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.     

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.     

Gallbladder metastasis of non-small cell lung cancer

BACKGROUND: Although non-small cell lung cancer is known for its potency to spread to almost any organ of the body, metastasis to the gallbladder with significant clinical manifestation is rarely reported in the literature. CASE REPORT: We report the case of a 45-year-old man with non-small cell lung cancer (NSCLC), who developed symptoms of acute cholecystitis caused by a metastasis of the gallbladder wall. Histological examination showed tumor cell invasion in regional gallbladder lymph nodes. A second primary tumor of the gallbladder was excluded by immunohistochemical methods. CONCLUSION: Our experience showed that acute cholecystitis can occur in association with metastases of lung cancer to the gallbladder.     

Clinical and histologic features of level 2 cutaneous malignant melanoma associated with metastasis

BACKGROUND: Metastatic melanoma developing in patients with a level 2 primary cutaneous malignant melanoma (CMM) is rare but has been reported in studies with follow-up periods ranging up to 15 years. The objective of this study was to investigate level 2 CMM associated with metastasis in a population-based retrospective study. METHODS: In this retrospective population-based study, all level 2 CMMs associated with metastases were identified in Western Australia during 1982-1989 and were followed up to the end of 1996. RESULTS: Pathology reports of 2834 patients were examined. Of these, 1716 had a CMM of maximum tumor thickness 1 mm or less recorded on the pathology report. Of these, 67 had a metastatic melanoma reported on follow-up. Histologic review of these 67 cases under blind conditions identified 5 cases with a level 2 primary CMM followed by metastasis without another primary CMM. All these level 2 CMM showed established regression. Eight other patients were identified with a level 2 CMM, metastatic melanoma, and another primary CMM of at least level 3 invasion. These subsequent primaries occurred before the metastasis had been reported. CONCLUSIONS: These findings suggest that metastasis from level 2 CMM without regression is very rare, if it occurs at all.     

Rapidly progressive subcutaneous metastases from gallbladder cancer: insight into a rare presentation in gastrointestinal malignancies

Background

Gallbladder cancer (GBCA) is the most common malignancy of the biliary tract. It has an aggressive biology that results in the ability to spread, seed and grow in disparate environments. It can metastasize via lymphatic, hematogenous, and peritoneal seeding. However, GBCA metastasis to distant subcutaneous sites is extremely rare.

Case presentation

This case report describes the presentation of metastatic GBCA with rapidly progressive subcutaneous metastases. A 58-year-old woman presented with acute onset right upper quadrant abdominal pain. Computed tomography (CT) revealed a calcified and thickened gallbladder with cholelithiasis and presumed cholecystitis. Diagnostic laparoscopy revealed a gallbladder mass. Biopsies were consistent with GBCA. The patient was referred to our cancer center for further surgical management. However, she was found to have rapidly growing subcutaneous nodules in the shoulders, chest, abdomen, and buttocks. Positron emission tomography (PET) demonstrated that these were fluorodeoxyglucose (FDG)-avid. A core needle biopsy of a chest wall lesion was consistent with metastatic GBCA. Therefore, the patient was diagnosed with stage IVB GBCA and was initiated on systemic chemotherapy.

Discussion

GBCA is known to have an incredible propensity to grow within the peritoneal cavity, as well as along needle biopsy tracts and at laparoscopic port sites. Several case reports have demonstrated that GBCA also has the potential to metastasize to distant subcutaneous sites, most often including breast metastases, while the current cases represents a more diffuse pattern of spread.

Conclusions

GBCA belongs to the short list of solid visceral malignancies that have the potential to develop remote subcutaneous metastases.     

Hypertrophic osteoarthropathy associated with metastatic melanoma

Hypertrophic osteoarthropathy (HOA) is one of the paraneoplastic syndromes most commonly associated with non-small-cell lung cancer. Although pulmonary metastasis is the second most common initial site of melanoma metastasis, HOA is rarely detected in patients with metastatic melanoma in the lung. We report a case of a 45-year-old woman with advanced melanoma who developed HOA after her disease had progressed through first-line systemic therapy. The patient's diagnosis of HOA was made on the basis of digital clubbing, arthralgia, pain, joint effusion and periosteal bone formation on X-ray with negative rheumatologic laboratory studies. Only six cases of HOA in metastatic melanoma have been reported previously. This diagnosis should be considered with lung metastases and the presentation of polyarthralgia with appropriate laboratory and imaging findings. Interestingly, the patient responded to bisphosphonates and second-line chemotherapy with carboplatin and paclitaxel, which is commonly used for lung cancer, not advanced melanoma. As with many paraneoplastic syndromes, successful treatment of the underlying disease was associated with a rapid resolution of the symptoms.     

