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Ewing's sarcoma in the nasal cavity
Ewing’s sarcoma in the nasal cavity LAJOS V. CSOKONAI, MD, PHD, BÁLINT LIKTOR, MD, GABRIELLA ARATÓ, MD, and FRIGYES HELFFRICH, MD, Budapest, Hungary
In the past decade, it has been revealed that Ewing’s sarcoma, originally described by James Ewing in 1921, originates from primitive neuroectodermal cells with various stages of differentiation. The classical Ewing’s sarcoma, localized in the bones, is a less-differentiated tumor, whereas the other extremity of the scale is represented by primitive neuroectodermal tumors (PNETs) of extraskeletal occurrence, consisting of well-differentiated cells. Both show similar histochemical characteristics and specific chromosome location (t11:22).1 Apparently all Ewing’s sarcomas contain this marker. Both the Ewing tumor and the PNET belong to the group of neoplasms usually referred to as small roundcell tumors. According to our present knowledge, the classical Ewing’s sarcoma and PNET are separate differentiated forms of the same tumor.2 Ewing’s sarcoma may appear in any bone of the body, most frequently in the diaphysis of long tubular bones and in the bones of the pelvis.2,3 In 2.3% of the cases, it develops on the face. It originates from the medullary space subsequently filling it entirely and spreading also into the cortex by infiltration. In most cases, the affected tissue is greyish-white, soft, and puslike. The bones increase in thickness. The radiologically characteristic “onion-skin layering” structure is formed by the elevation of the periosteum and the newly formed subperiosteal bone tissue. Tumors with similar histologic appearance developing in soft parts are referred to as Ewing’s sarcoma. The tumor discussed in this case report was immunohistochemically positive with neurogen markers (S-100 protein). Intracytoplasmic glycogen is also characteristic but not pathognomic.4 Occasional positivity of neuron-specific enolase indicates neural origin, however, detection of the 11/22
From the Department of Ear, Nose, and Throat Diseases (Drs Csokonai, Liktor, and Helffrich), and Department of Pathology (Dr Arató), Faculty of Health Sciences, Semmelweis University, Budapest. Reprint requests: Lajos Csokonai Vitez, MD, Department of Ear, Nose and Throat Diseases, Faculty of Health Sciences, Semmelweis University, 1135 Budapest, Szabolcs u. 35, Hungary; e-mail, [email protected]. Otolaryngol Head Neck Surg 2001;125:665-7. Copyright © 2001 by the American Academy of Otolaryngology– Head and Neck Surgery Foundation, Inc. 0194-5998/2001/$35.00 + 0 23/78/119486 doi:10.1067/mhn.2001.119486
chromosome translocation is more useful in the diagnosis. Elevated levels of p30/32 MIC2 glycoprotein can be detected in patients with Ewing’s sarcoma or peripheral neuroepthelioma. This glycoprotein is coded by the MIC2 gene located on the X and Y human chromosomes; O13 is a generally available antibody that reacts with the p30/32 MIC2 protein. Immunoreactivity of any small round-cell tumors to O13 antibody indicates that the tumor is most probably a Ewing’s sarcoma or a peripheral neuroepithelioma.5 CASE REPORT In December 1994, a 19-year-old male patient was admitted to our department because of suspected mesenchymal malignant tumor, after an endonasal “polypectomy” in another institute. Nasal endoscopy indicated a hyperplasia in the middle third of the lower edge of the middle right concha in the size of a pea. Clinically, it gave the impression of a tumor and was removed for histologic analysis. The cauliflower-like tumor was growing outward and was not connected in any way with the bony bottom; this was later proven by the histologic findings. Immunohistochemical tests and electron microscopic study performed at the Institute of Pathology and the Department of Oncopathology, Haynal Imre University of Health Science (now: Semmelweis University, Faculty of Health Sciences) and indicated Ewing’s sarcoma. Histologic Description Three pieces of greyish-white tissue (one the size of a pea and 2 the size of a lentil) entirely embedded in paraffin were provided for the tests. Microscopically, the pieces were covered with simple epithelial cells on the surface with cell-rich tumorous tissue underneath. The tumor cells were diffusely distributed and pressed tightly against each other. Cell nuclei were round or oval in shape and often invaginated (Fig 1). The chromatin matter was loose, and one central nucleolus could be seen. PAS positive clots that disappeared after digestion were observed in the narrow cytoplasm, therefore they corresponded to glycogen. Minimal amounts of argentable fibernetwork could be seen between the tumor cells. Immunohistochemical (EMA, keratin, LCA, NSE, S-100 protein) reactions were performed, and all proved negative. For the purpose of ultrastructural examination, a small piece was cut off from the embedded paraffin using microscopic control. The piece was subsequently deparaffinated and embedded in synthetic resin using the conventional protocol. The ultrastructural analysis indicated that the tumor cells were pressed tightly against each other with minimal extracellular matrix 665
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Fig 1. Monomorph round or ovoid cells are closely packed; nucleus has a prominent nucleolus. (Hematoxylin-eosin stain; original magnification ×250.)
