The Internet Journal of Pathology 2009 : Volume 9 Number 2

Malignant Melanoma of the Gall Bladder, A Case report and Literature Review.

Mowafak Hamodat MB,.CH,.B,. MSc,. FRCPC
Eastern Health of St.John’s. Health Sciences Centers. 300 Prince Philip Drive, Newfoundland, Canada Email address

Ahmed Alhumidi
King Khalid University Hospital, King Saud University, Saudi Arabia. MD

Citation: M. Hamodat & A. Alhumidi : Malignant Melanoma of the Gall Bladder, A Case report and Literature Review.. The Internet Journal of Pathology. 2009 Volume 9 Number 2


Abstract

Malignant melanoma is a highly unpredictable tumor, which can metastasize to any organ, including the gallbladder in 4–20% 1,2. Grossly and histologically, the distinction between primary and secondary lesions can be difficult to differentiate because they share many similar characteristics 2. Melanoma involving the biliary tree seldom causes relevant symptoms during life, and that is why few cases are reported in the literatures 2 and those documented in living patients are even fewer 3,5. Herein, we present a case of a 75-year-old female with metastatic melanoma to the gallbladder and a brief review of the literatures.


Case report

Our patient was a 75-year-old female who had a history of Clark's level IV malignant melanoma in her left forearm in 2001. In 2006, she had clinically palpable left axillary lymph nodes. She underwent right axillary dissection, and pathology confirmed multiple nodal metastases. Subsequently, she was followed with careful surveillance computed tomography (CT). In May, 2007, a suspicious 1.5 cm nodule in gallbladder was noticed. Due to paucity of symptoms and ambiguous radiological nature of this lesion, she was advised to follow with another surveillance CT scan in August 2007 which showed an increase in size to 2.5 cm (Fig 1) and she was advised to have cholecystectomy. Her complete blood count and liver function tests were within normal limits. The patient was taken to the operating room and underwent laparoscopic cholecystectomy.

Figure 1: computed tomography (CT) shows gallbladder nodule measures 2.5 cm
Figure 1: computed tomography (CT) shows gallbladder nodule measures 2.5 cm

Gross examination revealed 6 pieces of gallbladder tissue which showed dark firm serosal mass that measured 2 x 1.2 x 1 cm. Microscopic examination showed ulceration of the surface mucosa with an underlying spindle cell proliferation extending to the serosal surface (Fig 2-a). These cells had hyperchromatic nuclei, prominent nucleoli and showed frequent mitotic figures (Fig 2-b). The histological differential diagnosis included malignant gastrointestinal stromal tumor (GIST), Leiomyosacoma, malignant peripheral nerve sheath tumor, poorly differentiated carcinoma, and metstatic melanoma.

Figure 2-a: shows ulcerated surface mucosa with underling hypercellular spindle cell proliferation. (X4)
Figure 2-a: shows ulcerated surface mucosa with underling hypercellular spindle cell proliferation. (X4)

Figure 2-b: high power of the spindle cells shows hyperchromatic nuclei, prominent nucleoli, and brisk mitotic figures (X20).
Figure 2-b: high power of the spindle cells shows hyperchromatic nuclei, prominent nucleoli, and brisk mitotic figures (X20).

Immunohistochemistry showed that the neoplastic cells were diffusely positive for S100, melan-A, and CD117, focally positive for HMB45, and negative for CD34 (Fig 3 A-E). In conclusion, the histological features and immunohistochemical profile supported the diagnosis of metastatic melanoma of the gallbladder.

Figure 3 (A-E): Immunohistochemical study shows that the spindle cells are diffusely positive for S100 (A), Melan-A, (B), and C...
Figure 3 (A-E): Immunohistochemical study shows that the spindle cells are diffusely positive for S100 (A), Melan-A, (B), and CD117(C) , focally positive for HMB-45(D), and negative for CD34(E)





Discussion

In the gallbladder mucosa, some melanocytes are present because of the migration of melanin-producing cells from the neural crest during embryological development, and this warrants the possibility of the development of primary gallbladder melanoma 2, 4,5 ,. Both primary and metastatic melanoma of the gallbladder are extremely rare, indeed, only 20 cases of primary and over 60 cases of malignant melanoma (MM) metastatic to the gallbladder had been reported world wide 5, 6, 7,8,9 .

Melanoma metastatic to the gallbladder, although clinically rare, is the most common metastatic lesion involving this organ, and accounts for 30–60% of all gallbladder metastases 2, 10 . Gallbladder involvement has been found at autopsies in 15% of patients who died from disseminated melanoma 2, 11 . However, the clinical diagnosis is made only in less than 5% of patients 12 . The majority of primary melanoma metastasizing to the gallbladder arises in the skin, but the primary lesion may also be in the oral cavity, anorectal region, uveal tract or meninges 2 . Most patients with gallbladder metastasis have widespread diseases at the time of diagnosis 5 . Our patient had only axillary lymph nodes metastasis.

