Amelanotic Malignant Melanoma of the Rectum: Report of a Case

We describe herein a case of amelanotic melanoma of the rectum. Macroscopically, the tumor was lacking in pigmentation and microscopically, it was found to be deficient in melanin. Moreover, the tumor cells showed positive staining for HMB-45, the antimelanoma antibody, which led to a diagnosis of amelanotic melanoma. The patient died of metastatic tumors in the liver and bone 17 months after undergoing abdominoperineal resection of the rectum and dissection of the bilateral inguinal lymph nodes. Received: June 12, 2000 / Accepted: January 9, 2001     

Ocular Melanoma Metastatic to Skin: The Value of HMB-45 Staining

BACKGROUND: Cutaneous metastatic disease is an important finding that may represent the first sign of systemic cancer, or, if already known, that may change tumor staging and thus dramatically altered therapeutic plans. Although cutaneous metastases are relatively frequent in patients with cutaneous melanoma, they are less so from ocular melanoma. OBJECTIVE: To demonstrate the value of HMB-45, staining in the detection of ocular melanoma metastatic to skin. METHODS: The immunohistochemical stain HMB-45 a monoclonal antibody directed against intact human melanoma cells, was employed on a skin biopsy specimen from a cutaneous tumor. Results: HMB-45 staining was positive in the atypical hyperchromatic cells of the deep dermis. CONCLUSION: HMB-45 may be of value in the detection of ocular melanoma metastatic to skin. Cutaneous metastatic disease is a somewhat common and extremely important diagnosis. Although cutaneous metastases from cutaneous melanoma are relatively frequent, those from ocular melanomas are less so. Use of histochemical staining, especially the HMB-45 stain, allows confirmation of the diagnosis.     

HMB-45 immunohistochemical staining of sentinel lymph nodes: a specific method for enhancing detection of micrometastases in patients with melanoma

Despite the profound therapeutic and prognostic implications of nodal metastases in patients with melanoma, there is no consensus strategy for the optimal detection of metastases in sentinel lymph node biopsies. Traditional microscopic examination may be too crude to detect scattered, individual tumor cells. Conversely, molecular genetic techniques are prone to false-positive results. The authors evaluated the ability of HMB-45 immunohistochemistry to enhance detection of melanoma cells in histologically negative sentinel lymph nodes. Ninety-six sentinel lymph nodes, collected over a 25-month period from 66 consecutive patients with melanoma, were processed routinely and sectioned serially. Slides 1, 3, and 5 were stained with hematoxylin and eosin. HMB-45 staining was performed on an intervening slide in histologically negative nodes. To assess the background incidence of HMB-45-positive cells in lymph nodes draining the skin, the authors stained 244 cervical and axillary lymph nodes from patients without melanoma. Metastases were apparent microscopically in 12 (18%) of the 66 patients with melanoma. Of the remaining 54 patients, four patients (7%) had lymph nodes harboring individual, scattered HMB-45-positive cells. Benign nevocellular aggregates were present in four of the 96 sentinel lymph nodes (4% nodal incidence), but they were HMB-45-negative. The authors did not observe a single HMB-45-positive cell in the 244 lymph nodes from patients without melanoma. Immunohistochemistry appears to represent a specific means of enhancing tumor detection in sentinel lymph nodes from patients with melanoma.     

Primary malignant melanoma of the anterior mediastinum in a child

Primary malignant melanoma of the mediastinum is extremely rare. We report a case not previously reported of primary malignant melanoma located in the mediastinum in a 11-year-old boy. The tumor could not be completely resected as a result of extensive invasion of the large blood vessels. Histologically, the tumor was heavily pigmented and composed of vague fascicles of spindle cells intermingled with epithelioid cells. Immunohistochemical analysis showed vimentin, S-100 protein, Melan-A, and HMB-45 immunoreactivity in most of the tumor cells. Nearly 50% of the tumor cells were also positive for p53. It is suggested that primary malignant melanoma of the anterior mediastinum may have a histogenetic relationship to the recently described aggregates of nevus cells in the thymus or mediastinal lymph nodes.     

