Metastatic malignant melanoma of the gallbladder: a case report and review of the literature

Both primary and metastatic melanoma of the gallbladder are rare. Involvement of the gallbladder occurs in about 15% of all gastrointestinal metastatic localizations in post-mortem case records. It is often difficult to differentiate primary from metastatic lesions on the basis of clinical, radiological and histopathological features. Melanoma involving the biliary tree seldom causes relevant symptoms during life, and this is why cases reported in the literature are few and those documented in living patients even fewer. We report a case of a young woman with a metastatic gallbladder melanoma who presented with a long and vague clinical history of symptoms that mimicked chronic cholecystitis with epigastric right hypochondrial pain without instrumental evidence of disease until the development of acute cholecystitis. We report this case to emphasize the need for awareness of the possibility of gallbladder involvement in the melanoma patient and to underline the necessity of meticulous investigation of unclear lesions of the gallbladder and biliary tree in patients with a past history of malignant melanoma. The clinical presentation, diagnosis, histopathology, prognosis and treatment of primary and metastatic melanoma of the gallbladder are also discussed and reviewed.     

Metastatic melanoma of the gallbladder.

Metastatic involvement of the gallbladder in melanoma is rare, but constitutes the most common metastatic lesion involving this organ. Two cases of metastatic melanoma to the gallbladder with radiographic evidence of gallbladder abnormality prior to surgery are presented. These cases are compared to the nine previously reported cases of metastatic melanoma to the gallbladder with abnormal cholecystograms. All eleven cases presented with signs and symptoms compatible with cholecystitis. Nine of the eleven patients had a previous melanoma primary and most had other extrabiliary metastases. Associated cholelithiasis appeared to be only incidental. In addition, nine reported cases of "primary" biliary melanoma were reviewed. Clinical and pathologic presentations in the latter cases were similar to the former cases with metastases. Seventy-eight percent had extrabiliary sites of metastasis at some time in the course of their disease, tending to refute the impression of "primary" biliary melanoma. Melanoma in the gallbladder is much more likely to have metastasized from a regressed skin primary than to have arisen de novo. The two reported cases and the 18 cases from the literature indicate that the physician must consider gallbladder metastasis in melanoma patients presenting with symptoms compatible with cholecystitis.     

Melanoma metastatic to the gallbladder and small bowel: report of a case and review of the literature

From post-mortem case records, the small bowel is the most frequent site of metastatic melanoma in the gastrointestinal (GI) tract, with gallbladder involvement occurring in 15% of cases. However, few cases have been documented in living patients and, when found, are associated with a poor prognosis. We report a case of a Caucasian man with metastatic gallbladder and small bowel melanoma from an unknown primary. He presented with diffuse abdominal pain, vomiting and progressive asthenia; subsequently, intestinal obstruction occurred. He had no past history of malignant melanoma and the primary lesion was not found. The multiple lesions, together with the absence of mucosal involvement in both the gallbladder and small bowel, led us to believe that the lesions were metastatic deposits from a probably regressed primary melanoma. It should be emphasized that surgical resection for melanoma metastatic to the GI tract is recommended for palliative reasons and can be performed safely. The clinical presentation, diagnosis, treatment and prognosis of previously reported cases of melanoma metastatic to the gallbladder and small bowel are reviewed. The differences between primary and secondary GI tract melanomas are also discussed.     

Duodenal and gallbladder metastasis of regressive melanoma: a case report and review of the literature

Background

Malignant melanoma involving the gastrointestinal (GI) tract may be primary or metastatic. Small bowel is the commonest site of GI metastases from cutaneous malignant melanoma, metastatic lesion in the gallbladder is extremely rare.

Case presentation

This case report describes the presentation of metastatic melanoma in duodenum and gallbladder. A 45-year-old man has presented melena with intermittent abdominal pain. On physical examination we found a small lesion between the fourth and fifth toes, associated with inguinal lymph node. An Abdominal ultrasound revealed diffuse duodenal thickening. Upper endoscopy was performed and discovered an ulcerative lesion in the second part of the duodenum. The biopsy with immunohistochemical stains was in favor of a duodenal location of melanoma. Computed tomography (CT) revealed many circumferential thickening of ileal loops associated with a nodular lesion in the anterior wall of the gallbladder. The patient was treated by palliative chemotherapy.

