Keywords
COREAH - chondro-osseous respiratory epithelial adenomatoid hamartoma - sinonasal
mass
Introduction
A hamartoma is a benign mass consisting of mesenchymal tissues. These growths can
arise in virtually every organ in the body and are most commonly found within the
lungs, kidneys, and intestines.[1] They are characterized by their unique ability to create a disorganized proliferation
of cells reflecting mature organ tissue structure unique from the native cellular
architecture of the organ from which it arises.[2] Hamartomas differ from neoplasms due to their self-limited growth within the organ
itself and lack of spread to distant sites.[3] It is important to distinguish between a hamartoma and a tumor as proper identification
provides crucial information about management, including the avoidance of unnecessary
risk of morbidity and the extent of surgical management. Furthermore, distinguishing
hamartomas as the primary diagnosis is crucial for the early identification of syndromic
conditions such as tuberous sclerosis, neurofibromatosis, or Peutz–Jeghers syndrome.
Although many hamartomas are found in association with syndromic conditions, it is
more common they arise sporadically. They are categorized by the primary tissues from
which they develop and are classified according to the predominant tissue type.[3] Those that develop within the nasal cavity are most commonly composed of respiratory
epithelia, and therefore, the most common hamartomas found within the nasal cavity
are respiratory epithelial adenomatoid hamartomas (REAH). There exists an extremely
rare subset of REAH identified as chondro-osseous REAH (COREAH), which comprises both
cartilaginous and bony tissues in conjunction with respiratory epithelium.
Prior reports of COREAH originating from the nasal cavity, paranasal sinuses, or skull
base have been limited to case reports.[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18] In addition to the current case study, one previously reported case in the literature
demonstrated an attachment site along the skull base.[19] We present all previously reported cases of sinonasal and skull base COREAH in addition
to one additional account of a young patient who presented with complete bilateral
nasal obstruction and was subsequently found to have COREAH as well as ipsilateral
ethmoid osteoma. In this way, we aim to analyze the current literature and review
the methods of diagnosis, management, and treatment options for this benign tumor.
Patients and Methods
Study Design and Literature Review
This study was approved by the Institutional Review Board of the University of California,
Irvine. A retrospective chart review of patients with COREAH of the paranasal sinuses
and skull base treated at a tertiary academic medical center was performed. One patient
was identified and the subsequent case was presented.
A comprehensive MEDLINE database search was performed between inception and 2024 for
all cases of sinonasal and skull base COREAH. Search queries included “COREAH,” “chondro-osseous
respiratory epithelial adenomatoid hamartoma,” “chondroosseous respiratory adenomatoid
hamartoma,” “respiratory adenomatoid hamartoma” with “skull base,” “nasal cavity,”
and “paranasal sinuses” specified and filters provided for human subjects. Within
each case report, histology was obtained and confirmed to detail a diagnosis of COREAH.
Information on age, gender, presenting signs and symptoms, attachment site, laterality,
imaging modality, additional sites of involvement, number of open and transnasal endoscopic
procedures, recurrence, and clinical outcome were extracted ([Table 1]).
