Pancreatic resection for metastatic melanoma

M Nikfarjam, 1,2
P Evans,1,2 and C Christophi1,2

Author information Copyright and License information

This article has been cited by other articles in PMC.

Abstract
Go to:

Introduction

Metastases to the pancreas occur from a variety of primary neoplasms. In most cases,
metastastic disease is widespread and pancreatic resection offers no potential survival
benefit 1,2. However, in certain situations metastases are confined to the pancreas, and
this may be the main determinant of long-term survival.

The most common sites of primary malignancy associated with isolated pancreatic
metastases are the kidney, lung, breast, colon and skin 3. Potential survival benefits of
pancreatic resection in selected patients, especially those with metastases from renal cell
carcinoma, are established 4,5. However, experience with pancreatic resection for
metastatic melanoma is limited and controversial.

Two patients with pancreatic metastases from ocular melanoma were treated by
pancreatic resection. The available literature is reviewed to determine the survival
benefits of pancreatic surgery for metastatic melanoma.

Go to:

Patients

Case No. 1

A 45-year-old woman presented with several months of abdominal discomfort. There

was no history of weight loss, change in bowel habit or excessive alcohol intake.
Twelve years previously, an ocular melanoma had been diagnosed and treated by
transcleral resection. Histology had revealed a 10-mm diameter mixed spindle and
epithelioid cell melanoma. Twelve months after therapy, there was local recurrence
requiring laser therapy. Laser treatment was required on two further occasions to
manage recurrences. The patient had been free of any detectable ocular disease for at
least 3 years before her recent presentation and on examination she appeared well.
There was no abdominal tenderness, masses, organomegaly or abnormal skin lesions.
Ocular examination showed no evidence of recurrent melanoma.

Computed tomography (CT) and magnetic resonance imaging (MRI) showed a non-
discrete mass in the head of the pancreas (Figure 1a). Three-to-four well-defined
nodules measuring 510 mm in diameter were clustered together in the right lobe of the
liver. Full blood examination, liver function tests, urea and electrolytes and serum
amylase were normal. Carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9
(CA 19.9) were not elevated. Fine-needle aspiration of a liver nodule revealed
melanoma. Positron emission tomography (PET) scans to assess the extent of disease
showed high uptake only in the region of the pancreatic head (Figure 1b).

Figure 1.
(a) MRI scan showing a mass in the head of the pancreas (arrow). PET scan showing
focal uptake in the region of the pancreatic head. (b) H&E section of the melanoma
demonstrating mixed spindle and epithelioid cell types with minimal melanin
production ...

At laparotomy, a non-pigmented mass measuring approximately 30 mm in maximum

diameter was noted on the superior aspect of the pancreas, involving the distal common
bile duct. Frozen section confirmed melanoma. Three tumours measuring 510 mm
diameter were identified in segment 5 of the liver by intra-operative ultrasound. A
pylorus-preserving pancreatoduodenectomy and segmental liver resection were
performed to resect all macroscopic disease. Histopathology of the resected specimens
revealed a mixed spindle cell and epithelial cell melanoma, with positive staining for S-
100 and Melan A (Figure 1c and d). All resection margins were clear of tumour and
there was no lymph node involvement. The excised metastases had the same
morphological features as the previously treated ocular melanoma. The patient made a
complete recovery and was without evidence of disease 6 months postoperatively.

Case No. 2

A 55-year-old-man presented with 2 weeks of mild epigastric pain, without associated

weight loss or change in bowel habit. He was a non-smoker, with a 25-year history of
moderate alcohol intake (30 g/day). Enucleation of one eye for an ocular melanoma had
been performed 13 years previously, identifying a 12-mm diameter spindle cell
melanoma extending to the optic nerve. Physical examination revealed no abdominal
masses, lymphadenopathy or skin lesions.

CT of the abdomen showed an ill-defined mass in the head of the pancreas (Figure 2a).
The possibility of a malignant tumour arising from the duodenum could not be
excluded, and an upper gastrointestinal endoscopy was performed. Complete
visualisation of the duodenum showed no evidence of malignancy. Further
investigations to identify the nature of the mass included percutaneous fine-needle
aspiration, which was inconclusive. All blood tests including CEA and CA 19.9 were
normal. A CT scan of the thorax and brain, as well as whole-body PET scan were
performed to exclude the possibility of disease elsewhere. PET scan showed increased
uptake only in the region of the pancreatic head (Figure 2b). CT scans of the thorax and
brain were normal.

