MAXILLOFACIAL

Inverted Papilloma

Inverted papilloma is a lesion of the mucosal membrane of the nasal cavity and paranasal sinus. It is a rare tumor occurring in approximately 0.5% of the nasal tumors, thus representing approximately 4% of all nasal polyps. The earliest reference to a papilloma of nasal cavity was by Ward in 1854 with the microscopic appearance characterized by Ringertz in 1938. There are many different names used to describe different papillomas. These include fungiform papilloma, cylindrical cell papilloma, Schneiderian cell papilloma, epithelial papilloma, and many more.
The typical presentation is of unilateral polyps. This presentation would have the differential diagnosis of antral choanal polyp, allergic fungal sinusitis, squamous cell carcinoma, adenocarcinoma, esthesioblastoma, inverted papilloma and other rare tumors.
A through literature review was performed by Bielamowicz et. al. They found the average age of diagnosis to be 53 with a range from 6 years old to 91 years old. On review the most common site the lateral nasal wall. Less common sites are the vestibule, the septum, the floor of the nasopharynx, sphenoid and frontal sinus, and the lacrimal sac. The same study found the presenting symptoms to be nasal obstruction with other symptoms far less common such as epistaxis, pressure and pain, rhinorrhea, proptosis, and epiphora. Other symptoms not present in this study but found in literature were facial numbness, diplopia, hypo-nasal speech, facial pruritus, and anosmia.
Histology:
Inverted papilloma grossly looks like a polyp, but is usually firmer with significant bulk and has more of a granular mulberry type appearance. They are a variety of colors from red to pale pink. They are usually more vascular than the average polyp. Microscopically the lesion has a thickened epithelial covering with extensive invasion of the hyperplastic epithelium into the underlying stroma. The behavior of the invasion into the underlying stroma has been theorized to be due to a origin from the Schneiderian membrane.
The Schneiderian membrane is of ectodermal origin from the nasal placode, there may be some difference in the underlying stroma which permits inversion of the papilloma. The tumor has crypts which are subepithelial and maintain connection to the surface epithelium at all times, a finding which lead to the name inverted papilloma. Micro-cyst containing mucus are often trapped within the neoplastic epithelium. The covering epithelium can be squamous, respiratory, or transitional cell epithelium or a combination of all three. The cells show minimal nuclear atypia with the typical basilar layer mitosis. The stroma usually has acute and chronic inflammatory changes with areas of fibrosis and edema. The stroma is almost lacking in eosinophils which would be prevalent in an allergic polyp.
The tumor appears to invaginate or infold into the surrounding underlying bone yet does not invade in the absence of malignancy. To an inexperienced pathologist a specimen which is tangentially cut may lead to the misinterpretation that the epithelium is not connected to the surface, simulating stroma invasion.
The incidence of focal malignancy within inverted papilloma or a site adjacent to papilloma ranges from 1% to 53% (usually quoted as 5-15%) The development of carcinoma at the site of a previously removed inverted papilloma is a less common event. In the malignant areas of inverted papilloma the squamous epithelium shows marked atypia, increased nuclear to cytoplasmic relation, conspicuous nucleoli, atypical mitosis in the middle and upper layers, loss of polarity and dyskeratotic cells. The loss of polarity, anaplasia of cells and lack of maturation are the most reliable criteria. There is no clearly defined criteria for borderline cases of marked dysplasia or carcinoma in situ. The type of epithelium or stromal inflammation has no role in determining which lesion represents malignancy.
Etiology:
Inverted papilloma has an unknown etiology. There have been many causes suggested such as allergy, chronic sinusitis, and viral infections. Allergy is unlikely since most of the patients do not have an allergic history and the polyposis associated with allergic rhinitis is usually bilateral. The presence of sinusitis is thought more to be related to the obstructive nature of the disease and not the cause. The signs of chronic infection of the sinuses are much to common to be implicated in the rare case of inverted papilloma. Viruses have been implicated due to the well described finding in recurrent respiratory papillomatosis. A recent study has shown the presence of the human papilloma virus in specimens of inverted papilloma hybridized in situ with RNA probes to HPV 6, 11,16, and 18. No definite correlation has been found with subtype and dysplasia which is the case out side the sinonasal tract.
Work up:
The workup consist of a thorough history and physical exam. The associated symptoms are classically those of unilateral nasal obstruction of varied duration. The patient may have a history of facial pain, rhinorrhea, sinusitis or epistaxis. These are all quite rare. On endoscopic exam the polyp will usually originate from the medial maxilla, but on occasion has been found on the septum, vestibule or from the frontal sinus. A CT scan is essential in the evaluation of the tumor. This allows for the proper surgical approach and extent to be performed. A biopsy of the specimen is necessary to obtain a definitive diagnosis. All nasal biopsies must be taken seriously because of the chance of severe epistaxis or biopsy of the brain. If any question of skull base involvement or vascular tumor by imaging, further radiologic studies should be performed such as MRI or angiogram. With any question the biopsy should be performed in a control setting such as the operating room.
