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All of these epithelial types may be present in the same lesion, and their proportions may vary widely in different lesions or even in different areas of the same papilloma. Mitoses are not numerous and, if present at all, are seen primarily in the basal and parabasal epithelium. Inverted papilloma, low magnification. Note the endophytic growth and that the epithelial islands are well demarcated from the stroma.

Basement membrane is thin and delicate. These are not necessarily signs of malignancy, but they should alert the pathologist of the need for thorough evaluation of the papilloma. The stroma ranges from dense and fibrous to loose and myxoid, with or without an inflammatory component. The inflammatory cells, especially neutrophils, often transmigrate through the epithelium. Eosinophils and basement membrane thickening are not typically seen Fig.

Minor salivary glands are also sparse to absent because of the fact that the abnormal epithelium uses the salivary ducts and glands as scaffolds to extend into the stroma, thereby obscuring their normal appearance. As IPs enlarge, they may obstruct the drainage of nearby sinuses.

As a result, it is not uncommon to also find ordinary nasal polyps in IP specimens. They can usually be identified grossly by their more myxoid appearance and the fact that they will transilluminate, whereas IP will not. Although this might be a viral effect, immunohistochemical stains for HPV are invariably negative.

This change has no clinical significance other than it might be mistaken for a verrucous carcinoma see later section on differential diagnosis. Patients with IPs that are associated with carcinomas fall into three groups: 1 those who have primarily an IP with only a small focus of carcinoma, 2 those who have primarily a carcinoma with only a small focus of IP, and 3 those who have an IP and then years later develop a carcinoma in the area in which the papilloma arose.

For metachronous carcinomas, Lesperance and Esclamado 60 observed the mean interval between the onset of the IP and the development of carcinoma to be 63 months range, 6 mo to 13 years. Carcinomas complicating IPs vary from well to poorly differentiated and exhibit a broad range of behavior. Some are in situ and of little consequence, whereas others are locally aggressive or may even metastasize.

The carcinomas may actually arise within the papilloma carcinoma ex IP , as evidenced by a gradation of histologic changes ranging from dysplasia to carcinoma in situ to frankly invasive carcinoma; whereas in others, the carcinoma is merely associated with a histologically bland IP. Once a carcinoma is recognized, the pathologist should not only indicate the histologic type, the degree of invasion and differentiation, and the adequacy of resection margins if possible but also quantitate its volume e.

There is no correlation between the number of local recurrences of an IP and the subsequent development of carcinoma There is some evidence, however, to suggest that HPV 16 and 18 may be more carcinogenic than HPV 6 and 11 45 , 46 , In the studies of Klemi et al. Klemi et al. They indicated that if the papillomas were both HPV 16 positive and aneuploid, the incidence of malignant transformation was even higher.

Preliminary data suggest that alterations in p53, manifested by an increased protein expression or genetic mutation, may be used to predict which lesions are at risk for malignant changes 61 , 62 , CD44s may likewise prove useful. According to Ingle et al.

The differential diagnosis includes nasal polyps with squamous metaplasia, respiratory epithelial adenomatoid hyperplasia, inverted ductal papilloma IDP of minor salivary gland origin, and invasive carcinoma. In nasal polyps with squamous metaplasia, one will usually see thickening and hyalinization of the basement membrane, prominent minor salivary glands, and, often, a large number of inflammatory cells, especially eosinophils.

These features are absent in IP. In addition, the epithelium lining the minor salivary glands in nasal polyps is not multilayered, contains more mucous cells, and does not show the characteristic epithelial transmigration of neutrophils. The former is innocuous compared with the potentially locally aggressive behavior of the latter. In contrast to IP, which arises from the surface epithelium and grows endophytically, IDP arises from the excretory duct of minor salivary glands; hence it will grow intraluminally and be confined by the duct.

Invasive carcinoma can be distinguished from the ordinary IP by the presence of the following features in the former lesion and their absence in the latter: cellular pleomorphism, atypical mitoses, keratin pearls, loss of basement membranes, and unequivocal invasion associated with an inflammatory-desmoplastic stromal response.

Inverted papillomas are thought to enlarge by squamous metaplasia of the adjacent mucosa. Though histologically benign, they have an unlimited growth potential and, if neglected, can cause considerable morbidity or even death by extending into contiguous structures The preferred treatment for most lesions is a lateral rhinotomy and medial maxillectomy with meticulous removal of all mucosa in the ipsilateral paranasal sinuses 25 , In selected, very small tumors, one may, however, be able to effectively remove the lesion by a less aggressive approach using endoscopic sinonasal surgery Although surgery is, and should remain, the primary treatment modality for IP, Mendenhall et al.

Radiation therapy should also be considered as an adjunct in patients who have carcinomas arising in IPs. Recurrences typically appear within 2—3 years of therapy but, in some instances, are delayed for many years. Attempts to correlate histologic features with risk of recurrence have resulted in conflicting data. Some maintain that the presence of epithelial atypia and mucin cells render the patient at increased risk 3 , whereas others comment on the lack of association with any microscopic feature 2 , 30 , 53 , Even those with prominent mitotic activity and dysplasia do not invariably show an increased incidence of recurrence or malignancy.

Nevertheless, dysplasia, especially if moderate to severe, demands thorough microscopic evaluation of all resected tissue so as to avoid overlooking small foci of cancer. Whether the demonstration of HPV in IP is associated with a greater risk of local recurrences is also open to debate. Beck et al. Oncocytic Schneiderian papilloma OSP is the rarest of the three morphologic variants of Schneiderian papillomas 2 , 5 , 10 , 70 , 71 , It shows many features in common with the IP.

In fact, some regard it as only a variant of the IP. Microscopically, however, the two lesions are distinct. The youngest patient reported thus far in the literature has been a year-old woman OSP occurs exclusively on the lateral nasal wall or in the sinuses, usually the maxillary or ethmoid, and presents as a fleshy pink, tan, red-brown, or gray papillary or polypoid growth.

