A Systematic Review of Nasal Chondromesenchymal Hamartoma (NCMH) with a New Case Report

Abstract

Nasal chondromesenchymal hamartoma (NCMH) is a very rare, benign sinonasal tract tumor commonly affecting infants. In this paper, in addition to presenting a systematic review of the literature on NCMH, we also report an unusual case of NCMH in an adolescent patient. A systematic review conducted following the PRISMA guidelines. PubMed, EMBASE and manual search through references of relevant publication were utilised to gather all published case-reports of NCMH. Data collected from each case-report for patient demographics, site and size of NCMH, clinical presentation, co-morbidities, diagnostic methods, treatment options and follow-up methods. The systemic review collected sixty-two case-reports of NCMH (including our case) affecting 42 men and 21 women (2:1 male to female ratio). Mean average age was 5.1 years (age range: 1 day to 70 years). The anatomical sites of the tumor were: nasal cavity (n = 17), paranasal sinuses (n = 30), orbital region (n = 17), and the base of the skull (n = 16). The reported clinical manifestations were nasal obstruction or congestion (n = 29), nasal mass (n = 27), epistaxis (n = 6), orbital symptoms (n = 14). NCMH is a very rare cause of nasal masses in infants and toddlers. Our case and previous case reports confirm that NCMH can mimic other benign and malignant tumors, therefore we should be vigilant for rare pathologies that lead to nasal masses. Recently the link between DIECR1 mutation with NCMH has been established, so NCMH should be considered in any patient with nasal or orbital symptoms with a history of DICER1-related tumor spectrum.

Background

Nasal chondromesenchymal hamartoma (NCMH) is an extremely rare, benign tumor of nasal cavity and sinonasal tract. McDermott et al. (1998) first described the condition, and up to 2015, 48 cases have been reported in the English literature and majority of patients are young children and infants [1]. Up to this point only 6 cases of NCMH in adults have been reported. Hamartoma is a focal overgrowth of mature tissues that are common for the organ in which they are included, but they do not form a natural structure. Mesenchymal hamartoma, also called mesenchymal, has two or more mesenchymal components besides fibroconnective tissue [2]. The most common sites of involvement are the liver, chest wall, upper respiratory tract, and eyelids. NCMHs are structural complexes of mesenchymal and cartilaginous components; clinical manifestations depend on the location of the tumor in the paranasal sinuses or nasal cavity and the effect of local mass includes nasal congestion or obstruction, toothache, and facial pain [3].

Here, in addition to reporting a rare and uncommon case of NCMH in an adolescent, we propose a systematically updated review of NCMH demographics, diagnostic method, clinical manifestations, management, and prognosis.

Case Report

A 15-year-old female patient was referred to our hospital presenting with a mass in her right nasal cavity. She had noticed a lump growing insidiously inside her nose in the past 6 months. Apart from mild nasal congestion and occasional epistaxis she complained of no other symptoms.

Physical examination revealed a lobulated mass in the right side of the anterior nasal septum with about 0.4 cm attachment to the cartilage, slightly deviating the septum. Clinically, the mass had an appearance of a benign tumor confined to the nasal cavity and therefore no further imaging was arranged.

The differential diagnoses considered were: squamous papilloma, nasal polyp or inverted papilloma, and fibrocartilaginous mass.

An endonasal endoscopic excisional biopsy of the mass was caried out. In gross view, there was a cartilaginous mass measuring 0.6 cm × 2.3 cm × 2.1 cm. In histopathological diagnosis using hematoxylin and eosin (H&E) staining, cartilage and focal mature bone covered in the stratified squamous epithelium (Figs. 1, 2) were observed; they were surrounded by microscopically focally reactive bony trabeculae, and in the submucosal area, there was a nodular pattern. There were basophilic myxoid stroma, hyaline cartilage-like lobular foci bipolar, oval-spindle-shaped mesenchymal cells, with the local lacunar arrangement, hyperchromatic nucleated cells in the mass including fibroblast-like cells in a fascicular manner. However, no remarkable mitotic activity or necrosis was noted.

