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Pathology Quiz Case 2: Diagnosis

Pathology Quiz Case 2: Diagnosis Diagnosis: Esthesioneuroblastoma (ENB), grade III/IV Esthesioneuroblastoma (olfactory neuroblastoma) is a rare, malignant, neuroepithelial tumor that arises from the olfactory epithelium lining the cribriform plate and upper third of nasal cavity. Esthesioneuroblastoma, which was first described by Berger et al1 in 1924, accounts for 3% of malignant neoplasms of the nasal cavity.1 It has a bimodal age distribution, with an initial peak between the ages of 11 and 20 years and a later peak between the ages of 51 and 60 years,2 and a slight male predominance.3 The tumor can spread submucosally within the sinonasal cavity, cross the cribriform plate, and invade the meninges and brain. It can metastasize by blood, lymph, and cerebrospinal fluid. Metastasis occurs in 10% to 30% of cases.4 Cervical lymph nodes are the most common site of metastatic spread. Other less common sites include the lungs and pleura, brain, bone, spinal cord, breasts, and abdominal viscera. Because the initial symptoms are nonspecific, the diagnosis of ENB can be delayed. The common symptoms include unilateral nasal obstruction, nasal pain, epistaxis, and anosmia. The presence of symptoms related to the eyes, ears, and central nervous system indicate that there is tumor extension into neighboring structures. The most common physical finding in these cases is the presence of a polypoidal, reddish gray, soft, vascular nasal mass. The lesions appear as solid and contrast enhancing on CT scans. The presence of bone erosion on CT scans warrants magnetic resonance imaging to rule out orbital and cranial extension. Intralesional calcification is a characteristic feature of ENB.5 The presence of cystic lesions at tumor margins when there is intracranial extension yields a definitive radiologic sign of ENB.6 There are 2 commonly used radiologic staging systems. The Kadish staging system, which is predictive of disease-related mortality, consists of 3 stages: stage A, which is limited to the nasal cavity; stage B, which is limited to the nose and paranasal sinuses; and stage C, which extends beyond the nose and paranasal sinuses. The Biller staging system is used for the accurate staging of tumors with intracranial extension. It is better to perform radiologic investigations before proceeding to biopsy so that the “swelling” effect of the procedure can be avoided. The well-differentiated ENB is characterized by small, round or fusiform neuroepithelial cells with a rosette or pseudorosette formation. The true rosettes (Flexner-Wintersteiner type) show a ring of columnar cells surrounding a central space that appears clear on ordinary microscopy. In pseudorosettes (Homer-Wright type), the cells are loosely arranged around a central space containing fibrillary material. A distinctive feature of this type of tumor is a fibrillary intercellular background material that represents cellular cytoplasmic processes. The stroma is usually very vascular. The high-grade ENB shows small, anaplastic, hyperchromatic cells with numerous mitotic figures and scanty cytoplasm. It is difficult to differentiate high-grade ENBs from other small cell neoplasms of the nasal cavity on light microscopy. It has recently been reported that the HASH (human achaete-scute homologue) gene is expressed in immature olfactory cells. The expression of this gene may represent a useful tool for differentiating ENBs from poorly differentiated tumors of sinonasal origin.7 The pathologic differential diagnoses include malignant melanoma, lymphoma, rhabdomyosarcoma, Ewing sarcoma, plasmacytoma, anaplastic carcinoma, and neuroendocrine carcinoma. These tumors can be differentiated from ENB by immunocytochemical analysis and electron microscopy. Electron microscopy of ENB shows the presence of neuronal processes, neurosecretory granules, neurofilaments, and synapticlike junctions. Immunocytochemical analysis shows positive staining for