Primary Malignant Melanoma of the Lung With a Long‐Term Course: A Case Report

ABSTRACT

A 66‐year‐old man with a 20‐year history of recurrent haemoptysis presented with mild bronchiectasis and linear opacities detected on chest computed tomography (CT). The lesion was followed up annually and gradually enlarged into a mass over 10 years. Multiple bilateral pulmonary nodules were noted at 78 years of age. Surgical biopsy revealed malignant melanoma without evidence of other primary lesions on dermatological examination or positron emission tomography‐CT. The patient was treated with nivolumab and achieved stable disease for 8 months before discontinuation owing to immune‐related adverse events. Rapid disease progression was observed, and the patient died 14 months after initiating immunotherapy. Autopsy demonstrated extensive metastatic dissemination and marked tumour necrosis with CD8+ T‐cell infiltration in the lung tumour, indicating a therapeutic response to nivolumab. These findings highlight the potential association between chronic airway inflammation and tumour development and suggest that immunotherapy could play a role in treating PMML.

A 66‐year‐old man with a 20‐year history of recurrent haemoptysis presented with mild bronchiectasis and linear opacities detected on chest computed tomography (CT), and the lesion was followed up annually and gradually enlarged into a mass over 10 years. Multiple bilateral pulmonary nodules were noted at 78 years of age; therefore, surgical biopsy revealed malignant melanoma without evidence of other primary lesions on dermatological examination or positron emission tomography‐CT. Rapid disease progression was observed, and the patient died 14 months after initiating immunotherapy.

1. Introduction

Primary malignant melanoma of the lung (PMML) is an exceptionally rare tumour that accounts for less than 0.01% of all primary pulmonary malignancies [1]. Diagnosis requires the exclusion of cutaneous, mucosal and ocular primary lesions and the clinical course is typically aggressive [2]. We report a unique case of PMML with a nearly 30‐year history of recurrent haemoptysis before diagnosis.

2. Case Report

The patient was a 66‐year‐old man with a 20‐year history of recurrent haemoptysis that began at approximately 46 years of age. He had a history of smoking but no known dermatological conditions. He had undergone bronchial artery embolisation at another hospital for repeated episodes of massive haemoptysis.

At the initial presentation, chest computed tomography (CT) revealed mild bronchiectasis with linear opacities in the left lower lobe (Figure 1A). From that time, the lesion was followed up annually by CT and gradually enlarged into a mass over the next 10 years (Figure 1B). Although surgical resection was recommended, the patient declined treatment. At the age of 78 (12 years after the initial visit), multiple bilateral pulmonary nodules were noted (Figure 1C). Laboratory evaluation revealed elevated squamous cell carcinoma antigen levels, with other tumour markers within normal limits. Thoracoscopy revealed multiple round, darkly pigmented nodules in the right lung. Surgical biopsy was performed on one of the nodules in the right lower lobe (Figure 2A,B). Histopathological analysis revealed a malignant tumour composed of cells with abundant eosinophilic cytoplasm, melanin pigmentation and prominent nucleoli (Figure 2C). Lillie staining indicated the presence of melanin pigments. Immunohistochemically, the tumour cells were positive for HMB‐45 (Figure 2D) and S‐100. Dermatological examination revealed no evidence of primary cutaneous melanoma. Whole‐body positron emission tomography‐CT showed no other potential primary sites. Based on these findings, a diagnosis of PMML was established.

FIGURE 1.

Serial chest computed tomography (CT) images. (A) The initial CT image showed mild bronchiectasis with linear opacities in the left lower lobe. (B) Over 10 years, the lesion gradually enlarged into a mass. (C) Twelve years later, multiple pulmonary nodules were observed bilaterally. (D) Rapid disease progression was observed before the patient died.

FIGURE 2.

Histopathological findings from a surgical lung biopsy specimen and autopsy. (A) Gross appearance of the resected pulmonary nodule. (B) Cut surface of the same specimen showing darkly pigmented areas. (C) Haematoxylin and eosin staining at ×400 magnification revealing sheets of atypical cells containing melanin pigments and prominent nucleoli. These findings are consistent with those of malignant melanoma. (D) Immunohistochemical staining for HMB‐45 (×400), with subsequent Giemsa counterstaining to enhance contrast with the melanin pigment, revealed positive staining in the tumour cells. (E) Gross appearance of the entire bilateral lungs showing multiple tumour nodules. (F) Haematoxylin and eosin staining of the primary lesion in the left lung (×100) showing extensive tumour necrosis accompanied by lymphocytic infiltration. (G) Immunohistochemical staining for CD8 in the gallbladder (×400), with subsequent Giemsa counterstaining to enhance contrast with the melanin pigment, revealed infiltration of CD8‐positive T lymphocytes. (H) Haematoxylin and eosin staining (×100) demonstrated that the tumour was located beneath the intact bronchial ciliated columnar epithelium without evidence of ulceration, supporting a pulmonary origin.