The distinction between primary and metastatic lesions can be difficult to differentiate in terms of the histopathological features alone 2,13,14,15,16,17,18, 19 . Although metastatic disease tends to present as multiple, flat and infiltrative lesions, single polypoid lesions can occur 18. Some authors found that β€˜junctional changes’ (intra-epithelial extension) in the mucosa overlying the tumor associated with primary gallbladder melanoma is an important finding and confirm the gallbladder origin of the neoplasm 14,16,20,21 . However, other authors have also found junctional activity in metastatic tumors 5, 8,18,19 . In fact, most investigators believe that melanoma in the biliary tree is almost always metastatic and the majority of cases described as primary are secondary to an unrecognized or regressed extrabiliary site 2,16,19,21,22 .

Clinically, these tumors are often pauci-symptomatic, as is shown by the discrepancy between the number of published cases and the rate of detection at autopsy 2,19,23 . The most common presentation for gallbladder melanoma is cholecystitis with or without cholelithiasis, likely due to obstruction of the cystic duct by the tumour mass 24,25,26 . Other reported symptoms and signs of gallbladder metastatic disease were weight loss, food intolerance, nausea, vomiting and diarrhea 5 . Our case was asymptomatic.

The diagnosis is often not suspected preoperatively, because of the extreme rarity of gallbladder melanoma cases. Non-invasive radiographic studies rarely can be of help in uncovering the presence of gallbladder disease. Moreover, differentiation from chronic acalculus cholecystitis may be impossible in the majority of cases 6 . Computed tomography (CT) or ultrasound may show focal thickening of the gallbladder wall or intraluminal masses 5, 27 . Computed tomography (CT) of our patient showed a well defined single nodule.

Because of the rarity of metastatic melanoma of the gallbladder, the optimal therapy is unclear. In many cases, the diagnosis is not made before surgery. Aggressive surgical therapy, including cholecystectomy, appears to prolong survival and improve the quality of life in many patients, even in the face of disseminated disease 19,28 . The treatment options in metastatic cases depend on the extension of the disease and on the clinical status of the patient. Although surgical management is often possible, complete excision of tumour metastases is feasible only in about one third of patients 5 . Nevertheless, surgical removal, even in the presence of disseminated disease, seems to be a worthwhile palliative procedure 19,26 .

The prognosis of primary and metastatic melanoma of the gallbladder is very poor. Only a few cases were alive at the time they were reported. Survival ranged from a few weeks to several years 5,6 . The mean survival times for patients with primary and metastatic lesions are 20.1 months and 8.4 months, respectively 5,6,7,8,16,17,22,28,30,31,32,33,34 .

In summary, melanoma metastatic to the gallbladder is usually asymptomatic. If symptomatic, it mimics cholecystitis. Moreover, gallbladder involvement is not uncommon at autopsy in patients who died from disseminated melanoma. So, we would recommend maintaining a high index of suspicion for metastases to the gallbladder and liberal use of abdominal ultrasound as an adjunct to CT for the evaluation of abdominal pain in these patients. Cholecystectomy is the treatment of choice for such lesions in the absence of widespread disease. Palliative surgical removal, even in the presence of disseminated disease, seems to be worthwhile.

References

1. Dasgupta T, Brasfield R. Metastatic melanoma. A clinicopathopathological study. Cancer 1964;17:1323–1339. (s)

2. Das Gupta T, Brasfield R, Paglia MA. Primary melanomas in unusual sites. Surg Gynecol Obstet 1969; 128:841–848. (s)

3. Backman H. Metastasis of malignant melanoma in the gastrointestinal tract. Geriatrics 1999; 211: 112–120. (s)

4. Caputy GG, Donohue JH, Goellner JR, Weaver AL. Metastatic melanoma of the gastrointestinal tract. Arch Surg 1991; 126:1353–1358. (s)

5. Dong XD, DeMatos P, Prieto VG, Seigler HF. Melanoma of the gallbladder. A review of cases seen at Duke University Medical Center. Cancer 1999; 85:32–39. (s)

6. Velez AF, Penetrante RB, Spellman JE Jr, Orozco A, Karakousis CP. Malignant melanoma of the gallbladder: report of a case and review of the literature. Am Surg 1995; 61: 1095–1098. (s)

7. Naguib SE, Aterman K. Presumed primary malignant melanoma of the gallbladder: report of a case and a review of literature. Am J Dermatopathol 1984; 6: 231–243. (s)

8. Heath DI, Womack C. Primary malignant melanoma of the gallbladder. J Clin Pathol 1988; 41: 1073–1077. (s)

9. Nelms JK, Patel JA, Atkinson DP, Raves JJ. Metastatic malignant melanoma of the gallbladder presenting as biliary colic: a case report and review of literature. Am Surg. 2007 Aug;73(8):833-5. (s)

