Ординатура / Офтальмология / Английские материалы / Surgical Atlas of Orbital Diseases_Mallajosyula_2009

Figure 18.13: Basal cell carcinoma of eyelids with orbital extension

multiple applications. A course of radiotherapy is advocated for large tumors in older patients.

Photodynamic therapy and carbon dioxide lasers have emerged recently. Percutaneous delta aminolaevulinic acid is used with exposure to light in the 620-670 nm range. The success rate of photodynamic therapy in superficial BCC is 92 to 100%.44 Other modalities of treatment include intra-lesional and perilesional interferon α2 band 5-flurouracil.45,46

Management of basal cell carcinoma with orbital invasion should be very aggressive. Radical surgery includes wide excision under frozen section or Mohs micrographic surgery technique. It may require radical surgical procedures such as orbital exenteration, bony removal and even craniotomy.

Sebaceous Carcinoma of the Eyelid

Sebaceous gland carcinoma has an incidence of 1-5% of all eyelid malignancies.2 It has a much higher prevalence amongst the Asians and especially those of Indian origin. It occurs with increasing frequency in advancing age. The upper lid is most commonly involved in approximately 2/3rd of cases, followed by lower lid involvement and rarely the caruncle. Sebaceous gland carcinoma of eyelids is aggressive with a tendency for widespread metastasis. Clinical diagnosis at an early stage has a wide differential. It may masquerade as chronic blepharitis, blepharoconjunctivitis, chalazion, keratoconjunctivitis or basal cell carcinoma.47 The blepharoconjunctivitis associated with sebaceous gland carcinoma is due to

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the characteristic intraepithelial or pagetoid spread of the tumor which involves the basal layers of skin and mucous membrane in a radial fashion. It can also present as thickening of the lid on the tarsoconjunctival border with areas of conjunctival injection.

Histopathologic features of sebaceous gland carcinoma include the presence of cells of sebaceous origin confirmed by lipid stains (oil red O) on fresh tissue specimen. The tissue shows varying degrees of sebaceous differentiation and infiltration with loss of normal architecture of the gland which is replaced by pleomorphic cells with prominent vacuolated cytoplasm with high mitotic activity. The degree of differentiation starts from the periphery and progresses towards the center. Differentiated cells are vacuolated or foamy with slight basophilic cytoplasm. However, less differentiated tumor cells are more deeply basophilic and are anaplastic. Minimally invasive tumors are composed of lobules of varying sizes with minimal tumor extension. Invasive tumors are composed of diffuse cords of cells with minimum lobule formation that extends to the stroma. Rao and coworkers reported a histologic variant of sebaceous gland carcinoma called comedocarcinoma in which the tumor lobules undergo central areas of necrosis.48

Orbital extension of sebaceous gland carcinoma has an incidence varying from 6 to 35% and is associated with a 70 % mortality rate. There is 70 % involvement of preauricular, cervical and submaxillary lymph nodes. Lymphatic spread of the tumor may occur to lung, liver, skull and brain. The overall 5 year mortality is approximately 15%.2

The management of sebaceous gland carcinoma is surgical removal of the tumor under frozen section. Rarely, surgical extirpation enhances the long-term prognosis of the tumor (Figures 18.14A to C and 18.15A to E).

Patients with widespread lid involvement or orbital extension require exenteration. These patients require very close follow up with map biopsies because of its multicentric presentation and pagetoid spread. Involvement of the adjacent lymphatic gland requires radical resection. Role of radiotherapy in management of sebaceous gland carcinoma is very limited. Though the tumor is radiosensitive and

Figure 18.15D: 6 months later there was a mass in the orbit medially and HPE revealed a sebaceous gland carcinoma. This must have occurred due to incomplete removal of the primary tumor

Figure 18.15E: Secondary reconstruction was done with removal of the orbital mass along with excision of the medial part of the eyelid and medial canthus with reconstruction with forehead flap

responds to radiotherapy initially the recurrence rate is high. Thus radiotherapy is indicated in patients in whom surgery is not possible.

