Ocular, Orbital, and Adnexal Toxicity With High-dose Volumetric Modulated Arc Radiation Therapy for Orbital Malignancies.

PURPOSE: Conventional modalities of external-beam radiation therapy (EBRT) are associated with high incidences of severe vision-threatening ocular and orbital toxicities when used to treat orbital malignancies. We investigate toxicities associated with high-dose volumetric modulated arc therapy (VMAT), a commonly used contemporary treatment modality for these tumors. METHODS: Retrospective analysis of malignant orbital tumors managed with adjuvant high-dose VMAT preceded by globe-salvaging surgical therapy (GST) or exenteration. Dosimetric quantitation of target volumes and critical structures was performed. Incidence and severity of ocular, orbital, and adnexal toxicities were evaluated and assessed with regard to conventional EBRT toxicities for orbital malignancies described in the literature. RESULTS: Eighty-four subjects (mean age = 65.9 ± 9.7 years) were included (N = 48 and N = 36 in GST and exenteration subgroups, respectively). Mean dose was 64.8 ± 2.1 Gy to the planning target volume. Dosing to critical structures typically did not surpass known tissue tolerance limits. Median follow up was 18.3 months. Visual acuity in the GST subgroup was not significantly different after VMAT (0.25 ± 0.06) compared with baseline (0.23 ± 0.02; P = 0.302). Whereas severe toxicities reported by major systematic analyses in the literature with older EBRT modalities were relatively common-for example, retinopathy (16-40%), optic neuropathy (16%), and corneal perforation (13%)-toxicities with VMAT were typically mild and less common. The most common toxicities with VMAT were mild dry eye (81.3%; 39/48), cataract (21.1%; 8/38 phakic eyes), and periocular dermatitis (15.5%; 13/84). Vision-threatening toxicities, including severe corneal pathologies, retinopathy, or optic neuropathy, were rare. There were no contralateral ocular or adnexal toxicities. CONCLUSIONS: High-dose VMAT for orbital malignancies demonstrated low incidence and severity of eye-related toxicity, in contradistinction to adverse events reported from conventional forms of radiotherapy.

[Orbital Manifestation of IgG4-Related Disease: Three Case Reports]. / Orbitale Manifestation der IgG4-assoziierten Erkrankung: eine Fallserie.

IgG4-related orbital disease is rare. It belongs to an entity of a multisystemic disorder - IgG4-related disease - which has emerged recently. Differential diagnosis comprises idiopathic orbital inflammation, endocrine orbitopathy and orbital neoplasms. MRI imaging and orbital biopsy are essential in making the diagnosis. Patients respond well to systemic steroids. We now describe three clinically markedly different manifestations of IgG4-related orbital disease.

Orbital Extranodal Marginal Zone Lymphoma Following Radiotherapy: A Report of 2 Cases.

PURPOSE: To present 2 patients in whom orbital radiation preceded the development of periorbital extranodal marginal zone lymphoma by more than a decade and to investigate the likelihood of this representing irradiation-induced malignancy. METHODS: Retrospective chart review and histopathologic study with immunohistochemistry of 2 cases. RESULTS: The first patient was a 58-year-old woman who developed an orbital mass within the vicinity of the lateral rectus muscle 17 years after external beam proton radiation therapy for an inferotemporal choroidal melanoma. The second patient was a 32-year-old woman who developed a mass in the right lacrimal gland 12 years after external beam photon radiation therapy for chronic inflammatory dacryoadenitis. Histopathologic and immunohistochemical studies confirmed orbital extranodal marginal zone lymphoma in both cases. Retrospective review of older histopathologic slides from the second patient revealed underlying immunoglobulin G4-related disease. DISCUSSION: The unusual sequence of events in these 2 cases raises the question of whether orbital radiation may in rare instances promote the development of orbital extranodal marginal zone lymphoma. The literature pertaining to irradiation-induced secondary malignancy in the orbit is reviewed. CONCLUSIONS: Clinicians should consider the possibility of a secondary malignancy when evaluating a patient with an orbital mass and a history of prior local radiation exposure.

Orbital diffuse large B-cell lymphoma with combined variable immunodeficiency.