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.     

Biliary cancer brain metastases: a multi-institution case series with case reports

BackgroundBiliary cancers are rare, and few reported cases of brain metastases from primary biliary cancers exist, especially describing patients in the United States. This report assesses the proportion and incidence of brain metastases arising from primary biliary cancers [cholangiocarcinoma (CCA) and gallbladder cancer] at Stanford University and the University of California, San Francisco, describes clinical characteristics, and provides a case series.MethodsWe queried 3 clinical databases at Stanford and the University of California, San Francisco to retrospectively identify and review the charts of 15 patients with brain metastases from primary biliary cancers occurring between 1990 to 2020.ResultsAmong patients with brain metastases analyzed at Stanford (3,585), 6 had a primary biliary cancer, representing 0.17% of all brain metastases. Among biliary cancer patients at the University of California, San Francisco (1,055), 9 had brain metastases, representing an incidence in biliary cancer of 0.85%. A total of 15 biliary cancer patients with brain metastases were identified at the two institutions. Thirteen out of 15 patients (86.7%, 95% CI: 59.5–98.3) were female. The median overall survival from primary biliary cancer diagnosis was 214 days (95% CI: 71.69–336.82 days) and subsequent OS from the time of brain metastasis diagnosis was 57 days (95% CI: 13.43–120.64 days). Death within 90 days of brain metastasis diagnosis occurred in 66.67% of patients (95% CI: 38.38–88.17).ConclusionsBrain metastases from primary biliary cancers are rare, with limited survival once diagnosed. This report can aid health care providers in caring for patients with brain metastases from primary biliary cancers.     

胆囊癌中基质金属蛋白酶9表达与淋巴结转移及预后的关系

目的　研究胆囊癌中基质金属蛋白酶 9(MMP 9)表达的情况 ,探讨MMP 9表达的临床意义。方法　应用免疫组化Envision二步法测定 4 6例胆囊癌 (gallbladdercarcinomaGBC)和 12例慢性结石性胆囊炎、3例胆囊腺瘤中MMP 9表达。结果　MMP 9在胆囊癌组织中阳性表达率为 78 2 6 % ,胆囊癌组织与胆囊良性病变MMP 9表达水平之间有显著性差异 (P <0 0 0 1)。MMP 9表达与胆囊癌分化程度、临床分期、淋巴结转移、术后生存率有关。结论　MMP 9的表达可以作为判断胆囊癌淋巴结转移、评估预后的指标。     

Different manifestations of malignant melanoma in the breast: a report of 12 cases and a review of the literature

BACKGROUND: The breast is associated with a large number of diseases. Besides being the host of many benign and malignant tumors, breast skin and parenchyma are also metastatic sites for various tumors such as leukemia, lung cancer and melanoma. METHODS: Malign melanoma has different manifestations in the breast. All these manifestations are important not only as initial presentations of the disease, but also as indicators of the progression period of the disease. RESULTS: This study reports on 12 cases of cutaneous malignant melanoma in breast skin and tissue. Nine of these cases are primary cutaneous melanomas, while the others are breast metastases from a distant site cutaneous melanoma. In two of the nine primary cutaneous melanomas in-transit metastasis to the breast developed during the follow-up period. CONCLUSIONS: In this paper, the diagnostic and surgical approach to primary and metastatic melanoma of the breast, and the importance of the breast during the follow-up period are reviewed.     

