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From the Departments of Otolaryngology (M.J.C., D.T.L.) and Radiology (H.D.C.), Massachusetts Eye and Ear Infirmary; the Departments of Neurosurgery (W.T.C.), Pediatrics (D.H.E.), Radiation Oncology (T.I.Y.), and Pathology (W.C.F.), Massachusetts General Hospital; and the Departments of Otology and Laryngology (M.J.C., D.T.L.), Surgery (W.T.C.), Pediatrics (D.H.E.), Radiation Oncology (T.I.Y.), Radiology (H.D.C.), and Pathology (W.C.F.), Harvard Medical School all in Boston. N Engl J Med 2007;356:2721-30.
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On examination, the patient was a healthyappearing boy. There was no evidence of rhinorrhea or nasal inflammation. Endoscopy of the right naris disclosed a firm soft-tissue mass arising from the lateral nasal wall, displacing the right middle turbinate medially toward the septum (Fig. 1). The mucosa overlying the mass was erythematous and vascular. The left naris was clear, and the nasopharynx was patent. Examination of the ears, oral cavity, pharynx, and neck was normal. One month later, repeated CT without the administration of contrast material, performed for intraoperative image guidance, revealed a heavily calcified lesion, 2.2 cm by 1.4 cm by 2.9 cm, within the right ethmoid sinus, which remodeled the medial orbital wall. The lamina papyracea was identifiable but not completely separable from the lateral aspect of the mass, and the ethmoid roof visibly limited the superior aspect of the lesion. There was complete opacification of the right maxillary, the remaining anterior ethmoid, and the frontal sinuses; the ipsilateral posterior ethmoid air cells and the sphenoid sinus were clear. The upper nasal cavity and cribriform area were not involved. The left paranasal sinuses showed minor mucosal thickening. There was mild right proptosis. The next day, a consulting oculoplastic surgeon documented mild right hypertelorism, normal visual and stereo acuity, no evidence of optic neuropathy, and full extraocular motility. An anterior-segment and dilated-fundus examination was normal. One week later, a diagnostic procedure was performed.
Differ en t i a l Di agnosis
Dr. Michael J. Cunningham: May we see the imaging studies? Dr. Hugh D. Curtin: CT scans obtained at the Massachusetts Eye and Ear Infirmary (Fig. 2A and 2B) show a radiodense mass filling much of the anterior ethmoid sinus and protruding into the middle meatus, remodeling the bony margin of the nasolacrimal duct, flattening it, and pushing it anteriorly. The lesion has the density of bone or calcium. The ipsilateral frontal sinus, maxillary sinus, and remaining ethmoid sinus are opacified, apparently obstructed by the lesion. There is remodeling of the lamina papyracea and the roof of the ethmoid sinus, without frank destruction. There is no intracranial extension or involvement of the upper nasal cavity or cribriform plate. Dr. Cunningham: I cared for this patient and am aware of the diagnosis. A unilateral nasal mass in a child may be congenital, inflammatory (infectious), or neoplastic. The important diagnostic aspects of this case include the prolonged duration of symptoms, the anterolateral location of the nasal mass, and the CT findings.
Congenital and Inflammatory Nasal Masses
Nasal septum
The most common congenital nasal masses are dermoid cysts, nasal gliomas (heterotopic neural tissue), and meningoencephaloceles. All three types involve medial, rather than lateral, intranasal presentation, are typically apparent at a much younger age than that of this patient, and have different CT findings. Teratomas are congenital sinonasal lesions that may calcify; they rarely originate in the nasal cavity or paranasal sinus, but a nasopharyngeal teratoma arising from the lateral nasopharyngeal wall or midline basisphenoid region may extend to these areas. Nasal polyps of infectious, atopic, or inflammatory cause can present in a similar fashion. An antrochoanal polyp and, less commonly, a sphenochoanal polyp can manifest with gradual, prolonged nasal congestion and headache secondary to postobstructive sinusitis. The right nasal mass in this patient was not polypoid, and the radiographic findings are not consistent with nasal polyposis.
