Are iris masses in lung carcinoma always a metastasis: Two case reports

Abstract

BACKGROUND

Small cell lung cancer (SCLC) constitutes about 15% of lung cancers and is an aggressive disease with uveal metastasis. An isolated iris lesion in such patients may or may not be a manifestation of disseminated disease. We report two cases – one patient with SCLC and another with non-small cell lung cancer, each with varied presentation.

CASE SUMMARY

The first case was a 49-year-old female who presented with redness in the left eye. She was a known case of SCLC with multi-organ involvement. The best corrected visual acuity (BCVA) was 20/100. Slit-lamp bio-microscopy showed an iris mass with neovascularization. Cytology from anterior chamber paracentesis was suggestive of malignancy. Subsequently she received whole-brain radiotherapy followed by six cycles of platinum doublet chemotherapy. On follow-up, the iris lesion subsided with BCVA of 20/50. The second case was a 54-year-old female with lung adenocarcinoma and brain metastasis. She presented with pain and redness in the right eye (BCVA 20/200). Slit lamp bio-microscopy showed multiple iris nodules in the affected eye. Trabeculectomy was done due to raised intraocular pressure (IOP). Aqueous tap and tissue biopsy for cytology and histopathology respectively, were negative for secondaries. Postoperatively, BCVA improved to 20/70, with an IOP of 12 mmHg and resolution of the nodules.

CONCLUSION

Iris lesions in lung carcinoma patients may not necessarily be metastases. Sometimes they can be reactive nodules mimicking secondaries.

Key Words: Iris nodules; Iris metastasis; Osimertinib; Lung adenocarcinoma; Small cell lung cancer; Case report

Core Tip: Though iris metastasis is rare in cases of systemic malignancies, a relatively rich vascular supply of uveal tissue makes it vulnerable compared to other ocular structures. Iris masses are often unilateral, may be painful and are vision-threatening. The lesion can be single or multiple, usually well-defined, inducing anterior chamber reaction leading to secondary glaucoma. With treatment advances like platinum doublet chemotherapy and targeted therapy for specific mutations, the disease progression can be arrested with alleviation of symptoms. However, some cases may require surgical intervention to manage the complications.

INTRODUCTION

Lung cancer is histologically classified broadly into two primary types: Small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). These types differ significantly in their clinical behaviour, with SCLC being markedly more aggressive. SCLC and NSCLC account for approximately 15% and 85% of lung cancer cases, respectively[1]. While uveal metastases are the most common intraocular malignancy in adults, iris involvement is rare, representing less than 10% of such metastases[2]. The most frequent primary origins are breast (37%) and lung (27%) carcinomas followed by kidney (4%) and gastrointestinal tract (4%)[2-5]. Patients with iris mass usually present with blurring of vision, defect in visual field, pain and photophobia[2,5]. Clinical signs often include a unilateral, yellow-white, solitary or multifocal mass, which may be associated with posterior synechiae, localized neovascularization, hyphaema, anterior chamber cells, and secondary glaucoma[2,5]. Although clinical history is highly suggestive, diagnosis requires anterior segment imaging such as optical coherence tomography and ultrasound bio-microscopy (UBM) for localization and characterization. A systemic workup, including radiological investigation, is essential. While tissue biopsy or cytological analysis is the diagnostic gold standard, results can sometimes be inconclusive[6,7]. Management involves local radiotherapy (plaque brachytherapy or external beam radiotherapy) for tumour control. Intravitreal anti-vascular endothelial growth factor (VEGF) agents can address neovascularization, and systemic chemotherapy or targeted therapy is administered to treat the underlying malignancy and reduce metastatic risk[2,6]. A multidisciplinary approach is critical for supportive care and optimizing quality of life.

In this manuscript we report two different types of primary lung malignancies and their varied presentations. We are emphasizing that iris masses may not always the secondaries of the primary cancer, rather these may be due to inflammation. Our patient with SCLC was found to be having iris metastasis in the left eye, confirmed by cytopathological examination. But the other patient with NSCLC had multiple iris nodules in the right eye, and both cytology and tissue biopsy, were inconclusive for malignant cells.

