Metastatic Amelanotic Melanoma Research Articles

Characterization of alkaline phosphatase cytochemistry in canine neoplastic and non-neoplastic pulmonary mass aspirates.

Distinguishing primary and secondary pulmonary neoplasms can be challenging via cytology, and a rapid, inexpensive diagnostic tool to differentiate these neoplasms is unavailable. Alkaline phosphatase cytochemistry (ALP-CC) has been used to identify primary pulmonary carcinomas in human patients, and we hypothesized it could be applied to canine lung aspirates. We aimed to characterize ALP-CC expression in fine-needle aspirate (FNA) samples of canine pulmonary neoplastic and non-neoplastic tumors. A retrospective case search was conducted to identify cases with contemporaneous cytology and histopathology reports from pulmonary lesions, including neoplastic and non-neoplastic etiologies. Slides prepared from pulmonary aspirates were stained for ALP-CC activity, and the percentage of ALP-CC-positive primary pulmonary epithelial tumors was determined. To characterize the ALP-CC expression in non-neoplastic cellular constituents of pulmonary FNA samples, mesothelial cells were also evaluated. Forty-eight canine cases met the inclusion criteria. ALP-CC-positive cells were seen in both neoplastic and non-neoplastic lesions. In non-neoplastic lesions, pulmonary epithelial cells were ALP-CC positive. Eighty-nine percent of primary pulmonary epithelial neoplasms were ALP-CC positive, and no ALP-CC positivity was noted in mesothelial cells. ALP-CC-positive neoplastic cells were seen in a metastatic amelanotic melanoma. Primary pulmonary epithelial neoplasms are frequently ALP-CC positive, but such positivity is not restricted to this tumor type. Non-neoplastic pulmonary epithelial cells can be ALP-CC positive, whereas mesothelial cells are negative.

Fine-needle aspiration cytological findings in three cases of metastatic amelanotic melanoma to the parotid gland with divergent differentiation.

This report presents the clinical and pathologic findings of three cases of metastatic amelanotic melanoma to the parotid gland. Two of the patients had a primary cutaneous tumor. Fine-needle aspiration of the parotid showed clusters of epithelioid cells and/or spindle-shaped cells with vesicular nuclei, macronucleoli, and abundant eosinophilic cytoplasm. In addition, one had striking balloon-cell features. In the immunohistochemical study, the tumors expressed S-100, HMB-45 antigen, Melan-A, and SOX10, and focally smooth-muscle actin, cytokeratin, CD56, p63, and synaptophysin. The diagnosis was challenging because the tumors were clinically thought to be primary parotid lesion and showed unusual immunohistochemical labeling for SMA, cytokeratins, p63, and neuroendocrine markers. Furthermore, the long clinical history in two of the cases made the diagnosis of a metastatic lesion less likely. Diagnostic errors can be reduced by integrating cytomorphologic, histologic, immunohistochemical, and clinical findings.

SECONDARY HYPERTROPHIC OSTEOARTHROPATHY (PIERRE MARIE–BAMBERGER SYNDROME)

This article describes a clinical case of a cancer patient with secondary hypertrophic osteoarthropathy (Pierre Marie–Bamberger syndrome). The patient underwent complex examination including bone scan, X-ray, computed tomography and magnetic resonance imaging. According to the results of the examinations the patient was diagnosed with metastatic amelanotic melanoma in intrathoracic lymph nodes with unknown primary site and the Pierre Marie–Bamberger syndrome was confirmed.

Amelanotic Signet Ring Cell Melanoma Presenting as Breast Lump- A Diagnostic Conundrum

Amelanotic signet ring cell melanoma is one of the rare variants of malignant melanoma. Here we are presenting a case of a 58-year-old female with chief complaints of swelling in the left sternal region/breast, and right cervical region. Contrast Enhanced CT scan showed the two well circumscribed lobular mass lesions with central necrosis in the left breast. The radiologist opined the lesions as intramammary nodes. Biopsy from the larger breast mass lesion showed a tumour with cells arranged in discohesive pattern less with hetrogenos morphology. These tumour cells had a predominantly signet ring morphology along with markedly pleomorphic tumour cells and giant cells. These tumour cells were negative for pan CK and positive for S100, HMB45. So the case was diagnosed as metastatic amelanotic malignant melanoma with signet ring morphology.

