Primary malignant melanoma of the right colon

The small and large intestines are the most common sites for metastases from cutaneous malignant melanoma. However, primary melanomas in these sites are exceedingly rare. There are several case reports of patients with primary melanoma of the small bowel, but finding of a solitary primary melanoma in the colon is exceedingly rare. We describe a patient that was operated on for bowel obstruction due to colonic intussusception resulting from a right colonic tumor. Histopathological examination confirmed a diagnosis of malignant melanoma. A thorough postoperative investigation did not reveal a primary lesion in any other site. Two years after surgery, there was no evidence for recurrent disease. The treatment and prognosis of metastatic and primary melanoma of the gastrointestinal tract is discussed as well as the embryonic base for development of primary malignant melanoma of the intestine. Primary malignant melanoma of the intestine is an extremely rare lesion that may arise in the large bowel as well. It must be differentiated from other intestinal tumors and mandates a thorough investigation to rule out the possibility of being a metastasis from another more common primary site.     

Metastatic melanoma to the skin simulating blue nevus

Cutaneous metastases from melanoma can mimic primary melanoma and melanocytic nevi. Recognition of a metastatic lesion is of great importance for proper staging and treatment decisions. In this study, a potential diagnostic pitfall is described and discussed: dermal metastases from cutaneous melanoma simulating blue nevus, a phenomenon that has received little attention. Ten blue nevus-like lesions from three patients are presented. All contained pigmented melanocytes and melanophages in variable proportions arranged in a blue nevus-like growth pattern. The blue nevus-like metastases occurred in the same anatomic region as the primary tumor or, as in one patient, near the skin scar of a dissected lymph node metastasis. Histologic clues of metastatic melanoma included the presence of atypical epithelioid melanocytes, mitotic figures, and an associated inflammatory cell infiltrate at the periphery of the lesion. Although such histologic features facilitate the recognition of a metastasis, clinical correlation is essential for a definitive diagnosis.     

Eleven-year survival from an intra-dermal melanoma.

Stage IV metastatic malignant melanoma of unknown primary (TxNxM1a) is known to have a poor prognosis. However, some patients suffering from cutaneous disease originally thought to represent metastasis have fared much better than expected. We report a patient who has survived 11 years following such a diagnosis. Due to the prolonged survival and absence of an identified primary, it is unlikely that the lesion was metastatic but may represent one of a number of other possibilities. A small number of similar cases in the literature suggest a need for awareness of this unusual group of patients.     

Direct bony invasion of malignant melanoma

Malignant melanoma is known to spread by local extention, by the lymphatics by the blood stream. Direct invasion of the bone from a cutaneous melanoma is unknown. Hence, this case is presented in view of its rarity. A 75-year-old Caucasian lady presented with a small papillary lesion in the region of a recurrent chronic cellulitis on the lower third of the lateral aspect of the right leg. Histopathology diagnosed the lesion as locally advanced malignant melanoma. Radiological investigations by X-ray and magnetic resonance imaging revealed malignant infiltration of the tibia in its mid and lower third with two soft tissue metastatic masses adjacent. Histology following amputation confirmed malignant melanoma with cranial resection margin involvement. She underwent a further above-knee amputation followed by chemotherapy. The patient recovered from the amputation but subsequently died 6 months later due to bronchopneumonia from lung metastasis.     

Microdissection-based allelotyping: a novel technique to determine the temporal sequence and biological aggressiveness of colorectal cancer

Pathologic staging in colorectal adenocarcinoma (CA) is based on the concept that the timing of metastatic tumor spread is directly related to the depth of the primary tumor invasion. To evaluate the temporal sequence of CA metastasis, we performed microdissection mutational profiling at multiple microscopic sites of primary and metastatic CA specimens. Twenty-one cases of CA were selected from fixed-tissue archives. Primary tumors were microdissected at the deepest point of invasion. Comparative mutational profiling for different genomic loci [1p36(CCM = cutaneous malignant melanoma], 3p26(OGGI = 8 oxoguanine DNA glycosylase), 5q23 (APC, MCC = mutated in colorectal cancer), 9p21(p16/CDKN2A = cyclin-dependent kinase 2A), 10q23(PTEN = phosphatase and tensin homolog [mutated in multiple advanced cancers 11), 12p12(K-ras-2 point mutation), 17p13(TP53), 18q25(DCC= deleted in colorectal cancer) was carried out on each microdissected tissue target using microsatellite loss of heterozygosity determination or DNA sequencing. All primary and metastatic sites of CA manifested acquired mutational change in 18 to 91 per cent of the genomic markers. In 15/21 (71%) cases, metastatic sites lacked a specific allelic loss seen in the corresponding primary tumor, indicating that the metastasis occurred before maximal depth of primary invasion. This was further supported by discordant mutational profiles between primary and secondary tumors, requiring divergent clonal evolution. This is the first report describing the temporal sequence and significance of sequential mutational acquisition in clinical tissue specimens with potential implications for a new molecular pathology approach to classify human cancer.     

