Melanomas originate from neural crest melanocytes, and are usually derived from benign growth-stunted mole. The pathogenesis of melanomas is associated with genetic and environmental factors, among which family history is the biggest risk factor. Other factors include ultraviolet radiation, skin photosensitivity, autoimmune state, and the presence of melanocytes or dysplastic moles[2, 4, 5, 8]. The pathogenesis of malignant melanomas is very complex, including a series of complicated interactions among external events and endogenous triggers, genetic mutations of BRAF, NRAS, and KIT, as well as endogenous and immune-related factors of the tumor[2, 8]. Approximately 90% of malignant melanomas originate from the skin, while melanomas of lung and liver origin are very rare[3, 10, 11]. In this report, tissue biopsy results of both lungs and unhealed plantar puncture wound indicate the patient should be diagnosed as malignant melanoma.
This patient had a plantar puncture wound 3 years ago and manifested pulmonary symptoms such as coughing and expectoration about 1 year later. However, without enough attention and proper care, concomitant infection lead to persistently unhealed wound. The wound was at the heel, which was repeatedly compressed and rubbed during daily activities. Under the combined actions of multiple factors, normal cells mutated into tumor cells, which gradually invaded into the dermis. Subsequently, unhealed wound can help the tumor cells get in touch with blood and lymphatic systems and gradually spread from the original site[5]. In this case, there were no mole cells in the plantar lesion, and the change of normal cells into tumor cells may be stimulated by the protracted wound, which was different from the published pathogenesis of melanomas[2].
Due to the highly invasive and metastatic characteristics of malignant melanoma, for most of patients, metastasis has already occurred before diagnosis is confirmed. The lung and pleura are the most common sites of melanoma metastases and usually the primary sites of initial metastasis, possibly due to the convergence of blood and lymphatic systems, and the peripheral blood pumped from the right heart through the pulmonary artery [4, 5]. Clinically, about 10–20% of the patients with malignant melanomas have concurrent liver metastasis[16], while 5%-17% of the patients with stage IV melanomas have bone metastasis[17], which usually occur in the spine, pelvis, shoulder, and distal femur[18]. In this case, the patient has developed lung, liver, and thoracolumbar lesions, consistent with the published results.
For the patient in this case, it took nearly one year from the first visit due to cough and expectoration to the final diagnosis.The lung biopsy was not performed by the local doctor to confirm the diagnosis. Pathological diagnosis is the "gold standard" for pulmonary space-occupying lesions. For pulmonary fungal infection, scattered nodules, halo sign or crescent sign can be detected using CT scan[12, 13, 14, 15]. According to the diagnostic criteria specified by the European Fungal Research Organization for Cancer Therapy (EORTC), the crescent sign and the presence of cavities in pulmonary lesions are typical manifestations of pulmonary fungal infection[13].
In this case, the above characters were all detected using CT scan. Wound secretions from skin lesions were cultured by the local hospital and C. albicans was identified. Accordingly, it was considered as pulmonary fungal infection through skin lesions into the blood. However, lung biopsy was not performed at that time to confirm the diagnosis. For lung metastases, the most common manifestations are multiple pulmonary nodules, while pulmonary cavities may also occur[7, 9, 12]. Imageology characters of lung metastases are similar to those of pulmonary infection. Thus, it is quite difficult to make an accurate diagnosis only by imageology. The state-of-the-art mNGS technology would identify etiological pathogens, while the negative results might also provide useful information. In this case, the negative result of the lung biopsy further confirmed our diagnosis that the lung lesions were not caused by infection. In summary, before making a final diagnosis, the doctor should comprehensively evaluate clinical manifestations and examine the patient, especially the pathological results.