Larsen, Anne K. MD*; Krag, Christen PhD*; Geertsen, Poul PhD†; Jakobsen, Linda P. PhD*
From the *Department of Plastic Surgery, Herlev Hospital, University of Copenhagen, Herlev, Denmark; and †Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Received for publication September 24, 2013; accepted September 27,2013.
Disclosure: The authors have no financial interest to declare in relation to the content of this article. The Article Processing Charge was paid for by the authors.
Anne K. Larsen, Department of Plastic Surgery, Herlev Hospital, University Hospital of Copenhagen, Herlev Ringvej 75, Herlev 2730, Denmark, E-mail: email@example.com
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Malignant melanoma rarely metastasizes to the pancreas with isolated metastases. The literature on isolated metastatic melanoma to the pancreas is limited. There is no consensus on the management of isolated pancreatic melanoma metastasis.1–3
Metastatic tumors to the pancreas represent about 2% of all pancreatic malignancies. It is common that renal, breast, lung, and colon cancers metastasize to the pancreas, but less common is malignant melanoma. The malignant melanoma pancreatic metastases occur as either one manifestation in widespread disease or even more rare as an isolated metastasis.1,3,4
Commonly the appearance of distant metastases in melanoma patients is associated with a poor prognosis. Nikfarjam et al reports a study showing that 6 patients with isolated metastases to pancreas achieved a median survival of 24 months and 5-year survival of 50% after complete surgical resection.5
We report a unique case of isolated pancreatic metastatic malignant melanoma in a patient with history of cutaneous malignant melanoma. The isolated metastasis was surgical resected, and the patient is still alive with no sign of recurrence 22 years later.
A 32-year-old female was treated for a nodular cutaneous malignant melanoma (Clark level III, Breslow thickness 1.57 mm) on her upper back in 1988. The melanoma was excised in total 5.5 cm margin and in depth to the muscle fascia according to guidelines at that time. The skin defect was reconstructed with a split skin graft (Fig. 1).
In 1991, the patient developed upper abdominal pain, itching, and jaundice. An abdominal computed tomography (CT) scan and a transabdominal ultrasonography-assisted biopsy from the pancreas revealed a large malignant melanoma metastasis (5 cm in greatest dimension) localized in the head of the pancreas (Fig. 2). The patient received 3 cycles of systemic treatment with interleukin-2 and interferon-α over a period of 3 months. A CT scan after the first period of systemic treatment 1 month later showed regression of the tumor (Fig. 3). The systemic treatment was followed by 40 Gy radiotherapy (8 fractions of 5 Gy) resulting in complete remission 4 months later verified by a CT scan. Unfortunately, this last CT scan is not available, and only the description in the medical file is available.
In 1993, the 37-year-old patient developed upper abdominal pain and itching again. A CT scan of the abdomen showed recurrence of the tumor in the head of the pancreas. The pancreatic metastasis was radically resected by a pancreaticoduodenectomy (PD) ad modem Whipple. The final pathology was consistent with metastatic malignant melanoma, and the surgical margins and lymph nodes were negative. The postoperative stay was uneventful, and the patient was discharged 2 weeks later.
The patient was followed until December 2000 where the final CT scan was without malignancy.
The patient returned in 2011 with a melanoma on her left arm. A biopsy revealed a malignant melanoma (Clark level IV, Breslow thickness 2.34 mm). The melanoma was excised in 2-cm distance according to standard protocol, and the skin defect was closed directly. A sentinel node biopsy of a lymph node in the left axilla was negative. The 18-month follow-up was without sign of clinical recurrence, and in 2012, a transabdominal ultrasonography was normal. The patient declines further scans.
For this review, a PubMed search was undertaken with the keywords as referred. English written reports with isolated melanoma metastatic to the pancreas published between 1990 and 2012 were included.
The treatment of metastatic melanoma consists of surgery, chemotherapy, immunotherapy, and radiation, either in combination or individually. Patients with melanoma who have distant metastases have a median survival of less than 1 year.
