Malignant melanoma. Inflammatory mononuclear cell infiltrates in cerebral metastases during concurrent therapy with viral oncolysate

Five patients with advanced malignant melanoma, treated with viral oncolysate, had solitary central nervous system metastases that were removed surgically. Histologic examination revealed striking and significant mononuclear inflammatory cell infiltrates, consisting of a mean of 60% plasma cells and a lesser proportion of lymphocytes at the edges of the lesions, within their supporting fibrovascular trabeculae, and among the tumor cells. Comparable inflammatory changes were not found in solitary metastatic malignant melanomas removed surgically from the brains of 19 patients not treated with viral oncolysate. Similarly, multiple metastatic malignant melanomas obtained postmortem from the brains of 12 patients not treated with viral oncolysate showed minimal inflammatory responses. Ultrastructural examination of material from a single treated patient revealed morphologic abnormalities of the blood-brain barrier, changes that were perhaps conducive to infiltration of the neoplasm by inflammatory cells. The authors suggest that administration of viral oncolysate enhances the inflammatory cell response to metastatic malignant melanoma in the brain.     

A case of bilateral metastatic breast carcinoma from gastric carcinoma

The patient was a 48-year-old woman who had undergone radical surgery for gastric carcinoma in 1981. Seventeen months after the operation, recurrence of gastric carcinoma at the anastomotic stoma was found, and total gastrectomy was performed. Fourteen months after the second operation, she was revealed to have bilateral breast tumors and underwent exploratory excision. Histological examination suggested primary malignant tumor of the breast. Bilateral standard radical mastectomy was done seven days after the excision. Final histological examination revealed metastatic breast cancer originating from the stomach. She died from general metastasis seven months after the radical mastectomy in spite of adjuvant immunochemotherapy.     

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.     

A case of a malignant melanoma with late metastases 16 years after the initial surgery

We report a case of a pulmonary metastasis 16 years after the initial surgery for a malignant melanoma. The patient was a 58-year-old Japanese man. In 1976, he had a pigmented skin lesion with a diameter of 8 mm on his right third finger. He received an amputation of the finger and a dissection of the right axillary. Histological examinations of the tumor revealed a feature of a malignant melanoma with infiltration of the papillary layers of the dermis, 1.5 mm in thickness. The histological subtype was considered to be an acral lentiginous melanoma with a mixed spindle-epithelioid cell pattern. There was no regional lymph node metastasis. In December 1992, when he was 74-years-old, a round tumor in the left lower lung was discovered by chest radiography. In February 1993, he received a left lower lobectomy of the lung. Histological examination revealed a feature of a malignant melanoma with predominantly epithelioid cells and this was considered to be a metastasis from the initial skin lesion. Five months after the lobectomy, he died from a hemorrhage of a metastatic brain tumor. This case indicated the importance of periodic, life-long follow-up in treating malignant melanomas.     

Metastatic disease in patients with newly diagnosed malignant melanoma

In patients with stage I Clark's level III and IV malignant melanoma (MM), recurrence rates of 30-60% can be expected after resection of the primary lesion. If metastatic disease could be detected early and treated in such patients, survival might be prolonged. Ninety patients (37 males and 53 females) with newly diagnosed, resected stage I cutaneous MM, levels III and IV, were evaluated for metastatic disease at diagnosis using a physical examination; CBC; SMA 18; chest films; brain computed tomography (CT) scan; and radioisotope liver, spleen, and bone scans. Forty-four patients had level III and 46 had level IV melanomas ranging in thickness from 0.65 to 4.5 mm. None of these 90 patients was found to have metastatic disease. Such tests are not useful and can be replaced by a history and physical examination with substantially improved cost effectiveness.     

Novel biomarkers and therapeutic targets for optimizing the therapeutic management of melanomas

