An NRAS mutation in primary malignant melanoma of the lung: a case report

Abstract

Background Primary malignant melanoma of the lung (PML) is extremely rare. No precursor lesions of PML have been identified, and little is known about the genetic mutations associated with the disease. Typically, 15–20% of malignant melanomas possess NRAS gene mutations, but no cases of NRAS-mutated PML have been reported in the English literature. We present a case of PML involving an NRAS mutation. Case presentation Clinical summary A 74-year-old Japanese female presented with worsening dyspnea and was admitted to hospital. Computed tomography (CT) revealed a right lung (S10) mass and pleural dissemination. Cytology of the pleural effusion in the right lung was performed, and malignant melanoma or clear cell sarcoma was suspected. A dermatological examination and gallium scintigraphy were conducted to determine the primary tumor site, but no suspicious lesions, expect for the right lung mass, were found. After admission, CT showed complicating bilateral pneumonia, and an antibiotic drug was administered, but the pleural effusion got worse. About 2 weeks later, the patient died of respiratory failure and cardiac arrest. An autopsy was performed to determine the histological diagnosis. Autopsy findings A 26x15x20-mm black and pale yellow mass was found in the right lower lobe. Many disseminated nodules were found in the right lobe. The tumor had invaded the right diaphragm. Subcarinal lymph node metastasis was also detected. Immunohistochemically, the tumor cells exhibited positivity for S-100 and HMB45 staining. The patient was diagnosed with malignant melanoma. Sanger sequencing of the tumor detected an NRAS mutation. Conclusions We found an NRAS D54N mutation in PML, which has not been reported previously anywhere in the world. Previous reports indicated that most cases of PML can be classified into the triple-wild-type, but BRAF mutation status was only analyzed in a few cases. We should analyze the mutation patterns of PML to determine whether any subtypes other than the triple-wild-type exist. PML might be a form of de novo cancer.

FNBP1-BRAF fusion in a primary melanoma of the lung

“…1 However, S100 appeared to exhibit lower sensitivity for the ductal component of SP than SOX10. Consistent with previous studies, 3,7 the ductal component in the present case of SP showed diffuse and robust positivity for SOX10 but focal positivity for S100. Additionally, we examined the S100 immunohistochemistry for four MPs.…”

“…7 In the PML setting, although no evaluation of the tumour burden and no research for mutational signatures have been conducted, the initial investigations in 10 PML cases (mainly isolated case reports) have not identified mutations in BRAF, C-KIT and NF1 genes. 3 Therefore, the absence of common oncogenic drivers of cutaneous melanoma in PML suggests an extracutaneous origin for these cases, as similarly observed for mucosal melanomas. 8,9 By contrast, recent investigations by Yang et al of 10 additional PML cases revealed high tumour mutation burden, frequent RAF, NRAS, NF1, KIT, or KRAS mutations, and dominant UV-signature mutation profile, strongly arguing for a cutaneous primary origin in these 'PML' cases.…”

“…Overall, the histological and immunohistochemical findings were consistent with SP. 3 Recurrent oncogenic alterations in BRAF, followed by HRAS, have been reported in SP of the intraoral minor salivary glands, 7,8 but a mutation analysis for SP of the bronchus has not been reported. We thus extracted DNA from a formalin fixed, paraffin embedded specimen and performed targeted sequencing using the Ion AmpliSeq custom panel (Thermo Fisher Scientific, USA) for 23 cancer related genes, as described in detail elsewhere.…”

Giant lung metastasis of NRAS-mutant melanoma in a 24-year-old patient with a history of BRAF-mutant conventional melanoma harboring Spitzoid morphology: a case report

“…Possibility of primary pulmonary melanoma with no association with the initial AST is highly controversial [ 17 ]. However, primary pulmonary melanoma with NRAS mutation has been recently reported [ 18 ].…”