neuroendocrine markers (such as synaptophysin and chromogranin) and S100 protein, even though none of these stains are specific for ENB, and negative staining for epithelial, muscle, and lymphoid antigens. Melanoma can be differentiated from ENB by HMB-45 immunopositivity and the pattern of S100 protein staining (scattered and peripheral in ENB and diffuse and strong in melanoma). Lymphoma stains positively for common leukocyte antigen. Rhabdomyosarcoma is distinguished by the presence of rhabdomyoblasts and positive immunostaining with desmin, vimentin, and actin. The lack of staining with cytokeratin antibodies differentiates ENB from sinonasal undifferentiated carcinoma and neuroendocrine carcinoma. Ewing sarcoma stains positive for myc-2. The pathologic grading system proposed by Hyams et al8 considers 6 parameters: mitotic index, nuclear polymorphism, presence of fibrillary matrix, rosettes, necrosis, and preservation of lobular architecture. The treatment for ENB is surgery followed by radiotherapy. Radical surgery with a combined craniofacial approach provides good exposure and enables total resection of the tumor. Radiotherapy is used for better local control of the disease. Esthesioneuroblastoma has demonstrated varying responses to chemotherapy, which should be reserved for tumors that have spread beyond the nasal cavity and paranasal sinuses or for the treatment of distant metastasis. Both CT and magnetic resonance imaging may fail to exclude dural involvement by the tumor; therefore, the surgical team should always be prepared to resect and repair the dural defect in all cases. In cases without metastasis or intracranial extension, a 5-year survival rate of 50% has been reported.9 Local recurrence is the most common cause of death, and the rate of local recurrence after treatment is reportedly as high as 60%.10 Residents and fellows in otolaryngology are invited to submit quiz cases for this section and to write letters to the ARCHIVES commenting on cases presented. Quiz cases should follow the patterns established. See “Instructions for Authors.” Material for CLINICAL PROBLEM SOLVING: PATHOLOGY should be mailed to the Editor. Reprints are not available from the authors. References 1. Berger LLuc GRichard D L’esthesioneuroepitheliome olfactif. Bull Assoc Fr Etud Cancer 1924;13410- 421Google Scholar 2. Elkon DHightower SMeng L Esthesioneuroblastoma. Cancer 1979;441087- 1094PubMedGoogle ScholarCrossref 3. Simon JZhen WMcCulloch T et al. Esthesioneuroblastoma: the University of Iowa experience 1978-1998. Laryngoscope 2001;111488- 493PubMedGoogle ScholarCrossref 4. Shaari CCatalano PPost K Central nervous system metastasis from esthesioneuroblastoma. Otolaryngol Head Neck Surg 1996;114808- 812PubMedGoogle ScholarCrossref 5. Manelfe CBonafe AFabre PPessey JJ Computed tomography in olfactory neuroblastoma: one case of olfactory neuroepithelioma and four cases of esthesioneuroblastoma. J Comput Assist Tomogr 1978;2412- 420PubMedGoogle ScholarCrossref 6. Som PLidov MBrandwein MCatalano PBiller HF Sinonasal esthesioneuroblastoma with intracranial extension: marginal tumor cysts as a diagnostic finding. AJNR Am J Neuroradiol 1994;151259- 1262PubMedGoogle Scholar 7. Mhawech PBerczy MAssaly M et al. Human archaete-scute homologue (hASH1) mRNA level as a diagnostic marker to distinguish esthesioneuroblastoma from poorly differentiated tumors arising in the sinonasal tract. Am J Clin Pathol 2004;122100- 105PubMedGoogle ScholarCrossref 8. Hyams VJBatsakis JGMichaels L Tumors of the Upper Respiratory Tract and Ear. Washington, DC: Armed Forces Institute of Pathology; 1988:240-248 9. Portmann NMBonnard ET Sur un cas de tumeur nerveuse des fosses nasals (esthesioneuroblastoma). Acta Otolaryngol 1928;1352- 57Google ScholarCrossref 10. Biller HFLawson WSachdev VPSom P Esthesioneuroblastoma: surgical treatment without radiation. Laryngoscope 1990;1001199- 1201PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Otolaryngology - Head & Neck Surgery American Medical Association