Long-term survival of isolated malignant melanoma metastasis to the pancreas is rare according to the literature.6,8
Surgery, when possible, consists of a pancreatectomy procedure, dependent on the tumor location in the pancreas.
Systemic treatment options for patients with metastatic malignant melanoma have improved substantially the last decade. Immunotherapy with cytokines, such as interferon-α or interleukin-2, has demonstrated response rates of 10–15% in appropriately selected patients with metastatic malignant melanoma. Chemotherapy agents, such as Dacarbazine, Temozolomide, or Cisplatin, are some of the single agents showing response in the treatment of metastatic melanoma. The overall results of chemotherapy describe an overall response rate between 15% and 28%. The long-term remission rate is less than 2%.1,5–7
Ipilimumab has also shown effect on metastatic malignant melanoma. Hodi et al8 present a randomized, double-blind, phase 3 study in 403 patients with unresectable metastatic melanoma, showing an improved survival with Ipilimumab.
V-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor therapy, such as Dabrafenib, has shown response in BRAF (= v-raf murine sarcoma viral oncogene homolog B1) mutated metastatic melanoma patients. Hauschild et al12 present studies where BRAF inhibitor therapy has shown objective response rates of 70–80% in patients with metastatic melanoma, and as palliative therapy, the treatment seems to be valuable.
We report a case with a unique long-term survival after a pancreatic melanoma metastasis 22 years following a combination of immunotherapy, radiotherapy, and surgery. Studying the English literature, only 6 other cases with isolated malignant melanoma metastasis to the pancreas were identified (Fig. 1).
In the reviewed cases, the interval from primary malignant melanoma to pancreatic metastasis varied from 2.6 to 22 years, and the long-term survival from treatment to latest follow-up was 3–264 months with the present case (no. 7, Table 1) achieving by far the longest survival.
Of the 7 cases, 5 cases, the present case included, originated with cutaneous malignant melanoma and 2 as ocular malignant melanomas.
Our patient had the metastasis located in the head of the pancreas and received a PD, whereas the other 3 cases with metastasis location in the head of the pancreas received either a total pancreatectomy or a pylorus preserving PD (PPPD). In the 2 cases where the metastasis was located in the tail of the pancreas, the patients received a distal pancreatectomy (DP) and splenectomy. Eidt et al4 do not describe the location of the metastasis in the pancreas.
Based on the cases presented in Table 1, there is no obvious correlation between primary site of the melanoma, tumor location in the pancreas, the surgical treatment modality, and the long-term survival of the patient.
According to the literature, the PPPD procedure is growing increasingly popular compared with a traditional PD.13 In a PPPD, the pylorus and thus normal gastric emptying are preserved. It shows similar long-term survival as a PD (which is a PD and hemigastrectomy), but patients benefit from improved recovery of weight after a PPPD. Therefore, the PPPD is recommended when the tumor does not involve the stomach and when the lymph nodes along the gastric curvatures are not affected. When the tumor is located in the body or the tail of the pancreas, the surgical procedure should be a DP with splenectomy, as described in 2 cases reported by He et al10 and Portale et al.3,13
Our presented case received treatment with interleukin-2 and interferon-α and radiotherapy before surgery. Two cases (Eidt et al4 and He et al10) received adjuvant therapy and with a resulting relative long-term survival of 76 and 25 months. Unfortunately, no specific data concerning this adjuvant chemotherapy are presented in the articles. The 4 other cases did not receive any systemic treatment: 2 were reported dead after 3 and 14 months after treatment with PPPD, and 1 patient had a total pancreatectomy and was reported alive with no evidence of disease after 7 months. The last patient was treated with a DP and splenectomy and was alive with no evidence of disease 84 months after surgery. Furthermore, only our patient received radiotherapy. Radiotherapy for metastatic melanoma is generally associated with improved local and regional control rates without any survival benefit.11
The available material is too small to make any conclusions, but the reviewed cases may point to a role for systemic therapy in the treatment of isolated melanoma metastatic to the pancreas and maybe also for radiotherapy.
The current case shows that even after malignant melanoma metastasis to pancreas, long-term survival is possible.
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