hamartomas of the head and neck generally , as well as the sinonasal tract specifically , are very rare .
respiratory epithelial adenomatoid hamartoma ( reah ) and chondro - osseous respiratory epithelial adenomatoid hamartoma ( coreah ) are examples of hamartomas comprising both epithelial and mesenchymal components .
although invariably benign , these lesions may grow to relatively large sizes and pose clinical concerns .
we report herein what represents , to the best of our knowledge , the third case of coreah of the nasal cavity , emphasizing its clinicopathologic features and the importance of recognizing and differentiating it from other , potentially more aggressive lesions of the nasopharynx .
a healthy 38 year - old woman presented to our institution with a left nasal mass that was discovered on a computed tomography ( ct ) scan performed at an outside hospital .
she had complained of mild left nasal obstruction of a few months ' duration ; however , no epistaxis , rhinorrhea , or hyposmia was reported . a punch biopsy obtained at the referring institution
was interpreted as benign respiratory epithelium ( slides not reviewed ) . the ct scan was repeated and confirmed the presence of a 4.0    2.4    1.1-cm soft tissue mass with calcification located in the posterior aspect of the left nasal cavity .
the mass abutted the lateral wall of the cavity , extending into the left sphenopalatine foramen and the left ethmoid air cells , and protruded into the nasopharynx posteriorly ( figure 1 ) .
endoscopic examination revealed a lobulated , well - circumscribed , smooth , tan - white polypoid lesion occupying most of the left nasal cavity .
the lesion was not attached to any structure inside the nasal cavity proper , but its posterior aspect was minimally attached to the lateral nasopharyngeal wall .
axial computed tomography ( ct ) image of a left nasal chondro - osseous respiratory epithelial adenomatoid hamartoma ( coreah ) showing a large ( 4    2.4    1.1 cm ) , iso - intense mass with focal enhancement ( arrowhead ) causing mild deviation of the nasal septum to the right with no erosion of the bone .
the submitted specimen measured 4.0    2.3    1.1 cm , had a tan , smooth outer surface , and was accompanied by multiple small irregular fragments of soft and bony tissue .
microscopic sections exhibited respiratory - type epithelium with underlying submucosal glands , hypocellular fibromyxoid stroma , and mature bone .
the submucosal glands were irregular and exhibited focal mucinous metaplasia , but no significant thickening of the basement membrane was seen .
submucosal glandular proliferation originating from surface respiratory epithelium - lined mucosa , hypocellular fibromyxoid stroma , and mature bone .
the submitted specimen measured 4.0    2.3    1.1 cm , had a tan , smooth outer surface , and was accompanied by multiple small irregular fragments of soft and bony tissue .
microscopic sections exhibited respiratory - type epithelium with underlying submucosal glands , hypocellular fibromyxoid stroma , and mature bone .
the submucosal glands were irregular and exhibited focal mucinous metaplasia , but no significant thickening of the basement membrane was seen .
submucosal glandular proliferation originating from surface respiratory epithelium - lined mucosa , hypocellular fibromyxoid stroma , and mature bone .
hamartoma is defined as a mass - forming aberrant organization of specialized cellular components indigenous to a particular body site1 .
it does not clearly represent a neoplastic or an inflammatory process or have the capacity for continuous unimpeded growth2 .
hamartomas have rarely been reported to arise in the sinonasal region . until the early 1990s , the majority of the sinonasal hamartomas were reported to be mesenchymal , most frequently vascular , in origin3 . however , epithelial hamartomas , namely reahs , have since been more frequently reported2 
 4 
 5 
 6 .
reah was originally described in 1995 by wenig and heffner , who included in their series 1 case containing mixed epithelial and mesenchymal elements with osseous metaplasia2 . in a later abstract presentation , the authors designated this chondro - osseous lesion as coreah4 .
a formal literature review revealed only 2 other reports of coreah5 
 6 , making ours the third such case published .
two hypotheses have been proposed for the etiology of reah ( and by extrapolation coreah ) .
the first is that reah , similar to other hamartomatous lesions , is congenital in nature and results from an inborn developmental error .
the second explanation is that given the association of such hamartomas with chronic sinusitis , they may represent the effect of the inflammatory process on inflammatory polyps2 .
one study that investigated the molecular genetic changes in reah revealed a higher loss of heterozygosity ( loh ) at loci located on chromosome 9p and 18q than expected for a benign lesion7 .
interestingly , the 9p region is known to code for 2 structurally distant tumor suppressor proteins and is frequently affected in human neoplasms , while loh at 18q has been shown to be common in recurrent or metastatic squamous cell carcinoma of the head and neck and may therefore play a role in tumor progression7 . nevertheless , despite these reported molecular alterations , reah and coreah are completely benign lesions .
