A case of primary malignant melanoma of the esophagus

Abstract

Primary malignant melanoma of the esophagus (PMME) is an extremely rare esophageal malignancy that is often misdiagnosed or overlooked due to its atypical symptoms. We report a case of a 75-year-old male patient who presented with progressive dysphagia. Endoscopic examination revealed a black mass located 25 cm from the incisors. Further imaging studies, including computed tomography (CT) and emission computed tomography (ECT), showed significant thickening of the mid-esophageal wall with localized soft tissue mass formation and heterogeneous enhancement on contrast scans. Multiple lymph nodes around the lesion were visible, leading to an initial misdiagnosis of esophageal cancer. Additionally, metabolic abnormalities in the left scapula suggested possible bone metastasis of the tumor. The final pathological diagnosis was esophageal melanoma. After thorough evaluation of the patient's medical history and additional relevant tests, the primary origin was considered. Diagnosing primary malignant melanoma of the esophagus is a challenging task. This case, through the combination of endoscopic examination, imaging, and pathology, illustrates the characteristics of PMME, providing important insights for clinicians and emphasizing the necessity of comprehensive early evaluation to improve diagnostic accuracy and treatment outcomes.

Introduction

Primary malignant melanoma of the esophagus (PMME) is an extremely rare malignancy, accounting for less than 1% of all esophageal tumors, and has a poor prognosis [1,2]. Unlike the more common esophageal squamous cell carcinoma and adenocarcinoma, PMME originates from melanocytes in the esophageal mucosa. Due to its rarity and nonspecific clinical presentation, early diagnosis of PMME is often challenging. Imaging studies play a crucial role in the diagnosis and staging of PMME. Endoscopic examination combined with tissue biopsy is the gold standard for diagnosis, while imaging studies (such as CT, magnetic resonance imaging [MRI], and positron emission tomography-computed tomography [PET-CT]) are essential for evaluating the tumor's extent, invasiveness, and metastasis. This article reports a case of primary malignant melanoma of the esophagus diagnosed through imaging, endoscopy, and pathological examination. We illustrate the characteristics of this disease and discuss the related diagnostic and therapeutic challenges and strategies. Additionally, we provide a comprehensive review of the literature to enhance understanding and early diagnosis of PMME.

Case report

A 75-year-old male was admitted with progressive dysphagia persisting for over 1 month. The patient experienced swallowing difficulties without any obvious cause, with a sensation of obstruction during eating, which progressively worsened, accompanied by belching and acid reflux. His medical history included successfully treated pulmonary tuberculosis and an acute gastric antrum perforation in May 2016, for which he underwent laparoscopic exploration, ulcer repair, and lavage, with good postoperative recovery. He also had a history of penicillin allergy and suspected seafood allergy. Laryngoscopy revealed no significant abnormalities.

Endoscopy showed a black mass obstructing the esophageal lumen 25 cm from the incisors, with some food residue attached. The esophagus was narrowed, and the endoscope could barely advance to 28 cm from the incisors, where another black mass obstructed the lumen. Significant esophageal stenosis was noted, and further advancement of the endoscope was not possible due to bleeding upon contact (Fig. 1).

Fig. 1.

Endoscopic findings: A black mass obstructing the esophageal lumen was observed 25 cm from the incisors, with some food debris attached. The esophagus is narrowed, and the endoscope could only be advanced to 28 cm from the incisors, where the black mass still obstructed the esophageal lumen. The esophageal narrowing is significant, and further advancement of the endoscope was not possible. The mass was friable and prone to bleeding upon contact.

Chest CT (both plain and enhanced) demonstrated irregular thickening of the mid-esophageal wall with localized soft tissue mass formation, the largest section measuring approximately 4.1 × 6.9 cm. The mass showed heterogeneous enhancement, involved the serosal layer, and caused local luminal narrowing. Surrounding fat spaces were blurred, with esophageal dilation and fluid accumulation above the lesion, and several lymph nodes around the lesion and in the mediastinum, the largest being approximately 0.6 cm in diameter, showed uneven enhancement. Destruction of the left scapula was observed (Fig. 2). Imaging diagnoses suggested possible esophageal cancer with left scapular bone destruction, indicating metastasis. ECT findings confirmed abnormal bone metabolism in the left scapula, suggesting possible tumor bone metastasis (Fig. 3).

Fig. 2.

CT images: Axial unenhanced (A) and enhanced scans (B, C, E), and sagittal enhanced scan (D) show significant irregular thickening of the esophageal wall in the mid-esophagus, with associated soft tissue mass formation (purple arrows). The mass exhibits heterogeneous density with uneven enhancement on contrast scans, involving the serosal layer and causing localized esophageal narrowing. Surrounding fat planes are obscured, and there is esophageal dilation, fluid accumulation, and several enlarged lymph nodes in the perilesional and mediastinal areas (yellow arrows). Additionally, a rounded low-density lesion is observed on the right chest wall (green arrow), with a CT value of approximately -105 HU. The coronal bone window image (E) reveals bone destruction of the left scapula (blue arrow).