Fig. 1.

Histopathologic features of NCMH. Spindle cell component with fibrous matrix, variable myxoid change, and occasional sclerotic stroma (×100)

Fig. 2.

Histopathologic features of NCMH. The hyaline cartilage component is most prominent (×100)

The above findings confirmed the diagnosis of a nasal chondromesenchymal hamartoma. Our patient then underwent a surgical excision with no complication and she was followed up for 18 months, during which period no evidence of recurrence or complication was identified.

Methods

This systematic review followed the PRISMA guidelines [4]. Literature search (1975 to 14th March 2021) conducted through the international databases, including PubMed & EMBASE and other sources like manual search through references of relevant publications.

We searched for all published case-reports on NCMH in English, using the keywords of [(chondromesenchymal hamartoma) AND (sinus OR nasal OR maxillary OR sphenoid OR ethmoid OR orbit OR frontal OR cranial)], from 1975 to 14th March 2021. We reached 59 articles in total of which 2 were found to be a duplicate case report publication. Following a close review of the article contents, a further 12 were excluded; one was written in Chinese and 11 were not NCMH case-reports. Ultimately, forty-five were included in this systematic review, reporting 62 (except our case) cases of NCMH. The majority of these (37 articles) were from PubMed database. [5–10] (Fig. 3).

Fig. 3.

The flow diagram of study selection for the present literature review on case reports of the Nasal Chondromesenchymal Hamartoma (NCMH)

Data was collected on patient demographics (age, sex), size, site, symptoms, co-morbidities, diagnostic methods, treatment and follow-up.

Results of Systematic Review

The systematic review identified 62 case-reports of NCMH (except our case) in English literature. Most cases were males: 42 male and 21 female, with a male to female ratio of 2:1. The mean age was (age range: 1 day to 70 years). The high proportion of cases were 1 year old or under, and only 15 adult NCMH cases have been described. The anatomical location of the mass were nasal cavity (17 cases), paranasal sinuses (30 cases), orbital area (17 cases), base of the skull (16 cases), inside of the skull (10 cases), oral and pharyngeal involvement (2 cases) and nasopharyngeal site (5 cases) (Table 1).

Table 1.

NCMH cases systematic review (reported in the literature)