Metastatic melanoma of the lacrimal sac

The case history of a patient with metastatic melanoma obstructing the lacrimal sac is presented. To our knowledge, this case represents a unique metastatic pattern that has not been previously reported. The patient was first treated for a melanoma of the left arm, which was excised in continuity with the axillary lymph glands. She was free of disease for 3 years until she developed metastatic disease causing obstruction of the ipsilateral lacrimal sac. Anatomical details of the metastasis were provided by computed axial tomography. Treatment consisted of excision of the metastatic lesion with reconstruction using forehead and intranasal mucosal flaps, followed by irradiation, hyperthermia, and multiple-drug chemotherapy. Emphasis is placed here on the differential diagnosis of orbital adnexal tumors.     

Metastatic melanoma with striking adenocarcinomatous differentiation illustrating phenotypic plasticity in melanoma

We report on the highly unusual case of a 75-year-old woman who developed a biphasic right axillary mass of apparent melanoma and adenocarcinoma 13 years after a diagnosis of primary melanoma on her right upper back. The differential diagnosis included a collision tumor and metastatic melanoma with adenocarcinomatous transdifferentiation. We utilized immunohistochemical staining, DNA sequencing, and comparative genomic hybridization (CGH) to characterize this unusual tumor. By immunohistochemistry, the melanomatous component was positive for S100 and Melan-A, and had patchy positivity for cytokeratin. The adenocarcinomatous component was negative for melanoma markers, but was strongly positive for cytokeratin. In addition, the glandular component was positive for CDX-2 and Ber-EP4, giving the distinct histologic and immunohistochemical impression of a gastrointestinal metastasis nested within a deposit of metastatic melanoma. Clinical and radiologic workup failed to reveal a primary gastrointestinal malignancy. Molecular genetic analysis, including DNA sequencing and CGH, revealed that both areas contained an identical NRAS Q61K mutation and had highly similar CGH profiles, including gains of chromosome 1q and losses of 1p, 4, 9, and 10, which are archetypical of melanoma. The NRAS mutation was also identified in a deposit of metastatic melanoma resected 12 years earlier, but was not seen in the patient's nontumorous tissue, indicating that it was somatically acquired. Genetic analyses demonstrate that 2 morphologically distinct tumors arose from a common ancestor melanoma cell that harbored an NRAS mutation and subsequently divergently evolved by the acquisition of additional genomic alterations. Our findings illustrate the ability of molecular analyses to resolve lineage in complex neoplasms and illustrate the phenotypic plasticity of cancer cells.     

The curious incident of 3 melanomas and their possible origins—A case report and review of literature

BackgroundWe describe an unusual case of 2 intra-parenchymal breast melanomas with a concomitant subcutaneous melanoma in the ipsilateral upper limb and no definite primary lesion.Case reportOur patient is a 40-year-old Chinese female who presented with a breast lump in her left breast for which excision biopsy showed melanoma. A PET-CT revealed a second lesion in her breast. A left upper arm nodule with no overlying skin changes was also noted. She underwent a mastectomy and excision biopsy of the upper arm nodule. Histology showed that the second breast lesion was also a melanoma, while the arm nodule contained melanoma cells within a fibrous capsule.ConclusionThe presence of a melanoma in the breast should prompt a close and meticulous search for a primary lesion and potential signs of metastasis. Encapsulated subcutaneous nodules can be attributed to replaced lymph nodes or subcutaneous melanoma which can be either primary dermal melanoma or metastasis from an unknown primary.     

Very late cerebral metastasis from malignant melanoma

The appearance of cerebral metastases of malignant melanoma (MM) more than 10 years after the primary diagnosis is extremely rare. We report the case of a patient with a solitary brain metastasis of MM who came to our observation 11 years after the treatment of the cutaneous lesion. This patient, who up until then had appeared disease free, presented with two episodes of intracranial haemorrhage in a 5-month period. Neuroradiological findings (CT, MRI, angiogram) did not suggest a brain metastasis. The correct diagnosis was reached only after histopathological examination of the surgically removed lesion. On the basis of this experience, we stress the importance of a long-term clinical and radiological follow-up of all patients with MM.     