Figure 2.
(a) CT scan of the abdomen identifying an ill-defined mass in the pancreatic head
(arrow). (b) PET scan demonstrating significant uptake in the region of the pancreatic
head. (c) Resected pancreas and duodenum with multiple foci of highly pigmented
melanoma ...

At operation multiple pigmented lesions were noted in the pancreatic head,

predominantly in the uncinate process (Figure 2c). Isolated lesions measuring
approximately 5 mm in diameter were also identified in the pancreatic body and tail.
There was no suggestion of malignant disease elsewhere in the abdomen. A total
pancreatectomy was performed, with histology revealing metastatic spindle cell
melanoma confined to the pancreas, without lymph node involvement (Figure 2d). The
patient made an uncomplicated recovery. There was no evidence of recurrence 7 months
post-operatively.

Go to:

Discussion

The pancreas is frequently involved in metastatic disease. The incidence ranges from
3% to 10% in reported autopsy series 1,2. In most cases, pancreatic involvement is an
incidental finding in a patient with widespread metastatic disease. Isolated metastases to
the pancreas are rare. However, in patients with a previous history of malignancy, an
identified pancreatic mass is due to a secondary deposit in about 40% of cases 6. In all,
approximately 1% of pancreatic resections are performed for metastases 5.

The pancreas is a favoured site for isolated metastases from renal cell carcinoma 4,7.
Pancreatic resection for these patients may improve survival and may be curative 4,7.
However, the benefits of pancreatic surgery in patients with melanoma and other
primary malignancy are less certain. Pancreatic involvement with melanoma occurs in
approximately 50% of cases in which there is disseminated disease 8. Isolated pancreatic
metastases from melanoma are rare. They occur in no more than 2% of patients with
visceral metastases and originate disproportionately from primary ocular
melanoma 9,10,11.

It is generally accepted that specific clinical and pathological factors influence survival
in patients with primary melanoma. These include tumour depth, ulceration, histological
subtype, anatomical site and lymph node involvement 12. However, the prognostic
factors that determine survival for patients with metastases to the pancreas are
undetermined. The only factor that appears to be associated with improved survival is a
long disease-free interval after the treatment of primary malignancy 4,5,8,13. This
phenomenon is thought to reflect favourable tumour biology with a slow growth pattern
and the relative rarity of lymph node involvement 5.

The survival outcome of patients with visceral metastases from melanoma is dismal
regardless of histopatholgical features, with a median survival of 612 months 14,15,16.
The results of chemotherapy are generally disappointing, despite the development of
newer and more effective combination therapies. The overall response rates to
chemotherapy vary between 15% and 28%, and long-term remissions are reported in
<2% of treated cases 17,18. Presently, surgical resection appears to be the only potentially
curative treatment option. The exact role of operation in patients with melanoma
metastases is still undefined, however, particularly when more than one organ is
involved or in situations in which complete tumour resection is not possible.

The survival outcomes of patients undergoing complete surgical resection for isolated
pancreatic melanoma metastases are generally better than those managed by non-
surgical modalities4,5,10,14,16,19,20,21,22,23,24,25,26. In a series reported by Wood and colleagues 16,
six patients with isolated metastases to the pancreas were treated by complete surgical
resection. The median survival in this group was 24 months, and the 5-year survival was
50%. In all, 30 patients in this series had complete resection of isolated melanoma
metastases to the liver, adrenal, pancreas or spleen, with a 5-year survival of 23%. In the
same series, the 5-year survival of 778 patients with non-operative management of
visceral melanoma metastases was only 9%. Several other melanoma series support the
finding of improved survival in patients with complete resection of isolated pancreatic
metastases 15,24.