Squamous Cell Carcinoma of the Eyelid

Squamous cell carcinoma is the second most common cancer among whites.49,50 The relative incidence of BCC to SCC varies from 13:1 to 40:1.51

Risk factors for developing squamous cell carcinoma include increasing age,51 fair skin,49,50 history of sunlight exposure during childhood with a tendency to sunburns,52 PUV-A therapy,53,54 human

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papilloma virus55 exposure to ultraviolet radiation,56 immunodeficiency due to immunosuppressives following organ transplantation57 and exposure to arsenic.50 People with xeroderma pigmentosum, a condition characterized by defective DNA repair following UV radiation damage to DNA and oculocutaneous albinism are also predisposed.58

Squamous cell carcinoma of the eyelid (Figure 18.16) can arise de novo in relatively normal skin or from actinic keratosis.59,60 The mean age at presentation is around 60 years and is found to be higher amongst the males.61 It shows a tendency towards involving the lower lid and lid margin.50

Local spread of the tumor is more aggressive than basal cell carcinoma and it may also metastasize to regional lymph nodes (Figures 18.17A and B).50

The lesions present as firm hyperkeratotic papules or plaques with erythema of the surrounding skin and induration; ulceration may be present.

The tumor may spread perineurally and this is associated with a higher incidence of recurrence and metastasis.50,62 Orbital involvement from squamous cell carcinoma may occur due to neglected, longstanding tumors63,64 and occurs in 2.5 to 5.9% of cases.60,64 Presentation may be with pain or restriction of globe movement.

Poorly differentiated carcinomas, those arising from scars, tumor size > 2 cm and regional node involvement are associated with increased risk for recurrence or death.65 Metastasis occurs in 1-21% of eyelid SCC.66

Figure 18.16: Squamous cell carcinoma of the eyelid

Biopsy is required for confirmation of diagnosis. Usual treatment consists of the excision of the tumor with monitoring of the margins by Moh's micrography or frozen section. Local control with Moh s' surgery is 96.9% at 5 years.67

Radiotherapy may be preferred for patients who are unable to tolerate surgery or who have inoperable tumors. The five year tumor control rate with radiotherapy was 93.3%. Irradiation was equally successful in primary cases and in those recurrent following surgery.68 Cryotherapy may be used for tumors of large size to reduce their vascularity and size so that surgical excision and repair can be carried out with better surgical and functional results. It is also useful as a primary mode of therapy for small tumors with a wide base or those situated at the lid margin.69 Exenteration is required for tumors extending to the orbit.70

Other eyelid tumors that can extend into the orbit are malignant melanoma of eyelid and Merkels cell tumor.

Malignant Melanoma of Eyelid

Malignant melanoma of the eyelid is very rare. It may either arise denovo or from preexisting precursor lesions like lentigo maligna or Hutchinson's melanotic freckle, dysplastic naevus and giant naevus. In the last 10 years we had come across only 4 cases of melanoma of eyelid and only one case had orbital extension (Figure 18.18). The relative risk of malignant melanomas is extremely low for AfroCarrabian. Intra-orbital melanomas have the worst

survival experience.71 Based on the clinical and histological features the cutaneous melanomas are classified as superficial spreading, acral, nodular and lentigo melanoma. Of all the melanomas involving the eye and the adnexa, the melanomas involving the eyelid margins and conjunctiva have worse prognosis.72 Orbital extension of cutaneous or eyelid melanomas constitute less than 1% of secondary orbital tumors. Treatment is tailored to the size and extension of the tumor. The management of malignant melanoma of the eyelid is surgical removal

Figure 18.18: Eyelid melanoma with orbital extension

of the tumor under frozen section control. Rarely, surgical extirpation enhance the long-term prognosis of the tumor. Patients with widespread lid involvement or orbital extension requires exenteration. Our case of malignant melanoma of the eyelid with orbital extension was managed by total exenteration and socket reconstruction with temporalis muscle transfer.