Signet-ring cell melanoma. A rare morphologic variant of malignant melanoma

We recently received in consultation a lymph node involved by metastatic malignant melanoma with unusual and previously undescribed morphologic features. The neoplastic cells had a striking signet-ring appearance, similar to the signet-ring cells normally seen in mucin-producing adenocarcinoma and signet-ring cell lymphoma. Review of our consultation files of malignant melanomas revealed an additional case in which the neoplastic cells had a signet-ring cell appearance. Electron microscopic studies revealed that formation of signet-ring cells is caused by the presence of abundant vimentin filaments in the cytoplasm of neoplastic cells. Immunologic studies using a series of monoclonal and polyclonal antibodies, including S-100 protein, HMB-45, vimentin, cytokeratin, leukocyte common antigen, and Leu-M1, on both cases clearly established the diagnosis of this morphologically unusual variant of malignant melanoma for which we propose the term "signet-ring cell melanoma."     

HMB-45 staining of dysplastic nevi. Support for a spectrum of progression toward melanoma

Dysplastic nevi are melanocytic tumors that occupy intermediate positions in the spectrum of melanocytic proliferations. Although they are invariably cured if completely excised, their biologic potential if left untreated is unknown. We examined a series of such lesions with HMB-45, a melanocyte-specific antibody, in order to explore protein expression within these borderline lesions. HMB-45 has previously been shown to label intraepidermal melanocytes within melanomas and within all nevi. Intradermal melanoma cells also label with HMB-45, but dermal nevus cells within common melanocytic nevi do not normally stain. In contrast, we found mild to moderate staining of nevus cells within the papillary dermis of dysplastic nevi and within residual nevus cells adjacent to malignant melanomas. In the same lesions, we demonstrated strong staining of intraepidermal melanocytes. Thus, dermal nevus cells within dysplastic nevi and within residual nevus cells adjacent to malignant melanomas are expressing low-level amounts of a protein expressed by melanoma cells, but not by dermal nevus cells within wholly benign melanocytic tumors. This lends support to the concept of these lesions as precursor lesions with undetermined biologic potential.     

Solitary Renal Melanoma? A Case with Long Survival After Initial Treatment

A case of a solitary melanocytic renal tumor with no apparent primary lesion or metastasis is reported. Pathologically the tumor was composed of cells with brown pigmentation that strongly reacted to monoclonal antibody HMB-45 immunohistochemically. Few mitotic figures, mild nuclear atypia and nucleolar prominence were observed. These findings confirmed that the tumor cells were melanogenetic but the malignant potential of the tumor was low in comparison to that of typical malignant melanoma. The patient is doing well 44 months after partial resection of the renal tumor and postoperative chemotherapy. The interesting pathological feature may account for the unique clinical course.     

HMB-45 reactivity in conventional uterine leiomyosarcomas

We studied the human melanoma black-45 (HMB-45) reactivity in 25 uterine leiomyosarcomas including 23 conventional and 2 myxoid variants. Eleven tumors were poorly differentiated, and 14 were well to moderately differentiated. Nine uterine leiomyosarcomas labeled with HMB-45 in 10% or less of the tumor cells. Six were poorly differentiated and 3 were well differentiated. Our study indicates that 36% of conventional leiomyosarcomas focally express HMB-45. HMB-45 reactivity was more common in the poorly differentiated than in the well-differentiated group of leiomyosarcomas. In light of our findings and of those recently reported in the literature, we believe that the term PEComa should not be used for uterine leiomyosarcomas with clear cells or for conventional leiomyosarcomas that stain positively with HMB-45.     

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.

     

Primary Melanoma of the Adrenal Gland,a Continuous Dilemma: Report of a Case

The adrenal gland can frequently be the site of metastatic deposits, including malignant melanocytic tumors; however, primary melanoma of the adrenal gland is exceptional. We reviewed 18 cases reported in the English literature to date, and here add another case which occurred in a 78-year-old man. The patient underwent right suprarenalectomy and the pathology report showed a malignant melanoma of the adrenal gland. Immunohistochemical staining revealed a positive antibody-specific cytoplasmic reactivity to S-100 and HMB-45 proteins with a negative reaction for cytokeratin (AE1, AE3), synaptophysin, chromogranin and neuron-specific enolase. There are diagnostic criteria for accepting an adrenal melanoma as primary; however, an autopsy is the final step to confirm this infrequent pathology.     

