Disclaimer: The information contained within the Grand Rounds Archive is intended for use by doctors and other health care professionals. These documents were prepared by resident physicians for presentation and discussion at a conference held at Baylor College of Medicine in Houston, Texas. No guarantees are made with respect to accuracy or timeliness of this material. This material should not be used as a basis for treatment decisions, and is not a substitute for professional consultation and/or peer-reviewed medical literature. Inverted Schneiderian Papilloma History The first case of inverted Schneiderian papilloma described in the literature was by Ward in 1854. The following year Billroth described two cases. One of the patients which he reported was noted to have multiple recurrences. The first case which was published in the American literature was not until 1896 by Dickerman. In 1897 Wright emphasized the tendency of inverted Schneiderian papilloma to recur. Ringertz in 1938 is credited with describing the histologic characteristic of inversion of this lesion through the surface epithelium. He felt that inverted Schneiderian papillomas arose from nasal polyps. In 1971, Hyams published a series of 315 cases of nasal papillomas from the Armed Forces of Institute Pathology, which helped clarify many aspects of inverted Schneiderian papilloma. In 1977, Dr. Sessions described the technique for medial maxillectomy with en bloc ethmoidectomy. In 1984, Drs. Sachs and Conley described the use of the midface degloving approach for inverted Schneiderian papillomas. In 1992, Drs. Waitz and Wigand described the use of nasal endoscopy for removal of inverted Schneiderian papilloma. Epidemiology Inverted Schneiderian papillomas are thought to represent between 0.4 and 5% of primary nasal tumors. In a study by Buchwald et al, in 1995, he reported an incidence of 0.52 cases per 100,000 inhabitants per year in Copenhagen, Denmark. Like other authors, he noted an increasing incidence of these lesions in recent years. Inverted Schneiderian papilloma occurs about three times more commonly in men than in women, and is more common in Caucasian Americans than African Americans. These lesions typically occur in the 6th to 7th decades but have been reported in patients between age 6 and 90. Etiology While the etiology of inverted Schneiderian papilloma is unknown, and has been debated in the literature for many years, recent research suggests that human papilloma virus plays an important role in its pathogenesis. Early investigators favored an association between nasal polyposis and inverted Schneiderian papilloma. This is despite the fact that nasal polyps are common and inverted Schneiderian papillomas are rare, and that nasal polyps are typically bilateral, while inverted Schneiderian papillomas occur unilaterally 90% of the time. Debate persisted until Hyams report in 1971. In his review of 315 patients only 3 had a history of nasal polyps or allergy symptoms. Other proposed risk factors for inverted Schneiderian papilloma include chronic sinusitis, cigarette smoking, and working in the steel industry. Viruses where initially implicated because of their well known tendency to produce papillomas elsewhere in the body. The high rate of recurrence and tendency to involve large portions of the mucosa also supported a viral etiology. Other authors including Hyams, doubted a viral etiology. They argued inverted Schneiderian papilloma is uncommon in children, and children tend to be susceptible to most viruses, making a viral etiology is unlikely. Human papilloma virus is a DNA virus implicated in the development of warts, laryngeal papillomatosis, as well as cervical, vulvar, and penile carcinoma. Over 45 types of human papilloma viruses have been isolated. Human papilloma virus, types 6 and 11, have been isolated from both genital and laryngeal papillomas. In 1987, Respler et al, reported the presence of human papilloma virus type 11 DNA in an inverted Schneiderian papilloma by southern blot hybridization. This was significant since previous attempts to identify viral particles in inverted Schneiderian papillomas were unsuccessful using electron microscopy and immunocytochemical staining techniques. The following year, in 1988, Weber et al, reported 21 cases of inverted Schneiderian papilloma and found 76% of the specimens to contain human papilloma virus, types 6b and 11 DNA sequences using in-situ hybridization. Of the four patients who recurred, all were human papilloma virus positive. Respler suggested that similar to laryngeal papillomas, nasal inverted Schneiderian papilloma may be spread intrapartum. Fu et al, reported in 1995, that 8 of 9 patients with inverted Schneiderian papilloma had a history of anogenital warts, suggesting autoinoculation as a likely mode of transmission. Site of Origin Inverted Schneiderian papillomas typically arise from the lateral