glycogen and Melanoma

Clear cell melanoma is a rare clear cell malignancy. Accurate diagnosis of clear cell melanoma requires integration of immunohistochemical and morphologic findings, with molecular studies to rule out clear cell sarcoma. The differential diagnosis includes melanoma, carcinoma, perivascular epithelioid cell tumor, and epidermotropic clear cell sarcoma. We use a case of a lesion on the helix of an 86-year-old man as an example. Histologic examination revealed an ulcerated clear cell malignant tumor. Tumor cell cytoplasm contained periodic acid-Schiff-positive, diastase-sensitive glycogen. Tumor cells showed positive labeling for S100, HMB-45, and Melan-A, and negative labeling for cytokeratins, p63, and smooth muscle actin. Molecular studies demonstrated BRAF V600E mutation, copy gains at the 6p25 (RREB1) and 11q13 (CCND1) loci, and absence of EWSR1-ATF1 fusion. These findings supported a diagnosis of clear cell melanoma. The rare pure clear cell morphology occurs due to accumulation of intracytoplasmic glycogen. We review the differential diagnosis of clear cell melanoma and describe the utility of immunohistochemical and molecular studies in confirming this diagnosis.

Topics: Aged, 80 and over; Amino Acid Substitution; Biomarkers, Tumor; Cyclin D1; Diagnosis, Differential; DNA-Binding Proteins; Ear Auricle; Gene Dosage; Glycogen; Humans; Male; Melanoma; Mutation; Perivascular Epithelioid Cell Neoplasms; Proto-Oncogene Proteins B-raf; Sarcoma, Clear Cell; Skin; Skin Neoplasms; Transcription Factors; Up-Regulation

To facilitate efficient drug delivery to tumor tissue, several nanomaterials have been designed, with combined diagnostic and therapeutic properties. In this work, we carried out fundamental in vitro and in vivo experiments to assess the labeling efficacy of our novel theranostic nanoprobe, consisting of glycogen conjugated with a red fluorescent probe and gadolinium. Microscopy and resazurin viability assays were used to study cell labeling and cell viability in human metastatic melanoma cell lines. Fluorescence lifetime correlation spectroscopy (FLCS) was done to investigate nanoprobe stability. Magnetic resonance imaging (MRI) was performed to study T₁ relaxivity in vitro, and contrast enhancement in a subcutaneous in vivo tumor model. Efficient cell labeling was demonstrated, while cell viability, cell migration, and cell growth was not affected. FLCS showed that the nanoprobe did not degrade in blood plasma. MRI demonstrated that down to 750 cells/μL of labeled cells in agar phantoms could be detected. In vivo MRI showed that contrast enhancement in tumors was comparable between Omniscan contrast agent and the nanoprobe. In conclusion, we demonstrate for the first time that a non-toxic glycogen-based nanoprobe may effectively visualize tumor cells and tissue, and, in future experiments, we will investigate its therapeutic potential by conjugating therapeutic compounds to the nanoprobe.

Topics: Cell Line, Tumor; Cell Movement; Cell Survival; Contrast Media; Cytoplasm; Glycogen; Humans; Hydrogen-Ion Concentration; Lysosomes; Magnetic Resonance Imaging; Melanoma; Molecular Imaging; Molecular Probes; Multimodal Imaging; Nanotechnology; Spectrometry, Fluorescence; Staining and Labeling