Author/Publication Date	No	Age	Sex	Size (Cm)	Site	Symptoms	Co-morbidity	Diagnostic method	Treatment	Follow up
1-Mcdermot, 1998 [12]	1	5 D	M	ND	NC	Nasal Mass/ Respiratory Distress	ND	CT	Surgical Excision	No Recurrence After 2 Years
	2	3 M	F	ND	NC/Ethmoid Sinus/Intracranial Extension	Nasal Mass/Otitis Media	ND	MRI	Surgical Excision	No Recurrence After 2 Years
	3	3 M	M	ND	NC/Respiratory Distress	Choanal Mass	ND	ND	Surgical Excision /Subsequent Chemotherapy	No Recurrence After 4 Years
	4	2 M	M	ND	NC/Intracranial Extension	Nasal Mass	ND	ND	Surgical Excision	No Recurrence After 18 Months
	5	12 D	F	ND	NC/Intracranial Extension	Nasal Mass	ND	CT	Surgical Excision & Re-Excision After 16 Months	Persistent Tumor In NC After 12 Months
	6	14 D	M	ND	NC/Ethmoid Sinus/Intracranial Extension	Nasal Mass/ Hydrocephalus	ND	CT	Surgical Excision/VP Shunt	Tumoral Residue In Cranial Fossa At 9 Months
	7	7 Y	M	ND	NC/Sphenoid Sinus	Nasal Mass/ Nasal Congestion	PPB	ND	Surgical Excision	No Recurrence After 2 Months NB But At 2010 Reported By Priest Et Al [27]- With Several Recurrences In First 3 Years
2-Chae 1999 Korea [36]	8	3 M	F	3.5 × 7.5 × 2.5	NC/ Ethmoid Sinus/ Cribriform Plate	. Epistaxis/ Obstruction	ND	CT	Surgical Excision	ND
3-Kim D 1999 [37]	9	3 M	F	Right Size: ND	NC/ Ethmoid Sinus/ Intracranial Extension	Nasal Mass/ Otitis Media	None Stated	CT MRI	Surgical Excision With Bi-Frontal Craniotomy	No Recurrence After 18 Months
4-Kato, 1999 [24]	10	4 M	M	ND	NC/Extension To Left Orbit /Intracranial Extension	Nasal Mass/Respiratory Distress With Cyanosis During Feeding/Unilateral Opthalmoplegia	None Stated	CT	2 Surgical Excision Steps:1.Intracranial/Sinus Lesion,2.Intranasal Lesion/Then Post-Op Radiotherapy	No Recurrence After 13 Years
5-Hsueh 2001 [38]	11	0 D	M	ND	NC/ Ethmoid &Sphenoid Sinuses/Compression Of Left Orbit	Left Nasal Mass /Left Facial Swelling/ Respiratory Distress & Cyanosis During Feeding Proptosis At Last	None Stated	CT MRI	Surgical Excision With Lateral Rhinotomy/Craniofacial Approach	No Recurrence After 5 Years
	12	9 M	M	ND	NC/Maxillary Sinus	Asymmetric Face/Opthalmoplegia, Hypotropia /Enopthalmos	None Stated	CT MRI	Surgical Resection	No Recurrence After 9 Months
6-Alrawi 2003 [13]	13	16 Y	M	1.5 × 1.5	NC	Nasal Swelling	None Stated	CT MRI	Surgical Resection	No Recurrence After 8 Months
7-Shet, 2004 [25]	14	1 Y	M	ND	NC/ Sphenoid and Ethmoid Sinus /Extension Into The Left Orbit	Unilateral Proptosis And Facial Swelling	None Stated	CT	Left Maxillectomy And Surgical Excision After Chemotherapy	The Tumoral Residue After 1.5 Years Without Further Re-Growth /Stable
8-Kim B, 2004 [26]	15	5 M	M	ND	NC/ Left Ethmoidal Bone Defects /Compression Of Left Orbit/Anterior Cranial Fossa Defects	Left Eye Ptosis	None Stated	CT	Trans-Nasal Surgical Resection And Frontal Craniotomy	ND
9-Norman, 2004 [22]	16	11 Y	M	ND	NC	Headaches	None Stated	CT	Endoscopic Biopsy Then Anterior Craniofacial Resection	ND
10-Ozolek, 2005 [2]	17	11 Y	M	ND	NC/ Ethmoid Sinus/Left Orbit Extension	Nasal Mass	None Stated	ND	Surgical Resection	ND/ Surgery Then Care Undertaken In Another Hospital
	18	17 Y	F	ND	NC	Nasal Obstruction/Facial Pain	None Stated	ND	Surgical Excision	ND
	19	25 Y	M	8 × 5 × 3.5	NC/Nasopharynx /Maxillary Sinus	. Respiratory Distress Because Of Obstructing Oropharyngeal Tumor Then Emergency Tracheostomy	Several Intracranial Vascular Aneurysms /Inflammatory Polyp’	CT	Several Surgical Excisions During 1 Year; Tracheostomy And Bulbar Mass Surgical Resection, Surgical Resection Of The Nasal Tumor, Le-Fort Osteotomy&Additional Surgical Excision	ND
	20	69 Y	F	ND	NC/Ethmoid Sinus	ND	None Stated	ND	Surgical Excision	ND
