ARTÍCULO CLÍNICO

 

Gorlin-Goltz Syndrome. A 7 cases serie

Síndrome de Gorlin-Goltz: Serie de 7 casos

 

 

S. Rosón-Gómez¹, R. González-García², L. Naval-Gías³, J. Sastre-Pérez³, M.F. Muñoz-Guerra³, F.J. Díaz-González⁴

1 Medico Residente. H. Universitario La Princesa. Madrid. España
2 Medico Adjunto. H. Universitario Infanta Cristina. Badajoz. España
3 Médico Adjunto. H. Universitario La Princesa. Madrid. España
4 Jefe de Servicio. Servicio de Cirugía Oral y Maxilofacial. H. Universitario La Princesa. Madrid. España

Correspondence

 

 

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ABSTRACT

Nevoid Basal Cell Carcinoma Syndrome (NBCSS) or Gorlin- Goltz Syndrome is an autosomal dominant disorder principally characterized by cutaneous basal cell carcinomas, multiple keratocysts and skeletal anomalies. This report reviews current knowledge of this disorder that is important to us as specialists. The authors reviewed seven case files from the Department of Oral and Maxillofacial Surgery of H. U. La Princesa from 1992-2008. The average follow up was 10 years; we determine the frequency of the clinical features and treatment in our series of NBCCS.

Key words: Gorlin-Goltz; Basal cell carcinoma; Odontogenic keratocysts; Pits.

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RESUMEN

El Síndrome Névico Basocelular (SNBC) o Síndrome de Gorlin- Goltz es un trastorno autosómico dominante, caracterizado principalmente por carcinomas basocelulares, múltiples queratoquistes y anomalías esqueléticas. El presente trabajo revisa a este desconocido síndrome dada la importancia que tiene para nosotros como especialistas. Presentamos un total de siete casos recogidos por el Servicio Cirugía Oral y Maxilofacial desde 1992 al 2008, con seguimiento medio de 10 años, determinamos la frecuencia de las características clínicas en nuestra serie de SNBC y el manejo terapéutico de las mismas.

Palabras clave: Gorlin-Goltz; Carcinoma basocelular; Queratoquistes; Pits.

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Introduction

Nevoid Basal Cell Carcinoma Syndrome, also known as Gorlin- Goltz Syndrome, was described by Gorlin and Goltz in 1960. They were the first to name this entity by describing the classic clinical triad: multiple basal cell carcinomas, mandible cysts and skeletal anomalies.^1,2 It has a prevalence of 1/60,000,³ with greatest incidence among the white race, and has a similar distribution among both sexes. Clinical characteristics appear in the first 30 years of life.⁴ Gorlin-Goltz syndrome is a hereditary genetic disorder whose expression is dominant and penetrance. 60% of patients with NBCSS don't have a family history of the disorder, and within this group spontaneous mutations are responsible for 35-50% of the cases.^5-11

NBCCS is caused by mutations in "patched" gene, a tumor suppressing gene found in the long arm 9 chromosome (9q22.3-q21) that controls the growth and development of normal tissues.¹² Mutation of a single point of a patched allele can cause malformations. On the other hand the deactivation of both alleles causes the formation of tumors and cysts like basal cell carcinomas, odontogenic keratocysts and medulloblastoma.⁵

This project we apply our experience to the treatment of 7 patients affected by NBCCS.

 

Material and method

This is a study of seven patients with NBCCS are treated at the Maxillofacial and Oral Surgery Center in the University Hospital of the Princess, Madrid between 1992-2008.

Patient follow-up was carried out using OPG and periodic clinical exams. Average patient follow-up lasted 10 years which included clinical controls and periodic X-rays. We have carried out a retrospective study of all of the patients that had were odontogenic keratocysts operated on in the facial region at this hospital. Out of the 64 patients reviewed with odontogenic keratocysts in the maxilla-mandible revised for the study, they only selected those who met the NBCCS diagnosis criteria proposed by Evans.⁶Information was collected from clinical histories and epidemiological discoveries were reviewed. We also reviewed clinical characteristics, diagnostic techniques used, surgical procedures, immediate post surgical complications, histopathological characteristics and adjuvant treatment.