Fig 2. Electron microscopic picture of the tumor. Only a few mitochondria and glycogen granules are visible in the cytoplasm. There is no intercellular matrix. (Original magnification ×7400.)
between them. No cell junction structures were found. Cell nuclei were large and invaginated with prominent centrally located nucleolus. The cytoplasm was extremely undifferentiated, containing only glycogen granules, a few mitochondria, and a few intermediate filaments (Fig 2).
The results of the examinations (skull CT, whole body scintigraphy) indicated no tumor-like alterations in either the regional area or in the distant bones. On the basis of the histologic diagnosis, an extended Denker operation was carried out during which the affected soft parts and the bone struc-
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site of the surgery. Since then the patient has been entirely free from complaints and symptoms. In March 1998, the patient was asked to return for follow-up examination. Endoscopy and sinuscopy were performed showing intact, tumor-free mucosa both in the nasal cavity and in the maxillary sinus. The CT scan performed on December 7, 2000, showed no sign of a build-up of pathologic contrast material and no sign of recurrence (Fig 3). CONCLUSION
The disease discussed in this case report is exceptionally rare (its incidence in the US is 2.1 cases in 1 million children). Identification of the disease is particularly difficult because of the difficulties associated with the exact specification and pathologic classification of the various forms of small round cell tumors. REFERENCES Fig 3. CT scan prepared as control examination on December 7, 2000. Status after Denker surgery: no sign of a build-up of pathologic contrast material and no sign of recurrence.
tures in the lower nasal canal were removed. The patient received full-dose postoperative irradiation at the National Institute of Oncology (40+16 Gy telecobalt irradiation). In September 1995, an endoscopic follow-up examination was carried out. The results of the macroscopic examination and the histologic tests indicated no recidivism at and around the
1. Yoshida H, Nagao K, Ito H, et al. Chromosomal translocation in human soft tissue sarcomas by interphase fluorescence in situ hybridization. Pathol Int 1997;47:222-9. 2. Grier HE. The Ewing family of tumours: Ewing’s sarcoma and primitive neuroectodermal tumours. Pediatr Clin North Am 1997;44:991-1004. 3. Verril MW, Judson JR, Harmer CL, et al. Ewing’s sarcoma and primitive neuroectodermal tumour in adults: are they different from Ewing’s sarcoma and primitive neuroectodermal tumour in children? J Clin Oncol 1997;15:2611-21. 4. Cotran RS, Kumar V, Robbins SL. Robbins pathologic basis of disease, 4th ed. Philadelphia: WB Saunders Co; 1989. p. 1342-3. 5. Weidner N, Tjoe J. Immunohistochemical profile of monoclonal antibody O13: antibody that recognizes glycoprotein p30/32MIC2 and is useful in diagnosing Ewing sarcoma and peripheral neuroepithelioma. Am J Surg Pathol 1994;18:486-97.