Orbital Extension of Intracranial Tumors

The orbit is very rarely invaded by tumors other than meningiomas from the intracranial cavity. As a result this section will mainly focus on the management of meningiomas. Other tumors that do invade the orbit include parasellar tumors such as pituitary tumors and craniopharyngiomas.1,2,73,74 These tend to involve the superior orbital fissure and optic nerve foramen resulting in compression of structures at these sites.

Gliomas are the most common intracerebral malignancy. However, they rarely involve the orbit. It is only the high grade and aggressive glioblastoma multiforme that may invade the orbital contents either directly or via the foramina. Unfortunately, prognosis is poor for these tumors. External beam radiotherapy may temporarily halt growth and reduce short-term visual deterioration, but this treatment is only palliative.3/75

Meningiomas account for approximately 18 % of all intracranial neoplasms.4,76 Annual incidence is approximately 2 per 10000 per year afflicting females twice as often as males.5,77 Meningiomas originate from the meningoepithelial cells of the arachnoid villi. Consequently, they tend to originate at sites where the arachnoid villi are present. These include parasagittal regions, cavernous sinus and foramen magnum. The sites of interest with regards to orbital extension include the sphenoid wing, lamina cribrosa and tuberculum sella.6,78 There is still some debate as to the etiology of these tumors. Various theories have been proposed including trauma or viruses. However, as yet only ionizing radiation7,79 and deletions of chromosome 22 have been accepted.8,80 The alterations of chromosome 22 mean that there is also a link to neurofibromatosis type 2. It has also been noted that some meningiomas express progesterone receptors and that there is a preponderance for meningiomas in female breast

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cancer patients.9,81 Thus there may also be a hormonal driving force towards growth.

Meningiomas have been classified into 15 subtypes under the WHO classification system.10,82 94% are thought to be benign, 5% atypical and 1% malignant.11,83 As the majority are benign they mostly exert their effects locally by compression or more distantly through mass effect or raised intracranial pressure. Consequently, it is apparent that the structures affected will be dependent on the site of the tumor.

Orbital invasion most commonly presents with early unilateral painless visual loss. The visual loss is usually gradual, but in less than 5 % of cases may be acute.12,84 Other symptoms may include headache, nausea and diplopia. Examination may reveal optic atrophy or papilloedema (Figure 18.19A).

Meningiomas also display bone involvement showing hyperostosis and less frequently lysis. This can be visualized well with CT. MRI can be used to define the involvement of local structures (Figure 18.19B). With the increasing availability of 3 dimensional reconstruction planning of therapy is now much easier.

The aim of surgery is to completely excise the tumor (Figure 18.19C). If this is not possible then aggressive debulking should be attempted with

Figure 18.19A: Intracranial meningioma with orbital extension

Figure 18.19B: CT scan showing a mass in the temporal fossa with extension into the orbit and shows hyperostosis of the temporal bone, sphenoidal bone and inferolateral orbital bones

Figure 18.19C: 1 week postoperative following removal of the meningioma by orbito-temporal approach

postoperative radiotherapy. A combined surgical approach can be performed with a neurosurgical craniotomy and an ophthalmic orbitotomy. Ideally, both neurosurgical and ophthalmic teams are involved, although increasingly excision is performed solely by neurosurgeons. Orbitotomy sites vary with position of extension of the meningioma into the orbit. Whilst craniotomies can be fronto-temporal, pterional, supraorbital ridge or subfrontal. For cases in which an operative approach may not be suitable external beam radiotherapy(EBRT) or IMRT can be applied. Newer treatments such as chemotherapy with hydroxyurea seems to have achieved little success in tumor debulking.13/85 Whilst hormonal therapy with anti-progesterone receptor agents seems to have had some success with selected tumors.14/86

Final success depends on recurrence. The recurrence rate of meningiomas varies between 10 and 20%. They may recur upto 20 years after initial excision and yearly close follow up with CT scanning is advocated.15,87 Recurrence tends to yield large bulky tumors that affect local structures and require extensive debulking thus resulting in an increased morbidity.