Gastric metastases from conjunctival melanoma

The aim of the study is to discuss the pattern and risk factors for metastatic disease in conjunctival melanoma. We draw comparisons with cutaneous metastatic melanoma. We describe the clinical course of a patient with recurrent conjunctival melanoma in the context of primary acquired melanosis with atypia. The local disease was eventually treated with a lid splitting exenteration. The patient suffered from an isolated distant metastasis to the gastric wall that was managed by partial gastrectomy. Conjunctival melanoma has many similarities with its cutaneous counterpart. In both conditions the regional lymph nodes are the most common site for metastases, however, isolated distant metastases can occur. Gastric metastases are frequently seen in cutaneous melanoma. This is the first report of an isolated gastric metastasis from a conjunctival melanoma.     

The Biology of Melanoma Brain Metastasis

Brain metastases are clinically diagnosed in the majority of patients with metastatic melanoma. The prognosis for patients with melanoma brain metastasis is poor with a median survival time of 6 months after diagnosis. Development of better therapies requires a better understanding of the biology of melanoma brain metastasis. The development of a relevant in vivo model offers this possibility. The intracarotid injection of different murine or human melanoma cells into syngeneic or nude mice produces metastases in different regions of the brain. This site-specific metastasis is not due to patterns of initial cell arrest, motility, or invasiveness, but rather to the ability of melanoma cells to proliferate in the brain parenchyma or the meninges. The blood–brain barrier is intact in metastases that are smaller than 0.25mm in diameter. Although in larger metastases the blood–brain barrier is leaky, the lesions are resistant to many chemotherapeutic drugs. We have also analyzed the malignant behavior of several melanoma cell lines isolated from brain or visceral metastases of patients. The cells from brain metastases showed a slower growth rate and exhibited lower metastatic potential than cells from visceral metastases, indicating that brain metastases do not necessarily represent the end stage in the metastatic cascade. Rather, brain metastases are likely to originate from a unique subpopulation of cells within the primary neoplasm.     

Carcinomatous Meningitis as the Presenting Manifestation of Gallbladder Carcinoma: Case Report and Review of the Literature

The primary tumors that typically cause carcinomatous meningitis include lung cancer, breast cancer, leukemia, lymphoma and melanoma. A variety of neurological signs and symptoms can be seen depending on the extent and location of the meningeal metastasis. Once the diagnosis of carcinomatous meningitis is confirmed, the search for the primary tumor can be a challenge and at times may require extensive radiographic or even surgical evaluation to obtain specimen for pathological confirmation. Here we report a patient who presented with bilateral cranial nerve VIII and cerebellar symptoms, and was diagnosed with carcinomatous meningitis. Only after an exploratory laporatomy did it become clear that the initial symptoms were related to a metastatic gallbladder carcinoma.     

23例恶性黑色素瘤小肠转移临床病例分析

目的：总结恶性黑色素瘤小肠转移的临床病例特点。方法：我院诊治1例,通过中国知网、万方医学网以及 MEDLINE（或 PUBMED）检索到国内外报道的黑色素瘤小肠转移病例共23例,并进行统计分析。收集一般情况、黑色素瘤原发部位、原发肿瘤至小肠转移间隔时间以及临床症状等。结果：23例（男14例,女9例）,平均年龄54.7岁,初次诊断至发现转移平均时间间隔为6.33年（0-20年）。主要临床表现为腹痛16例（69.6%）,黑便/便血7例（30.4%）,肠梗阻或肠套叠14例（60.9%）。肿瘤最大直径平均为5.82cm（2-15cm）。47.8%为小肠多发转移。结论：恶性黑色素瘤小肠转移主要临床表现为腹痛、黑便,易于发生肠梗阻或肠套叠;肿瘤常多发转移,且发现小肠转移距初次诊断时间间隔较长。     

Medical history and the risk of biliary tract cancers in Shanghai, China: implications for a role of inflammation

Several lines of evidence suggest that inflammation may play a role in the etiology of biliary tract cancers. To examine further the role of inflammation, we evaluated the associations between self-reported inflammatory-related medical conditions and the risk of biliary tract cancers in a population-based case-control study in Shanghai, China. Our analysis included 368 gallbladder cancer cases, 191 bile duct cancer cases, 68 ampulla of Vater cancer cases, and 959 healthy subjects. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for biliary tract cancers in relation to six inflammation-related conditions. Gallbladder cancer was significantly associated with cholecystitis occurring at least 5 years prior to interview (OR = 1.7, 95% CI 1.1-2.9). Even though biliary stones did not significantly modify the associations between cholecystitis and gallbladder cancer, 90% of the gallbladder cancer cases with cholecystitis also had biliary stones, indicating that stones likely play an important role in the link between cholecystitis and gallbladder cancer. Among subjects who smoked and drank alcohol, a history of gastric (OR = 4.3, 95% CI 1.2-15.0) or duodenal ulcers (OR = 3.7, 1.2-12.0) was associated with an excess risk of gallbladder cancer. Although the mechanisms are unclear, our results further support the role for inflammation in the etiology of biliary tract cancers.     