Unilateral nasal obstruction and intermittent epistaxis are the most common symptoms. Although this may be a sampling problem, it does suggest that the OSP is not etiologically linked to this virus. Microscopically, OSP exhibits both exophytic and endophytic patterns of growth. The epithelium is multilayered, 2—8 cells thick, and is composed of tall columnar cells with swollen, finely granular cytoplasm reminiscent of oncocytes Fig. Barnes and Bedetti 70 have shown that the cells not only resemble oncocytes but also possess a high content of cytochrome c oxidase and ultrastructurally are distended with mitochondria, thus clearly establishing their oncocytic character.

The nuclei are either small dark and uniform or slightly vesicular with barely discernible nucleoli. Cilia in varying stages of regression may be observed in a few of the outermost cells. Oncocytic Schneiderian papilloma. Observe the multilayered oncocytic epithelium and intraepithelial mucin-filled cysts and microabscesses.

The epithelium characteristically contains numerous small cysts filled with mucin or neutrophils microabscesses; Fig. The stroma varies from edematous to fibrous and may contain modest numbers of lymphocytes, plasma cells, and neutrophils, but few eosinophils. Minor salivary glands are sparse to absent. As in IP, the carcinoma complicating OSP may actually arise within the papilloma, as evidenced by a gradation of histologic changes ranging from dysplasia to in situ to invasive carcinoma, or it may merely be associated with the OSP.

Prognosis depends on the histologic type, degree of invasion, and the extent of tumor. In some instances, the carcinoma is in situ and of little consequence to the patient, whereas others are locally aggressive and may even metastasize.

The intraepithelial mucin-filled cysts, because of their spheroidal nature and mucicarminophilia, are often mistaken for rhinosporidiosis. In rhinosporidiosis, however, the organisms are not limited to the epithelium but also involve the stroma and, moreover, never induce a diffuse oncocytic change in the epithelium.

The OSP is also occasionally mistaken for a low-grade papillary adenocarcinoma. The presence of intact basement membranes, the lack of nuclear pleomorphism, mitotic activity, perineural invasion, and the absence of extensive bone destruction on radiographs are features that point to the benignity of the tumor. Furthermore, the stratified oncocytic epithelium of an OSP is in distinct contrast to the single-layered, nononcocytic epithelium seen in a low-grade adenocarcinoma.

The clinical behavior parallels that of the IP. Effective treatment consists of a lateral rhinotomy and medial maxillectomy. Smaller tumors may be treated endoscopically. Hamartomas from the Greek, hamartia, meaning fault or defect are benign, nonneoplastic overgrowths of tissue s indigenous to the area of their occurrence They may be composed entirely of epithelial or mesenchymal elements or of both and should be distinguished from teratomas and dermoids 77 , 78 , 79 , 80 , 81 , 82 , 83 , Hamartomas of the sinonasal tract are uncommon and most often of the epithelial type.

Their importance lies in the fact that they may be confused with more aggressive lesions, particularly the IP and sinonasal adenocarcinoma. Of the 31 REAHs described by Wenig and Heffner, 27 occurred in men and 4 in women who ranged in age from 27 to 81 years median, 58 years. A few, however, were bilateral. The remaining cases occurred in the nasopharynx and paranasal sinuses.

Nasal stuffiness, obstruction, epistaxis, and chronic rhinosinusitis were the most common manifestations. REAHs are typically polypoid or exophytic, rubbery, tan-white to red-brown, and range up to 4. Histologically, they are composed of small to medium sized, round to oval glands lined by ciliated respiratory epithelium, often with numerous, admixed mucin-secreting goblet cells Fig.

The glands arise from invagination of the surface epithelium into the lamina propria and, consequently, often maintain direct continuity with the surface. The glands are widely spaced and characteristically surrounded by thick, eosinophilic basement membranes Fig 7.

The stroma is well vascularized, edematous, or fibrous and contains scattered chronic inflammatory cells. Respiratory epithelial adenomatoid hamartoma frequently mistaken for an inverted papilloma. Lesion composed of numerous glands lined by ciliated respiratory epithelium. Respiratory epithelial adenomatoid hamartoma. Note that each gland is surrounded by a thick, eosinophilic basement membrane. Compare with Figure 4. Mucoserous minor salivary glands are also occasionally seen in a lobular configuration.

Whether they are part of the hamartoma or just a reactive hyperplastic response to the inflammation is uncertain, although the latter is favored A few may also contain chondro-osseous foci The presence of excess glands lined by respiratory epithelium readily distinguishes this lesion from a nasal polyp. In contrast to REAH, which occurs primarily on the nasal septum, IPs arise almost exclusively on the lateral nasal wall in the vicinity of the middle turbinate and ethmoid sinus area.

IPs are also composed predominantly of hyperplastic islands of squamous epithelium with few interspersed mucous goblet cells and a prominent intraepithelial component of neutrophils. Respiratory epithelium may also be seen but is usually not dominant. The basement membranes around the epithelial islands in IPs are also thin and delicate, not thick and hyalinized as seen in REAH. Mucoserous glands are also sparse to absent in IPs. Adenocarcinomas are characterized by a back-to-back arrangement of their glands, occasional nuclear pleomorphism, prominent mitotic activity, perineural invasion, and a desmoplastic response to stromal invasion.

These features are not seen in REAH. Many of these are readily recognized as being of mucoserous minor salivary gland origin and can be appropriately subclassified according to standard categories, such as adenoid cystic carcinoma, mucoepidermoid carcinoma, and so on. Others are less familiar and present histologic patterns that resemble adenocarcinoma of the colon or, in some instances, villous adenomas 92 , A few may even resemble normal small intestinal mucosa Such tumors have been referred to by a variety of names, including colonic-type adenocarcinomas, mucinous adenocarcinomas, heterotopic tumors with intestinal mucous membrane, enteric-type adenocarcinomas, papillary adenocarcinomas, or nonspecific adenocarcinomas.