Table 1
Literature representation of COREAH
|
Study
|
Case #
|
Age (y)
|
Gender
|
Laterality
|
Attachment site
|
Symptoms
|
Duration of symptoms (mo)
|
Imaging modality
|
In-office biopsy vs. intraoperative biopsy
|
Clinical outcome (recurrence)
|
Follow-up (mo)
|
|
Flavin et al[4]
|
1
|
11
|
M
|
U
|
Lateral nasal wall, middle turbinate
|
Nasal obstruction
|
6
|
CT, MRI
|
OR
|
None
|
6
|
|
Fang et al[5]
|
2
|
3
|
M
|
U
|
Nasal roof
|
Nasal obstruction
|
NS
|
CT, MRI
|
IO
|
None
|
6
|
|
Nomura et al[6]
|
3
|
7
|
F
|
B
|
Superior turbinate
|
Nasal obstruction
|
18
|
NS
|
NS
|
Recurrence after 12 mo, required second surgery
|
NS
|
|
Peric et al[7]
|
4
|
68
|
F
|
B
|
Posterior middle turbinate
|
Nasal obstruction, mucopurulent rhinorrhea, postnasal drainage, snoring
|
24
|
CT
|
OR
|
None
|
12
|
|
Li et al[8]
|
5
|
49
|
F
|
U
|
Superior turbinate
|
Nasal congestion, nasal obstruction, headache, facial pain, and pressure
|
36
|
CT
|
OR
|
None
|
3
|
|
Roffman et al[9]
|
6
|
59
|
M
|
U
|
Posterior nasal septum
|
Nasal obstruction, headaches
|
36
|
CT
|
OR
|
Partially resected, 12 mo later definitive excision
|
12
|
|
Chatzopoulos et al[19]
|
7
|
64
|
F
|
NS
|
Olfactory cleft
|
Nasal obstruction
|
12
|
CT
|
OR
|
None
|
12
|
|
Daniel et al[10]
|
8
|
83
|
F
|
U
|
Posterior nasal septum
|
Headaches, perioral paranesthesia
|
48
|
CT, MRI
|
NS
|
None
|
6
|
|
Yu et al[11]
|
9
|
54
|
F
|
U
|
Sphenoethmoidal recess
|
Nasal obstruction, hyposmia, rhinorrhea
|
NS
|
CT
|
OR
|
None
|
12
|
|
10
|
57
|
M
|
U
|
Superior turbinate
|
Nasal obstruction, bloody mucopurulence
|
6
|
CT
|
IO
|
None
|
8
|
|
Nikolopoulos et al[12]
|
11
|
66
|
F
|
U
|
Middle turbinate
|
Nasal obstruction, midface pain, headache
|
36
|
CT, MRI
|
OR
|
NS
|
NS
|
|
Fedda et al[13]
|
12
|
38
|
F
|
U
|
Lateral nasal wall
|
Nasal obstruction
|
NS
|
CT
|
NS
|
None
|
NS
|
|
Nayani et al[14]
|
13
|
55
|
F
|
U
|
Lateral nasal wall
|
Nasal obstruction, rhinorrhea, smell disturbances, epistaxis
|
48
|
CT
|
OR
|
None
|
6
|
|
Temmermand et al[15]
|
14
|
75
|
M
|
U
|
Anterior–inferior nasal septum
|
Epistaxis
|
NS
|
NS
|
OR
|
NS
|
NS
|
|
Choi et al[16]
|
15
|
34
|
F
|
U
|
Ethmoid
|
Nasal congestion, facial pain, hyposmia, poor sense of taste
|
NS
|
CT, MRI
|
IO
|
None
|
9
|
|
Idris et al[17]
|
16
|
46
|
F
|
U
|
Lateral nasal wall
|
Nasal obstruction, rhinorrhea, anosmia
|
36
|
CT
|
OR
|
NS
|
NS
|
|
Beattie et al[18]
|
17
|
31
|
M
|
U
|
Middle turbinate
|
Nasal obstruction, sore throat, odynophagia, pharyngitis, epistaxis
|
0.75
|
NS
|
NS
|
NS
|
NS
|
|
18
|
60
|
M
|
U
|
Lateral nasal wall
|
Nasal congestion, facial pressure, rhinorrhea
|
NS
|
CT
|
NS
|
NS
|
NS
|
|
This work
|
19
|
18
|
M
|
U
|
Middle turbinate
|
Nasal obstruction, facial pressure, hyposmia, and thick nasal discharge
|
18
|
CT
|
OR
|
None
|
48
|
Abbreviations: B, bilateral; COREAH, chondro-osseous respiratory epithelial adenomatoid
hamartoma; CT, computed tomography; F, female; IO, in-office; M, male; MRI, magnetic
resonance imaging; NS, not specified; OR, intraoperative; U, unilateral.