nasal wall in the area of the middle meatus and middle turbinate. According to Phillips, et al in 1990, 82% of inverted Schneiderian papillomas involve the nasal cavity and sinuses, 13% involve the nasal cavity alone, and 5% only involve the sinuses. In Vrabec's series of 101 cases, 69 involved the maxillary sinus, 41 involved the ethmoids, 27 involved the frontal sinus and the sphenoid was involved in 5 cases. According to Myers et al in 1990, 8% of the lesions may be from the nasal septum and 4% may be bilateral. Inverted Schneiderian papilloma has also been reported in the oropharynx, nasopharynx, posterior pharyngeal wall, the lacrimal sac and within a branchial cleft cyst. Bone erosion is most commonly seen in the lateral nasal wall, medial orbital wall, and anterior wall of the maxillary sinus. Presenting symptoms Patients with inverted Schneiderian papilloma typically present to an otolaryngologist complaining of a history or unilateral nasal obstruction for greater than one year, a history of "polyps", and a history of multiple surgical procedures.In Vrabec's series 87% of patients complained of nasal obstruction, predominately unilateral, while 31% complained of nasal drainage or facial pain, 17% had epistaxis or anosmia, 14% had frontal headache, 14% had sinusitis, 7% had epiphora. Other symptoms he reported include foul taste in mouth, otalgia, numbness, neck mass, nasal vestibule mass, hoarseness, and tinnitus. Other symptoms may be related to the anatomic location of the lesion. Patients with sphenoid sinus involvement often complain of persistent deep-seated frontoparietal or occipital headaches radiating down the neck or deep behind the eye. With respect to the duration of symptoms, Benninger in 1995 reported that 65% of patients had symptoms for greater than 1 year and 30% had symptoms for greater than 3 years. Vrabec noted one patient with symptoms for 45 years prior to presentation. According to Phillips, et al, in 1990, 58-63% of patients with inverted Schneiderian papilloma had a history of multiple surgical procedures in the past, most commonly nasal "polypectomies." Physical findings Physical examination may reveal a bulky polyp-like mass present in the nasal cavity, typically in the middle meatus. Evidence of erosion of the lateral nasal wall may be noted on sinus endocopy. The nasal cavity may also appear inflamed with purulent exudate present from superimposed sinusitis caused by anatomic obstruction of the ostiomeatal complex. More infrequently, patients may present with proptosis. Diagnosis Congenital, infectious, inflammatory, neoplastic, and traumatic disorders may also present with unilateral nasal obstruction. With the exception of neoplastic and traumatic lesions, the majority of these disorders most commonly present with bilateral nasal obstruction. When a patient presents with unilateral nasal obstruction, one should pursue an aggressive diagnostic work-up. No symptom, physical finding, or radiologic abnormality heralds inverted Schneiderian papilloma or rules out the presence of malignancy. Clinicians must maintain a high index of suspicion, especially in patients with unilateral nasal obstruction, patients with evidence of bone erosion on nasal exam, and in patients whose clinical course does not improve with standard therapies. The diagnosis can only be made by histopathologic examination. Nasal endoscopy should be performed preoperatively in patients with unilateral nasal obstruction and biopsies should be taken if suspicious lesions are found. When performing routine nasal "polypectomies", it is important to send all tissue for pathologic examination so that the diagnosis of inverted Schneiderian papilloma is not missed. Pathology On gross examination, inverted Schneiderian papillomas appear thickened and granular with a polypoid appearance. They appear more vascular then nasal polyps and may range in color from yellow to red to gray. Histologic examination reveals hyperplastic epithelium invaginating into the fibrovascular connective tissue stroma. Initially, the basal layer of respiratory mucosa is involved with preservation of the ciliated cells. With increasing proliferation, these vertically arranged cells are lost and appear intermediate between columnar cells and squamous cells. Cellular atypia, and mitosis may be seen. It is believed that inverted Schneiderian papillomas arise from proliferation of reserve cells of the mucosa. The predominant cell type is epidermoid. Other variations of inverted Schneiderian papillomas include fungiform papillomas of the septum, cylindrical cell papillomas which appear similar with the addition of goblet cells, and oncocytic papilloma which may be confused with adenocarcinoma by pathologists. Radiology After the diagnosis of inverted Schneiderian papilloma has been confirmed histologically, radiographs should be obtained to assist in management of the lesions. Plain