The term that has currently emerged as the most preferred is intestinal-type adenocarcinoma ITAC. Although ITACs are uncommon, they have generated interest not only because of their unusual histologic appearance but also, epidemiologically, as a result of their association with occupational exposure to wood and, occasionally, leather dust 95 , 96 , 97 , 98 , 99 , , , , , , , , , , The tumor came into prominence in the s when Hadfield astutely observed an increased incidence of adenocarcinomas of the sinonasal tract among woodworkers employed in the furniture industry of Oxfordshire and Buckinghamshire, England.

It soon became apparent that the risk for developing ITAC was not limited to these geographic areas but also involved woodworkers in many other countries 98 , 99 , , , , , , , In a review of patients with sinonasal malignant tumors from 17 countries, Mohtashamipur et al. The risk for developing ITAC in the furniture worker exposed to wood dust is 70— times that of the nonwoodworker 95 , The inhaled particles are concentrated in the anterior portion of the nasal septum and middle turbinate, where they induce cuboidal or squamous metaplasia with impairment of the mucociliary clearance mechanism , This results in prolonged mucosal contact of the dust.

The carcinogen in wood dust still has not been identified. The average interval from first dust exposure to the appearance of ITAC is 40 years range, 7—69 years The length of dust exposure has been highly variable. This, however, seems to be a singular experience. The length of dust exposure in other studies has ranged from 5 to 55 years The risk for ITAC does not appear to decrease for at least 15 years maybe more after termination of occupational exposure Although the majority of tumors associated with wood dust exposure are ITACs, there is also an increased incidence of squamous cell carcinomas, especially among woodworkers in Japan Interestingly, in contrast with ITACs, which are associated with hard wood exposure, squamous cell carcinomas and undifferentiated carcinomas are more common in individuals exposed to dust from soft woods pine and spruce , It has also been suggested that workers with an occupational exposure to wood dust may also be at risk for developing other malignancies.

There may be differences between the two. The male predominance is probably related to the fact that very few women are employed as woodworkers. The average age at diagnosis for both types is about 58 years range, 12—86 years. Although almost all ITACs occur in the sinonasal tract, they are not unique to this site.

Spiro et al. Lopez and Perez have also reported another case in the pharynx. The most common presenting symptom is unilateral nasal obstruction, followed by epistaxis and purulent or clear rhinorrhea 92 , , , , , , Cervical lymph node and distant metastases are rarely present at the time of initial presentation. On physical exam, the tumors are polypoid, papillary, or nodular and dark red, gray-white, or pink-gray. Most are friable. Some are ulcerated and hemorrhagic, whereas others are mucoid.

Barnes has described one patient with an advanced tumor of the maxillary sinus that was associated with a pretreatment borderline abnormal serum level of carcinoembryonic antigen. Whether this laboratory test has any role in monitoring the course of the disease is uncertain. Radiologic studies are essential in determining the extent of disease and the operative approach. Early lesions will show only a soft tissue mass with little, if any, evidence of bone destruction.

Other tumors may be associated with considerable osteodestruction and invasion of contiguous structures such as the orbit and cranial cavity. A few may even involve the contralateral sinonasal tract. As the tumor enlarges, it may interfere with drainage of nearby sinuses. The ensuing obstructive sinusitis then may interfere with optimal preoperative evaluation and staging. Several histological classifications of ITACs have been proposed , , , The one proposed by Kleinsasser and Schroeder, however, seems to be gaining acceptance for its ease of use, reproducibility, and clinical correlation According to them, ITACs can be subclassified into four categories: papillary tubular cylinder cell PTCC , alveolar goblet cell, signet ring cell, and transitional.

The columnar cells may be polarized, with their long axes perpendicular to the basement membrane, or stratified and crowded. These cells have pink cytoplasm and round to oval nuclei that vary from vesicular to hyperchromatic, with or without nucleoli. In some tumors, goblet cells are found admixed with columnar cells in a ratio similar to that seen in the intestine.

In others, the fronds may be covered exclusively by columnar or goblet cells. Mitoses may or may not be prominent. Although some papillary tumors are clearly invasive, others remain noninvasive in situ over a broad front much like papillary urothelial carcinoma in situ of the urinary bladder. A few are rather bland cytologically and may resemble a villous adenoma or even normal intestinal mucosa, yet are locally aggressive and destructive.

The PTCC II moderately differentiated, also known as the colonic type is composed of well to moderately differentiated glands and more closely resembles adenocarcinoma of the large intestine than does any of the other variants Fig. At times, one may also see cystic glandular spaces with intracystic papillary projections. The PTCC III poorly differentiated, also know as the solid type is composed of a diffuse proliferation of smaller, more cuboidal cells with amphophilic to pink cytoplasm, occasionally with mucin droplets, and round, vesicular nuclei, often with nucleoli.

There is little attempt at gland formation. The signet ring variant also known as mucinous type is composed of small groups or isolated signet ring cells floating in pools of mucus. No strips of epithelium are apparent. The transitional cell type also known as mixed type is composed of two or more of the preceding growth patterns. ITAC, regardless of histologic type, may contain Paneth and enterochromaffin cells as well as a muscularis mucosa.

The enterochromaffin cells may express a variety of peptides, including gastrin, glucagon, serotonin, cholecystokinin, and leu-enkephalin 93 , , Although Schmid et al. If they do transform, the transformation is usually to one of the more aggressive types. On the basis of the work of Cheng and Leblond and of Kirkland, it has been suggested that multidirectional differentiation of a common stem cell could account for the variety of cells Paneth, endocrine, absorptive, goblet observed in ITAC 94 , , The stem cell, either by direct transformation or by induction of adjacent mesenchyme, might also give rise to the muscularis mucosa noted in a few tumors.