Case Presentation
This case is of an 18-year-old male without significant past medical history who presented
with a 1.5-year history of complete bilateral nasal obstruction. He endorsed right-sided
forehead and cheek pressure, bilateral nasal obstruction, hyposmia, and thick nasal
discharge. Prior treatment attempts included two courses of antibiotics, one course
of prednisone, and an unsuccessful attempt to utilize steroid nasal spray due to complete
nasal obstruction. At our tertiary care center, nasal endoscopy established the presence
of a large, bony polypoidal mass that completely obstructed the right nasal cavity,
wrapped around the choana, and extended into the left nasopharynx. It was visualized
despite thick white mucus along the floor of the nasal cavity. Additionally, there
was severe polyposis involving all sinuses.
Computed tomography (CT) of the paranasal sinuses determined the extent of the osseous
obstruction. CT demonstrated right-sided pansinusitis with a hyperostotic right middle
turbinate along with osteogenesis, indicating that the lesion appeared to originate
from the vertical part of the right middle turbinate and was directly attached to
the skull base ([Fig. 1A]). Additionally, CT incidentally identified a left-sided 5 mm ethmoid osteoma.
Fig. 1 (A) Computed tomography image of the patient prior to surgery, demonstrating fully opacified
paranasal sinuses. (B) Intraoperative endoscopic endonasal image of the mass within the left nasopharynx.
Informed consent was obtained for elective endoscopic surgical resection of the mass
([Fig. 1B]). Histological analysis intraoperatively confirmed the diagnosis of COREAH ([Fig. 2]). Repeat CT at 15 months postoperatively demonstrated mild to moderate right frontal
and ethmoid edema with no evidence of COREAH recurrence. Postoperative recommendations
included utilizing steroid rinses directed within the nasal cavity twice daily for
3 months, then as needed for symptomatic management. The patient continues to remain
asymptomatic with excellent nasal breathing, no facial pressure, and with intact sense
of smell.
Fig. 2 Sinus polypoid respiratory epithelial adenomatoid hamartoma (REAH) showing edematous
stroma, with prominent glandular proliferation (A); closer view showing those glandular structures vary in size (B); areas of glands admixed with cartilaginous tissue (C); with osseous formation (D). Features are consistent with chondro-osseous REAH.
Results
The Medline database was searched between inception and 2024, with the search strategy
designed to identify all reports of COREAH originating in the nasal cavity, paranasal
sinuses, or skull base. When the search was narrowed from REAH to COREAH, the number
of articles reduced from 137 to 16. All identified studies were classified as case
reports, with one as a poster presentation and two of which also provided a literature
review from articles. The earliest report of COREAH was from 2004 and the literature
publications range between 2004 and 2024. Including the single case from this case
report, a total of 18 patients were included in this review. ([Table 1])
Among the cases, the mean age at diagnosis was 46.2 years, with the ranges between
3 and 83 years. The primary sites were most frequently found along the lateral nasal
wall, middle turbinate, superior turbinate, and nasal septum. Two patients (10.5%)
had attachments along the skull base, including the patient in this reported study.
All patients underwent endoscopic resection with histologically proven COREAH. Fourteen
cases reported recurrence rates, with only one recurrence (7.1%) after 1 year of follow-up,
and with one revision surgery (7.1%) after incomplete resection was performed. Twelve
(85.7%) patients had no recurrence on follow-up, with the mean time of follow-up being
11.7 months and range between 3 and 48 months.
Discussion
A hamartoma is a benign mass of mixed mesenchymal tissues arising either during embryonic
germinal layer development or via sporadic proliferation.[3] Hamartomas can be classified depending on the primary tissue they are composed of.