10. Blecker D, Abraham S, Furth EE, Kochman ML. Melanoma in the gastrointestinal tract. Am J Gastroenterol 1999; 94:3427–3433. (s)

11. De la Monte SM, Moore GW, Hutchins GM. Patterned distribution of metastases from malignant melanoma in humans. Cancer Res 1983; 43:3427–3433. (s)

12. Reintgen DS, Thompson W, Garbutt J, Seigler HF. Radiologic, endoscopic and surgical consideration of melanoma metastatic to the gastrointestinal tract. Surgery 1984; 95:635–639. (s)

13. Vieting H, Hamdi G. Uber die physiologische und pathologische Melaninpigmentierung und den epithelialen Urcprung der Melanoblastome. Ein primares Melanoblastom der Gallenblase. Beitr Path Anat 1907; 42: 23–84. (s)

14. Walsh TS Jr. Primary melanoma of the gallbladder with cervical metastasis and fourteen and a half year survival. Cancer 1956; 9: 518–522. (s)

15. McFadden PM, Krementz ET, McKinnon WM, Pararo LL, Ryan RF. Metastatic melanoma of the gallbladder. Cancer 1979; 44: 1802–1808. (s)

16. Peison B, Rabin L. Malignant melanoma of the gallbladder: report of three cases and review of the literature. Cancer 1976; 37: 2448–2454. (s)

17. Carle G, Lessells AM, Best PV. Malignant melanoma of the gallbladder: a case report. Cancer 1981; 48: 2318–2322. (s)

18. Higgins CM, Strutton GM. Malignant melanoma of the gallbladder – does primary melanoma exist? Pathology 1995; 27: 312–314. (s)

19. Murphy MN, Lorimer SM, Glennon PE. Metastatic melanoma of the gallbladder: a case report and review of the literature. J Surg Oncol 1987; 34:68–72. (s)

20. Allen AC, Spitz S. Malignant melanoma: a clinicopathological analysis of the criteria for diagnosis and prognosis. Cancer 1953; 6:1–45. (s)

21. Sierra-Callejas JL, Warecka K. Primary malignant melanoma of the gallbladder. Virchows Arch A Pathol Anat Histopathol 1976; 370:233–238. (s)

22. Jones CH. Malignant melanoma of the gallbladder. J Pathol Bacteriol 1961; 81: 423–430. (s)

23. Goldin EG. Malignant melanoma metastatic to the gallbladder: case report and review of the literature. Am Surg 1990; 56: 369–373. (s)

24. Henriques CQ. A case of secondary melanoma of the gallbladder presenting as acute cholecystitis. Br J Surg 1955; 42: 663–665. (s)

25. Ostick DG, Haqqani MT. Obstructive cholecystitis due to metastatic melanoma. Postgrad Med J 1976; 52: 710–712. (s)

26. Bowdler DA, Leach RD. Metastatic intrabiliary melanoma. Clin Oncol 1982; 8: 251–255. (s)

27. Stutte H, Muller PH, d’Hoedt B, Stroebel W. Ultrasonographic diagnosis of melanoma metastases in liver, gallbladder, and spleen. J Ultrasound Med 1989;8(10):541–547. (s)

28. Cellerino P, Corsi F, Morandi E, Foschi D, Trabucchi E. Metastatic melanoma of the gallbladder. Eur J Surg Oncol 2000;26(8):815–816. (s)

29. Langley RGB, Bailey EM, Sober AJ. Acute cholecystitis from metastatic melanoma to the gallbladder in a patient with a low-risk melanoma. Br J Dermatol 1997; 136: 279–282. (s)

30. Guida M, Latorre A, Mastria A, De Lena M. Subcutaneous recombinant interleukin-2 plus chemotherapy with cisplatin and dacarbazine in metastatic melanoma. Eur J Cancer 1996; 32: 730–733. (s)

31. Hatanaka N, Miyata M, Kamiike W, Okumura K, Hashimoto T, Yamaguchi T, et al. Radical resection of primary malignant melanoma of the gallbladder with multiple metastases: report of a case. Surg Today 1993; 23: 1023–1026. (s)

32. Rosenthal SR. Primary melanocarcinoma of the gallbladder. Am J Cancer 1931; 15: 2288–2300. (s)

33. Hatae Y, Kikuchi M, Segawa M, Yonernitsu K. Malignant melanoma of the gallbladder. Pathol Res Pract 1978; 163: 281–287. (s)

34. Guida M, Cramarossa A, Gentile A, Benvestito S, De Fazio M, Sanbiasi D, Crucitta E, De Lena M. Metastatic malignant melanoma of the gallbladder: a case report and review of the literature. Melanoma Res. 2002 Dec;12(6):619-25. (s)

This article was last modified on Wed, 04 Nov 09 22:37:43 -0600

This page was generated on Fri, 19 Mar 10 20:52:02 -0500, and may be cached.