Neoplasms in the Nasal Cavity
Figure 1. Endosocopic Image of the Right Naris Showing a Mass Arising from the Lateral Nasal Wall. The mucosa overlying the mass is erythematous and RETAKE 1st AUTHOR Cunningham ICM vascular. 2nd
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Many benign and malignant neoplasms of nasal, nasopharyngeal, and sinus origin can present as
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a unilateral nasal mass in children and adolescents. One of the more common neoplasms is juvenile nasopharyngeal angiofibroma. This neoplasm occurs almost exclusively in males, usually adolescents or young adults, although cases in preadolescent patients have been reported. Prolonged nasal obstruction, typically unilateral and often in association with epistaxis, is the classic presentation. Juvenile nasal angiofibroma arises within the nasopharynx in the region of the sphenopalatine foramen. Neither the sinonasal location of the lesion in this patient nor the extensive calcifications are consistent with juvenile nasopharyngeal angiofibroma. Peripheral-nerve-sheath tumors, particularly schwannomas, can arise within the nasal cavity and present with progressive nasal congestion.1 The CT finding of extensive calcification, however, argue against this diagnosis.
Soft-Tissue Sarcomas and Lymphomas
formity are the common presenting symptoms of craniofacial lesions. However, sinonasal involvement is not seen.
Ossifying Fibroma
Ossifying fibroma is a solitary lesion that usually presents in the third or fourth decade of life, although it may occur in children. The maxilla is the second most common craniofacial site of involvement. Radiographically, these lesions tend to be well circumscribed. There is limited associated bone destruction, often with an eggshell-
Rhabdomyosarcoma and fibrosarcoma are the most common soft-tissue sarcomas to arising within the sinonasal region. Fibrosarcoma, in particular, can have an indolent course. Both types have an aggressive appearance on imaging, with bony destruction at the margins of an erosive soft-tissue mass. This childs imaging studies do not support these diagnoses. Non-Hodgkins lymphoma can also occasionally have a primary sinonasal presentation in childhood. Children with lymphomas tend to have more acute systemic manifestations, and the radiologic appearance is very different.
Fibro-osseous Lesions
The CT findings in this case indicate calcification. The most common benign fibro-osseous lesions are fibrous dysplasia, ossifying fibroma, and juvenile (aggressive) ossifying fibroma. All involve the replacement of normal bone with benign fibrous tissue containing varying amounts of mineralized material; hence, all are characterized by some degree of calcification on imaging.
Fibrous Dysplasia
Fibrous dysplasia is an idiopathic, benign, slowly progressive disorder of unknown cause that usually presents in the first two decades of life and may be monostotic or polyostotic. The craniofacial skeleton is involved in approximately 20 to 25% of monostotic cases and in approximately 50% of polyostotic cases. Painless swelling and facial de-
Figure 2. Preoperative Imaging Studies. An axial CT scan of the head (Panel A) shows a lesion corresponding to the density of calcium or bone (arrow) RETAKE 1st AUTHOR Cunningham duct (arrowhead) ICM that remodels the nasolacrimal ante2nd REGThe F FIGURE 2a&b of 5 riorly. maxillary sinus (M) is obstructed. A coronal 3rd CASE TITLE CT image (Panel B) shows that the calcified Revised abnormality EMail Line 4-C fills the right ethmoid sinus. There is no cortical rim or SIZE Enon ARTIST:The mst H/T sclerotic margin. superior aspect H/T of the tumor abuts, 16p6 FILL Combo but does not erode, the roof of the ethmoid sinus (white AUTHOR, NOTE: arrow). The inferior marginPLEASE remodels or erodes the attach Figure has been redrawn and type has been reset. ment of the inferior turbinate (black Please check carefully.arrow). The lesion does not involve the upper nasal cavity (arrowhead), since it is separated from the cavity by a plate of bone. JOB: 35626 ISSUE: 6-28-07
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thin rim of bone around the lesion creating a so-called punched-out appearance. This childs presentation could reflect ossifying fibroma of the nasoethmoidal region, although the absence of a distinct (sharp) bony margin argues against this diagnosis.
