Introduction
Nasal chondromesenchymal hamartoma is a rare pathology first described by McDermott et al. in 1998.Reference McDermott, Ponder and Dehner1 Embryologically, nasal chondromesenchymal hamartomas are derived from mesoderm. They are mostly benign, slow-growing lesions that have self-limiting proliferation. They do not regress following cessation of growth, and they cause local compression and obstruction necessitating complete surgical resection.
Nasal chondromesenchymal hamartoma has been linked to another important pathology: pleuropulmonary blastoma via the Dicer 1 gene.Reference Schultz, Yang, Doros, Williams, Harris and Stewart2 Knowledge of this link is important for all specialties treating this condition.
The diagnosis, investigation, treatment and further management of nasal chondromesenchymal hamartoma cases should be known by all ENT clinicians who may diagnose and treat nasal masses. We present the most extensive literature review and analysis of nasal chondromesenchymal hamartoma cases as well as presentation of three new cases managed in a tertiary paediatric centre with multimodal surgical resections. This represents the largest series of infants and young children with nasal chondromesenchymal hamartoma reported since the original description in 1998.
Materials and methods
The literature was systematically reviewed to identify all nasal chondromesenchymal hamartoma cases presenting either with or without pleuropulmonary blastoma.
We reviewed the nasal chondromesenchymal hamartoma literature using PubMed, Embase, Scopus, Web of Science and Google Scholar databases. We composed a search syntax combining synonyms for nose, (chondro)mesenchyme and hamartoma. For PubMed, the search syntax was: (nasal[tiab] OR nose[tiab] OR ‘Nose Diseases’[Mesh] OR ‘Nose’[Mesh]) AND (chondromesenchymal[tiab] OR mesenchymal[tiab] OR ‘Mesoderm’[Mesh]) AND (hamartoma[tiab] OR hamartoma[MeSH]).
For Embase the syntax was: (nasal:ti,ab OR nose:ti,ab) AND (chondromesenchymal:ti,ab OR mesenchymal:ti,ab) AND hamartoma:ti,ab.
We performed the literature review including all published articles between 1975 and the search date (1 June 2020). We screened reference lists of included nasal chondromesenchymal hamartoma cases to identify any additional relevant publications. No critical appraisal of the selected literature was performed. Data were extracted on the following variables: age at diagnosis, gender, presenting complaint, lesion site, performed diagnostics and treatment, nasal chondromesenchymal hamartoma recurrence follow-up length, and additional pleuropulmonary blastoma diagnosis. This report has been written according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Reference Moher, Liberati, Tetzlaff, Altman and Group3
Before the disease entity was formally called nasal chondromesenchymal hamartoma in 1998, it is speculated that nasal chondromesenchymal hamartoma was previously reported as a ‘nasal hamartoma’, a ‘congenital benign mesenchymoma’ or a ‘chondroid hamartoma’. We decided to only include cases that were histologically classified as nasal chondromesenchymal hamartoma to avoid inaccurate data presentation; therefore, these diagnoses are not included in our report. For our own three cases, we retrospectively reviewed the clinical notes for presenting complaints, investigations, operative interventions, histopathology and follow up.
Results
The results from the literature review are presented in full in Table 1.Reference McDermott, Ponder and Dehner1,Reference Mirchia and Naous4–Reference Jeyakumar, McEvoy and Fettman48 In total, we identified 56 individual cases of nasal chondromesenchymal hamartoma. Cases showing histological similarities that were not definitively labelled as nasal chondromesenchymal hamartoma were excluded. Duplicate cases were combined to give a clear picture of the actual number of reported cases. Although the vast majority of patients were paediatric, there were reported cases in adults, including one case where the patient was 70 years old.Reference Mirchia and Naous4 The average age at diagnosis was 9.6 years (range, 5 days to 70 years). There were 23 cases in children under two years of age. The male-to-female ratio was 1.9:1 (Table 1).
Table 1. Cases of nasal chondromesenchymal hamartoma in the literature
PPB = pleuropulmonary blastoma; n.a. = not applicable; n.r. = not recorded CT = computed tomography; MRI = magnetic resonance imaging; n.t. = not tested
As expected with an enlarging nasal mass, the common presenting symptoms were nasal obstruction (46 per cent) and ocular symptoms (29 per cent), most commonly ophthalmoplegia and proptosis. Other reported symptoms were dependent on the progression of the mass but encompassed headache, hydrocephalus, dental mobility and epistaxis. The lesions were predominantly in the nasal cavity, with a predilection for ethmoidal air-cell involvement and orbital extension, with occasional cribriform plate and skull base involvement. In terms of the common investigations for these cases, the mainstay has been computed tomography (CT) alone or CT and magnetic resonance imaging (MRI) in combination. Four patients had pre-operative angiography.Reference McDermott, Ponder and Dehner1,Reference Kato, Ijiri, Tanaka, Hara and Sekido5,Reference Ozolek, Carrau, Barnes and Hunt19,Reference Finitsis, Giavroglou, Potsi, Constantinidis, Mpaltatzidis and Rachovitsas26
By far the most common treatment modality was complete surgical resection. Only one patient underwent pre-operative embolisation before resection. One patient received radiotherapy, which resulted in regression of the mass.Reference McDermott, Ponder and Dehner1 Only one patient had a nasal chondromesenchymal hamartoma that underwent a malignant change, which was managed with post-operative chemoradiotherapy.Reference Li, Fan and Jiao21 Residual disease post-surgical resection was seen in three cases and one patient who had persistent tumour growth. Recurrent disease was seen in 8 cases (14.5 per cent; Table 1). Table 1 demonstrates that there were 11 nasal chondromesenchymal hamartoma cases that were diagnosed in association with pleuropulmonary blastoma. Eight of these cases had pleuropulmonary blastoma before nasal chondromesenchymal hamartoma diagnosis.
