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。     

Central nervous system as exclusive site of disease in patients with melanoma: treatment and clinical outcome of two cases

The central nervous system (CNS) is a favourite site of metastasis in advanced melanoma and, despite the improvement obtained in the control of brain metastasis, most patients die as a result of extracranial progression of the disease. CNS primary malignant melanoma is a rare entity and the diagnosis is generally made after the exclusion of a primary cutaneous or mucosal/retinal malignant melanoma, as differential histological diagnosis between primary and metastatic origins is often difficult. From a review of the literature, patients with primary brain melanoma or exclusive (and limited) brain metastasis in the absence of extracranial melanoma present a relatively good prognosis if adequately treated with aggressive locoregional treatments (neurosurgery and/or radiotherapy) and, later, with drugs able to cross the blood-brain barrier (i.e. fotemustine). In this letter, we describe the history, treatment and favourable clinical outcome of two patients with melanoma and CNS as the exclusive site of disease.     

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.     

Cutaneous melanoma with tonsillar metastasis

Metastases to the tonsillar fossa due to hematogenous dissemination is an extremely rare phenomenon associated with advanced-stage disease and poor prognosis. In the present report we describe a case of cutaneous melanoma with a metastasis to the tonsil approximately 4 years after the initial diagnosis of the primary disease treated with palliative radiation therapy.     

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)     

Surgical approach to malignant melanoma in the gastrointestinal tract

The gastrointestinal (GI) tract is a common site for malignant melanoma. Diagnosis of lesions in the GI tract is usually delayed until complications occur, such as obstruction, bleeding, or perforation of the GI tract. Of 348 patients with malignant melanoma treated during a 10-year period, 11 had GI involvement either in a metastatic form or as a primary melanoma. Three of these patients were treated surgically for metastatic lesions in the small bowel causing intussusception, two for peritonitis secondary to perforation of the small bowel, and one for massive bleeding from metastatic melanoma in the stomach. Another patient had a primary melanoma in the esophagus and underwent esophagectomy. Three patients had primary melanomas of the anal canal and one of the rectum. Three of them underwent abdominoperineal resections, and two had bilateral groin dissection in addition. Six of the patients are alive 6 months to 4 years following diagnosis. The remaining five died of metastatic melanoma from 6 months to 4 years post-surgery.     

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.     

人原发性小肠恶性黑色素瘤裸鼠原位移植高转移模型的建立

目的 建立人原发性小肠恶性黑色素瘤裸小鼠原位移植高转移模型.方法 将手术切除的人原发性小肠恶性黑色素瘤原发灶和肝转移灶新鲜瘤组织块分别植入裸鼠小肠黏膜层内,观察原位移植的成瘤率、移植瘤的侵袭性和转移率,并进行形态学、流式细胞分析和染色体核型分析.结果 人小肠恶性黑色素瘤原发灶和肝转移灶新鲜组织均移植成功,建成人原发性小肠(原发灶)恶性黑色素瘤裸鼠原位移植高转移模型(ttSIM-0602)和人原发性小肠(肝转移灶)恶性黑色素瘤裸鼠原位移植肝转移模型(HSIM-0603).HSIM4)602和HSIM-0603模型分别传至21代和23代,共移植裸鼠227只,其肿瘤移植生长率和液氮冻存复苏成活率均为100%.HSIM-0602模型肝转移率为65.7%,肺转移率为84.8%,淋巴结转移率为63.8%.HSIM-0603模型肝转移率为100%,肺转移率为46.7%,淋巴结转移率为71.3%.移植瘤组织病理学为小肠高度恶性黑色素瘤.免疫组织化学显示,S-100蛋白和HMB-45均为阳性表达.电镜下,瘤细胞浆内可见大量的黑色素小体,也可见黑色素复合体.HSIM-0602模型移植瘤细胞DNA指数为1.59±0.07,HSIM-0603模型移植瘤细胞DNA指数为1.71±0.12,均为异倍体.染色体核型分析显示,HSIM-0602模型移植瘤细胞染色体数为55～57条,HSIM-0603模型移植瘤细胞染色体数为57～59条.结论 HSIM-0602和HSIM-0603模型是成功的人原发性小肠恶性黑色素瘤裸鼠原位移植自发性高转移模型,完整地模拟了人原发性小肠恶性黑色素瘤患者的自然临床病理过程,为研究原发性小肠恶性黑色素瘤转移生物学和抗转移治疗提供了理想的动物模型.     

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.     

Regression of primary melanoma with metastases.