After identifying a metastatic glycogen-rich balloon cell malignant melanoma, originally thought to be a benign clear cell tumor of the lung, we investigated the extent of positive reactions, or "positivity," of malignant melanoma to periodic acid-Schiff (PAS) staining.. Frequency, intensity, and distribution of PAS positivity was studied in 61 excisional biopsy specimens from 58 patients with malignant melanoma. For comparison, 17 benign nevi from 10 patients were examined.. Positivity for PAS was seen in all cases. All malignant melanomas and benign nevi were characterized by weak, diffuse, diastase-resistant PAS positivity. Additionally, focal or diffuse, strong diastase-sensitive PAS positivity was observed in 9 of 61 melanomas (15%); 7 were metastatic and 2 were primary invasive melanomas. Strong diastase-sensitive PAS positivity was seen in all lesions with 30% or more balloon cell features and only in advanced primary or metastatic lesions. The presence of glycogen was confirmed by transmission electron microscopy.. Cutaneous malignant melanomas have weak, diastase-resistant PAS positivity. Strong diastase-sensitive PAS positivity, consistent with the presence of intracytoplasmic glycogen, is seen in many primary and metastatic melanomas with balloon cell features. Depending on the content of the balloon cells, these melanomas are best categorized as either glycogen-rich malignant melanomas or glycogen-rich balloon cell malignant melanomas. Because many tumors with clear cell features contain glycogen, such content often is an unreliable differential feature.

Topics: Biopsy; Biopsy, Needle; Glycogen; Humans; Immunohistochemistry; Lung; Lung Neoplasms; Male; Melanoma; Microscopy, Electron; Middle Aged; Neoplasm Invasiveness; Periodic Acid-Schiff Reaction

To characterize the canine melanoma antigen recognized by the murine monoclonal antibody IBF9 as to its cellular location, molecular size, protein and glycogen contents, and distribution in cell lines.. 7 cultured canine melanoma cell lines.. Molecular characteristics of the antigen were determined by western blotting, enzymatic digestion studies, and tunicamycin inhibition studies. Distribution of the antigen in the cultured melanoma cell lines was determined by flow cytometry.. The antigen consists of 2 proteins with molecular mass of 89 and 85 kd. Tunicamycin and enzymatic digestion studies indicated that these proteins contained little glycosylation. Immunogold and immunofluorescence studies localized the antigen to the cell surface. Antigen expression was consistent within each cell line, with > 90% of the cells positive for all cell lines except 1 (80%). Percentage of positive cells and relative intensity of immunostaining were constant throughout all phases of the cell cycle.. The antigen identified by MAB IBF9 is a well-conserved and highly expressed cell surface protein present during all phases of the cell cycle in all malignant canine melanoma cell lines examined.. Because of consistency in expression, the antigen may have potential for use in dogs for melanoma immunodiagnostics and immunotherapy.

Topics: Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Blotting, Western; Cell Cycle; Cell Membrane; Dog Diseases; Dogs; Flow Cytometry; Fluorescein-5-isothiocyanate; Glycogen; Immunoenzyme Techniques; Immunohistochemistry; Melanoma; Microscopy, Electron; Tumor Cells, Cultured

We report the cytogenetic findings in a case of malignant melanoma of soft parts. Overrepresentation of 1q together with a del(1)(q42), extra copies of chromosomes 7 and 8, and t(12;22)(q13;q13) were found. These findings allow further delineation of the chromosomal pattern found in this uncommon neoplasm.

Topics: Adult; Chromosome Aberrations; Glycogen; Hand; Humans; Immunohistochemistry; Male; Melanoma; Reticulin; Soft Tissue Neoplasms

A clear cell sarcoma that developed on the left back of a 19-year-old Japanese female was studied ultrastructurally. The findings included basal laminae, desmosomelike junctions, cytoplasmic interdigitations, lamellar bodies, and immature melanosomes. These findings suggest schwannian differentiation of this tumor, since they are not usual features of malignant melanoma except for melanosomes. Therefore this tumor seems to be more akin to malignant schwannoma than to malignant melanoma.

Topics: Adult; Cell Differentiation; Female; Glycogen; Humans; Melanoma; Microscopy, Electron; Sarcoma; Schwann Cells; Soft Tissue Neoplasms

Malignant melanomas of soft parts from 4 patients were studied by light microscopy, immunocytochemistry for S-100 protein, and electron microscopy. Each patient presented with a deep soft tissue mass in an extremity. Histologically, the tumors were composed of epithelioid and spindle cells, and in one, neoplastic giant cells were present. The tumors did not stain for melanin but were all positive for S-100 protein. Ultrastructurally, premelanosomes were identified in every tumor and in a cell line established from one tumor. Schwann cell features were present in one of the tumors. Although the clinical presentation of malignant melanoma of soft parts is similar to that of epithelioid sarcoma and synovial sarcoma, the combined light microscopic, immunocytochemical, and ultrastructural features should serve to distinguish it from other soft tissue sarcomas.

