bromochloroacetic-acid and Esthesioneuroblastoma--Olfactory

Although the definitions of sinonasal neuroendocrine and neuroectodermal neoplasms did not change substantially in the 5th edition WHO Classification of Head and Neck Tumours, the diagnosis of olfactory neuroblastoma (ONB), small cell neuroendocrine carcinoma, and large cell neuroendocrine carcinoma remains quite challenging in practice. Ambiguities surrounding the amount of keratin expression allowable in ONB and the amount of neuroendocrine differentiation seen in sinonasal undifferentiated carcinoma (SNUC) lead to significant diagnostic discrepancies at the high grade end of this tumor spectrum. Furthermore, a group of problematic neuroepithelial tumors that show overlapping features of ONB and neuroendocrine carcinoma have never been recognized in formal classification schemes. Since publication of the 5th edition WHO, two new tumor entities have been proposed that help resolve these problems. Olfactory carcinoma is defined by high grade keratin-positive neuroectodermal cells with frequent intermixed glands and shows recurrent Wnt pathway, ARID1A, and RUNX1 alterations. IDH2-mutant sinonasal carcinoma is a molecularly-defined category that encompasses tumors with undifferentiated (SNUC), large cell neuroendocrine, and neuroepithelial phenotypes. This review will provide a practical overview of these emerging entities and their application to diagnostic challenges in the post-WHO sinonasal neuroendocrine and neuroectodermal tumor classification.

Topics: Carcinoma, Neuroendocrine; Esthesioneuroblastoma, Olfactory; Humans; Keratins; Maxillary Sinus Neoplasms; Nasal Cavity; New Orleans; Nose Neoplasms; Paranasal Sinus Neoplasms

Esthesioneuroblastoma (ENB), also called olfactory neuroblastoma, is a cancerous tumor originating from the olfactory neuroepithelial cells frequently invading the brain through the cribriform plate. The optimal therapy is the multimodality treatment involving a group of physicians trained in different medical specialties. Establishing a careful histopathological diagnostic and treatment planning based on a multidisciplinary approach is of paramount importance. The treatment of ENB correlates with the extent of the lesion, with surgery being the mainstay of therapy followed by postoperative irradiation. Surgery, when complete, image-verified and associated with radiation therapy results in long-term survival and presents a very low probability of illness recurrence. We present the case of a 46-year-old female with ENB, who was operated on in the Clinic of Neurosurgery of the National Institute of Neurology and Neurovascular Diseases in Bucharest, Romania, through a bifrontal craniotomy approach. Gross total resection of the intracranial extent was performed. The pathological diagnosis revealed an aggressive olfactory neuroblastoma. Three weeks after discharge from hospital, the tumor was completely resected through a lateral rhinotomy performed by an otorhinolaryngologist. Six weeks later, the patient received adjuvant therapy (radiotherapy and chemotherapy). The outcome was favorable, with no tumor recurrence at 20 months postoperatively. Our case demonstrates that even when dealing with a visibly aggressive tumor, a correct diagnosis, accurate classification and grading along with appropriate therapy ensure a favorable outcome.

Topics: Cell Proliferation; Esthesioneuroblastoma, Olfactory; Female; Humans; Keratins; Ki-67 Antigen; Magnetic Resonance Imaging; Middle Aged; S100 Proteins; Tomography, X-Ray Computed

Olfactory neuroblastoma (ONB) is a malignant neuroectodermal tumor that typically occurs in the superior nasal cavity. It is a distinct entity with features that include nesting, low-grade stippled nuclei, and neurofibrillary stroma with formation of pseudorosettes. It has a distinctive immunoprofile that includes keratin negativity, neuroendocrine marker positivity, and S100 positive sustentacular cells, which surround the nests of tumor in a supportive manner. Although the typical clinicopathologic features leave little room for misinterpretation, the wide variability in this tumor may cause diagnostic difficulty. This includes immunophenotypic diversity or patchy staining with immunomarkers, wide spectrum of grade and histology, posttreatment changes, and occasional divergent differentiation. In addition, problems in sampling, preservation, and clinical localization may make the diagnosis more challenging. A large group of tumors may show morphologic overlap with ONB, with some mimicking low-grade tumors, whereas others mimic high-grade tumors. This differential diagnosis has important treatment and prognostic implications. Further complicating the issue is that many of the mimics themselves may show great morphologic and immunophenotypic variability. This manuscript will review the typical clinical and pathologic features of ONB, address the great variability of ONB in our experience, will focus on the differential diagnosis and report on recent findings in these tumors including molecular genetics where applicable.