Seven cases of spontaneous and complete regression of primary melanoma with metastasis are reported. The ages of the patients ranged from 33 to 68 years. There were five men and two women. All patients had had a cutaneous pigmented lesion that underwent a two-stage course: enlargement and darkening, then flattening and depigmentation. Within a few months to 4 years after depigmentation, regional node(s) developed and were removed, confirming the diagnosis of melanoma. An histopathologic examination of the primary sites failed to show residual malignant cells and characteristic features. Primary melanomas that have completely regressed are easily overlooked.     

A case report of primary adenocarcinoma of small intestine

This is an account of a case of primary adenocarcinoma of the small intestine with peritoneal dissemination successfully treated with chemotherapy. A 64-year-old woman was admitted with a complaint of severe abdominal distension. Abdominal computerized tomography revealed a bowel obstruction with tumor and the remarkable small bowel dilation of oral side of tumor. The tumor was found at surgery to be at the ileum 15 cm proximal from the ileocecal region. Peritoneal dissemination was recognized around the ileocecal region, so ileum partial resection was performed for the primary cancer lesion and dissemination region. Pathological diagnosis of the resected specimen was adenocarcinoma with lymph nodes metastasis. The peritoneal dissemination consisted of metastatic adenocarcinoma from small intestine. After an operation, internal use of S-1 was performed as adjuvant chemotherapy. But a recurrent lesion at the ovarium was detected 6 months after surgery. The patient was subsequently treated with resection of the ovarium. For lung metastasis, the combination chemotherapy with mFOLFOX6 + bevacizumab was administered. Primary small intestinal adenocarcinoma is a rare disease, and it is often diagnosed as advanced cancer because of few characteristic symptoms. So carcinoma of the small intestine usually has a poor prognosis.     

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.     

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.     

Oncogene status as a diagnostic tool in ocular and cutaneous melanoma

The majority of human tumours can be easily and correctly diagnosed based on clinical information and pathological assessment. In some cases however, correct diagnosis can prove difficult. In such cases, molecular approaches can be of significant diagnostic value. In recent years, the understanding of genetic alterations has greatly increased. In cutaneous melanoma, it is now well recognised, that 70–80% of tumours harbour BRAF and NRAS mutations. These mutations never occur in uveal melanoma. On the other hand activating GNAQ and GNA11 mutations are found in ∼90% of uveal melanomas, and are exceptionally rare in other melanomas (<1%).Here, we demonstrate a number of melanoma cases, where distinguishing if a tumour was of cutaneous or ocular origin was not possible based on clinical and pathological assessment. In these cases there was either atypical clinical presentation or metastasis of unclear primary. Histological distinction between uveal and cutaneous melanomas, especially at the stage of metastasis, is not reliable as they can be morphologically very similar.In all cases we present, a simple genetic assessment of oncogene mutation status was able to clearly define the melanoma type. This type of genetic assessment is of great diagnostic value and due to its simplicity could be performed in routine clinical practice even in smaller institutions.     

Attributes and survival patterns of multiple primary cutaneous malignant melanoma

From a series of 1495 patients with primary cutaneous malignant melanoma (PCMM), 26 patients (1.73%) had multiple primary cutaneous malignant melanoma (MPCMM). This report describes the attributes and survival patterns in this small, but important, subgroup of patients with PCMM. Of 26 patients, 23 had two primaries, two had three primaries, and one had six primaries. Five patients had synchronous and 21 patients had metachronous MPCMM. The median interval between the occurrence of the first and subsequent PCMM in these patients was 1.93 years. The estimated 5-year survival rate from the first melanoma was 83.5%; that from the last melanoma was 53.1%. In summary, MPCMM is a distinct biologic phenomenon. A second or subsequent malignant melanoma should be treated like a primary melanoma.     

Primary cutaneous melanoma: surgical management and other treatment options

Opinion statement The incidence of primary cutaneous melanoma continues to increase and is a growing public health problem. By virtue of its metastatic potential, melanoma accounts for most of the deaths from cutaneous malignancies. Management of cutaneous melanoma has undergone a paradigm shift in recent years. Clinical studies have furthered our understanding of the biology of this disease and have changed the standards of care. Specifically, sentinel node biopsy and interferon as the first effective postsurgical therapy have had a significant impact on the treatment of patients with melanoma. Surgery remains the primary treatment modality for cutaneous melanoma. An adequate excision of the primary lesion accomplishes durable local control and is curative for patients without micrometastatic disease. Although the extent of surgical resection has decreased in recent years, the standard treatment for primary cutaneous melanoma remains wide surgical excision with histologically negative margins. The extent of excision is based on the theory that the incidence and radial extent of local recurrences can be predicted by specific primary tumor histopathologic characteristics. Tumor thickness and ulceration are the most important histologic features associated with prognosis and are the basis for the current recommendations for surgical treatment of the primary tumor. The extent of surgical therapy for primary melanoma is an area of ongoing debate. No clinical trial has shown a survival disadvantage for narrow versus wide excision regimens for melanoma of any thickness. Ongoing clinical trials will determine the relationship between the extent of surgical therapy for the primary tumor and the outcomes of recurrence and survival in patients with melanoma.     