CASE PRESENTATION

Chief complaints

Case 1: A 49-year-old female presented with chief complaints of redness and decreased distant vision in the left eye for the last month.

Case 2: A 54-year-old woman presented with complaints of decreased vision in oculus dexter (OD) for the last month, along with pain, redness, and watering.

History of present illness

Case 1: The symptoms were sudden in onset and progressive in nature. There was associated chest pain and cough for the last two months.

Case 2: She had a sudden onset of decreased vision in OD with dull aching pain and redness one month prior to presentation. She consulted a physician in her locality and was started on antiglaucoma medications.

History of past illness

Case 1: There were no similar episodes of ocular symptoms in the past.

Case 2: There were no similar episodes of ocular symptoms in the past. The patient was diagnosed with stage IV adenocarcinoma of the lungs five years ago. After genetic analysis, she was started on (mutation-based targeted treatment) Erlotinib for the initial three years and then switched to Osimertinib for the next two years.

Personal and family history

Case 1: She had a history of biomass fuel exposure for over 30 years and was a non-smoker. There was no family history of any malignancy.

Case 2: There was no family history of any malignancy, and she was a non-smoker.

Physical examination

Case 1: On ophthalmic examination, OD had best-corrected visual acuity (BCVA) of 20/30 and intraocular pressure (IOP) of 14 mm without any congestion. The BCVA was 20/100 in oculus sinister (OS) with an IOP of 20 mmHg. On slit-lamp examination of OS, there was ciliary congestion, presence of an iris mass from 11 o’clock to 1 o’clock along with neovascularization of the iris (NVI) (Figure 1A), associated with whitish flocculent material deposits on the iris and in the anterior chamber (Figure 1B). The pupil was sluggishly reacting to torchlight and poorly dilating with mydriatics. The fundus view of OS was not clear. The fundus of OD was normal.

Figure 1 Case 1. A: Slit-lamp bio-microscopy image of the left eye showing congestion and iris mass from 11 o'clock to 1 o'clock (orange arrow) with whitish flocculated materials deposition over iris and in the anterior chamber; B: Higher magnification (16 ×) image showing dispersed whitish flocculent material in the anterior chamber and neovascularization of iris (arrow); C: Post chemotherapy appearance of the left eye shows the disappearance of the iris mass and the flocculent materials, with post-inflammatory ectropion uvea and posterior synechiae from 12 o'clock to 3 o'clock (orange arrow).

Case 2: Her BCVA was 20/200 in OD and 20/30 in OS. The IOP in OD and OS was 36 and 12 mmHg, respectively. On slit lamp examination of OD, ciliary congestion was noted, and multiple semi-transparent iris nodules of varying sizes and shapes were found in different quadrants (Figure 2A). There was NVI between 7 o'clock and 9 o'clock (Figure 2B) in the affected eye. There were pigments on the endothelium (Figure 2C), and flare 2+ was noted in the anterior chamber. Gonioscopy revealed open angles in oculus uterque (OU) with localized peripheral anterior synechiae in OD (Figure 2D). Dilated fundus examination showed glaucomatous optic disc changes having vertical cup-disc ratio (VCDR) of 0.9 in OD; Fundus findings of OS were normal with VCDR of 0.4.

Figure 2 Iris nodules at presentation (Case 2). A: Multiple semi-transparent, jelly like nodules were found in multiple quadrants (arrows); B: Neovascularization of the iris between 7 o'clock and 9 o'clock Figure (arrow); C: There were pigments on the endothelium (arrow); D: Gonioscopy revealed open angles in both eyes with localized peripheral anterior synechiae (asterisk).

Laboratory examinations

Case 1: Aspiration from the anterior chamber and of the flocculent material on the iris mass was done using a 26 G needle with a tuberculin syringe, and the cytology report was positive for malignancy (Figure 3). Endobronchial biopsy confirmed SCLC.

Figure 3 Case 1. A: Hematoxylin-eosin stained smear of aspirated material from the anterior chamber shows the hypercellularity under 10 × magnification; B: May-Grunwald Giemsa stained smear under 40 × magnification shows small blue round cells with high N:C ratio.