Topics: Diagnosis, Differential; Esthesioneuroblastoma, Olfactory; Humans; Immunohistochemistry; Keratins; Nasal Cavity; Nose Neoplasms; S100 Proteins

The sinonasal cavities harbour a variety of rare tumour types. Many carry a poor prognosis while therapeutic options are limited. Histopathological classification can be difficult, especially for poorly differentiated tumours such as olfactory neuroblastoma (ONB), sinonasal neuroendocrine carcinoma (SNEC) and sinonasal undifferentiated carcinoma (SNUC). We analysed Affymetrix OncoScan genome-wide copy number profiles of these three tumour types, both as originally diagnosed and as regrouped by their cytokeratin (Ck) and neuroendocrine (Ne) expression pattern, aiming to find a relation between phenotype and genotype. According to the original histopathological classification our series consisted of 24 ONB, 11 SNEC and 19 SNUC, while immunohistochemistry indicated 11 Ck-Ne+/ONB, 18 Ck+Ne+/SNEC, 24 Ck+Ne-/SNUC, and 1 Ck-Ne-/unclassified. As originally diagnosed, the three tumour types showed similar copy number profiles. However, when regrouped by Ck/Ne immunostaining we found a distinct set of gains and losses; Ck-Ne+/ONB harboured few and predominantly whole chromosomes abnormalities, Ck+Ne+/SNEC carried both gains and losses in high frequency, and Ck+Ne-/SNUC showed mostly gains. In addition, each tumour carried a number of unique chromosomal deletions. Genome-wide copy number profiling supports the value of immunohistochemical CkNe staining of ONB, SNEC and SNUC for tumour classification, which is important for prognosis and therapeutic decision-making.

Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Neuroendocrine; Cell Differentiation; Esthesioneuroblastoma, Olfactory; Gene Expression Profiling; Genotype; Humans; Keratins; Maxillary Sinus Neoplasms

Topics: Adult; Biomarkers, Tumor; Carcinoma, Neuroendocrine; Diagnosis, Differential; Esthesioneuroblastoma, Olfactory; Humans; Keratins; Male; Nasal Cavity; Nose Neoplasms

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.

Topics: Animals; Cerebrum; Chromogranin A; Dog Diseases; Dogs; Esthesioneuroblastoma, Olfactory; Keratins; Liver; Liver Neoplasms; Lung; Lung Neoplasms; Male; Nasal Cavity; Neoplasm Recurrence, Local; Nose Neoplasms; Phosphopyruvate Hydratase

Topics: Actins; Carcinosarcoma; Craniopharyngioma; Diagnosis, Differential; Esthesioneuroblastoma, Olfactory; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Nasal Cavity; Nose Neoplasms; Paranasal Sinus Neoplasms; Pituitary Neoplasms; Teratoma; Vimentin

Our purpose was to evaluate the diagnosis and combined modality treatment of esthesioneuroblastoma treated at 1 institution.. A retrospective analysis of clinical information regarding presentation, immunohistochemical results, treatment and outcome was performed on 21 patients with esthesioneuroblastoma.. Two patients had Kadish A, 12 had Kadish B and 7 had Kadish C disease. The mean follow-up was 41.9 months. Immunohistochemical stains were performed in 17 cases, and the tumors were focal positive or showed positive immunoreactivity to neuron-specific enolase (17/17, 100%), synaptophysin (13/17, 76.5%), S-100 protein (8/17, 47.1%), epithelial membrane antigen (5/17, 29.4%), chromogranin A (4/17, 23.5%), vimentin (3/17, 17.6%) and cytokeratin (2/17, 11.8%). Generally, the patients were treated with preoperative radiotherapy (Kadish A and Kadish B) and preoperative chemoradiotherapy (Kadish C) after the initial biopsy, followed by surgery. Surgical approaches (n = 21) consisted of 12 lateral rhinotomies, 5 craniofacial resections, 3 endoscopic sinus surgeries and 1 midfacial degloving approach. The 5-year crude overall survival rate was 76.2%.. Esthesioneuroblastoma is an uncommon malignant tumor. Thorough histological evaluation is the key to correct diagnosis and differentiation. Preoperative radiotherapy or chemoradiotherapy can give surgeons the chance to choose different surgical approaches, especially the endoscopic surgical techniques, in the future.

Topics: Adult; Antineoplastic Agents; Biopsy; Child; Chromogranin A; Combined Modality Therapy; Esthesioneuroblastoma, Olfactory; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Nasal Cavity; Nose Neoplasms; Phosphopyruvate Hydratase; Radiotherapy; Retrospective Studies; S100 Proteins; Synaptophysin; Vimentin; Young Adult