Surgical procedures:
Medial Maxillectomy:
Medial maxillectomy through lateral rhinotomy incision is the gold standard for the removal of inverted papilloma. It has the advantages of excellent exposure of the lateral nasal wall and paranasal sinuses. The success is related to the en bloc resection of the lateral nasal wall, ethmoid labyrinth, and medial portion of the maxilla which are the sites of formation and extension of this tumor.
This is a procedure that allows visualization of the tumor margins while allowing preservation of the orbital rim, the eye and its attachments, the lacrimal apparatus, the nasal pyramid, and the palate. The medial maxillectomy allows an en bloc removal of the ethmoidal labyrinth and the medial aspect of the maxilla from the cribriform plate superiorly to the floor of the nose inferiorly; and from the anterior extent of the ethmoidal cells back to the area of the optic nerve. The lamina papyracea is included in the tissue block. This technique can be expanded to involve the removal of the cribriform plate when combined with an intracranial approach.
A lateral rhinotomy incision is made beginning in the medial aspect of the eyebrow, angling around to midway up the lateral wall of the nose and into the alar groove. A notch can be made in the medial canthal area to prevent webbing. The exposure should be adequate without cutting the lip which also leaves better final cosmesis. A subperiosteal dissection is performed exposing the anterior wall of the maxillary sinus. The infraorbital nerve is identified and protected. The medial wall of the orbit is dissected exposing the anterior and posterior ethmoid artery which will be the superior most aspect of the dissection. The lacrimal sac is dissected out of its sulcus and at its most distal aspect divided. An antrostomy in to the maxillary sinus is performed and then the remainder of the maxillary sinus is removed taking care to preserve the infraorbital nerve.
A lateral osteotomy of the nasal bone is performed to give better visual exposure. The first major cut is along the floor of the sinus. This cut is made in the inferior meatus from the anterior tip of the inferior turbinate to the most posterior aspect. The second bone cut entails the medial most part of the orbital rim which is drilled down using a cutting bur until into the floor of the orbit. This aspect my be omitted but may give better visual access with minimal structural defect. The third cut is made along the anterior aspect of the maxillary sinus involving the lacrimal fossa, anterior to the middle turbinate and into the ethmoid cells. The anterior bony rim forming the piriform aperture and the nasal rim is left intact.
If the lacrimal duct is left in place the cut is made posterior to it. It is usually cut and marked for stenting later in the operation. The fourth cut involves retracting the orbital contents to expose the frontoethmoidal suture line and the anterior ethmoid artery. A small osteotome is used to perforate the ethmoidal cells and the nasal cavity is entered inferior to the suture line, beginning anteriorly in the lacrimal fossa and extending posteriorly.
The suture line and the ethmoidal arteries establish the position of the cribriform plate. If more posterior dissection is needed the anterior ethmoid artery may be ligated. The fifth cut involves freeing the posterior and lateral aspect of the lamina papyracea the cut is extended along the posterior part of the lamina with a curved mayo scissors and goes along the inferior part of the orbit along the rim just medial to the infraorbital nerve. This will then join with the drilled incision through the rim. The remaining bony attachment of the lateral nasal wall is that portion of the palatine bone that is anterior to the pterygoid process of the sphenoid bone. This attachment extends from the nasal floor up to the superior turbinate. The en bloc specimen is gently rocked bimanual to reveal the remaining attachments. The using a right-angled scissors starting interiorly through the nose placing the lateral blade in the maxillary sinus while the medial blade lies in the inferior meatus. The curved scissors will make a cut just anterior to the pterygoid plate which is the posterior aspect of the inferior and middle turbinates. The superior aspect of the incision is technically impossible to perform using the scissors.
A bimanual maneuver using your index fingers place in the maxillary sinus and the other in the nose the bone is used to fracture this area. The attached mucosa must then be cut. The en bloc specimen is delivered through the nasal aperture. All the mucosa should be removed from all the involved sinuses. All bony spicules should be burred smooth and all sinuses opened widely into one large cavity which makes for easy post operative examinations.
Antibiotic coated nugauze is the packed in the nose. The nasal bone is returned and secured. The lacrimal drainage is handled by placing silastic tubing into the sac and securing this with a purse string suture. This will be left in place for 6 weeks to form a mucosalized lining to secure adequate drainage. The medial canthal ligament and periosteum is secured in its proper position.
The most common complication found was epiphora. Other complications discribed are transient diplopia, mucocele, CSF leakage, epistaxis, and scar formation. The amount of epiphora has improved with DCR management of the lacrimal sac at the time of surgery.