In the past decade, it has been revealed that Ewing’s sarcoma, originally described by James Ewing in 1921, originates from primitive neuroectodermal cells with various stages of differentiation. The classical Ewing’s sarcoma, localized in the bones, is a less-differentiated tumor, whereas the other extremity of the scale is represented by primitive neuroectodermal tumors (PNETs) of extraskeletal occurrence, consisting of well-differentiated cells. Both show similar histochemical characteristics and specific chromosome location (t11:22).1 Apparently all Ewing’s sarcomas contain this marker. Both the Ewing tumor and the PNET belong to the group of neoplasms usually referred to as small roundcell tumors. According to our present knowledge, the classical Ewing’s sarcoma and PNET are separate differentiated forms of the same tumor.2 Ewing’s sarcoma may appear in any bone of the body, most frequently in the diaphysis of long tubular bones and in the bones of the pelvis.2,3 In 2.3% of the cases, it develops on the face. It originates from the medullary space subsequently filling it entirely and spreading also into the cortex by infiltration. In most cases, the affected tissue is greyish-white, soft, and puslike. The bones increase in thickness. The radiologically characteristic “onion-skin layering” structure is formed by the elevation of the periosteum and the newly formed subperiosteal bone tissue. Tumors with similar histologic appearance developing in soft parts are referred to as Ewing’s sarcoma. The tumor discussed in this case report was immunohistochemically positive with neurogen markers (S-100 protein). Intracytoplasmic glycogen is also characteristic but not pathognomic.4 Occasional positivity of neuron-specific enolase indicates neural origin, however, detection of the 11/22
From the Department of Ear, Nose, and Throat Diseases (Drs Csokonai, Liktor, and Helffrich), and Department of Pathology (Dr Arató), Faculty of Health Sciences, Semmelweis University, Budapest. Reprint requests: Lajos Csokonai Vitez, MD, Department of Ear, Nose and Throat Diseases, Faculty of Health Sciences, Semmelweis University, 1135 Budapest, Szabolcs u. 35, Hungary; e-mail, [email protected]. Otolaryngol Head Neck Surg 2001;125:665-7. Copyright © 2001 by the American Academy of Otolaryngology– Head and Neck Surgery Foundation, Inc. 0194-5998/2001/$35.00 + 0 23/78/119486 doi:10.1067/mhn.2001.119486
chromosome translocation is more useful in the diagnosis. Elevated levels of p30/32 MIC2 glycoprotein can be detected in patients with Ewing’s sarcoma or peripheral neuroepthelioma. This glycoprotein is coded by the MIC2 gene located on the X and Y human chromosomes; O13 is a generally available antibody that reacts with the p30/32 MIC2 protein. Immunoreactivity of any small round-cell tumors to O13 antibody indicates that the tumor is most probably a Ewing’s sarcoma or a peripheral neuroepithelioma.5 CASE REPORT In December 1994, a 19-year-old male patient was admitted to our department because of suspected mesenchymal malignant tumor, after an endonasal “polypectomy” in another institute. Nasal endoscopy indicated a hyperplasia in the middle third of the lower edge of the middle right concha in the size of a pea. Clinically, it gave the impression of a tumor and was removed for histologic analysis. The cauliflower-like tumor was growing outward and was not connected in any way with the bony bottom; this was later proven by the histologic findings. Immunohistochemical tests and electron microscopic study performed at the Institute of Pathology and the Department of Oncopathology, Haynal Imre University of Health Science (now: Semmelweis University, Faculty of Health Sciences) and indicated Ewing’s sarcoma. Histologic Description Three pieces of greyish-white tissue (one the size of a pea and 2 the size of a lentil) entirely embedded in paraffin were provided for the tests. Microscopically, the pieces were covered with simple epithelial cells on the surface with cell-rich tumorous tissue underneath. The tumor cells were diffusely distributed and pressed tightly against each other. Cell nuclei were round or oval in shape and often invaginated (Fig 1). The chromatin matter was loose, and one central nucleolus could be seen. PAS positive clots that disappeared after digestion were observed in the narrow cytoplasm, therefore they corresponded to glycogen. Minimal amounts of argentable fibernetwork could be seen between the tumor cells. Immunohistochemical (EMA, keratin, LCA, NSE, S-100 protein) reactions were performed, and all proved negative. For the purpose of ultrastructural examination, a small piece was cut off from the embedded paraffin using microscopic control. The piece was subsequently deparaffinated and embedded in synthetic resin using the conventional protocol. The ultrastructural analysis indicated that the tumor cells were pressed tightly against each other with minimal extracellular matrix 665
666 CSOKONAI et al
Otolaryngology– Head and Neck Surgery December 2001
Fig 1. Monomorph round or ovoid cells are closely packed; nucleus has a prominent nucleolus. (Hematoxylin-eosin stain; original magnification ×250.)
