Introduction
Gorlin's syndrome
Gorlin's syndrome, also known as Gorlin–Goltz syndrome or basal cell naevus syndrome, was first described in 1960. It is an autosomal dominant condition with high penetrationReference Stoelinga, Peter, Van de Staak and Cohen1 and variable phenotype expression.Reference Gorlin and Goltz2 The condition is uncommon, with a low incidence of one in 56 000 persons.Reference Bale3
The aetiology of Gorlin's syndrome is thought to relate to chromosomal instability arising in chromosome nine.Reference Shafei-Benaissa, Savage, Babin, Larregue, Papworth and Tanzer4, Reference Farndon, Del Mastro, Evans and Kilpatrick5 The gene involved is the human homologue of the drosphilia segment gene,Reference Johnson, Rothman, Xie, Goodrich, Bare and Bonifas6, Reference Kimonis, Mehta, Digiovanna, Bale and Pastakia7 and has been patched as PTCH1.Reference Gailani8 It is thought that the associated protein has a role in deoxyribonucleic acid maintenance, repair and/or replication,Reference Shafei-Benaissa, Savage, Babin, Larregue, Papworth and Tanzer4 functioning as a tumour suppressor gene in its active state.Reference Hahn, Wicking, Zaphiropoulous, Gailani, Shanley and Chidambaram9 The condition is usually passed down by familial inheritance, although sporadic cases have been reported.Reference Diaz-Fernandez, Infante-Cossio, Belmonte-Caro, Ruiz-Laza, Garcia-Perla-Garcia and Gutierrez-Perez10, Reference Tabuchi, Okubo, Takahashi, Uemaetomari, Shimoyamada and Nakayama11
The disorder is characterised by multiple basal cell carcinomas, particularly on the face and at an early age, together with maxillary keratocysts. Other, less frequent clinical characteristics noted in Kimonis and colleagues' series of 82 patientsReference Gailani8 include calcification of the falx cerebri (79 per cent) and tentorium cerebelli (20 per cent), bridging of the sella turcica (68 per cent), abnormal frontal sinus aeration (18 per cent), bifid ribs (26 per cent; most commonly the third, fourth and fifth ribs), calcification of the nuchal ligament (18 per cent), fusion of vertebrae (10 per cent), hemivertebrae (15 per cent), polydactyly (4 per cent),Reference Hermes, Liekenbrocker, Korner, Kapp and Wedi12 ovarian fibromas (17 per cent of the women), and meningiomas (5 per cent). Other features recorded include palmar or plantar pits,Reference Gailani8 schizophrenia and learning difficulties,Reference Johnson, Rothman, Xie, Goodrich, Bare and Bonifas6 retinal hamartoma,Reference Boutimzine, Laghmari, Karib, Karmane, Bencherif and Albouzidi13 and soft tissue tumours such as leiomyosarcoma.Reference Garcia-Prats, Lopez-Carreira, Mayordomo, Ballestin, Rivera and Diaz-Puente14 Five per cent of patients with the condition develop childhood medulloblastoma. A third of these patients have been shown to have lost the wild type allele of the PTCH gene on chromosome nine, a fact which generated the hypothesis that the PTCH gene was the tumour suppressor gene responsible for the condition.Reference Cowan, Hoban, Kelsey, Birch, Gattamaneni and Evans15
Malignant features and transformation have also been noted. Khalifa et al. reported a case of endometrial adenocarcinoma associated with ovarian fibroma and Gorlin's syndrome.Reference Khalifa, Patterson-Cobbs, Hansen, Hines and Johnson16 Wolfer et al. documented a case of transformation of basal cell carcinoma (BCC) to squamous cell carcinoma in a human immunodeficiency virus (HIV) positive patient with the condition.Reference Wolfer, Blume-Peytavi, Almond-Roesler, Gollnick and Orfanos17 Yilmaz et al. reported the concurrence of basal cell naevus syndrome and adenoid cystic carcinoma in a patient who also had distant metastases in the lungs,Reference Yilmaz, Goldberg, Schechter, Kemp and Ruiz18 a feature seen by other authors in this and other sites.Reference Diaz-Fernandez, Infante-Cossio, Belmonte-Caro, Ruiz-Laza, Garcia-Perla-Garcia and Gutierrez-Perez10, Reference Winkler and Guyuron19
Gorlin's syndrome in otolaryngology
Although not characteristically considered to be associated with otolaryngological pathology, Gorlin's syndrome may affect soft tissue in any part of the body. Hence, ENT cases such as the above salivary gland adenocarcinoma have been reported. Al-Anazy and Zakzouk reported a case of progressive nasal obstruction and hearing loss associated with multiple dental cysts, bifid ribs and calcification of the falx cerebri.Reference al-Anazy and Zakzouk20 Computed tomography scans revealed a large, cystic mass in the left maxillary sinus, protruding into the nasal cavity. The external auditory meati may also be involved,Reference Cowan, Hoban, Kelsey, Birch, Gattamaneni and Evans15, Reference Lobo, Timms and Puranik21 and orbital or tarsal BCCs may also extend into and/or obliterate the orbit and ethmoidal sinuses.Reference Gailani8, Reference Honavar, Shields, Shields, Eagle, Demirci and Mahmood22 To date, no cases with involvement of the upper aerodigestive tract have been documented.