films have a limited role in the diagnosis and management of inverted Schneiderian papilloma but typically show unilateral opacification of the sinuses and nasal airway. According to Buchwald et al in 1990, plain films do not assist the surgeons choice of surgical procedure, and are of no value in patients status-post surgical intervention. Computed tomography is the imaging modality of choice in inverted Schneiderian papilloma. Computed tomography can be used define the anatomy for surgical planning and determine the extent of bone erosion. Inverted Schneiderian papillomas appear homogenous and do not typically enhance with contrast administration. This may be useful in distinguishing inverted Schneiderian papilloma from esthesioneuroblastomas which do enhance. Previous surgeries and other local processes may alter the anatomy and make interpretation difficult. Computed tomography also has a role in determining which lesions can be managed conservatively. Despite their value, there are no pathognomonic findings on CT scan suggestive of a diagnosis of inverted Schneiderian papilloma. On CT, inverted Schneiderian papillomas may cause opacification of the sinuses by obstruction or directed extension. Advanced tumors may be noted to spread to adjacent paranasal sinuses, the orbit, the pterygopalatine fossa, or they may extend intracranially. Bone erosion demonstrated on CT scan may be caused by pressure atrophy or pseudoinvasion rather than frank infiltration, and should not be interpreted as representing malignancy. Bone sclerosis can be caused by superimposed chronic sinusitis. Phillips, et al, in 1990 noted that plain films demonstrate bone erosion in 12% of cases; this is in contrast to first generation coronal CT scans which show bone erosion in 52% of cases, and more current, hi-resolution CT scans which reveal bone erosion 75% of the time. A retrospective review of 10 inverted Schneiderian papillomas imaged with magnetic resonance imaging by Yousem et al, in 1992 failed to distinguish inverted Schneiderian papillomas from other intranasal lesions. Stankiewicz et al in 1993 found MRI helpful in distinguishing the extent of inverted papilloma, which appears isointense on T2 weighted images, from sinusitis which appears hyperintense on T2 weighted images. According to Momose et al in 1980, carotid angiography, ultrasonography and radionuclide scanning add very little additional information. Treatment Much of the literature on inverted Schneiderian papillomas deals with the complicated issue of management. According to Kramer and Som the treatment of choice in 1935 was total extirpation using diathermy followed by radiation therapy. They stated that intranasal removal alone is inadequate as were many of the more radical procedures of the day. Today's literature focuses on conservative therapy versus traditional aggressive procedures. Due to the low incidence of this lesion, the literature is mainly composed of small retrospective series, without good anatomic staging, which make statistical comparisons difficult. It is clear, in patients who are medically fit for general anesthesia, surgery is the treatment of choice. Since recurrence is a direct reflection of inadequate resection, the ideal surgical procedure completely removes the lesion. Other considerations when choosing a surgical approach, include obtaining adequate exposure, allowing for an unobstructed view for postoperative examination, and minimizing cosmetic deformity and functional limitation. Conservative procedures are described in the literature and may be indicated in properly selected patients. Conservative approaches include the intranasal or transantral sphenoethmoidectomy, which is mostly of historical interest due to poor visualization and unacceptably high recurrence rates; transnasal-endoscopic approaches; and the use of KTP/532 laser in combination with an endoscopic approach. Standard approaches for a inverted Schneiderian papilloma localized to the lateral nasal wall include medial maxillectomy via the lateral rhinotomy incision, and medial maxillectomy via the midface degloving approach. Septal translocation has also described as a possible approach. More extensive lesions will require a larger procedure which may include medial maxillectomy with en bloc ethmoidectomy as described by Sessions; anterior craniofacial resection; or a skull base approach. For lesions involving the sphenoid or frontal sinus, Calcaterra et al in 1980, recommended opening the sinus and curetting out all of the mucosa. Radiation therapy may be beneficial in recurrent and aggressive lesions and is indicated in inverted Schneiderian papillomas associated with squamous cell carcinoma. Conservative Therapy Several authors including Dolgin et al in 1992 advocate a conservative approach, saving other techniques for extensive or recurrent lesions. According to Lawson et al, in 1983, conservative excision