Orbital Extension of Conjunctival Tumors Squamous cell carcinoma of the conjunctiva

The incidence of conjunctival squamous cell carcinoma is 1-2.8 per100, 000.88 It affects the elderly with a mean age of 60 year. Over 70% of the patients are male.88,89 Sunlight exposure due to UV-B radiation90 is a risk factor.91 HPV has also been implicated especially in types 16 and 18.92,93 Ultraviolet induced mutations in TP53 have also been implicated. It occurs at a younger age and is more aggressive in patients with immunosuppression.

The lesion occurs commonly in the interpalpebral area, with the majority being perilimbal. The presentation varies from a gelatinous mass or nodule to a flat patch of leukoplakia or a diffuse invasive lesion (Figure 18.20A).88,94 The commonest presenting symptoms are red eye and ocular irritation.95 Squamous cell carcinoma mimicking sclerokeratitis has also been reported.

The tumor may involve the underlying sclera in one third of the cases with intraocular involvement in 11-13% and orbital invasion in 11-15% (Figure 18.20B).87,95 Risk of orbital involvement may be higher with mucoepidermoid variants.96 Impression

cytology may aid in the diagnosis by displaying keratinized dysplastic cells, hyperkeratosis, syncytial-like groupings and prominent and large nucleoli.97 UBM can show intraocular extension of conjunctival squamous cell carcinoma (Figure 18.20C).

Management of OSSN requires adequate excision and careful follow up to monitor any recurrence.98 Recurrence following excision depends on histopathological grade of tumor and involvement of surgical margins.99,100 Cryosurgery, topical 5-fluorouracil or mitomycin C treatment following

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surgical excision has been shown to decrease the recurrence rate.101,102 Topical interferon α2b has been used in the treatment of presumed recurrent corneal and conjunctival intraepithelial neoplasia.103 Once the orbit is involved exenteration may be required.

Malignant Melanoma of the Conjunctiva

Malignant melanoma of the conjunctiva has an incidence of 0.2 to 0.8 per 1000 in whites104-106 and comprises 2-3% of ocular tumors107,108 and is less commonly seen in the pigmented races.106 It has

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increasing preponderance with age109 and arises de novo or from a nevus. However, most commonly110 these develop from primary acquired melanosis (PAM) with atypia (Figure 18.21).111,112 The most common site of origin is the limbus.104 Other sites include the fornices, palpebral conjunctiva and caruncle (Figures 18.21A and B).

Folberg R and Co-workers had reported that 50% of PAM with atypia may progress to malignant melanoma.113-115 PAM appears as flat, patchy pigmentation in the conjunctival epithelium and can remain dormant for years or show slow progression or may wax and wane.116,117 Development of thickening within areas of PAM may indicate invasive growth. However, a junctional nevus may be indistinguishable from PAM with atypia histologically. Junctional nevi are seen in childhood while PAM occurs in middle-aged and elderly individuals. Biopsy of lesions that are widespread, large, thickened, dark, palpebral, unusually vascular or progressive has been suggested.118

Conjuctival melanoma arising from pre-existing nevus119,120 may be characterized by change in color, nodularity or bleeding. The 10 year survival rate in one series was 77.7%. Unfavorable tumor location (palpebral conjunctiva, fornix, caruncle, corneal stroma, eyelid), age greater than 55 years, higher TNM category, tumor thickness more than 10 mm, high mitotic index and more epitheloid cells were associated with higher risk of tumor related death. Tumors with unfavorable location, higher TNM grade, and excision alone as initial therapy had a

higher probability of local relapse than favorably located (bulbar and limbal conjunctiva) tumors, lower TNM grade, and excision plus adjuvant therapy.121,122 Orbital extension of malignant melanoma of conjunctiva occurs far less frequently when compared to intraocular melanomas in the ratio of 4:23.123

