CT and PET/CT findings of primary pulmonary malignant melanoma: a case report and literature review

Abstract

Primary malignant melanoma of the lung (PMML) is an extremely rare and refractory tumor, and its diagnosis is a significant challenge. The current study presents the case of a 62-year-old man who presented to the Department of Cardiothoracic Surgery (Lishui Municipal Central Hospital, Lishui, China) with chest tightness and fatigue for 3 months. Chest computed tomography (CT) revealed a 1.5- × 1.9-cm mass with irregular borders and heterogenous density located in the right lower lung lobe. Contrast-enhanced CT revealed slight enhancement of the mass, but there was no clear evidence of malignancy. Positron emission tomography (PET)/CT revealed a defined-margin mass, with slightly high uptake (standardized uptake value [SUV]: 3.6). The patient underwent video-assisted thoracoscopic surgery (VATS), and the final diagnosis was PMML on the basis of the results of the pathological examination. The patient received four courses of immunotherapy after the operation, and eventually declined further immunotherapy owing to the high cost. The patient was followed-up for 1 year without metastasis or recurrence.

Introduction

Malignant melanoma (MM) is an unusual neoplasm that frequently occurs in the skin ¹ and less frequently in the liver, larynx, cervix, ovaries, respiratory tract, esophagus, and oral cavity. ² Primary malignant melanoma of the lung (PMML) is considered extremely rare. In most studies of primary lung tumors, the incidence of PMML is only 0.01%. ³ As of 2020, only 52 articles and 76 cases had been reported. ⁴ Owing to the rarity of the tumor, the clinical behavior, diagnostic approach, and therapeutic options are still uncertain. Furthermore, owing to developments in modern medicine, numerous examination tools and treatment methods have been developed, and whether positron emission tomography (PET)/computed tomography (CT) is helpful for diagnosis requires further exploration. Therefore, the current study presented a case of PMML in a 62-year-old man and reviewed the imaging characteristics and treatment strategies of previously reported cases.

Case Presentation

The reporting of this study conforms to the CARE guidelines. ⁵ A 62-year-old man presented to the Department of Cardiothoracic Surgery of Lishui Municipal Central Hospital, Lishui, China, with chest tightness and fatigue for 3 months. He had a history of smoking 20 cigarettes per day for 30 years, with no history of hypertension, diabetes mellitus, hepatitis, tuberculosis, coronary disease, surgery, or malignancy. Physical examination revealed no abnormal signs in the skin, head, eyes, neck, lymph nodes, and lung. Blood counts, serum electrolyte concentrations, and biochemical data were within normal limits, and electrocardiography, cardiac ultrasonography, and lung function examinations were normal. Chest CT revealed a 1.5- × 1.9-cm mass with irregular borders and heterogenous density located in the right lower lung lobe. Contrast-enhanced CT showed slight enhancement of the mass. PET/CT revealed an oval mass with a clear boundary (Figure 1). The maximum standardized uptake value (SUV) was 3.6, and other parts of the body had no abnormal increase in [18F]-2-fluoro-2-deoxy-D-glucose (FDG) metabolism, such as the mediastinal lymph nodes, liver, brain, and bone marrow. Owing to the possibility that the tumor was malignant, video-assisted thoracoscopic surgery (VATS) was performed. The patient underwent right lower lobectomy and mediastinal lymphadenectomy of the lymph nodes of stations 2, 4, 7, 9, 10, 11, and 12. Histopathological examination revealed that the right lower lobe mass contained a large number of spindle cells with pigment cell differentiation (Figure 2). Immunohistochemically, the tumor was positive for S-100 (Figure 3), human melanoma black 45 (HMB45) (Figure 4), and Melan-A (Figure 5) and negative for P63, P40, cytokeratin (CK)7, and napsin A. On the basis of the PET-CT findings and pathological examination results, the final diagnosis was PMML. After obtaining a clear diagnosis, four courses of sintilimab injectable immunotherapy were successfully administered. The patient eventually declined further immunotherapy because of the high cost. He was followed-up for 1 year without metastasis or recurrence.

Figure 1.

PET/CT showing an oval mass with a clear boundary in the lower lobe of the right lung

Figure 2.

Histopathological examination showing that the surgical specimen contains a large number of spindle cells with pigment cell differentiation (hematoxylin and eosin, ×200).

Figure 3.

Immunohistochemically, the tumor is strongly positive for S-100 (×200).

Figure 4.

Immunohistochemically, the cytoplasm of the malignant cells stained positive for HMB45 (×200). HMB45, human melanoma black 45.

Figure 5.

Immunohistochemically, the tumor stained positive for Melan-A (×200).

