A Case of CD8+ T Cell Lymphoma Occurring during Treatment for In situ Malignant Melanoma of the Palate

A 53-year-old Japanese male noticed pigmented lesions on his right upper gingiva and hard palate in February of 1986. Histological examination revealed in situ malignant melanoma. Chemotherapy, β-interferon, and oral BCG were given. However, tumors subsequently developed in the nasal cavity in March of 1989. The patient died in April of 1990 after developing Garcin's syndrome and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Autopsy revealed aggressively infiltrating, whitish tumor masses invading the hard palate, the nasal cavity, the paranasal sinuses, the base of the skull, cranial nerves I-X, and the pituitary body, as well as severe necrosis of the soft palate. However, there was no evidence of malignant melanoma. Instead, these oval tumor cells had atypical nuclei and scanty cytoplasm. They contained no melanin granules, were negative for S-100 protein, and were also negative for various melanoma-associated antigens. They were positive for CD2, CD3, and CD8 by avidin-biotin-peroxidase complex immunohistochemistry. It was concluded that the patient had CD8⁺ non-Hodgkin's malignant lymphoma (diffuse, large cell type) of the nasopharyngeal region, which was preceded by in situ malignant melanoma of the palate.     

Melanoma in private practice: Do dermatologists make a difference?

Malignant melanoma is a major contributor to Australian morbidity and mortality. In this era of resource rationalisation, we seek to address the issue of whether routine full-skin examination by a dermatologist, rather than focussed examination of flagged lesions, will increase melanoma diagnosis. A retrospective chart review was undertaken between 1 July 2007 and 30 June 2008 in a private dermatology group practice in order to ascertain the number and characteristics of incidentally detected melanomas on routine skin examination. A total of 94 melanomas were detected during this 12-month period. Of these, 57 (60.6%) were incidentally detected by the dermatologist, 41 (71.9%) were in situ melanomas and 16 (28.1%) were invasive melanoma. Of the invasive lesions, 15 (94%) were 'thin' (less than 1.0 mm Breslow thickness). The majority of melanomas were found in men, and were distributed in areas of high cumulative sun exposure. Nine (9.6%) lesions were clinically misdiagnosed by the dermatologists and picked up on histopathology. This audit reaffirms the usefulness of routine full-skin examination by dermatologists in detecting de novo melanoma as part of the global strategy in reducing the burden of melanoma in Australia.     

A Case of Superficial Spreading Melanoma In situ 2.5 mm in Diameter

A 60-year-old woman with superficial spreading melanoma in situ, measuring 2.5 mm in diameter, was examined. She had noticed a very small pigmented lesion 1.2 mm in diameter on her left lower leg in April of 1989. By April of 1990, it had grown to 2.5 mm in diameter. Its edge was irregular, and its color was variegated black to brown. Skin surface markings had disappeared in the center portion. Histopathologically, the lesion was asymmetrical. Atypical large cells nested in the lower epidermis and were scattered singly in the mid and upper epidermis, as seen in Paget's disease. At the periphery of the lesion, single large tumor cells were scattered in the mid epidermis. The tumor cells reacted to monoclonal anti-melanoma antibody HMB-45.     

Primary Malignant Melanoma of the Penis

A 50-year-old man had a primary malignant melanoma of the penis associated with granuloma telangiectaticum in the pigmented lesion. The patient had an operation for phimosis at the age of 20 and after the operation, he noticed a pigmented lesion at the operation site. We examined the literature and found 16 cases of primary malignant melanoma of the penis in Japan.     

Accuracy in the Clinical Diagnosis and Pattern of Malignant Melanoma at a Dermatological Clinic

The diagnostic pattern of malignant melanoma and clinical suspicion rate has been investigated at a dermatological university clinic. Of 174 histologically proven malignant melanomas, 60 (34%) were not clinically suspected as melanomas. The accuracy of clinical diagnosis increased with level of experience. Physicians with <1 year experience in dermatology were able to detect malignant melanoma as the first diagnosis in 31% of the cases in contrast to 63% for those with >10 years experience. Of 50 patients immediately referred from the dermatologic clinic to surgery departments, 12 did not have melanoma.     

皮肤黑素瘤70例临床与病理特征分析

目的探讨皮肤黑素瘤的临床和病理特点。方法回顾分析1983-2010年本院病理诊断为皮肤黑素瘤患者的临床资料,重新阅片,再次进行确认诊断和病理分型,对病理诊断不明确者行免疫组化检查,并进行统计学分析。结果皮肤黑素瘤高峰发病年龄为51~60岁,肢端、非肢端部位黑素瘤各占70.00%和30.00%,肢端雀斑样黑素瘤最多,占67.14%,其次为恶性雀斑样痣型黑素瘤(11.43%)和浅表扩散型黑素瘤(10.00%),本研究中结节型仅有3例(4.29%),非暴露与暴露部位在原发损害、原位和侵袭的分布上差异有统计学意义(P=0.045,0.013)。甲下黑素瘤手部明显多于足部(P=0.000)。结论国内黑素瘤发病可能有年轻化趋势;外伤在肢端部位黑素瘤发生中作用有待进一步证实;临床的ABCD标准敏感性较高,可推广使用和作为患者自检的方法。     