may be indicated in patients with lesions localized to the middle or inferior turbinate and their corresponding meatus, with limited extension to the ethmoid labyrinth and maxillary sinus. They state that conservative procedures are contraindicated in patients who have had a recurrence. This is in contrast to Waitz and Wigand who in 1992, advocated endoscopic excision of lesions involving the sphenoid sinus, anterior and posterior ethmoids, nasofrontal duct, as well as recurrent lesions. They recommend sterilizing the underlying bone using a drill with a diamond burr. According to Waitz and Wigand, endoscopic techniques are only contraindicated when tumors cannot be sufficiently visualized endoscopically, with invasion of extranasal tissues, with a history of previous extranasal surgeries, and in cases with malignant transformation. The advantage of endoscopic removal of inverted papilloma is that limited lesions can be completely and safely removed without external incisions or cosmetic deformity. Other advantages include shorter hospitalization, less blood loss, and improved visualization of the tumor. Disadvantages of endoscopic removal include the lack of large case series with long term follow-up to support this approach, and possible increased risk of recurrence if this procedure is performed by inexperienced sinus surgeons. In a paper from June 1995, Dr. Levine recommended the use of the KTP/532 laser for excision of well-circumscribed lesions limited to the lateral nasal wall without evidence of carcinoma. The laser has the advantage of keeping the field dry, does not require an external incision, may reduce hospital stays, and expedite return to normal activity. Of the 13 patients with well circumscribed lesions, 12 have not had recurrence during 6 to 18 months of follow-up. The one recurrent lesion was removed under local anesthesia using the laser. It is interesting to note that the KTP/532 laser was also used under local anesthesia in two patients with extensive lesions who were not candidates for general anesthesia. Both patients had significant palliation for a period of about 18 months. While the follow-up in this series is not adequate to judge the efficacy of this technique, it is evident that there may be a role for laser excision of inverted papilloma in patients who are not candidates for general anesthesia. Medial Maxillectomy Medial maxillectomy is the standard procedure for removal of lesions limited to the lateral nasal wall. Medial maxillectomy allows for the removal of the lateral nasal wall en bloc, instead of in a piecemeal fashion. Exposure can be attained through lateral rhinotomy or midface degloving approach. After the proper exposure is achieved the anterior wall of the maxillary sinus is removed with care to preserve the infraorbital nerve. The extent of the lesion is determined and biopsies may be taken for frozen section examination. Bone cuts are made using a chisel or sagittal saw from the superior nasal aperture laterally below the orbital rim and then inferiorly near the infraorbital foramen to meet a second horizontal cut at the level of the floor of the nose. Posteriorly directed osteotomies are performed along the floor of the nose and top of the middle meatus. Intranasal cuts are completed using mayo scissors. Exposed ethmoid cells are fully opened and residual turbinate tissue is removed. The cavity is then packed. Medial Maxillectomy with En Bloc Ethmoidectomy Tumors which involve the ethmoid air cells in addition to the maxillary sinus and lateral nasal wall can be removed by medial maxillectomy with en bloc ethmoidectomy as described by Sessions in 1977. Patients undergoing this procedure should undergo preoperative evaluation by an ophthalmologist. Medial maxillectomy with en bloc ethmoidectomy requires separation of the medial canthal tendon and marsupilazation of the lacrimal sac. An attempt to restore the integrity of the medial canthal ligament and lacrimal drainage system should be undertaken at the completion of the procedure. This diagram outlines the bone which is removed which includes portions of the ethmoid, palatine, and lacrimal bones as well as the medial wall of the maxilla. Midface degloving Medial maxillectomy and medial maxillectomy with en bloc ethmoidectomy can be performed through a midface degloving approach. The midface degloving approach provides bilateral exposure to the lateral nasal wall without external incisions. This approach also allows exposure to the septum, nasal cavity, ethmoid, maxillary, and sphenoid sinuses as well as the nasopharynx and clivus. The approach is carried out using a columellar transfixion incision, and intercartilaginous incisions between the upper lateral cartilage and the lateral crus of the alar cartilage which effectively separate the nasal tip from the nasal dorsum. The incision is then extended around the piriform margin and nasal