Cutaneous malignant melanoma is the most aggressive form of skin cancer with an extremely poor survival rate for the patients diagnosed with locally invasive and metastatic disease states. Intensive research has led in last few years to an improvement of the early detection and curative treatment of primary cutaneous melanomas that are confined to the skin by tumor surgical resection. However, locally advanced and disseminated melanomas are generally resistant to conventional treatments, including ionizing radiation, systemic chemotherapy, immunotherapy and/or adjuvant stem cell-based therapies, and result in the death of patients. The rapid progression of primary melanomas to locally invasive and/or metastatic disease states remains a major obstacle for an early effective diagnosis and a curative therapeutic intervention for melanoma patients. Importantly, recent advances in the melanoma research have led to the identification of different gene products that are often implicated in the malignant transformation of melanocytic cells into melanoma cells, including melanoma stem/progenitor cells, during melanoma initiation and progression to locally advanced and metastatic disease states. The frequent deregulated genes products encompass the oncogenic B-RafV600E and N-RasQ61R mutants, different receptor tyrosine kinases and developmental pathways such as epidermal growth factor receptor (EGFR), stem cell-like factor (SCF) receptor KIT, hedgehog, Wnt/β-catenin, Notch, stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) and vascular endothelial growth factor (VEGF)/VEGFR receptor. These growth factors can cooperate to activate distinct tumorigenic downstream signaling elements and epithelial-mesenchymal transition (EMT)-associated molecules, including phosphatidylinositol 3'-kinase (PI3K)/Akt/ molecular target of rapamycin (mTOR), nuclear factor-kappaB (NF-κB), macrophage inhibitory cytokine-1 (MIC-1), vimentin, snail and twist. Of therapeutic relevance, these deregulated signal transduction components constitute new potential biomarkers and therapeutic targets of great clinical interest for improving the efficacy of current diagnostic and prognostic methods and management of patients diagnosed with locally advanced, metastatic and/or relapsed melanomas.     

髋臼周围肿瘤切除术后重建

目的探讨对髋臼周围肿瘤手术切除及重建骨盆稳定性的方法，最大限度保留肢体功能，减少复发。方法2002～2005年15例髋臼周围肿瘤患者，其中软骨肉瘤8例，恶性纤维组织细胞瘤3例，Ewing肉瘤2例，转移瘤2例；6例配合化疗，4例行瘤段灭活再植，1例行瘤段灭活再植＋人工全髋置换，10例行人工假体置换（包括全髋）。结果1例术后死亡，1例感染，清创后股骨头旷置；14例术后随访9～33个月，4例软骨肉瘤复发，其他病例均能保留患肢部分功能和骨盆稳定性。结论恶性纤维组织细胞瘤、Ewing肉瘤化疗有效者保肢率高，局部复发率低；软骨肉瘤复发率高；瘤段灭活再植因骨愈合时间长，影响功能；股骨头旷置肢体短缩，跛行明显；人工假体置换可最大限度地保留肢体功能；单纯转移瘤为提高生存质量，减轻痛苦，可考虑手术治疗，但年龄大，全身脏器应急能力差者，手术应慎重。     

Evaluation of premalignant and malignant lesions during the induction of mouse melanomas

The objective of the present study was to evaluate the malignant and premalignant lesions that arise in C57BL/6 mice after treatment with 7,12-dimethylbenz(a)anthracene and croton oil. Tissues from 70 treated mice were evaluated by histological and transplantation techniques, and 17 (24%) were found to have malignant tumors. Eleven of the tumors were diagnosed as malignant melanomas, three as spindle cell sarcomas, and three as squamous cell carcinomas. The incidence of malignant melanomas (15.7%) in this group of mice was similar to that in our initial study on the induction of melanomas with 7,12-dimethylbenz(a)-anthracene and croton oil, in which two of 20 mice developed malignant melanomas. Mice that developed melanomas had been treated with croton oil for an average of 7 mo, and the mean latent period for tumor development was 11 mo. Seven of eight melanomas grew rapidly after transplantation to syngeneic C57BL/6 mice. Pigmented nevi and/or draining lymph nodes from nine of 11 mice with melanomas grew progressively after transplantation to athymic nude mice. Pooled nevi from one mouse with no apparent tumors grew into a histologically malignant melanoma after transplantation to a nude mouse. Nevi from three mice with sarcomas, one mouse with a carcinoma, and 42 tumor-free treated mice failed to grow in nude transplant recipients. Thus, only nevi from mice with either apparent or occult malignant melanomas exhibited progressive growth in nude mice. These results confirm that malignant melanomas can be induced in C57BL/6 mice at a regular, predictable rate and further indicate that this is an excellent system in which to study melanoma induction, progression, and therapy.     

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.     

Structure, expression and chromosome mapping of MLZE, a novel gene which is preferentially expressed in metastatic melanoma cells.

