A 41-Year-Old Woman with a Late Cerebral Metastasis 16 Years After an Initial Diagnosis of Cutaneous Melanoma.

BACKGROUND Late cerebral metastasis more than 10 years after the diagnosis of cutaneous melanoma is very rare. This report is of a woman with late cerebral metastasis 16 years after an initial diagnosis of cutaneous melanoma. CASE REPORT A 41-year-old woman had been diagnosed with malignant melanoma 16 years prior from a biopsy of a dish-pattern tumor on the back, for which she received chemotherapy for 5 times (therapeutic regimen and medications were not available). She had not had a diagnosis of skin melanoma in the past 16 years. Before presentation to the Emergency Department, she had a progressive disturbance of consciousness for 6 weeks and sudden coma for 6 h. A head computed tomography scan indicated intracranial masses located at the right frontal and temporal lobes. The patient underwent surgery for tumor and hematoma removal. During surgery, dural metastasis with widespread dissemination in adjacent temporal bone, temporalis, and hypodermis was confirmed. Postoperative histopathology analysis confirmed the diagnosis of malignant melanoma metastasis. On the second day after surgery, the patient developed recurrent bleeding in the right frontal lobe, which led to deteriorated consciousness. She received hematoma evacuation and craniectomy and lived in a poor condition with drowsiness and hemiplegia of the left limb for 3 months and died 5 months after craniectomy. CONCLUSIONS This report has presented a rare occurrence of late cerebral metastasis 16 years after the initial diagnosis of a primary cutaneous melanoma. More recent primary melanoma of the skin was not identified, which supports the need for long-term follow-up of patients with a history of primary cutaneous melanoma.

Background

Melanoma is the third most common source of brain metastases, following lung and breast cancers [1], and has one of the highest tendencies to develop brain metastases, with a prevalence of nearly 45% in patients with stage IV melanoma and 75% upon autopsy [2-5]. For most patients newly diagnosed with melanomas, wide excision, sentinel lymph node biopsy, and additional treatment of regional or distant metastatic disease are essential procedures according to the updated National Comprehensive Cancer Network (NCCN) guidelines for melanoma [6]. Regular clinical follow-up is recommended as the most important means of detecting cutaneous melanoma recurrence. The American Academy of Dermatology guidelines recommend surveillance intervals and follow-up tests, physical examination with emphasis on assessment of local recurrence, particularly for the lentigo maligna subtype, and a full skin check to evaluate for new primary cutaneous melanoma at least every 6 to 12 months for 1 to 2 years and annually thereafter for patients with stage 0 (melanoma in situ). For stages IA to IIA cutaneous melanoma, comprehensive history, review of systems, and physical examination with specific emphasis on the skin and regional lymph nodes are recommended at least every 6 to 12 months for 2 years and at least yearly thereafter. For stages IIB to IIC, the recommended follow-up interval is every 3 to 6 months for 2 years, then at least annually thereafter [7]. Generally, patients who are disease-free 10 years after diagnosis are considered nearly synonymous with cure and are discharged from follow-up. However, late recurrences, defined as occurrences 10 years or more after diagnosis, have been reported in several studies, with incidence rates ranging from 1.01% to 12.75% [8-11]. Owing to the limited population of patients and lack of extensive longitudinal follow-up, it is difficult to estimate the frequency, predisposing factors, and prognostic implications of late recurrence of melanoma. Among all the recurrent locations, very few publications have described late cerebral metastasis (late recurrences involving the brain) [12, 13]. In a cohort of 1372 patients with stage I-II melanoma who were disease-free 10 years after diagnosis, only 10 patients (7.3%) were found to have distant metastases involving the brain [8]. In another collection of 1881 patients with stage I or II melanoma, only 1 patient (0.5%) was identified as having late cerebral metastasis [11].

Late cerebral metastasis that occurs more than 10 years after the diagnosis of cutaneous melanoma is very rare. This report is of a 41-year-old woman with a diagnosis of late cerebral metastasis 16 years after an initial diagnosis of cutaneous melanoma.

Case Report

A 41-year-old woman was sent to the Emergency Department (ED) because of progressive disturbance of consciousness for 6 weeks and sudden coma for 6 h. The patient was diagnosed with malignant melanoma 16 years before from the biopsy of a dish-pattern tumor on the back, for which she received chemotherapy for 5 times (therapeutic regimen and medications were not available). She had not had any other diagnoses of skin melanoma in the past 16 years. Five years before presentation, the patient had persistent dry cough and discomfort in the chest; a suspected metastatic mass was then detected in the right lung by computed tomography (CT) scan. The patient received chemotherapy (paclitaxel, caspofungin, and sorafenib) but failed treatment after 3 times, presenting with weakness, loss of appetite, and nausea. Then, 6 weeks ago, the patient had vomiting after eating accompanied by drowsiness, which was relieved with mannitol. After a sudden coma as well as incontinence for 6 h, she was sent to the ED with suspicion of cerebral apoplexy.

