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This nerve is maintained but sometimes alterations occur exposed in the sphenopalatine fossa by producing a clinical condition called vaso- removing the posterior wall of the maxillary motor rhinitis cheap 20 mg nolvadex amex. Psychogenic instability and palatine ganglion to the opening of the emotional conditions buy nolvadex 20 mg, hormonal changes as pterygoid canal and is sectioned purchase genuine nolvadex on line. A antihypertensive agents, local decongestants, polyp is pedunculated hypertrophied oede- and antidepressants are some such factors. Polypi commonly arise from the ethmoid Clinical Features labyrinth and sometimes may arise from the The disease is more common in females than maxillary antrum. When this projects males particularly during adolescent years of posteriorly in the nasopharynx it is called an life. These Aetiology symptoms may be associated with sneezing, Aetiology of polyposis is uncertain. Various headache, facial pains and generalised views have been put forward to explain the fatigue. The conjunctivae are not alteration in the polysaccharides of the usually involved. Vasomotor Imbalance: Polyposis may occur this water-logged mucosa leads to polyp due to an imbalance between the sympa- formation. Role of allergy: Allergic reactions of the nasal tissues to infection and the allergy itself mucosa produce vasodilatation and may be to bacterial proteins, hence it is increased permeability of the vessels as a contended that both allergy and infection result of which fluid moves out of the are in aetiological factors. This oede- matous mucosa subsequently presents as Macroscopically, the polypi appear as pale, a polypoidal mass. Histologically the polypoi- ing infection gives rise to perilymphangitis dal tissue shows fibrillar stroma with wide and periphlebitis resulting in poor absorp- spaces filled with intercellular fluid in the tion of tissue fluid in the mucosa and thus submucosa. The blood vessels and nerve fibres Nasal Allergy, Vasomotor Rhinitis and Nasal Polyposis 205 are scanty. Epithelium may be of the ciliated antihistamines, decongestants and/or anti- columnar type or may have undergone biotics. This procedure The main symptoms are nasal obstruction, helps to preserve the normal function hyposmia and postnasal drip. These are usually bilateral are removed under general or local and multiple and are seen in all ages but are anaesthesia with the help of a nasal more commonly in adults. Antrochoanal Postoperatively, antihistaminics are given polyp arising from the antrum goes towards for a prolonged period and lavage of the the posterior choana and is seen on posterior antrum if needed may be done to clear the rhinoscopy as a pale, polypoidal mass in the infection as recurrence is common. The soft palate is sometimes ethmoidal polypi are dealt with by perform- displaced downwards and the polyp may ing ethmoidectomy either via an endoscopic or an present in the oropharynx. This condition is mostly unilateral and diseased mucosa (ethmoidectomy) can be and the polyp is usually single. Antrochoanal done either by the intranasal route, external polyps occur in the young, commonly during approach or through the transantral approach. Ethmoidectomy should be done carefully to X-ray examination of the paranasal sinuses avoid damage to the orbital contents, optic helps in diagnosis. Treatment of Antrochoanal Polyp Polypectomy is done either using a long-bladed nasal Treatment of Nasal Polyp speculum and visualising the pedicle under A. Medical Treatment: This involves the use endoscopic vision, which is then grasped and of local and systemic corticosteroids, avulsed, or alternatively the soft palate is 206 Textbook of Ear, Nose and Throat Diseases retracted and the polyp is grasped, avulsed the region of the middle meatus may and delivered orally. This is In the postoperative period, antrum lavage usually single and has an opaque and may be necessary to clear the antrum of fleshy look. Meningocele: A prolongation of meninges polypi were treated by the Caldwell-Luc may occur in the nasal cavity and appear approach previously and that the diseased as soft, cystic polyp-like swelling parti- mucosa of the antrum was removed along cularly in young children. Hence, it is with the polyp but this procedure is now always advisable to aspirate a polypoidal largely out of favor. Malignancy of nose: A malignant lesion in A variety of lesions may present as polypoidal the nose (carcinomatous, sarcomatous or masses in the nose. Ethmoidal and antro- melanotic) may present as a polypoidal choanal polyps have already been described. Sometimes poly- turbinate may sometimes be mistaken for poidal changes are associated features of a polyp. Therefore, all polyps removed sensitive to touch as compared to an from the nose should be examined ethmoidal