Fig. 3.

ECT shows clear skeletal imaging with normal morphology. There is heterogeneous distribution of radioactivity, with localized radioactive uptake in the left scapula, indicating abnormal bone metabolism in this region. The remaining skeletal structures and joints exhibit generally uniform and symmetrical radioactive distribution. Additionally, there is hydronephrosis in the left kidney.

Biopsy pathology revealed tumor cells distributed in sheets with large cell volume, abundant cytoplasm containing significant pigment, round or oval nuclei with eosinophilic nucleoli, high nuclear-cytoplasmic ratio, and significant atypia. Necrosis was present around the tumor nests (Fig. 4). Immunohistochemistry results were: Melan-A(+), HMB45(+), S-100(-), SOX-10(+), Vim(+), CyclinD1(+), CD117(-), CK(-), P16(-), P53(+; approximately 60%), CK5/6(-), P40(-), P63(-), Ki-67(+; approximately 20%). The pathological diagnosis was primary esophageal melanoma. BRAF gene testing was negative.

Fig. 4.

Pathological Results. (Panels A and B) show histopathological images (×100 and ×200 magnification, respectively) revealing tumor cells arranged in sheets. The cells are large with abundant cytoplasm, containing significant pigmentation. The nuclei are round or oval, with eosinophilic nucleoli. The nuclei-to-cytoplasm ratio is high, with marked atypia. Necrosis is observed around the tumor nests.

Further inquiry and additional examinations did not reveal melanoma at other sites, confirming the diagnosis of primary malignant melanoma of the esophagus with bone metastasis. Given the advanced stage of the tumor, surgery was not considered. Treatments such as radiotherapy, chemotherapy, and immunotherapy were recommended, but due to the patient's frail condition and advanced age, the potential effectiveness of these treatments was uncertain. After family discussion, they decided not to pursue further treatment.

Discussion

Malignant melanoma (MM) is an exceptionally rare disease, categorized into cutaneous melanoma and mucosal melanoma. Among these, PMME, originating from the esophageal mucosa, is particularly rare and prone to misdiagnosis or oversight. Its rarity presents significant challenges for diagnosis and treatment.

Accurate diagnosis of PMME depends on the integration of clinical assessment, endoscopic examination, imaging studies, and pathological analysis. Endoscopy is crucial for the initial visualization of the lesion and for biopsy, though the appearance can vary from pigmented to nonpigmented masses, complicating visual diagnosis. CT and MRI are instrumental in assessing the local extent of the disease and its invasion into surrounding structures. PET-CT helps identify metabolic activity and potential metastatic sites. Given the aggressive nature of PMME and its propensity for early metastasis to regional lymph nodes, liver, lungs, and bones, early detection and accurate staging are essential.

Primary malignant melanoma of the esophagus is extremely rare, accounting for approximately 0.1% to 0.2% of primary esophageal malignancies [3,4]. Its rarity presents significant challenges for diagnosis and treatment. PMME predominantly occurs in elderly individuals around the age of 70, with a higher prevalence in males compared to females, at a ratio of approximately 2:1 [5]. It predominantly occurs in the mid to lower esophagus (in over 90% of cases), with the upper esophagus being the least affected [6,7]. Approximately 40%-80% of newly diagnosed PMME patients present with distant metastases [8]. The exact pathogenesis of PMME remains unclear. Some researchers suggest that epithelial hyperplasia or chronic esophagitis, leading to an increase in melanocytes in the basal layer of the epithelium, may be an important contributing factor to the development of this disease [9,10]. The clinical presentation of PMME is nonspecific and often includes symptoms such as dysphagia, odynophagia, weight loss, retrosternal pain, and melena [11,12]. These symptoms are similar to those of other esophageal tumors, which can easily lead to misdiagnosis or missed diagnosis.

CT imaging: The CT characteristics of PMME include a mass with heterogeneous density. Calcification is typically not observed within the mass, and necrotic or cystic changes are relatively uncommon. On contrast-enhanced CT, the mass predominantly exhibits moderate enhancement during the arterial phase, with persistent enhancement noted during the venous or delayed phases. Surrounding vascular structures may appear enlarged.