Radiculopathy due to malignant melanoma in the sacrum with unknown primary site

Melanoma is an interesting tumor, showing the appearance of metastasis without any trace of its primary lesion. To report a very rare case of malignant melanoma in the sacrum with unknown primary origin. The authors present a case of a 52-year-old man who was admitted with increasing lower back, left buttock, and left lower extremity pain, and dysuria. Plain radiograph, computed tomography scan, and magnetic resonance imaging revealed a destructive lesion in the sacrum and left ilium, which infiltrated the spinal canal and sacroiliac joint. The tumor cells were immunoreactive for HMB-45. The pathological diagnosis was malignant melanoma. No obvious primary malignant melanoma was detected on the skin surface, on the oral or anal mucosa, or in the fundus oculi. Following radiotherapy and chemotherapy, the severe buttock pain disappeared and the patient was able to walk without impediment. However the patient died nine months after initial diagnosis. Malignant melanoma in the sacrum with an unknown primary site, showing S1 radiculopathy is reported for the first time. The melanoma could have been a metastatic tumor of the sacrum, although the primary site was not detected. The incidence of primary melanoma is increasing faster than any other cancer. Thus treatment of patients with spinal metastasis of melanoma is an important challenge for orthopedic surgeons.

     

Case report: Successful removal of solitary metastatic cerebral malignant melanoma

A 26-year-old female patient presented with a previous history of cutaneous malignant melanoma. She displayed signs of an expanding cerebral lesion due to a solitary metastasis of malignant melanoma; this was removed in toto, suggesting a cure.     

p53变异与结肠癌肝转移肝部分切除术后病人生存期的关系

目的 了解ｐ５３基因及其蛋白在结肠癌发生、转移过程中的动脉变化以及ｐ５３变异与生存期的关系。方法 ｐ５３基因ｅｘｏｎ５－９以ＤＧＧＥ及自动ＤＮＡ序列分析来检测。结果 ４１例大肠癌病人中,２６例呈ｐ５３变异（６３％）,其中６例公在肝转移灶发现ｐ５３变异,其余均为原发灶、转移灶一致性的变异。另有３例原发灶即有ｐ５３变异的病人,在转移灶出现了新增加的变异。生存分析显示,在肝转移灶含变异型ｐ５３的病人比含野生型Ｐ５３者具有更长的术后生存期。结论 在结肠癌肝转移过程中,ｐ５３变异主要开始于肠癌原发灶,并被保持于转移至肝脏的癌细胞内,小部分ｐ５３变异也可以始发于转移灶。对于实施肝部分切除术的病人,术后生存期在转移癌灶含变异型ｐ５３者长于含野生型ｐ５３者。     

Clinical and pathologic distinction between primary and metastatic mucosal melanoma of the head and neck

Metastatic mucosal melanoma is extremely rare. Only 0.6% to 9.3% of patients with cutaneous malignant melanoma will have metastases to the mucosa of the upper aerodigestive tract. The records of all patients with mucosal melanoma of the head and neck at the University of California, Los Angeles Medical Center during the past 30 years were reviewed. Patients with primary tumors were separated from those with metastatic involvement from a cutaneous primary site. These two groups were compared for differences in clinical symptoms, histopathologic findings, treatment, and survival characteristics. Frequent sites of metastatic involvement included the base of tongue and nasal cavity. These arose from a variety of cutaneous sites including the trunk and extremities and, in most instances, did not arise until 2 to 7 years after the initial cutaneous lesion. Most of those with metastases to the head and neck mucosa had disseminated disease. The histopathologic distinction between the two groups is described with photomicrographs. Junctional activity in the overlying or adjacent mucosa distinguishes primary mucosal melanoma from metastatic disease, in which the overlying mucosa is usually intact. This difference is useful in determining workup and treatment options. Aggressive surgical resection is suggested in treatment of primary melanomas, whereas surgery is at best palliative in those with metastatic disease. (OTOLARYNGOL HEAD NECK SURG 1995;112:700-6.)     

Spontaneous regression of metastatic melanoma

Spontaneous regression of malignant melanoma is a well-known but rare event. It seems to be caused by immunological enhancement similar to the regression observed after intralesional injection of Bacille Calmette-Guérin into cutaneous melanoma metastases. A patient is presented in whom an incisional biopsy of a metastatic melanoma in an inguinal lymph node was followed by complete disappearance of the metastasis. Reviewing the literature, several similar patients were found in whom spontaneous regression of a metastatic melanoma occurred after an incomplete excision or biopsy of the tumor. It appears that in rare instances, an unspecific mechanical stimulus may trigger an increase in immunocompetence, although laboratory evidence for this has only rarely been produced. A plea is made for serial immunological studies in consecutive patients with melanoma, to further elucidate these puzzling phenomena.     

Familial melanoma

Approximately 5% to 10% of cases of cutaneous melanoma occur in families that have a hereditary predisposition for this disease. In 20% to 40% of such melanoma families, germline mutations in the CDKN2A gene have been identified. Apart from a high risk of melanoma, a proportion of kindreds that have familial melanoma also have an increased risk of pancreatic carcinoma. Guidelines for management of familial melanoma and the issue of genetic testing for CDKN2A germline mutations are discussed.     

