A case of pedunculated malignant melanoma of the vaginal mucosa.

We report an 84-year-old Japanese woman who presented with a pedunculated malignant melanoma of the vaginal mucosa. Mucosal melanoma is believed to be more common in Japan than other countries, but such tumors of the vulvovaginal region are quite unusual. In our patient, three tumors were connected by a narrow pedicle. Three black tumors measuring 5-10 mm in diameter with a common pedicle were seen on the vaginal mucosa at five o'clock from the cervix. The tumors were hanging from the narrow pedicle. On histologic examination, they were diagnosed as malignant melanoma. Resection was done with a distal margin of 3 cm from the tumors and a margin of 1 cm from the cervix. The patient has had no evidence of local recurrence or distant metastasis. In our patient, the three main tumors had a common pedicle, which seems to be a unique finding. Since pedunculated malignant melanomas are rare, making a clinical diagnosis is difficult. Although pedunculated melanomas are recognized as having a high malignant potential because these lesions are generally thick, a relatively good outcome is sometimes reported. In our patient, there was no tumor infiltration into the dermis of the pedicle, and this may be one reason for the good outcome at present. There has been no previous report of a mucosal melanoma consisting of three tumors like those in the present patient.     

Double cancer of plantar malignant melanoma and vulvar extramammary Paget’s disease

A 75‐year‐old woman presented with a 2‐year history of a pigmented nodular lesion on her left sole and a 9‐year history of a red infiltrative plaque on the vulva. The plantar lesion was a 15‐mm ulcerated nodule located at the center of a 25‐mm atypical pigmentation region; the nodule was clinically suspected to be a malignant melanoma. Histopathological analysis of the vulvar lesion biopsy sample indicated extramammary Paget’s disease (EMPD). There was no evidence of metastasis in the computed tomography (CT) and ¹⁸F‐fluorodeoxyglucose positron emission tomography scans. We simultaneously performed a wide excision of both lesions and a left inguinal sentinel lymph node biopsy. Melanoma cells were identified in the sentinel lymph nodes, and left radical lymph node dissection was performed after a course of neoadjuvant chemotherapy. All the lymph nodes that were resected during the second operation tested negative for melanomas, and the plantar lesion was diagnosed as a stage IIIB malignant melanoma (pT4b, Na2, M0). Thereafter, we administrated four courses of chemotherapy, and 8 months after the operation, there was no evidence of recurrence or metastatic lesions. We present a case report of double cancer: a plantar malignant melanoma and vulvar EMPD, and also discuss the possible genetic mutations responsible for these two tumors.     

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.     

A case of Werner syndrome with three primary lesions of malignant melanoma

Three primary lesions of malignant melanoma developed in a 44-year-old Japanese woman with Werner syndrome. One lesion was on the right large pudental lip and the others in distinct locations on her left sole. After the wide local excision of these tumors, the wound of the large pudental lip was sutured, and the defects on the sole were covered with skin grafts. After one course of chemotherapy consisting of dacarbazine, nimustine, vincristine sulfate and local injection of Interferon beta were performed, severe myelosupression occurred and continued for two months. Defective production of WRN protein was confirmed by Western blotting, although the three representative mutations in Japanese patients, mutations 1, 4 and 6, which include over 90% of the Japanese patients, were not detected. We also reviewed 26 cases of malignant melanoma associated with Werner syndrome (WS), including ours.     

Diagnostic utility of magnetic resonance imaging in malignant melanoma.

BACKGROUND: Dermatologists sometimes have difficulty in making the diagnosis of a melanocytic tumor. OBJECTIVE: Our purpose was to establish a noninvasive method for the diagnosis of malignant melanoma. We investigated the diagnostic usefulness of magnetic resonance imaging (MRI) in 23 lesions of primary malignant melanoma, metastatic malignant melanoma, and benign pigmented skin tumors. METHODS: The morphologic characteristics and the signal intensity of the tumors were analyzed to differentiate malignant and benign pigmented skin tumors by means of the tumor-to-fat contrast ratio of the signal intensity. RESULTS: The morphologic characteristics of the tumors obtained by MRI were not an absolute criterion for diagnosis of malignant melanoma, but the signal intensity of the tumor assessed by the tumor-to-fat contrast ratio on T2-weighted images clearly differentiated between primary malignant melanoma and benign pigmented skin tumors. CONCLUSION: These findings indicated that MRI is useful for noninvasive diagnosis of malignant melanoma.     