Discussion
Along with the previous cases reported in the literature, we included the three cases we treated in our centre; this represents the largest case series in infants and young children since the first reported cases in 1998.Reference McDermott, Ponder and Dehner1 It is important that ENT surgeons recognise this rare condition as a potential cause of a myriad of symptoms related to the nose and eyes that can commonly present in out-patient settings. A thorough clinical examination and appropriate investigation choice of any intranasal mass is key to timely diagnosis before cases progress.
It is important to recognise that this is a condition that crosses the spectrum of age groups but particularly affects children. In terms of nasal obstruction in children, it is important to add nasal chondromesenchymal hamartoma to the working differential diagnosis, especially considering the associated condition of pleuropulmonary blastoma. This is important because of the poor prognosis of pleuropulmonary blastoma, which makes early diagnosis in its most curable stage preferable.Reference Schultz, Williams, Kamihara, Sterwart, Harris and Bauer44
Regarding the investigation of suspected nasal chondromesenchymal hamartoma or other nasal masses in children, our experience has been with the use of both CT and MRI to both establish the extent of local progression and involvement of local structures but also to plan complete surgical resection. This correlates with the majority of cases in the reported literature. We have not found it necessary to use angiography in our cases, and the available evidence suggests that this is not needed for successful treatment, unless there is an obvious vascular component.
Definitive diagnosis is only available with adequate histological findings because there are no specific pathognomonic features on imaging. Nasal chondromesenchymal hamartoma does display amorphous calcifications with rings and arcs, so-called ‘popcorn’ lesions, but this is also found in other chondroid lesions. Small tissue samples of this pathology can easily lead to diagnostic confusion, so adequate biopsies are essential for diagnostic accuracy.
The mainstay of successful treatment has proven to be surgical resection. All three of the cases in our unit have been treated either entirely or partially with a transnasal navigation assisted endoscopic resection. This technique can minimise the impact of the operation on the patient. Since the previous literature review,Reference Mason, Navaratnam, Theodorakopoulou and Chokkalingham11 the most recent reported cases have seen an increase in surgery utilising a transnasal endoscopic excision. It may be necessary to work with allied surgical specialties, especially neurosurgery and ophthalmology, when managing this condition.
The pre- and post-operative imaging results from two of our cases can be seen in Figures 1–6. Clinicians in ENT should particularly be aware of nasal chondromesenchymal hamartoma's association with pleuropulmonary blastoma. In our series one patient was found to have a Dicer 1 loss of function mutation on blood sample genetic analysis. Patients who test positive for this mutation should be made aware of the future risk of pleuropulmonary blastoma, and those patients who have previously had pleuropulmonary blastoma should be made aware of the future risk of developing nasal chondromesenchymal hamartoma. The exact risk of pleuropulmonary blastoma is not known, but patients with Dicer 1 mutations have a total neoplasm risk of 19 per cent.Reference Schultz, Williams, Kamihara, Sterwart, Harris and Bauer44 In the out-patient setting, clinicians should take particular care in the presence of previous pleuropulmonary blastoma or Dicer 1 mutations. This involves a thorough nasal, neck and general examination in particular. This is not only because of the risk of nasal chondromesenchymal hamartoma but also the other Dicer 1 line tumours, such as pituitary and thyroid neoplasia or multinodular goitres.Reference Li, Fan and Jiao6,Reference Schultz, Williams, Kamihara, Sterwart, Harris and Bauer44 Unfortunately, the testing of the nasal chondromesenchymal hamartoma patients in the literature is sporadic, so discerning the true prevalence is difficult.
Fig. 1. Pre-operative coronal plane magnetic resonance image for patient 1.
Fig. 2. Post-operative coronal plane magnetic resonance image at six months for patient 1.
Fig. 3. Post-operative coronal plane computed tomography image at six years for patient 1.
Fig. 4. Pre-operative coronal plane magnetic resonance image for patient 2.
Fig. 5. Pre-operative axial plane computed tomography image for patient 2.
Fig. 6. Post-operative coronal plane computed tomography image at 18 months for patient 2.
Conclusion
This review of the literature, with the addition of the further reported cases over the last five years, has helped confirm the most useful management strategy for patients with suspected nasal chondromesenchymal hamartoma. Patients should be discussed at the paediatric skull base multidisciplinary team meeting following imaging of the paranasal sinuses and brain with CT and an MRI. Given the advances in endoscopic skills and equipment, the majority of cases have been able to be resected via the endonasal route, even very young patients. In order to effectively resect these tumours, giving the patient the best chance of disease-free survival and limiting local complications, a multidisciplinary approach should be considered.
Competing interests
None declared