Discussion

PMML is an extremely rare tumor. The early clinical manifestations are not obvious, the progression is rapid, and the prognosis is very poor. ² According to previous reports, approximately 53.9% of affected patients have metastasis-related symptoms. ⁴ Other symptoms comprise cough, hemoptysis, shortness of breath, chest pain, weight loss, and dark sputum. ⁴ A small number of patients, approximately 9.2%, are asymptomatic. ⁴

PMML is widely recognized as having the following criteria: (1) solitary lung tumor; (2) pathological features of malignant melanoma; (3) no history of mucosal, skin, or eye surgery or melanoma; and (4) no melanoma identified in other areas of the body. ⁶ PMML should be distinguished from lung cancer, lymphoma, pneumonitis pseudotumor, and pulmonary hamartoma. ⁴ Lung cancer is one of the most common malignant tumors. ⁷ CT images of lung cancer often reveal a round mass, often with irregular borders, lobulation, visible burr sign, pleural depression, vacuole sign, and vascular cluster sign. ⁸ If the pleural cavity is involved, pleural effusion and mediastinal lymphadenopathy may occur, and enhanced CT may show moderate enhancement. ⁸ Most lesions tend to affect the right lung and upper lobe. ⁹ In contrast, PMML presents as a soft tissue density with clear boundaries and mild enhancement on enhanced imaging, and most lesions affect the left lung. Additionally, 71% of PMML lesions are located in the central lung region. ⁴ Currently, the most common type of lung cancer, lung adenocarcinoma, occurs mainly in the peripheral lung. These patterns should be considered in the differential diagnosis of PMML. Additionally, patients with PMML have metastases at diagnosis, but only one third of patients have mediastinal lymph node involvement, and most patients have distant metastases. ⁷ Lymphatic progression of PMML has a different behavior than that of lung cancer; ⁴ however, more well-documented cases are needed to evaluate this difference. Pulmonary hamartomas have smooth, neat edges of nodules or masses, without deep lobulation or the burr sign, and no satellite lesions. ¹⁰ Calcification may occur in some cases, and “popcorn” calcification is a characteristic feature of lung hamartoma. Pneumonitis pseudotumor is a nonspecific inflammatory proliferative tumor-like lesion of lung parenchyma. ¹¹ It is a mass formed by granuloma, organization, fibrous connective tissue hyperplasia, and related secondary lesions caused by chronic inflammation in the lung. CT reveals a well-defined mass shadow in pneumonitis pseudotumor, and a cavity may appear in some cases. Therefore, it is difficult to distinguish PMML from lung disease, and the immunostaining results are important. ²

PET-CT has high sensitivity and specificity for the diagnosis of lung cancer, lymphoma, and other malignant diseases; ¹² however, it is unclear whether PET-CT is helpful in the diagnosis of PMML. Deng et al. ² reported a case of a 57-year-old man with PMML. CT revealed a space-occupying lesion in the lower lobe of the right lung adjacent to the pleura, with a clear boundary. PET-CT was performed and revealed a malignant space-occupying lesion in the lower lobe of the right lung, with liver metastasis; however, the SUV values were not specified. Lazarou et al. ¹³ reported a patient with PMML in the right lower lung with multiple mediastinal lymph nodes and left adrenal gland metastases. PET-CT indicated an SUV value of 4.8, indicating malignancy. In our case, PET-CT examination showed that the mass was located in the right lower lung with an SUV value of 3.6, which was considered malignant, and no metastases were identified. As PMML is prone to early metastasis, PET-CT may be a better choice to accurately stage the tumor, understand the severity and prognosis, and determine clinical treatment plans; however, more cases are needed to confirm this.

Surgical resection combined with immunotherapy, when feasible, is the main treatment for PMML; however, the prognosis for most patients is poor. ⁴ Lazarou et al. ¹³ reported a case of an 82-year-old male non-smoker with PMML who underwent total right lung resection. Postoperative rib metastases developed, and radiotherapy was administered, but the clinical response was incomplete, and the patient died 13 months after diagnosis. Takahashi et al. ¹⁴ reported a case of PMML with brain metastasis. Neutrophil counts and the hemoglobin concentration decreased after treatment with nivolumab, and the patient died 9 months later, after disease progression. A small number of patients have been reported with a better prognosis. Bernal et al. ¹⁵ reported a case of unresectable PMML with clinical stage IIIB (T4N2M0) disease. The patient obtained a partial response to pembrolizumab and underwent radical surgery. The patient was free of metastasis and recurrence more than 24 months after surgery. In our case, the patient was treated with thoracoscopic right lower lobectomy combined with postoperative injectable sintilimab immunotherapy. At the time of writing, there was no metastasis or recurrence during the 1-year follow-up.

Conclusion

PMML is very rare. CT findings do not show lobulation, burr sign, and other common imaging findings of lung cancer, and these tumors are easily misdiagnosed as other tumors. PET-CT may be helpful in the diagnosis of PMML. Despite the poor prognosis, surgical resection combined with immunotherapy remains the main treatment for PMML.