Juvenile Ossifying Fibroma
Juvenile ossifying fibroma, also known as cementoossifying or psammomatoid ossifying fibroma, is more aggressive than ossifying fibroma, with invasion of bone and adjacent structures. Most patients are younger than 15 years of age. These lesions have a predilection for the maxilla and ethmoid and frontal bones. Symptoms include nasal obstruction, proptosis, visual disturbances, and headache. This childs clinical and radiologic presentation is consistent with juvenile (aggressive) ossifying fibroma.
Osteosarcoma and Chondrosarcoma
cases developing during the fourth to sixth decades, and no sex predilection. About 20% of cases involve patients younger than 20 years of age.3 The diagnosis of olfactory neuroblastoma is usually delayed, because its symptoms are nonspecific. Unilateral nasal obstruction is the most common symptom, followed by epistaxis or anosmia, headache and facial pain, proptosis or visual disturbance, epiphora, and infraorbital neuralgia or other cranial-nerve findings. Physical examination commonly reveals a unilateral mass in the superior nasal cavity, which may be soft or hard and gray to red, with variable superficial vascularity. A contrast-enhancing, solid soft-tissue mass is seen on CT, characteristically with intralesional calcification. The clinical and radiologic characteristics of this childs lesion are consistent with an olfactory neuroblastoma, although the origin of the lesion in the lateral ethmoid sinus, as opposed to the superior cribriform plate, is atypical.
Summary
Osteosarcoma and chondrosarcoma are the most common osseous malignant tumors arising within the jaw bones. About two thirds of these tumors arise in the mandible, and one third in the maxilla and paranasal sinuses. Both types pre sent predominantly in young adulthood. Mesenchymal chondrosarcoma is reported to occur more commonly in the sinonasal region. It is an aggressive neoplasm that occurs most frequently in women in the third or fourth decade of life, but presentation in a child as young as 11 years of age has been described.2 CT scanning demonstrates a soft-tissue mass with mineralization and more aggressive bony destruction than are seen in other fibro-osseous lesions. This patients age and the radiologic characteristics of the lesion argue against an osteosarcoma or chondrosarcoma. Inverting papilloma, although an unlikely possibility in this child, should be mentioned, since it is an intranasal lesion that may show diffuse calcification on imaging studies. However, this childs age and the apparent origin of the lesion in the ethmoid sinus are not consistent with this diagnosis.
Olfactory Neuroblastoma
Three diagnoses were considered preoperatively as the cause of this childs clinical and radiologic presentation: ossifying fibroma, juvenile (aggressive) ossifying fibroma, and olfactory neuroblastoma. Of these, I favored the last two diagnoses. The diagnostic procedure was a biopsy of the lesion performed while the patient was under general anesthesia. Calcification but no diagnostic features were seen on histopathological assessment of frozen sections. Endoscopic removal of all gross tumor was performed in conjunction with a wide maxillary antrotomy, a right anteroposterior ethmoidectomy, and a right frontal sinusotomy.