The value of operative treatment in patients with melanoma and multiple metastases
involving a single organ or more than one visceral site is far less convincing. There are
a few reports of long-term survival after resection of multiple metastases from
melanoma 15,16,26,27,28. Salmon and associates 29 reported on surgical resection for
melanoma combined with chemotherapy in 18 patients with multiple liver metastases
(mostly bilobar) and one patient with an isolated liver secondary. The overall median
survival was 22 months, which was significantly better than that quoted for historical
controls. In a series of 14 patients with melanoma involving more than one abdominal
viscus, the median survival was 27.5 months and 5-year survival was 25% 16. However,
there are no specific reports of survival outcomes for patients with metastatic melanoma
treated by combined pancreatic and liver resection; combined bowel and solid organ
resection is far more common 15.

Surgical resection is considered incomplete if resection margins contain malignancy or

when not all metastases are treated surgically. Wood's series 16 included two patients
with metastatic melanoma to the pancreas that had incomplete resection, with a median
survival of 8 months; this figure was no better than the survival of untreated patients.
The situation was similar in those with incomplete resection of liver or adrenal
metastases. Incomplete surgical resection appears to have no survival benefit.

Some authorities consider the ability to achieve complete tumour clearance as more
important than the number of detectable metastatic lesions 16,29. This policy makes the
identification of all distal disease extremely important. In patients with metastatic
melanoma being considered for surgical intervention, PET scanning appears to be a
particularly useful assessment tool 30. PET has a higher sensitivity and specificity than
conventional imaging for detecting metastatic melanoma in all regions of body except
the thorax 30,31. In a study by Rinne and co-workers 31, PET was able to detect abdominal
metastases in all known cases (25 of 25), compared with a 32% sensitivity (8 of 25)
with conventional imaging. However, the sensitivity of PET is lower for tumours <1
cm, because of limitations of scanner resolution. In addition, detailed anatomical
localisation of metastatic disease usually requires conventional imaging. Therefore, PET
and conventional scanning should be considered complementary imaging modalities.

Currently there is no satisfactory non-surgical treatment for metastatic melanoma.

Surgical resection of metastases to the pancreas after thorough assessment for occult
distal disease can provide long-term survival. However, all metastatic disease needs to
be excised if operation is to offer any survival benefit.

Go to:

References
1. Willis RA. Butterworth; London: 1973. The Spread of Tumors in the Human
Body3rd edn; pp. 21617.

2. Cubilla AL, Fitzgerald PJ. Moosa AR. Willimans & Wilkins; Baltimore: 1980.
Surgical pathology of tumors of the exocrine pancreas, Tumors of the Pancreas; pp.
15963.

3. Z'Graggen K, , Fernandez-del Castillo C, , Rattner DW, , Sigala H, , Warshaw

AL.. Metastases to the pancreas and their surgical extirpation. Arch Surg 1998
;133:41317; discussion 41819. [PubMed]

4. Hiotis SP, Klimstra DS, Conlon KC, Brennan MF. Results after pancreatic resection
for metastatic lesions.Ann Surg Oncol. 2002;9:6759. [PubMed]

5. Harrison LE, Merchant N, Cohen AM, Brennan MF. Pancreaticoduodenectomy for

nonperiampullary primary tumors. Am J Surg. 1997;174:3935. [PubMed]

6. Roland CF, van Heerden JA. Nonpancreatic primary tumors with metastasis to the
pancreas. Surg Gynecol Obstet. 1989;168:3457. [PubMed]
7. Hirota T, Tomida T, Iwasa M, Takahashi K, Kaneda M, Tamaki H. Solitary
pancreatic metastasis occurring eight years after nephrectomy for renal cell carcinoma.
A case report and surgical review. Int J Pancreatol. 1996;19:14553. [PubMed]

8. Das Gupta TK, Brasfield RD. Metastatic melanoma of the gastrointestinal tract. Arch
Surg. 1964;88:96973. [PubMed]

9. Assessment of metastatic disease status at death in 435 patients with large choroidal
melanoma in the Collaborative Ocular Melanoma Study (COMS): COMS report no.
15. Arch Ophthalmol 2001 ;119:6706.[PubMed]

10. Brodish RJ, McFadden DW. The pancreas as the solitary site of metastasis from
melanoma. Pancreas.1993;8:2768. [PubMed]