 

 

The descriptive statistical study was carried out using SPSS 16.00.

 

Results

There were a total of 7 patients included in this study from 1992 to 2008. The ratio of men to women was 6:1. Patients' ages ranged from 13-78 at the time of diagnosis.

The most common clinical manifestation that occurred in six out of the seven patients (85.7%) was multiple basal cell carcinomas whose diameter measured an average of 1.6 cm. The most common location for these carcinomas was the facial area (100% of patients) followed by anterior face of the torso, the back and the limbs. Therefore, the BBC's are the most prevalent manifestation in our study. They are more common in Caucasian males. The treatment of choice for all the cases analyzed (34 BBC's) was surgery, one of which required post operative radiotherapy. Anatomicophatological diagnosis was basal cell epithelioma; 26 pieces (79.4%) had a solid surface, 6 pieces (17.4%) infiltrating solid and 2 pieces (8.2%) sclerosing solid. In 7 cases (17.64%) surgical borders were reached (3 cases: solid infiltrating, 2 cases: surface solid 1 case sclerosing solid) all of which the borders were amplified. During follow up there was a 57% recurrence rate. One patient who had 10 synchronized lesions needed to be treated with 35mg/day of Acitretin in order to decrease the number of new lesions.

There were palmar and plantar pits in 42.8% of the patients making it the second most common skin manifestation and the 4th most prevalent clinical manifestation in this study. Treatment for 33% of the palmar plantar pits was surgical removal, while the other 66% maintained an expectant attitude.

The odontogenic keratocysts in our series make up the 2nd most prevalent clinical manifestation (71.4%), observed in 5 out of the 7 patients, diagnosed in a total of 13 primary lesions and 6 recurrences. The average age when these lesions appeared was 28 (ranging from 14-60). The male/female distribution in this series was 4/1. The most common site was the maxilla 53% (incisor-canine 28.5%, molar tubercle 71.4%) 47% of lesions were found n the mandible (molar-area 100%), averaging 2.8cm in size(from 1-4cm) In the OPG they looked like radiolucent, expansive lesions occupying the space (Fig. 1). The treatment for 16 of these lesions (84.2%) was their complete removal. Progress was favorable, without immediate postoperative problems and the consolidation time was 9 months (Fig. 2). In three odontogenic keratocysts decompression was carried out using drainage and washing tubes. In 2 of these cases (66%) posterior marsupialization was carried out after 9 months, while in the other (33%) they did a cystectomy. Complications when treating this lesion decrease to a fistula oro antal, that requires exeresis and closure using a Bichat ball. In all of the cases the pathological anatomy confirms the keratinized keratocyst diagnosis. The recurrence rate in our series was 38.5%, and the average time free from illness was 2.5 years. Recurrence location was the mandible region in 100% of cases (incisor-canine 50% and molar-area 50%). Other odontogenic alterations included multiple dentals in 51% of cases, diastem and gingival hyperplasia.

 

 

 

3 patients had skeletal alterations, they included: tarsal coalition, scaphoid calcaneus, polydactyl, pectus deformity, cyphosis, bifid ribs and bone links between posterior and anterior clinoids. Calcification of the falx cerebri was found in 4 patients (57.1%) (Fig. 3). Balling of the sella turcica (28.5%), sub cortical- cortical atrophy (42.5%), pineal gland calcification, callous body agenesis, tri ventricular dilatation and calcifications associated with epilepsy.

 

 

In 2 cases macrocephaly was observed at birth. Both patients suffered from hydrocephaly that called for peritoneal valve placement. In addition, one of them had meningomyelocele and absence seizure. 42.8% of cases had facies that are characteristic of implants below the ears, wide forehead, Crouzon's disease and triangular cranium. One patient had hypgonadism and another medulloblastoma.

 

Discussion

NBCSS is not a very frequent entity in our population. It is associated with an autosomal dominant genetic make up, except in a minority of patients affected, where the entinty is caused by spontaneous mutations.