Case report
A 39-year-old man with a known diagnosis of Gorlin's syndrome presented to the otolaryngology clinic with a one-year history of progressive dysphagia, as well as intermittent, left-sided facial pain and otalgia. He had no nasal obstruction, anosmia, rhinorrhoea or otorrhoea, and the nasal, dental and aural examinations were normal. The patient's Gorlin's syndrome had been diagnosed six years previously, when he had had multiple mandibular keratocysts removed. The diagnosis was confirmed had been genetic screening, and an orthopantomogram had shown the facial asymmetry and hemi-mandibular hyperplasia characteristic of the diagnosis. At the time of this previous presentation, the patient had not developed the BCCs usually observed in the condition.
The patient underwent magnetic resonance imaging of the skull base to neck region, which showed a large mass lesion arising from the tongue base (Figure 1).
Fig. 1 Sagittal T2-weighted magnetic resonance imaging scan of the patient, showing a large mass lesion in the tongue base.
The patient underwent endoscopy under general anaesthetic, which revealed a large, round lesion arising from the tongue base, with smooth overlying mucosa. The lesion was surgically debulked and sent for histological analysis. In view of its large size, it was not possible to completely excise this lesion without compromising tongue function.
Macroscopically, the specimen comprised firm, rubbery, cream-coloured tissue measuring at least 90 mm in cross section. Microscopically, the tissue consisted of a mixture of adipose and vascular spindle cells (Figure 2). The former were mostly normal, mature adipocytes, but with scattered cells containing multiple globules of fat. The spindle cell component comprised cells with fairly uniform, spindle and ovoid, blunt-ended nuclei and well defined, spindled, eosinophilic cytoplasm. These stained positively with smooth muscle antigen and desmin. They were scattered amongst the adipose tissue but also formed large sheets. Mitoses were not seen, and there was no evidence of malignancy; however, ectatic blood vessels were a prominent component. Mast cells were also seen throughout the lesion. In conclusion, the rare diagnosis of myolipoma was given.
Fig. 2 Photomicrograph showing a mixture of vascular spindle cells scattered amongst normal, mature adipocytes, consistent with myolipoma. No evidence of malignancy was observed (Haematoxylin & Eosin; ×40).
The patient was subsequently followed up at the out-patient clinic. Nine months after surgery, he underwent further debulking of the slow-growing, benign tumour. Complete excision was deemed inappropriate due to the likelihood of impairment of swallowing function.
Discussion
Gorlin's syndrome is a rare condition with variable features, of which many variants have been reported. The current report represents the first documented case of an associated tumour of the upper aerodigestive tract. This case is particularly atypical given the lack of BCCs usually so characteristic of the condition.
Myolipoma is also a rare condition, usually affecting the deep soft tissues of the abdomen and/or retroperitoneum. It has not previously been reported in the tongue or pharynx. It is a benign lesion consisting of a variable tissue mass, including smooth muscle fibres containing spindle-shaped eosinophilic cells with cigar-shaped nuclei, and islands of mature adipocytes.Reference Behranwala, Chettiar, El-Bahrawy, Stamp and Kakker23 No areas of necrosis, mitosis, vascular infiltration or proliferation, or malignant meta- or dysplasia are seen, concurring with the benign nature of these lesions. The present case showed these classical features despite its unusual location. The differential diagnosis for such a mixed tissue tumour includes lipoleiomyoma and fibrolipoleiomyoma.
• Gorlin's syndrome, also known as Gorlin–Goltz syndrome or basal cell naevus syndrome, is an autosomal dominant condition with high penetration and variable phenotype expression, first described in 1960
• The disorder is characterised by multiple basal cell carcinomas, particularly on the face and presenting at an early age, together with maxillary keratocysts
• This paper reports the first case of tongue base myolipoma associated with Gorlin's syndrome
• The coexistence of these two conditions appears to represent a new variant in the broad spectrum of features of Gorlin's syndrome
As mentioned, myolipomas are benign and hence carry a good prognosis. In this case, symptomatic resolution was achieved after surgical debulking, and further treatment was therefore considered necessary only for symptomatic control. It should be remembered, however, that malignant transformation of BCCs has been noted in Gorlin's syndrome, albeit in a patient immunocompromised by HIV infection. It is of course possible that the present case of myolipoma represents no part of the spectrum of Gorlin's syndrome and is a coincidental finding in a patient with a pre-existing diagnosis. However, as soft tissue tumours have previously been reported in Gorlin's syndrome patients, Reference Garcia-Prats, Lopez-Carreira, Mayordomo, Ballestin, Rivera and Diaz-Puente14 it seems likely that this case represents yet another variant of this condition, being as it is an oncological syndrome associated with the loss of a tumour suppressor gene.
Conclusion
This case demonstrates the coexistence of two rare conditions in an atypical fashion, and appears to represent a new variant in the broad spectrum of features of Gorlin's syndrome.