Common variable immunodeficiency (CVID) is a primary immunodeficiency manifesting as a reduction in the level of total immunoglobulin (Ig) G, a reduction in the level of either IgA or IgM, poor response to polysaccharide vaccine, and usually frequent infections. The association of CVID with an increased risk of malignancy, specifically lymphoma, is well known. A 63-year-old female with a past medical history significant for CVID presented with a 1-month history of dull, left eye pain with proptosis, hypoglobus, and left upper lid fullness without a discrete palpable mass. Magnetic resonance imaging (MRI) of the orbits revealed a diffuse infiltrating orbital mass superonasally with extension into the superior rectus muscle, medial rectus muscle, and optic nerve up to the orbital apex and ethmoid sinus. A superonasal orbital biopsy with a caruncular approach was performed and demonstrated a sparse lymphoid infiltrate that was suggestive for a large B-cell neoplasm. Positron emission tomography (PET) scan demonstrated a hypermetabolic right lymph node, anterior to the right submandibular gland, which was biopsied and histopathology confirmed diffuse large B-cell lymphoma (DLBCL). Our patient achieved a very good response to chemotherapy with minimal residual disease on PET scan at the end of treatment. She attained a complete remission after radiation therapy. In conclusion, patients with new orbital and adnexa masses in the setting of a primary immunodeficiency can have an aggressive malignancy such as DLBCL and early diagnosis and systemic treatment carries a good prognosis.

Pseudoadenomatous Hyperplasia of the Inferior Forniceal Conjunctiva Due To Prosthetic Irritation in an Anophthalmic Socket.

Secondary complications in an anophthalmic socket can include late appearing shrinkage due to scarring and squamous cell carcinoma. This article reports a 51-year-old man who 27 years after an enucleation developed an inability to retain his ocular prosthesis due to an acquired multilobular fleshy mass in his inferior fornix. The patient had worn his prosthesis without removal for years at a time. Microscopic evaluation of the excised lesion disclosed a pseudoadenomatous (pseudoglandular) hyperplasia of the conjunctival epithelium with myriad goblet cells and accompanying chronic inflammation. In cross section, these structures microscopically resembled an adenoma but were found to display multifocal origins from the surface epithelium resembling exaggerated pseudoglands of Henle. Simple excision without recurrence 6 months later has permitted a new prosthesis to be comfortably worn with stability.

Orbital medulloepithelioma in an adult patient: Radiation-induced second neoplasia?

Second cancers in survivors of hereditary retinoblastoma occur much more commonly than in the general population. This can be attributed both to the germline mutation of the RB gene and chemoradiation used for treatment of this paediatric cancer. Medulloepithelioma is an uncommon tumor of neuroectodermal origin, seen largely in the paediatric population and rarely reported in adults. Though the incidence of second malignancies is common in retinoblastoma, medulloepithelioma as a second malignancy in retinoblastoma survivors is rare, with only one case reported so far. Herein, we present a case of a 29-year-old patient presenting with medulloepithelioma of the right orbit, arising in the radiation field of previously treated retinoblastoma. This case was also peculiar in that though the origin of tumor was in the eyeball it had a very aggressive clinical course.

Unusual case of traumatic neuroma of the orbit.

Traumatic or amputation neuromas are neoformations developing after damage to a peripheral nerve. They are not proper tumors but rather a reactive process or a frustrated attempt of nerve regeneration. Traumatic neuromas are potentially found in every sensory peripheral nerve and often at the site of past surgical intervention, including orbital surgery. A 29-year-old Northern African migrant presented progressive exophthalmos and progressive loss of acuity in left eye, which had started about 6 months before after a cranio-facial trauma caused by a violent assault. MRI of the orbits showed a massive intra-orbital, intra-conical lesion, clearly compressing and dislocating the optic nerve and extending posteriorly to the orbital apex. Surgery was performed through lateral approach of Kroenlein and led to complete excision of the lesion. Histology revealed fibrotic, adipose and striated muscle tissues, a disordered, non-neoplastic overgrowth of small and large fascicles of nerves, inflammatory infiltrates, and fibrosis with sparse calcifications were diffusely observed in a background of fat, scar and striated muscle tissued. Patient was discharged on the fifth day in good health condition, without deficit of eye motion but without recovery of visual acuity. In conclusion, this case demonstrates that traumatic neuromas may arise in the orbit in patients with minor direct trauma to nerves and without previous surgical treatment.