恶性黑素瘤的分级与预后

恶性黑色素瘤是皮肤肿瘤中恶性程度较高、发展迅速、严重威胁患者生命的严重疾病。一旦发生转移，尽管采取治疗亦难奏效。近年来本病的发生率有上升趋势， 对该病进行分级体系有利于早期诊断和治疗， 使预后良好。现就近年相关分级体系整理如下。     

恶性黑色素瘤选择性表达孕激素受体并与PCNA呈负相关性

目的探讨孕激素受体(PR)在恶性黑色素瘤(MM)中的表达情况及意义。方法以免疫组化法检测35例MM患者标本,8例痣细胞痣PR及增殖性细胞核抗原(PCNA)的表达,并结合临床及组织病理学资料进行分析。结果在MM中PR的阳性表达率为25.7%,在痣细胞痣中无表达。MM中PR表达与PCNA表达显著负相关。女性、年龄≤55岁、病程>1年、溃疡以及非肢端型组织亚型PR阳性比例增高,但均无统计学意义。结论PR在MM中选择性表达并可能具有抗增殖作用。     

Prognostic Evaluation of Cutaneous Malignant Melanoma Based on the pTNM Classification

The prognoses of 100 consecutive melanoma patients were analyzed on the basis of Breslow's thickness and Clark's levels as well as according to stage employing the 1987 UICC pTNM classification. Among patients with lesions ≦1.50 mm thick, the 10-year survival rate was 100% for both pT1 (n=13) and pT2 (n=6) disease, 73.4% for pT3a disease (n=26), 62.2% for pT3b disease (n=15), 69.3% for pT3 (n=41) disease, and 38.7% for pT4 disease (n=38). Significant differences in survival were found between the pT4 group and the pT1/pT3a or pT3 groups. The 10-year survival rate was 100% for level II (n=13) and level III (n=13) disease, 58.3% for level IV (n=46) disease, and 34.5% for level V (n=26) disease. Significant differences were found between level V and other levels. The survival rate at 10 years was 100% for stage I (n=18), 63.3% for stage II (n=24), and 52.5% for stage III (n=55). In stage IV (n=3), there was only one patient who survived for 42 months. There were significant differences in survival among all stages except I and II. The 10-year survival rate in 3 subgroups of stage III was 58.9% for pT4pN0M0 patients (n=14), 63.2% for pT,pN1M0 patients (n=31), and 20% for pT,pN2M0 patients (n=10). Significant differences were found between the pT,pN1M0 and pT,pN2M0 subgroups. These findings indicate that the survival of pT1, pT2 and stage I patients is extremely good. In contrast, the prognosis of patients with pT3, pT3b or pT4, and stage III or IV disease is significantly poor. Within stage III, the prognosis of the pT,pN2M0 subgroup is significantly poor, and the classification of pN2 patients may need to be reconsidered.     

无色素性黑素瘤误诊为表皮囊肿1例

患者男,39岁。头部红色结节、斑块2年。2年前患者头部出现一黄豆大红色结节,当地医院以"表皮囊肿"相继予激光和手术治疗,皮损均复发。皮损组织病理示:表皮与真皮交界处和真皮内瘤细胞呈巢状分布,肿瘤细胞大小不等,核深染,具显著异型性,肿瘤细胞内无明显黑素颗粒。免疫组化检查:瘤细胞表达S-100及Melan-A。CT检查示肺转移癌。诊断:无色素性黑素瘤。     

突变型P53蛋白在皮肤黑素瘤中的检测及临床意义

目的探讨突变型P53蛋白在黑素瘤组织中的检测及临床意义。方法SP免疫组化法检测突变型P53蛋白在40例原发性皮肤黑素瘤中的水平,以20例色素痣作为对照。结果突变型P53蛋白在皮肤黑素瘤和色素痣中的阳性率分别为80.00%和20.00%,其在黑素瘤中的水平明显高于色素痣中,两组相比差异有统计学意义(P<0.05)。突变型P53蛋白分布与黑素瘤病理学类型、病理分级、分期、淋巴结转移及预后相关。结论突变型P53蛋白在皮肤黑素瘤中的较高水平,对皮肤黑素瘤的辅助诊断及预后评估具有重要的临床意义。     