MRI imaging: The melanin components in the tumor are paramagnetic, making PMME highly sensitive to MRI. Consequently, on T1-weighted images (T1WI), the tumor often appears as a high-signal lesion, whereas on T2-weighted images (T2WI), it appears as a low-signal lesion. This signal pattern is generally opposite to that of other tumors. If the melanoma cells contain few or no melanin granules or if there is associated bleeding or necrosis, the MRI appearance may be diverse. Melanomas can be classified on MRI into melanotic, nonmelanotic, mixed, and hemorrhagic types based on their imaging characteristics.

PET-CT Imaging:On PET-CT, there is a notable increase in 18F-FDG metabolism, which assists in identifying smaller or occult lesions, thereby improving the detection rate of early metastatic sites.

Early and accurate diagnosis of primary malignant melanoma of the esophagus (PMME) relies on imaging techniques such as endoscopy, CT, MRI, and PET-CT; however, histopathological examination remains the gold standard for confirming the diagnosis. Pathologically, PMME typically presents as solitary or multiple polypoid lesions, which may be pedunculated or sessile, and often exhibit pigmentation. Microscopically, the tumor cells vary in size and can be round, polygonal, or irregular, with melanin granules visible within the cytoplasm. The tumor cells exhibit a diffuse growth pattern and may invade the submucosa and even the muscularis propria. Immunohistochemically, most tumor cells are positive for Melan-A, HMB-45, S-100, and SOX-10, while CK is generally negative, and Ki-67 shows a proliferation index of approximately 40%-45%.

Differentiating PMME poses a significant challenge due to its imaging features, which can be similar to those of other esophageal malignancies and benign lesions. The differential diagnosis of PMME includes esophageal squamous cell carcinoma, esophageal leiomyoma/leiomyosarcoma, Kaposi sarcoma, and metastatic melanoma. (1) Esophageal Squamous Cell Carcinoma: As the most common malignant esophageal tumor, it typically presents with irregular wall thickening and narrowing. On CT, squamous cell carcinoma usually shows uniform or ring-like enhancement, which contrasts with the heterogeneous enhancement seen in PMME. However, distinguishing between these 2 conditions based on imaging alone is often insufficient, and histopathological examination is required for definitive diagnosis. (2) Esophageal Leiomyoma/Leiomyosarcoma: Leiomyoma, a benign tumor, appears as a round or oval mass within the esophageal wall, often with uniform density on CT. Leiomyosarcoma, a malignant counterpart, typically presents as a larger, more irregular mass with potential necrotic areas. Differentiation from PMME necessitates a combination of imaging and histological analysis. (3) Esophageal Kaposi Sarcoma: This condition may present as multiple submucosal nodules or polypoid lesions. Accurate diagnosis requires a comprehensive assessment involving clinical, pathological, and imaging features. (4) Metastatic Melanoma:** Metastatic melanoma can present as multiple lesions, with a history of melanoma at other sites being a key diagnostic clue. The presence of multiple lesions and a known primary melanoma aids in distinguishing metastatic melanoma from PMME.

Given the overlap in imaging features among various esophageal lesions, definitive diagnosis of PMME relies on integrating imaging studies with pathological analysis.

PMME is a rare and highly aggressive malignancy. Due to its rarity and complexity, treatment regimens have not been fully standardized and typically require a combination of therapeutic approaches. Currently, radical surgical resection is considered the treatment of choice for early-stage resectable PMME patients. Other treatment modalities include radiotherapy, chemotherapy, and immunotherapy. For patients with specific genetic mutations, such as the BRAF V600E mutation, targeted therapy may be effective. Treatment for PMME needs to be individualized, taking into account the patient's specific condition, tumor characteristics, and overall health. A multidisciplinary approach should be employed to enhance treatment outcomes and improve the patient's quality of life.

Conclusion

This case report describes a rare instance of PMME. Due to its atypical clinical symptoms, imaging characteristics, rarity, and early metastatic tendencies, the diagnosis and treatment of PMME present significant challenges. Imaging studies play a crucial role in determining the extent of the tumor, assessing the depth of invasion, and detecting distant metastases. A definitive diagnosis can be made by integrating clinical presentation, imaging studies, endoscopic findings, and pathological analysis. Surgical resection remains the primary treatment modality, and combining it with immunotherapy may improve prognosis. This case underscores the importance of a multidisciplinary team in the diagnosis and management of PMME and suggests that clinicians should consider PMME as a potential diagnosis when confronted with atypical esophageal lesions. The aim of sharing this case is to enhance awareness of PMME, promote early diagnosis, and optimize treatment strategies to improve patient outcomes.

Patient consent

Written informed consent was obtained from a legally authorized representative for anonymized patient information to be published in this article.

Funding

This project was supported by the National Natural Science Foundation of China (82160327, and 82271977), the Hainan Academician Innovation Platform Fund, and the Hainan Province Clinical Medical Center.