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Clinical Observations |
1 Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, New
Jersey Medical School, University of Medicine and Dentistry of New Jersey, 140
Bergen St., Ste. E1620, Newark, NJ 07103.
2 Department of Radiology, Division of Nuclear Medicine, New Jersey Medical
School, University of Medicine and Dentistry of New Jersey, Newark, NJ.
3 Department of Pathology, New Jersey Medical School, University of Medicine and
Dentistry of New Jersey, Newark, NJ.
Received August 11, 2008;
accepted after revision September 17, 2008.
Address correspondence to E. G. Cohen
(coheneg{at}umdnj.edu).
Abstract
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CONCLUSION. Benign sinonasal papilloma may be associated with intense FDG uptake on PET/CT. FDG PET/CT does not appear to reliably differentiate benign from malignant sinonasal papilloma.
Keywords: FDG PET • inverted papilloma • PET/CT • sinonasal papilloma • squamous cell carcinoma
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Treatment of sinonasal papillomas is primarily by complete surgical resection, most commonly either open or endoscopic medial maxillectomy. Recurrence of inverted papilloma has been reported in 18% of patients treated by standard open surgical techniques in a pooled analysis [2]. Common postsurgical follow-up consists of serial nasal endoscopy and CT or MRI. It is often difficult to differentiate postoperative mucosal thickening and fibrosis from recurrent papilloma on clinical examination and routine radiologic imaging.
Case reports of FDG uptake in several types of papillomas have been published, including tonsillar papilloma (unspecified type) [3], maxillary sinus papilloma (unspecified type) [4], pulmonary glandular papilloma [5], choroid plexus papilloma [6], and intraductal papilloma of the breast [7]. A case of inverted papilloma with intense FDG uptake (standardized uptake value [SUV], 9.0 at 1 hour and 18.1 at 2 hours) [8] and a case of sphenoid sinus oncocytic papilloma with intense uptake (mean SUV, 11.26; maximum SUV, 18.86) [9] have also been reported. Two reports have indicated that PET can be used to differentiate squamous cell carcinoma from inverted papilloma. Significantly higher FDG uptake was reported in five cases of carcinoma (SUVs, 10.40-19.3) than in five cases of sinonasal inverted papilloma (SUVs, 1.98-4.65) [10], whereas another series reported SUVs of 4.9-7.3 associated with three cases of benign inverted papilloma and higher SUVs of 8.9 and 20.9 associated with squamous cell carcinoma [11].
We performed a retrospective review of our experience with FDG PET/CT scintigraphy in the preoperative evaluation of patients with histopathology-proven sinonasal papilloma.
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Combined PET/CT was performed using a combined PET/CT scanner (Discovery LS, GE Healthcare) and relatively standard techniques. No IV diuretics or hydration was administered, and no bladder catheterization was performed. Patients fasted for a minimum of 4 hours before PET acquisition. After confirmation of a blood glucose level < 200 mg/dL, 555 MBq (15 mCi) of sterile FDG was administered IV followed by a radiotracer uptake phase of approximately 60 minutes. Patients voided before administration of FDG and again before image acquisition. Positron emission data sets were acquired typically from the base of the skull to the mid thigh, with separate acquisition of the head and neck region from the vertex to the thoracic inlet, for 5 minutes at each bed position. PET images were reconstructed using the OSEM (ordered subset expectation maximization) algorithm. Low-dose CT was acquired and used for attenuation correction and was fused onto the PET images for anatomic correlation.
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Case 1
A 92-year-old woman presented with epistaxis from the right side. Her
medical history was significant only for hypercholesterolemia. Physical
examination revealed an exophytic lesion involving the right lateral nasal
wall. The remainder of the head and neck examination was normal. Transnasal
biopsy results were interpreted as inverted papilloma. A CT scan of the
sinuses with IV contrast material and an MRI scan with gadolinium were
obtained (Figs. 1A and
1B). A PET/CT scan revealed
extremely intense FDG uptake in the right maxillary sinus and anterior ethmoid
sinus, with a mean SUV of 30.0 and maximum SUV of 43.0 (Figs.
1C and
1D). The patient underwent an
open medial maxillectomy.
Final pathology revealed an oncocytic papilloma (a variant of cylindric cell papilloma) with reactive atypia, without an inverted growth pattern, and with no evidence of squamous cell carcinoma.
Case 2
A 64-year-old man presented with an incidental finding of left maxillary
lesion on MRI. He had a history of a cerebrovascular accident 1 year earlier.
MRI of the brain at that time revealed a right transverse sinus arteriovenous
malformation with an incidental finding of a maxillary sinus lesion extending
into the nasopharynx (Fig. 2A).
He denied any nasal obstruction, epistaxis, pain, or congestion. Physical
examination of the head and neck was within normal limits. Nasal endoscopy
revealed a lobulated lesion protruding from the maxillary sinus into the nasal
cavity and posterior choana that was presumed to be an antrochoanal polyp. A
CT scan of the sinuses was obtained (Fig.
2B). Endoscopic polypectomy was planned; however, on
intraoperative examination, the lesion was not consistent with an antrochoanal
polyp. Endoscopic maxillary antrostomy and partial resection for tissue
diagnosis were performed.
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Case 3
A 52-year-old man with no significant medical or surgical history presented
with complaints of progressive nasal obstruction over a 20-year period
associated with rare epistaxis. Physical examination revealed a large
obstructing lesion in the left nasal cavity. The remainder of the head and
neck examination was normal. An intranasal biopsy specimen was consistent with
inverted papilloma. A CT scan of the sinuses with IV contrast material and an
MRI scan with gadolinium were obtained. A PET/CT scan revealed increased FDG
uptake in the left nasal cavity that extended into the left maxillary and
ethmoid sinuses and nasopharynx (mean SUV, 3.3; maximum SUV, 4.6). The uptake
was heterogeneous, with more intense uptake in the maxillary sinus and
nasopharynx. The patient underwent an open medial maxillectomy.