Evaluation of micrometastases in sentinel lymph nodes of cutaneous melanoma: higher diagnostic accuracy with Melan-A and MART-1 compared with S-100 protein and HMB-45

Accurate diagnosis of micrometastases in sentinel lymph nodes of cutaneous melanoma is critical for proper clinical management. S-100 protein and HMB-45 are the traditional immunomarkers widely used for this purpose. However, the interpretation of micrometastases by these markers is difficult with significant reduction in the diagnostic accuracy. S-100 protein demonstrates immunoreactivity for other nonmelanoma cells and obscures nuclear details, which are crucial for the interpretation of single cell metastases. We compared the new melanoma markers, Melan-A (clone A103) and MART-1 (clone M2-7C10), with S-100 protein and HMB-45, by examining 77 formalin-fixed paraffin-embedded sections of sentinel lymph nodes from 13 cases of primary cutaneous melanoma. CD68 (PG-M1) and hematoxylin-eosin-stained sections were also studied. Four pathologists interpreted the staining pattern after concealing the identity of each immunomarker. Az values (area under receiver operating characteristic curve) with receiver operating characteristic curve were higher with Melan-A (0.9742) and MART-1 (0.9779) compared with S-100 protein (0.8034) and HMB-45 (0.8651), demonstrating a higher diagnostic accuracy with Melan-A and MART-1 with superior detection of melanoma micrometastases. Melan-A and MART-1 showed sharp cytoplasmic immunoreactivity, almost exclusively restricted to the melanoma cells. Therefore, Melan-A and MART-1 are recommended for the evaluation of micrometastases in sentinel lymph nodes of cutaneous melanoma as a routine alternative to S-100 protein and HMB-45.     

Is MAGE-1 expression in metastatic malignant melanomas really helpful?

Melanoma antigen-encoding gene (MAGE-1) has been introduced as a sensitive immunohistochemical marker to aid in the diagnosis of malignant melanomas, in particular, those that are HMB-45 negative. Our goal was to determine the consistency of positive staining in melanomas on the basis of the usefulness of MAGE-1 in comparison with tyrosinase and MART-1. We studied 56 malignant melanomas using immunohistochemical markers to MAGE-1, tyrosinase, MART-1, HMB-45, and S-100. Six of 17 HMB-45-negative cases were strongly positive for MAGE-1 (35%), while 9 of 39 HMB-45-positive cases were positive for MAGE-1 (23%), overall, 27% positivity (n = 56). Tyrosinase and MART-1 were both strongly positive in 42 of 56 cases (75%). Fifty-two of 56 cases were strongly positive for S-100 (93%). We found MAGE-1 to be less sensitive than described in other studies, and overall, not very helpful, especially as a predictor of aggressive behavior. Although MAGE-1 expression has been considered as a target for immunomodulation therapy, our findings do not indicate consistent expression of this epitope in a majority of melanomas. S-100 protein, tyrosinase, and MART-1 immunomarkers were more frequently positive in our melanoma cases and appear to constitute a useful panel of markers to aid in the diagnosis of metastatic malignant melanomas, especially in patients with an unknown primary.     

Primary small bowel melanoma. A case report and a review of the literature

Primary malignant melanoma originating from the small intestine is extremely rare. Only a limited number of cases are described in the literature. Most commonly small intestine is affected by metastatic tumors from other primary lesions. We present a case of a 68-years old male diagnosed with primary malignant melanoma as an ulcerated and bleeding mass in the jejunum - located 40 cm away from the Treitz band. In our case the diagnosis was confirmed at laparotomy and enterectomy. Histology revealed a neoplastic infiltration involving the entire intestinal mucosa, with atypia of neoplastic cells and immunoreactivity to HMB45(+), Melan A(+) and S100(+), confirming the diagnosis of melanoma. There was not revealed a primary lesion in the skin, eye, anus, rectum or in other location by the post-operative investigation. An eleven-month close follow-up has not revealed any metastasis. Therefore a definitive diagnosis of primary malignant melanoma was set.     

Malignant Melanoma and Adenocarcinoma of a Barrett Oesophagus

An adenocarcinoma with a malignant melanoma in a Barrett oesophagus is extremely rare. We did not find any other cases in the English literature. The diagnosis of a malignant melanoma can be difficult but can be made by tissue examination with a special immunoreaction with several markers to see it expresses S-100, but lacks activity for KER and EMA. S-100 is relatively non-specific as a single immunodeterminant in the diagnostic separation of melanoma and anaplastic carcinoma, but very sensitive. Immunohistochemically, these tumours react to S-100 protein, neuron-specific enolase and HMB-45 antibody (less sensitive than S-100), but not to cytokeratin or CEA. In our case it was obvious that there were two different tumours because the MM was negative for cytokeratin, but the adenocarci-noma was positive for cytokeratin.     

