- Email: [email protected]
Meningioma associated with Gorlin’s syndrome
Case Reports / Journal of Clinical Neuroscience 21 (2014) 349–350
349
Meningioma associated with Gorlin’s syndrome Chun-Wai Lee, Tze-Ching Tan ⇑ Department of Neurosurgery, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong
a r t i c l e
i n f o
Article history: Received 12 November 2012 Accepted 20 February 2013
Keywords: Gorlin’s syndrome Meningioma Naevoid basal cell carcinoma syndrome
a b s t r a c t Gorlin’s syndrome or naevoid basal cell carcinoma syndrome is a rare autosominal dominant condition characterised by a variety of congenital anomalies and various malignancies. The chief manifestations include multiple basal cell naevi, mandibular cysts, plantar and palmar pits, vertebral and rib abnormalities and intracranial calcifications. We report a patient with Gorlin’s syndrome associated with meningioma treated at our institution. The clinical and radiological features together with the management strategies of this unusual disease entity are discussed. Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction Gorlin’s syndrome or naevoid basal cell carcinoma syndrome (NBCCS) was first reported in 1960.1 It is an uncommon autosomal dominant disease with significant penetrance associated with basal cell carcinoma (BCC). The estimated prevalence varies from 1/57,000 to 1/256,000, with a male to female ratio of 1:1.2 Gorlin’s syndrome is due to mutations causing inactivation of the PTCH1 gene which is located on chromosome 9q22.3-q31. This links with a second hit mutation (often in p53) and leads to the formation of multiple BCC.2 In view of the multi-organ involvement, Gorlin’s syndrome requires multidisciplinary follow-up by a dermatologist, neurosurgeon, odontologist and geneticist. Life expectancy is not significantly altered but complications can be substantial.2
Although having BCC constitutes one of the major criteria, Gorlin’s syndrome may often present without skin manifestation. BCC was absent in 20% of Caucasians and 62% of African–Americans with Gorlin’s syndrome in one study.4 Ectopic calcifications of
2. Case report A 25-year-old woman presented after her first episode of generalised tonic–clonic seizure. It lasted for 5 minutes and resolved spontaneously. An examination revealed ocular hypertelorism and frontal bossing. Her neurological examination was normal. A plain CT scan of the brain showed calcifications in the falx and the tentorium (Fig. 1A). MRI confirmed a 4 cm contrast-enhancing solid mass in the right frontal region with a wide dural base abutting the inner table of the skull vault. The tumour was associated with extensive perifocal oedema causing compression of the right lateral ventricle with midline shift (Fig. 1B). Radiographs of the chest and mandible showed a bifid rib (Fig. 2A) and mandibular cysts (Fig. 2B). The patient underwent a craniotomy. Intraoperatively, an extra-axial convexity tumour was excised and the histology was confirmed as meningioma (World Health Organization grade I). The patient made a good recovery and was discharged home. She was referred to the Clinical Genetic Service upon discharge for genetic counselling and follow-up.
Fig. 1. (A) Sagittal CT scan of the brain showing prominent calcifications in the falx and tentorium, and (B) axial MRI of the brain showing a 4 cm contrast-enhancing solid mass in the right frontal region with a wide dural base abutting the inner table of the skull vault, consistent with a meningioma.
3. Discussion Gorlin’s syndrome is clinically diagnosed based on specific criteria, with confirmation by gene mutation analysis (Table 1).3 The diagnosis is made in a patient fulfilling two major criteria or one major and two minor criteria.3 ⇑ Corresponding author. Tel.: +852 2958 6029; fax: +852 2384 5594. E-mail address: [email protected] (T.-C. Tan).
Fig. 2. Anterior-posterior radiographs of (A) the chest showing bifurcation of the second rib, and (B) of the mandible showing a cyst over the angle of the right mandible.
