Widespread Metastatic Uveal Melanoma with Gastrointestinal and Gallbladder Involvement: A Case Report

Abstract

Introduction

Melanoma is a malignant tumour arising from melanocytes, with cutaneous melanoma accounting for the vast majority of cases. Less frequently, melanomas originate from extracutaneous melanocytes, including those of the uveal tract. Although primary gastrointestinal melanomas exist, gastrointestinal involvement by melanoma more commonly represents metastatic disease. Recognition of gastrointestinal metastatic lesions and their variable endoscopic appearance has become increasingly relevant with the advances in systemic therapies.

Case Presentation

We report a case of a 74-year-old man referred for investigation of iron-deficiency anaemia. Esophagogastroduodenoscopy revealed multiple flat, dark millimetric lesions in the distal oesophagus, stomach, and duodenum. Histopathological examination with immunohistochemistry revealed melanoma. Cross-sectional imaging and positron emission tomography demonstrated widespread metastatic disease involving the liver, lungs, brain, bone, and gallbladder, as well as a hypermetabolic intraocular lesion. Ophthalmological and dermatological evaluation was consistent with primary uveal melanoma, with no evidence of a cutaneous primary. The patient experienced rapid neurological deterioration due to brain metastases and died shortly after diagnosis.

Conclusion

Gastrointestinal metastases of melanoma are rare, particularly in uveal melanoma, and are often clinically silent. Endoscopic findings are heterogeneous and may be detected during the investigation of nonspecific symptoms such as anaemia. This case highlights the importance of recognising and sampling atypical pigmented gastrointestinal lesions, as endoscopy may play a key role in the diagnosis of advanced melanoma and prompt multidisciplinary management.

Introduction

Melanoma is a malignant tumour caused by the unregulated proliferation of melanocytes. Cutaneous melanoma is one of the most common cancers worldwide [1], and it represents over 95% of all melanoma cases [2]. Rarely, melanomas can arise from extracutaneous melanocytes in the mucosal membranes of the oral and nasal cavities, conjunctiva, and other mucosae [3]. Uveal melanoma is the most common primary intraocular tumour and the second most common type of melanoma [4]. Although primary gastrointestinal melanomas exist, melanoma involvement of the gastrointestinal tract more commonly represents metastatic disease [2]. Importantly, given the declining mortality rates of metastatic melanomas due to targeted therapies [1], recognising these lesions and their varying endoscopic appearance is of growing importance.

Case Presentation

A 74-year-old man with a history of epilepsy, arterial hypertension, and diabetes was referred to the endoscopy unit for investigation of iron-deficiency anaemia. The patient did not report previous overt blood loss, abdominal pain, dysphagia, or any other gastrointestinal symptoms. There was no history of alcohol abuse or smoking. Colonoscopy was unremarkable. The oesophagogastroduodenoscopy revealed multiple dark, flat millimetric lesions in the lower oesophagus, the body of the stomach, and all of the duodenum (shown in Fig. 1), and multiple biopsies were performed. The histopathological analysis and immunohistochemical staining revealed neoplastic cells with cytoplasmic positivity for HMB45, Melan A, and S-100. The cervico-thoracic-abdominopelvic computed tomography (CT) scan showed bilateral lung nodules, multiple liver focal lesions, and multiple gallbladder wall nodules, suggestive of metastasis (shown in Fig. 2). The cranioencephalic CT scan also revealed multiple cortico-subcortical supra and infratentorial lesions, and one hyperdense right intraocular nodule, measuring 14 × 9 × 16 mm. PET scan also showed a hypermetabolic spot in the external region of the right ocular globe, compatible with a primary tumour, as well as multiple hypermetabolic spots in the brain, liver, lungs, and bone (shown in Fig. 3). The patient underwent a complete dermatological examination, which found no suspicious nevi, as well as an ophthalmological evaluation, which described a solid right intraocular tumour, compatible with primary uveal melanoma.

Fig. 1.

Esophagogastroduodenoscopy findings: multiple dark, flat millimetric lesions in the lower oesophagus, the body of the stomach, and the duodenum. a Distal oesophagus. b Body of the stomach. c First portion of the duodenum. d Second portion of the duodenum.