We isolated a novel gene, termed MLZE, from a B16-BL6 cDNA library after subtraction of B16-F10 mRNA. Expression levels of mouse MLZE (mMLZE) increased in accordance with metastatic ability of B16 melanoma sublines. Human homolog of mMlze (hMlze) contained one leucine zipper structure and two potential nuclear localizing signals. Northern blot analysis of multiple human tissues showed that hMLZE was expressed primarily in trachea and spleen. We mapped the hMLZE gene (by fluorescence in situ hybridization) to 8q24.1 - 2, which contains the c-myc gene and is often amplified in malignant melanoma. Immunohistochemistry revealed that the number of hMlze-positive cases was significantly larger in Clark levels III, IV and V melanomas (6 / 11 = 55%) than in Clark levels I and II melanomas (2 / 15 = 13%). In two cases of hMlze-positive melanomas, the strength of hMlze staining increased substantially in the deep component of the tumor. Considering that melanomas above Clark level II are more metastatic than those below Clark level III, these findings suggested that MLZE is one of the genes whose expression is upregulated during the course of acquisition of metastatic potential in melanoma cells.     

Structure, Expression and Chromosome Mapping of MLZE, a Novel Gene Which Is Preferentially Expressed in Metastatic Melanoma Cells

We isolated a novel gene, termed MLZE , from a B16-BL6 cDNA library after subtraction of B16-F10 mRNA. Expression levels of mouse MLZE (mMLZE ) increased in accordance with metastatic ability of B16 melanoma sublines. Human homolog of mMlze (hMlze) contained one leucine zipper structure and two potential nuclear localizing signals. Northern blot analysis of multiple human tissues showed that h MLZE was expressed primarily in trachea and spleen. We mapped the h MLZE gene (by fluorescence in situ hybridization) to 8q24.1-2, which contains the c-myc gene and is often amplified in malignant melanoma. Immunohistochemistry revealed that the number of hMlze-positive cases was significantly larger in Clark levels III, IV and V melanomas (6/11=55%) than in Clark levels I and II melanomas (2/15=13%). In two cases of hMlze-positive melanomas, the strength of hMlze staining increased substantially in the deep component of the tumor. Considering that melanomas above Clark level II are more metastatic than those below Clark level III, these findings suggested that MLZE is one of the genes whose expression is upregulated during the course of acquisition of metastatic potential in melanoma cells.     

Melanome der Vulva

Melanomas of the vulva are very rare malignant tumors. Often they are first diagnosed at an advanced stage and have a poor prognosis. The screening examination to detect cutaneous changes in the vulvar area is thus of particular importance. The diagnostic criteria according to Bandman also apply to vulvar melanomas. A simplified formula for the macromorphological examination to establish the suspected diagnosis is the ABCD rule. If clinical investigations and diagnostic work-up do not suggest metastases, treatment of vulvar melanoma consists of surgical resection. Analogous to the increasing trend toward conservative surgery as primary treatment of vulvar carcinoma, the primary surgical management of vulvar melanoma has developed in the direction of a local, less radical approach. The stepwise excision strategy has become established in many centers as the primary surgical procedure to treat cutaneous melanoma. Radiotherapy for the primary treatment of vulvar melanomas is only indicated in exceptional cases. There are no recommendations available specifically pertaining to vulvar melanoma with regard to systemic treatment in the metastasized stage of the disease.     

Soft tissue masses of the chest wall and axilla: has metastatic melanoma been considered?

Isolated axillary and chest wall soft tissue masses are an uncommon presentation of metastatic cancer. The authors present three patients in whom malignant melanomas metastatic to these sites had been misdiagnosed, leading to inappropriate oncologic treatment planning in all three cases. The presumed diagnoses, even after fine-needle aspiration or trucut biopsies, were soft-tissue sarcoma (n = 2) and undifferentiated breast cancer (n = 1). The combination of taking a thorough history and performing proper immunohistochemical analysis of the biopsy material would have suggested the presence of malignant melanoma in all cases. As the disease appeared locoregionally limited in all patients, radical surgical resection with extended lymphadenectomy was performed without significant dysfunction of the upper extremity. One patient agreed to postoperative immunotherapy with interferon-alpha. Two patients are currently alive 17 and 14 months after operation. One patient was found to have systemic recurrence at 5 months, one experienced two isolated local recurrences in a prior operative site that were amenable to reresection and presently has no evidence of disease 12 months after resection, and one patient remains free of disease at 14 months. Clinical presentation, suggested diagnostic workup, and therapeutic implications are discussed to avoid misdiagnoses in this setting of possible clinical presentations of metastatic melanoma.     

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.     