The similarity of ITAC to intestinal tumors extends beyond the light-microscopic to the ultrastructural and, to some extent, the immunohistochemical level 93 , 94 , , Batsakis et al. These structures are thought to be important in identifying tumors of intestinal epithelium or tumors arising from metaplastic intestinal-type epithelium. The immunohistochemical profile of ITAC is discussed in the next section of this article.

Wu et al. The differential diagnosis includes a metastasis from a gastrointestinal carcinoma, papillary rhinosinusitis, and papillary adenocarcinoma of the nasopharynx. Metastases to the nasal cavity and paranasal sinuses from a primary adenocarcinoma of the gastrointestinal tract are not common , In a study of 82 tumors metastatic to the maxilla, nose and paranasal sinuses, Bernstein et al.

The maxillary, ethmoid, and frontal sinuses and nasal cavity were involved in descending order. In some of these patients, the head and neck metastasis was the initial manifestation of an otherwise clinically occult carcinoma. For this reason, examination of the gastrointestinal tract in all patients with ITAC, especially the PTCC II colonic variant, would seem prudent, although in the absence of relevant signs and symptoms, such studies will generally prove negative.

Immunohistochemical stains for chromogranin, neuron-specific enolase NSE , and carcinoembryonic antigen CEA may offer some limited help in distinguishing ITAC from metastatic colorectal adenocarcinoma. Because ITACs tend to contain more endocrine cells than colorectal adenocarcinomas, they will usually show a more diffuse and stronger intensity when stained for chromogranin and NSE In contrast, colorectal adenocarcinomas are diffusely and strongly positive for CEA, whereas ITACs tend to show only focal, weak reactivity Staining for cytokeratin 7 is also helpful in distinguishing ITAC from metastatic adenocarcinoma of the colon ITAC is consistently positive for this marker, whereas adenocarcinoma of the colon is negative.

Sinusitis, at times, may have a papillary configuration, but in these instances, the papillae are short and blunt and not highly branched, as one sees in some ITACs. P-ITAC, in contrast to PACN, occurs primarily in the nasal cavity and paranasal sinuses and is often not invariably associated with an occupational exposure to wood dust. P-ITAC also tends to be less glandular and more papillary. Rather than cuboidal cells, the papillae are covered by tall columnar and goblet cells, the latter of which are sparse to absent in PACN.

Such cells are not seen in PACP. Last, PACP tends to be associated with a hemorrhagic, inflammatory background and often recurs after therapy. Tumor necrosis with sepsis is often a problem and may be life threatening. Perez et al. Treatment consists of surgical excision using a lateral rhinotomy or, at times, even a cranial base approach. The use of radiotherapy is dictated by the extent and resectability of the tumor. An elective neck dissection is not warranted. Prognosis depends on the histologic type, degree of differentiation, stage of the disease, and the adequacy of resection margins.

PTCC I has the best prognosis. It may recur but rarely metastasizes. The other types are more virulent, with a greater propensity for dissemination. Over the course of time, a few tumors may change from one histologic type into another. This may be an ominous finding, signaling a tumor with increased aggressiveness. Woodworkers seem to have a better prognosis than those individuals with sporadic ITAC. This probably relates to the fact that the woodworker is under heightened surveillance for this tumor and that in this group, the tumors are more often found in the nasal cavity or ethmoid sinus and can therefore be detected earlier by the patient.

In contrast, patients with sporadic tumors are not in early detection programs and have neoplasms that are relatively more common in the maxillary sinus, which are difficult to detect early. The vast majority of malignant tumors of the nasopharynx are either keratinizing or nonkeratinizing squamous cell carcinomas or malignant lymphomas , Exceptionally, adenocarcinomas may also arise from the mucosa, and when they do, they are typically papillary and are referred to as papillary adenocarcinomas of the nasopharynx , Most present with airway obstruction.

Other less common symptoms include serous otitis media with or without hearing loss and postnasal drip with blood-tinged sputum. Rarely the tumor may be an incidental finding after adenoidectomy. PACN are typically confined to the nasopharynx and, on physical examination, present as exophytic or pedunculated masses with a papillary, nodular, or cauliflower-like appearance. The tumors range from 0. There are no known risk factors associated with the development of this tumor.

None of the patients thus far has had a significant history of tobacco or alcohol abuse or occupational, environmental, or radiation exposure The tumors arise from the surface epithelium of the nasopharynx and may remain in situ or become invasive. They are characterized by papillary and glandular growth patterns Fig. The papillae have fibrovascular cores and often show arborization, whereas the glands have a back-to-back, often cribriform arrangement.

Both papillae and glands are covered or lined by one or more layers of cuboidal to columnar cells with pink cytoplasm and round to oval nuclei that vary from hyperchromatic to optically clear. Mild to moderate nuclear pleomorphism may be seen, but nucleoli, mitoses, and necrosis are uncommon.

A few tumors may also contain psammoma bodies. Vascular, lymphatic, or neural invasion are not seen. Papillary adenocarcinoma of the nasopharynx. The tumor is composed of both papillae and glands and arises from the mucosa of the nasopharynx. PACN typically contain periodic acid—Schiff, diastase-resistant intracytoplasmic granules and stain focally positive for intracellular or luminal mucin They are also diffusely reactive for cytokeratin and epithelial membrane antigen and focally positive for carcinoembryonic antigen.

They are negative for glial fibrillary acidic protein, S protein, and thyroglobulin. Because of the papillae and the occasional presence of psammoma bodies and optically clear nuclei, PACN can easily be mistaken for metastatic papillary thyroid carcinoma. PACN, however, are negative for thyroglobulin and will typically show dysplasia or in situ changes of the surface epithelium. Furthermore, it arises submucosally from minor salivary glands rather than from the surface, as does the PACN.

Staining for S protein may also be helpful. PACN is a slow-growing, indolent neoplasm that rarely recurs and has thus far not metastasized to either cervical lymph nodes or more distant sites. The treatment of choice is surgery, using a transpalatal approach. Wenig et al. The tumor recurred within months after treatment. The patient subsequently underwent surgical excision and was reported free of disease 11 years later.

