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RESPIRATORY EPITHELIAL ADENOMATOID HAMARTOMAS:

BENIGN NEOPLASM MINMICKING INTRANASAL POLYPOSIS * Adrienne L Childers MD, * Eric N Appelbaum MD, ‡ Woon N. Chow MD PhD, ‡ Celeste N. Powers MD PhD, * Evan R Reiter MD, FACS

*Department of Otolaryngology-Head and Neck Surgery and ‡Department of Pathology,

Virginia Commonwealth University School of Medicine, Richmond, Virginia

INTRODUCTION

DISCUSSION

CASE REPORT

ABSTRACT

METHODS AND MATERIALS

CONCLUSIONS

REFERENCES

Correspondence:

Objectives: To review the case of a 69 year-old female with history of nasal polyposis found to have respiratory epithelial adenomatoid hamartoma (REAH) of bilateral nasal passages. We will present a review of current literature with discussion of epidemiology, evaluation, and treatment. Methods: Case report and literature review. Results: 69 year-old female with remote history of adenocarcinoma of lung and pT1N0 cutaneous melanoma of right cheek presented to clinic for routine surveillance with complaint of persistent postnasal drip. Patient reported that she had previously undergone surgical debridement of nasal polyposis on two occasions. Nasal endoscopy revealed localized smooth gray/white polypoid lesions in bilateral upper nasal vaults. CT Sinuses was obtained with note of abnormal thickening of the nasal septum anteriorly and decision was made to proceed with nasal endoscopy with debridement. In the OR, patient again noted to have bilateral non-obstructing polyps medial to the middle turbinate within the superior nasal vault. Polypoid tissue removed with final pathology read as REAH. REAH is a benign entity that was first described in 1995 (Wenig and Heffner). Growth results from abnormal proliferation of glandular tissue lined by pseudostratified, ciliated respiratory epithelium. Etiology of this disease process is unknown at this time and presentation is often confused chronic sinusitis. Curative treatment is surgical excision with low rate of recurrence. Conclusions: REAH is a rare entity often found incidentally on pathologic review of specimen. Clinically, REAH is difficult to diagnose as patients have symptoms indistinguishable from chronic sinusitis. These lesions can also be misinterpreted as inflammatory nasal polyposis, inverting papilloma or low-grade adenocarcinoma on pathology, so it is imperative that an experienced pathologist review histology to ensure adequate resection is completed. Treatment of REAH is surgical excision, which is curative in most cases.

Adrienne Childers MD VCUHS Department of Otolaryngology- Head and Neck Surgery 1200 East Broad Street West Hospital 12th Floor, South Wing, Suite 313 PO Box 980146 Richmond, VA 23298-0146 achilder@mcvh-vcu.edu

Respiratory epithelial adenomatoid hamartoma (REAH) is a benign entity first described in 1995 by Wenig and Heffner. Growth results from abnormal proliferation of glandular tissue lined by pseudostratified, ciliated respiratory epithelium. No specific causative etiology is known and presentation is often confused chronic sinusitis.

Case report and literature review.

A 69 year-old female with remote history of adenocarcinoma of lung and pT1N0 cutaneous melanoma of right cheek presented for routine tumor surveillance with complaint of persistent clear postnasal drip. She had previously undergone surgical resection of nasal polyposis on two occasions in the remote past. Nasal endoscopy revealed smooth gray/white polypoid lesions bilaterally in the upper anterior nasal vaults. Sinus CT revealed soft tissue thickening of the anterior nasal septum and decision was made to proceed with endoscopic treatment. Intraoperatively the patient was noted to have bilateral non-obstructive polyps arising from the septum medial to the middle turbinates within the superior nasal vault. Final pathology was read as REAH.

Respiratory epithelial adenomatoid hamartomas (REAH) are uncommon, benign, glandular tumors of the upper airway. Hamartoma in general is an abnormal benign proliferation composed of more than one tissue type indigenous to the body site of presentation. REAH was first characterized by Wenig and Heffner in a case series of 31 patients with hamartomas occurring in the nasal cavity, paranasal sinuses, and nasopharynx1. These are rather rare entities. Prior to Wenig and Heffner’s 1995 case series, only thirteen cases had been reported in the literature4. Recently, publication of several large case series have greatly expanded the data on these lesions5—7. As characterized in the initial case series, REAH most commonly arises in men in the third through ninth decades of life1,8. The mean age at presentation is approximately 58 years old5. Studies have shown a male predominance of over 3:11,5. Presenting symptoms are similar to other obstructive sinonasal processes, with nasal obstruction (56.9%) and nasal congestion (37.3%) most commonly, and other symptoms including hyposmia/anosmia, headache/facial pressure, rhinorrhea/postnasal drip, epistaxis, and ear plugging occurring less frequently5. REAH has been described in the nasal cavity, paranasal sinuses, and nasopharynx1,3,8-10. In Wenig and Heffner’s series, 71% of their 31 cases arose in the nasal cavity, with a majority of these occurring on the posterior nasal septum1. However Vira et al. found a majority of lesions (81%) occurring in the paranasal sinuses compared to the nasal cavity6.