Treatment includes extensive tumor removal, cryotherapy and topical mitomyin C with amniotic membrane allograft for diffuse conjunctival and corneal melanoma arising from primary acquired melanosis (Figure 18.20B).124

As primary and adjuvant therapy, topical mitomycin yielded an overall recurrence rate of 50%.125 Survival rates were found to be worst for those with intraorbital spread.107

Orbital Extension of Tumors of the Nasal Cavity and Paranasal Sinus

Malignant tumors of this region are a diverse group of neoplasms. They are relatively rare and as a result few definitive studies have been performed into their management. The studies that have been undertaken illustrate that prognosis and management vary depending on the type and site of tumor diagnosed.

Growth is often large prior to symptoms from these tumors, partly due to the nature of the cavities from which they arise. Since only a thin bony wall separates the nasal cavity and sinuses from important structures, invasion of nerves, brain and orbit are frequent.

These tumors are more commonly found in males with 80% presenting between the ages of 45 and 85. There is an increased risk in people living in developing countries.126

Due to the non-specific nature of presentation diagnosis is often difficult. Patients may present with nasal obstructive symptoms, rhinorrhea, epistaxis and less commonly pain. If the orbit is involved then proptosis and ocular motility may be affected depending on the site of the original tumor. Vision is usually affected later unless the orbital apex is involved whilst conjunctival congestion may result from a larger mass in the orbit. Thus when nasal symptoms are persistent cases should be investigated further. Endoscopy and more detailed radiography have indeed improved earlier pick up. The maxillary sinus is the most common site of primary tumor origin (55%) (Figure 18.22), followed by the nasal cavity (35%) and then the ethmoids (9%). The sphenoidal and frontal sinuses are rarely involved but when they are they confer a poor prognosis.2,127

The majority of tumors are squamous cell carcinomas (80%)127,128 with adenocarcinoma and adenoid cystic carcinoma making up the majority of the rest. The orbit is thus also most frequently invaded by squamous cell carcinoma. Routes include the foramina, perineural spread or direct invasion via bony erosion. Lymphatic spread is however rare.

Squamous cell carcinomas most commonly arise from the turbinates. Consequently, they present more commonly with signs of congestion and nasolacrimal duct obstruction. Up to 80 % have bony erosion of the orbit at the time of diagnosis.129 Nickel and chrome workers have a higher incidence of squamous carcinomas.130 It is also increasingly thought that smoking is a risk factor for development of these tumors.131 Biopsy is often important as the various different forms of squamous carcinoma confer different modes of spread and hence affect prognosis.

Adenocarcinoma is more common in woodworkers and is linked to other chemicals for instance those found in the leather tanning industry.132

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The prognosis from these tumors varies with histological grading. They commonly invade the base of skull and the orbit affecting vital structures. However, distant metastasis is rare. Undifferentiated carcinomas have a very poor prognosis, usually being picked up at a late stage. Unlike squamous carcinomas they are commoner in women than men. Small cell carcinomas are similar to their lung counterparts and may present with early proptosis, epistaxis and obstructive symptoms.

X-ray was the initial tool for diagnosis and is still useful in determining location, size and presence of bony erosion.129 However, it has now been surpassed by computed tomography which highlights bony involvement. MRI T2 weighted helps differentiate tumor from surrounding tissue and edema. Bowing of tumor-fat interface in fat saturated images gives a clue as to invasion. If this changes from smooth to irregular, invasion is far more likely.133

