A 52-year-old woman presented to our Dermatology department referred from her general practitioner with four skin lesions in her face suspected of being malignant. These lesions were diagnosed as basal cell carcinomas (BCC) on histology. A rare syndrome was suspected and a radiographic work-up was made.
On physical examination four skin lesions in the head were present. These lesions were submitted to histologic characterization, which revealed BCC. In addition palmar pitting was also noticed. Some teeth were missing too.
Plain skull X-ray showed the presence of falx cerebri calcifications (Fig. 1). Brain CT confirmed the falx cerebri calcifications and also shown tentorium cerebelli calcifications (Fig. 2).
Chest X-ray revealed that 3rd and 4th ribs on the right were bifid (Fig. 3). Spine X-ray showed a marked right-sided dorsal scoliosis (Fig. 4a). Given the clinical context, a CT was performed as these aspects, although unapparent on X-ray, could be in relation with hemivertebra or vertebral synostosis. CT excluded vertebral segmentation anomalies (Fig. 4b).
Head CT showed and extensive cystic lesion in the right maxilla, in relation to odontogenic keratocyst (Fig. 5)
Gorlin-Gotz syndrome (GGS), also known as Nevoid basal cell carcinoma syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57, 000 to 1/256, 000 [1]. It was first reported in 1894 [1, 2, 3] but delineated by Gorlin and Goltz in 1960, as a distinct entity consisting of ectodermal and mesodermal abnormalities [4].
GGS is caused by mutations in the PTCH1 gene and is transmitted in an autosomal dominant manner with high penetrance and variable expressivity. There is no sexual predilection. Individuals with no known affected family members may comprise up to 60% of all affected individuals [1].
Many different signs and symptoms may be associated with GGS. Main clinical manifestations include basal cell carcinomas, which may appear very early (2 years of age); odontogenic keratocysts that generally develop in the first, second and third decades; palmar and/or plantar pits, and ectopic calcifications of the falx cerebri. These manifestations are considered as the major criteria for diagnosis. The disorder is also characterized by congenital skeletal abnormalities, macrocephaly with frontal bossing, cleft lip and/or palate, and eye anomalies. Various low-frequency neoplasms, such as medulloblastomas, meningiomas, and ovarian and cardiac fibromas have been also reported [1, 5].
Evans et al. [6] first established major and minor criteria for diagnosis of this rare entity, later modified by Kimonis et al. [7] According to them diagnosis of GGS can be established when two major or one major and two minor features are present [1, 5, 8] (Fig. 6)
In our case, four major criteria (multiple BCC, palmar pits, maxillary odontogenic keratocysts [although not histologically proven] calcification of falx cerebri and tentorium and bifid ribs) were detected.
The radiologic protocol for the diagnosis of this syndrome may include panoramic radiography to detect multiple jaw cysts, skull radiography for evaluation of falx cerebri calcification, chest radiography to detect bifid, fused or splayed ribs, and computed tomography as well as magnetic resonance images to find further abnormalities [9].
Gorlin-Goltz syndrome
Based on the provided head CT, chest X-ray, and maxillofacial CT images, the following main features are observed:
• Head/Skull Imaging: Calcification in the falx cerebri and tentorium is seen on axial and coronal CT images, appearing as high-density linear or patchy calcifications.
• Maxillofacial CT: Suspected cystic changes in the maxilla or mandible, suggesting the possibility of odontogenic keratocysts (OKC).
• Chest X-ray: Bifid or developmentally abnormal ribs are visible in the frontal view of the chest, indicative of typical skeletal abnormalities.
Considering the patient’s multiple basal cell carcinomas (BCC), cystic jaw lesions (possibly OKC), intracranial calcifications, and rib abnormalities, combined with clinical presentation and literature data, the following diagnoses and differential diagnoses are proposed:
1) Gorlin-Goltz Syndrome (GGS)
– Cause: Involves PTCH1 gene mutations with clear hereditary features.