Basal cell carcinomas associated with NBCSS have a peak incidence between puberty and the age of 35. On the other hand, in our study, the average age was 43, 10 years older that the age indicated by the literature. The most common BBC location in patients affected by NBCSS was the thoracic and cervico facial region (periorbitary region parpados, nose, jugular region and the upper lip),¹³ data that corresponds with out study. The NBCSS, the number of BBC is very variable, in a single patient the number can range fro 1-100. In our series the range was from 2 lesions, in the mildest cases, to more than 10 lesions in the more aggressive cases. In the anatomicophatological study of these lesions the majority are on the surface and don't passover the epidermis. Treatment of BBC in the NBCSS has particularities. These are due to the great umber of lesions that are present, the early age of appearance and its high recurrence rate. Electrodisection, cauterization and crettage are conservative treatments that can be used in small, welld fined lesions that are not histologically aggressive. Cryosurgery has proven to be useful in the treatment of single and multiple lesions of BBC but not in their recurrence. As an alternative certain authors propose the combination of CO₂ laser and surgery. Another valid option for surface lesions is photodynamic therapy associated with the topical application of delta-aminolevneico acid. Other therapuetic proposals include the topical application of 0.1% of flourouracil or intra lesion application of alpha interferon 2b. For more aggressive cases, one alternative to keep in mind is oral retinoid (Placitazel Taxol^®) which are used to prevent or slow the development and recurrence of BBC's despite their significant toxicity.^14,15

There has not been a consensus about how to treat multiple basal cell carcinomas therefore there is a great variety of therapeutic measures reviewed in the literatures. However, all of the authors do agree that a less aggressive treatment is the best choice because of its high local recurrence rate. We propose simple surgical excision as the treatment of choice for these types of lesions, given its effectiveness and low complication rate. Therefore it is important to keep an exhaustive medical control in an attempt to treat small lesions inturn decreasing post surgical consequences. The appearance of BBC's over the palmar and plantar pits is exceptional. The treatment used in 66% of the cases in our study was conservative. Therefore, given the infrequent malignization of these lesions and the fact that they are asymptomatic we think that monitoring these lesions should be the first therapeutic measure taken.

Odontogenic keratocysts appear in more than 75% of the patients with NBCSS.⁹ They start in the first 10 years of life and are one of the first clinical manifestations. They are usually diagnosed accidentally during a routine ortopantograph or because of the appearance of symptoms. The keratocysts that are associated with the NBCSS have a high recurrence rate, between 30 and 60%, while the in the general population they only represent 7%.¹¹

It is always important to be as conservative as possible because of the young appearance age, possiblity of reccurence and difficult management of these lesions. In our series the treatment of choice for odontogenic keratocysts smaller than 3 cm was complete removal. 9 months after surgery we had good results and bone consolidation. However for those that were between 3 and 4 cm in size we decided to surgically decompress them using a drainage and washing tube to reduce the initial size. Later this allowed us to be able to carry out marsupialization or cystectomy a second time. In turn lengthening the consolidation process but providing good long term results. Currently there is not a study that compares conservative radical treatments for patients affected by NBCSS. In recent studies, like the one by Kolokythas et al.,¹⁶ they found positive change in the odontogenic keratocyst behavior. Surgical depression lowered aggresiveness and recurrence rates. This is due to the inhibition of the IL- 1a, the cell dedifferentiation factor and the loss of citokeratine- 10 production. Although the study does not include patients with NBCSS, because of the positive results it could still help us choose an appropriate treatment.

NBCSS is an uncommon entity in our field, but we should know how to properly diagnose it and treat it early. We suggest simple excision for basal cell carcinoma because of its effectiveness and low complication rate. For keratocysts smaller than 3 cm we suggest cystectomy while for those larger than 3 cm we suggest treatment with surgical decompression. Therefore, in conclusion due to the high reccurence rates for these lesions, NBCSS requires early detection, a multidisciplinary exhaustive follow-up and an efficient conservative treatment.

 

 

Correspondence:
Silvia Rosón Gómez
Servicio de Cirugía Oral y Maxilofacial.
Hospital Universitario de la Princesa. España.
C/ Diego de León, 62 - 28006 Madrid
E-mail: silviarosongo@yahoo.es

Recibido: 13.04.2009
Aceptado: 24.09.2009

 

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