CASE REPORT Primary Gastric Melanoma: a Diagnostic Challenge Riti Aggarwal & Shashi Dhawan & Prem Chopra # Springer Science+Business Media New York 2013 Introduction Melanoma originates from melanocyte, a pigmented dendritic cell located in the basal layer of the epidermis, hair bulb, eyes, ears, and meninges. Cutaneous melanoma accounts for 91.2 % of all malignant melanoma (MM) cases. Of the non- cutaneous melanoma group, ocular melanoma accounts for 5.2 %, mucosal for 1.4 %, and melanoma of unknown origin for 2.2 % [1]. Within the mucosal subgroup, the most common gastrointestinal mucosal site to be involved is anorectum. In rare instances, esophagus, stomach, and small intestine may also be involved. Isolated cases of gastric melanoma have been documented in literature. These can be either primary or secondary. Most of the melanomas found in the stomach are metastases from cutaneous sources. Primary gastric melano- ma (PGM) is very rare [2–6]. Its diagnosis requires the con- cordance of clinical, morphological, histochemical, and immunophenotypic features. We present a case of PGM in a 74-year-old woman whose detailed clinical and laboratory workup failed to reveal primary site elsewhere. Case Report A 74-year-old woman presented to a tertiary care hospital with history of recurrent epigastric pain, weight loss, and severe hematemesis for 3 weeks. A hard non-tender epigastric mass was felt per abdomen. On gastroscopy, a large necrotic ulcer- ated mass was seen in the stomach. CT scan revealed marked diffuse irregular thickening of the gastric wall along with a large excavating ulcer, more along the lesser curvature. The mass was also adherent to the body of the pancreas and spleen (Fig. 1). The rest of the gastrointestinal tract (GIT) did not show any abnormality. Gastric biopsy showed sheets of highly pleomorphic tumor cells with prominent nucleoli and eosino- philic cytoplasm. Some of the cells were plasmacytoid (Fig. 2). To categorize the undifferentiated neoplasm, immu- nohistochemical markers were done. The tumor cells were negative for CK, LCA, MPO, CD138, and CD117, thereby ruling out the possibility of carcinoma, lymphoma, granulo- cytic sarcoma, plasmacytoma, and gastrointestinal stromal tumor, respectively. Subsequently, HMB-45 and S-100 were done and the tumor was strongly and diffusely positive for these (Fig. 3a, b). No melanin was appreciated on the biopsy. Based on morphology and immunohistochemistry, a diagno- sis of amelanotic gastric melanoma was made. The patient was then examined thoroughly for primary MM elsewhere. There was no primary lesion anywhere in the body and no Fig. 1 CT scan showing marked diffuse irregular thickening of the gastric wall along with a large excavating ulcer R. Aggarwal (*) : S. Dhawan : P. Chopra Department of Pathology, Sir Ganga Ram Hospital, New Delhi 110060, India e-mail: [email protected]P. Chopra e-mail: [email protected]J Gastrointest Canc DOI 10.1007/s12029-013-9530-6
Transcript
CASE REPORT
Primary Gastric Melanoma: a Diagnostic Challenge
Riti Aggarwal & Shashi Dhawan & Prem Chopra
# Springer Science+Business Media New York 2013
Introduction
Melanoma originates from melanocyte, a pigmented dendriticcell located in the basal layer of the epidermis, hair bulb, eyes,ears, and meninges. Cutaneous melanoma accounts for91.2 % of all malignant melanoma (MM) cases. Of the non-cutaneous melanoma group, ocular melanoma accounts for5.2 %, mucosal for 1.4 %, and melanoma of unknown originfor 2.2% [1].Within the mucosal subgroup, the most commongastrointestinal mucosal site to be involved is anorectum. Inrare instances, esophagus, stomach, and small intestine mayalso be involved. Isolated cases of gastric melanoma havebeen documented in literature. These can be either primaryor secondary. Most of the melanomas found in the stomach aremetastases from cutaneous sources. Primary gastric melano-ma (PGM) is very rare [2–6]. Its diagnosis requires the con-cordance of clinical, morphological, histochemical, andimmunophenotypic features. We present a case of PGM in a74-year-old woman whose detailed clinical and laboratoryworkup failed to reveal primary site elsewhere.
Case Report
A 74-year-old woman presented to a tertiary care hospital withhistory of recurrent epigastric pain, weight loss, and severehematemesis for 3 weeks. A hard non-tender epigastric masswas felt per abdomen. On gastroscopy, a large necrotic ulcer-ated mass was seen in the stomach. CT scan revealed markeddiffuse irregular thickening of the gastric wall along with a
large excavating ulcer, more along the lesser curvature. Themass was also adherent to the body of the pancreas and spleen(Fig. 1). The rest of the gastrointestinal tract (GIT) did notshow any abnormality. Gastric biopsy showed sheets of highlypleomorphic tumor cells with prominent nucleoli and eosino-philic cytoplasm. Some of the cells were plasmacytoid(Fig. 2). To categorize the undifferentiated neoplasm, immu-nohistochemical markers were done. The tumor cells werenegative for CK, LCA, MPO, CD138, and CD117, therebyruling out the possibility of carcinoma, lymphoma, granulo-cytic sarcoma, plasmacytoma, and gastrointestinal stromaltumor, respectively. Subsequently, HMB-45 and S-100 weredone and the tumor was strongly and diffusely positive forthese (Fig. 3a, b). No melanin was appreciated on the biopsy.Based on morphology and immunohistochemistry, a diagno-sis of amelanotic gastric melanoma was made. The patientwas then examined thoroughly for primary MM elsewhere.There was no primary lesion anywhere in the body and no
Fig. 1 CT scan showing marked diffuse irregular thickening of thegastric wall along with a large excavating ulcer
R. Aggarwal (*) : S. Dhawan : P. ChopraDepartment of Pathology, Sir Ganga Ram Hospital,New Delhi 110060, Indiae-mail: [email protected]
history of any concurrent or previously removed atypical lesionof the skin. A total gastrectomy was done and the gastricmucosa showed a black-pigmented fungating tumor (Fig. 4a).