Treatment of nasal and sinus tumors usually falls beyond the domain of ophthalmologists. Specialists from the fields of head and neck surgery and maxillofacial surgery provide the best hope for patients. Surgeons with skills in facial reconstruction may also help the patients once treatment is completed. There is still some debate over the best modality of treatment partly due to the lack of adequate research. However, in a recent meta-analysis, surgery alone seemed to be better than combination with radiation. Worst of all appeared to be radiation alone.134 Often radiotherapy is given to help reduce the size of the tumor prior to surgery, however, as yet there is little evidence that this improves long-term survival. Thus, surgery with wide local margins still seems to be preferred for low stage cancers and surgery with some adjunctive radiotherapy used for higher stage cancers. Different approaches have been used to gain access dependent on the size and position of the tumor. Recently, endoscopic approaches have been used to reduce postoperative morbidity with complete transnasal resections, although this is still a developing field.135 Another area of debate is the role of exenteration with orbital involvement. Studies have shown that preservation of the eye has not affected survival rates.136 Indeed if adequate reconstruction is performed a good functional outcome can be achieved in up to 90% of cases.137

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However, we recommend orbital exenteration with involvement of the orbital apex, extraocular muscles, bulbar conjunctiva and sclera.Radiotherapy has been used for some time in the treatment of head and neck tumors. However, high doses of radiation are required for successful treatment. Since the tumors are found close to structures that are highly radiosensitive, morbidity is often high following treatment. In a review of 48 patients treated with curative radiotherapy 33% developed unilateral blindness whilst 4 developed bilateral blindness secondary to optic nerve damage.138 However, irradiation can be used in rarer instances when cervical lymph node spread has occurred.

Chemotherapy is usually reserved for certain types of tumor. These include lymphoma, neuroendocrine, enthesioneuroblastoma and undifferentiated carcinomas. The trouble in the past has been the systemic side effects. However, increasingly a local approach has been attempted with some success.

Prognosis from a recent review suggests an overall survival of around 40%. Prognosis varied with site and type of lesion. Nasal fared better than ethmoidal which in turn had better survival than maxillary. There was also a worse prognosis for frontal and sphenoidal involvement due to increased invasion of the brain and dura. Glandular carcinomas had a better prognosis than squamous carcinomas.134

Figure 18.22: Carcinoma of maxillary sinus with involvement of paranasal sinus,nasal cavity, the orbit and surrounding adnaxae leading to extreme lateral displacement of the right orbit

Other studies have shown that although orbital involvement is not detrimental per se, and deep orbital involvement leads to a poorer survival, hence the advice for exenteration when these tissues do become involved.139/140

Orbital Extension of Nasopharyngeal Tumor

Although nasopharnygeal tumors are found in close proximity to those of the nasal cavity, they have an altogether different pattern of presentation partly because of the vast lymphatic network present in the region. They are almost a distinct entity affecting a generally younger age group, between 45-55. There is a higher incidence amongst males with the highest incidence amongst the southern Chinese populations. Here 15-30 males per 100,000 are diagnosed with the condition per year. However, in other parts of the world the disease is relatively rare. There is thought to be a genetic element as the risk continues to remain high even in second generation Chinese emigrants despite the change of environment factors.141/142 Epstein-Barr virus has been implicated as the environmental agent as carcinoma cells have been found to contain viral DNA.143 Changes in the make up of these cells are thought to result in squamous cell carcinoma. Unlike nasal tumors they are far more likely to incur systemic spread.

Patients tend most commonly to present with a neck mass secondary to regional lymphnode metastasis. This is often linked with dysphagia. Other symptoms include nasal symptoms such as rhinorrhea and nasal congestion, auditory problems such as hearing loss, fullness and recurrent otitis media. If the orbit is involved then symptoms may include proptosis, reduced vision, ocular motility disorders and pain. The orbit is rarely involved and is usually affected later than other structures.144 Direct invasion through bone is rare. However, common routes include pterygopalatine fossa, inferior orbital fissure and then secondarily through the paranasal sinuses. Either CT or MRI can be used to help detect the pathway of tumor entry into the orbit.145

Unlike nasal and paranasal sinus tumors surgery plays only a minor role in the management of these tumors, because local metastatic spread is already likely to have occurred. Thus radiotherapy is the primary treatment modality for orbital invasion. Chemotherapy is used as an adjunctive treatment for