Telangiectasia macularis eruptiva perstans,a form of cutaneous mastocytosis,associated with malignant melanoma

A 62‐year‐old obese woman presented with a malignant melanoma (Stage la). In addition, she had disseminated telangiectatic macules on both thighs. Intensive rubbing of lesions resulted in wheals. Biopsy revealed increased numbers of mast cells. We diagnosed telangiectasia macularis eruptiva perstans, a rare clinical form of adult maculopapular cutaneous mastocytosis, a group which also includes urticaria pigmentosa. No evidence was found for systemic involvement. Possible associations with malignant tumors and the possible role of c‐kit mutations both in development of melanoma and mastocytosis are discussed.     

A potential predictive marker for response to interferon in malignant melanoma

The methylthioadenosine phosphorylase (mtap) gene is localized on chromosome 9p21, a chromosomal region often affected by deletion in several kinds of malignant tumors. Studies on malignant melanoma have revealed loss of MTAP expression in vitro and in vivo; however, loss of MTAP expression is mainly regulated by promoter hypermethylation. Loss of MTAP was shown to have an effect on tumor invasion and metastasis. In a recent study, MTAP not only had a role as tumor suppressor but was also implicated in lack of therapeutic response of patients with recurrent malignant melanoma. There is evidence that loss of MTAP results in an inhibition of STAT signaling pathways regulated by interferon. This in turn leads to ineffectiveness of interferon therapy. Determination of the MTAP status in the primary tumor could, therefore, potentially lead to a selection of patients who benefit from interferon treatment.     

The association between malignant melanoma and noncutaneous malignancies

BACKGROUND: Both increases and decreases in the incidence of subsequent malignancies in melanoma patients have been reported. We examined the database of the Indiana University Cancer Center to determine whether there is an association between malignant melanoma and noncutaneous malignancies. OBJECTIVE: We searched for evidence of noncutaneous malignancies in a cohort of melanoma patients. METHODS: Patients with microscopically confirmed malignant melanoma diagnosed between January 1987 and March 2001 were analyzed. This cohort was investigated for noncutaneous malignancies occurring either before or after the diagnosis of melanoma. The standardized incidence ratios (SIR) were calculated as the ratio of the observed to the expected number of patients with second malignancies, and 95% confidence intervals (95% CI) around the SIR were estimated from the cumulative Poisson distribution. RESULTS: A total of 955 patients with melanoma (498 males and 457 females) were documented over the 14-year period. Sixty-nine noncutaneous malignancies were identified in 59 (6.2%) melanoma patients (39 males and 20 females). There was a higher risk of non-Hodgkin's lymphoma (SIR = 1.91; 95% CI, 0.88-3.62) in men and renal cell carcinoma (SIR = 2.41, 95% CI, 0.97-4.97) in men. In female patients, however, there was no higher risk of noncutaneous malignancies. CONCLUSIONS: This study did not show a higher risk of prostate cancer, gastrointestinal cancer, leukemia, endometrial cancer, or cancer of the nerve and neuroendocrine systems in melanoma patients. No female patients incurred a higher risk of noncutaneous cancers. The increased risk of non-Hodgkin's lymphoma and renal cell carcinoma in men might be attributed to a mutual carcinogenic exposure, an aberration of cell-mediated immunity, a shared genetic susceptibility, increased medical surveillance among cancer patients, a post-therapy effect after cancer management, or factors not as yet clear. Close monitoring of melanoma patients for signs of second malignancy is warranted.     

Cutaneous malignant melanoma, sun exposure, and sunscreen use: epidemiological evidence

Summary Background  Cutaneous malignant melanoma is the most serious form of skin cancer and accounts for about three-quarters of all skin cancer deaths. Over the last few decades the incidence and mortality rates of melanoma have been increasing worldwide. The risk of melanoma is higher in individuals with both phenotypic susceptibility and a history of sun exposure. Therefore, recommended sun protection behaviours include wearing long-sleeved clothing, seeking shade, avoiding the sun when it is strongest, and using sunscreen lotion with a sun protection factor of 15 or higher. It has been reported, however, that the use of sunscreens does not protect against melanoma and seems to increase the duration of recreational sun exposure.
Methods  Published epidemiological studies examining sunscreen use and melanoma have been reviewed from an epidemiological point of view, taking into account potential biases. We have classified case–control studies into four categories: (1) inconclusive studies because of major bias in control population and/or the lack of multivariate analysis; (2) no association between sunscreen use and melanoma after controlling for confounders; (3) negative association (i.e. protective effect of sunscreen); and (4) positive association. Various other epidemiological studies were also analysed.
Results  These results are controversial. Two case–control studies show a protective effect of sunscreen use, while three studies showed a significant risk associated with sunscreen use. However, the discordant results, the low relative risks, the lack of dose–effect relationship and the numerous biases, especially the uncertainty that exposure (sunscreen use) preceded melanoma do not suggest a causative association between sunscreen use and melanoma. Several hypotheses could partly explain these contradictory results.     

Six cases of metastatic malignant melanoma with apparently occult primary lesions.