Traumatic Presentation of a Periorbital Dermoid Cyst: A Case Report.

Dermoid cysts are largely considered benign, developmental neoplasms that frequently present during childhood. Orbitofacial dermoids represent a unique group of embryologically derived soft tissue masses that often present as localized, well-circumscribed swellings along the embryonal suture lines. Clinical presentation is variable, but in rare instances, may be preceded by local trauma, possibly suggesting an inciting event as the initial stimulus to cyst enlargement. Although dermoid cysts tend to remain clinically benign, their natural history of gradual enlargement necessitates complete surgical excision to prevent complications.

Childhood Ewing Sarcoma of the Orbit.

In the span of the last 48 years, only 33 cases of children with orbital Ewing sarcoma have been reported. This study is to present 3 cases that were admitted to Children's Cancer Hospital Egypt 57357, during the period from 2009 to 2013. We have 2 cases treated using the hospital standard Ewing sarcoma treatment protocol, to completion, whereas the third discontinued treatment. All tumors have confirmed CD99 positivity, although translocation (11;22) was positive in 1 patient and negative in the third. With earlier diagnosis and adequate surgical resection and integration of chemotherapy and radiotherapy 1 patient survived for about 4 years, whereas the other 2 cases died due to disease progression or recurrence.

Multiple nevoid basal cell carcinoma syndrome associated with congenital orbital teratoma, caused by a PTCH1 frameshift mutation.

Gorlin-Goltz syndrome, or nevoid basal cell carcinoma syndrome (NBCCS), is a rare autosomal dominant disorder caused by mutations in the PTCH1 gene and shows a high level of penetrance and variable expressivity. The syndrome is characterized by developmental abnormalities or neoplasms and is diagnosed with 2 major criteria, or with 1 major and 2 minor criteria. Here, we report a new clinical manifestation associated with this syndrome in a boy affected by NBCCS who had congenital orbital teratoma at birth. Later, at the age of 15 years, he presented with 4 major and 4 minor criteria of NBCCS, including multiple basal cell carcinoma and 2 odontogenic keratocysts of the jaw, both confirmed by histology, more than 5 palmar pits, calcification of the cerebral falx, extensive meningeal calcifications, macrocephaly, hypertelorism, frontal bosses, and kyphoscoliosis. PTCH1 mutation analysis revealed the heterozygous germline mutation c.290dupA. This mutation generated a frameshift within exon 2 and an early premature stop codon (p.Asn97LysfsX43), predicting a truncated protein with complete loss of function. Identification of this mutation is useful for genetic counseling. Although the clinical symptoms are well-known, our case contributes to the understanding of phenotypic variability in NBCCS, highlighting that PTCH1 mutations cannot be used for predicting disease burden and reinforces the need of a multidisciplinary team in the diagnosis, treatment, and follow-up of NBCCS patients.

[Plexiform neurofibroma of the upper eyelid and orbit in a patient with von Recklinghausen's disease--case report]. / Nerwiakowlókniak splotowaty powieki górnej i oczodolu w przebiegu choroby von Recklinghausena--opis pacjenta.

Neurofibromatosis type 1 is an autosomal dominant genetic disease, which belongs to the neuro-oculo-cutaneous syndromes (phakomatoses). The authors present a case of a girl with familial neurofibromatosis. In addition to typical skin lesions and Lisch nodules on the iris, the plexiform neurofibroma of the upper eyelid and orbit as well as hamartoma of the central nervous system were observed. Due to the massive infiltration of the left upper eyelid causing its complete ptosis and, in turn, the amblyopia of the left eye, the tumour was partially rexcised. This lesion is not totally removable in most cases due to the early development of neurofibroma during the fetal period and its strong adhesion to the healthy tissues. A massive eyelid infiltration causing amblyopia and dissociation of binocular vision is an indication for early surgery.

Orbital granular cell tumor in a patient with Churg Strauss syndrome: the importance of biopsy.