11-Low 2006 [39]	21	11 Y	M	ND	NC/Nasopharynx/Epistaxis	Nasal Obstruction/Chronic Sinusitis	None Stated	CT	Surgical Excision	No Recurrence After 2 Months
12-Tabatabaei 2006 [40]	48	23Y	M	7 × 5 × 3	NC/Orbital Roof/Ethmoid	Anosmia,Right Gaze Diplopia/ Proptosis/ Epistaxis	None Stated	CT	Surgical Excision, Reconstructed By Periosteal Flap	ND
13-Johnson, 2007 [35]	22	15 Y	F	ND	NC/Nasopharynx	Chronic Sinusitis/Nasal Obstruction	PPB/Sertoli-Leydig Cell Tumor Of Ovary	CT	Endoscopic Surgical Excision	No Recurrence After 6 Months
14-Silkiss, 2007 [27]	23	7 M	M	3.2 × 1.4	NC/Cribriform Plate Erosion/ Orbital Compression	Ptosis/ Strabismus /Extropia/ Stertor	3. Congenital Phthisi Bulbi	CT MRI	Surgical Excision/ Right Lateral Rhinotomy	No Recurrence After 18 Months
15-Nakagawa 2008 [41]	24	12 Y	M		NC/ Ethmoid & Sphenoid&Maxillary Sinuses	Nasal Obstruction	None Stated	CT	Surgical Resection /After Recurrence Additional Surgical Excision	Recurrence After 2 Months /5 Months After Second Surgery Without Recurrence
16-Finitsis, 2009 [42]	25	12 M	M	4 × 4.2	NC/ Maxillary Sinus & Left Orbit; Ompression/Nasopharynx	Respiratory Distress	None Stated	CT MRI	Surgical Resection After Pre-Operative Embolization	ND
17-Kim J, 2009 [28]	26	19 M	M	2.7 × 3.5	NC/ Orbital Extension/Intracranial Extension	Watery Rhinorrhea/Nasal Obstruction	None Stated	CT MRI	Two Steps Endoscopic Surgical Resection	Recurrence After 1 Year; /10 Months After Second Surgery Without Recurrence
18-Priest, 2010 [43]	–	7 Y	M	ND	1. Sphenoid Sinus	NC/ Nasal Congestion/ Nasal Mass	PPB Type II-III/Lung Cysts	ND	Four Resections Over 3 Years	After 13 Years Followed Up With Several Recurrences In The First 3 Years
		15 Y	F	ND	NC	Nasal Congestion/Chronic Sinusitis/Facial Pain	PPB Type II	ND	Surgical Resection	No Recurrence After 51 Months
	27	10 Y	F	ND	NC	Chronic Sinusitis	PPB Type III	CT	Surgical Resection	No Recurrence After 21 Months
	28	11 Y	M	ND	NC	Nasal Obstruction	PPB Type III	ND	Surgical Resection	No Recurrence After 4 Months
19-Sarin, 2010 [29]	29	2.5 Y	M	ND	NC	Nasal Obstruction	ND	MRI	After Biopsy Lateral Rhinotomy For Excision	ND
20-Eloy 2011 [30]	30	18 M*	M	0.5 × 0.4	NC	Right Eye Oculomotor Impairment	None Stated	CT MRI	Endoscopic Surgical Resection	ND
21-Jeyakumar 2011 [31]	31	7 D	F	ND	NC	Nasal Obstruction	None Stated	CT MRI	Surgical Excision	ND
22-Mattos 2011 [32]	32	3 Y	M	ND	NC	Nasal Mass	None Stated	CT MRI	Surgical Excision	Recurrence After 21 Months Requiring Additional Resection
23-Behery, 2012 [44]	33	11 Y	M	ND	ND	Eye Infections/ Nasal Obstruction	PPB	ND	Surgical Resection	ND
24-Uzomefuna, 2012 [45]	34	8 Y	M	ND	Sphenoid Sinus	Frontal Headache	ND	CT MRI	Surgical Resection	No Recurrence After 6 Months
25-Cho, 2013 [6]	35	14 Y	M	5 × 5.3 × 4	NC	Swelling And Pain To The Left Face	None Stated	CT	Subtotal Maxillectomy, Floor Remove	No Recurrence After 4 Years
26-Li Y, 2013 [46]	36	40 Y	F	ND	NC	Nasal Obstruction	None Stated	CT MRI	Complete Radical Resection	Recurrence After 3 Months With Malignant Transformation
27-Li Gy 2013 [14]	37	23 Y	M	3.2 × 2.5	NC/ Ethmoid Sinus/ Lacrimal Sac & Left Orbit Extension	Left Lacrimal Sac Mass/ Lateral Displacement Of Globe/ Proptosis	None Stated	ND	Surgical Excision	No Recurrence After 3 Months
28-Moon, 2014 [33]	38	9 M	F	ND	NC/Maxillary Sinu/Orbital Wall Erosion	No Nasal Symptoms /Inability To Abduct Right Eye	None Stated	CT MRI	Surgery	Caring In Another Hospital
29-Wang, 2014 [47]	39	5 Y	M	2.5 × 3.6 × 4.3	NC/ Ethmoid Sinus/ Intracranial Extension	Nasal Obstruction/Recurrent Sinusitis	None Stated	CT MRI	Surgical Resection	No Recurrence After 3 Years
