Intravitreal bevacizumab in treatment of iris metastasis from primary lung carcinoma

Abstract

Iris metastases secondary to primary malignancy are rare and usually have poor overall survival. We report a case of a man aged 60 years who presented with chief complaints of progressive pain and redness of right eye of 5 days duration. Slit-lamp examination revealed a greyish white irregular nodular mass, arising from anterior iris surface reaching up to mid-periphery. With a clinical suspicion of iris metastasis, systemic investigations were requested. CT scan of chest reported a well-defined lobulated lesion in the lower lobe of lung with presence of multiple satellite nodules in both lungs suggestive of primary malignant neoplasm of lung. Tissue diagnosis was obtained through an iris lesion biopsy, which was opted for relative ease of approach. Histopathology and immunohistochemistry confirmed the diagnosis of iris metastasis secondary to non-keratinising squamous cell carcinoma of lung. Local intravitreal injection of antivascular endothelial growth factor was administered for tumour regression along with systemic chemotherapy.

Background

Iris lesions may have varied ocular and systemic aetiology, thereby posing a diagnostic dilemma to clinicians and pathologists. We present a case, describing the differential diagnoses of iris mass lesions, role of multimodal imaging and management of iris metastasis, from primary lung carcinoma.

Case presentation

A man aged 60 years presented with complaints of pain and redness in the right eye of 5 days duration. On examination, his best-corrected visual acuity was 20/40 in both eyes. Slit-lamp examination of the right eye revealed circumciliary congestion with corneal stromal oedema. Anterior chamber had 2+ cells and neovascularisation of the iris at pupillary border. A greyish white irregular nodular mass with surface vascularity, measuring 4×2×1 mm extending from 7 to 9’o clock position arising from the anterior iris surface and reaching up to mid-periphery was noted. The posterior extent of the lesion could not be elicited. Few broad-based posterior synechiae were noted and there was grade 2 nuclear sclerosis. Gonioscopy showed whitish irregular mass originating from the anterior iris surface and extending till anterior part of trabecular meshwork. Intraocular pressure (IOP) measured 22 mm Hg in the right eye and 16 mm Hg in the left eye (Goldmann applanation tonometer). Anterior segment of the left eye was normal. Both eyes fundus examination was unremarkable with normal disc and macula.

Investigations

Slit-lamp photography in diffuse and oblique illumination documented the extent of tumour and presence of surface vascularity (figure 1A and B). Anterior segment optical coherence tomography demonstrated a homogenous solid mass on the anterior iris surface with posterior shadowing (figure 1C and D). Anterior segment fluorescein angiography in the late phase revealed leakage of the dye within the tumour suggestive of highly vascularised tumour and leakage from pupillary border due to neovascularisation (figure 1E). A provisional diagnosis of iris mass lesion, inflammatory or neoplastic, possibly metastatic was considered.

Figure 1.

(A) Diffuse slit-lamp photograph of the right eye showing greyish white irregular nodular iris mass (4×2×1 mm) extending from 7 to 9’o clock position. (B) High magnification photo of iris tumour showing nodular, irregular surface with intrinsic vascularity (blue arrow). (C and D) Anterior segment optical coherence tomography showing homogenous solid mass on the anterior iris surface with posterior shadowing. (E) Anterior segment fluorescein angiography in late phase showing leakage around the pupillary border along with leakage within the mass lesion. (F) Diffuse slit-lamp photograph at 1 month follow-up showing reduction in size of tumour (2×1 mm) as well as vascularity.

Initial laboratory work revealed leucocytosis (14 400 per cubic millimetre). A high-resolution CT of the chest showed presence of a well-circumscribed lobulated soft tissue dense lesion in the superior and posterior segments of left lower lobe of lung encasing the segmental bronchi. There was presence of consolidation and cavitation, along with scattered multiple satellite nodules in both the lungs. Left hilar and subcarinal region showed enlarged nodes. Multiple osteolytic lesions were noted in sternum and thoracic vertebrae. A clinicoradiological diagnosis of primary lung carcinoma with multiple metastases was made and the patient was referred to a surgical oncologist who preferred an iris biopsy over a lung biopsy, considering the location of tumour in lower lobe of lung and risk of complications related to biopsy. On histopathology, small fragments of cohesive epithelial cells were noted with abundant clear to pale eosinophilic cytoplasm, large nucleus with prominent eosinophilic nucleoli (figure 2A; H&E, 40×). Foci of suppuration were also noted. With a suspicion of an epithelial malignancy and a differential diagnosis of amelanotic melanoma, immunohistochemistry was performed. Tumour cells expressed pancytokeratin ((AE1/AE3); figures 2B, 40×) and p63 (figures 2C, 40×). They were negative for HMB-45 (figures 2D, 40×) and thyroid transcription factor 1 (TTF-1). Thus, a final diagnosis of metastatic non-keratinising squamous cell carcinoma metastatic to iris was made. The patient was referred to oncologist for systemic chemotherapy.

