant metastases may be considered in patients with esthesioneuroblastoma.

A Population-Based Analysis of Nodal Metastases in Esthesioneuroblastomas of the Sinonasal Tract.

OBJECTIVE: Esthesioneuroblastoma is an uncommon malignancy of the sinonasal tract arising from the olfactory epithelium. Surgical management of the primary site, often via an endoscopic approach, with or without adjuvant radiation, is often curative. There is growing but ultimately limited data regarding management of the neck and the risk of nodal metastases. In this study, we examine the incidence and patterns of esthesioneuroblastoma-related cervical nodal metastases using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: The SEER registry was queried for all patients with esthesioneuroblastomas diagnosed between 1973 and 2012. Patient data was then analyzed with respect to age, sex, race, modified Kadish stage, grade, survival functions, and nodal disease including specific nodal basins. RESULTS: Three hundred and eighty-one cases of esthesioneuroblastoma with information on nodal metastases were identified. The overall cervical nodal metastasis rate was 8.7%. Level II metastases were most common (6.6%). A total of 4.5% of cases presented with multiple positive nodal basins. Male sex (P = 0.009) and higher tumor grade (P = 0.009) correlated with the presence of level II metastases. There was no association of primary tumor site to the presence of nodal metastases (P > 0.05). The presence of nodal disease significantly predicted poorer overall (P = 0.001) and disease-specific survival (P = 0.017). CONCLUSION: The incidence of nodal metastases in esthesioneuroblastoma at diagnosis is rare, and elective management of the neck remains controversial. Primary tumor site does not appear to predict metastases at specific nodal basins. Higher tumor grade may be a harbinger of eventual nodal metastases. LEVEL OF EVIDENCE: NA Laryngoscope, 129:1025-1029, 2019.

Esthesioneuroblastoma with widespread distant metastasis: Case report and literature review.

Esthesioneuroblastoma (ENB) is an uncommon sinonasal tract tumor, and it is even more uncommon among all neoplasms. Literature regarding the incidence and spread of the disease is limited. The prognosis of metastatic disease is poor. In this report, we present a case of recurrent ENB in a young woman involving metastasis to the neck, lungs, and ovary. Metastasis to the cervical lymph nodes is relatively common, but metastasis to the lungs is rare. Furthermore, to our knowledge, no cases of ovarian metastases of ENB have been reported. This case highlights the potential for widespread metastatic disease, suggesting the need for more frequent and thorough surveillance of patients diagnosed with recurrences of this tumor.

Comprehensive molecular profiling of advanced/metastatic olfactory neuroblastomas.

Olfactory neuroblastoma (ONB) is a rare, locally aggressive, malignant neoplasm originating in the olfactory epithelium in the nasal vault. The recurrence rate of ONB remains high and there are no specific treatment guidelines for recurrent/metastatic ONBs. This study retrospectively evaluated 23 ONB samples profiled at Caris Life Sciences (Phoenix, Arizona) using DNA sequencing (Sanger/NGS [Illumina], n = 15) and gene fusions (Archer FusionPlex, n = 6), whole genome RNA microarray (HumanHT-12 v4 beadChip, Illumina, n = 4), gene copy number assays (chromogenic and fluorescent in situ hybridization), and immunohistochemistry. Mutations were detected in 63% ONBs including TP53, CTNNB1, EGFR, APC, cKIT, cMET, PDGFRA, CDH1, FH, and SMAD4 genes. Twenty-one genes were over-expressed and 19 genes under-expressed by microarray assay. Some of the upregulated genes included CD24, SCG2, and IGFBP-2. None of the cases harbored copy number variations of EGFR, HER2 and cMET genes, and no gene fusions were identified. Multiple protein biomarkers of potential response or resistance to classic chemotherapy drugs were identified, such as low ERCC1 [cisplatin sensitivity in 10/12], high TOPO1 [irinotecan sensitivity in 12/19], high TUBB3 [vincristine resistance in 13/14], and high MRP1 [multidrug resistance in 6/6 cases]. None of the cases (0/10) were positive for PD-L1 in tumor cells. Overexpression of pNTRK was observed in 67% (4/6) of the cases without underlying genetic alterations. Molecular alterations detected in our study (e.g., Wnt and cKIT/PDGFRA pathways) are potentially treatable using novel therapeutic approaches. Identified protein biomarkers of response or resistance to classic chemotherapy could be useful in optimizing existing chemotherapy treatment(s) in ONBs.

Volumetric analysis of olfactory neuroblastoma skull base laterality and implications on neck disease.