Pathology Quiz Case 2: Diagnosis

Archives of Otolaryngology - Head & Neck Surgery , Volume 131 (7) – Jul 1, 2005

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References (10)

Publisher
American Medical Association
Copyright
Copyright © 2005 American Medical Association. All Rights Reserved.
ISSN
0886-4470
eISSN
1538-361X
DOI
10.1001/archotol.131.7.644-b
Publisher site
See Article on Publisher Site

Abstract

Diagnosis: Esthesioneuroblastoma (ENB), grade III/IV Esthesioneuroblastoma (olfactory neuroblastoma) is a rare, malignant, neuroepithelial tumor that arises from the olfactory epithelium lining the cribriform plate and upper third of nasal cavity. Esthesioneuroblastoma, which was first described by Berger et al1 in 1924, accounts for 3% of malignant neoplasms of the nasal cavity.1 It has a bimodal age distribution, with an initial peak between the ages of 11 and 20 years and a later peak between the ages of 51 and 60 years,2 and a slight male predominance.3 The tumor can spread submucosally within the sinonasal cavity, cross the cribriform plate, and invade the meninges and brain. It can metastasize by blood, lymph, and cerebrospinal fluid. Metastasis occurs in 10% to 30% of cases.4 Cervical lymph nodes are the most common site of metastatic spread. Other less common sites include the lungs and pleura, brain, bone, spinal cord, breasts, and abdominal viscera. Because the initial symptoms are nonspecific, the diagnosis of ENB can be delayed. The common symptoms include unilateral nasal obstruction, nasal pain, epistaxis, and anosmia. The presence of symptoms related to the eyes, ears, and central nervous system indicate that there is tumor extension into neighboring structures. The most common physical finding in these cases is the presence of a polypoidal, reddish gray, soft, vascular nasal mass. The lesions appear as solid and contrast enhancing on CT scans. The presence of bone erosion on CT scans warrants magnetic resonance imaging to rule out orbital and cranial extension. Intralesional calcification is a characteristic feature of ENB.5 The presence of cystic lesions at tumor margins when there is intracranial extension yields a definitive radiologic sign of ENB.6 There are 2 commonly used radiologic staging systems. The Kadish staging system, which is predictive of disease-related mortality, consists of 3 stages: stage A, which is limited to the nasal cavity; stage B, which is limited to the nose and paranasal sinuses; and stage C, which extends beyond the nose and paranasal sinuses. The Biller staging system is used for the accurate staging of tumors with intracranial extension. It is better to perform radiologic investigations before proceeding to biopsy so that the “swelling” effect of the procedure can be avoided. The well-differentiated ENB is characterized by small, round or fusiform neuroepithelial cells with a rosette or pseudorosette formation. The true rosettes (Flexner-Wintersteiner type) show a ring of columnar cells surrounding a central space that appears clear on ordinary microscopy. In pseudorosettes (Homer-Wright type), the cells are loosely arranged around a central space containing fibrillary material. A distinctive feature of this type of tumor is a fibrillary intercellular background material that represents cellular cytoplasmic processes. The stroma is usually very vascular. The high-grade ENB shows small, anaplastic, hyperchromatic cells with numerous mitotic figures and scanty cytoplasm. It is difficult to differentiate high-grade ENBs from other small cell neoplasms of the nasal cavity on light microscopy. It has recently been reported that the HASH (human achaete-scute homologue) gene is expressed in immature olfactory cells. The expression of this gene may represent a useful tool for differentiating ENBs from poorly differentiated tumors of sinonasal origin.7 The pathologic differential diagnoses include malignant melanoma, lymphoma, rhabdomyosarcoma, Ewing sarcoma, plasmacytoma, anaplastic carcinoma, and neuroendocrine carcinoma. These tumors can be differentiated from ENB by immunocytochemical analysis and electron microscopy. Electron microscopy of ENB shows the presence of neuronal processes, neurosecretory granules, neurofilaments, and synapticlike junctions. Immunocytochemical analysis shows positive