This singular experience certainly casts doubts on the efficacy of radiation therapy. In , Gaffey et al. The authors speculated that the tumor arose from the middle ear mucosa and proposed the term aggressive papillary middle ear tumor. As experience with the tumor accumulated, it became apparent that the middle ear was not always involved, thus casting doubt on its alleged origin from this site In a review of 20 additional cases, Heffner concluded that the tumor actually arose from the endolymphatic sac and only secondarily involved the middle ear.

He, therefore, suggested the term low-grade adenocarcinoma as being more appropriate because it called attention to its potential aggressive behavior and eliminated all reference to the previous misconception that it arose from the middle ear. In this review, low-grade papillary adenocarcinoma LGPA will be used. LGPA is a slowly growing, locally aggressive tumor of the temporal bone that has been described in patients from 15—71 years of age average, 41 years , It affects both sexes about equally.

In a collective review of 30 cases, 13 occurred in males and 17 in females , There is no significant lateralization of the tumor to either side of the body. Of 20 cases in which the side of origin was indicated, 8 involved the right ear, 11 the left ear, and in the remaining case, the side was not indicated Bilateral lesions, either synchronous or asynchronous, have been described but are exceptional and should always arouse suspicion of von Hippel-Lindau disease see discussion later in this article Some also manifest with facial nerve paralysis.

Physical examination may be unremarkable or may reveal a blue or red mass behind an intact, sometimes perforated tympanic membrane. Occasionally the tumor may even project into the external auditory canal Von Hippel-Lindau disease VLD is an autosomal-dominant disorder characterized by a variety of abnormalities, chief of which include hemangioblastomas of the retina, cerebellum, medulla oblongata, and spinal cord; hemangiomas of the liver and kidney; renal cell carcinoma; and cysts of the pancreas and kidney.

Linkage studies have mapped the VLD gene to the short arm of chromosome 3, and a mutated tumor suppressor gene has been identified in both normal and neoplastic tissue from VLD patients , According to Gaffey et al. This is especially so if the tumors are bilateral Radiologic studies typically show a lytic temporal bone lesion, often with extension into the posterior cranial cavity, manifesting as a cerebellopontine angle neoplasm The epicenter of the lesion lies at or near the posterior-medial surface of the temporal bone.

According to Megerian et al. In order of frequency, they generally progress 1 posteriorly to the cerebellopontine angle and posterior fossa, 2 laterally via the mastoid cell tract to the middle ear and external auditory canal, 3 superiorly toward and into the middle cranial fossa, and 4 medially along the petrous ridge to the clivus and cavernous and sphenoid sinuses. Angiograms show the tumor to be highly vascular with a dual extracranial and intracranial blood supply As a result, it is often mistaken for a jugulotympanic paraganglioma.

Histologically, the tumor is composed of papillary-cystic components Fig. The papillae are well vascularized and covered by a single layer of cuboidal cells, which have clear to pink cytoplasm and uniform round nuclei. Cellular pleomorphism and mitoses are absent. The cystic spaces characteristically contain pink colloid-like material, imparting a thyroid-like appearance. The secretory material is strongly positive with the periodic acid—Schiff stain and negative with mucicarmine.

Areas of closely packed glands, fibrosis, hemorrhage, and cholesterol clefts may also be seen. Low-grade papillary adenocarcinoma of the middle ear. The glands contain colloid-like secretions. The epithelial cells contain glycogen but no intracytoplasmic mucin. The cells are also usually positive for epithelial membrane antigen, NSE, and vimentin. The differential diagnosis includes middle ear adenoma, jugulotympanic paraganglioma, metastatic papillary thyroid carcinoma and renal cell carcinoma, and choroid plexus papilloma—carcinoma.

Middle ear adenomas are not papillary and do not invade or destroy bone as one sees in LGPA. Metastatic renal cell carcinoma may be the most difficult entity to exclude, especially because both LGPA and renal cell carcinoma can contain clear cells, glycogen, and papillary-cystic areas. Immunohistochemical stains may offer some help. Renal cell carcinomas are negative for glial fibrillary acidic protein and synaptophysin and, according to Medeiros et al.

Perhaps the best way to distinguish between the two is to obtain a computerized tomogram of the kidneys. Choroid plexus papilloma and carcinoma almost always originate within the ventricles of the brain, whereas LGPAs are typically extradural. Staining for transthyretin may also be helpful. Otherwise, there is too much overlap in immunohistochemical stains keratin, epithelial membrane antigen, NSE, glial fibrillary acidic protein, and vimentin to allow one to distinguish between these two neoplasms with confidence , , , , , Knowledge of the clinical and radiologic findings may be the best way to separate LGPA from a choroid plexus tumor.

Complete surgical excision, if possible, is the treatment of choice. Radiation is largely untested but has been ineffective in the few cases in which it has been used Intraoperatively, the surgeon usually observes a blue, red, or white hypervascular, nonencapsulated lobular mass that often encases the ossicles and facial nerve. Though encased, the latter structures can often be dissected free without sacrifice.

Bleeding may be profuse. Despite frequent intracranial extension, invasion of the brain has only been documented in one instance Of 30 cases contained in the reviews of Gaffey et al. Twenty percent of the patients experienced recurrence after initial attempts at excision. Although the tumor is rare and a large series of cases with long-term follow-up is not available, experience thus far indicates that LGPA is only a locally destructive tumor with little, if any, capacity to metastasize.

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Clin Otolaryngol ; 15 : — Association of DNA aneuploidy with human papillomavirus-induced malignant transformation of sinonasal traditional papillomas. Siivonen L, Virolainen E. Transitional papilloma of the nasal cavity and paranasal sinuses. Clinical course, viral etiology and malignant transformation.