We report here six cases of malignant melanoma in which metastatic lesions were detected first. Of these, two cases showed some peculiar features: one exhibited widespread subcutaneous bleeding, probably due to venous rupture, and the other case had a rare primary lesion on the penis. In the Japanese literature, there have been 46 cases of malignant melanoma in which metastatic lesions were detected prior to the initial ones. The preferential site for metastasis was the lymph node (32 cases). The primary lesion was unknown in 35 patients. The outcomes were available for 36 of the 46 patients; 23 died, including 18 who died within two years.     

Metastatic malignant melanoma presenting with hypercalcaemia and bone marrow involvement

We report a 75-year-old female patient with a background of malignant melanoma who presented with hypercalcaemia to our institution. She was aggressively treated but declined clinically. Computed tomography head and X-ray studies were suggestive of multiple myeloma, but bone marrow examination was significant for metastatic malignant melanoma. Very few patients with melanoma present with these features, and it further exemplifies the importance of close follow-up and the aggressive nature of this disease process.     

Nodular malignant melanoma with Spitz nevus-like pathological features finally confirmed by the pathological feature of the sentinel lymph node

The clinical and histopathological similarities of nodular melanoma and Spitz nevus currently still make a definitive diagnosis difficult. We report here a case of nodular melanoma that was extremely difficult to diagnose both clinically and histopathologically. The primary tumor was a blackish nodule on the scalp and biopsy was performed for pathological diagnosis. Although our first impression was malignant melanoma, we asked two dermatopathologists for second opinions; however, one diagnosed a melanoma and the other a Spitz nevus. Faced with this clinical dilemma, an operation was performed with sentinel node biopsy. Only one sentinel node suggested a metastasis. Histopathological diagnosis to establish whether it was a melanoma metastasis or nodal nevi was also difficult, and we again asked for second opinions from another dermatopathologist in the USA. According to its clinical course and the histopathology of the sentinel lymph node with additional immunohistochemistry, this case was finally diagnosed as a nodular melanoma (T4aN1aM0, stage IIIA). To date, the patient has been given five courses of chemotherapy at 6-month intervals, with no local recurrence or distant metastases so far.     

A case of epidermotropic metastatic malignant melanoma with multiple nodular lesions of the scalp

Epidermotropic metastatic malignant melanoma (EMMM) is a form of metastatic malignant melanoma that has dermal cell nests with epidermotropism and specific histopathological features. We report a patient with eight nodular lesions of the scalp with histopathological findings compatible with EMMM. The tumors developed one year before consultation and increased in size simultaneously. The histopathological findings of all eight tumors were very similar. The tumor cells were located mainly in the dermis and partly in the basal layer of the epidermis. They contained melanin pigments and were positive for anti-HMB45 antibody. The tumors did not respond to combination chemotherapy with dacarbazine, nimustine, vincristine, and interferon-beta. Therefore, all the tumors were surgically removed. No local relapse, distant metastasis or re-elevation of plasma 5-S-cysteinyldopa was identified during nine months of follow-up. Histopathologically, all eight tumors lacked apparent vascular invasion, which may be related to a slow clinical course of the present case.     

AgNOR (nucleolar organizer regions) staining in malignant melanoma.

Nucleolar organizer regions (NORs) are loops of ribosomal DNA seen in nuclei, which are demonstrable as black dots (AgNOR) in tissue sections by silver (Ag) colloid staining. The number of such AgNORs is correlated with cellular activity and is an indicator of the degree of malignancy. In this study, 76 melanocytic lesions were analyzed by AgNOR staining, and the clinical and histopathological characteristics of malignant melanoma and melanocytic nevi were considered. Although the AgNOR counts for melanocytic nevi were significantly different from those in malignant melanoma, an obvious overlap between them was detected. The number of AgNORs in melanocytic nevi per cell was usually 1 or 2. On the other hand, the number of AgNORs per malignant melanoma cell was variable. Morphologically, malignant melanoma cells often showed dispersal of AgNORs throughout the nucleus as well as multiple nucleoli containing clustered AgNORs, whereas melanocytic nevus cells tended to have a regular nucleolus with tightly clustered AgNORs. The correlation between AgNOR count and pathological staging was uncertain, but a slight correlation between AgNOR count and thickness of the primary lesion was obtained. However, the AgNOR count in malignant melanoma was not a prognostic factor for the disease. Therefore, the AgNOR method is difficult to use for differential diagnosis between benign pigmented lesions and malignant melanoma. Nonetheless, an AgNOR count of more than two per cell favors a diagnosis of malignant melanoma.     