11. Patel JK, Didolkar MS, Pickren JW, Moore RH. Metastatic pattern of malignant
melanoma. A study of 216 autopsy cases. Am J Surg. 1978;135:80710. [PubMed]

12. Ahmed I. Malignant melanoma: prognostic indicators. Mayo Clin

Proc. 1997;72:35661. [PubMed]

13. Le Borgne J, Partensky C, Glemain P, Dupas B, de Kerviller B.

Pancreaticoduodenectomy for metastatic ampullary and pancreatic
tumors. Hepatogastroenterology. 2000;47:5404. [PubMed]

14. Sharpless SM, Das Gupta TK. Surgery for metastatic melanoma. Semin Surg
Oncol. 1998;14:31118.[PubMed]

15. Overett TK, Shiu MH. Surgical treatment of distant metastatic melanoma.
Indications and results. Cancer.1985;56:122230. [PubMed]

16. Wood TF, DiFronzo LA, Rose DM, et al. Does complete resection of melanoma
metastatic to solid intra-abdominal organs improve survival? Ann Surg
Oncol. 2001;8:65862. [PubMed]

17. Crosby T, , Fish R, , Coles B, , Mason MD.. Systemic treatments for metastatic
cutaneous melanoma. Cochrane Database Syst Rev2000 :CD001215.

18. Woll E, Bedikian A, Legha SS. Uveal melanoma: natural history and treatment
options for metastatic disease. Melanoma Res. 1999;9:57581. [PubMed]

19. England MD, Sarr MG. Metastatic melanoma: an unusual cause of obstructive
jaundice. Surgery.1990;107:5956. [PubMed]

20. Rutter JE, De Graaf PW, Kooyman CD, Van Leeuwen MS, Obertop H. Malignant
melanoma of the pancreas: primary tumour or unknown primary? Eur J
Surg. 1994;160:1920. [PubMed]
21. Pingpank JF, Jr, , Hoffman JP, , Sigurdson ER, , Ross E, , Sasson AR, , Eisenberg
BL.. Pancreatic resection for locally advanced primary and metastatic nonpancreatic
neoplasms. Am Surg 2002 ;68:33740; discussion 3401. [PubMed]

22. Cunningham JD, Cirincione E, Ryan A, Canin-Endres J, Brower S. Indications for

surgical resection of metastatic ocular melanoma. A case report and review of the
literature. Int J Pancreatol. 1998;24:4953.[PubMed]

23. Bianca A, Carboni N, Di Carlo V, et al. Pancreatic malignant melanoma with occult
primary lesion. A case report. Pathologica. 1992;84:5317. [PubMed]

24. Wong JH, Skinner KA, Kim KA, Foshag LJ, Morton DL. The role of surgery in the
treatment of nonregionally recurrent melanoma. Surgery. 1993;113:38994. [PubMed]

25. Histopathologic characteristics of uveal melanomas in eyes enucleated from the

Collaborative Ocular Melanoma Study. COMS report no. 6. Am J Ophthalmol 1998
;125:74566. [PubMed]

26. Meyer T, Merkel S, Goehl J, Hohenberger W. Surgical therapy for distant

metastases of malignant melanoma. Cancer. 2000;89:198391. [PubMed]

27. Fletcher WS, Pommier RF, Lum S, Wilmarth TJ. Surgical treatment of metastatic
melanoma. Am J Surg.1998;175:41317. [PubMed]

28. Agrawal S, Yao TJ, Coit DG. Surgery for melanoma metastatic to the
gastrointestinal tract. Ann Surg Oncol. 1999;6:33644. [PubMed]

29. Salmon RJ, Levy C, Plancher C, et al. Treatment of liver metastases from uveal
melanoma by combined surgery-chemotherapy. Eur J Surg Oncol. 1998;24:127
30. [PubMed]

30. Prichard RS, Hill AD, Skehan SJ, O'Higgins NJ. Positron emission tomography for
staging and management of malignant melanoma. Br J Surg. 2002;89:389
96. [PubMed]

31. Rinne D, Baum RP, Hor G, Kaufmann R. Primary staging and follow-up of high
risk melanoma patients with whole-body 18F-fluorodeoxyglucose positron emission
tomography: results of a prospective study of 100 patients. Cancer. 1998;82:1664
71. [PubMed]