	40	6 W	F	2.6 × 3.4 × 3.9	NC/Pressure Remodeling Of Adjacent Bones	Recurrent Sinusitis/ Rhinorrhea/ Nasal Obstruction	None Stated	CT MRI	Surgical Resection	No Recurrence At 10 Months
30-Obidan, 2014 [48]	41	ND	M	ND	Bilateral Ncs	Nasal Obstruction	PPB	CT	Surgical Resection	ND
31-Stewart, 2014 [15]	–	7 Y	M	ND	ND	Nasal Congestion	PPB/ Lung Cysts	ND	Surgical Resection	Multiple Recurrences
		15 Y	F	Bilateral	NC	Nasal Congestion/ Chronic Sinusitis/Facial Pain	PPB/ Ovarian Tumor /Sertoli-Leydig Cell	ND	Surgical Resection	No Recurrence
		10 Y	F		ND	Chronic Sinusitis	PPB	ND	Surgical Resection	No Recurrence
		11 Y	M		ND	Nasal Congestion	PPB	ND	Surgical Resection	No Recurrence
	42	8 Y	M	ND	ND	Nasal Congestion	PPB	ND	Surgical Resection	No Recurrence
	43	13 Y	F	ND	ND	ND	PPB/ Papillary Carcinoma Of Thyroid/Sertoli-Leydig Tumor	ND	Surgical Resection	No Recurrence
	44	8 Y	M	ND	ND	ND	PPB	ND	Surgical Resection	No Recurrence
	45	6 Y	F	ND	ND	Chronic Sinusitis	PPB/Cystic Nephroma	ND	Surgical Resection	No Recurrence
	46	21 Y	F	ND	ND	ND	PPB Sertoli-Leydig Tumour	ND	Surgical Resection	Recurrence After 4 Years
32-Chandra 2014 [49]	47	12 Y	M	ND	NC	Nasal Congestion/ Septal Deviation/	None Stated	CT MRI	Surgical Excision	No Recurrence After 5 Months
33-Mason 2015 [16]	49	49 Y	M	0.5 × 2 × 2	NC//Nasal Mass, Ethmoid Sinus/Extension Into The Right Orbit	Nasal Obstruction	None Stated	None	Surgical Excision	No Recurrence After 4 Years
34-Cha 2015 [50]	50	10 M	M	ND	NC	Nasal Congestion /Mouth Breathing/ Snoring	None Stated	CT MRI	Surgical Excision	No Recurrence After 18 Months
35-Adnan 2016 [51]	51	13Y	M	6.1 × 3.3	NC/ Extension Into Maxillary, Frontal And Sphenoid Sinuses	Nasal Obstruction /Nasal Mass	None Stated	CT MRI	Surgical Excision	No Recurrence After 1 Y
36-Avci 2016 [52]	52	5Y	M	ND	NC/Extending To The Olfactory Cleft	Nasal Congestion, Obstruction	None Stated	CT MRI	Surgical Excision	ND
37-Nakaya 2017 [53]	53	3Y	M	3.5 × 5.3 × 4.5	NC/Extending To The Skull Base	NC/ Lacrimation/ Proptosis/ Disturbed Eye Movement	ND	CT MRI	An Endonasal Approach Without Extra Facial Incision	No Recurrence After 3 Years
38-Mirchia 2018 [17]	54	70Y	F	2.5 × 2.1	Maxillary Sinus	Chronic Maxillary Sinusitis/Mass	ND	CT	Surgical Excision	ND
39-Golbin 2018 [18]	55	25 M	F	ND	NC	Nasal Obstruction	ND	MRI CT	Two Steps Endoscopic Surgical Resection	No Recurrence After 12 Months
40-Kitayama 2019 [19]	56	23Y	M	6 × 5 × 4	NC	Numbness/ Feeling Of Pressure In Left Cheek/ Pain Behind The Eye/ Occipital Pain/ Lacrimation	ND	CT MRI	Endoscopic Nasal/Paranasal Surgery	No Recurrence
41-Cui 2020 [54]	57	7 Y	F	4 × 3.5 × 1	NC	Nasal Obstruction /Epistaxis	ND	CT MRI	Endoscopic Sinus Surgery	Tumoral Recurrence 45 Months After Surgery
42-Moseley 2021 [55]	58	Young	M	ND	NC	Nasal Congestion	ND	MRI	Endoscopic Sinus Surgery	No Recurrence
43-Peric 2021 [20]	59	42 Y	M	4.1 × 2.5	Nasopharyngeal Space	Nasal Obstruction/ Snoring/Intermittent Mucopurulent Nasal Discharge/ Postnasal Hemorrhage	ND	CT	Endoscopic Excision	No Recurrence After 12 Months
	60	48 Y	M	1.5 × 1	Nasopharyngeal Space	Nasal Obstruction/ Mucopurulent Postnasal Drip/Sensation Of A Foreign Body In The Throat	Recurrent Otitis Media With Effusion	CT	Endoscopic Excision	No Recurrence After 4 Months
44-Vijayasundaram 2021 [21]	61	42Y	F	4 × 3	NC Involving Bilateral Ethmoid Sinus	Epiphora/Nasal Obstruction	Asymptomatic	CT MRI	Endoscopic Excision	No Recurrence
45-Daniel Schaerer 2021 [56]	62	Newborn	M	4	NC Extension Into The Anterior Cranial Fossa	Compromised Airway	ND	MRI	Two Steps Endoscopic Surgical Resection	No Recurrence After 15 Months
Javadirad 2020 (Present Study)	63	15 Y	F	0.6 × 2.3 × 2.1	NC	Nasal Congestion/Epistaxis/Nasal Mass	ND	ND	Surgical Excision	No Recurrence After 18 Months