REAH is a rare entity often found incidentally on pathologic review of specimen. Clinically, REAH is difficult to diagnose as symptoms are indistinguishable from chronic sinusitis or other nasal lesions, and appearance is similar to inflammatory polyps or other benign pathologies. REAH can also be misinterpreted as inflammatory polyposis, inverting papilloma or low-grade adenocarcinoma on pathology, so consideration of this entity, and careful interpretation of pathologic specimens is imperative to ensure proper diagnosis. Treatment of REAH is surgical excision, which is curative in most cases.

1. Wenig BM, Heffner DK. Respiratory epithelial adenomatoid hamartomas of the sinonasal tract and

nasopharynx: A clinicopathological study of 31 cases. Ann Otol Rhinol Laryngol. 1995; 104:639—645

2. Endo R et al. Respiratory Epithelial Adenomatoid Hamartoma in the Nasal Cavity. Acta Otolaryngol.

2002; 122: 398—400

3. Caltabiano R et al. Respiratory epithelial adenomatoid hamartoma: case report and literature review.

Pathologica. 2008; 100: 185—188

4. Fitzhugh VA and Mirani N. Respiratory Epithelial Adenomatoid Hamartoma: A Review. Head and Neck

Pathology. 2008; 2:203—208.

5. Lee JT et al. Sinonasal respiratory epithelial adenomatoid hamartomas: Series of 51 cases and

literature review. American Journal of Rhinology & Allergy. 2013; 27:322—328

6. Vira D, Bhuta S, Wang MB. Respiratory Epithelial Adenomatoid Hamartomas. Laryngoscope. 2011;

121:2706—2709.

7. Hawley KA, Pabon S, Hoschar AP, and Sindwani R. The presentation and clinical significance of

sinonasal respiratory epithelial adenomatoid hamartoma (REAH). Int Forum Allergy Rhinol. 2013;

3:248—253.

8. Kessler HP, Unterman B. Respiratory epithelial adenomatoid hamartoma of the maxillary sinus

presenting as periapical radiolucency: A case report and review of the literature. Oral Surg, Oral

Med, Oral Path, Oral Rad, and Endo. 2004; 97:607—612

9. Athre R, Ducic Y. Frontal sinus hamartomas. American Journal of Otolaryngology. 2005; 26:419—421

10. Picciotti PM et al. Rhino sinusal bilateral hamartoma: A case report. Auris Nasus Larynx. 2008; 35:

569—571

11. Ozolek JA, Hunt JL. Tumor suppressor gene alterations in respiratory epithelial adenomatoid

hamartoma (REAH): Comparison to sinonasal adenocarcinoma and inflamed sinonasal mucosa. Am

J Surg Path. 2006; 301576—1580

12. ZhiWei C et al. Respiratory epithelial adenomatoid hamartoma of bilateral olfactory clefts associated

with nasal polyposis: Three cases report and literature review. Auris Nasus Larynx. 2010; 37: 352—

356

REAH often occurs in the setting of increased sinonasal inflammation. Vira et al found 81% of REAH arose in the setting of chronic sinusitis or chronic allergic sinusitis, with 9 cases (17%) associated with nasal polyposis6. Although the etiology of REAH has not entirely been elucidated, the association with chronic inflammatory conditions suggests this may play some role in the development of these lesions. Though REAH is classified as a benign lesion, research has shown allelic loss at a higher rate (31%) than would be expected for a non-malignant entity11. Treatment of REAH consists of resection of the lesion, which can typically be accomplished endoscopically. Symptoms generally resolve after removal of the mass12. REAH generally do not recur after complete excision, although recurrences have been reported. Vira et al. found recurrence in 2 of 54 cases (3.7%), occurring after a mean of 3.8 years, both of which were then treated successfully with repeat surgery6. Histologically, REAH exhibits glandular proliferation of pseudostratified, columnar epithelium, typical of the respiratory tract, without atypia or malignant change2,3. Histologic identification of these lesions is important to distinguish them from them from other, similar-appearing lesions. Low-grade adenocarcinoma, inverted papilloma, and inflammatory polyps require a more aggressive surgical approach, inappropriate for REAH1,6,12.

Figure 1: Low-power view (scale bar = 500 µm) of a hematoxylin and eosin stained tissue section showing a well-differentiated polypoid proliferation of generally small- to medium-sized round to oval glandular structures separated by an edematous stroma; some of these glands are distended from being filled with mucus

Figure 2: .High- power view (scale bar = 100 µm) shows the glandular structures to be lined by a ciliated stratified or pseudostratified respiratory-type epithelium with occasional goblet cells. A thickened and eosinophilic basement membrane surrounding the glands is commonly observed. As demonstrated here, the glandular structures are often in direct continuity with the surface epithelium (arrow).

DISCUSSION (continued)