OBJECTIVE: To determine if the laterality of primary tumors in patients with olfactory neuroblastoma (ONB) influenced the pattern and development of neck disease. METHODS: Using a retrospective cohort study design from 1994 to 2015, the primary tumors of patients who either presented with or developed neck disease were volumetrically analyzed using iPlan software (version 3.0.0, BrainLAB, Feldkirchen, Germany) by two independent observers. Agreement of volume-derived sidedness was assessed with a kappa statistic, whereas agreement in volume-derived degree of tumor laterality was evaluated with an intraclass correlation coefficient. A one-sample t test was used to assess the difference in dominant percentage between the two observers. RESULTS: Sixty-one patients with histological diagnosis and treatment of ONB at our institution were identified. Twenty-four patients exhibited neck involvement, 13 of whom could be volumetrically analyzed. Tumors that were greater than 75% eccentric to one side all exhibited contralateral disease, whereas the majority of unilateral neck disease was associated with relatively midline masses. Within the entire cohort, ipsilateral level 2 lymph nodes displayed the highest involvement (83%, 20 of 24), followed by ipsilateral level 1 (54%, 13 of 24), contralateral level 2 (46%, 11 of 24), contralateral level 1 (21%, 5 of 24), and ipsilateral level 3 (21%, 5 of 24). CONCLUSION: Ipsilateral neck involvement frequently was observed; however, the degree of ONB primary site laterality did not appear to have implications on the development of contralateral neck disease. Therefore, when considering elective therapy to the neck, ONB laterality should not be used to justify unilateral neck treatment. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:864-870, 2018.

Aggressive esthesioneuroblastoma with divergent differentiation: A taxonomic dilemma.

The authors describe an esthesioneuroblastoma (olfactory neuroblastoma) that occurred within the nasal cavity and brain in a 31-year-old man. Following excision, the tumor recurred in the left orbit and in mediastinal lymph nodes. Treatment included orbital excision and systemic chemotherapy. Histopathology showed a high-grade neuroepithelial tumor with positive immunohistochemical markers for neuroendocrine and epithelial components, an unusual combination raising issues concerning taxonomy.

Possible esthesioneuroblastoma metastasis to paranasal sinuses: Clinical report and literature review.

BACKGROUND: Local recurrence, and regional and distant metastases, respectively, develop in 30% and 15% of patients with esthesioneuroblastoma (ENB). METHODS: This case report includes 3 patients with unusual recurrences of ENB in the sinonasal tract. RESULTS: Patient 1 developed ENB in the bilateral maxillary sinuses after unilateral endoscopic resection of a left ENB followed by postoperative proton radiotherapy. Patient 2 developed ENB at the left optic-carotid recess 7 years after a craniofacial resection and postoperative radiotherapy. Patient 3 developed ENB over the left zygomatic process of the maxilla 4 years after a cranioendoscopic resection and postoperative radiation therapy for ENB of the ethmoid sinuses with intracranial extension. The possibility of venous tumor emboli must be considered as a likely etiology. However, alternative explanations include the development of a second primary or potential transformation because of tumor signaling. CONCLUSION: We present 3 cases that may represent metastasis of ENB within the sinonasal tract.

Esthesioneuroblastoma With Poor Outcome Despite Extensive Treatment.

Esthesioneuroblastoma is a rare malignant tumor of neuroectodermal origin. It usually presents with nonspecific symptoms, such as nasal obstruction, epistaxis, and pain, but has an aggressive course if the treatment is delayed. The authors report a case of esthesioneuroblastoma in a 47-year-old woman, treated with extensive surgical resection, radiotherapy, and chemotherapy. Despite intensive treatment, the patient developed a local recurrence with systemic metastasis and succumbed 4 months later.

Olfactory neuroblastoma: the long-term outcome and late toxicity of multimodal therapy including radiotherapy based on treatment planning using computed tomography.

BACKGROUND: Olfactory neuroblastoma (ONB) is a rare tumor originating from olfactory epithelium. Here we retrospectively analyzed the long-term treatment outcomes and toxicity of radiotherapy for ONB patients for whom computed tomography (CT) and three-dimensional treatment planning was conducted to reappraise the role of radiotherapy in the light of recent advanced technology and chemotherapy. METHODS: Seventeen patients with ONB treated between July 1992 and June 2013 were included. Three patients were Kadish stage B and 14 were stage C. All patients were treated with radiotherapy with or without surgery or chemotherapy. The radiation dose was distributed from 50 Gy to 66 Gy except for one patient who received 40 Gy preoperatively. RESULTS: The median follow-up time was 95 months (range 8-173 months). The 5-year overall survival (OS) and relapse-free survival (RFS) rates were estimated at 88% and 74%, respectively. Five patients with stage C disease had recurrence with the median time to recurrence of 59 months (range 7-115 months). Late adverse events equal to or above Grade 2 in CTCAE v4.03 were observed in three patients. CONCLUSION: Multimodal therapy including radiotherapy with precise treatment planning based on CT simulation achieved an excellent local control rate with acceptable toxicity and reasonable overall survival for patients with ONB.

Proton therapy for pediatric and adolescent esthesioneuroblastoma.

