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Address for correspondence and reprint requests: Noraidah Masir, Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia,Jalan Yacob Latif, 56000 Cheras, Kuala Lumpur

Malaysian J Pathol 2003; 25(1) : 57 – 61

CASE REPORT

Malignant melanoma of the gastrointestinal tract presenting as ableeding gastric ulcer

M Noraidah MPath and *AY Jasmi FRCS

Departments of Pathology and *Surgery, Universiti Kebangsaan Malaysia, Kuala Lumpur

Abstract

Malignant melanoma involving the gastrointestinal tract is diagnosed antemortem in only a smallpercentage of patients with the disease. Presenting symptoms are often non-specific, causing adiagnostic problem. The vast majority of such melanomas are metastatic from a cutaneous primary,however there is evidence that the tumour can arise de novo in the gastrointestinal system. We reporta 74-year-old man with malignant melanoma with an unusual presentation simulating a symptomaticgastric ulcer. He presented with epigastric pain, haematemesis and melaena. Explorative laparotomyrevealed a large ulcerated tumour with several pigmented satellite nodules in the proximal stomach,multiple ileal nodules and widespread nodal and liver metastases. Proximal gastrectomy and limitedsmall bowel resection was performed. Histology revealed the tumour to be composed of nests ofepithelioid cells with melanin pigment. The tumour cells showed immunohistochemical positivityfor S100 protein and HMB45 antibodies. This report emphasizes that melanoma should be adiagnostic consideration in patients with gastric ulcer.

Key words: Gastrointestinal tract, melanoma, diagnosis

tumour has not been identified.8,9 We describehere a case of malignant melanoma to thegastrointestinal tract presenting as a bleedingulcer in the stomach, in the absence of a clinicallyobvious primary lesion elsewhere.

CASE REPORT

A 74-year-old man presented with a one weekhistory of epigastric pain, haematemesis andmelaena. He had no previous history of pepticulcer disease or chronic analgesic ingestion.Clinically he was very pale. The abdomen wassoft with mild tenderness in the epigastrium. TheHb was 5.1 gm/dL.

An upper gastrointestinal endoscopy revealeda large ulcer on the lesser curve of the stomachwith raised edges and blood clot on the ulcerfloor. There were three to four other nodulesadjacent to the ulcer. A biopsy was taken andhistologically an epithelioid stromal sarcomawas the primary diagnostic consideration. Adifferential diagnosis of metastatic melanomawas also considered.

Due to persistent melaena, a laparotomy wascarried out. A large lobulated mass with centralulceration was found in the proximal stomach

INTRODUCTION

Although the vast majority of gastrointestinaltract (GIT) melanoma is metastatic, primarymelanoma can also arise from the mucosalepithelial lining of the GIT.1 Preoperativediagnosis is often difficult due to non-specificsymptoms. Signs and symptoms may occur lateand these include nausea, vomiting, abdominalpain, weight loss and anaemia.2 Aggressivesurgical therapy has been shown to prolongsurvival and provide important symptomaticpalliation.3 Accurate diagnosis is thereforeimportant to decide on the most appropriatetherapy.

Primary malignant melanoma of the GIT isrecognised to occur in the anorectum4 and theoesophagus.5 Rare cases have been reported inthe small bowel6 and stomach.7 Pathologicallythe tumour grows as a submucosal lesion whichmay enlarge into a polypoidal mass and undergoulceration. The well recognized morphologicaldiversity of malignant melanomas may causediagnostic difficulties in differentiating it fromadenocarcinoma, gastrointestinal stromal tumours(GIST), hemangiopericytoma and lymphoma,particularly in biopsy specimens where a primary

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with several pigmented umbilicated satellitenodules. Multiple metastatic nodules were alsoseen in the ileum, root of the mesentery, parailiacnodes, paraaortic nodes and the liver. Proximalgastrectomy, splenectomy and limited smallbowel resection with end to end anastomosiswas performed. A thorough search for a primarylesion was unsuccessful.

Postoperatively recovery was uneventful. Thepatient was well on discharge but defaultedfollow-up.

Pathology

Gastric biopsyThe specimen, comprising of two mucosalfragments, showed proliferation of epithelioidcells arranged in nesting pattern, expanding thesubmucosa but sparring the overlying mucosa(Fig. 1). The cells were not pigmented anddisplayed large pleomorphic nuclei withprominent eosinophilic nucleoli (Fig. 2). Thecytoplasm was abundant and exhibitedcytoplasmic vacuolation. Mason Fontana staindid not reveal any melanin pigment and mucinstains were negative. Immunohistochemistryshowed weak cytoplasmic staining for vimentin.Staining for S100 protein which was performedmuch later was also positive. Cytokeratin,leucocyte common antigen, chromogranin anddesmin were negative. A diagnosis of epithelioidstromal sarcoma with a differential diagnosis ofmetastatic melanoma was made.