前哨淋巴结活检在皮肤恶性黑色素瘤中的应用现状及进展

前哨淋巴结活检（sentinel lymph node biopsy,SLNB）是皮肤恶性黑色素瘤诊治过程中不可或缺的手段,在进行准确分期、预后判断以及治疗指导等方面都发挥着重要的作用。SLNB的操作方法已基本成熟,但在适应症的选择方面还存在一定的争议,仍无足够的证据表明前哨淋巴结活检联合区域淋巴结清扫（complete lymph node biopsy,CLND）能够延长转移患者的生存。此外,由于国内恶性黑色素瘤的发病率较低,SLNB尚未得到广泛开展,相关的操作方法也较为落后。近年来,随着恶性黑色素瘤发病率增高,其外科治疗也受到越来越多的关注。本文通过总结分析近年来的相关文献,对SLNB在皮肤恶性黑色素瘤中的应用现状和进展进行综述。      

Cutaneous melanoma and sentinel lymph node biopsy: where are we today?

Malignant cutaneous melanoma is the cancer which has the most increased these last ten years. His prognose is linked with melanoma thickness, tumoral ulceration and lymph node metastasis. The research of these node metastasis is important for the prognosis and the treatment. The sentinel lymph node biopsy is used since 1991 and is now considered as a reliable choice for the patient staging. However, his therapeutic interest remains discussed. We discussed the used of the sentinel lymph node biopsy for malignant cutaneous melanoma with the last publications.     

Malignant melanoma and pregnancy

Confusion exists concerning the influence of pregnancy on survival in patients with malignant melanoma. To evaluate this problem a retrospective computer-aided study was performed of women in the child-bearing years treated for Stage I cutaneous melanoma at the Duke University Comprehensive Cancer Center. Fifty-eight women were identified who had melanoma arise during pregnancy (Group 1) and 43 patients were noted who became pregnant within 5 years of diagnosis of their melanoma (Group 2). Appropriate control groups matched for the clinical variables of age, primary site, and stage of disease and the pathologic variables of Clark's Level, tumor thickness, ulceration, and histologic type were selected from the cohort of 2938 melanoma patients seen at Duke. Actuarial survivals for Group 1 and 2 patients did not differ from their respective controls, although the small number of deaths in each group resulted in wide confidence intervals. When actuarial disease-free intervals were plotted, there was a significant difference between women who had melanoma develop during pregnancy when compared to their controls (P = 0.04). In a multivariate regression analysis, after adjustment for the influence of the more significant prognostic factors for Stage 1 melanoma, including Clark's Level, ulceration and tumor thickness, the effect of pregnancy on disease-free interval became more apparent (P = 0.02). No difference in actuarial disease-free interval was noted in the melanoma patients who elected to become pregnant within 5 years of diagnosis (P = 0.31). A multivariate regression analysis confirmed this finding. These data indicate that although an intercurrent melanoma during pregnancy has a worse prognosis than the control groups, once a woman has been diagnosed as having a cutaneous melanoma, a subsequent pregnancy has no effect on recurrence rate or survival.     

Melanoma metastatic to the spine: a review of 133 cases

Although spine metastasis from melanoma is an uncommon event, it can pose a complex management problem. The presentation and natural history of melanoma metastatic to the spine has not been described in the medical literature. We have conducted a review of the records of 133 patients with melanoma metastatic to the spine in order to obtain retrospective data on demographic information, clinical presentation, disease course and survival. Patients with cutaneous, ocular and mucosal melanoma were all represented, but those with primary cutaneous tumours of the trunk were more prevalent than expected. Other sites of metastatic disease were present in nearly all patients and metastases to other skeletal sites were not unusual. Pain was the most common presenting symptom. The radiographic diagnosis was generally made easily by plain radiographs, computed tomography or magnetic resonance imaging, with the most frequent finding being a destructive lesion. Bone scan gave false-negative results 15% of the time. The median survival for the group was 4 months. It is concluded that melanoma metastatic to the spine represents a late event in the evolution of this illness. Palliation should be the goal of treatment, but symptom management should be individualized, bearing in mind the short anticipated survival of these patients.