|Year : 2014 | Volume
| Issue : 3 | Page : 733-736
Metastatic malignant melanoma affecting stomach
Jamal Eivazi-Ziaei1, Heidarali Esmaili2
1 Department of Internal Medicine and Pathology, Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2 Department of Pathology, Tabriz University of Medical Sciences, Tabriz, Iran
|Date of Web Publication||14-Oct-2014|
Prof. Jamal Eivazi-Ziaei
Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz
Source of Support: None, Conflict of Interest: None
Malignant melanoma has been reported to affect all organs of the human body with the metastasis. Stomach metastases are quite rare in cases of the most commonly reported primaries including, melanoma and breast, and lung carcinomas. This report involves, a 56-year-old man suffering from melanoma of the lower extremity that developed into gastric, pulmonary, and brain metastases. The patient who experienced epigastric pain with suspicious melanoma was referred to undergo endoscopy. A black and white ulcer with dimensions of 1 × 1.5 cm and a mass of 1 × 2 cm mass were found at D1 and lesser curvature. Physical examination revealed a 2 × 3 cm black lesion at his right heel. Pathologic examination provided multiple pieces of creamy soft-tissue measuring 0.3 × 0.2 × 0.1 cm showing pigmented tumor cells in lamina propria. Staining biopsy samples with anti-HMB-45 and Fontana demonstrated a higher degree of positivity in tumor cells. The patient was admitted to the hospital, but unfortunately his general conditions were deteriorated and he developed convulsion and deceased four days after admission.
Keywords: Melanoma, metastasis, stomach
|How to cite this article:|
Eivazi-Ziaei J, Esmaili H. Metastatic malignant melanoma affecting stomach. J Can Res Ther 2014;10:733-6
| > Introduction|| |
Malignant melanoma has been known capable of inducing metastasis in most of the human organs. While it is commonly seen in metastasizing gastrointestinal tract (GIT), a melanoma detected in the gastric mucosa is an uncommon tumor. Utilizing radiological and endoscopic methods, gastrointestinal (GI) metastases are seldom diagnosed before death.GI metastases could be seen in different morphological shapes; hence, immunohistochemistry is valuable in differentiating malignant melanoma from other malignancies.  Melanoma could arise at any part of the digestive tract, where most of those lesions are naturally metastatic. When regression occurred, the primary lesions may be discrete.
Individuals suffering with end stage of melanoma, gastric metastases and small bowel metastases are commonly observed.  In two large series of studies involving autopsy, gastric metastases and small bowel metastases were reported in about 20% and 35.6-58% of the patients respectively. ,
Distinguishing metastasis between a primary GI lesion and an occult cutaneous melanoma may be challenging in cases of solitary GI localization. 
Here, we are reporting a case of melanoma at the lower extremity, which was developed to gastric, pulmonary and brain metastases.
| > Case Report|| |
The patient was a 56-year-old male with a previous history of melanoma at right heel since 2 years ago, which had undergone to lesion resection with no radiation or chemotherapy. He suffered from epigastric pain with suspicious melanoma when was referred to endoscopy. A 1 × 1.5 cm white and black colored ulcer and 1 × 2 cm mass was found at D1 and lesser curvature. Physical examination provided a 2 × 3 cm black colored lesion in right heel [Figure 1]. No adenopathy in inguinal or axillary regions was seen. Examinations of lungs and heart, and abdominal region were shown to be normal. Laboratory findings were: ESR: 61/69, creatinine: 1.1 mg, uric acid: 4.3 mg, CRP: +++, WBC: 9390/um 3 , Hb: 14.6 g/dl, Plt: 375000/um 3 , CXR: multiple nodules in both lung fields, brain Computed tomography scan: Multiple hypodense lesions in the right and left frontal and left parietal regions along with massive edema and mass effect. Pathologic examination revealed multiple pieces of creamy soft tissue measuring 0.3 × 0.2 × 0.1 cm, which showed pigmented tumoral cells in lamina propria [Figure 2]. Staining with anti-HMB-45 and Fontana showed strong positivity in tumoral cells [Figure 3] and [Figure 4]. The patient was admitted to the hospital, but unfortunately his general conditions deteriorated and he developed convulsion. Endoscopic examination for getting figures was not possible. He passed away 4 days after admission. Informed consent was obtained from the Partner. Of the patient for publication of this case report and any accompanying images.