polyp and is firm to feel unlike histologically. Nasopharyngeal angiofibroma: Nasopharyn- cannot be passed around the turbinate as geal angiofibroma (Figs 36. Rhinosporiodiosis: This fungal infection of history of epistaxis in an adolescent male the nose produces a bleeding polypoidal with a lobulated mass in the nasopharynx mass in the nose usually arising from indicates a nasopharyngeal lesion rather the septum and is strawberry like in than antrochoanal polyp. It is common in people living prominent vessels are visible on the in coastal areas of India. A malformation consisting of a tumour-like careful examination reveals its site of growth of tissue. Transitional cell or squamous papilloma: according to size and location and but it Papilloma arising from the lateral wall in rarely becomes malignant. It is are isolated which include Pneumococcus, usually the maxillary sinus which gets Streptococcus, Staphylococcus, Haemophilus involved. The local symptoms depend upon the sinus The acute inflammation of the sinus mucosa involved, the most important feature being commonly follows an attack of acute rhinitis pain. In maxillary sinusitis the pain is felt in as in common cold or influenza when the the cheeks below the eyes, it may be referred bacteria invade as secondary organisms. Pain is aggravated on follow dental infections, particularly of the stooping or coughing. The sinus may get In ethmoiditis, the pain is localised over the infected after trauma or through a blood- nasal bridge, inner canthus and behind the borne infection. Other contributory factors which the forehead and the patient complains of play a role in the development of sinusitis headache. The pain is severe in the morning include a deflected nasal septum, nasal polypi and gradually subsides towards noon as the and other benign tumours of the nose. Patients infected material gets drained out from the of chronic suppurative lung disease constantly sinus. Inflamma- Sinusitis 209 tion of more than one sinus is marked by pain Tenderness on applying pressure over the over all the sinuses. Presence of mucopus Signs in the nose is suggestive of sinus infection and its position determines the sinus involved. Usually no external signs are present except Posterior rhinoscopy also reveals the in fulminating cases where, there may be presence of mucopus and congestion. The X-ray examination of paranasal sinuses, occipitomental view (Water’s view), is helpful in revealing the condition of the sinuses (Figs 37. Usually penicillin or broad-spectrum antibiotics like amoxycillin, cefuroximes and amoxycillin- clavulinic acid combinations are prescribed. However, if the symptoms do not subside, particularly in frontal sinusitis with increasing cellulitis, then drainage of the frontal sinus is done through the floor of frontal sinus above the inner canthus. Occasionally chronic sinusitis may be due to both aerobic and anaerobic organisms or may even be fungal in origin. The cilia get damaged by the infection with resultant inadequate drainage of the sinus cavity, particularly the maxillary sinus where the ostium is situated Fig. The retained secre- haziness of the left maxillary sinus (maxillary sinusitis) tions thereby lead to reinfection.

Negative controls effective nolvadex 10 mg, or blanks order nolvadex discount, are substances such as sterile generic nolvadex 20mg without prescription, deionized water, saline or 6 other media that are expected to cause little or no change in the test system. All manipula- tions specifed in the protocol (including removal of the tested solutions) should also be con- ducted using the negative control (Ulrey et al. The use of negative controls provides 7 valuable information that is highly useful in interpreting the results obtained in in vivo and in vitro studies (Ulrey et al. Whereas some interventions were signifcantly better than the untreated control, no inter- 9 vention was better than the control treatment. Low levels of re-osseointe- gration were achieved for non-machined implant surfaces (Claffey et al. Citric acid showed no statistically signifcant differences in effectiveness as compared 6 with water or saline. A possible explanation for this result is the small sample sizes used in both studies (three surfaces per treatment), which could be responsible for the lack of power 7 and thus the lack of signifcant results. In that study, almost total bone fll was observed in all groups, and bone-to-implant contact ranged from 39% to 46%. They allowed some threads to protrude in the oral cavity to permit plaque accumulation and the development of peri-implant dis- ease. The contaminated parts of each implant were treated using three different techniques: (1) swabbing with citric acid for 30 s, (2) cleansing with a toothbrush and saline for 1 min and (3) swabbing with 10% hydrogen peroxide for 1 min. Next, the treated