Malignant melanoma is a common skin neoplasm bearing poor prognosis when presenting with metastases. Rarely melanoma metastases present without an identifiable primary cutaneous lesion despite exhaustive workup. We describe the case of a solitary lung metastasis in a patient with neurofibromatosis type 1 without an identifiable primary tumour. The rapid progression of this malignant neoplasm that led to the patient’s death within 1 year is described.
A 65-year old man with neurofibromatosis type 1 (NF1) underwent a chest X-ray following a three-week history of cough productive of white sputum. He was otherwise asymptomatic but had a 30-pack-year smoking history. The radiograph revealed a solitary coin lesion of the right lower lobe. The patient underwent a CT scan which demonstrated a 3.3 cm right lower lobe lesion, separate to the pleura and suspicious for primary lung carcinoma (Figure
CT imaging of lung metastasis in coronal (a) and axial (b) planes.
Histological analysis of lung biopsy. Tissue was negative for primary lung cancer ((a) CK stain and (b) TTF-1 stain) and was positive for melanoma ((c) Melan A stain and (d) S100 stain).
Physical examination to establish the primary lesion was complicated by the presence of numerous neurofibromas and hyperpigmented café au lait spots, and the search ultimately proved unsuccessful. A PET/CT demonstrated a focal nodule in the right lung and several other masses with poor radiotracer uptake consistent with neurofibromas. Crucially the scan did not elicit a primary melanoma. The patient’s ECOG performance status was 0 and therefore VATS metastasectomy with clear histological margins was performed. The tissue was stained for the BRAF V600 mutation but was negative and thus, the prescription of Vemurafenib was not deemed beneficial. Because the risk of systemic relapse was extremely high, the patient was followed with active surveillance.
The patient had undergone two surgical resections of large superficial plexiform neurofibromas 20 years ago. After the PET scan had proved negative, the possibility that these operations had removed the primary melanoma was considered. While attending the plastic surgery department 2 months after his VATS procedure for removal of an elbow neurofibroma, a pigmented lesion of the patient’s skin, buried within his beard, was noted (Figure
H&E stains on initial biopsy (a), metastasectomy (b), and primary melanoma excised from the neck (c).
One month after diagnosis, the patient suffered an acute stroke like episode, with subsequent CT brain indicating the presence of 6 intracranial lesions (Figure
CT imaging of brain metastases in the coronal (a) and axial (b) planes.
NF1 patients are at increased risk of neural crest derived neoplasms [
Because melanoma is associated with late metastasis [
MUP should be investigated with PET/CT to locate the primary lesion and to stage the disease [
Regardless of the origin of the metastasis in this case, the benefit of performing metastasectomy was twofold. Firstly, a definitive diagnosis of the mass could be made as the oligometastatic lesion could have been manifesting as part of our patient’s complex syndrome (NF1), while the possibility of a sarcoma still existed. And secondly a survival advantage would be conferred to the patient. The literature suggests aggressive surgical treatment is warranted in such cases. For all patients with unknown primary melanomas, the 5-year survival rate for those undergoing surgical resection (38.8%) was significantly better than that for patients who received no treatment (19.6%) [
This case illustrates a primary cutaneous melanoma presenting with a solitary pulmonary metastasis in a patient with NF1. This case is unusual due to the rapid progression of this patient’s disease. Bearing in mind the close association and causative relationship of NF1 and malignant melanoma, a thorough physical examination of the patient who presents with a metastatic deposit of melanoma must be carried out in an effort to identify the primary lesion and to expedite the appropriate management strategy.
The authors declare that there is no conflict of interests regarding the publication of this paper.