|Figure 2: Gastric mucosa with pigmented tumoral cells in deep lamina propria (H and E)|
Click here to view
| > Discussion|| |
Metastasis of malignant melanoma has been shown to different organs of the human body with a rare incidence involving GIT. Invasion of GIT is often associated with other visceral organs. Melanoma is a great mimicker of other neoplastic circumstances and could cause a major diagnostic hurdle while presented at an intra-abdominal location. The small bowel and stomach are the most common sites to be affected respectively. 
Gastric cancer occurred as secondary metastasis is a rare clinical event and a challenging problem in respect with diagnosis, prognosis and treatment. Diagnosing such metastases in affecting the stomach without autopsy data is rarely occurred. Utilizing esophagogastroduodenoscopy in detecting such lesions has improved the overall survival of these patients. Although, the patient in this report had upper GI symptoms, the frequently asymptomatic character of GI melanoma explains why it largely eludes detection. Other symptoms may include abdominal pain and anorexia. 
It is necessary not to neglect the possibility of metastatic malignancies in the differential diagnosis of the patient affected by gastric lesion. 
Due to presentation of metastases to the stomach prior to the declaration of primary malignancy, there is a risk of misdiagnosing these metastases for primary gastric cancer hence failing to distinguish the true primary.In this case, the presence of severe malignant lesion at our patient's heel could provide the origin of the gastric metastasis. Melanoma may metastasize after the primary has subsided. There are published cases of unknown primary melanoma challenging clinicians in differentiating diagnosis in between primary gastric cancer and metastatic involvement. The normal GI tumor markers and atypical metastatic pattern may aid in diagnosis. 
Based on the photograph of the patient's tumor, it appears that this patient had an acral lentiginous melanoma (ALM), which is a relatively rare subtype. The majority of ALM is found on the lower limbs, even though the surface area of the palms and soles is similar. The sole of the foot is constantly exposed to pressure, friction, maceration, and irritation. 
BRAF mutations are found in 10-15% of these lesions,  while KIT expression by melanoma cells can be as high as 84%. It seems that ALM express KT in a higher proportion of cases compared with other "non-ALM (found to express KIT in roughly 65% of the cases), except for uveal melanomas. 
Curtin et al.studied the frequencies of KIT aberrations (i.e., mutations or copy number increases) in different melanoma subgroups. 
A detailed analysis of the 4q12 chromosomal region in mucosal and acral melanomas identified frequent incidence of increased copy number (×25%) and mutations (10-20%) of the KIT receptor tyrosine kinase gene in these subtypes. 
Although, we not found stomach metastasis from ALM in the literature, but pulmonary and bone metastases had addressed in many reports. ,
A particular interest to the pathologist in respect with adenocarcinomas of GI or pancreatobiliary origin may involve the gastric glands and pits. Preserving this morphology while pits themselves are destroyed, mimic an in-situ "pseudoprimary" gastric lesion. 
The appearance of cells typical for melanoma and its positive reaction with anti-HMB-45 and Fontana staining supports the diagnosis in our patient. 