implants and one pris- tine implant (control) were installed to the full implant length on the contralateral sides of the mandibles. The amount of osseointegration did not vary signifcantly, either between the different treatment modalities or in comparison with the new, sterile implant. These studies demonstrated that the method of decontamination used for the titanium surface might not …contaminated titanium surfaces: a systematic review 155 1 be a determining factor if the recipient site is healthy. Nevertheless, the implants used had a smooth or a minimally rough surface that facilitated the decontamination process (Denni- son et al. Furthermore, in clinical reality, peri-implant tissues are likely to be infamed, 2 which can impair healing. H2O2 has been used in clinical protocols for the treatment of infected implant surfaces 3 (Mombelli & Lang 1998). First, although the binding of endotoxin to the root surface appears to be weak (Nakib et al. Further, endotoxin is a char- 7 acteristic component of the cell wall of gram-negative bacteria and it plays a signifcant role in the binding process of these bacteria and in initiation of the host response. Bacterial endotoxin 9 has been shown to inhibit fbroblastic growth and attachment to root surfaces (Layman & Diedrich 1987). In our opinion, it is more clinically relevant to grow bioflms on titanium surfaces to test various chemical treatments. Furthermore, this approach can pro- vide information regarding both the killing and removal abilities of these agents. The only study to investigate the killing capacities of antimicrobials was that reported by Chin et al. This method is clearly not quantitative and thus does not allow us to draw any 4 defnitive conclusions. The real incidence of peri-implantitis is probably underestimated (Esposito et al. Thus, the need for effcient treatment and further maintenance of successfully treated implants will increase in the near future. This fnding does not mean that 7 all current treatments are ineffective (Esposito et al. In our opinion, a systematic approach to the treatment of contaminated implant surfaces should be initiated. The available treatment 8 modalities should be categorized and evaluated separately in a controlled manner. Review- ing the literature for this type of studies on chemical decontamination of titanium surfaces 9 was rather disappointing. Considering the number of studies that have been published on the technical aspects and aesthetic outcomes of implant surgery, it is striking that so little controlled research has been undertaken to determine how the titanium implants should be maintained in order to reduce the chances of biological complications (perimucositis and peri-implantitis) and further how to treat the titanium surfaces in the event of such compli- cations. Finally, the greatest challenge will be to determine the treatment protocol that best balances decontamination (Persson et al. To date, the killing effect of citric acid has not been investigated on titanium surfaces. Additionally, the assessment of surface decontamination should involve quantifcation of the residual bioflm. The results obtained using rough titanium surfaces are more clini- cally relevant and increase the applicability of the fndings. Finally, in vivo studies should be 7 performed to test the in vitro fndings and to establish an evidence-based protocol for the treatment of peri-implant diseases. Confict of interest and source of funding statement: The authors declare that they have no confict of interest. Ntrouka contributed to the conception, design, acquisition, analysis, interpretation of data, drafted the manuscript. Slot contributed to the design, analysis, interpretation of data, critically revised the man- uscript for important intellectual content. Louropoulou contributed to the conception, design, analysis, interpretation of data, criti- cally revised the manuscript for important intellectual content. Journal and chemical properties of different surfaces of Periodontology 65: 942–948. The International Re-osseointegration on rough implant surfaces Journal of Oral & Maxillofacial Implants 16: 5 previously coated with bacterial bioflm: an 783–792. Clinical Oral Implants for replacing missing teeth: treatment of Research 2: 81–90. Prevalence of subjects with progressive bone loss Claffey N, Clarke E, Polyzois I, Renvert S. Lindhe J, Meyle J, Group D of European Workshop (2005) Treatment of peri-implantitis by the Vector on Periodontology. Clinical Oral Implants Research 16: 288– consensus report of the sixth European 3 293. The International Journal of Oral & Maxillofacial Clinical Oral Implants Research 9: 185–194. Clinical Oral carbon dioxide laser and hydrogen peroxide: an in Implants Research 14: 373–380. Applied and of periodontally healthy and diseased human Environmental Microbiology 63: 3352–3358.