clinically , reah has been noted to arise in the posterior nasal cavity in the majority of cases2 .
however , other sites , including the nasopharynx and the ethmoid , maxillary , and frontal sinuses , have been described2 
 8 .
the presenting symptoms include nasal obstruction and stuffiness , chronic sinusitis , rhinorrhea , hyposmia , and headache8 .
the 2 coreah lesions previously reported in the literature were also located in the nasal cavity . grossly , they were fleshy to firm and polypoid , with white smooth outer surfaces and solid cut surfaces with occasional mucus filled cysts5 
 6 .
microscopically , they resembled reah , with features including a predominantly glandular submucosal proliferation with round to oval glands varying from small to markedly dilated and lined by ciliated respiratory epithelium originating from the surface mucosa .
these glands were separated by stromal tissue with no evidence of complex growth or cribriform architecture .
other histological features included changes typically seen in association with inflammatory sinonasal polyps , namely stromal edema , polypoid growth , increased numbers of seromucinous glands , vascular and fibroblastic proliferation , and mixed acute and chronic inflammatory cells2 
 5 
 6 .
glandular hamartomas , inflammatory polyps , inverted papillomas , and low - grade sinonasal adenocarcinoma are included in the list of clinical differential diagnoses for both reah and coreah2 
 9 .
glandular ( seromucinous ) hamartoma must be included in the differential diagnosis , as both lesions have similar clinical presentations and may overlap microscopically .
glandular hamartomas consist of an epithelial proliferation of mixed small and large glands with serous acini / tubules growing in clusters or lobules or randomly .
the larger glands are usually lined by ciliated respiratory epithelium or attenuated flat cells , while the lining cells of the small glands are flat to cuboidal and may contain intra - cytoplasmic eosinophilic granules .
although reah / coreah and glandular hamartomas may all fall within the spectrum of sinonasal epithelial hamartomas , they are distinguished histologically by the presence of proliferating serous acini and the absence of chondro - osseous metaplasia9 .
reah and coreah can be distinguished from inflammatory polyps on both clinical and histological grounds .
clinically , most reahs are solitary masses arising in the posterior nasal septum2 , whereas inflammatory polyps are bilateral and arise most commonly in the middle meatus .
the presence of adenomatoid proliferation and stromal hyalinization are distinguishing histological features of reah as opposed to the pauciglandular loose edematous stroma of inflammatory polyps .
their clinical course , unlike that of reah , is characterized by bone destruction , extension along mucosal surfaces , invasion into adjacent structures , local recurrence , and potential for malignant transformation2 .
in addition , inverted papilloma has a known predilection for the lateral nasal wall , and only few arise from the septum10 .
histologically , the endophytically growing stratified squamous epithelium of inflammatory polyps is not seen in reah .
features such as cribriform architecture , absence of ciliated epithelium lining the glands , desmoplastic stroma , and an elevated mitotic rate would strongly favor adenocarcinoma8 .
unlike inverted papilloma and sinonasal adenocarcinoma , reah / coreah is treated by choice by complete local excision11 .
cases followed up for up to 5 years showed no evidence of recurrence2 
 11 . in conclusion ,
reah / coreah is an interesting although exceedingly rare benign hamartomatous lesion of the sinonasal area that may be clinically mistaken for more common , and potentially more aggressive , tumors of the head and neck .
awareness of this peculiar entity and its radiologic and pathologic characteristics is important to guide the clinician to an appropriately conservative and invariably curative surgical treatment .
 summary 
 introduction :  chondro - osseous respiratory epithelial adenomatoid hamartoma ( coreah ) is a benign lesion of the nose and sinuses that is extremely rare , with only 2 cases reported in the literature to date . 
 
 case report :  we present herein the third reported case of coreah , in a 38-year - old woman who presented with left nasal obstruction and a mass in her left nasal cavity . 
 the mass was completely resected endoscopically . microscopic examination showed hamartomatous proliferation of respiratory - type glands with mucinous metaplasia admixed with numerous spicules of mature bone , characteristic of coreah . 
 
 conclusion :  coreah is a benign hamartomatous proliferation of respiratory epithelium , submucosal glands , and chondro - osseous mesenchyme . the clinical differential diagnoses for such lesions include glandular hamartoma , inflammatory polyp , inverted papilloma , and low - grade sinonasal adenocarcinoma . 
 recognition of this lesion as benign despite its potentially worrisome radiographic appearance is important to avoid an unnecessarily radical surgical procedure . 
Introduction
Case Report
Pathology
Discussion