Y years, M months, D days, M male, F female, NC nasal cavity, ND not documented, PPB pleuropulmonary blastoma, CT computed tomography, MRI magnetic resonance imaging

Symptoms that patients presented with included: nasal obstruction or congestion (n:29), nasal mass (n:27), recurrent sinusitis (n:7), epistaxis (n:6), orbital signs (proptosis, enophthalmos, hypotropia, strabismus, exotropia etc.) (n:14), facial pain or headaches (n:7), facial swelling (n:9), otitis media (n:2), respiratory distress (n:11), ophthalmoplegia (n: 4), rhinorrhea (n:4), hyposmia (n:2), toothache (n: 2), hydrocephalus (n:1), and asymptomatic (n:5) (Table 1).

All patients had resection of NCMH mass with surgical approach depending on the tumor’s anatomical location. One patient received preoperative chemotherapy due to initial histopathological misdiagnosis as spindle cell sarcoma. In another case, surgical resection was performed following a preoperative embolization to avoid blood loss during surgery.

Follow-up periods were reported in 33 cases, mean time was 24 months (2 to 156 months). Recurrence or persistent disease had been reported in 13 cases: 9 required further operation, 5 had a persistent condition. No further information had been recorded for the rest. The first and only reported case of malignant transformation of NCMH was described by Li et al. [11].