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Stress and Insufficiency Fractures Stress and insufficiency fractures commonly involve the pelvis effective nolvadex 20 mg. Stress fractures are commonly identified in the proximal femur and typically occur along the medial as- pect of the femoral neck purchase cheapest nolvadex and nolvadex. Pubic rami stress fractures are one cause of groin pain cheap 10 mg nolvadex amex, and imaging will help to differ- entiate these injuries from injuries to the anterior abdom- inal wall musculature and the adductor muscle origins [17, 18]. Common sites include the sacrum, pubic rami, and the ileum, including the supra-acetabular ileum. Insufficiency fractures of the subchondral portion of the femoral head have recently been recognized [19-21]. Previously, these lesions were often diagnosed as tran- sient osteoporosis of the hip. Etiologies include transient osteoporosis of the acetabular labrum with histologic correlation. Czerny C, Hofmann S, Neuhold A et al (1996) Lesions of the to differentiate these various entities. Miyanishi K, Yamamoto T, Nakshima Y et al (2001) Subchondral Hodler J (2002) The contour of the femoral head-neck junction changes in transient osteoporosis of the hip. Resnick D (1999) Gluteus medius tendon tears and avulsive Arthritis & Rheumatism 43:2423-2427 injuries in elderly women: imaging findings in six patients. Palmer2 1 Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Ultrasound is useful in the evaluation of overuse conditions of the patellar ten- don [8]. Also, sonography easily demonstrates popliteal Imaging Modalities (Baker’s) cysts [9]. Radiographs demon- ning complex orthopedic procedures, and for post-opera- strate joint spaces and bones, but are relatively insensitive tive evaluation. Maximal diagnostic information may ne- to soft-tissue conditions (except those composed largely cessitate reformatting the transversely acquired dataset of calcium or fat), destruction of medullary bone, and into orthogonal planes and/or 3D projections [10]. In patients with acute sitions with thin collimation (sub-millimeter, if possible) trauma, performing the lateral examination cross-table al- are preferred [11]. The ternal derangements, including meniscal and articular addition of oblique projections increases the sensitivity of cartilage injuries [12, 13]. The tunnel projection is useful to demonstrate tions, and evaluate treatment for a wide variety of ortho- intercondylar osteophytes. Bone scanning is a useful adjunct in the evaluation of Use of a local coil is mandatory to maximize signal-to- painful knee arthroplasties [5]. Images are acquired in transverse, coro- Imaging of the Knee 27 nal, and sagittal planes, often with mild obliquity on the to retraction of the proximal fragment by the pull of the sagittal and coronal images to optimize visualization of quadriceps. A combination of different spines of the tibia may affect the attachment points of the pulse sequences provides tissue contrast. Elevation of a fracture fragment may weighted images demonstrate hemorrhage, as well as ab- occur due to the attachment of one of the cruciate liga- normalities of bone marrow, and extraarticular structures ments. For example, a (long repetition time, short effective echo time) sequences fracture of the lateral tibial rim (Segond fracture) is a are best for imaging fibrocartilage structures like the strong predictor of anterior cruciate ligament disruption, menisci [24]. T2- or T2*-weighted images are used to eval- while an avulsion of the medial head of the fibula (arcu- uate the muscles, tendons, ligaments, and articular cartilage ate fracture) indicates disruption of at least a portion of [25, 26]. These fluid-sensitive sequences can be obtained the posterolateral corner [36, 37]. Suppressing the signal from fat increases the sensi- radiographs for nondisplaced fractures. Bone and Articular Cartilage On gradient-recalled, proton-density-weighted, and non- fat-suppressed T2-weighted images, fractures lines and Osseous pathology in the knee encompasses a spectrum marrow edema are often not visible. Marrow edema is of traumatic, reactive, ischemic, infectious, and neoplas- most conspicuous on fat-suppressed T2-weighted or tic conditions. Injuries to the articular surfaces often produce changes Trauma in the underlying subcortical bone. In children, these in- juries are usually osteochondral, while in adults they may Most fractures are visible radiographically. The osteochondral infractions are vis- marthrosis indicates an intraarticular fracture, which may ible radiographically, most often involving the lateral as- be radiographically occult, if it is nondisplaced [33]. On T2-weighted images, a surface(s) determine the treatment and prognosis of tibial thin line of fluid-intensity signal surrounding the base of plateau fractures. The images need to accurately depict the lesion indicates that the fragment is unstable. The most difficult cases only shows the number and position of fracture planes, are those in which there is a broad