Fig 2. Electron microscopic picture of the tumor. Only a few mitochondria and glycogen granules are visible in the cytoplasm. There is no intercellular matrix. (Original magnification ×7400.)
between them. No cell junction structures were found. Cell nuclei were large and invaginated with prominent centrally located nucleolus. The cytoplasm was extremely undifferentiated, containing only glycogen granules, a few mitochondria, and a few intermediate filaments (Fig 2).
The results of the examinations (skull CT, whole body scintigraphy) indicated no tumor-like alterations in either the regional area or in the distant bones. On the basis of the histologic diagnosis, an extended Denker operation was carried out during which the affected soft parts and the bone struc-
Otolaryngology– Head and Neck Surgery Volume 125 Number 6
CSOKONAI et al
667
site of the surgery. Since then the patient has been entirely free from complaints and symptoms. In March 1998, the patient was asked to return for follow-up examination. Endoscopy and sinuscopy were performed showing intact, tumor-free mucosa both in the nasal cavity and in the maxillary sinus. The CT scan performed on December 7, 2000, showed no sign of a build-up of pathologic contrast material and no sign of recurrence (Fig 3). CONCLUSION
The disease discussed in this case report is exceptionally rare (its incidence in the US is 2.1 cases in 1 million children). Identification of the disease is particularly difficult because of the difficulties associated with the exact specification and pathologic classification of the various forms of small round cell tumors. REFERENCES Fig 3. CT scan prepared as control examination on December 7, 2000. Status after Denker surgery: no sign of a build-up of pathologic contrast material and no sign of recurrence.
tures in the lower nasal canal were removed. The patient received full-dose postoperative irradiation at the National Institute of Oncology (40+16 Gy telecobalt irradiation). In September 1995, an endoscopic follow-up examination was carried out. The results of the macroscopic examination and the histologic tests indicated no recidivism at and around the
1. Yoshida H, Nagao K, Ito H, et al. Chromosomal translocation in human soft tissue sarcomas by interphase fluorescence in situ hybridization. Pathol Int 1997;47:222-9. 2. Grier HE. The Ewing family of tumours: Ewing’s sarcoma and primitive neuroectodermal tumours. Pediatr Clin North Am 1997;44:991-1004. 3. Verril MW, Judson JR, Harmer CL, et al. Ewing’s sarcoma and primitive neuroectodermal tumour in adults: are they different from Ewing’s sarcoma and primitive neuroectodermal tumour in children? J Clin Oncol 1997;15:2611-21. 4. Cotran RS, Kumar V, Robbins SL. Robbins pathologic basis of disease, 4th ed. Philadelphia: WB Saunders Co; 1989. p. 1342-3. 5. Weidner N, Tjoe J. Immunohistochemical profile of monoclonal antibody O13: antibody that recognizes glycoprotein p30/32MIC2 and is useful in diagnosing Ewing sarcoma and peripheral neuroepithelioma. Am J Surg Pathol 1994;18:486-97.