人原发性小肠恶性黑色素瘤裸小鼠原位移植肝转移模型的建立

目的为探讨小肠恶性黑色素瘤的发病机制和实验治疗提供理想的动物模型。方法将原发性小肠恶性黑色素瘤患者术中原发灶和肝转移灶新鲜瘤组织块分别植入裸小鼠的小肠黏膜层，观察原位移植成瘤率，移植瘤的侵袭和肝转移率。进行形态学[光镜、电镜和免疫组织化学（免疫组化）]染色体核型和流式细胞分析。结果人小肠恶性黑色素瘤原发灶和肝转移灶新鲜瘤组织均获移植成功。建成一株人原发性小肠（原发灶）恶性黑色素瘤裸鼠原位移植模型（HSIM-0501）和一株人原发性小肠（肝转移灶）恶性黑色素瘤裸鼠原位移植肝转移模型（HSIM-0502）。移植瘤组织病理学为高度恶性黑色素瘤；免疫组化显示S-100蛋白；黑色素瘤单克隆抗体45阳性；电镜下瘤细胞质内可见大量黑色素颗粒及黑色素复合体。染色体众数55～59条；流式细胞DNA指数值1．49-1．61；均为异倍体。HSIM-0501和HSIM-0502分别传至25代和27代；共移植裸鼠317只；肿瘤移植成瘤率和液氮冻存复苏成活率均为100％。HSIM-0501肝转移率为46．2％，淋巴结转移率为36．7％；HSIM-0502肝转移率和淋巴结转移率均为100％。移植瘤在裸鼠小肠内自主侵袭生长，发生血液转移、淋巴结转移和腹腔内种植性转移。结论HSIM-0501和HSIM-0502是首次成功建立的人原发性小肠恶性黑色素裸鼠原位移植肝转移模型，可用于小肠恶性黑色素瘤的发病机制、侵袭和转移及抗转移实验治疗的研究。     

皮肤恶性黑色素瘤手术结合大剂量罗扰素治疗的疗效分析

目的探讨皮肤恶性黑色素瘤手术结合大剂量罗扰素治疗的疗效。方法1998年1月～2005年12月，收治皮肤恶性黑色素瘤患者33例，男20例，女13例；年龄17～79岁。病程2个月～7年，中位病程3．5年。9例Ⅰ期患者行单纯病灶扩大切除结合中厚植皮（或邻位皮瓣）修复创面，23例Ⅱ期患者行病灶扩大切除及区域淋巴结清扫术（或截肢），1例Ⅲ期患者姑息性病灶切除。所有患者术后均辅以大剂量罗扰素生物治疗。结果9例Ⅰ期患者术后切口愈合好，获随访7个月～8年，无复发。Ⅱ期患者中，2例切口愈合延迟，经换药愈合；1例失访，余22例获随访5个月～7年，其中1例复发，部位于大腿原发灶旁，再次予病灶广泛切除后，大剂量罗扰素治疗。1例Ⅲ期患者治疗1年6个月后因肺部转移并发呼吸衰竭死亡。结论手术结合术后大剂量罗扰素综合治疗恶性黑色素瘤疗效满意。     

Metastatic melanoma of the pituitary gland. Case report

The authors report on the clinical features and imaging studies in a case of metastatic melanoma of the pituitary gland. Cerebral metastatic melanoma and pituitary metastasis from any source are commonly associated with systemic metastasis, whereas pituitary metastatic melanoma without widespread disease dissemination is distinctly rare. This 46-year-old man presented with diabetes insipidus and anterior pituitary dysfunction 5 years after he underwent resection of a cutaneous malignant melanoma of the neck. Magnetic resonance imaging demonstrated the presence of melanin within a sellar tumor mass. Transsphenoidal resection was performed and histopathological examination of tumor material confirmed metastatic melanoma. Postoperative [18F]fluorodeoxyglucose-positron emission tomography revealed no other focus of hypermetabolism in the patient's body.     

Primary malignant melanoma of the kidney

The fourth patient with a solitary malignant melanoma of the kidney with no apparent primary lesion or metastasis is reported.     

Rupture of liver metastasis of malignant melanoma —A case of hepatic resection—

A case is reported in which resection of the left lateral segment of the liver was performed for rupture of a metastatic malignant melanoma in an attempt to control hemorrhaging. The primary lesion was located in the skin of the head, and there were multiple metastases to the lung, liver and distant nodes. The patient, a 47-year-old woman, had been undergoing systemic chemotherapy for the disseminated disease, but she presented with intraabdominal bleeding from a metastatic nodule in the left lateral segment of the liver. An emergency operation was performed, and the immediate postoperative course was uneventful. She was discharged 10 days after the operation. The patient died, however, of hemorrhagic shock due to renewed intraabdominal bleeding on the 39th postoperative day. It is concluded from the above case that hepatic resection for a bleeding metastasis of malignant melanoma is a viable option even in patients with disseminated disease.