Figure 2.

On light microscopy, cohesive epithelial cells were noted with abundant clear to pale eosinophilic cytoplasm. There was presence of nuclear pleomorphism and conspicuous eosinophilic nucleoli (A; H&E, 40×). Tumour cells showed strong cytoplasmic expression of cytokeratin (B; 40×) and p63 (C, 40×), but did not express HMB-45 (D, 40×).

Differential diagnosis

The following differential diagnoses were considered:

1. Iris granuloma secondary to either tubercular or sarcoid origin: considering the amount of inflammation and nature of iris lesion, laboratory investigations such as erythrocyte sedimentation rate, Mantoux test, serum ACE, serum calcium were also requested; and were within normal limits/negative.

2. Amelanotic iris melanoma: a high index of suspicion for amelanotic iris melanoma was kept, considering the nature of tumour and vascularity. As the tumour originated from the anterior surface of iris, not stroma and the systemic investigations confirmed primary lung carcinoma, a diagnosis of iris metastasis was made.

3. Iris cyst: most of the congenital iris lesions are benign and lack signs of inflammation. Traumatic iris cyst was ruled out in absence of history of trauma.

Treatment

Considering radiological diagnosis of primary lung carcinoma, an iris tumour punch biopsy was undertaken along with intravitreal injection of bevacizumab 1.25 mg in 0.05 mL. After the final diagnosis of iris metastatis from non-keratinising squamous cell carcinoma of lung with multiple metastases was made, the patient was referred to medical oncologist to initiate systemic chemotherapy as a palliative treatment.

Outcome and follow-up

One month after bevacizumab injection, the iris mass decreased in size (2×1 mm) as well as vascularity (figure 1F) with reduction in IOP to 16 mm Hg. The patient felt symptomatically better with decrease in pain and redness with one-line improvement in visual acuity (20/30). Further follow-up of patient was not possible as patient succumbed to systemic complications of the disease.

Discussion

Metastatic tumours to the eye are common intraocular malignancy. Choroid (88%) is the most common site due to its rich vascular supply followed by iris (9%) and rarely ciliary body (2%).¹ Breast carcinoma in females (47%) and lung carcinoma in males (21%) are common primary tumour known to metastasise to the eye.¹ Majority of patients with iris metastasis present with progressive loss of vision secondary to rapid progression of underlying primary malignancy. In cases where the underlying primary malignancy is undiagnosed, iris metastasis can masquerade as iridocyclitis or iris granuloma with associated intractable glaucoma secondary to either direct infiltration of the angle or neovascularisation of iris.²

Iris metastasis from underlying primary malignancy has a poor overall survival and hence necessitates an early referral to oncologist to detect the primary malignancy and initiate systemic chemotherapy.¹ Local therapy is equally important since the ocular penetration of the systemic chemotherapeutic agents is poor. Targeted local treatment could include external beam radiotherapy, brachytherapy, photodynamic therapy, surgical resection where possible and in extreme event, an enucleation of the eye.³ In associated neovascular glaucoma off label use of intravitreal bevacizumab, a monoclonal antivascular endothelial growth factor (anti-VEGF) antibody is an alternate effective option.^{2 4 5}

Angiogenesis plays a key role in the pathogenesis of iris metastases from primary carcinoma as well as iris neovascularisation and neovascular glaucoma. Bevacizumab blocks angiogenic growth factors from binding to receptor sites on vascular endothelial cells. Thus, the process of vascular endothelial cell proliferation is inhibited and it also facilitates regression of existing vessels. Therapeutically, it decreases iris neovascularisation and reduces the tumour size by obliterating its blood supply.⁶

Considering the location of tumour in our patient, intracameral injection of anti-VEGF should have been the ideal route. But we preferred intravitreal route to avoid possible leakage of injected bevacizumab from the anterior chamber after a reasonably large sutured limbal wound constructed for tumour tissue biopsy. Intravenous bevacizumab is primarily used for gastrointestinal and colon carcinoma⁷ and it helped to reduce the IOP, tumour size and the intrinsic vascularity in our case. With this rationale, there could be a role of the anti-VEGF molecule in local targeted treatment of intraocular tumours or in preventing various ocular side effects of radiation therapy.

Learning points.

• Multimodal imaging helps to differentiate various iris mass lesions.

• Tissue biopsy may be needed to confirm histopathological nature of tumour.

• Intraocular antivascular endothelial growth factor injection may be tried in selected instances to reduce the tumour size and control intraocular pressure.

• Timely referral and multidisciplinary approach help treat iris metastasis lesions effectively.