floor, passing the knife through the epithelium, soft tissue and periosteum. A sublabial incision is then carried out across the midline extending to just above the first molars. After exposure is achieved, a medial maxillectomy can be performed. Lateral rhinotomy Lateral rhinotomy used to be the standard incision used for medial maxillectomy and medial maxillectomy with en bloc ethmoidectomy until the midface degloving approach was devised. Advantages of the lateral rhinotomy approach over midface degloving is that it allows better access the to the anterior ethmoid and frontal sinuses, and may be useful when there is soft tissue involvement overlying the nasal dorsum. The major shortcoming of the lateral rhinotomy approach is the presence of an external scar in the midface. However, when properly placed, it may be cosmetically acceptable. The lateral rhinotomy approach starts by placing an incision parallel to the lower border of the eyebrow, and turning downward between the medial canthus and dorsum of the nose, where the incision is broken up with a W-plasty. The incision continues into the nasofacial sulcus and around the base of the nasal vestibule where it is extended internally to the piriform aperture. In instances which require more exposure, the lip may be split. Periosteal elevators are used to raise the soft tissue from the maxilla to the nasal bone and a medial maxillectomy or medial maxillectomy with en bloc ethmoidectomy can be performed. Radiation When planning treatment for inverted schneiderian papilloma it is important to remember that it is a benign process. According to Mendenhall, et al. in 1985, radiation is indicated as an adjunct to surgery in cases of inverted Schneiderian papilloma with malignant transformation. Based on their experience with five patients, Mendenhall et al suggest that radiation may be effective in controlling "advanced biologically aggressive" lesions, unresectable lesions, and incompletely resected lesions. Lesions with multiple recurrences may also benefit. Complications Complications related to the natural history of inverted Schneiderian papillomas, include invasion of the orbit and skull base. Sphenoid sinus lesions may cause impairment in the function of cranial nerves III, IV and VI and orbital apex syndrome may occur. Surgical complications include exposed dura, CSF leak, meningitis, diplopia, intermittent epiphora, acute dacryocystitis, blepharitis, epistaxis, crusting, dental anesthesia, oroantral fistula, conductive hearing loss, and mucocele formation. If the medial canthal ligament is disrupted and not repaired, hypertelorism may result. Additionally, the midface degloving approach has been associated with nasal vestibular stenosis and hemipalatal anesthesia. Radiation treatment is associated with development of osteoradionecrosis and radiation dermatitis. There are also reports in the literature linking radiation therapy with malignant transformation of inverted papilloma. Recurrence Recurrence rates reported in the literature vary between 3-73% according to Benninger et al in 1991. Due to the retrospective nature of the literature and small number of cases, it is difficult to draw conclusions on which procedure yields the lowest recurrence rate. Studies can be found in the literature to support or detract from any method over another. Selection of the procedure which completely removes the lesion, is essential to reduce the incidence of recurrence. The best procedure can only be determined by the characteristics of a particular patient's lesion and the surgeon's judgment. The median time to recurrence was 5 years with a range of 6 months to 13 years according to Buchwald et al in 1995. Favored sites of recurrence include the sphenoid sinus, posterior and supraorbital ethmoid cells, the frontal sinus, and along the cribriform plate. Factors correlated with recurrence include inadequate surgical resection, bulky lesions, and the presence of cellular atypia or mucin producing cells on histologic examination. Phillips et al in 1990 reported that patients with frontal sinus involvement recurred in 37.5% of cases, maxillary sinus involvement 25%, ethmoid involvement 21%, sphenoid sinus 20% and no sinus 10%. An interesting study by Beck et al in 1995, examined pathology specimens from 32 patients with inverted Schneiderian papilloma using the polymerase chain reaction to identify human papillomavirus. 