Presence of human papillomavirus type-6 related sequences in inverted nasal papillomas. Mod Pathol ; A majority of inverted sinonasal papillomas carries Epstein-Barr vius genomes. Cancer ; Weiner JS, Sherries D. Relationship of human papilloma virus to schneiderian papillomas. Papillomatosis of nasal cavity and paranasal sinuses inverted papilloma, squamous papilloma. A clinicopathologic study. Vrabec DP. The inverted schneiderian papilloma. A year study.

Sinonasal papillomas: a report of 82 cases in a Copenhagen County, including a longitudinal, epidemiological and clinical study. Inverted papilloma of the head and neck: the UCLA update. Otolaryngol Head Neck Surg ; Inverted papilloma of the nasal cavity and the paranasal sinuses: using CT for primary diagnosis and follow-up.

Am J Roentgenol ; Woodruff W, Vrabec D. Inverted papilloma of the nasal vault and paranasal sinuses: Spectrum of CT findings. Clinical and histopathological correlation of nasal polyps: are there any surprises? Clin Otolaryngol ; Inverted papilloma: an analysis of 87 cases. CD44 expression in sinonasal inverted papilloma and associated squamous cell carcinoma. Immunohistochemistry of p53 in sinonasal inverted papilloma and associated squamous cell carcinoma.

Am J Rhinol ; Kennedy DW. Functional endoscopic sinus surgery. Arch Otolaryngol ; Endoscopic management of sinonasal inverted papilloma. Preliminary report: endoscopic versus external surgery in the management of inverted papilloma. Management of inverted papilloma. Brors D, Draf W. The treatment of inverted papilloma. Current opinion. Otolaryngol Head Neck Surg ; 7: Different options for treatment of inverted papilloma of the nose and paranasal sinuses: a report of 41 cases.

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Sino-Nasal IPs involved the left side in 20 cases In terms of SNP recurrence, 13 cases Table 2. Gender and percentage of Sino-Nasal Papilloma. Table 3. Sino-Nasal Papilloma recurrence side in patients. All cases involved the nasal cavity, while 11, 27, 16, and 2 cases extended to the frontal, maxillary, ethmoidal, and sphenoidal sinuses, respectively.

Gender wise, post-operative recurrence of SNIP was found to be approximately equivalent in males and females with Figure 1. Bar charts comparing the recurrences of the ISNPs with gender A difference and side of the tumor accordingly. Of the 13 cases with post-operative recurrence, 8 cases The main presenting symptoms associated with SNIP were nasal blockage in 36 cases All patients were managed with a pure endoscopic sinus approach and no adjunctive external surgical approaches were required or applied.

Four patients Most post-operative recurrences were found to be in patients earlier categorized as stage T2. No statistical significance was determined between Krouse classification and recurrence rate at P -value of 0. Table 4. Demographic and clinical data of Sino-Nasal Papilloma. Primary lesion was left sided, and it extended from the nasal cavity to the ethmoidal, frontal and maxillary sinuses, and was classified as Krouse stage T3.

The patient was initially diagnosed in and underwent endoscopic sinus surgery with post-operative chemotherapy and histopathology confirmed the diagnosis of squamous cell carcinoma SCC. After that, he developed multiple recurrences, in which the first was in and the second was in No distant metastasis was found Figure 2.

Human Papilloma Virus analysis was not done for any of the cases in our center, except for one patient who had positive history of recurrence of disease within a one-year interval. That was one of the limitations we came across in our study for determination of relevance of positive HPV result with recurrence of the disease. Figure 2. A Coronal T1 post contrast. Heterogenously mildly enhancing residual soft tissue mass lesion centered within the left ptyrogoid plate and nasopharangeal wall showing extension into the masticator space and medical ptyrogoid muscle; B Axial T1 post contast.

Intracranial and extra axial extension of the tumor is noted reaching into cavernous sinus anteriorly with erosive changes of the left greater wing of the sphenoid. C and D A fragment of sinonasal mucosa lined focally by respiratory type epithelium; The underlying submucosa is infiltrated by nests of moderately pleomorphic cells with eosinophilic cytoplasm and distinct nucleoli.

Multiple foci of necrosis and mitotic figures are noted. The exophytic subtype and least commonly the oncocytic subtype in literature [1] follow. Our study showed 49 cases of Sino-Nasal Papilloma; of which 37 cases This was concordant with current literature [28] [29]. The mean age for SNIP patients was This was consistent with current literature that stated SNIP has preponderance in males.

However, unlike most literature, our patients mean age was in the fourth decade and not the fifth decade of their lives [30] [31]. In terms of recurrence of disease, 13 cases There is still much controversy regarding the causative agents and the roles of different factors on the recurrence and persistence of IPs. However, in our study it was moderate in recurrence In our study, Sino-Nasal IPs involved the left side in 20 cases Of those 13 cases with recurrence, 8 cases The side of Sino-Nasal IP was not statistically related to the rate of recurrence or persistence of IPs, while lesion localization was of relative significance.

Also in accordance with other literature [29] [32], IP arising from the maxillary sinus, nasal cavity and ethmoidal sinuses were most frequently found. In our study, the most common was the nasal cavity followed by the maxillary sinus. The frontal sinus however, was high in prevalence in our study, which was contradictive with literature [33] [34] [35].

Recurrence was found to be in 13 cases This may be explained by the limitation of surgical accessibility to remove all tumors or due to surgeon discrepancies [36] [37] [38] [39] [40]. In recent literature, endoscopic surgery is a very effective and accurate treatment method for patients with IP [39]. In a study by Gil et al. In our study, all patients were managed by pure endoscopic methods. The clinical staging of IPs has been identified using the Krouse classification system, which is the most widely used staging system currently [43] [44], while certain literature has emphasized on the role of IP stage with IP recurrence [45] [46].

In a recent study [47], the authors did not identify an association between the Krouse stage and incidence of recurrence, which was compatible with the result of our study. In our study, 4 patients Most recurrences were found to be in patients previously found with stage T2, and a statistical p value of 0. In our study, only one patient underwent malignant transformation and was confirmed to be squamous cell carcinoma. This comprised 2. Most commonly, SCC was associated with malignant transformation of IPs, however, other types of carcinoma like adenocarcinoma, mucoepidermoid carcinomas, nasal undifferentiated carcinomas, small cell carcinomas and NOS not specifically specified were associated with IPs [44].