Discussion

Malignant melanoma of the GI tract may be primary or secondary. The small bowel is the most affected, but it’s rare in the gallbladder. The clinical presentation can mimic the other intestinal tumors, and the diagnosis is based on imaging; CT scan and GI endoscopy have a key role on the diagnosis, and the treatment depends on the location and the number of lesions.

Conclusions

Metastases of melanoma in the GI tract are uncommon, the diagnosis must be suspected in any patient with a history of melanoma with digestive signs.     

Mixed Response to Ipilimumab in a Melanoma Patient with Brain Metastases: Case Report and Review of the Literature

Management of patients suffering from metastatic malignant melanoma and brain metastasis remains challenging in routine clinical practice. The inhibitory anti-CTLA-4 antibody ipilimumab has recently been approved as second-line therapeutic option for melanoma patients. Increasing evidence suggests distinct therapeutic activity on central nervous system metastases, although this continues to be actively debated. Here, we present the case of a patient suffering from metastatic melanoma, including symptomatic brain metastasis, who showed a partial response to ipilimumab in extracranial tumor manifestations, while the disease was progressing intracranially. Subsequently, intracranial disease progression could be managed by local irradiation. An overview of currently available literature on the efficacy of ipilimumab in melanoma patients with central nervous system metastases is provided.Key words: Ipilimumab, Melanoma, Brain metastases, Survival     

Role of radiation therapy in the treatment of melanoma

Melanoma has been widely described as radioresistant but this should not be construed as meaning that melanoma is radioincurable. Many melanoma cell lines are as radiosensitive as other tumors commonly treated successfully with radiotherapy (RT). The use of RT requires careful planning resulting in the administration of a tumoricidal dose to the tumor cells with adequate sparing of normal tissues. RT has been used for primary therapy, postresection adjuvant therapy and palliation of symptomatic melanoma. Curative RT has been given for uveal melanoma yielding patient survival equivalent to enucleation. RT has been administered to patients with unresectable disease yielding relatively favorable results. As an adjuvant therapy postoperatively, RT has been used selectively to improve local disease control. Finally, RT is used successfully as a palliative maneuver for symptoms related to distant metastatic melanoma in patients with incurable disease.     

Malignant melanoma of the gallbladder. Report of a case

A case of malignant melanoma in a 31-year-old man is described to add to the eight cases previously reported in the literature. The tumor in this case shares many common gross and microscopic features with those previously reported. These similarities, in addition to the clinical absence of any primary melanoma in the more common site of occurrence, indicate that the tumor in this case is primary in the gallbladder.     

The left ventricle as the first site of uveal melanoma metastasis 13 years after treatment of the primary tumor

Treatment of patients with metastatic uveal melanoma is very challenging because the tumor commonly spreads to the liver, surgical resection of metastases is rarely possible, and there is no standard effective systemic therapy. We report the case of a 38-year-old man, who presented with metastatic involvement of the left ventricle as the first site of uveal melanoma recurrence 13 years after treatment of his primary tumor. The metastatic tumor was considered unresectable. We describe the patient's medical management over the next 3 years, the course of his disease, and the results of our review of the literature.     

Spontaneous regression of metastatic melanoma – Clinical evidence of the abscopal effect

Introduction

Metastatic melanoma is poorly understood. Regression of primary lesions has been associated with poor prognosis, but spontaneous regression of all metastatic disease is clearly beneficial. A patient's own immune responses occasionally appear to stimulate spontaneous regression of metastatic disease in melanoma.

Patients and methods

We present six interesting cases of complete or nearly complete spontaneous regression of metastatic melanoma, suggest possible causes and review the literature.

Results and conclusions

These cases show clear radiological, pathological or clinical evidence of spontaneous regression of metastatic melanoma. This remains a poorly understood phenomena warranting further investigation and may prove useful in the development of immune mediated solutions.     

Palliative radiation therapy for primary gastric melanoma

Introduction

Primary gastric melanoma is an exceedingly rare cause of upper gastrointestinal bleeding (GI bleeding). Prior reports of primary gastric melanoma have mostly been treated with surgery with utilization of radiation therapy being unreported. Radiation therapy has been used to palliate bleeding of other cancers including lung, bladder, cervix, and more recently primary gastric cancers.

