Named by Bourneville, one of its earliest discoverers, tuberous sclerosisis a heritable neurocutaneous syndrome that is classically manifested by theVogt triad of mental deficiency, epilepsy, and adenoma sebaceum.1 Despitethe classic triad of findings, tuberous sclerosis is a protean disorder characterizedby the presence of hamartomas (benign neoplasms composed of cellular elementsnormally present in tissue) in multiple organ systems, including the brain,kidneys, heart, spleen, lungs, and eye.2,3 Osseousinvolvement is known to occur in the skull, long bones, pelvis, and metacarpaland metatarsal bones. We report a case of tuberous sclerosis that manifestedas a bony mass arising from the inferior (maxillary bone) orbital rim. Histopathologicexamination of the excised lesion revealed a hamartoma composed of maturebone. Based on our MEDLINE review of the English-language literature, thisis the first reported case of a bony hamartoma arising from this locationof the facial skeleton in a patient with tuberous sclerosis.
A 6-year-old girl with known tuberous sclerosis had a mass involvingthe right inferior orbital rim. The lesion was first noticed by her parentsat 1 year of age, and it slowly enlarged during the next 5 years. The patientwas diagnosed as having tuberous sclerosis at the age of 6 months based onthe characteristic symptoms and signs of a seizure disorder, developmentaldelay, and classic skin lesions, including adenoma sebaceum along the bridgeof the nose and an ash leaf spot on the back of the right calf. There wasno other significant medical or family history. The patient's fraternal twinwas unaffected. Although the mass did not cause any functional symptoms, thepatient's parents were concerned about the progressive increase in size andthe obvious facial deformity.
On initial examination, a 1.5 × 1.0-cm firm, nontender, immobilemass was identified along the right inferior orbital rim and cheek area (Figure 1). In addition, a 1.0 × 0.5-cmhyperpigmented, slightly elevated skin lesion was noted overlying the inferiororbital rim mass. There were also several small skin lesions involving themidface and nose, which appeared to be adenoma sebaceum, and an ash leaf spoton the back of the right calf. Visual acuity without correction was 20/25OD and 20/30 OS. The remainder of the ophthalmic examination findings wereunremarkable. A computed tomographic scan of the head and orbits showed abony lesion arising from the upper portion of the right maxillary bone justbelow the orbital rim (Figure 2).The lesion was sessile in appearance and measured 1.0 cm along the base andapproximately 1.5 cm in the anteroposterior projection. There was no evidenceof bony erosion or excavation, and the mass was described as a bony exostosis.Additional radiologic findings included a dense 4-mm calcification in thesubependymal space lining the left frontal horn, as well as multiple areasof low-density attenuation consistent with cortical tubers within the cortexof both cerebral hemispheres. The right maxillary sinus was noted to be nearlycompletely filled with what appeared to be a retention cyst associated withchronic sinusitis. Because of the prominent location of the lesion and associatedfacial distortion, the decision was made to proceed with surgical excisionof the bony mass and the overlying skin lesion.
Patient with a large elevatedmass along the right inferior orbital rim and cheek area measuring 1.5 ×1.0 cm.
Enhanced axial computed tomographicscan of the orbits and facial bones showing a bony mass protruding from theupper portion of the right maxillary bone.
The overlying skin lesion was removed first via an elliptical skin excision.Dissection then proceeded through the layer of orbicularis muscle, and thebony lesion was identified (Figure 3).The lesion was whitish and firm and had a bony consistency on palpation. Theperiosteum surrounding the mass, which was normal in appearance, was incisedand reflected. An angled oscillating saw was used to remove the lesion flushwith the anterior plane of the maxilla, and a 5-mm cutting burr was used tosmooth the edges. In the same setting, an ear, nose, and throat specialistperformed a right endoscopic maxillary antrostomy for treatment of the right-sidedchronic maxillary sinusitis noted on computed tomography.
Surgical excision showing theexposed bony lesion just before removal.
The bony lesion consisted of medullary bone surrounded by dense fibrosis.Numerous interconnecting bony trabeculae were present within normal bone marrow.Osteoblasts were present on the surface of the trabeculae (Figure 4). The skin lesion showed a localized area of fibrosis andvascular proliferation consistent with an angiofibroma.
Low-power microscopic examinationshowing medullary bone surrounded by dense fibrosis and numerous interconnectingbony trabeculae within normal bone marrow (hematoxylin-eosin, original magnification×20).
Tuberous sclerosis, otherwise known as Bourneville disease, is an autosomaldominant syndrome with an incidence of 1 case per 6000 to 29 900 peopleper year.4 Despite its capability of followingclassic Mendelian patterns, approximately two thirds of cases are sporadicand seem to arise from new somatic mutations. Genetic research has implicatedmutations at 2 gene loci, 9q34 (TSC1) and 16p13 (TSC2), in the pathogenesis of tuberous sclerosis.5 These genes are thought to be tumor suppressors.Historically, the clinical criteria for diagnosing tuberous sclerosis includefacial adenoma sebaceum, mental deficiency, seizures, and retinal astrocytomas(hamartomas), although not all of the criteria need to be met to make thediagnosis.1- 3 Inaddition to skin and retina, hamartomas have been identified throughout thebody in locations such as the iris, brain, bones, kidneys, lungs, heart, andtongue.2,3,6,7
Bony abnormalities in patients with tuberous sclerosis have been previouslydescribed in the skull, long bones, pelvis, and metacarpal and metatarsalbones, with the hands and feet the most commonly involved. These lesions canbe focal or diffuse; tend to be round, oval, or flame shaped; and range insize from a few millimeters to several centimeters. These bony lesions typicallymanifest as small cortical cysts or areas of dense periosteal sclerosis, theresult of fibrous replacement of the normal trabecular bone pattern, and canproduce an undulation in the bony contour.2,8,9 Bonyabnormalities can be found in the cranium in up to 45% of patients with tuberoussclerosis.9 Radiographs of the skull mayreveal sclerotic areas of dense bone formation, often due to hyperostosisof the diploë trabeculae of 1 or both tables of the cranial vault. Thecalvaria is thinned, marrow spaces are replaced by fat, and the periosteumis thickened.2,8,9
After an extensive review of the peer-reviewed English-language literatureusing MEDLINE, we found only 1 report describing an osseous abnormality ofthe facial skeleton and orbit in a patient with tuberous sclerosis and nonewith histopathologic confirmation of a bony hamartoma in this location. Breningstallet al10 reported a case of a sclerotic lesionof the sphenoid bone in a 9-year-old girl with tuberous sclerosis who hadleft-sided proptosis. Skull radiographs and computed tomography revealed markedsclerosis and thickening of the left wing of the sphenoid bone, which wasattributed to fibrous dysplasia. However, no histopathologic analysis wasprovided.
To our knowledge, this case of a large bony hamartoma arising from theinferior orbital rim in a patient with tuberous sclerosis provides the firstclinicopathologic confirmation of a bony hamartomatous lesion involving thefacial skeleton in the setting of tuberous sclerosis. Physicians treatingpatients with tuberous sclerosis should be aware of this presentation.
The authors have no relevant financial interest in this article.
Corresponding author: Dale R. Meyer, MD, Lions Eye Institute of AlbanyMedical Center, 35 Hackett Blvd, Albany, NY 12208.
Abel A, Brockbank DT, Farber M, Meyer DR. Bony Hamartoma of the Inferior Orbital Rim in a Patient With TuberousSclerosis. Arch Ophthalmol. 2004;122(5):780-782. doi:10.1001/archopht.122.5.780