Joseph DiNorcia III, Resident; Beth A. Schrope, Assistant Professor, Department of Surgery, Columbia University College of Physicians & Surgeons, New York, NY
Ocular melanoma is a rare neoplasm that can occur in any part of the eye. Medium and large tumors are treated by enucleation or radiation. Tumors can recur even after a prolonged disease-free period with metastases that characteristically involve the liver. Although far less common, ocular melanoma can metastasize to any organ, and a complete metastatic workup must be done when planning treatment. Localized metastatic disease should be resected if no distant disease is present. Systemic chemotherapy or immunotherapy alone is relatively ineffective, and surgical resection of solitary metastases remains the best treatment for improving pa?tient survival. The authors report a case of ocular melanoma metastatic to the duodenal papilla without liver involvement that was treated successfully with pancreaticoduodenectomy.
Joseph DiNorcia III, MD, MS
Beth A. Schrope, MD, PhD
Department of Surgery
Columbia University College of Physicians & Surgeons
New York, NY
Malignant melanomas arise from the transformation of normally nonproliferating melanocytes into highly invasive ones and can occur in any tissue where melanocytes reside.1 Uveal melanoma arises from melano?cytes of the uveal tract and is the most common primary intraocular malignancy in adults.2-4 Although uveal and cutaneous melanomas share a common progenitor cell, they behave quite differently, particularly in their patterns of metastases.2,3 Cutaneous melanoma metastasizes via the lymphatics to lymph nodes or via the bloodstream to any organ.2,3 Lymph nodes, followed by the lungs and liver, are the most common sites of spread, and other organs are usually found to have metastasis when liver involvement is discovered.2 In contrast, uveal melanoma metastasizes only hematogenously because the uveal tract lacks lymphatics.3 The liver is the most common site of spread, and, for most patients, it is the only organ in?volved when metastatic disease is found.2-4 Although the overall survival rate for patients with metastatic uveal melanoma is poor, several case reports highlight pro?longed survival after aggressive surgical resection of metastasis.2-4 This prolonged survival coupled with the decreasing morbidity and mortality of pancreatic resection makes pancreaticoduodenectomy the preferred treatment for me?tastatic disease involving the pancreas.5 We report a case of optic nerve melanoma metastatic to the duodenal papilla with no evidence of liver involvement. We successfully performed a pancreaticoduodenectomy without complications, and the patient was doing well at 4-month follow-up.
A 49-year-old woman presented with intermittent right upper quadrant pain, fevers, and jaundice, which had worsened during the previous 2 weeks. She also noted light-colored loose stools, dark urine, and nausea with nonbilious vomiting, which resulted in a 50-lb weight loss over 1 year. The patient was admitted for workup of obstructive jaundice.
The patient's history was significant for enucleation of her right eye for optic nerve melanoma 20 years earlier; me?l?anoma recurrence in the hard palate after the excision; chronic active hepatitis C, which persisted despite interferon therapy; intravenous drug abuse, which resulted in endocarditis and bilateral arm and leg cellulitis; depression; and gastroesophageal reflux disease. Her medications included furosemide, methadone, zolpidem, amitriptyline, lansoprazole, and metoclopramide. She had a 30-year history of smoking five cigarettes per day but reported no current alcohol or drug abuse.
On physical examination, the patient was afebrile with stable vital signs. She was a thin, jaundiced woman with multiple scars on her arms and legs. She had a right orbital prosthesis, and scleral and mucosal icterus were present. A 1-cm, pink papule with irregular borders was noted on her scalp. Her abdomen was soft, mildly distended with a fluid wave, and tender to deep palpation in the right upper quadrant, with a negative Murphy's sign. Hepatosplenomegaly was noted. The remainder of the physical examination was normal.
The results of laboratory tests taken on presentation were significant for abnormal liver function: total bilirubin, 8.6 mg/dL (normal, 0.2?1.3 mg/dL); direct bilirubin, 4.4 mg/dL (normal, 0.04?0.38 mg/dL); aspartate aminotransferase, 75 U/L (normal, 12?38 U/L); alanine aminotransferase, 141 U/L (normal, 7?41 U/L); and alkaline phosphatase, 296 U/L (normal, 33?96 U/L). A hepatitis panel was positive for the hepatitis C antibody.
A chest radiograph showed a right lower lobe nodule that was stable compared with a study taken when she had presented previously for pulmonary-related symptoms. An abdominal radiograph was within normal limits. Ab?do?min?al ultrasonography showed hep?ato?splenomegaly, dilatation of the intra- and extrahepatic biliary tree, and gallbladder dilatation with sludge. Com?puted tomography (CT) scans of the chest, abdomen, and pelvis showed the pulmonary nodule and revealed a mass in the head of the pancreas with pancreatic ductal dilatation (Figure 1). Endoscopic retrograde pancreatography found large, deep ulcers suspicious for tumor surrounding friable, nodular mucosa at the papilla. A cholangiogram revealed a 6-cm distal common bile duct stricture. Sphinc?ter?otomy and stent placement were performed, and multiple biopsies were taken.
When the results of the ampullary biopsies confirmed malignant melanoma, further staging workup was begun. Positron-emission tomography scanning showed avid disease in the ampullary region of the duodenum and a mild focus of activity in the right thigh. The patient's scalp lesion and lung nodule did not show activity. Magnetic resonance imaging delineated a subcutaneous lesion larger than 1 cm along the anterolateral portion of the right proximal thigh. No brain metastases or evidence of local recurrence of the ocular melanoma were detected. Dermatology performed biopsies of the scalp and thigh lesions. The scalp biopsy revealed excoriation, and the thigh biopsy revealed scar tissue, likely secondary to skin-popping.