Vemurafenib-associated neutrophilic panniculitis in a patient with metastatic amelanotic melanoma presenting with cancer of unknown primary origin

Vemurafenib-associated neutrophilic panniculitis in a patient with metastatic amelanotic melanoma presenting with cancer of unknown primary origin

Recurrent Metastatic Melanoma Despite Multiple Surgical Interventions and Biological Targeted Therapy

A 40 year old Caucasian male was referred to our plastic surgery unit with a rapidly growing mass in his left groin. A biopsy was taken which showed the lesion was metastatic amelanotic melanoma. No primary was identified. He had a history of a halo naevus on his lower back that had fully regressed

Vemurafenib-associated neutrophilic panniculitis in a patient with metastatic amelanotic melanoma presenting as cancer of unknown primary origin

Abstract The treatment of metastatic melanoma is challenging. BRAF gene mutation is found in 40–60% of melanoma cases, the most common being the V600E mutation. Vemurafenib was approved by the Food and Drug Administration in 2011 as target therapy for the treatment with BRAF V600 mutation-positive metastatic melanoma. We report a case of metastatic amelanotic melanoma with unknown primary cancer as the initial presentation. The patient presented with neutrophilic septal panniculitis 1 week after vemurafenib treatment, which is a rare cutaneous toxicity of BRAF inhibitor. We also review the current literature on management of BRAF inhibitor-related adverse skin effects.

Accuracy of routine cytology and immunocytochemistry in preoperative diagnosis of oral amelanotic melanomas in dogs.

Amelanotic melanomas are one of the most common oral malignancies. The cytologic and histopathologic differentiation between amelanotic melanoma, sarcoma, and poorly differentiated carcinoma is often difficult or even impossible. The aim of this study was to assess the reliability of routine cytology and immunocytochemistry in preoperative diagnosis of canine oral amelanotic melanoma. Cytologic preparations from undifferentiated canine oral tumors were stained with Giemsa and by immunocytochemistry (ICC) using anti-cytokeratin, anti-vimentin, and anti-Melan A antibodies. The final cytologic diagnosis (including ICC) was compared to the final diagnosis based on histopathology and immunohistochemistry (IHC) results, and sensitivity and specificity of cytologic examination were determined. Final cytologic diagnoses of 38 cases agreed well with the histopathologic/immunohistochemical diagnoses, thus both specificity and sensitivity of combined routine cytology and ICC were 100% (95% confidence interval 90.8-100%). Of 32 oral tumors, diagnosis of amelanotic melanoma, sarcoma, and carcinoma was made using routine cytology and ICC. In 4 of 6 aspirates taken from lymph nodes, a preliminary diagnosis of metastatic amelanotic melanoma corresponded with the final diagnosis. Both sensitivity and specificity of routine cytology in diagnosis of amelanotic melanomas were considered moderate (66.7% and 85.7%, respectively). In conclusion, routine cytology is a reliable diagnostic method for canine oral amelanotic melanoma and metastatic amelanotic melanoma, and ICC, using anti-cytokeratin, anti-vimentin, and anti-Melan A antibodies, is an excellent supporting method for presurgical diagnosis of poorly differentiated oral malignancies in dogs.

Amelanotic metastatic cutaneous melanoma

Dermatoscopy of melanocytic lesions has guided the decision of when or not to biopsy a lesion. The use of this tool has increased clinical examination's sensitivity and specificity in 89% and 96% respectively. However, dermatoscopic evaluation of amelanotic or hypomelanotic melanomas, as well as metastases, can be difficult. There is still no standardization for the analysis of these pathologies, which relies mostly on their vascular pattern. We describe the dermatoscopy of acral metastatic amelanotic melanoma.