13/15 patients in which human papillomavirus was identified, had recurrence. None of the 10 patients who where human papillomavirus negative recurred. These findings were statistically significant suggesting that it may be possible to select patients with less aggressive disease who could be treated with more conservative surgery. Malignant transformation The ability of inverted Schneiderian papilloma to undergo malignant transformation has been recognized since 1897. The incidence of malignancy is reported to be between 5 and 15 percent and will vary based on the referral pattern for a particular institution. Symptoms can not reliably distinguish malignant lesions from benign ones. Number of recurrences is not correlated with the development of malignancy. In a study of 51 inverted Schneiderian papillomas, Lesperance et al in 1995 found 14 squamous cell carcinomas. They attributed their high rate of malignancy to the referral pattern of their institution. Of the 14 squamous cell carcinomas, 8 were metachronous and 6 were synchronous. Mean onset for metachronous lesions was 63 months with a range of 6 months to 13 years. Of their 14 cases the orbit was involved in 8 and intracranial extension was present in 6. According to Lesperance, wide surgical excision is indicated with postoperative radiation therapy for patients with advanced lesions. The disease free survival rate for lesions limited to the nasal cavity and sinuses was 57% compared to 14% for lesions extending beyond the sinuses and unresectable lesions. Adenocarcinoma and small cell carcinomas within inverted Schneiderian papillomas have been reported but occur infrequently. Summary In summary, to diagnose inverted Schneiderian papilloma, clinicians must maintain a high index of suspicion particularly in patients with unilateral nasal obstruction, and unilateral sinusitis refractory to medical management. All "polyps" which are removed during routine intranasal surgery should be sent for histopathologic examination. Inverted Schneiderian papillomas are benign lesions which tend to recur. The can invade bone and surrounding structures and are associated with malignant transformation in 5-15% of cases. Treatment requires complete surgical excision. Conservative approaches such as endoscopic removal should only be used in properly selected patients by experienced surgeons. Long-term follow-up includes frequent sinus endoscopy and biopsies if suspicious areas exist or computed tomography. The role for lasers and the presence of HPV by polymerase chain reaction in routine clinical settings has yet to be defined but seems promising. Case Presentation A 41 year-old male presented to the Houston Veteran's Affairs Medical Center complaining of a 9 month history of left-sided nasal obstruction. The patient had previously been followed by a private physician for nasal polyps. Endoscopic examination in clinic revealed a light yellow, glistening, polypoid mass filling the nasal cavity on the left. A biopsy revealed inverted Schneiderian papilloma. Coronal, non-contrast enhanced, computed tomography of the paranasal sinuses revealed an extensive left-sided lesion involving the nasal cavity, lateral nasal wall, maxillary, ethmoid, and frontal sinuses with evidence of bone erosion. The patient was admitted to the hospital, and underwent a left medial maxillectomy via the midface degloving approach. The lesion diffusely involved the ethmoid sinuses and eroded the lamina papyrecea. The frontal sinus was entered through a separate left frontal sinusotomy and the mucosa was removed. The patient's postoperative course was uncomplicated, and he was discharged home on the third postoperative day with follow-up in the Otolaryngology clinic. Bibliography Astor FC, Donegan JO, Gluckman JL. Unusual presentations of inverting papilloma. Head Neck Surgery 1985; 7:243-245. Batsakis JG. Nasal (Schneiderian) Papillomas. Ann Otol Rhinol Laryngol 1981; 90:190-191. Batsakis JG. 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Price JC, Holliday MJ, Johns ME, Richtmeier WJ, Mattox DE. The versatile midface degloving approach. Laryngoscope 1988; 98:291-298. Respler DS, John A, Pater A. Isolation and characterization of papilloma virus DNA from nasal inverting papillomas. Ann Otol Rhinol Laryngol 1987; 2:170-172. Sachs ME, Conley J, Rabuzzi DD, Blaugrund S, Price JC. Degloving approach for total excision of inverted papilloma. Laryngoscope 1984; 94:1595-1598. Sessions RB, Larson DL. En bloc ethmoidectomy and medial maxillectomy. Arch Otolaryngol 1977; 103:195-202. Sim DW. Co-existent inverted papilloma and squamous cell carcinoma of the nasal septum. J Laryngol Otol 1989; 103:774-775. Skolnick EM, Loewy A. Friedman JE. Inverted papilloma of the nasal cavity. Arch Otolaryngol 1966; 84:61-67. Sofferman RA. The septal translocation procedure: an alternative to lateral rhinotomy. Otolaryngol Head Neck Surg 1988; 98:18-25. Som PM, Shapiro MD, Biller HF, Sasaki C, Lawson W. 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Arch Otolaryngol 1985; 111:806-811. Yousem DM, Fellows DW, Kennedy DW, Bolger WE, Kashima H, Zinreich SJ. Inverted Schneiderian papilloma: evaluation with MR imaging. Radiology 1992;185(2):501-5. Grand Rounds Archive | Department Home page BCM Public | BCM Intranet | Privacy Notices | Contact BCM | BCM Site Map | ©2001-2006 Baylor College of Medicine
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