No past medical history was documented for 51 patients. One of the adult patients had a history of multiple vascular aneurysms, and 11 cases had been diagnosed with pleuropulmonary blastoma prior to NCMH detection [4, 5, 7, 10].

The possibility of reporting bias through publication bias is a potential shortcoming of this study. This bias should be considered threefold:

1. Providing inadequate information on case reports by the author, like missing to document co-morbidities or follow up times etc.

2. There is a possibility of NCMH cases that have not been reported and therefore are not included in the systematic review.

3. The possibility of underreporting of true NCMH cases due to excluding “Mesenchymal chondrosarcoma” [8], “nasal hamartoma” [7], “congenital mesenchymal” [9], “nasopharyngeal hamartoma” [10] cases that were reported prior to 1998, when McDermot et al. first described NCMH.

Discussion

Chondromesenchymal hamartomas are mostly benign lesions with the locally destructive manner and because of their aggressive presentation they can be mistaken for malignant lesions. NCMHs usually slow-growing hence a delayed presentation. Histopathologically, these lesions are analogous to other mesenchymal hamartomas, contain chondroid tissue islands such as hyaline cartilage, foci of calcification, and elements of mesenchymal cells like myxoid stroma and spindle cell. McDermott et al. were the first to describe NCMH as a discrete clinicopathological entity in 1998. They explained a case series of seven patients with nasal congestion and paranasal sinuses with a mass in the nose [12]. In his case series, six patients out of 7 were newborns and infants < 3 months old. Our systematic review demonstrates chondromesenchymal hamartoma mostly present in infants under one years old and young children, however, there have now been fourteen case-reports of adults with chondromesenchymal hamartoma up to the age of 70 years old [2, 11, 13–21]. The first and only reported case of malignant transformation of a chondromesenchymal hamartoma was in 2013. Their patient was a 40-year-old woman presenting with nasal obstruction, bloody rhinorrhea, and a heterogeneous polypoid soft-tissue mass filling the nasal cavity extending into the maxillary and ethmoid sinus. Histological and immunohistochemical studies exhibited an area of the mass that was consistent with typical NCMH. However, some regions of the mass showed cytologic atypia, foci of necrosis, and marked mitotic activity. The atypical mesenchymal spindle cells were immunoreactive for vimentin, smooth muscle actin (SMA), and CD99 diffusely. The cartilaginous cells were immunopositive for S-100 protein. Also, the Ki-67 index was high in atypical regions, accounting for 50%. A rapid mass recurrence was observed at the original site just 3 months after surgery. At last, the NCMH with malignant transformation was diagnosed [11].

Preoperative imaging of these type of tumors provides valuable information on the involvement of adjacent structures like paranasal sinuses, intracranial cavities, and orbit. On computed tomography (CT) imaging, NCMH is often seen as a non-encapsulated, poorly-defined mass with a cysticcomponents [22]. Magnetic resonance imaging (MRI) of chondromesenchymal hamartoma demostrates a heterogeneous mass on T1 weighted images and T2 weighted images demonstrate cystic components. MRI is superior in comparison to CT to elicit the invasion of tumor to the adjacent structures [23]. Due to the rarity of NCMH, despite all thorough clinical and radiological examinations, misdiagnosing remains a possibility. Differential diagnoses include aneurysmal bone cysts, inverted papilloma, ossifying fibromas, chondrosarcoma, nasoethmoidal encephalocele, nasal lymphoma, rhabdomyosarcoma, and nasal glioma. A histopathological study following the surgical excision is mandatory to reach an accurate diagnosis.

Patients with NCMH usually present with nasal symptoms such as nasal obstruction, nasal mass, or, rarely, ophthalmic signs. Tumor can extend to intra-occular space and patients may present with eye symptoms [24–33]. In addition, there has been a report of a patient with intra-oral symptoms due to oral cavity involvement [6]. Patients with NCMH can present to ophthalmology, otolaryngology, or maxilla-facial departments, so clinicians should be vigilant of this rare pathology. Our patient did not have any ophthalmic or cranial symptoms, but she did notice a slow growing mass inside her nasal cavity.