Fig. 2.

CT findings showing gallbladder metastasis (arrow).

Fig. 3.

PET and cranioencephalic CT scans showing the primary tumour and metastasis. a Hypermetabolic spot in the external region of the right ocular globe on the PET scan (white arrow). b Hyperdense right intraocular nodule on the cranioencephalic CT scan (white arrow). c Brain metastasis and surrounding brain oedema on the cranioencephalic CT scan (star). d Hypermetabolic spots in the liver.

The patient was assessed by the oncology team, which requested the BRAF mutation testing, but the patient quickly developed paraesthesia secondary to the brain metastasis. Prednisolone was started due to concern that the paraesthesia was secondary to peritumoural brain oedema, but 2 weeks later, the patient was brought to the emergency department in a stuporous state, and a cranioencephalic CT scan showed multiple actively bleeding brain lesions. The patient was admitted for symptomatic care and, unfortunately, died 24 days after diagnosis.

Discussion

Metastatic involvement of the gastrointestinal tract by malignant melanoma is uncommon and usually reflects advanced disease. Uveal melanoma has a distinct biological behaviour from cutaneous melanoma, with marked tropism for the liver and, frequently, exclusive hepatic involvement [4] due to predominantly haematogenous spread [4, 5]. Metastasis to the gastrointestinal tract, although possible, is rare and is associated with a high mortality rate [4]. Metastatic melanoma to the gallbladder, in particular, is rarely diagnosed, although melanoma is the most common primary tumour identified in gallbladder metastases [6]. Multiorgan dissemination at diagnosis, such as observed in our patient, is rare and associated with a particularly poor prognosis.

Gastrointestinal melanomas are often asymptomatic or present with nonspecific symptoms and may remain undetected during patients’ lifetime. Endoscopic findings are also heterogeneous, ranging from pigmented to amelanotic lesions, and from flat mucosal lesions to ulcerated or polypoid masses [7]. In this case, the presence of multiple flat, dark lesions throughout the upper gastrointestinal tract illustrates a remarkable endoscopic presentation and highlights the need for a high index of suspicion and biopsy of atypical mucosal findings.

Distinguishing between primary gastrointestinal melanoma and metastatic disease still represents a diagnostic challenge [7]. The absence of suspicious cutaneous lesions, combined with ophthalmological findings and whole-body imaging, was crucial in identifying the uveal origin of the tumour, one of the few malignancies that can be diagnosed based on clinical and imaging finding without tissue sampling. Immunohistochemical positivity for melanocytic markers, including HMB45, Melan-A, and S-100, confirmed the diagnosis of melanoma [8].

The prognosis of metastatic uveal melanoma remains poor, particularly in the presence of liver and brain metastases [9]. Although recent advances in targeted and immunotherapies have improved outcomes in cutaneous melanoma [1], systemic therapies in metastatic uveal melanoma are still limited [5, 9]. The rapid clinical deterioration observed in this patient underscores the aggressive nature of the disease.

In conclusion, this case emphasises the importance of recognising metastatic melanoma as a potential cause of atypical gastrointestinal lesions and iron-deficiency anaemia. Endoscopists should be aware of the diverse endoscopic appearances of melanoma metastases, as early recognition may facilitate prompt diagnosis and multidisciplinary management.

Statement of Ethics

Approval by the Ethics Committee was waived in accordance with local regulations. Consent to publish this case report and accompanying images was obtained from the patient’s family. The CARE Checklist for this case report is available as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000551817)

Conflict of Interest Statement

The authors have no relevant conflicts of interest to disclose.

Funding Sources

This paper was not supported by any sponsor or funder.

Author Contributions

Raquel Oliveira: conceptualisation, data curation, and writing – original draft; Margarida Portugal: data curation and writing – review and editing; Joana Roseira and Bruno Peixe: writing – review and editing.

Funding Statement

This paper was not supported by any sponsor or funder.

Data Availability Statement

All data generated or analysed during this study are included in this article. Further enquiries can be directed to the corresponding author.