Case 2: On genetic analysis, EGFR exon 19 deletion and T790M (Exon 20) mutation were detected. Aqueous sample aspiration was done using 26G needle with tuberculin syringe and the sample was sent for cytopathological examination, and the report was negative for malignant cells. During trabeculectomy, repeat aqueous aspiration done and sent for cytological examination. The iris tissue with a nodule was excised and sent for histopathological examination in a formalin-containing container. Neither report showed any evidence of malignancy. Cytopathology showed only inflammatory changes. On immunohistochemistry tissue was negative for TTF-1 and Napsin A.

Imaging examinations

Case 1: Ultrasonography of the posterior segment and optical coherence tomography (OCT) didn’t reveal any mass in the choroid and posterior segment. UBM didn’t reveal any ciliary body mass. Contrast-enhanced computed tomography (CECT) of the thorax and abdomen revealed a mass in the right lung with endobronchial growth in the right intermediate bronchus, along with metastasis to the right adrenal gland and spine. Magnetic resonance imaging (MRI) of orbits showed an enhancing lesion in the anterior chamber abutting the lens and iris in OS. MRI of the brain showed pineal gland metastasis. The bone scan was suggestive of D4 vertebra metastasis.

Case 2: Posterior segment ultrasound and OCT didn’t reveal any mass in the choroid or posterior segment. UBM didn’t reveal any ciliary body mass. CECT of the thorax and abdomen revealed multiple lesions in the bilateral lungs, liver, and bones suggestive of metastasis. CEMRI of the brain showed bilateral cerebral and right cerebellar hemisphere lesions suggestive of disseminated disease. Positron emission tomography CT suggested focal FDG avidity in the above-said organs, and no pathological hypermetabolic lesion was found elsewhere in the body.

FINAL DIAGNOSIS

Case 1

A diagnosis of left eye iris metastasis secondary to SCLC was made.

Case 2

Considering the above history and clinical findings, she was diagnosed to have right eye secondary open-angle glaucoma with reactive iris nodules with stage IV adenocarcinoma of the lung.

TREATMENT

Case 1

The patient received whole-brain radiotherapy (WBRT) for brain metastasis, and subsequently, six cycles of platinum doublet chemotherapy were given.

Case 2

She was managed medically at first, but as the target IOP was not achieved with maximum antiglaucoma medications, trabeculectomy was done. Pulmonary consultation opined to continue Osimertinib as the disease was stable.

OUTCOME AND FOLLOW-UP

Case 1

Post chemotherapy, the OS was quiet with a normal IOP of 14 mmHg and a vision of 20/50. The iris mass, the NVI, and also the white flocculent material disappeared. Instead, there was ectropion uvea and post-inflammatory posterior synechiae from 12 o’clock to 3 o’clock (Figure 1C). The lens showed early cataractous changes. Fundus examination was normal with a VCDR of 0.4 in OU.

Case 2

Postoperatively, the OD was quiet with a vision of 20/70, iris nodules, and NVI showed regression (Figure 4A and B). IOP was 12 mmHg with a well-functioning bleb, and without any antiglaucoma medication (Figure 4C), and the cornea was clear (Figure 4D).

Figure 4 Postoperatively (Case 2). A: Iris nodules showed some regression (arrow); B: Neovascularization of the iris also regressed (arrow); C: Intraocular pressure was controlled with diffuse, moderately elevated relatively avascular bleb (arrow); D: Cornea was clear with no endothelial deposits.

DISCUSSION

According to previously reported literature, different theories postulate uveal metastasis. The basis behind all these theories is seedlings from primary cancer and a rich vascular supply of uveal tissue, making it prone to secondaries. Once the tumour cells settle in one tissue, these cells drive metabolic activity and clearance of metabolic byproducts initiates, which drives neovascularization in and around the secondaries[6]. Among the uveal tissue, the choroid is the most common site, whereas the iris metastasis has an incidence of less than 10% of all uveal metastases[2]. Among iris tumours, primary melanoma accounts for nearly half of the tumours[8]. Iris metastases were documented in breast cancer; lung cancer is the next most common malignancy to present with iris metastases[2-5]. Iris metastasis usually presents with decreased vision, visual field defects, bleeding in the anterior chamber, and angle-closure or open-angle glaucoma. Our patients presented with a blurring of vision and iris masses with increased IOP. Raised IOP was also reported by Lu et al[9], Sobol et al[10], and Konno et al[11]. In our second case, trabeculectomy was performed due to uncontrolled high IOP with maximum medication, as supported by Konno et al[11].