An estimated 3% of all endonasal tumors are olfactory neuroblastomas, also known as esthesioneuroblastomas or olfactory neuroepitheliomas. There is a wide age distribution, with a predominance of
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Figure 3. Biopsy Specimen of the Ethmoid Sinus (Hematoxylin and Eosin). Fibrovascular tissue with extensive calcification (Panel A) surrounds focal crushed neoplastic cells. There is tumor involvement of lamellar bone of the ethmoid sinus (Panel B). Focal collections of neoplastic cells are seen (Panel C) in a sheetlike arrangement with adjacent extracellular calcifications. The tumor (Panel D) are uniformly small, RETAKE cells 1st AUTHOR Cunningham ICM 2nd delicate cytoplasm within with round, dark nuclei, coarse granular inconspicuous nucleoli, and scanty REG F chromatin, FIGURE 2a&b of 5 3rd a neurofibrillary background that isCASE characteristic features are consistent with olfactory TITLE of neuroblastoma. These Revised neuroblastoma. EMail Line 4-C
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stroma was fibrillar in areas, suggestive a tum, the superiormedial portion of the superior Figure has beenof redrawn and type has been reset. Please check carefully. neurofibrillary matrix (Fig. 3D). These histologic turbinate, and the cribriform plate. Although features are consistent with anJOB: olfactory neuro- the disease typically develops in these locations, 35626 ISSUE: 6-28-07 blastoma, but the differential diagnosis also in- an ectopic origin within the lower nasal cavity and cluded other small, round blue-cell tumors. Immu- paranasal sinuses, as seen in this patient, has nohistochemical staining showed that the tumor been reported.7,8 Histologically, in most cases, was positive for synaptophysin, neuron-specific there are morphologic features of neuroblastoma, enolase, and vimentin, and negative for keratin, with a fibrillary cytoplasmic background of neurodesmin, S-100, and CD99. On the basis of these nal-cell processes and sometimes rosettes of the features, a diagnosis of olfactory neuroblastoma Homer Wright or FlexnerWintersteiner type.9 was made. However, given the patients young age, Olfactory neuroblastomas lack the t(11:22) transthe unusual site of presentation, and the exten- location that is characteristic of Ewings sarcosive osseous invasion, clinical evaluation to rule out ma10,11 and are genetically heterogeneous, disa metastatic neuroblastoma was recommended. tinct from conventional neuroblastoma, but with Olfactory neuroblastoma4-6 is thought to arise some overlapping genetic features.12,13 from basal progenitor cells of the specialized olOlfactory neuroblastomas are classified acfactory mucosa located in the superior nasal sep- cording to the histologic grading system of Hy-
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Figure 4 (facing page). Craniofacial Resection. The craniofacial resection was begun by the neurosurgical team, with a bicoronal skin incision (Panel A); a subgaleal plane was created posterior to the skin incision, and the pericranium was incised, elevated, and reflected anteriorly along with the scalp flap down to the orbital rims. A bifrontal craniotomy was cut through the frontal sinus, exposing the frontal lobe dura (Panel B). The mucosa and the posterior bony wall of the frontal sinus were removed. The dura overlying the cribriform plate was excised, and the olfactory nerve rootlets were divided. This maneuver provided full extradural access to the floor of the anterior cranial fossa, exposing the full extent of the cribriform plate; sagittal and coronal representations of the area to be resected are shown (Panels C and D, respectively). The otolaryngological team then performed a right lateral rhinotomy (Panel E), exposed the nasal bone and the right anterior maxillary wall, retracted the right orbital contents laterally, and dissected posteriorly within the orbit along the lamina papyracea and the orbital roof, exposing and ligating the anterior and posterior ethmoidal arteries. With circumferential exposure around the ethmoid sinuses, bone cuts were then made through the maxilla, along the floor of the orbit and the right nasal bone, isolating the tumor. While the head and neck surgeons protected the orbital contents by retracting laterally and by direct vision, the neurosurgical team connected the bony cut through the floor of the frontal sinus to the cut across the nasal bone. Mucosal attachments were severed, and the specimen, including the inferior turbinate, the cribriform plate, the nasal septum, the anterior maxillary wall with the lacrimal complex, the tumor, and the lamina papyracea, was removed through the rhinotomy incision. Total ethmoidectomies were performed. The defect in the skull base was reconstructed by suturing the pericranial flap to the inferior frontal lobe dura, posterior to the bone cut in the planum sphenoidale. The surgical specimen (Panel F), removed en bloc, included the inferior turbinate, the cribriform plate (at the top), the nasal septum, the anterior maxillary wall with the lacrimal complex, the tumor, and the lamina papyracea.
ams, from 1 (low grade) to 4 (high grade)14; however, with the exception of grade 4 tumors, histologic grading is not reliable for predicting clinical behavior and prognosis.15 Tumors of all histologic grades have the potential to metastasize to the lymph nodes, lung, and bone. Calcifications are considered a low-grade feature. The lesion in this patient was considered to be Hyams grade 1, with low-grade histologic features and extensive calcifications.
