Baylor University Medical Center Proceedings April 2017 - 222

Figure 2. Hematoxylin and eosin-stained right nasal biopsy showing inflamed
polypoid fragments of respiratory mucosa with features consistent with respiratory
epithelial adenomatoid hamartoma. (a) 4× power, (b) 40× power.

reported no improvement of olfaction. MRI of the brain for
unrelated reasons 27 months postoperatively revealed no evidence of recurrence.
DISCUSSION
The histopathological features of REAH are dominated by
a polypoid pseudoglandular proliferation (4). These characteristics include widely spaced, small- to medium-sized pseudoglands that invaginate directly into the submucosa and are
separated by stroma tissue. The glands are round to oval and are
composed of multilayered ciliated respiratory epithelium (3).
These features were identiﬁed in the lesions resected from the
bilateral olfactory clefts of our patient (Figure 2).
When REAH was ﬁrst described in 1995, it was considered
extremely rare and isolated (2). We now know that REAH is
not as uncommon as originally thought and is often present
with other inﬂammatory processes (3). In a case series, 73% of
45 patients with REAH had an additional associated pathological process, most commonly nasal polyposis (NP) (9). Recent
studies have shown that REAH was found in 35% to 47% of
patients with NP who were treated surgically (10-12). Supporting the hypothesis of an inﬂammatory pathogenic mechanism,
Gu et al identiﬁed signiﬁcantly higher levels of T-helper cells
(Th9) that secrete a proinﬂammatory cytokine IL-9 in REAH
patients versus controls. They suggested that Th9 cells may play
a signiﬁcant role in the development of REAH (13). One prospective study suggested that those with a ≥10-year history of
NP, patients requiring more than one NP-related surgery, and
patients with NP and a comorbidity of asthma have an increased
222

risk of developing REAH (14). With our patient's 20+ years of
anosmia, it is unclear when REAH formed and if an inﬂammatory process was associated with its formation.
One of the most common presenting symptoms of REAH
is hyposmia or anosmia (8). This is likely caused by local impingement or loss of olfactory nerves within the aﬀected olfactory clefts. In one study, the prevalence of anosmia among
participants diagnosed with REAH dropped from 72% to 44%
with surgical resection (12). Our patient had no changes to his
anosmia after surgery. His history of dementia and length of
symptoms may have played an independent role in his anosmia
and the lack of improvement in his olfaction despite adequate
resection of the hamartomas. To date, there are no reported
studies investigating the relationship between the duration of
anosmia and postoperative olfactory outcomes in patients with
REAH.
It is important to diﬀerentiate REAH from more aggressive
tumors to avoid excessive surgical intervention. In one retrospective study of REAH surgical subjects, no diﬀerence was noted
in outcomes between standard endoscopic sinus surgery and
aggressive resection with subperiosteal dissection and drilling
into the adjacent bone (8). Along with a computed tomography
scan and MRI with contrast medium to evaluate the site and the
extent and features of the lesion(s), some have recommended a
preoperative biopsy in cases of a unilateral lesion or widening of
the olfactory cleft (1-3, 8, 15). Appropriate caution should be
taken when considering the diﬀerential of olfactory cleft masses
to minimize surgical risks to patients. While there is insuﬃcient
evidence tracking the recurrence of REAH, available data have
shown no beneﬁt in preventing recurrence with more aggressive removal, including subperiosteal dissection (8). Standard
endoscopic resection without subperiosteal involvement was
performed to remove REAH from our patient, and there has
been no evidence of recurrence on endoscopy in a 14-month
postoperative period or by MRI in a 27-month period.
1.

Al Hawat A, Mouchon E, De Bonnecaze G, Vergez S, Serrano E. Our
experience with respiratory epithelial adenomatoid hamartomas of the
olfactory cleft. Eur Arch Otorhinolaryngol 2015;272(10):2867-2870.
2. Wenig BM, Heﬀner DK. Respiratory epithelial adenomatoid hamartomas
of the sinonasal tract and nasopharynx: a clinicopathologic study of 31
cases. Ann Otol Rhinol Laryngol 1995;104(8):639-645.
3. Nguyen DT, Gauchotte G, Arous F, Vignaud JM, Jankowski R. Respiratory epithelial adenomatoid hamartoma of the nose: an updated review.
Am J Rhinol Allergy 2014;28(5):187-192.
4. Wenig BM. Respiratory epithelial adenomatoid hamartoma. In Barnes
L, Eveson JW, Reichart P, Sidransky D, eds. World Health Organization
Classiﬁcation of Tumours. Pathology and Genetics: Head and Neck Tumours.
Lyon, France: IARC Press, 2005:33.
5. Albergotti WG, Psaltis AJ, Schlosser RJ. Respiratory epithelial adenomatoid hamartoma of the olfactory groove: a report of 4 cases and a review
of the literature. Ear Nose Throat J 2016;95(3):E19-E27.
6. Kessler HP, Unterman B. Respiratory epithelial adenomatoid hamartoma
of the maxillary sinus presenting as a periapical radiolucency: a case report
and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 2004;97(5):607-612.
7. Fitzhugh VA, Mirani N. Respiratory epithelial adenomatoid hamartoma:
a review. Head Neck Pathol 2008;2(3):203-208.
8. Bignami M, Volpi L, Karligkiotis A, De Bernardi F, Pistochini A,
AlQahtani A, Meloni F, Verillaud B, Herman P, Castelnuovo P.

Baylor University Medical Center Proceedings

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