area of high signal in- but also demonstrates associated soft-tissue lesions – tensity that is less intense than fluid at the interface. In such as meniscus and ligament tears – that may affect these instances, the high signal intensity may represent surgical planning [35]. Patellar fractures with a horizontal component re- event: Gadolinium tracking around the base of the lesion quire internal fixation when they become distracted due indicates a loose, in-situ fragment [39]. Palmer In the knee, chondral injuries mimic meniscal tears label any area of marrow edema as a “bone bruise. Arthrographic images show The focal bone-marrow edema pattern is nonspecific, and contrast filling a defect in the articular cartilage. Most of is seen in a variety of other conditions – from ischemic, the traumatic cartilage injuries are full-thickness and to reactive (subjacent to areas of degenerative chondro- have sharp, vertically oriented walls (unlike degenerative sis), to neoplastic and infectious. A frequent associat- in the femoral condyles [49], sometimes precipitated by ed finding is focal subchondral edema overlying the de- a meniscal tear or meniscectomy. Often the appears as sclerosis of the subchondral trabeculae, even- subchondral abnormality will be more conspicuous than tually leading to formation of a subchondral crescent and the chondral defect [41]. In the diaphyses, established Stress fractures – whether of the fatigue or insuffi- infarcts have a serpiginous, sclerotic margin. At this radiographs show a band of sclerosis perpendicular to the stage, bone scintigraphy will be positive (albeit non- long axis of the main trabeculae, with or without focal specifically) in the reactive margin surrounding the in- periosteal reaction. Initially, however, stress fractures are radiographical- may show decreased tracer activity. The imaging ap- signal, either in the medullary shaft of a long bone or in pearance is similar to that of traumatic fractures. The signal intensity of scans show a nonspecific, often linear, focus of intense the subchondral fragment and of the reactive surrounding uptake, with associated increased blood flow (on three- bone vary based on the age of the lesion and other fac- phase studies). As the infarction evolves, a typical serpiginous re- sity fracture line surrounded by a larger region of marrow active margin becomes visible, often with a pathogno- edema. The proximal tibia is a common location for in- monic double-line sign on T2-weighted images: a periph- sufficiency fractures, especially in elderly, osteoporotic eral low signal intensity line of demarcation surrounded patients. Marrow edema without a fracture line in a patient with a history of chronic repeti- Replacement tive injury represents a “stress reaction.

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Primordial cysts arise from the epithe- lium of the enamel origin before the formation of the dental tissue order genuine nolvadex. Cysts of eruption arise over a tooth that premaxillary elements of the palate order nolvadex without a prescription, has not erupted from the remains of the so as to cause separation of the dental lamina purchase nolvadex once a day. Nasoalveolar cysts occurring in the deciduous or permanent molar tooth, lateral half of the nasal floor, ante- appearing as small bluish swellings. When large they Chronically infected dead teeth or roots cause nasal obstruction and may thin produce a granulomatous reaction at the bony nasal floor. This granuloma contains sometimes mistakenly incised as epithelium and it is this epithelium that furuncles, only to recur later. Therefore, the dead tooth or root These are derived from the epithelium that is usually seen in conjunction with such has been connected with the development a cyst although it must be remembered of the tooth concerned. Any of these cysts may be thin- All cysts tend to expand gradually without walled and histologically show pain unless infected. They Radiographic appearance is usually diag- may occur in the midline of the nose and nostic in showing a clear outline in typical may extend into the septum; others may positions. When the outline is not clear or there occur at the inner and outer parts of the is a multiple appearance, hyperparathyroi- orbital margins, viz. Follicular cysts usually have a tooth follicle Mucoceles occur most commonly in the present within them. Radiographic examination Differential Diagnosis shows multiple radiolucent areas which Differential diagnosis is from any lesion which are symmetrical and widespread through- can produce a clearly defined radiolucent area out the lower and/or upper jaws. Haemorrhagic bone cysts: These are found Complete removal or marsupialisation is the in the mandible and it is thought that the treatment of choice. It is probable Paranasal Sinuses that an intraosseous haemorrhage leads to excessive osteoclastic activity which slowly Fungal infections commence in the nose and regresses, leaving the cyst behind. There is widespread Most common type of fungal infection of nose