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Case Reports / Journal of Clinical Neuroscience 21 (2014) 349–350
Table 1 Major and minor criteria for diagnosis of naevoid basal cell carcinoma syndrome3 Major criteria >2 basal cell carcinomas, or 1 under 30 years, or 10 basal cell naevi any odotegenic keratocyst (jaw cyst) or polyostotic bone cyst palmar or plantar pits (3 or more) ectopic calcification or early (<20 years) falx calcification family history of Gorlin syndrome (naevoid basal cell carcinoma syndrome)
Minor criteria congenital skeletal anomoly: bifid, fused, splayed or missing rib or bifid, wedged or fused vertebra cardiac and/or ovarian fibroma medulloblastoma lymphomesenteric cysts congenital malformation: cleft lip and/or palate, polydactyly, eye anomaly (cataract, colobma, microphtalmia, nystagmus)
the falx and tentorium early in life are well-known associations of Gorlin’s syndrome and constitute part of the major diagnostic criteria.2 Radiographs of the chest and mandible and CT scans of the brain are useful in screening for the disease. Gorlin’s syndrome is caused by a PTCH1 gene mutation which leads to a higher risk of developing BCC and hypersensitivity to radiation-induced tumorigenesis.5 Central nervous system abnormalities have been noted since the first patient report.1 The primary brain tumour most frequently associated with this syndrome is medulloblastoma, with an estimated frequency of about 20%.6 Meningioma is less commonly reported. From a study of CT scans of 82 patients with Gorlin’s syndrome, 5% were found to have radiological features suggestive of meningioma.7 There are no population-based studies to our knowledge for estimating the true figure. From patient reports of Gorlin’s syndrome-associated medulloblastoma treated with radiotherapy, seven out of eight patients reported developed a secondary intracranial tumour.7 Our patient had no preceding history of medulloblastoma or radiotherapy exposure. As a general rule, radiotherapy is not recommended as a treatment for Gorlin’s syndrome. Brain irradiation itself may cause secondary intracranial neoplasm. The true incidence of radio-induced neoplasms is currently unknown and the relationship between the dose delivered and the malignancy of the secondary tumour is still unclear.9 No quantification of the relative risk of intracranial radiation-induced neoplasm has been reported in the doi:http://dx.doi.org/10.1016/j.jocn.2013.02.033
recent literature8 but patients with NBCCS and associated medulloblastoma have been known to develop secondary brain tumours following radiotherapy.10 Further studies are needed to conclude the actual relative risk. 4. Conclusions Recognition of Gorlin’s syndrome is important as it is an autosomal dominant disease with significant penetrance. Early referral for genetic counselling is recommended as 70–80% of patients have an affected parent. Antenatal ultrasonography screening can be helpful to detect developmental abnormalities such as macrocephaly which may cause obstetrical complications.2 Radiotherapy should be avoided if possible in view of the genetic propensity for radiation-induced tumorigensis in these patients.2 Conflict of interest/disclosure The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. References 1. Gorlin RJ. Multiple nevoid basal-cell epithelioma, jaw cysts and bifid rib. A syndrome. N Engl J Med 1960;262:908–12. 2. Lo Muzio L. Nevoid basal cell carcinoma syndrome (Gorlin syndrome). Orphanet J Rare Dis 2008;3:32. 3. Evans DG, Ladusans EJ, Rimmer S, et al. Complications of the naevoid basal cell carcinoma syndrome: results of a population based study. J Med Genet 1993;30:460–4. 4. Kimonis VE, Goldstein AM, Pastakia B, et al. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet 1997;69:299–308. 5. Mancuso M, Pazzaglia S, Tanori M, et al. Basal cell carcinoma and its development: insights from radiation-induced tumors in PTCH 1 deficient mice. Cancer Res 2004;64:934–41. 6. Evans DG, Farndon PA, Burnell LD, et al. The incidence of Gorlin syndrome in 173 consecutive cases of medulloblastoma. Br J Cancer 1991;64:959–61. 7. Kimonis VE, Mehta SG, Digiovanna JJ, et al. Radiological features in 82 patients with nevoid basal cell carcinoma (NBCC or Gorlin) syndrome. Genet Med 2004;6:495–502. 8. Choudry Q, Patel HC, Gurusinghe NT, et al. Radiation-induced brain tumours in nevoid basal cell carcinoma syndrome: implications for treatment and surveillance. Childs Nerv Syst 2007;23:133–6. 9. Pettorini BL, Park YS, Caldarelli M, et al. Radiation-induced brain tumours after central nervous system irradiation in childhood a review. Childs Nerv Syst 2008;24:793–805 Epub 2008 Apr 8. 10. Mortimer PS, Geaney DP, Liddell K, et al. Basal cell naevus syndrome and intracranial meningioma. J Neurol Neurosurg Psychiatry 1984;47:210–2.