Acute hepatic failure secondary to extensive hepatic replacement by metastatic amelanotic melanoma: an autopsy case report.

Metastatic malignant melanoma (MM) of the liver evolving into acute hepatic failure is a rare occurrence. We describe the case of an 82-year-old man with a history of MM on the left thumb treated with amputation and chemotherapy 40months previously. On admission, he had abdominal pain, weight loss, lethargy and jaundice. Radiologic investigations such as enhanced computed tomography and abdominal ultrasound failed to establish an etiologic diagnosis. A liver biopsy revealed amelanotic melanoma cells diffusely infiltrating the hepatic parenchyma. His liver injury progressed and the patient died of hepatic failure on the 13th hospital day. Autopsy revealed >70% infiltration by metastatic amelanotic melanoma in the liver.

Karzinom-in-Karzinom-Metastasierung eines amelanotischen Melanoms in ein Nierenzellkarzinom

A 54-year old man was admitted because of motor aphasia, behavioral changes and weight loss and suffered from a widely disseminated cancer with unknown primary origin (CUP) syndrome. The autopsy revealed that he was affected by two malignant neoplasms simultaneously: an amelanotic malignant melanoma metastasizing into a localized renal cell carcinoma. Cancer-to-cancer metastasis is an exceedingly rare, but well documented phenomenon. This is the third reported case of a malignant melanoma as donor tumor spreading into a renal cell carcinoma. Well-vascularized and slowly growing renal tumors are typical recipients for cancer-to-cancer metastases. The amelanotic character of the melanoma exerted a special diagnostic challenge. Clinical and autopsy findings as well as the immunophenotypical features of the metastatic amelanotic melanoma (HMB-45, Melan-A/MART-1, S100) and the renal cell carcinoma are described with a review of the relevant literature.

Treatment of an Amelanotic Melanoma Using Radiation Therapy in a Lesser Madagascar Hedgehog Tenrec (Echinops telfairi)

A 15-yr-old, male lesser Madagascar hedgehog tenrec (Echinops telfairi) presented with a mass caudal to the right ear. Cytology suggested a sarcoma. Surgical removal was attempted. Histology was consistent with a soft tissue sarcoma. The mass recurred within 331 days post operation. Radiation therapy was initiated. Computed tomography was used for staging in conjunction with three-dimensional computerized treatment planning software to permit accurate lesion localization and to optimize normal tissue sparing. A total dose of 6,480 cGy was administered in 24 fractions over 46 days. Transient hind limb paresis developed during the course of the radiation therapy, but resolved after 7 days with prednisone treatment. Minimal acute radiation toxicity was observed. The mass responded with at least a 90% reduction in volume following radiation treatment. The animal survived 266 days from the initiation of treatment. On necropsy, a small mass and granulation tissue were found at the site of the initial neoplasm, indicating good regional control of the tumor; however, extensive metastases to the spleen and liver were present. Immunohistochemically, the original, recurrent, and metastatic populations were strongly positive for HMB 45 and weakly positive for S-100, and the final diagnosis was metastatic amelanotic melanoma.

8721 Evaluation of objective response as a predictor of survival in bevacizumab-treated patients with glioblastoma at first or second relapse in the BRAIN Study

The nitrosoureas BCNU, CCNU, ACNU, and Fotemustine covalently deactivate thioredoxin reductase, glutathione reductase and ribonucleotide reductase by alkylating their thiolate active sites. Since thioredoxin reductase and glutathione reductase function as alternative electron donors in the biosynthesis of deoxyribonucleotides, catalyzed by ribonucleotide reductase, the inhibition of these electron transfer systems by the nitrosoureas could determine the cytostatic property of this homologous series of drugs. A detailed study of the kinetics and mechanism for the inhibition of purified thioredoxin reductases from human metastatic melanotic and amelanotic melanomas by the nitrosoureas showed significantly different inhibitor constants. This difference is due to the regulation of these proteins by calcium. Calcium protects thioredoxin reductase from deactivation by the nitrosoureas. In addition, it has been shown that reduced thioredoxin displaces the nitrosourea-inhibitor complex from the active site of thioredoxin reductase to fully reactivate enzyme purified from human metastatic amelanotic melanoma. It has been possible to label the active sites of thioredoxin reductase and glutathione reductase by using chloro[14C]ethyl Fotemustine, resulting in the alkylation of the thiolate active sites to produce chloro[14C]ethyl ether-enzyme inhibitor complexes. These complexes can be reactivated via reduced thioredoxin and reduced glutathione, respectively, by a β-elimination reaction yielding [14C]ethylene and chloride ions as reaction products.