Case presentation

This case documents an 87-year-old male who presented with fatigue and melena, and was found to have severe anemia. Endoscopy with biopsy revealed an isolated focus of melanoma. After discharge, he presented two days later and was found to have continued bleeding. Because he was deemed a poor surgical candidate he elected to undergo palliative radiation therapy for bleeding control.

Discussion

The diagnosis of primary verses metastatic melanoma is a topic of debate. Case reports of patients with no known extra-gastric primary have undergone surgical treatment with varying outcomes. Patients with metastatic gastric melanoma have relied on chemotherapy and radiation in addition to surgery, with radiation being used in the palliative setting. The use of radiation to control bleeding in other cancers including primary gastric adenocarcinoma has been previously studied. This case documents the utilization of radiation therapy in bleeding due to primary gastric melanoma.

Conclusions

Radiation therapy can provide adequate bleeding palliation in patients with primary gastric melanoma.     

Metastatic melanoma of the gallbladder

A 38-year-old man arrived at our clinic with symptoms and investigation results (U.S. scan and MR) suggestive of acute calculous cholecystitis. He gave a past history of excision of a stage I melanoma of the shoulder. Metastatic disease was suspected following measurement of CA 19.9 levels and the CT scan. The patient underwent laparotomy and cholecystectomy; pathological examination confirmed the presence of a malignant melanoma metastatic lesion of the gallbladder.     

Positive sentinel lymph node metastasis from a metastasis in Melanoma

The rationale for certain patterns of metastatic spread seen in melanoma is not well understood. Currently, there is no clear experimental evidence to support the potential for metastases to form metastases in this disease. We report a case of a 31‐year‐old woman, with metastatic melanoma, who developed axillary lymph node metastases hypothesized to originate from a breast metastasis rather than the primary disease. Improved understanding of the underlying molecular processes involved in systemic spread would facilitate development of improved adjuvant therapies and prognostic markers.     

Post-menopausal bleeding: a rare presentation of metastatic uveal melanoma

Uveal melanoma differs from cutaneous melanoma in many ways, including its pattern of metastasis, and exhibits latency with clinical evidence of metastasis sometimes appearing many years after primary diagnosis. Most patients develop metastasis within the liver, but some may present with metastasis to other sites. We report a case of uveal melanoma that presented with post-menopausal bleeding due to metastasis. Further investigation revealed widespread metastatic disease and the patient was not fit for chemotherapy. She died two months after presentation: autopsy revealed metastases in many sites, including the uterus, right ovarian fibroma, kidney, mesentery, liver, lung, thyroid, bone marrow and skin. The immediate cause of death was cardiac tamponade due to a malignant effusion secondary to cardiac metastasis. This case illustrates the widespread metastatic potential of uveal melanoma and highlights the potential for unusual presentation of metastatic disease from this eye tumor.(Pathology Oncology Research Vol 12, No 3, 184–187)     

Primary, extranodal, follicular non-Hodgkin lymphoma of the gallbladder: case report and a review of the literature

We report the first case of isolated primary extranodal non-Hodgkin lymphoma follicular grade 2 limited to the gallbladder, found in the laparoscopic cholecystectomy specimen from a 70 year old woman with symptomatic cholelithiasis. The pericystic duct lymph node, surgical margins, and other lymph nodes, were not involved with lymphoma. According to the medical literature in English language, mucosa associated lymphoid tissue lymphoma (6 cases) is the most frequent type (38%) of primary gallbladder lymphomas (15 reported cases plus our case). Our case demonstrates that follicular lymphoma can be limited to the gallbladder, and confirm that it can occur in an organ normally devoid of lymphoid tissue.     

A case with advanced carcinoma of the gallbladder responding to UFT monotherapy

Gallbladder carcinoma is a fatal disease with highly metastatic potential, and the chemotherapeutic regimen has not been established yet. We reported here a case of gallbladder carcinoma with lung and liver meatstases responding to a single agent, UFT. A 70-year-old female with advanced carcinoma of the gallbladder and bilateral pulmonary metastases were treated with UFT 600 mg/day weekday for half a year. Pulmonary metastases disappeared completely, and the primary lesion shrank markedly 6 months after. Unfortunately, the patient died 1.5 years after the start of treatment due to relapse of liver and lung lesions.     