Malignant melanoma and adenocarcinoma of a Barrett oesophagus

An adenocarcinoma with a malignant melanoma in a Barrett oesophagus is extremely rare. We did not find any other cases in the English literature. The diagnosis of a malignant melanoma can be difficult but can be made by tissue examination with a special immunoreaction with several markers to see it expresses S-100, but lacks activity for KER and EMA. S-100 is relatively non-specific as a single immunodeterminant in the diagnostic separation of melanoma and anaplastic carcinoma, but very sensitive. Immunohistochemically, these tumours react to S-100 protein, neuron-specific enolase and HMB-45 antibody (less sensitive than S-100), but not to cytokeratin or CEA. In our case it was obvious that there were two different tumours because the MM was negative for cytokeratin, but the adenocarcinoma was positive for cytokeratin.     

人原发性小肠恶性黑色素瘤裸鼠肺转移模型的建立

目的 建立原发性小肠恶性黑色素瘤肺转移动物模型.方法 采用人原发性小肠恶性黑色素瘤肺转移瘤的新鲜瘤组织块植入裸鼠小肠黏膜层内,当裸鼠体内形成肺转移瘤后重复筛选4次,再将肺转移瘤植入另一只裸鼠小肠黏膜行鼠问连续传代.观察原位移植成瘤率和转移率,进行形态学、染色体核型和流式细胞仪分析.结果 建成的人原发性小肠恶性黑色素瘤裸鼠肺转移模型命名为HSIM-0601,瘤细胞胞质内可见大量黑色素颗粒及黑色素复合体,S-100、HMB-45呈阳性表达.染色体数57～59条;流式细胞DNA指数值1.49,均为异倍体.HSIM-0601已传至26代,共移植裸鼠173只,成瘤率和液氮冻存复苏成活率均为100%.肺转移率为100%(173/173),淋巴结转移率为61.3%(106/173).结论 首次成功地建立了人原发性小肠恶性黑色素瘤裸鼠原位移植肺转移模型HSIM-0601.完整地模拟了人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肺转移机制和抗转移治疗提供了理想的动物模型.     

Metastatic malignant melanoma resembling malignant peripheral nerve sheath tumor: report of 16 cases

We report 16 cases of metastatic malignant melanoma presenting clinically as lymphadenopathy or a soft-tissue mass and histologically resembling malignant peripheral nerve sheath tumor (MPNST). In two cases, the metastatic malignant melanoma was preceded by a primary cutaneous malignant melanoma; in four cases, it presented synchronously with such a tumor; and in 10 cases, there was no evidence of a previous or concomitant malignant skin lesion. Histologically, the tumors were characterized by a malignant-appearing spindle cell proliferation arranged in fascicles, often accompanied by a peritheliomatous growth pattern, alternating hypercellular and hypocellular areas, numerous mitoses, and foci of necrosis. In nine cases, there was residual lymph node tissue. In none of the cases was there evidence of an anatomic connection with a nerve, a coexistent neurofibroma, or the stigmata of neurofibromatosis. Fourteen of the cases showed strong and generally diffuse immunoreactivity for S-100 protein, and five cases showed positivity for HMB-45. Four of eight patients with follow-up information died of the disease. Tumors with a microscopic appearance compatible with MPNST but showing strong diffuse S-100 protein staining and featuring remnants of lymph node may represent metastatic malignant melanomas and should elicit a search for a previous or concomitant tumor in the skin and other sites. The similarities these tumors share with MPNST are probably related to their common neuroectodermal histogenesis.     

Malignant epithelioid angiomyolipoma ('sarcoma ex angiomyolipoma') of the kidney: a case report and review of the literature

Malignant epithelioid angiomyolipoma is a recently described rare tumor of the kidney. Its existence has been questioned, however, on the basis of incomplete evidence of malignant behavior, the absence of an associated classic angiomyolipoma component, or the absence of immunoreactivity for HMB-45 in some cases. We describe a case that was HMB-45-positive and arose in association with a classic angiomyolipoma. The patient was treated with a partial nephrectomy. Three years later, she developed rapidly enlarging liver nodules. A fine-needle aspiration of the liver confirmed the presence of pleomorphic epithelioid cells morphologically and immunohistochemically identical to those comprising the primary renal tumor. After two cycles of treatment with doxorubicin, there was a 50% reduction in the size of the tumors with marked improvement in performance status. We believe this case confirms the existence of a malignant epithelioid angiomyolipoma.