A case of metastatic brain tumor causing multifocal cerebral embolism

The patient was a 72-year-old woman who had previously undergone treatment for femoral chondrosarcoma (histologically rated as myxofibrosarcoma). She suddenly developed left homonymous hemianopsia and was diagnosed with cerebral embolism. Because she had atrial fibrillation, we treated her for cardiogenic cerebral embolism. About 3 months later, however, she developed left hemiplegia, and head magnetic resonance imaging revealed multiple tumorous lesions affecting the previously detected infracted area and several new areas. We assumed that a tumor embolus had caused cerebral embolism, which resulted in growth of the tumor from the embolus and formation of a metastatic brain tumor. The metastatic foci formed from the tumor embolus were visualized by diagnostic imaging, and histological examination of the resected tumor confirmed that the brain tumor had occluded the brain vessel (tumorigenic cerebral embolism). No such case has been reported to date, and this case seems to be important.     

Needle aspiration cytologic diagnosis of metastatic malignant melanoma of unknown primary origin: report of a case and review of the literature

A rare case of metastatic malignant melanoma of unknown primary origin in a 49-year-old woman is reported. The swelling, localized in the right inguinal region, was partially immovable and associated with progressively increasing pain. Initial diagnosis was set by needle aspiration cytology and was confirmed postoperatively by histologic examination of a surgical specimen. Cytomorphologic features of metastatic malignant melanomas are described and the difficulties of identification discussed. A brief review of the literature is also made, and the rarity of the case and the value of cytologic diagnosis are emphasized.     

Plantar malignant melanoma -- a challenge for early recognition

The incidence of malignant melanoma has been continuously increasing over the last few decades. Non-plantar melanomas are nowadays usually diagnosed and treated surgically at an early stage. In contrast, melanoma in a plantar location is usually diagnosed at an advanced tumour stage, conferring a poor prognosis. To discover the reasons for this remarkable difference in recognition and prognosis, we analysed our cases of plantar malignant melanoma in a retrospective study. From 1990 to 1997, we treated 925 melanoma patients. Of these, 68 cases (7%) were classified as plantar melanoma. For non-plantar melanoma patients the mean age was 52.6 years, the mean Clark level was 2.8 and the mean tumour depth was 1.22 mm. In contrast, the mean age of patients with plantar melanoma was 63.3 years, the mean Clark level was 3.61 and the mean tumour depth was 2.55 mm. The mean time between the first observation of the plantar skin lesion and the first consultation with a physician (patients' delay) was 4.8 years and, on average, it took an additional 7 months before adequate surgical treatment was performed (physicians' delay). The prognosis of our patients was poor. In 98.5% (n = 67) further metastases were observed on follow-up. Since there is still no cure for advanced plantar malignant melanoma, the early detection and subsequent surgical treatment of plantar melanoma is decisive for the prognosis. Based on our results, the poor survival can be improved by a significant reduction in the time period between the first observation of a plantar skin lesion and surgical treatment. Therefore there is an urgent need for special preventive health care campaigns to reduce significantly both the patients' and the physicians' delay.     

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.     

A case of interleukin-6-producing malignant fibrous histiocytoma originating in the heart.

Primary cardiac malignant fibrous histiocytoma is extremely rare and its pathophysiological characteristics remain largely unknown. We treated a female patient with persistent fever and disseminated intravascular coagulation. Since ultrasonic echocardiography revealed the presence of a cardiac tumor and her serum interleukin-6 level was elevated, we speculated she had a cardiac myxoma. Histological examination of the surgically resected specimen, however, revealed that the tumor was malignant fibrous histiocytoma. Although her disseminated intravascular coagulation and heart failure were transiently improved after operation, local recurrence and systemic metastasis occurred and she died 7 weeks after operation. Using the autopsied specimen, we examined whether the malignant fibrous histiocytoma constitutively synthesized interleukin-6. The interleukin-6 content in the tumor was high, consistent with interleukin-6 production by the tumor. This was confirmed by immunohistochemical analysis. To our knowledge, this is the first report demonstrating interleukin-6 production by a cardiac malignant fibrous histiocytoma.     

Primary malignant melanoma of the small bowel: a case report and review of the literature

Although small bowel involvement by malignant melanoma is most frequently metastatic, a primary origin at this site has been reported in rare cases. The biological and clinical features of these cases have not yet been summarized. Here, another case of small bowel melanoma is described, and a review of the existing literature is given. An 81-year-old man presented with anemia and gastrointestinal bleeding. A tumor of the ileum was detected by video capsule endoscopy and removed by segment resection. Histological examination revealed a malignant melanoma of the ileum. Another primary site could be excluded by clinical and radiographic examination. The patient felt well five months after surgery. Only 18 cases of primary small bowel melanoma (including the present one) have been reported to date. A literature review reveals that this rare neoplasm is associated with a slight predilection for the male gender, a predilection for the ileum and a poor prognosis.