Stomach, ileum and spleenThe gastrectomy specimen revealed two largeulcerated polypoid tumour measuring 7 cm and4 cm respectively with six smaller pigmentedsatellite nodules. A segment of the ileummeasuring 7 cm long was received separatelyand revealed two ulcerated pigmented nodulesmeasuring 1.5cm and 1cm respectively.

Microscopically, sections from the stomachand ileum showed sheets of pleomorphicepithelioid cells expanding the submucosa,infiltrating the overlying surface mucosa andinvading the underlying muscular and serosallayers. In the smaller nodules, the tumour wasconfined mainly to the submucosa leaving thesurface mucosa intact. The malignant cells werepigmented, exhibited large vesicular nuclei withprominent nucleoli and abundant granulareosinophilic cytoplasm. Numerous mitoticfigures and a few multinucleated giant cellswere present. In the ileum, spindled malignantcells were seen adjacent to epithelioid areas. In-

situ change was not observed in the overlying oradjacent gastrointestinal epithelium. MasonFontana stain indicated intracytoplasmic melaninpigment. Immunohistochemical staining forS100 protein and HMB45 were positive.

The splenectomy specimen did not show anydiagnostic abnormality.

DISCUSSION

In this report we describe a case of malignantmelanoma of the stomach in a patient where athorough search for a primary lesion elsewhereproved futile. The case is of interest in severalrespects. It demonstrates that gastric melanomamay simulate a symptomatic gastric ulcerclinically and endoscopically. Preoperativediagnosis is often difficult and delayed. In thepresent case, the clinical and pathologicalevidence support a diagnosis of a primarymelanoma of the stomach. Lack of concurrent orprevious history of melanoma or atypicalmelanocytic lesion from the skin and thepresence of extensive involvement of thestomach, are important features which supportthe diagnosis. Microscopical examinationhowever failed to show in situ change in theoverlying or adjacent epithelium, an importantcriteria in the diagnosis of primary melanoma.This feature is reported in 40-100% of primaryGIT melanomas.10 Despite the presentingfeatures described above, the possibility of thetumour being metastatic cannot be totallyexcluded as metastatic melanoma may occur inthe absence of a clinically obvious primarylesion. The patient’s disease could have resultedfrom an undiscovered, spontaneously regressing,primary cutaneous lesion.

The initial gastric biopsy posed a diagnosticproblem and a definite histological diagnosiscould not be made. Clinically the lesion wasthought to be a primary tumour and epithelioidstromal sarcoma being more common thanprimary melanoma, was the preferred diagnosisat that time. It was supported by vimentinpositivity and cytokeratin negativity in theimmunohistochemical studies. Even though therewas positive staining for S-100 in the biopsy,the definitive diagnosis of melanoma was madefrom the resected specimen only 5 weeks later.The delay in diagnosis can be attributed toseveral reasons. Firstly, the possibility ofmalignant melanoma was not thought of, as it isa rare primary tumour of the stomach. Secondlyand more importantly, the tumour cells from thegastric biopsy were not pigmented and were

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FIG. 1: Arrow shows melanoma cells filling the gastric submucosa. The overlying mucosa isintact. H&E X40.

composed of epithelioid cells, without a spindlecell component. This closely resembled acarcinoma or an epithelioid GIST. The nestingpattern of the tumour cells and their polygonalshape also suggest the possibility of aneuroendocrine tumour. The morphologicalsimilarity between melanoma and other tumours

and the recruitment of immunohistochemicalmarkers are points of interest discussed here.

Like GIST, malignant melanoma may becomposed of proliferation of spindle-shaped cellsand epithelioid cells. The typical nuclear featuresof melanoma which include round nuclei withprominent nucleoli, glassy eosinophilic

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cytoplasm and the presence of intranuclearpseudoinclusions, are diagnostically helpful butmay be absent. The diagnosis of melanoma ismade easy when intracellular melanin can beidentified. Fifty to 70% of mucosal lesions arepigmented leaving others amelanotic.11 In thepresent case, the biopsy was not pigmented andMason Fontana conventionally used todemonstrate melanin was negative. Based onmorphology, besides epithelioid stromalsarcoma, other lesions considered in thedifferential diagnosis include poorlydifferentiated carcinoma, small cell carcinomaand lymphoma. In a review of 335 malignantmelanomas by Nakleh8 to identify the variantmorphologic patterns, unusual histologicalfeatures were found in 27 amelanotic neoplasms.These included adenoid and pseudopapillarypattern, small cell neoplasms,hemangiopericytoma-like tumours, tumours withprominent myxoid stroma and tumours withsignet-ring cell configuration.