Histologically, the tumor cells were infiltrating the full thick-ness of the gastric wall into the perigastric soft tissues, regionallymph nodes, and pancreas (Fig. 4b). The spleen was free oftumor. There was abundant intracytoplasmic melanin in somecells which stained dark blue by Masson Fontana stain, therebyconfirming the diagnosis of PGM. During the postoperativeperiod, the patient developed respiratory complications anddied after 12 days.
Discussion
Malignant melanomas account for 1–3 % of all malignanttumors of the GIT [7]. Most of the GI melanoma cases arefound at autopsy and only 1–4 % of patients are diagnosedantemortem. Commonly, these tumors are secondary lesionsrepresenting metastatic spread of a primary tumor. The mostcommon GI melanoma site to be involved primarily is theanorectum. Primary melanoma of the esophagus, small intes-tine, and colon has been mentioned in the literature [8–11].However, PGM is very uncommon and represents 0.5 % of allnon-cutaneous melanomas [12].
Fig. 2 Gastric biopsy revealing sheets of tumor cells having hyper-chromatic nuclei, large prominent nucleoli, and eosinophilic cytoplasm.(H&E, ×100; inset, ×400)
Fig. 4 a Total gastrectomyspecimen with diffusely ulceratedmucosa and thickened wall withblackish discoloration; b tumorcells with similar morphology asin Fig 2. Inset shows abundantmelanin pigment. (H&E, ×100;inset, ×400)
J Gastrointest Canc
The clinical manifestations of PGM are nonspecific andinclude anemia, weight loss, and upper GI bleed. Intestinalobstruction and perforation are less frequent findings. Thus, itis important for clinicians to consider the possibility of malig-nant melanoma in a case admitted with a gastric mass.
Preoperative diagnosis of PGM may be difficult. Endoscop-ically, the tumor may appear as ulcerated melanotic nodulesarising on normal rugae, submucosal masses with ulcerations,andmass lesions with necrosis andmelanosis [13]. Gastric ulcerswith no visible melanin pigment are difficult to diagnose endo-scopically. In present case, gastric biopsy was devoid of melaninpigment and was a diagnostic dilemma on conventional micros-copy. A high index of suspicion on histology along with appro-priate histochemical and immunohistochemical staining is ofutmost significance for a definite diagnosis of PGM.
Whenever a seemingly primary melanoma is detected in GIT,it is prudent to conduct a battery of tests that include thoroughhistory, physical examination, and investigations to consider thepossibility of metastasis. Considering the tendency of primarycutaneous melanoma to spontaneously regress, one cannot def-initely preclude the possibility of metastatic melanoma [14].Blecker et al. [15] proposed a criteria for a diagnosis of primarymelanoma in GIT: (1) absence of any primary lesion, (2) nohistory of removal of a melanoma or atypical melanocytic lesionfrom the skin or other organs, (3) absence of extraintestinalmetastatic spread of melanoma, and (4) presence of intramucosallesions in overlying or adjacent epithelium.
The pathogenesis of PGM is cloudy. Speculation still existsregarding the nature of this entity as normal stomach epithe-lium that lacks melanocytes. The concept of ectopic migrationof melanocyte precursors or neoplastic transformation of theamine precursor uptake and decarboxylation cells to melano-cytes has been proposed as a possible mechanism for thedevelopment of primary MM [16].
There is no formal recommendation on treatment protocolfor GI melanomas especially for PGMbecause of the very fewcase reports on this entity. Whenever possible, curative surgi-cal resection is done not only for palliation of symptoms butalso for improvement in survival. The role of chemotherapy,immunotherapy, radiation, vaccination, and other effectivetreatment options is being investigated [17].
To conclude, the present case report highlights that PGMmust be considered in the differential diagnosis of a poorlydifferentiated carcinoma in the stomach especially when rele-vant epithelial markers are negative and biopsy does not showany melanin pigment. Typical morphology comprising roundnuclei, prominent nucleoli with intranuclear pseudo-inclusion,and glassy cytoplasm warrant immunohistochemistry forHMB-45 and S-100. Despite the innocuous gastrointestinalsymptoms, the possibility of metastatic gastric melanomashould be kept in mind in any patient with a previously docu-mented melanoma. In fact, given no such history, it is necessary
to screen the patient thoroughly for any primary site. PGMs areaggressive tumors and associated with a poorer prognosis asalso exemplified in the present case. Early diagnosis is manda-tory to avoid delay in therapeutic intervention and thereby toprevent extensive dissemination. This case of PGM is presentedbecause of its rare site, absence of primary lesion elsewhere,and challenges in diagnosing it.
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