349
Meningioma associated with Gorlin’s syndrome Chun-Wai Lee, Tze-Ching Tan ⇑ Department of Neurosurgery, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong
a r t i c l e
i n f o
Article history: Received 12 November 2012 Accepted 20 February 2013
Keywords: Gorlin’s syndrome Meningioma Naevoid basal cell carcinoma syndrome
a b s t r a c t Gorlin’s syndrome or naevoid basal cell carcinoma syndrome is a rare autosominal dominant condition characterised by a variety of congenital anomalies and various malignancies. The chief manifestations include multiple basal cell naevi, mandibular cysts, plantar and palmar pits, vertebral and rib abnormalities and intracranial calcifications. We report a patient with Gorlin’s syndrome associated with meningioma treated at our institution. The clinical and radiological features together with the management strategies of this unusual disease entity are discussed. Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction Gorlin’s syndrome or naevoid basal cell carcinoma syndrome (NBCCS) was first reported in 1960.1 It is an uncommon autosomal dominant disease with significant penetrance associated with basal cell carcinoma (BCC). The estimated prevalence varies from 1/57,000 to 1/256,000, with a male to female ratio of 1:1.2 Gorlin’s syndrome is due to mutations causing inactivation of the PTCH1 gene which is located on chromosome 9q22.3-q31. This links with a second hit mutation (often in p53) and leads to the formation of multiple BCC.2 In view of the multi-organ involvement, Gorlin’s syndrome requires multidisciplinary follow-up by a dermatologist, neurosurgeon, odontologist and geneticist. Life expectancy is not significantly altered but complications can be substantial.2
Although having BCC constitutes one of the major criteria, Gorlin’s syndrome may often present without skin manifestation. BCC was absent in 20% of Caucasians and 62% of African–Americans with Gorlin’s syndrome in one study.4 Ectopic calcifications of
2. Case report A 25-year-old woman presented after her first episode of generalised tonic–clonic seizure. It lasted for 5 minutes and resolved spontaneously. An examination revealed ocular hypertelorism and frontal bossing. Her neurological examination was normal. A plain CT scan of the brain showed calcifications in the falx and the tentorium (Fig. 1A). MRI confirmed a 4 cm contrast-enhancing solid mass in the right frontal region with a wide dural base abutting the inner table of the skull vault. The tumour was associated with extensive perifocal oedema causing compression of the right lateral ventricle with midline shift (Fig. 1B). Radiographs of the chest and mandible showed a bifid rib (Fig. 2A) and mandibular cysts (Fig. 2B). The patient underwent a craniotomy. Intraoperatively, an extra-axial convexity tumour was excised and the histology was confirmed as meningioma (World Health Organization grade I). The patient made a good recovery and was discharged home. She was referred to the Clinical Genetic Service upon discharge for genetic counselling and follow-up.
Fig. 1. (A) Sagittal CT scan of the brain showing prominent calcifications in the falx and tentorium, and (B) axial MRI of the brain showing a 4 cm contrast-enhancing solid mass in the right frontal region with a wide dural base abutting the inner table of the skull vault, consistent with a meningioma.
3. Discussion Gorlin’s syndrome is clinically diagnosed based on specific criteria, with confirmation by gene mutation analysis (Table 1).3 The diagnosis is made in a patient fulfilling two major criteria or one major and two minor criteria.3 ⇑ Corresponding author. Tel.: +852 2958 6029; fax: +852 2384 5594. E-mail address: [email protected] (T.-C. Tan).
Fig. 2. Anterior-posterior radiographs of (A) the chest showing bifurcation of the second rib, and (B) of the mandible showing a cyst over the angle of the right mandible.