Nuclear DNA profiles in primary melanomas and their metastases

DNA-aneuploid primary melanomas are said to show a greater propensity to metastasize than those without an aneuploid profile. A higher aneuploid rate has also been reported in metastatic melanomas than in primary lesions. The ploidy profile was determined of 26 primary melanomas and their first subsequent secondaries on Feulgen-stained sections from routinely processed material using a computerized video image-analysis system. In 18 of 26 cases, both primary and secondary tumor showed similar corresponding DNA patterns. These were aneuploid in 13 of 18 of the cases. A hyperdiploid pattern was present in one case in both the primary and its metastasis, and a diploid pattern was seen in four cases. There were only eight cases in which a disparity between the nuclear ploidy profile in the primary and secondary tumor was evident. Although the results suggest that ploidy studies are not useful for predicting the metastatic potential of a primary melanoma, the maintenance of similar DNA profiles in the metastases in most of these cases was interesting in regard to tumor biology.     

Pancreatic Resection for Metastatic Melanoma. Case Report and Review of the Literature

Introduction

Pancreatic metastasis from several malignancies are increasingly encountered in clinical practice, and the usefulness of surgical resection has been suggested for certain neoplasms. Isolated pancreatic metastasis from malignant melanoma is a rare occurrence, and the role of surgery as an adjunct to systemic therapy for melanoma metastatic to a solitary or multiple sites is still debated.

Case Report

We report a patient with melanoma of unknown primary site metastatic simultaneously to the lung and pancreas 3 years after axillary lymph node dissection. Distal pancreatectomy with splenectomy and video thoracoscopic assisted resection of pulmonary metastasis were performed. The postoperative course was uneventful, but 6 months after surgery, the patient experienced single pulmonary recurrence. During chemotherapy with different drugs, pulmonary lesion remained stable for 1 year, and no abdominal recurrence occurred. After then, the size of the lesion progressively increased and a second metastasis occurred in the lung. Five months later, brain metastases occurred, and the patients died 24 months after surgery. Sixteen pancreatic resections for metastatic malignant melanoma, reported with adequate clinical details, were also retrieved from the literature.

Conclusion

In spite of the very limited experience, it appears that surgical resection is only a palliative procedure, because long-term survival is a rare event. However, considering the lack of effective systemic therapy, surgery may be considered as a part of an aggressive multidisciplinary approach in selected cases with malignant melanoma metastatic to single or multiple visceral sites.     

Gastrointestinal metastases from malignant tumors of the lung

Autopsy data of 423 cases of primary tumor of the lung over a 36-year period were evaluated for the presence of gastrointestinal tract metastases. Fifty-eight cases (14%) were found and were analyzed for histologic nature of tumor, anatomic location, symptomatology and complications. The most common histologic type of lung tumor causing gastrointestinal tract metastasis was squamous cell (19 cases, 33%), followed by large cell (17 cases, 29%), and oat cell (11 cases, 19%). The esophagus was the most common site of involvement (33 cases). Fourteen of the 33 cases were involved by direct extension of the tumor. The middle third of the esophagus had metastases more commonly (16/33, 49%) than the other two sites. Most patients with gastrointestinal metastases had no symptoms. In those patients with symptoms, dysphagia was most common when the tumor involved the proximal gastrointestinal tract (esophagus, stomach), whereas, pain was most commonly seen with involvement of the distal gastrointestinal tract (small bowel, large bowel). Six of 20 patients (30%) with small bowel involvement experienced perforation and peritonitis as complications of metastatic involvement and two patients with large bowel metastasis had obstruction; a third had dehiscence of a previous anastomotic site. Gastrointestinal tract metastases from primary carcinoma of the lung are more common than previously thought and may be associated with serious clinical complications.     

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.