These distinctions are made depending on whether they are predominantly comprised
of bone, cartilage, fiber, or nonmatrix tissues.[3] Nasal hamartomas have been occasionally described in the literature, the most common
of these being REAH. Another rare lesion described in the literature is nasal chondromesenchymal
hamartoma (NCMH). COREAH are, in contrast, exceedingly rare. To the best of our knowledge,
only 18 patient cases of COREAH have been reported in the literature to date.[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18] COREAH differs from other hamartomas histologically as it consists of both mesenchymal
and epithelial tissues. Unlike REAH, which is composed of only respiratory epithelium,
and NCMH, which is composed of cartilaginous tissues, COREAH is unique because it
consists of respiratory epithelium-lined glands, cartilaginous tissues, and osseous
stroma.[3]
[7]
[21] COREAH has been diagnosed in a wide range of patients, whereas REAH typically affects
predominately male patients in their third to ninth decade of life, and NCMH is predominantly
found in individuals younger than 3 months and is associated with a DICER1 genetic
mutation.[10]
[20]
[22]
[23]
The pathogenesis of COREAH is still largely undetermined. A formal literature review
reveals that it has affected patients ranging from the ages of 3 to 83 years, which
makes it highly unlikely that COREAH results only from congenital overgrowth of the
germinal matrix.[10] We must assume, therefore, that like other hamartomas, COREAH can arise spontaneously
as we age and is likely acquired. Because COREAH is related to REAH, much can be understood
with an understanding of the pathogenesis of REAH. Similar to COREAH, REAH typically
presents with symptoms of nasal obstruction, deviated septum, sinusitis and rhinorrhea,
repeat sinus surgery, hyposmia, and headache, and is largely associated with chronic
inflammation of the nasal passages and nasal polyps.[13]
[23]
[24]
[25] Because REAH commonly occurs in concert with inflammatory process it has been suggested
to be due to a chronic reaction induced by inflammation.[25] Tryptase-producing mast cells have been implicated in the inflammatory component
that may be contributing to REAH growth.[26] It is possible that many of these features of REAH also pertain to COREAH, though
there is much more to be discovered about this rare tumor. Despite the modest information
on COREAH genesis, it is widely accepted that endoscopic resection, whenever possible,
is the most favorable option for successful treatment.[27]
[28]
[29]
Prior to surgery, COREAH must be distinguished clinically and histologically from
inflammatory polyps, inverted papilloma, and sinonasal adenocarcinoma to ensure effective
treatment.[10]
[23] Obtaining the correct pathological diagnosis is particularly important in COREAH
because it is so rare and can be mistaken for a neoplasm. Overtreatment is a risk
in the management of these lesions and with the correct diagnosis, surgeons will successfully
avoid over-treating these benign hamartomas with endoscopic craniofacial resection.
COREAH can be differentiated from other diagnoses through its clinical and histological
presentation. A CT scan is a valuable tool in distinguishing regional predilections
of COREAH, and contrasting it with regions more commonly afflicted by benign and malignant
sinonasal and skull base lesions. Clinically, COREAH tends to present unilaterally
and will affect the posterior nasal septum more often than inflammatory polyps do.[23]
[24]
[27] COREAH can also be distinguished from a diagnosis of sinonasal adenocarcinoma because
sinonasal adenocarcinoma typically involves the middle turbinate or will often develop
within the ethmoid sinus.[23] In contrast to COREAH, inverted papilloma will frequently involve the lateral nasal
wall and present with aggressive areas of bone erosion.[8]
[13] Inverted papilloma also have the capacity for malignant transformation, thus it
is especially important to distinguish this from a benign COREAH.[13]
[23]
[30] Histologically, COREAH consists of respiratory epithelium along with an abundance
of chondro-osseous stroma.[3]
[7]
[21] This is distinguished from nasal polyposis, which presents as seromucinous glandular,
edematous tissue.[13]
[23] Sinonasal adenocarcinoma is highlighted by its cribriform architecture composed
of ciliated epithelium and glandular tissue, and inverted papilloma consists of stratified
squamous epithelium mixed with mucin and microcysts.[23]
[24]
Once correctly identified, COREAH may be managed with endoscopic resection and appears
to have favorable outcomes overall. COREAH has only one reported recurrence in the
literature, and only 4.1% of patients with REAH have been reported to show recurrence
after endoscopic resection.[6]
[28] However, long-term surveillance and monitoring, as well as noting changes in symptoms,
remains important.
Conclusion
COREAH is an extremely rare hamartoma consisting of prominent glandular proliferation
separated by cartilaginous and osseous stroma. COREAH is symptomatic in 100% of reported
cases in the literature, and complete surgical resection of COREAH is curative in
the majority of patients, including the patient we present in this report.