Differentiation from other diagnoses dependson positive immunohistochemical staining forS-100, HMB-45 and Melan A/Mart1. In general,melanomas react strongly with S-100 and is

FIG. 2: The malignant cells are polygonal and display pleomorphic and hyperchromatic nuclei with vacuolatedcytoplasm. H&E X200

widely used in the immunoprofile screen tosupport a diagnosis of melanoma. However ithas been reported to be negative in signet-ringcell melanoma12 and small cell melanoma.13 Anadditional marker is recommended in conjunctionwith S-100 protein when confirming themorphological diagnosis. In a study of 56 casesof melanoma, Duray9 found that monoclonalHMB-45 reacted with over 90% of all tumours.It appears specific for melanoma cells, with nocross reactivity with nonmelanocytic malignanttumours, unlike polyclonal anti S-100 protein.Melan-A/Mart 1 is a recently identified newmelanocytic differentiation marker. It has beenfound to be more sensitive than HMB-45especially in metastatic tumours.14 The antibodywas not used in this case as it was not availablein our laboratory. Some melanomas may exhibitan aberrant immunophenotype and may expresscytokeratin15 and also some melanomas arenegative for HMB-45 by immunoperoxidase.12

In these cases, it has been recommended that apanel of antibodies with more than one markerin each category should be used for identifyingmelanosomes.

It can be concluded that malignant melanoma

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should be included in the differential diagnosisof a gastric ulcer even though a history of aprimary tumour is not elucidated. Ancillarystudies designed to detect melanocyticdifferentiation are important in such a tumourwith diverse histological guise.

REFERENCES

1. Schuchter L, Green R, Fraker D. Primary andmetastatic diseases in malignant melanoma of thegastrointestinal tract. Curr Opin Oncol 2000;12:181-5.

2. Blecker D, Abraham S, Furth E, Kochman M.Melanoma in the gastrointestinal tract. Am JGastroenterol 1999: 94 3427-33.

3. Gallino G, Belli F, Bonfati G, et al. Surgicaltreatment of gastric metastases from cutaneousmelanoma: experience of the National CancerInstitute of Milan. Tumori 2001;87:229-31.

4. Cheong WK, Teh LB, Ho J, et al. Case report -melanoma of the anorectum. Singapore Med J1992;33:411-2.

5. Chalkiadis MD, Wihlm JM, Morand G, et al.Primary malignant melanoma of the esophagus.Ann Thoracic Surg 1985;39:473-5.

6. Kaldivar TF, Vanek VW, Krishnan EU. Primarymalignant melanoma of the small bowel: A casestudy. Am Surg 1992;58:418-21.

7. Macak J. Melanoma of the stomach: reality orfiction? Pathologica 1998;90:388-90.

8. Nakleh RE, Wick MR, Rocamora A, Swanson PE,Dehner LP. Morphologic diversity in malignantmelanomas. Am J Clin Pathol 1990; 93:731-40.

9. Duray PH, Palazzo J, Gown AM, Ohuchi N.Melanoma cell heterogeneity. Cancer 1998;61:2460-8.

10. Christova S, Meinhard K, Mihailov L, et al. Threecases of primary malignant melanoma of thealimentary tract. Gen Diagnostic Pathol1996;142:63-7.

11. Batsakis JG, Regezi JA, Solomen AR, Rice DH.The pathology of the head and neck: mucosalmelanomas. Head and Neck Surg 1982;4:404-18.

12. Gatter KC, Rafkiaer E, Skinner J, Brown D, HeryetA, Pulford KA, Hou-Jensen K, Mason DY. Animmunohistochemical study of malignant melanomaand its differential diagnosis from other malignanttumours. J Clin Pathol 1985;38:1353-7.

13. Attanoos R, Griffith DFR. Metastatic small cellmelanoma to the stomach mimicking primary gastriclymphoma. Histopathology 1992;21:173-5.

14. Busam KJ, Jungbluth AA. Melan-A, a newmelanocytic differentiation marker. Adv Anat Pathol1999;6:12-8.

15. Banarjee SS, Harris M. Morphological andimmunophenotypic variations in malignantmelanoma. Histopathology 2000;36:387-402.