8718 A review of the use of anti-epileptic drugs (AEDs) in high grade gliomas

The nitrosoureas BCNU, CCNU, ACNU, and Fotemustine covalently deactivate thioredoxin reductase, glutathione reductase and ribonucleotide reductase by alkylating their thiolate active sites. Since thioredoxin reductase and glutathione reductase function as alternative electron donors in the biosynthesis of deoxyribonucleotides, catalyzed by ribonucleotide reductase, the inhibition of these electron transfer systems by the nitrosoureas could determine the cytostatic property of this homologous series of drugs. A detailed study of the kinetics and mechanism for the inhibition of purified thioredoxin reductases from human metastatic melanotic and amelanotic melanomas by the nitrosoureas showed significantly different inhibitor constants. This difference is due to the regulation of these proteins by calcium. Calcium protects thioredoxin reductase from deactivation by the nitrosoureas. In addition, it has been shown that reduced thioredoxin displaces the nitrosourea-inhibitor complex from the active site of thioredoxin reductase to fully reactivate enzyme purified from human metastatic amelanotic melanoma. It has been possible to label the active sites of thioredoxin reductase and glutathione reductase by using chloro[14C]ethyl Fotemustine, resulting in the alkylation of the thiolate active sites to produce chloro[14C]ethyl ether-enzyme inhibitor complexes. These complexes can be reactivated via reduced thioredoxin and reduced glutathione, respectively, by a β-elimination reaction yielding [14C]ethylene and chloride ions as reaction products.

Unusual presentation of metastatic amelanotic melanoma of unknown primary origin as a solitary breast lump

Breast is an uncommon site for metastasis from other malignancies especially melanomas. A 40-year-old lady presented with a rapidly growing, painless, solitary breast lump for 3 months. Past history was unremarkable for skin lesions, biopsy or any surgery. The lump was hard and freely mobile with normal overlying skin, nipple, and areola. Careful examination of the skin did not reveal any lesion. Grossly the tumor was partially circumscribed and gray white. Microscopically, a highly cellular lesion was seen showing nests and sheets of large anaplastic cells with atypical mitotic figures without any evidence of cytoplasmic pigment. Immunoreactivity for S-100 and HMB-45, confirmed the diagnosis of amelanotic melanoma. It is important to be aware of this atypical presentation of amelanotic melanoma in the breast and to utilize immunohistochemistry to differentiate from other commoner high-grade malignant tumors.

Metastatic amelanotic nodular melanoma during pregnancy

This case report presents a very aggressive course of amelanotic nodular melanoma during pregnancy resulting in death five months after delivery. A 34 year-old Caucasian woman at 19th week of the second pregnancy was diagnosed having amelanotic nodular melanoma (tumor thickness - 2.5 mm) with metastases to the regional right inguinal lymph node. Amelanotic nodular melanoma represents malignant melanocytic tumor of the skin, which clinically mimics a variety of benign and malignant skin conditions and therefore commonly leads to delayed diagnosis. Though primary tumor was excised immediately, other treatment procedures as radical lymphadenectomy and chemotherapy were delayed, and immunotherapy was not given totally. At the 29th week of pregnancy, the woman via naturalem delivered a healthy female child, and the chemotherapy was started. Since pregnancy limits the prescription of immunotherapy and chemotherapy, the prognosis for melanoma during pregnancy detected later than in the second stage is poor and can be illustrated by our reported case. Such patients seems to be at higher risk to develop metastasis of melanoma in the internal organs and occasionally even in the fetus; therefore, they should be timely informed about that.