On physical examination, the patient was in a deep coma, with a Glasgow Coma Scale score of 5 points. A soft mass measuring 2×2 cm in diameter was palpated in the right frontal scalp. The right pupil dilated to 4 mm without any direct and indirect light reflection. The whole body was scattered with sub-cutaneous nodules. There was a positive Babinski sign in the left limb, but no movement in the right limb.

Head CT scans revealed multiple intracranial masses located at the right frontal and temporal lobes (). With severe brain compression, tumoral hemorrhage shifted the midline over 1 cm, resulting in acute cerebral herniation. Meanwhile, a scalp tumor was also found in the frontal region (). A lung CT scan indicated a foliated mass measuring 3.7×2.6×3.3 cm in the lower lobe of the right lung (). Compared with the CT scan taken 5 years earlier (), small nodules in the upper lobe of left lung had disappeared, but new round nodules were found in both lungs this time. In addition, a metastasis of the 12th vertebra was suspected according to the low density detected in the CT scan ().

The patient underwent tumor resection surgery through a trans-frontal approach. After the skull flap was removed, the dura mater was found to be invaded extensively by the tumor (). The extradural part grew infiltratively through the skull to the subcutaneous tissue. Small melanic dots were disseminated in a widespread fashion in adjacent temporal bone, temporalis, and hypodermis (). The intradural part was about 4.3×4.1×5.2 cm in size with abundant blood supply. Total removal of the tumor, hematoma, and dura was performed. The boundary between the tumor and surrounding brain tissue was clear. On the second day after surgery, the patient developed recurrent bleeding in the right frontal lobe, which led to deteriorated consciousness again (). Intracranial hematoma evacuation and craniectomy were performed, but the patient’s consciousness did not improve after surgery. Palliative care was provided at the request of the family for supportive treatment. Histopathology confirmed diagnosis of malignant melanoma metastasis (). The patient lived in a poor condition with drowsiness and hemiplegia of the left limb for 3 months and died 5 months after craniectomy.

Discussion

Although late recurrence of melanoma (disease-free 10 years after initial diagnosis) is rare, researchers have begun to focus on this scenario, which can require life-long follow-up. To date, there are 9 cases reported in the literature of late cerebral metastasis occurring in patients with cutaneous melanoma [12-17]. The number of reported cases of late recurrence of melanoma involving the brain has significantly decreased owing to the development of radiological techniques and updates to the melanoma management guidelines in recent years. Established knowledge has indicated tumor thickness, ulceration, mitosis rate, invasion level, patient age, localization, and type of recurrence as the prognostic factors of melanoma, but there are no clear data about predictive and prognostic factors for late recurrence [18-23]. Possible factors associated with late recurrence of melanoma include thinner primary melanomas, non-ulceration, non-head/neck location, younger patient age, and female sex [9,11,24], but these are still debated [25].

In contrast to other late recurrent sites of melanoma, brain metastasis presents unique characteristics. Most lesions in the cerebral parenchyma are cystic, as seen in past cases [12-17]. However, the metastasis in our present case was solitary because of the involvement of the dura matter. Another interesting finding is that there were few metastases involving only brain tissue. In previous cases as well as in the current case, it was found that patients presented with accompanying metastatic lesions in the lung. It is suggested that regular radiological follow-up of the lungs can help detect early metastases to the brain [26], but a large number of cases and controlled trials are still needed to verify this hypothesis. PETCT is recommended in the detection of cerebral metastases of melanoma and is helpful in diagnosis and staging of melanoma recurrence [27], particularly if surgery is being considered. Intracranial hemorrhage is a common complication of melanoma brain metastases and a major factor resulting in poor prognosis [28]. Intracranial hemorrhage should be noted in patients with neurological deficits.

The prognosis for patients presenting with distant recurrence of melanoma is poor, with a 5-year survival of 6.5% to 11% [29]. The median survival in patients with brain metastases is less than 1 year despite treatment [30]. The treatment has not been standardized till now, and surgical resection is the best treatment when the lesion is unique, accessible, and circumscribed. Immediate evacuation of the intracranial hematoma can be a life-saving procedure. Some surgeons have suggested that resections should be performed even in the progressive cases in which the metastases cause severe neurological symptoms [31]. Radiation therapy and stereotactic radiosurgery are feasible for patients in which the lesion is inaccessible or widespread [32]. Life expectancy does not exceed a few months owing to the progression of the systemic diseases. Novel targeted therapy (BRAF inhibitors) [33] and immunotherapy (anti-CTLA antibody) [34] have also shown favorable responses on survival and prognosis.

Conclusions

This report has presented a rare occurrence of a late cerebral metastasis at 16 years after the initial diagnosis of a primary cutaneous melanoma. More recent primary melanoma of the skin was not identified, which supports the need for long-term follow-up of patients with a history of primary cutaneous melanoma.