Pathology results revealed an inverted papilloma with no evidence of squamous cell carcinoma. Thickened mucosa from the lateral aspect of the maxillary sinus, sent as a separate specimen, showed respiratory epithelial adenomatoid hamartoma.
Case 4
A 47-year-old man with HIV and a 6-year history of recurrent inverted
papilloma involving bilateral nasal cavities and the pharyngeal wall presented
with recurrent nasal obstruction and new-onset cervical lymphadenopathy. The
patient had undergone multiple previous resections at multiple institutions
and had also received radiotherapy. Previous pathology results were consistent
with inverted papilloma without invasive carcinoma. At the time of
presentation, CT scans revealed recurrent inverted papilloma that was not
completely resectable. Endoscopic partial excision of the inverted papilloma
on the right and endoscopic excision of a small recurrent papilloma on the
left were performed for symptomatic relief. A cervical lymph node biopsy was
performed as well.
Pathology confirmed papilloma with both inverted and exophytic growth patterns without invasive carcinoma. The cervical lymph node biopsy revealed Hodgkin's lymphoma. A PET/CT scan was then obtained for lymphoma staging. Intense FDG uptake was noted in the right nasal cavity, ethmoid and maxillary sinuses, and pharynx (mean SUV, 6.2; maximum SUV, 9.0), corresponding to known areas of residual inverted papilloma.
Case 5
A 43-year-old HIV-positive man presented with a left nasal mass noted while
blowing his nose, slowly growing in size. Physical examination revealed a 1-cm
pedunculated lesion along the left anterior nasal septum. PET/CT scans
revealed intense uptake corresponding to the nasal mass (mean SUV, 4.7;
maximum SUV, 8.5). The patient underwent endoscopic excision of the mass.
There was no cartilage involvement noted.
Final histopathology revealed sinonasal papilloma with both inverted and exophytic growth patterns associated with moderate to severe dysplasia involving approximately 50% of the lesion, but no invasive carcinoma.
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These findings suggest that although FDG PET scintigraphy may be useful in detecting sinonasal papillomas, the degree of uptake cannot be used to reliably differentiate squamous cell carcinoma from benign papilloma even when intense uptake is present. A lack of specificity of FDG uptake has been reported at several other head and neck locations. A lack of correlation of SUV with malignancy in parotid tumors has been well documented, with a similar degree of uptake reported for parotid carcinomas, Warthin tumors, and pleomorphic adenomas [12]. Similarly, investigators have reported that SUV does not correlate with malignancy in incidentally discovered thyroid lesions because 50% of nodules with focal FDG uptake are due to benign tumors or nonneoplastic conditions [13]. False-positive PET scans may also result from inflammatory conditions such as infection, granulomatous disease, asymmetric muscle activity, physiologic uptake, and inflammation and granulation at surgical sites [14, 15]. Reported causes of the reduced sensitivity of FDG PET for the detection of malignancy include partial volume averaging of small tumor volumes, non-FDG-avid tumors, and lesions occurring in areas of physiologically high FDG background [14, 15].
In this study, FDG PET scintigraphy was performed after biopsy. Biopsies performed close to the time of PET may have led to increased FDG uptake due to inflammation from the procedure. However, in this study, imaging was consistently performed more than 4 weeks after biopsy, making it unlikely that inflammation resulting from the biopsy affected the degree of uptake.
In case 1, the finding of an extremely high SUV was not associated with carcinoma. The oncocytic cells seen on routine H and E staining contained abundant mitochondria ultrastructurally, which may explain the high metabolic activity and FDG uptake. Others have attributed intense FDG uptake in inverted papilloma to the presence of marked inflammatory response within the lesion [8].
Case 2 shows the potential for the use of FDG PET scintigraphy in the postoperative setting. In this case, endoscopic partial resection was performed as a diagnostic procedure. The residual inverted papilloma had only moderate FDG uptake, but could be differentiated from adjacent edematous mucosa. Routine use of FDG PET scintigraphy in the postoperative setting cannot be recommended given its cost and radiation exposure, as well as lack of availability in some areas; however, selective use may be helpful in clinical decision making when physical examination, CT, and MRI are equivocal.
Case 3 showed heterogeneous uptake, and two separate histopathologic diagnoses were made. Most of the lesion was inverted papilloma and corresponded to the region of the most intense uptake—that is, the nasopharynx. The lateral maxillary sinus mucosa contained respiratory epithelial adenomatoid hamartoma. It is difficult to ascertain whether the uptake on PET in the maxillary sinus region was due to inverted papilloma, respiratory epithelial adenomatoid hamartoma, or both. No carcinoma was seen in any part of the specimen.
Cases 4 and 5 showed intense FDG uptake in sinonasal papillomas with both inverted and exophytic growth patterns and without invasive carcinoma. Although pathologic examination in case 5 revealed moderate to severe dysplasia, no carcinoma was seen. The degree of FDG uptake in case 5 was similar to that in case 4, which was not associated with dysplasia.
In conclusion, our findings suggest that the degree of FDG uptake on PET/CT is not a reliable indicator of malignancy associated with sinonasal papilloma because moderate to extremely intense uptake was seen with benign sinonasal papillomas. Nonetheless, FDG PET/CT scintigraphy may be useful in showing the presence and extent of sinonasal papilloma and may help in differentiating papilloma from postoperative fibrosis and mucosal edema in cases of suspected recurrent or residual papilloma.
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