A laparoscopy with core needle liver biopsy was performed for staging and to evaluate the degree of hepatitis Ccirrhosis for predicting perioperative morbidity and mortality. No peritoneal seeding or liver lesions were evident. Laparoscopic ultrasonography confirmed that there were no liver lesions and highlighted the dilated intrahepatic ducts. The core needle liver biopsies were consistent with mildly active chronic hepatitis C cirrhosis.
It was determined from the staging workup that the lesion was confined to the duodenum and the patient was a low-to-moderate operative risk. We opted to perform a pancreaticoduodenectomy be?cause prolonged survival has been well documented after aggressive resection of metastases. Final pathology from the uncomplicated Whipple procedure confirmed melanoma metastatic to the duodenal papilla with extensive, dense fibrotic reaction in the ampulla, distal common bile duct, and head of the pancreas (Figure 2). The patient had an uneventful recovery and was discharged from the hospital on postoperative day 14. At 10-month follow-up, the patient was as?ym?p?tomatic with no identifiable me?ta?static disease.
Ocular melanoma is the most common primary ocular malignancy in adults, and the eye is the most common noncutaneous site of melanoma.2-4 In general, how?ever, ocular melanoma is relatively un?common with a reported incidence be?tween 3,500 and 4,000 cases per year.4 It usually arises in the uveal tract but can occur anywhere in the eye.6 The disease is typically unilateral, affects men and women equally, and generally occurs be?tween the fifth to seventh decades of life.6 The overall 5-year survival rate for pa?tients with ocular melanoma is estimated to be be?tween 50% and 70%.4
Enucleation is the preferred treatment for medium and large ocular me?l?an?omas.7,8 It has been suggested that manipulation of the globe during surgery is responsible for the dissemination of malignant cells, but more recent research indicates that malignant cell migration is not caused by manipulation because it occurs early in the course of the disease.7,8 These early metastatic cells re?main dormant and may reactivate years after initial enucleation or other treatment, helping to explain ocular me?la?noma's characteristically unpredictable clinical course.7 Fulminant metastatic disease is known to occur after prolonged disease-free periods, with one report citing metastasis to the retroperitoneum 51 years after initial diagnosis and enucleation.8,9
Ultimately, 40% to 60% of patients with ocular melanoma develop metastases.4 The peak incidence of metastases from uveal melanoma ranges from 2 to 5 years after initial treatment, yet one third of metastases develop after 5 years.2 Up to 40% of patients have hepatic metastases at initial diagnosis.10 This high frequency of hepatic involvement with uveal melanoma contrasts with the much lower incidence found in patients with cutaneous melanoma.10 For those who develop metastatic disease, the liver becomes involved in as many as 98% of cases.4 Metastases occur much less commonly in other organs, with the lungs, lymph nodes, skin, and bones being the next most frequent sites.2
Our patient had no evidence of hepatic involvement despite the presence of significant metastatic disease in the duodenum. While metastatic spread of cutaneous melanoma to the duodenum and other parts of the gastrointestinal tract has been well documented, we found no reports of isolated ocular melanoma to the duodenum.1,6 A report by Cunningham and colleagues was the only one we found concerning a solitary ocular mel?anoma metastatic to the gallbladder with an enlarged lymph node invading the head of the pancreas.6 A successful pancreaticoduodenectomy was performed on the patient, and there was no evidence of recurrence 1 year later.
Patients with metastatic ocular mel?anoma generally have a poor prognosis. The median survival after a diagnosis of liver metastasis ranges from 2 to 7 months, and the 1-year survival rate is estimated to be 10%.4 We found no survival statistics for the rare patient with liver-sparing metastasis. Metastatic ocular melanoma localized to the liver has proven to be resistant to most available chemotherapy and immunotherapy regimens.4 Several retrospective series, however, indicate that surgical resection of metastatic disease is associated with long-term survival in a select group of patients. Aoyama and associates report on 12 patients who underwent surgical removal of metastatic uveal melanoma and had recurrence-free and overall survival periods of 19 and 27 months, respectively.2 Camp and colleagues also report that metastasectomy can improve the survival of patients with metastatic ocular melanoma, noting that patients with skin and soft tissue metastases, isolated distant metastases, and long disease-free intervals benefit the most from resection.3
While surgical resection remains the single best treatment for metastatic ocular melanoma, only 10% of patients have resectable metastatic disease.3 Most pa?tients have multiple, diffuse metastases that exclude the possibility of surgical intervention.2,4 Moreover, even after complete resection of all visible metastases, almost all patients have subclinical disease.3 Research into the molecular and cellular biology and genetics of ocular melanoma currently is under way to better understand the pathogenesis of its site-specific metastasis and to design more effective systemic therapies.7 Cyto?reductive surgery combined with systemic therapy may play a role in future treatment of patients with melanoma metastatic to multiple visceral sites.3
In our review of the literature, we did not find any reports of an isolated ocular melanoma metastatic to the duodenum that was resected by pancreaticoduode?nectomy. Based on our experience with this case, the absence of liver metastasis does not preclude the possibility of metastatic ocular melanoma in a patient with a history of the disease who presents with obstructive jaundice. Because metastatic ocular melanoma is resistant to most available chemo-, immuno-, and radiotherapies, even radical surgical treatment should be considered after an exhaustive search for diffuse metastatic disease. Several reports indicate that re?section of other metastatic lesions to the gastrointestinal tract can be performed with low operative mortality and prolonged survival, and the few reports of resection of ocular melanoma metastases also show prolonged survival. Occult metastatic disease likely exists elsewhere, and effective adjuvant therapies are needed to increase survival and help surgery achieve more than just palliation.
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