haematological and intracranial spread and paranasal sinuses, are due to Aspergillus. Dry and hot climate acts patients who are on systemic steroids or as a predisposing factor. Allergic form: This occurs in young adults Clinical Features with history of asthma or polyps and Fungal rhinosinusitis can occur in four clinical produces pansinusitis but without soft forms: tissue or bone erosion. The fungus in the Treatment form of green brown sludge or fungus ball Systemic antifungal therapy with surgical may fill the sinus cavity. Exenteration and resistance the noninvasive form can spread craniofacial resection may be needed in to adjacent structures like soft tissues of fulminant forms. The close anatomical relationship between nasal passages and the adjacent sinuses results in rapid involvement of one from the other. The tumour shows inversion of the epithelium into the underlying stroma instead of growing Papilloma outwards as in other papillomas; the surface Squamous papilloma may arise from the nasal of the tumour being covered by alternating vestibule (Fig. Tumours of the Nose and Paranasal Sinuses 227 pedunculated mass from the anterior part of the septum. Surgical excision with healthy margins of the mucoperichondrium is done to prevent recurrence. It is of darker appearance, denser than Hence the tumour is also called transitional cell polypus, and of firmer texture on probing or papilloma. It arises from the lateral wall of the nose vascular and in their site of origin (Fig. Origin is near epiphyseal centre line (as in long bones) and ceases to grow when the affected Haemangiomas bone ceases to grow (as in long bones). Arnold’s osteoma develops in remnants of cartilage remaining unossified in ethmoid. That they arise in the periosteum, in areas Cysts: Due to blockage of mouth of a gland either torn of by trauma or by the initiation and gradual expansion of gland by retained of chronic inflammation. It may present as a bleed- Symptoms Pressure with increasing obstruc- ing polypoidal or sessile mass in the nose, in tion, pressure-atrophy and destruction of older age group, with symptoms of nasal obs- neighbouring bone and neuralgia. Causse (1934) describes: (a) a period of sub- Squamous cell carcinoma may arise from jective phenomena (b) early objective pheno- the vestibule, lateral wall, and nasal septum mena (c) advanced objective phenomena with and extend to the adjacent columella, upper compression of neighbouring parts. If no symptoms, leave alone or removal, by Advanced tumours need radiotherapy with removing bone around the base and whole tumour detached. Section shows—typical osteitis fibrosa with increased vascularity and a few giant cells. Diagnosis—smooth, solid, hard and ill- defined inflammation or other physical signs makes the diagnosis obvious. Adenoma Histologically they contain cavities lined with cuboid or cylindrical epithelium and filled with mucoid material. Olfactory Neuroblastoma This is a neuroectodermal tumour and may arise from the cribriform plate of the olfactory area. It occurs most frequently in the frontal sinus followed by ethmoids and maxillary sinus. Symptoms are produced by pressure on the nerves or extension of the tumour into surrounding tissues. Fibrous Dysplasia It is a condition in which normal bone is replaced by collagen, fibroblasts and varying amounts of osteoid tissue. It presents as involvement a bony hard, diffuse and painless swelling usually at puberty. These are rare tumours arising from the The growth ceases at 20 to 25 years of age. Two clinical types are generally recognised, Most patients are over the age of 50 years. Radiology most common symptoms are nasal obstruc- shows ground glass appearance of the bone tion and epistaxis with a blackish mass inside depending upon the relative amount of the nose. Treatment is Tumours of the Nose and Paranasal Sinuses 231 surgical removal of the abnormal bone. Carcinoma of Paranasal Sinuses Though the paranasal sinuses are lined by ciliated columnar epithelium, yet the most common malignant neoplasm of the paranasal sinuses is squamous cell carcinoma. Classification Two vertical lines are drawn through the There has been no agreement on classifying medial canthi, which separate the ethmoid tumours at these sites because of late diagnosis and nasal fossa from the maxillary sinus, the of the disease in these inaccessible deep nasal septum separates the ethmoid and nasal recesses of the nasal cavities. Infrastructure sites (inferior region) Ohngren’s classification An imaginary line is a. Tumours simultaneously involving the through the pupils downwards, thus dividing hard palate and antrum or hard palate the maxilla into four quadrants, namely and floor of nose anterosuperior, anteroinferior, postero- d. Respiratory portion of the nasal fossa nosis as such tumours are difficult to resect c. Lateral nasal wall (including inferior two horizontal lines, one through the floor of turbinate). Lederman’s classification is based on the T4 Massive tumour with invasion of the above mentioned regions and sites.