The definitive diagnosis of metastasis needs to be confirmed by cytopathology or biopsy. Aqueous and the flocculent material on the iris mass was also aspirated and sent for cytopathological examination, which confirmed the diagnosis (Figure 2A and B) in one of our patients. In our second patient we have sent aqueous aspiration sample on presentation, which came out to be negative for malignancy. So, keeping in mind that aqueous aspiration using a 26G needle might have yielded a low cell count due to its smaller bore size, we went for repeat aspiration of aqueous and tissue biopsy during trabeculectomy. Both cytology and the histopathology of the sample containing iris tissue were found to be inconclusive for malignant cells, as reported by Shields et al[7] and showed only inflammatory cells. The iris tissue was also negative for TTF-1 and Napsin A.

Due to inherent disseminated conditions, chemotherapy with WBRT has been the treatment available for over three decades. Because of the systemic disease with distant metastasis, chemotherapy is the first choice in the treatment of iris metastasis. Our first case received WBRT and platinum doublet chemotherapy, following which the iris mass and NVI resolved. In our second case, the patient denied WBRT and was on osimertinib, a third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI). According to literatures, regression of iris mass was noted with erlotinib, a first-generation EGFR-TKI monotherapy as described by Ye et al[12], and Kim et al[13] reported regression of iris mass when treated with erlotinib and three intravitreal bevacizumab injections; Maturu et al[14] described gefitinib, a first-generation EGFR-TKI with four intravitreal bevacizumab injections helped in regression of mass; Chen et al[15] demonstrated complete resolution of iris mass with osimertinib monotherapy; whereas, Wong et al[16] reported osimertinib along with three intravitreal bevacizumab injections caused regression of the mass.

Due to the paucity of reported literature, it is unclear whether EGFR-TKI monotherapy or combination with intravitreal anti-VEGF is more effective in the regression of iris masses. A randomized controlled trial should be conducted to consider the different modalities of treatment for a better understanding.

In the present study follow-up period was 6 months for both of our patients. None of our patients had received anti-VEGF injections during treatment. Our patients had received topical antibiotics and non-steroidal anti-inflammatory drugs after the aqueous aspiration in both cases; after tissue biopsy and trabeculectomy in second case. As our second patient had been on osimertinib for the last two years, there were multiple nodules, and cytology showed only inflammatory cells; we thought those to be reactive iris nodules due to the drug as reported by Deitch-Harel et al[17].

CONCLUSION

These contrasting cases highlight the diagnostic and therapeutic complexities of iris lesions in patients with advanced lung carcinoma. We demonstrate that while iris masses can represent metastatic disease, as confirmed by cytology in our SCLC case, they may also manifest as reactive, inflammatory nodules secondary to targeted therapies like osimertinib, as evidenced by negative histopathology in our NSCLC patient.

A high index of clinical suspicion is paramount. Diagnosis hinges on a multimodal approach, combining advanced ocular imaging with cytopathological and histopathological analysis, though results can be inconclusive. Treatment must be highly individualized; systemic chemotherapy and radiotherapy effectively addressed the metastatic lesion in SCLC, while targeted EGFR-TKI therapy alone led to the regression of inflammatory nodules in NSCLC, with surgical intervention (trabeculectomy) required for managing secondary glaucoma.

These outcomes underscore that iris abnormalities in oncology patients are not always malignant and may reflect a spectrum of disease, from direct metastasis to treatment-related inflammation. A collaborative, multidisciplinary strategy is essential to optimize both oncologic and ophthalmic outcomes, preserving vision and quality of life. Further research is needed to establish definitive diagnostic criteria and treatment protocols for EGFR-TKI-associated inflammatory iris nodules.