Mohajeri et al. Unfortunately, in our study, we did not have sufficient HPV testing, and that was considered as one of the limitations of this study. Smoking and exposure to tobacco was reported in While, nonsmokers in our study were reported to be This demonstrated that tobacco exposure was not a significant variable in terms of recurrence of the disease in this study sample. However, this is contradicted in literature that has identified smoking as an important risk factor of IP recurrence [44] [48].

Other factors have been documented regarding the role of genetic alterations such as p53, p21, p16, inflammatory genes, anti-apoptotic factors and intercellular adhesion molecules into SNIP malignant transformation [49]. Keles et al. This retrospective study summarized our findings in terms of clinical characteristics, post-operative recurrence rate, malignant transformation and other factors affecting the rate of recurrence.

The earlier the time of diagnosis and the earlier the Krouse staging at diagnosis, the more accurate and complete the surgical intervention would be. Rates of recurrence minimize with thorough resection of tumors at initial surgery. One of the limitations of this study was the missed long-term follow-up of these patients to detect recurrence in a timely manner.

Further studies are required for identification of risk factors and certain etiologies in the pathogenesis of Sino Nasal Inverted Papilloma as there are many controversies in the etiology of such papillomas. A special thanks to the pathology and radiology department members for providing the patients data.

We extend our thanks to Training Directorate, Ministry of Health, Kingdom of Bahrain, for their support and encouragement. All authors were involved with the conception and design of the study, analysis and interpretation of the data, and have approved the final manuscript. Modern Pathology, 15, Fukuoka Acta Medica, , Clinical Otolaryngology, 31, In: Barnes, L.

The Laryngoscope, , Otolaryngology-Head and Neck Surgery, , American Journal of Rhinology, 12, Cancer Research, 75, CAN [ 16 ] Scheel, A. Polish Journal of Otolaryngology, 71, Head and Neck Pathology, 8, Rhinology, 47, The Laryngoscope, 95, The Laryngoscope, 90, American Journal of Otolaryngology, 27, Journal of Institute of Medicine, 34, Otolaryngology—Head and Neck Surgery, , European Archives of Oto-Rhino-Laryngology, , Clinical Otolaryngology and Allied Sciences, 24, Supplement, 22, Brazilian Journal of Otorhinolaryngology, 86, Laryngoscope, , Journal of Craniofacial Surgery, 19, Laryngorhinootologie, 94, Annals of Oncology, 29, International Journal of Cancer, , Home Journals Article.

Israa M. This not only removes the obstruction caused by the polyps themselves, but allows medications such as saline irrigations and topical steroids to become more effective. Specially designed long nozzles had been developed to use postoperatively to deliver steroids into those areas after sinus surgery for polyps. Surgery lasts approximately 45 minutes to 1 hour and can be done under general or local anesthesia.

The person should expect some discomfort, congestion, and drainage from the nose in the first few days after surgery, but this should be mild. Many physicians recommend a course of oral steroids prior to surgery to reduce mucosal inflammation, decrease bleeding during surgery, and help with visualization of the polyps. Therefore, continued follow up with a combination of medical and surgical management is preferred for the treatment of nasal polyps.

Nasal polyps resulting from chronic rhinosinusitis affect approximately 4. From Wikipedia, the free encyclopedia. Noncancerous growths within the nose or sinuses. Medical condition. Allergic fungal sinusitis Kartagener's syndrome Young's syndrome Eosinophilic granulomatosis with polyangiitis Nasal mastocytosis.

Therapeutics and Clinical Risk Management. PMC PMID ISBN Essentials of Human Diseases and Conditions. Elsevier Health Sciences. Metin; Ferguson, Berrylin J. Middleton's Allergy: Principles and Practice. Nelson Textbook of Pediatrics. Ferri's Clinical Advisor. Professional Guide to Diseases. Upper Airway Disorders. Retrieved University of Kansas School of Medicine. Archived from the original on Ear, Nose and Throat Histopathology. Cummings Otolaryngology.

ISSN Classification D. Diseases of the respiratory system. Community-acquired Healthcare-associated Hospital-acquired. Broncho- Lobar. Atelectasis circulatory Pulmonary hypertension Pulmonary embolism Lung abscess. Mediastinitis Mediastinal emphysema. Gynaecology Gynecologic oncology Maternal—fetal medicine Obstetrics Reproductive endocrinology and infertility Urogynecology. Category Commons Wikiproject Portal Outline. Categories : Nose disorders.

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Download as PDF Printable version. Wikimedia Commons. Trouble breathing through the nose, loss of smell , decreased taste, post nasal drip , runny nose [1]. Sinusitis , broadening of the nose [2] [3]. Unclear [1]. Allergies , cystic fibrosis , aspirin sensitivity , certain infections [1].

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Our study showed 49 cases of Sino-Nasal Papilloma; of which 37 cases This was concordant with current literature [28] [29]. The mean age for SNIP patients was This was consistent with current literature that stated SNIP has preponderance in males. However, unlike most literature, our patients mean age was in the fourth decade and not the fifth decade of their lives [30] [31].

In terms of recurrence of disease, 13 cases There is still much controversy regarding the causative agents and the roles of different factors on the recurrence and persistence of IPs. However, in our study it was moderate in recurrence In our study, Sino-Nasal IPs involved the left side in 20 cases Of those 13 cases with recurrence, 8 cases The side of Sino-Nasal IP was not statistically related to the rate of recurrence or persistence of IPs, while lesion localization was of relative significance.

