Primary Melanoma of the Adrenal Gland, a Continuous Dilemma:

Report of a Case

Surg Today (2004) 34:554–556

Introduction

• Primary malignant melanoma of the adrenal gland is extremely rare, with only 18 cases reported in the English literature.

• It is always difficult to differentiate a primary melanoma from either a metastatic melanoma of the adrenal gland or from a pigmented pheochromocytoma.

• This report describes another case of primary adrenal melanoma (PAM) using clinical and radiological methods confirmed by immunohistochemical staining.

Case Report

• A 78-year-old man suddenly experienced right flank pain associated with fever, nausea, and vomiting.

• The patient was known to have atrial fibrillation and he was presently being treated with anticoagulants; he had a history of nonactive hepatitis B, appendectomy, and a vocal cord polypectomy.

• Abdominal ultrasound and a chest/abdomen computed tomography (CT) scan showed an enlarged, well-encapsulated right suprarenal gland (8 cm), pneumopathy at the right base, and pleural infusion.

• On general examination no abnormality was observed, with blood pressure within the normal range. On cardiac examination an irregular cardiac rhythm with no cardiac murmurs was recorded. Slight hepato and splenomegaly were observed on abdominal examination.

• An endocrinologist diagnosed the patient as having asymptomatic pheochromocytoma or lymphoma, and he was thus referred to a surgeon to undergo a right suprarenalectomy, but he was unable to undergo surgery because of his cardiac condition.

• Three months later he was referred to our center.

• An abdominal CT scan showed the same findings as those recorded earlier, and splenomegaly with two cystic lesions (Figs. 1 and 2).

Fig. 1.Adrenal tumor (a) with a splenic cyst (b)

Fig. 2.Primary melanoma of the adrenal gland (a) involving the upper pole to the right kidney

• Fine-needle cytology was contraindicated by the radiologist.

• A full endocrine workup was done with the conclusion of an inactive right adrenal tumor.

• Plasma catecholamines(儿茶酚胺 ) showed increased noradrenaline and adrenaline levels, while urinary catecholamines showed increased dopamine, metanephrine(甲氧基肾上腺素 ), and methoxytyramine(甲氧酪胺 ) levels.

• The patient underwent a right suprarenalectomy(肾上腺切除 ), right nephrectomy(肾切除 ), and splenectomy(脾切除 ).

• The adrenal gland was removed with the right kidney because there was infiltration on the upper pole of the kidney.

• The right lateral wall of the inferior vena cava had to be removed with the tumor.

• No para-aortic lymph node invasionwas found; however, a splenectomy was performed because of splenic metastasis.

• The pathology report showed a malignant melanoma of the adrenal gland measuring 11 cm in size.

• Microscopically, the sections were stained using the hematoxylin–eosin and Fontana–Masson melanin methods. The tumor was composed of pleomorphic and pigmented cells, having polygonal and spindle cell proliferation with no neurosecretory granules.

• A splenic metastasis of malignant melanoma measuring 4 cm in size was observed which was composed of pleomorphic and nonpigmented cells.

• Immunohistochemical staining revealed a positive antibody-specific cytoplasmic reactivity to S-100 and HMB-45 proteins with a negative reaction for cytokeratin(细胞角蛋白 )(AE1, AE3), synaptophysin(突触酶 ), chromogranin(嗜铬粒蛋白 ), and neuron-specific enolase(神经元特异性烯醇化酶 ).

• A histopathologic diagnosis of malignant melanoma of the adrenal gland was followed by meticulous anamnesis and a physical examination of the patient while paying careful attention to possible cutaneous, ungual, mucosal, and ocular lesions. No melanotic cutaneous or mucosal lesions were found, the patient having never previously had any skin lesions removed.

Discussion

• Up to now only 18 cases of PAM have been reported in the English literature, of which only 6 are well documented (Table 1).

• Primary adrenal melanoma is a highly aggressive tumor that affects middle-aged adults and manifests itself as a painful flank mass, although distant lymph node metastasis can be seen on the initia examination.

• The size of the lesions ranges from 8 to 17 cm in maximal diameter and the tumors are composed of soft gray-brown to brown-black tissue with areas of hemorrhage and necrosis.

• A histologic study reveals polygonal or spindle cells displaying an oval-to-round nucleus with a prominent nucleolusand containing brown intracytoplasmic pigment.

• Masson–Fontana and hydrogen peroxide staining techniques have been used to demonstrate the melanotic nature of this pigment.

• Radiologic features are not specific and calcification is not common.

• Malignant melanoma originating outside the skin, squamous mucous(鳞状上皮 ) membranes, eyes, and leptomeninges(软脑膜 ) is rare.

• The existence of primary melanoma of the adrenal gland is explained by the neuroectodermal origin of the medulla, chromaffin cells and melanocytes have a common embryogensis.

• Many authors have expressed great reluctance to accept malignant melanomas as primary in the adrenal gland because the frequency of adrenal involvement by metastasis from cutaneous or ocular melanomas can be as high as 50%.

• In many cases, the primary lesion can be small, hidden, or easily overlooked. In rare instances it can also regress spontaneously.

• For this reason we tried to establish the criteria to differentiate primary from metastatic melanoma.

• In 1984, Carstens et al. 4 established four strict criteria for diagnosing adrenal melanoma as primary:

(1) The presence of a primary malignant melanoma in only one of the adrenals;

(2) No prior or current malignant melanoma elsewhere; (3) No previous removal of pigmented skin, or mucosal or eye les

ions; (4) Exclusion by autopsy of the presence of a hidden primary lesi

on.

• Our patient satisfied the first three of these criteria, but this could not be confirme by autopsy because the patient is still alive, asymptomatic and free of disease after 1 year.

• The spleen tumors could not be primary, and thus must be considered to be metastatic deposits. We believe that these diagnostic criteria are practical and easy to apply; however, only an autopsy is a definitive step to confirm this infrequent pathology.

• It is difficult to prove that a visceral malignant melanoma is a primary lesion because malignant melanomas in more common locations may metastasize widely.

• Metastatic involvement of the regional lymph nodes, small bowel, and bone have been noted in two cases at the time the adrenal lesion was detected, and there are other cases in the literature with hepatic metastasis,but our case is the only one to demonstrate splenic metastasis.

• Another important differential diagnosis is between PAM and pigmented pheochromocytoma, based largely on neuroendocrine markers (immunoreactivity to synaptophysin and chromogranin, and the detection of neurosecretory granules under electron microscopy) present in pheochromocytomas but absent in melanomas, as observed in the present case.

• For such patients undergoing surgery, a nephroadrenalectomy appears to be the treatment of choice, because adhesion of the adrenal lesion to the adjacent kidney is very common and frequently requires the removal of the affected kidney.

• In two cases radiotherapy was given, one with a surgical resection and the other without surgery.