– Characteristics: Multiple BCCs, jaw OKCs, intracranial calcifications (especially in the falx and tentorium), and rib abnormalities (such as bifid or fused ribs). Often associated with palmar-plantar pits and other manifestations.
2) Simple Multiple Basal Cell Carcinomas
– Mechanism: Although multiple basal cell carcinomas can occur without a syndrome, the presence of additional skeletal or dental-jaw region pathologies necessitates ruling out hereditary syndromes.
– In this case, because of multisystem involvement, simple multiple BCCs alone are less likely.
3) Other Genetic Syndromes Involving Skin and Skeletal Abnormalities
– For instance, some rare neurocutaneous syndromes. However, the involvement patterns and imaging features (cranial calcifications, OKCs, rib abnormalities) are less characteristic than those of GGS, so they have lower priority.
Taking into account the patient’s age of onset, histological confirmation of multiple facial BCCs, presence of palmar-plantar pits (clinical manifestation), suspected OKC-like lesions in the jaw, intracranial dural calcifications, and rib anomalies, the findings are consistent with Gorlin-Goltz Syndrome (GGS).
Therefore, the most likely final diagnosis is: Gorlin-Goltz Syndrome.
If further confirmation of the nature of the jaw cysts (OKC) is required, surgical intervention or aspiration/biopsy for pathological diagnosis may be considered for a more precise treatment plan.
In accordance with the current understanding of GGS, a comprehensive management and long-term follow-up strategy is needed in the following areas:
1) Management of Skin Lesions
– For confirmed multiple basal cell carcinomas, evaluate the extent and depth of the lesions and consider surgical excision, curettage with electrodessication, cryotherapy, or topical agents (such as 5-FU or imiquimod).
– Schedule regular dermatological follow-ups, practice proper sun protection, and avoid excessive UV exposure that may trigger new BCC lesions.
2) Management of Maxillofacial Cysts
– Periodically monitor the cysts with imaging to track size and growth. Surgical curettage or resection may be indicated if necessary to alleviate local bone destruction and mitigate the risk of deformities.
3) Monitoring Other Skeletal or Visceral Tumors
– Conduct regular imaging assessments of the head, chest, and abdomen to detect potential bone or soft tissue tumors at an early stage, such as vertebral anomalies or fibromas.
4) Rehabilitation and Exercise Prescription
Principles: Gradual progression, individualization, and prioritizing safety. Considering possible skeletal abnormalities, high-impact activities that may increase fracture risk should be avoided.
• Type of Exercise: Start with low-impact exercises such as walking, swimming, or using a stationary bike to minimize stress on bones and joints.
• Frequency: 3–5 sessions per week, 20–30 minutes each time, with gradual increases according to tolerance.
• Intensity: Aim for moderate intensity (feeling slightly out of breath but able to speak) and adjust based on individual fitness.
• Duration: Begin with 15–20 minutes, gradually extending to 30–45 minutes, adjusting according to the patient’s fatigue and skeletal health status.
• Progression (FITT-VP):
F (Frequency): Increase from 2–3 times per week to a steady 3–5 times;
I (Intensity): Gradually move from light-moderate to moderate intensity;
T (Time): Extend the duration of each session progressively;
T (Type): Transition from low-impact to moderate weight-bearing exercises as tolerated;
V (Volume): Adjust total exercise volume according to patient tolerance;
P (Progression): Proceed incrementally without causing significant pain or fatigue, and avoid excessive volume at once.
• Precautions: If the patient has spinal or rib anomalies, avoid heavy loads or high-risk movements. Closely monitor for pain and fatigue, adjusting the plan as needed.
Disclaimer: This report is for reference purposes only and is not a substitute for an in-person consultation or professional medical diagnosis and treatment. If you have any questions or notice any changes in your condition, please seek medical attention promptly.
Gorlin-Goltz syndrome