Molecular testing revealed no BRAF mutations; however, programmed death‐ligand 1 (PD‐L1) expression was weakly positive (tumour proportion score: 1%–10%). Based on standard treatment protocols for cutaneous melanoma, nivolumab (240 mg/body weight) was initiated biweekly. After 10 cycles of nivolumab, the patient developed fever and generalised fatigue. Laboratory tests revealed markedly low cortisol (0.5 μg/dL) and adrenocorticotropic hormone (ACTH) (3.9 pg/mL) levels. In the corticotropin‐releasing hormone (CRH) stimulation test, neither cortisol nor ACTH increased, leading to a diagnosis of isolated ACTH deficiency. Therefore, the treatment was temporarily discontinued. Thirteen cycles were completed, resulting in stable disease for approximately 8 months. Subsequently, the disease progressed rapidly (Figure 1D), and the patient died 14 months after initiating immunotherapy. Autopsy revealed multiple black metastatic nodules in both lungs (Figure 2E), the brain, pleura, diaphragm, gallbladder, pancreas, stomach, intestines and nearby lymph nodes. The primary tumour was located in the left lower lobe and measured 44 × 40 mm. Histologically, extensive necrosis and infiltration of numerous CD8‐positive T cells were observed in the lung and gallbladder tumours, indicating nivolumab‐induced T‐cell activation (Figure 2F,G). Moreover, heterogeneity in tumour necrosis and T‐cell infiltration was observed across different sites and organs. The primary lesion was situated beneath the intact bronchial ciliated columnar epithelium without evidence of ulceration (Figure 2H), strongly supporting a pulmonary origin. The cause of persistent haemoptysis was considered to be the disruption of blood vessels in the airways.

3. Discussion

To the best of our knowledge, no previous case of primary malignant melanoma of the lung (PMML) has demonstrated a prolonged clinical course after symptom onset. Aberrant melanocytes derived from neural crest cells have been hypothesised to persist in the respiratory tract mucosa and undergo malignant transformation under certain conditions [3]. Another theory suggests that pluripotent or neuroendocrine cells within the bronchial epithelium differentiate into melanocytes [3]. In our case, the tumour developed in a chronically inflamed bronchiectatic region with recurrent haemoptysis over nearly three decades. This suggests that chronic airway inflammation and repeated epithelial injury contribute to melanocyte dysregulation and oncogenesis. Although causality cannot be definitively proven, this case indicates that a chronic inflammatory microenvironment could play a role in the development of PMML.

In addition to its prolonged natural history, this case illustrates the potential benefits of ICI therapy for PMML. The patient was treated with nivolumab, achieved stable disease for 8 months and survived for 14 months after treatment initiation. Although PD‐L1 expression was low and the therapy was discontinued early because of an immune‐related adverse event (isolated ACTH deficiency), autopsy findings revealed extensive tumour necrosis and marked infiltration of CD8‐positive T cells. These findings suggest that nivolumab successfully induced T‐cell activation and exerted a partial therapeutic effect despite the early termination of therapy. Although ICIs, such as nivolumab, have shown efficacy in cutaneous melanoma [4], their use in PMML remains rare. A recent systematic review identified only a few reported cases of PMML treated with ICIs, none of which included pathological confirmation of the treatment response [5]. To the best of our knowledge, this is the first reported case of PMML in which the therapeutic effects of ICI therapy were pathologically confirmed via autopsy. This case report highlights the potential role of immunotherapy in the treatment of PMML.

Moreover, in the early phase of this case, the clinical course was so indolent that a malignant neoplasm was not initially suspected, making the diagnosis difficult. However, the disease subsequently progressed rapidly. This clinical course suggests that the initial stage of PMML may not be aggressive. The fact that some postoperative cases exhibit prolonged survival from the time of diagnosis further supports this hypothesis [5].

Author Contributions

Y.F. and M.A. conceived the idea of the study. M.K., K.M., Y.M., S.N. and T.U. contributed to the interpretation of the results. Y.F., M.A. and Y.M. drafted the original manuscript. M.A. supervised the conduct of this study. All authors reviewed the manuscript draft and revised it critically on intellectual content. All authors approved the final version of the manuscript to be published.

Funding

The authors have nothing to report.

Consent

The authors declare that written informed consent was obtained for the publication of this manuscript and accompanying images using the consent form provided by the Journal.

Conflicts of Interest

The authors declare no conflicts of interest.

Fukushima Y., Azuma M., Miyagi Y., et al., “Primary Malignant Melanoma of the Lung With a Long‐Term Course: A Case Report,” Respirology Case Reports 14, no. 1 (2026): e70464, 10.1002/rcr2.70464.

Data Availability Statement

Research data are not shared.