Treatment with Ipilimumab: A Case Report of Complete Response in a Metastatic Malignant Melanoma Patient

Introduction

Over the past year, 3 agents have been approved for the treatment of melanoma by the Food and Drug Administration. These include pegylated interferon α-2b for stage III melanoma, vemurafenib for unresectable or metastatic melanoma with BRAF V600E mutation, and ipilimumab for unresectable or metastatic melanoma.

Case Presentation

We present here the case of a 65-year-old Caucasian male diagnosed with advanced melanoma in April 2011 and treated with ipilimumab (Yervoy^®), a monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), as second-line treatment after progression with dacarbazine, for (wild-type BRAF) metastatic melanoma. The patient was referred to us for several painful lumps on his right arm. A biopsy of one of them revealed melanoma. CT and PET scans did not show any other lesions or a primary site. The patient was started on first-line chemotherapy with dacarbazine 850 mg/m² on day 1, every 3 weeks. After 3 cycles, the patient showed disease progression with an increase in size of the skin metastasis. Second-line treatment was started with ipilimumab 3 mg/kg on day 1, every 3 weeks. At the end of the treatment, after 4 cycles, we documented a complete clinical response with total resolution of the skin metastasis. At the time of writing this paper, our patient had finished his treatment more than 9 months earlier and is still in complete remission.

Conclusion

This is a paradigmatic case where, despite extensive metastatic disease, treatment with ipilimumab has confirmed its efficacy. It is still an open question why only a minority of patients have such a remarkable response, and further trials are warranted to address this important question.Key words: Melanoma, Ipilimumab, Complete response     

Nonsurgical management of gallbladder cancer: cytotoxic treatment and radiotherapy

Carcinoma of the gallbladder is a rare tumor entity. Apart from surgical intervention, there is no therapeutic measure with curative potential. Therefore, patients with advanced – i.e., unresectable or metastatic – disease present a difficult problem to clinicians, whether to choose a strictly symptomatic treatment or expose the patient to the side effects of potentially ineffective treatment. Despite anecdotal reports about symptomatic palliation and survival advantages, only unrandomized Phase II studies too small to draw meaningful conclusions have been published thus far. Since there is no standard therapy for advanced gallbladder cancer, patients should be offered the opportunity to participate in controlled clinical trials.     

Electrocoagulation: palliative surgery to control metastatic cutaneous malignancy.

The adaptation of the principles of electrocoagulation to controlling symptomatic cutaneous metastatic disease is discussed. The technique permits minimal anesthesia, excellent hemostasis, local control, satisfactory cosmesis with reduced hospitalization. Two illustrative cases are reported of metastatic malignant melanoma and metastatic leiomyosarcoma.     

胆囊罕见恶性透明细胞肿瘤的临床病理观察

目的:探讨胆囊罕见恶性透明细胞肿瘤的临床病理特征、免疫表型、诊断和鉴别诊断、治疗以及预后特点，以提高病理医生对其临床及病理改变的认识。方法:对收治于我院的胆囊透明细胞腺癌和胆囊转移性肾细胞癌的临床资料及病理学特征进行回顾性分析，对石蜡包埋组织切片进行HE染色和免疫组化染色，并复习相关文献进行讨论。结果:本文于国内首次报道了1例转移至双侧附件的胆囊原发性透明细胞腺癌和5例罕见胆囊转移性肾细胞癌。镜下两者形态非常相似，大部分肿瘤细胞核圆居中、深染，胞浆透亮，细胞界限清楚，形成实性巢状或腺泡状结构；但胆囊透明细胞腺癌伴有高级别上皮内瘤变和普通型腺癌的成分，而胆囊转移性肾细胞癌中不伴随其他肿瘤性成分，并且大部分胆囊转移性肾细胞癌的病例中肿瘤细胞可见嗜酸性小核仁，而胆囊透明细胞腺癌中则未见核仁。免疫组化方面，胆囊透明细胞腺癌表达CA19-9、CEA、Keratin和p53，而胆囊转移性肾细胞癌表达EMA、CD10、Keratin、RCC、Pax-2、Pax-8和Vimentin。结论:胆囊具有“透明细胞形态特征”的良恶性病变种类颇多，形态学上有所重叠，仔细观察这些透明细胞的镜下特点、排列方式、分布特点以及有无伴随其他肿瘤性成分等情况并结合免疫组化特点和特殊染色结果有助于病理医师做出正确的诊断。