Midfacial degloving:
Midfacial degloving is an excellent alternative open procedure. It also provides excellent exposure bilaterally and does not require and external scar. The midfacial degloving procedure utilizes a combination of four facial incisions with or without osteotomies of the nasal bone and frontal process of the maxilla. Literature first describes a similar approach in 1927 by Protmann and Retrouvey who performed a sublabial-transoral radical maxillectomy. The procedure has been used extensively since 1969 by Maniglia, Conley and Price. It has been used for benign tumors such as inverted papilloma and also malignant tumors.
In this technique four incisions are made. (1) bilateral sublabial; (2) complete transfixion between the columella and septum; (3) bilateral piriform aperture incisions extending to the vestibule; and (4) Either a intercartlaginous or a marginal incision (used with an external rhinoplasty). It is best to overlap at right angles at the corners to prevent rounding and web formation. The lower frame work of the nose is released similar to a septorhinoplasty approach. The periosteum of the maxilla is elevated preserving the infraorbital nerves. The skin, lower 1/3 of the nose can be elevated to the glabella and orbit. This is secured and retracted with a penrose through the nostrils. The Internal maxillary artery may be encountered and ligated as it enters the pterygopalatine fossa.
If exposure of the nasofrontal duct or cribriform plate is needed, medial, lateral and superior osteotomies are done to expose this area by retracting the nasal bones and frontal process. This area must be repositioned and secured at the end of the case. Exploration of the orbit is possible with retraction of the periorbit. The zygoma also may be widely exposed by extending laterally the periosteal elevation.
Excellent visualization of the nasopharynx is possible with wide removal of the anterior maxillary wall, ethmoidectomy and lateral retraction of the turbinates.
The midfacial degloving procedure can give exposure for pathology involving the frontal sinus by combining it with a frontal sinus osteoplastic flap. The osteotomies performed and removal of the medial maxillectomy may be performed in a similar fashion as stated above.
After the tumor is removed, the nasal tip is brought back to its normal position, and using 4-0 chromic suture the septocolumellar junction is secured. The sublabial incisions are approximated. Packing is placed in the nasal and maxillary cavities . Nasal splint can be applied for added support.
The disadvantages to this approach are (1) The potential for nasal vestibular stenosis, and (2) Difficulty with superior ethmoid exposure in large tumors. The vestibular stenosis can be avoided with proper incision design. Other complications include oroantral fistula, epistaxis, and nasal crusting which are present with the medial maxillectomy as well as the midfacial degloving. The advantage is avoidance of a facial scar and allows bilateral exposure.
Endoscopic approach:
Two studies have advocated endoscopic resection of Inverted papilloma. Waitz and Wigand reported a series of 51 patients with a mean F/U of 46 months. They reported a 19% recurrence rate with extranasal approach and 17% with endoscopic approach. This study is probably biased with selection of very small lesions with no evidence of malignancy. These lesions appeared to be less aggressive with a lower overall final malignancy rate 4% compared to literature average about 11%. ESS is still a promising option in the future when the technique is perfected. Kennedy uses endoscopic control for two types (1) very small, or (2) skull base involvement to avoid craniofacial resection with a benign disease.
Radiation therapy:
Radiation is usually not a recommended option to surgery. It has been suggested that it may be effective in the treatment of advanced aggressive tumors or patients who are poor surgical candidates. There has been some concern with the use of radiation therapy for the treatment of inverted papilloma without an associated malignancy. A study by Mayberry, et al reported 4 out of 14 patients treated for benign disease with radiation therapy. Two other studies by Weissler, et al and Mendenhall, et al. have shown no conversion to malignancy and excellent control rates. Combined surgical and radiation therapy appears to be effective in patients found to have SCCA associated with their inverting papilloma.
Medical therapy:
With some of the new data suggesting the Human Papilloma Virus may be a potential etiologic factor in the development of inverted papilloma the use of antiviral agents may be beneficial. Interferon has been suggested for the use of a patient with multiple recurrences, advanced disease, or spread to the orbit and skull base. This is still investigational.
Conclusion:
Inverted papilloma represents a benign neoplastic proliferation with a high recurrence rate. It has the propensity for invasion into adjacent structures, such as the orbit and CNS even in the absence of malignancy. The tumor is classified as an “intermediate” tumor and needs to be handled by an en bloc surgical approach. The recurrence rate is related to the adequacy of surgical excision. Simple excision with polypectomy or Caldwell Luc approach resulted in 67 to 78% recurrence and when lateral rhinotomy and medial maxillectomy were performed recurrence was 0 to 14%. Even this is quite high for a benign disease and is probably thought to be related to a multicentric disease process. Incomplete removal of the tumor is the most important factor in recurrence. Involvement of the paranasal sinuses, nasofrontal duct, lacrimal fossa and the infraorbital recess of the maxillary sinus are sites associated with high recurrences. It is rare the recurrence will occur 2 years after surgery. The practice of sending all tissue removed at time of surgery including nasal polyps for histopathological examination may result in earlier and more accurate of the tumor.