body positron-emission tomography (PET) with 18F-fluorodeoxyglucose (fludeoxyglucose F 18) as a tracer to rule out metastatic neuroblastoma from another site. Dr. Curtin: Postoperative CT showed a small amount of tissue with the density of bone that was separated from the roof of the ethmoid sinus, a finding consistent with residual tumor. CT of the chest and abdomen showed no evidence of metastases. Bone scanning and PET showed no abnormalities other than postsurgical changes. Dr. Ebb: These examinations ruled out another Dis cus sion of M a nage men t site for a primary tumor, and the patient was conStaging of Olfactory Neuroblastoma sidered to have Kadish stage B olfactory neuroDr. David H. Ebb: The first report of this entity in the blastoma. English literature was by Schall and Lineback16 here at the Massachusetts Eye and Ear Infirmary in Surgical Management 1951, when they described three cases of primary Dr. William T. Curry: The treatment of olfactory neuintranasal neuroblastoma. The staging system for roblastoma typically combines surgery and radiaolfactory neuroblastoma in current use was subse- tion therapy, on the basis of retrospective studies quently proposed by Kadish and associates17 at the demonstrating improved survival rates when surMassachusetts Eye and Ear Infirmary in 1976. gery is followed by radiation therapy, as compared Kadish stage A tumors involve the nasal cavity with either treatment alone.3 A meta-analysis of alone, stage B tumors involve the nasal cavity in the literature from 1990 to 200018 on outcomes addition to one or more of the paranasal sinuses, among patients who had a minimum of 5 years and stage C tumors are characterized by involve- of follow-up, reported survival rates of 48% with ment of sites beyond the nasal cavity, including the surgery alone, 37% with radiation therapy alone, orbit, base of the skull or intracranial cavity, cervi- and 65% with surgery and radiation therapy comcal lymph nodes, and distant metastases. bined. Since even when the surgical margins In this case, repeated CT of the patients head are clean, postoperative radiation therapy seems and neck was performed to assess the extent of to confer a survival advantage, it appears to be residual tumor, followed by CT of the chest and warranted in all patients, except perhaps those abdomen, radionuclide bone scanning, and whole- who present with small Kadish stage A tumors
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Bicoronal skin incision
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Area to be resected
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COLOR FIGURE
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Figure 6. Photograph of the Patient Taken after Completion of Therapy, Showing an Excellent Cosmetic Result despite the Facial Incision.
Figure 5. CT Images for Radiation Planning of Proton-Beam Therapy. A coronal view of the radiation planning CT scan shows RETAKE 1st AUTHOR Cunningham the ICM distribution of the radiation doses that were deliv2nd REG F FIGURE 5a&b of 5 ered to the tumor bed (Panel A). The innermost red 3rd CASE TITLE line indicates the site of the original tumor Revised volume EMail 4-C (target dose, 54 cobalt Gray Line equivalent [CGE]), SIZE and the Enon ARTIST: the mst H/T H/T pink line includes area at risk for microscopical dis16p6 FILL Combo ease (target dose, 45 CGE). A sagittal view (Panel B) of AUTHOR, PLEASE NOTE: the dose distribution shows the abrupt decrease in Figure has been redrawn and type has been reset. proton radiation atPlease the edge ofcarefully. the treatment field, with check sparing of the optic chiasm (green), pituitary (yellow), hypothalamus (blue), and brain. ISSUE: 6-28-07 JOB: 35626
Because olfactory neuroblastoma typically arises against the cribriform plate and can easily extend through its fenestrae, both the olfactory epithelium and the cribriform plate with the dura overlying it must be removed to ensure complete resection of the tumor. Anterior craniofacial resection, performed by a combined otolaryngological and neurosurgical team, is currently the most common surgical procedure; it allows for en bloc resection
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of the anterior skull base, minimizing risk to the orbital contents, the optic nerves, the internal carotid arteries, and the brain parenchyma. Although this approach has never been examined in a randomized clinical trial, most studies show an improved survival rate with craniofacial resection, as compared with older studies in which a transfacial approach alone was used.19,20 Endoscopic resection has also been proposed for patients with coexisting conditions21 or in combination with an anterior craniotomy,22 as a way of avoiding a facial incision. However, endoscopic case series have included small numbers of patients and short follow-up periods, and we did not elect to use this approach in this patient. The procedure that we recommended for this patient was an anterior craniofacial resection with a lateral rhinotomy. Dr. Derrick T. Lin: The issue of elective treatment of the cervical lymph nodes in olfactory neuroblastoma is controversial. Metastases to cervical lymph nodes are present in 15 to 30% of patients at presentation,23 and they develop later in another 17 to 33% of patients; thus, some institutions electively treat the neck with radiation therapy in the immediate postoperative period.24 It is not clear that prophylactic neck irradiation alters the natural history of the disease or adds a survival benefit.25 Thus, we do not treat the uninvolved portion of the neck but, rather, perform salvage neck dissection in patients in whom cervical metastases develop. This patient had no evidence of involvement of the cervical lymph nodes, and we did not think that prophylactic treatment of the cervical nodes was warranted.