The key diagnostic histopathology findings in NCMH were cellular cartilaginous islands and areas that contained fibro-osseous and mesenchymal components. The cartilaginous part was composed of cellular cartilage foci with a hyaline cartilaginous matrix. Areas of bone tissue with a lamellar structure were present. The cells of the foci had a very low level of mitotic activity with no sign of atypia.

The main differential diagnosis based on histological examination including squamous papilloma, nasal polyp or inverted papilloma, and fibrocartilagenous mass [1–3, 15].The etiology of NCMH is thought to be caused by an underlying genetic predisposition, such as association with DICER1 mutations. Therefore, NCMH is mostly affecting very young individuals. The DICER1 familial tumor susceptibility syndrome imposes a higher risk for pleuropulmonary blastoma, ovarian sex cord-stromal tumors, juvenile granulosa cell tumor, Sertoli-Leydig cell tumor, and gynandroblastomas. Less commonly, the DICER1 tumor spectrum includes: thyroid gland neoplasia, cystic nephroma (CN), multinodular goiters, adenomas, and other thyroid cancers. DICER1 is inherited in an autosomal dominant manner with decreased penetrance. Thus, the children of parents with a DICER1 pathogenic variant have a 50% chance of inheriting the mutated gene. The penetrance of each DICER1-associated conditions is not fully understood. PPB, lung cysts, and thyroid nodules appear to be the most common manifestations in persons with germline loss-of-function mutations. Although people with a germline loss-of-function mutation mostly have 0 to 2 sites of disease, those with mosaic “hot spot” mutations are more likely to have more than a single-site manifestation [34].

Stewart et al. (2014) identified germline mutations in DICER1 in 6/8 (75%) NCMH patients. They utilized the genetic testing to investigate their patients. Genetic testing and counseling are recommended for those who have a history of at least one major or two minor indications of testing and/or who have one minor indication with a family history of a major or minor indication [15, 34].

Our systematic review contains 11 cases with a history of PPB. Five of them had other DICER1 tumors. Compared to other DICER1 tumors, NCMH presents earlier due to its location [35].We have insufficient data to declare what percentage of patients with a DICER1 mutation will develop NCMH.

Successful management of NCMH involves a complete resection of the tumor to prevent recurrence. However, complete excision is not always technically possible, particularly in NCMH with an intracranial extension. Unfortunately, incomplete resection results in a higher recurrence, where symptoms progress and tumor growth continues. In this systematic review, 13 patients had disease recurrence, most likely because of incomplete surgical resection.

Conclusions

We report a quite rare case of NCMH in an adolescent patient without obstructive nasal symptoms, due to the tumor attachment to the nasal septum. A systematic review of literature, highlighted the fact that clinical presentation is correlated to tumor location, with nasal mass, nasal obstruction and ophthalmic symptoms being the most common ones. The vast majority of NCMH tumors have been reported in children and infants under the age of 1 years old. NCMH is less reported in adults. The treatment of choice is surgical resection with a low recurrence rate. There has been a single report of malignant transformation. A link between NCMH and DICER1 mutation has recently been established, therefore NCMH should be considered in patients with a new nasal or orbital symptoms with a background history of DICER1-related tumor spectrum. Both our case and the systematic review underlined the fact that NCMH can mimic other benign and malignant tumors, therefore clinicians should be aware of rare pathologies presenting with nasal masses.

Author Contributions

Contribution to conception and design: JE, AJ, MS; Contribution to the acquisition of data, analysis, and interpretation: JE, MS, SS; Involved in drafting the manuscript & revising it critically: JE, AJ.

Funding

Open Access.

Data Availability

Not applicable.

Code Availability

Not applicable.

Declarations

Conflict of interest

The authors declare that they have no conflict of interest.

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