A 65-year-old woman presented with a long standing, progressive exophthalmos of the right eye. Her medical history was significant for Churg Strauss syndrome, and was treated with immunosuppressive therapy. She had undergone two previous orbital biopsies showing inflammatory reactive lymphoid hyperplasia. A diagnosis of orbital inflammation in Churg-Strauss syndrome was suspected, and the immunosuppressive therapy was increased. Because of the lack of response to therapy, a further biopsy was performed, by lateral orbitotomy approach. Biopsy of the mass revealed a granular cell tumor composed of S-100 positive cells with an acidophilic granular cytoplasm and peripheral lymphocytic infiltration. A granular cell tumor, which is very rare in the orbit, should be considered in the differential diagnosis of orbital tumors, and if suspected, an excisional biopsy must be undertaken. Typical histopathological aspect of the granular cell tumor is characterized by the presence of S-100 positive closely packed polygonal cells with a granular cytoplasm.

[Bilateral orbital myeloid sarcoma: the circumstance of the discovery of acute myeloid leukemia (a case report)]. / Sarcome myéloïde orbitaire bilatérale: circonstance de découverte d´une leucémie aiguë myéloïde (à propos d´un cas).

Myeloid sarcoma is a rare ocular manifestation of acute myeloid leukemia. Bilateral manifestation preceding any clinical signs of leukemia is even rarer. We here report the case of a 16-month-old patient with rapidly progressive, inflammatory, acute bilateral exophthalmos associated with exposure keratitis. Computed tomography (CT) scan of the orbit and of the brain showed bilateral tissue-like infiltration into the orbital cavity. Blood tests showed biologic inflammatory syndrome, bicytopenia and circulating blasts 83%. Myelogram was performed based on the presence of circulating blasts; it showed acute myeloid leukemia (grade 4). Clinicians should suspect myeloid sarcoma in patients with bilateral exophthalmos and conduct a careful interpretation of blood test results.

Synchronous radiation-induced orbital meningioma and multiple cavernomas.

Synchronous radiation-induced tumours are extremely rare. We present the first reported case of synchronous radiation-induced orbital meningioma and cavernomas of the cerebellum and bilateral basal ganglia, presenting 16 years after ionizing radiation therapy for parietal anaplastic ependymoma, at the age of five. This case again underscores the risks of radiotherapy to children.

[Malignant peripheric nerve sheath tumor of the orbit: first description of orbital location in a patient with NF1]. / Tumor maligno de la vaina del nervio periférico (MPNST) glandular de la órbita: primera descripción de la literatura de localización orbitaria en un paciente con neurofibromatosis tipo 1.

INTRODUCTION: The malignant peripheric nerve sheath tumor (MPNST), is a malignant neoplastic lesion originated in Schwann cells of the lining sheath of peripheral nerves. This neoplasia may appear with benign or malignant heterologous components, with divergent differentiation, as the glandular one. AIM: To describe for the first time in the literature, a case of a glandular MPNST, located at the orbit and to revise the literature on this tumoral lesion. CLINICAL CASE: Nine year old male, with a base diagnosis of NF1, who had exophthalmos, retro-ocular pain, headache, facial asymmetry and descent of the right eyeball, that started 1 year earlier. This patient showed in the Computed Tomography an Magnetic Resonance, a well delimited, lobulated, solid mass at the eyeball, which extended to the fontal and temporal brain parenchyma. A right Fronto-temporal craniotomy was made with fronto -orbital- zygomatic resection of the tumoral lesion. Later, a dural plasty and reconstruction with titanium mesh was made at the skull base. At present, the patient is asymptomatic after 4 months of follow up. A malignant biphasic neoplastic lesion was observed, reactive in the mesenchymal elements S100, PGP 9.5, neurofilaments and vimentin. The glandular component was positive for AE1/AE3, EMA, CEA and focally for CD57. There was also reactivity to cromogranin, synaptophysin, serotonin and somatostatin. The diagnosis of Glandular MPNST was made. CONCLUSION: For the first time in the literature a case of Glandular MPNST located at the orbit, which occurred in child with NF1, is described. This extremely uncommon neoplasia must be taken into account, in the study of biphasic malignant lesions, as its diagnosis is of great importance because of the bad prognosis of the affected patients.