staining for neuroendocrine markers (such as synaptophysin and chromogranin) and S100 protein, even though none of these stains are specific for ENB, and negative staining for epithelial, muscle, and lymphoid antigens. Melanoma can be differentiated from ENB by HMB-45 immunopositivity and the pattern of S100 protein staining (scattered and peripheral in ENB and diffuse and strong in melanoma). Lymphoma stains positively for common leukocyte antigen. Rhabdomyosarcoma is distinguished by the presence of rhabdomyoblasts and positive immunostaining with desmin, vimentin, and actin. The lack of staining with cytokeratin antibodies differentiates ENB from sinonasal undifferentiated carcinoma and neuroendocrine carcinoma. Ewing sarcoma stains positive for myc-2. The pathologic grading system proposed by Hyams et al8 considers 6 parameters: mitotic index, nuclear polymorphism, presence of fibrillary matrix, rosettes, necrosis, and preservation of lobular architecture. The treatment for ENB is surgery followed by radiotherapy. Radical surgery with a combined craniofacial approach provides good exposure and enables total resection of the tumor. Radiotherapy is used for better local control of the disease. Esthesioneuroblastoma has demonstrated varying responses to chemotherapy, which should be reserved for tumors that have spread beyond the nasal cavity and paranasal sinuses or for the treatment of distant metastasis. Both CT and magnetic resonance imaging may fail to exclude dural involvement by the tumor; therefore, the surgical team should always be prepared to resect and repair the dural defect in all cases. In cases without metastasis or intracranial extension, a 5-year survival rate of 50% has been reported.9 Local recurrence is the most common cause of death, and the rate of local recurrence after treatment is reportedly as high as 60%.10 Residents and fellows in otolaryngology are invited to submit quiz cases for this section and to write letters to the ARCHIVES commenting on cases presented. Quiz cases should follow the patterns established. See “Instructions for Authors.” Material for CLINICAL PROBLEM SOLVING: PATHOLOGY should be mailed to the Editor. Reprints are not available from the authors. References 1. Berger LLuc GRichard D L’esthesioneuroepitheliome olfactif. Bull Assoc Fr Etud Cancer 1924;13410- 421Google Scholar 2. Elkon DHightower SMeng L Esthesioneuroblastoma. Cancer 1979;441087- 1094PubMedGoogle ScholarCrossref 3. Simon JZhen WMcCulloch T et al. Esthesioneuroblastoma: the University of Iowa experience 1978-1998. Laryngoscope 2001;111488- 493PubMedGoogle ScholarCrossref 4. Shaari CCatalano PPost K Central nervous system metastasis from esthesioneuroblastoma. Otolaryngol Head Neck Surg 1996;114808- 812PubMedGoogle ScholarCrossref 5. Manelfe CBonafe AFabre PPessey JJ Computed tomography in olfactory neuroblastoma: one case of olfactory neuroepithelioma and four cases of esthesioneuroblastoma. J Comput Assist Tomogr 1978;2412- 420PubMedGoogle ScholarCrossref 6. Som PLidov MBrandwein MCatalano PBiller HF Sinonasal esthesioneuroblastoma with intracranial extension: marginal tumor cysts as a diagnostic finding. AJNR Am J Neuroradiol 1994;151259- 1262PubMedGoogle Scholar 7. Mhawech PBerczy MAssaly M et al. Human archaete-scute homologue (hASH1) mRNA level as a diagnostic marker to distinguish esthesioneuroblastoma from poorly differentiated tumors arising in the sinonasal tract. Am J Clin Pathol 2004;122100- 105PubMedGoogle ScholarCrossref 8. Hyams VJBatsakis JGMichaels L Tumors of the Upper Respiratory Tract and Ear. Washington, DC: Armed Forces Institute of Pathology; 1988:240-248 9. Portmann NMBonnard ET Sur un cas de tumeur nerveuse des fosses nasals (esthesioneuroblastoma). Acta Otolaryngol 1928;1352- 57Google ScholarCrossref 10. Biller HFLawson WSachdev VPSom P Esthesioneuroblastoma: surgical treatment without radiation. Laryngoscope 1990;1001199- 1201PubMedGoogle ScholarCrossref

Journal

Archives of Otolaryngology - Head & Neck SurgeryAmerican Medical Association

Published: Jul 1, 2005

Keywords: magnetic resonance imaging,rhabdomyosarcoma,ewing's sarcoma,carcinoma, neuroendocrine,olfactory neuroblastoma,lymphoma,melanoma,neoplasm metastasis,nasal cavity,neoplasms,paranasal sinuses

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