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Dr. Curry: An anterior craniofacial resection through a bifrontal craniotomy (Fig. 4A, and see Fig. 1 of the Supplementary Appendix, available with the full text of this article at www.nejm. org) combined with a lateral rhinotomy was performed by the neurosurgery and otolaryngology teams. An en bloc resection of the tumor (Fig. 4B), including the cribriform plate and the overlying dura, the right inferior turbinate, the nasal septum, the right anterior maxillary wall with the lacrimal complex, the tumor, and the right lamina papyracea, was performed. Dr. Faquin: The craniofacial resection showed an olfactory neuroblastoma near the region of the nasolacrimal duct extending into the deep soft tissue of the ethmoid sinus and invading bone. Separately submitted margins were negative for tumor.
Radiation Therapy
Dr. Torunn I. Yock: Radiation therapy can be used both after surgical resection of olfactory neuroblastoma, to maximize local control and diseasefree survival,18 and for tumors that are deemed unresectable.26 Radiation doses in the preoperative or postoperative setting range from 50 to 60 Gy, whereas definitive radiation therapy for gross disease requires doses ranging from 60 to 70 Gy. Although olfactory neuroblastoma is a radiosensitive tumor, radiation therapy alone is inadequate for cure in most cases.27 We chose 54 cobalt Gray equivalent to maximize local control in this patient and minimize side effects. Even though radiation therapy clearly improves local control and the rate of disease-free survival, it has the potential for serious side effects, including blindness, endocrine deficits, and damage to irradiated brain. The use of radiation therapy A nat omic a l Di agnosis has even greater implications in children than in adults because of the greater risk of a second can- Olfactory neuroblastoma, grade 1 of 4, with excer in children and the detrimental effects of radia- tensive calcification and invasion of bone. tion on developing tissues. Modern techniques of No potential conflict of interest relevant to this article was rethree-dimensional CT-planned and computer- ported.
References 1. Case Records of the Massachusetts General Hospital (Case 14-1995). N Engl J Med 1995;332:1285-91. 2. Knott PD, Gannon FH, Thompson LDR. Mesenchymal chondrosarcoma of the sinonasal tract: a clinicopathologic study of 13 cases with a review of the literature. Laryngoscope 2003;113:783-90. 3. Broich G, Pagliari A, Ottaviani F. Es-
assisted delivery of radiation doses, including intensity-modulated radiation therapy (IMRT), help to reduce the risk of severe side effects. However, proton radiation therapy is an improvement over IMRT, because the proton beam can be stopped at a specified depth in tissue, thus sparing normal tissue exposure to radiation as the beam exits.28-30 For this reason, we elected to treat this patient with protons (Fig. 5). This approach virtually eliminates the risks of blindness, neurologic defects, and endocrine deficiency. However, the patient does remain at risk for diminished growth of his nose and there is also a small lifetime risk of a radiation-induced cancer in the radiation field. Dr. Cunningham: On the basis of this patients Kadish stage and the initial treatment protocol, his chance of disease-free survival is estimated to be approximately 85% at 5 years.31 To date, there are no epidemiologic, molecular, or pathological features that are of additional prognostic value. Relapses are typically local or regional, and there may be a long interval between treatment and relapse, with a mean of 6 years; the longest reported time to regional relapse is 10 years.31 Because of this risk of late relapse, as well as the potential for radiation-induced secondary cancers, prolonged follow-up is necessary for this child. Dr. Yock: The patient completed therapy a year and a half ago, and he has had an excellent cosmetic result (Fig. 6). He has anosmia, occasional excessive tearing of the eyes, and nasal crusting requiring endoscopic dbridement approximately every 3 months. He is being followed with both CT and MRI studies approximately every 6 months.