Topics: Adult; Aged; Basement Membrane; Female; Glycogen; Humans; Intercellular Junctions; Male; Melanoma; Microscopy, Electron; S100 Proteins; Tendons

The activities of glycogen synthase and phosphorylase were measured and compared to the growth-related variations of glycogen accumulation in three cultured human tumor cell lines: HT-29 (colon carcinoma); MeWo (malignant melanoma); and RT-4 (carcinoma of the urinary bladder). A similar pattern of variations in the enzyme activities was found in the three cell lines. The activities of the a + b forms of glycogen phosphorylase increased throughout the culture period. Maximal activity of phosphorylase a coincided with low intracellular concentrations of glycogen during the period of exponential growth. When the rate of cell division decreased, phosphorylase a activity also decreased while the glycogen levels increased. Glycogen synthase was almost entirely in b form during the entire culture period, i.e., in both the exponential and the stationary phases. In vitro incubation of the cellular extracts without NaF showed, however, that the enzyme could be partially converted to the a form by the endogenous phosphatases. The A0.5 values of the enzyme for glucose-6-phosphate (Glc-6-P) were of the same order of magnitude as the intracellular Glc-6-P concentrations which ranged from 2.2 to 5.4 mM (almost 10 times those reported in normal cells). Similar Glc-6-P values were obtained by two different extraction methods controlled by the intracellular ATP and ADP concentrations. The Km values for uridine-5'-diphosphoglucose were always 2 to 3 times lower than the intracellular uridine-5'-diphosphoglucose concentrations. These results suggest that: (a) in these tumor cells, glycogen is essentially synthesized by glycogen synthase b via an allosteric activation by intracellular Glc-6-P; (b) there is no obvious growth-related control of glycogen synthase activity; and (c) the activity of glycogen phosphorylase seems to be growth dependent with maximal phosphorylase a activities associated with the period of high division rate.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Cell Line; Colonic Neoplasms; Glucose-6-Phosphate; Glucosephosphates; Glycogen; Glycogen Synthase; Humans; Kinetics; Melanoma; Neoplasms; Uridine Diphosphate Glucose; Urinary Bladder Neoplasms

Topics: Cell Nucleus; Choroid Neoplasms; Ciliary Body; Cytoplasm; Eye; Eye Neoplasms; Glycogen; Golgi Apparatus; Humans; Melanins; Melanoma; Microscopy; Microscopy, Electron; Mitochondria; Ribosomes

Topics: Acid Phosphatase; Alkaline Phosphatase; Cell Nucleus; Culture Techniques; DNA, Neoplasm; Glycogen; Histocytochemistry; Humans; Melanoma; RNA, Neoplasm; Skin Neoplasms; Succinate Dehydrogenase

Topics: Cell Division; Cytoplasm; Eye Neoplasms; Glioma; Glycogen; Humans; Melanoma; Necrosis

Topics: Eye Neoplasms; Glioma; Glycogen; Humans; Melanoma

Topics: Alkaline Phosphatase; Alkylating Agents; Animals; Antineoplastic Agents; Aziridines; Busulfan; Carcinoma, Ehrlich Tumor; Dihydrolipoamide Dehydrogenase; DNA; DNA, Neoplasm; Electron Transport Complex IV; Glycogen; Histocytochemistry; Lipids; Lymphoma, Non-Hodgkin; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Melanoma; Mice; Neoplasms; Neoplasms, Experimental; Nitrogen Mustard Compounds; Pharmacology; Research; RNA; RNA, Neoplasm; Sarcoma; Sarcoma, Experimental; Succinate Dehydrogenase; Tissue Culture Techniques

Topics: Glucose; Glycogen; Insulin; Melanoma; Melanoma, Experimental; Neoplasms