皮肤恶性黑素瘤凋亡相关基因Survivin Bax表达及其与端粒酶的关系

目的探讨凋亡相关基因Survivin,Bax及人端粒酶逆转录酶(hTERT)在皮肤恶性黑素瘤中的表达及其临床意义。方法SP免疫组化染色检测63例皮肤恶性黑素瘤和21例色素痣组织中Survivin,Bax蛋白水平;原位杂交技术检测上述组织中人端粒酶逆转录酶(hTERT)mRNA水平。结果①凋亡相关蛋白Survivin在皮肤恶性黑素瘤中的表达明显强于其在色素痣中的表达,Bax在二者中的表达无明显差异,hTERTmRNA表达与Survivin相似;②Survivin蛋白和hTERTmRNA表达均与恶性黑素瘤病理学类型、淋巴结转移、浸润深度及预后相关,Bax表达与之无相关;③hTERTmRNA在黑素瘤中的表达水平与Survivin呈高度正相关,与Bax表达无关,Survivin与Bax表达水平无明显相关性。结论皮肤恶性黑素瘤形成和发展与肿瘤细胞抗凋亡(Survivin)和促进增殖(hTERT)均密切相关;Survivin和hTERT对皮肤恶性黑素瘤的辅助诊断及预后评估具有重要的临床意义;Bax表达与皮肤恶性黑素瘤的发生发展无明显相关性。     

Ultrastructural Study of Anti-Tumor Effects of Tamoxifen in Two Malignant Melanoma Patients

In order to clarify the mode of action (tumor cell death) of tamoxifen in treatment for estrogen receptor (ER) negative malignant melanoma, we administered the usual adult dose (20 mg/day) or a low dose, 1/4 of the usual dose (5 mg/day), of tamoxifen for 2 months to 2 male patients and investigated ultrastructural changes in their melanoma cells from metastatic lesions before and after the treatment. After the 2-month adminisration, metastatic nodules in both patients were reduced in size by approximately 50%. Histologically, their reduced nodules presented coagulation necrosis around the blood vessels. Electron microscopy of the necrosis revealed that melanoma cells were degenerated and disappeared; numerous aggregated melanosomes, free melanosomes, granular endoplasmic reticula, and lysosomes were present in the extracellular matrix and in the space between collagen fibers. The remaining melanoma cells had swollen cytoplasm and mitochondria with vacuolar changes. Cristae of mitochondria had disappeared. There was no infiltration of lymphocytes or histiocytes into the nodules. The organic changes of necrosis lesions were not observed. Because our two patients were ER negative, these effects of tamoxifen could be attributable to an action not mediated by ER.     

Melan‐A positive dermal cells in malignant melanoma in situ

The presence of Melan‐A positive dermal cells in excisions for melanoma in situ represents a frequent conundrum for pathologists. These cells may represent superficially invasive melanoma, benign, incidental, dermal nevi or non‐specific staining of dermal melanophages. Occasionally, rare, Melan‐A positive dermal cells are present which do not clearly correspond to the above three categories. Our objective was to further characterize these Melan‐A positive dermal cells. To do this, immunoperoxidase staining for Melan‐A and SOX‐10 was performed on 188‐cutaneous excisions, including examples of melanoma in situ, atypical junctional melanocytic hyperplasia and non‐melanocytic tumors. These were evaluated for the presence of Melan‐A and SOX‐10 positive dermal cells. Dermal cells, positive for both markers, were identified in 17% of the excisions. The cells were present in 10% of cases from the melanocytic group and 31% of the cases from the non‐melanocytic group. These cells did not exhibit cytologic atypia and resembled neither the co‐existing neoplasm nor melanophages. We conclude that positivity of these rare Melan‐A positive cells for SOX‐10 argues that they represent true melanocytes and not non‐specific staining. The absence of cytologic atypia in these cells and their presence in excisions of non‐melanocytic neoplasms argues that they are benign, reactive, dermal melanocytes.     

Malignant Melanoma Developing in an Area of Palmoplantar Keratoderma (Greither's Disease)

We report a case of malignant melanoma arising on the hyperkeratotic sole of a patient with palmoplantar keratoderma (PPK). Hyperkeratotic lesions were also seen on the dorsa of both hands and feet and the extensor aspects of elbows and knees. The patient's PPK appeared to have been transmitted by an autosomal dominant gene. Histologically, the hyperkeratotic lesions showed acanthosis, marked hyperkeratosis without parakeratosis, and hypergranulosis. All the findings corresponded to those of Greither's disease with malignant melanoma.     

Superficial Spreading Melanoma Arising in a Longstanding Melanocytic Nevus on the Sole

In Asians, the plantar surface is the commonest site for cutaneous melanoma, and most melanomas arising in this region are the acral lentiginous type. Herein we describe a rare case of superficial spreading melanoma arising in a longstanding melanocytic nevus on the sole of a Korean.     

Active Specific Immunotherapy of Malignant Melanoma with Anti-idiotypic Monoclonal Antibodies

In this study, we have utilized the human high molecular weight-melanoma associated antigen (HMW-MAA) as a target for active specific immunotherapy with mouse anti-idiotypic (anti-id) monoclonal antibodies (mAb) in patients with malignant melanoma. After having summarized the characteristics of HMW-MAA which account for its selection as a target for immunotherapy, we describe the development and characterization of mouse anti-id mAb MK2-23 which bears the internal image of HMW-MAA. Furthermore, we describe the results of the first clinical trial performed with mouse anti-id mAb MK2-23 in patients with malignant melanoma.