thesioneuroblastoma: a general review of the cases published since the discovery of the tumour in 1924. Anticancer Res 1997; 17:2683-706. 4. McCormack LJ, Harris HE. Neurogenic tumors of the nasal fossa. JAMA 1955;157: 318-21. 5. Theilgaard SA, Buchwald C, Ingeholm P, Kornum Larsen S, Eriksen JG, Sand
Hansen H. Esthesioneuroblastoma: a Danish demographic study of 40 patients registered between 1978 and 2000. Acta Otolaryngol 2003;123:433-9. 6. Berger L, Luc G, Rachard D. Lesthsi oneuropithliome olfactif. Bull Assoc Franc Etude Cancer 1924;13:410-21. 7. Chacko G, Ghandi SM, Chandy MJ. Primary sphenoid and petrous apex esthe-
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RJ, Morris CG, Mendenhall WM. Radiation therapy for esthesioneuroblastoma: rationale for elective neck irradiation. Head Neck 2003;25:529-34. 25. Beitler JJ, Fass DE, Brenner HA, et al. Esthesioneuroblastoma: is there a role for elective neck treatment? Head Neck 1991; 13:321-6. 26. Fitzek MM, Thornton AF, Varvares M, et al. Neuroendocrine tumors of the sinonasal tract: results of a prospective study incorporating chemotherapy, surgery, and combined proton-photon radiotherapy. Cancer 2002;94:2623-34. 27. Gruber G, Laedrach K, Baumert B, Caversaccio M, Raveh J, Greiner R. Esthesioneuroblastoma: irradiation alone and surgery alone are not enough. Int J Radiat Oncol Biol Phys 2002;54:486-91. 28. Yock TI, Tarbell NJ. Technology insight: proton beam radiotherapy for treatment in pediatric brain tumors. Nat Clin Pract Oncol 2004;1:97-103. 29. Case Records of the Massachusetts General Hospital (Case 4-2004). N Engl J Med 2004;350:494-502. 30. Case Records of the Massachusetts General Hospital (Case 5-2006). N Engl J Med 2006;354:741-8. 31. Loy AH, Reibel JF, Read PW, et al. Esthesioneuroblastoma: continued follow-up of a single institutions experience. Arch Otolaryngol Head Neck Surg 2006;132:1348.
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Lantern Slides Updated: Complete PowerPoint Slide Sets from the Clinicopathological Conferences
Any reader of the Journal who uses the Case Records of the Massachusetts General Hospital as a teaching exercise or reference material is now eligible to receive a complete set of PowerPoint slides, including digital images, with identifying legends, shown at the live Clinicopathological Conference (CPC) that is the basis of the Case Record. This slide set contains all of the images from the CPC, not only those published in the Journal. Radiographic, neurologic, and cardiac studies, gross specimens, and photomicrographs, as well as unpublished text slides, tables, and diagrams, are included. Every year 40 sets are produced, averaging 50-60 slides per set. Each set is supplied on a compact disc and is mailed to coincide with the publication of the Case Record. The cost of an annual subscription is $600, or individual sets may be purchased for $50 each. Application forms for the current subscription year, which began in January, may be obtained from the Lantern Slides Service, Department of Pathology, Massachusetts General Hospital, Boston, MA 02114 (telephone 617-726-2974) or e-mail Pathphotoslides@partners.org.
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