350
Case Reports / Journal of Clinical Neuroscience 21 (2014) 349–350
Table 1 Major and minor criteria for diagnosis of naevoid basal cell carcinoma syndrome3 Major criteria >2 basal cell carcinomas, or 1 under 30 years, or 10 basal cell naevi any odotegenic keratocyst (jaw cyst) or polyostotic bone cyst palmar or plantar pits (3 or more) ectopic calcification or early (<20 years) falx calcification family history of Gorlin syndrome (naevoid basal cell carcinoma syndrome)
Minor criteria congenital skeletal anomoly: bifid, fused, splayed or missing rib or bifid, wedged or fused vertebra cardiac and/or ovarian fibroma medulloblastoma lymphomesenteric cysts congenital malformation: cleft lip and/or palate, polydactyly, eye anomaly (cataract, colobma, microphtalmia, nystagmus)
the falx and tentorium early in life are well-known associations of Gorlin’s syndrome and constitute part of the major diagnostic criteria.2 Radiographs of the chest and mandible and CT scans of the brain are useful in screening for the disease. Gorlin’s syndrome is caused by a PTCH1 gene mutation which leads to a higher risk of developing BCC and hypersensitivity to radiation-induced tumorigenesis.5 Central nervous system abnormalities have been noted since the first patient report.1 The primary brain tumour most frequently associated with this syndrome is medulloblastoma, with an estimated frequency of about 20%.6 Meningioma is less commonly reported. From a study of CT scans of 82 patients with Gorlin’s syndrome, 5% were found to have radiological features suggestive of meningioma.7 There are no population-based studies to our knowledge for estimating the true figure. From patient reports of Gorlin’s syndrome-associated medulloblastoma treated with radiotherapy, seven out of eight patients reported developed a secondary intracranial tumour.7 Our patient had no preceding history of medulloblastoma or radiotherapy exposure. As a general rule, radiotherapy is not recommended as a treatment for Gorlin’s syndrome. Brain irradiation itself may cause secondary intracranial neoplasm. The true incidence of radio-induced neoplasms is currently unknown and the relationship between the dose delivered and the malignancy of the secondary tumour is still unclear.9 No quantification of the relative risk of intracranial radiation-induced neoplasm has been reported in the doi:http://dx.doi.org/10.1016/j.jocn.2013.02.033
recent literature8 but patients with NBCCS and associated medulloblastoma have been known to develop secondary brain tumours following radiotherapy.10 Further studies are needed to conclude the actual relative risk. 4. Conclusions Recognition of Gorlin’s syndrome is important as it is an autosomal dominant disease with significant penetrance. Early referral for genetic counselling is recommended as 70–80% of patients have an affected parent. Antenatal ultrasonography screening can be helpful to detect developmental abnormalities such as macrocephaly which may cause obstetrical complications.2 Radiotherapy should be avoided if possible in view of the genetic propensity for radiation-induced tumorigensis in these patients.2 Conflict of interest/disclosure The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. References 1. Gorlin RJ. Multiple nevoid basal-cell epithelioma, jaw cysts and bifid rib. A syndrome. N Engl J Med 1960;262:908–12. 2. Lo Muzio L. Nevoid basal cell carcinoma syndrome (Gorlin syndrome). Orphanet J Rare Dis 2008;3:32. 3. Evans DG, Ladusans EJ, Rimmer S, et al. Complications of the naevoid basal cell carcinoma syndrome: results of a population based study. J Med Genet 1993;30:460–4. 4. Kimonis VE, Goldstein AM, Pastakia B, et al. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet 1997;69:299–308. 5. Mancuso M, Pazzaglia S, Tanori M, et al. Basal cell carcinoma and its development: insights from radiation-induced tumors in PTCH 1 deficient mice. Cancer Res 2004;64:934–41. 6. Evans DG, Farndon PA, Burnell LD, et al. The incidence of Gorlin syndrome in 173 consecutive cases of medulloblastoma. Br J Cancer 1991;64:959–61. 7. Kimonis VE, Mehta SG, Digiovanna JJ, et al. Radiological features in 82 patients with nevoid basal cell carcinoma (NBCC or Gorlin) syndrome. Genet Med 2004;6:495–502. 8. Choudry Q, Patel HC, Gurusinghe NT, et al. Radiation-induced brain tumours in nevoid basal cell carcinoma syndrome: implications for treatment and surveillance. Childs Nerv Syst 2007;23:133–6. 9. Pettorini BL, Park YS, Caldarelli M, et al. Radiation-induced brain tumours after central nervous system irradiation in childhood a review. Childs Nerv Syst 2008;24:793–805 Epub 2008 Apr 8. 10. Mortimer PS, Geaney DP, Liddell K, et al. Basal cell naevus syndrome and intracranial meningioma. J Neurol Neurosurg Psychiatry 1984;47:210–2.