BACKGROUND: Esthesioneuroblastoma (EN) of the paranasal sinus comprises less than 3% of tumors of in pediatric and adolescent patients [1]. The collective adult literature indicates a critical role for radiotherapy in attaining cure [2], yet pediatric outcome data is limited. Radiation in pediatric patients with EN can cause significant morbidity due to the proximity of critical structures. Proton radiotherapy offers a potential dosimetric benefit that may improve long-term survival and toxicity outcomes in the pediatric population [3]. METHODS: We retrospectively identified eight patients treated for EN with proton radiotherapy from 2000-2013. Times to event clinical endpoints are summarized using the Kaplan-Meier methods and are from the date of radiotherapy completion. Toxicities are reviewed and graded according to CTCAE v. 4.0. RESULTS: Median follow up was 4.6 years for survivors (range 0.8-9.4 years). The 4 year overall survival was 87.5%. Four of eight patients (one elective) had comprehensive neck radiotherapy. No local or regional failures were observed. Two patients failed distantly with diffuse leptomeningeal disease and intraparenchymal brain metastases, at 0.6 and 1.3 months respectively. Four patients developed radiation related late toxicities including endocrine dysfunction, two cases of grade 2 retinopathy and one case of grade 3 optic neuropathy. CONCLUSIONS: In a limited cohort, proton radiotherapy appears to provide excellent locoregional disease control even in those patients with locally advanced disease and intracranial extension. Distant failure determined overall survival in our cohort. Toxicities were acceptable given disease location and extent.

Metastasizing Esthesioneuroblastoma in a Dog.

A 7-year-old Afghan hound presented with a history of disorientation, loss of vision, and seizures. Magnetic resonance imaging helped identify a mass at the level of the main olfactory bulb that compressed and displaced adjacent tissues in the cribriform plate into the nasal cavity and nasopharynx. Bony structures were osteolytic. After removing almost 80% of the mass, the tumor recurred a few months later. Due to severe respiratory distress and subsequent to an ultrasound diagnosis of a liver tumor, the dog was euthanized. In addition to the nasal mass, a single nodule in the liver and multiple nodules in the lung were present. All masses had similar cell morphology and were diagnosed as metastasizing esthesioneuroblastoma. The neoplastic cells expressed neuron-specific enolase and chromogranin A, and a few cells within the nasal mass were positive for cytokeratin. This is the first description of a canine esthesioneuroblastoma with distant metastases.

[Esthesioneuroblastoma]. / Les esthésioneuroblastomes.

Esthesioneuroblastoma is an uncommon malignancy originating from olfactive epithelium. Men are more frequently affected than women. Nasal symptoms are the most common revealing signs. Immunohistochemistry helps diagnosis. There is no randomized trial evaluating treatment due to the low incidence of this tumor. Radiotherapy and surgery are the standard of care. Radiotherapy is benefic even in early stage disease. Chemotherapy is indicated in case of locally advanced or metastatic disease.

[Late neck metastasis in esthesioneuroblastoma: a case report]. / Estesyonöroblastomda geç boyun metastazi: Olgu sunumu.

Esthesioneuroblastoma is a rare malignancy of olfactory neuroepithelium arising from sinonasal region. It has biologically an aggressive behavior. The tumor is characterised by common local recurrence, atypic distant metastasis and poor long-term prognosis. Cervical metastasis accounts for 20-30% of the patients. Late metastases are seen particularly six months or later following primary treatment. In this article, we present a 43-year-old female case with Kadish B stage esthesioneuroblastoma who underwent extracranial tumor resection and postoperative radiotherapy. Eleven years later (at 132 months) right neck cervical metastasis was occurred and we applied right functional neck dissection and adjuvant radiotherapy to treat. We also review the treatment of late neck metastasis in the light of the current literature data.

The developing management of esthesioneuroblastoma: a single institution experience.

Esthesioneuroblastoma remains a challenging disease because of its rarity, the complexity of surrounding structures, missing opinions of optimal treatment protocol, and complications associated with necessary surgery. Our objective was to analyse the management and outcome of a cohort of patients with esthesioneuroblastoma from 1990 to 2009 in a tertiary medical centre. There were 17 eligible patients (8 males and 9 females) with the median age of 53 years (range 20-75 years). An obvious inconsistency was noted in the management of the various tumours of the present series during the two decades due to a lack of a uniform treatment protocol. The median follow-up time was 57.5 months (range 3-158 months). Nine patients (seven with curative treatment intent) died of the disease with the median time from diagnosis to death of 60 months (range 3-161 months). Eight patients had no evidence of the disease at last follow-up visit (median 76 months, range 24-119 months). Recurrences were documented in seven of the patients. The median time from end of primary treatment to a recurrence was 57 months (range 6-110 months). The 5-year overall survival and disease-free survival was 68 and 62%, respectively. The management of ENB should be planned by an experienced head and neck surgeon as part of a multidisciplinary team in a tertiary referral setting. Multimodality therapy with long-term follow-up is preferable and should be set based on the available disease-specific classifications for clinical staging and histopathological grading.