Furthermore, esophagus and anorectum are considered as the most frequent sites for the primary GI melanomas and their presence in the rest of the GIT is under concern. Anyhow, where diagnosis is made based on a biopsy, which potentially could miss the characteristics of a primary GI melanoma, we may not completely rule out the possibility of a primary in the stomach. Patients that have lost their lives due to GI melanoma have been frequently revealed by autopsy. However, little evidence has been found by antemortem diagnosis and only in accordance with emergency status such as obstructions, bleeding or perforation. The asymptomatic nature of GI melanoma frequently explains why it largely leads to misdiagnosis. Symptoms mainly include GI bleeding, abdominal pain, anorexia, nausea, and vomiting, weight loss, progressive dysplasia, obstruction, and occasionally acute perforation. Melena in a melanoma patient appears to be a primary symptom for GI metastasis, even if the other symptoms are lacking. It has been reported that almost all of the areas of the human body could be affected by melanoma metastases. Three main morphological types comprise the endoscopic classification of the gastric metastases.First of all, there are melanotic nodules, often ulcerated at the tip, which are the most frequently observed through endoscopic examination. Secondly, there are submucosal tumor masses, melanotic or not, which are ulcerated and elevated at the tip. This would be the typical appearance of so called "bull's eye" lesions. The third morphological type with varying degrees of necrosis and melanosisis known as mass lesions. Furthermore, gastric metastases could even be seen as a simple ulcer. Regarding the anatomical location of the gastric metastases, the majority of them are reported to be occurred in the body and the fundus; usually at the greater and lesser curvature lesions are not common. 
Mucosal melanoma is other entity that should be distinguished from metastatic melanoma. Mucosal melanomas are rare but may occur in almost every part of mucosal membranes, the majority of them originate from the oral and nasal cavity or sinuses. Mucosal melanomas have aggressive behavior with less favorable prognosis compared to other subtypes.Lack of early and specific signs together with its occurrence in occult sites contributes to late diagnosis, and poor prognosis. Unlike cutaneous melanomas, BRAF (serine/threonine kinase) mutations have been rarely found in mucosal melanomas;  however, they may frequently have mutations in the KIT gene.  Small intestine, colon, and stomach are the most common sites of metastatic melanoma, but stomach is extremely rare site of origin in mucosal melanoma, so, metastatic melanoma from another primary site must be ruled out when the site of rare occurrence is involved. Junctional or in-situ melanoma component with intact epithelium overlaying invasive melanoma is the main criteria for diagnosis of primary melanoma.However, diagnosis of mucosal melanomas is usually delayed and many lesions are ulcerated at diagnosis, so this criterion is not easy to assess. Hence, the absence of junctional change in an ulcerated lesion does not preclude the possibility that the lesion is a primary melanoma. Amelanotic appearance makes the diagnosis even more difficult. 
Lack of concurrent or previous removal of a melanoma or atypical melanotic lesion from the skin, lack of other organ involvement and in-situ change in the overlying or adjacent GI epithelium are suggestive criteria of the primary nature of gastric melanoma. The latter may be reported in 40-100% of primary GI melanomas and could be recognized histologically by the presence of atypical melanotic cells in the basal layer of the epithelium and extending in a "pagetoid" fashion into the more superficial epithelium.Since, 50% of patients with metastatic melanoma will have died at 12 months from diagnosis, disease free survival of at least 12 months after curative surgical excision of the involved organ has been proposed as a criterion for the distinction of a primary lesion from metastatic one. Early detection of primary GI melanomas and treatment with curative surgical excision can provide long-term disease free interval. 
In patient of this report, the endoscopic picture of the gastric lesion demonstrated that it was melanotic at the lesser curvature and the first part of the duodenum. The pathological assessment could confirm the metastatic nature of the melanoma lesion. GIT metastases could appear in different morphological forms hence immunohistochemistry is usually beneficial in diagnosing a malignant melanoma from other malignancies.Surgical treatment has been tried in some melanoma patients suffering from GI metastases. However, surgery seems to be of limited clinical value and would be conducted only in certain patients with complications. The poor general condition of our patient by the time of the diagnosis, complicated with other organ (brain, stomach and lungs) metastases, did not allow any surgical treatment.
Patients with GI and/or liver metastases usually have disseminated disease and the median survival has been reported to be not more than 2-4 months. 
Our patient was referred to our oncology clinic for chemotherapy after the diagnosis, but we ruled out any treatment because of his clinical deterioration.
| > Conclusion|| |
Stomach metastasis due to a malignant melanoma is very rare, and such metastases are hardly ever reported among gastric metastases. This case is the first gastric and duodenal metastases observed in our clinic due to malignant melanoma.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]