Also in accordance with other literature [29] [32], IP arising from the maxillary sinus, nasal cavity and ethmoidal sinuses were most frequently found. In our study, the most common was the nasal cavity followed by the maxillary sinus. The frontal sinus however, was high in prevalence in our study, which was contradictive with literature [33] [34] [35]. Recurrence was found to be in 13 cases This may be explained by the limitation of surgical accessibility to remove all tumors or due to surgeon discrepancies [36] [37] [38] [39] [40].

In recent literature, endoscopic surgery is a very effective and accurate treatment method for patients with IP [39]. In a study by Gil et al. In our study, all patients were managed by pure endoscopic methods. The clinical staging of IPs has been identified using the Krouse classification system, which is the most widely used staging system currently [43] [44], while certain literature has emphasized on the role of IP stage with IP recurrence [45] [46].

In a recent study [47], the authors did not identify an association between the Krouse stage and incidence of recurrence, which was compatible with the result of our study. In our study, 4 patients Most recurrences were found to be in patients previously found with stage T2, and a statistical p value of 0. In our study, only one patient underwent malignant transformation and was confirmed to be squamous cell carcinoma. This comprised 2. Most commonly, SCC was associated with malignant transformation of IPs, however, other types of carcinoma like adenocarcinoma, mucoepidermoid carcinomas, nasal undifferentiated carcinomas, small cell carcinomas and NOS not specifically specified were associated with IPs [44].

Mohajeri et al. Unfortunately, in our study, we did not have sufficient HPV testing, and that was considered as one of the limitations of this study. Smoking and exposure to tobacco was reported in While, nonsmokers in our study were reported to be This demonstrated that tobacco exposure was not a significant variable in terms of recurrence of the disease in this study sample.

However, this is contradicted in literature that has identified smoking as an important risk factor of IP recurrence [44] [48]. Other factors have been documented regarding the role of genetic alterations such as p53, p21, p16, inflammatory genes, anti-apoptotic factors and intercellular adhesion molecules into SNIP malignant transformation [49]. Keles et al. This retrospective study summarized our findings in terms of clinical characteristics, post-operative recurrence rate, malignant transformation and other factors affecting the rate of recurrence.

The earlier the time of diagnosis and the earlier the Krouse staging at diagnosis, the more accurate and complete the surgical intervention would be. Rates of recurrence minimize with thorough resection of tumors at initial surgery. One of the limitations of this study was the missed long-term follow-up of these patients to detect recurrence in a timely manner.

Further studies are required for identification of risk factors and certain etiologies in the pathogenesis of Sino Nasal Inverted Papilloma as there are many controversies in the etiology of such papillomas. A special thanks to the pathology and radiology department members for providing the patients data. We extend our thanks to Training Directorate, Ministry of Health, Kingdom of Bahrain, for their support and encouragement.

All authors were involved with the conception and design of the study, analysis and interpretation of the data, and have approved the final manuscript. Modern Pathology, 15, Fukuoka Acta Medica, , Clinical Otolaryngology, 31, In: Barnes, L. The Laryngoscope, , Otolaryngology-Head and Neck Surgery, , American Journal of Rhinology, 12, Cancer Research, 75, CAN [ 16 ] Scheel, A.

Polish Journal of Otolaryngology, 71, Head and Neck Pathology, 8, Rhinology, 47, The Laryngoscope, 95, The Laryngoscope, 90, American Journal of Otolaryngology, 27, Journal of Institute of Medicine, 34, Otolaryngology—Head and Neck Surgery, , European Archives of Oto-Rhino-Laryngology, , Clinical Otolaryngology and Allied Sciences, 24, Supplement, 22, Brazilian Journal of Otorhinolaryngology, 86, Laryngoscope, , Journal of Craniofacial Surgery, 19, Laryngorhinootologie, 94, Annals of Oncology, 29, International Journal of Cancer, , Home Journals Article.

Israa M. Mandeel 1 , Jehad H. Hammad 1 , Reem J. Radhi 2 , Sayed Ali I. DOI: Abstract Background: Inverted Papilloma IP is the most common benign neoplasms arising from the mucosal lining of the of the Sino-Nasal tract with single or multifocal attachment sites.

Share and Cite:. Qadmi, I. Clinical variables including age, gender, presenting symptoms, anatomical site Table 1. A B Figure 1. Conflicts of Interest The authors declare no competing interests. References [ 1 ] Barnes, L. Journals Menu. Contact us. All Rights Reserved. Barnes, L. Xu, B. Yasumatsu, R. Karkos, P. Myers, E. Bielamowicz, S. Kashima, H. McKay, S. Cheung, F. Hwang, C. Kraft, M.

Mohajeri, S. Lee, H. Dager, A. Scheel, A. Nowosielska-Grygiel, J. Lewis, J. Exophytic papilloma. Oncocytic papilloma. Malignant transformation carcinoma ex sinonasal papilloma. S , CD45 and other nonepithelial markers. Sample pathology report.

Maxillary sinus, left; biopsy: Sinonasal papilloma, inverted type. Differential diagnosis. Additional references. Mod Pathol ; Board review style question 1. Which of the following statements about this sinonasal lesion is false? Board review style answer 1. This is an oncocytic papilloma.

Comment Here Reference: Sinonasal papilloma. Board review style question 2. Which of the following statements about sinonasal papilloma is true? Both inverted and oncocytic papilloma may show endophytic growth pattern Oncocytic sinonasal papilloma has a negligible risk of malignant transformation Standard of care for sinonasal papilloma is observation or excision for symptom control Subtypes of papilloma that may be related to human papillomavirus HPV are oncocytic and exophytic subtypes; inverted papilloma has no significant association with HPV.

Board review style answer 2. Both inverted and oncocytic papilloma may show endophytic growth pattern Comment Here Reference: Sinonasal papilloma. Sign up for our Email Newsletters. Click here for information on linking to our website or using our content or images. Home About Us Advertise Amazon. Telephone: ; Email: Comments pathologyoutlines. This website is intended for pathologists and laboratory personnel but not for patients. We welcome suggestions or questions about using the website.

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