Metastatic amelanotic malignant melanoma with unknown primary — A case report

Malignant melanoma is a relatively common neoplasm of melanocytes. The lesion is classically pigmented although amelanotic melanomas are known to occur. The tumour is prone to metastasize early with lymph node metastases presenting earlier than haematogenous metastases [1]. Melanomas presenting with unknown primaries are rare. We describe a case of a metastatic amelanotic melanoma with an unknown primary in a young woman.

悪性黒色腫の頭蓋内転移 悪性黒色腫が嚢胞を伴う無色素性悪性黒色腫として頭蓋内転移したと思われる１例

A case of intracranial metastatic amelanotic melanoma with cyst is presented. The case is a 51-year-old female with malignant melanoma arising on her right chest. Two years after wide excision, skin and brain metastasis occurred. Brain MR images demonstrated a tumor with cyst in the left occipital lobe. And this metastatic melanoma was recognized as amelanotic melanoma, because the tumor showed low intensity on T1 weighted images and high intensity on T2 weighted images. There are only a few earlier reports of melanoma with cyst. Moreover, intracranial amelanotic melanoma is also very rare. [Skin cancer (Japan) 2002; 17: 182-188]

Cytodiagnosis of amelanotic metastatic malignant melanoma: an immunocytochemical study.

Malignant melanomas are known to present diverse patterns and this can result in considerable difficulties for an interpretation of malignancy type from cytohistologic material. Such difficulties are further compounded, if melanin pigment cannot be demonstrated by conventional histochemical stains; unfortunately many cases do exhibit this feature, especially in its metastases. This study was designed to review cases of amelanotic metastatic malignant melanomas in a variety of cytologic samples which were received from 40 patients with a known history of malignant melanoma. Cytomorphologically, the cases were classified as classical, carcinoma-like, spindle cell type, lymphoma-like, and undifferentiated type (Table I). While in 36 of the cases, the diagnosis of metastases from a melanoma was confirmed based on an immunopositivity to a variety of melanoma markers (Table III), in four of the cases, the immunostaining indicated metastases from another primary source, which was subsequently found. Based on our study, we are of the opinion that an immunologic characterization is useful to conclusively diagnose the majority of cases of metastatic amelanotic malignant melanomas. Furthermore, we feel that a reliance on a single melanoma marker is not justified, and a panel of antibodies should be used to distinguish a metastatic amelanotic malignant melanoma from other metastatic neoplasms.

Activation of protein kinase C-alpha isoform in murine melanoma cells with high metastatic potential.

Metastasis is a multistep process in which protein kinase C (PKC) appears to be significantly involved. We analysed the activity and expression of classical (alpha, beta, gamma) and novel PKC epsilon isoforms in B16-F1 and B16-BL6 melanoma cells maintained under different culture conditions in vitro. We used high and low concentrations of tyrosine and phenylalanine in different media (DMEM or RPMI 1640 respectively) that affect the metastatic potential and also the proliferative capacity of the cells. We also tested a weakly metastatic amelanotic B78-H1 melanoma cell line which is unaffected by the different culture conditions. In both B16 melanoma cell lines activation of PKC alpha (without increased expression) occurred under growth conditions permissive of metastasis (DMEM). In contrast, the weakly metastatic amelanotic B78-H1 cell line showed a substantial inactivation of this isoform in the two different culture media, suggesting a specific involvement of PKC alpha in the metastatic process. Moreover, in B16 melanoma cells, novel PKC epsilon was activated under culture conditions which stimulated growth but not metastasis (RPMI 1640). In order to define the relationship between PKC activation and the metastatic process we also determined the release of cathepsin B. No correlation between PKC activity and cathepsin B release in either B16 melanoma cell lines could be demonstrated.