PUVA and cancer risk: the Swedish follow-up study

There is concern about the long-term carcinogenic effects of psoralen and ultraviolet A radiation (PUVA) for treatment of skin disorders. Many authors have found an increased risk for cutaneous squamous cell carcinoma (SCC). Except in anecdotal reports, malignant melanoma had not been observed in patients treated with PUVA until recently. In the U.S.A., a 16-centre prospective study of 1380 patients showed for the first time that there might also be an increased risk for malignant melanoma in patients treated with high cumulative dosages of PUVA. We have therefore followed up the Swedish PUVA cohort until 1994. This cohort had previously been followed up until 1985. Information from 4799 Swedish patients (2343 men, 2456 women) who had received PUVA between 1974 and 1985 was linked to the compulsory Swedish Cancer Registry in order to identify individuals with cancer. The average follow-up period was 15.9 years for men and 16.2 for women. We did not find any increased risk for malignant melanoma in our total cohort of 4799 patients treated with PUVA or in a subcohort comprising 1867 patients followed for 15-21 years. For cutaneous SCC there was an increase in the risk: the relative risk was 5.6 (95% confidence interval, CI 4. 4-7.1) for men and 3.6 (95% CI 2.1-5.8) for women. Significant (P < 0.05) increases were also found in the incidence of respiratory cancer in men and women and of kidney cancer in women. In conclusion, we did not find any increased risk for malignant melanoma in our patients treated with high doses of PUVA and followed up for a long time. We confirm previous reports of an increase in the incidence of cutaneous SCC in patients treated with PUVA, and recommend that patients should be carefully selected for PUVA and rigorously followed up.     

Early detection of lymph node metastases by 7.5 MHz-ultrasound examination in a patient with primary malignant melanoma of the lung

Primary malignant melanoma of the lung (PMML) is a rare neoplasm that may be misdiagnosed as one of the more common types of lung cancer. Most cases are characterized by a very poor prognosis, ultimately leading to the patient's death. Since an optimal systemic treatment schedule is not established so far, early detection of lymph node metastases may be important for surgical interventions. We report on a 55-year-old male patient with a primary bronchial malignant melanoma of his left lower lobe that was treated by pneumonectomy. 11 and 17 months after removal of the PMML, suspicious lymph nodes in the patient's left axilla were identified by 7.5 MHz-ultrasound examinations. Again surgical treatment was performed and histopathology showed lymph node metastases of malignant melanoma. During adjuvant therapy with interferon alpha (3 x 6 Mio IE per week) no further relapse has been observed with a follow-up of 8 months after the last operation. An overview of primary melanoma of the lung is given and diagnostic options are discussed. The 7.5 MHz-ultrasound examination appears to be especially helpful in the early detection of lymph node metastases leading to early initiation of surgical treatment possibly associated with a prolonged survival in our patient.     

Isolated amelanotic malignant melanoma of the heart

We report a 58-year-old woman presenting with dyspnoea and recurrent pulmonary embolism. Echocardiography revealed pericardial effusion and a tumour located in the atrioventricular groove. Surgical exploration showed tumorous infiltration of the ventricle wall and of parts of the atrium. Curative excision was not possible and the operation was discontinued. Histology revealed an amelanotic malignant melanoma. No other tumour location was detected by scanning procedures. This case represents a very rare manifestation of melanoma exclusively located in the atrioventricular groove of the heart leading to recurrent pulmonary embolism. A review of the literature on cardiac involvement of melanoma is provided.     

Squamous cell carcinoma, malignant melanoma and malignant fibrous histiocytoma arising in burn scars

Summary The most common cancer arising from an old burn scar is squamous cell carcinoma, while malignant melanoma is rare. There are only four reports in the literature on the combination of the more common tumour with a malignant melanoma and only two cases of malignant fibrous histiocytoma alone. This paper reports the first occurrence of the combination of all three types of cancer in burn scars of the same patient. The factors that promote malignant transformation, such as immunological factors and karyotype, are discussed. We also performed an immunohistochemical study using anti-p53 antibodies.     

Epidermotropic Metastatic Melanoma Clinically Resembling Agminated Spitz Nevi

Herein, we report a 36-year-old Asian male patient who presented with grouped multiple erythematous waxy papules and nodules on his right medial thigh. He had undergone amputation of the right second toe because of a stage IIa malignant melanoma, 3 years previously. At the time of surgery for the primary tumor, right inguinal lymph node dissection revealed no nodal involvement. Three years after the diagnosis of the primary tumor, crops of multiple erythematous papules and nodules developed. Initial histopathologic evaluation of the papules showed nests of small epithelioid cells similar to compound nevi. However, cytologic features, including high mitotic figures, lack of maturation, and some hyperchromatic nuclei suggested metastatic melanoma. In addition to the pathologic findings, the tumors were on the right thigh, which was the same side as the primary malignant melanoma. The patient underwent wide excision of the tumor and split-thickness skin grafting.