Nevoid malignant melanoma: morphologic patterns and immunohistochemical reactivity.

The term "nevoid malignant melanoma" (nevoid MM) is used here to describe rare nodular malignant melanomas that may escape detection in routine histological sections due to the lack of a prominent intraepidermal component, sharp lateral circumscription and evidence of partial maturation with descent in the dermis. Nevoid MM mimic ordinary compound or intradermal melanocytic nevi when the melanoma cells are small, or Spitz's nevi when the cells are large. The patterns of HMB-45 staining in 12 nevoid MM were compared with those in 107 melanocytic nevi. HMB-45 staining was strong in the dermal component of the nevoid MM, even in the absence of a junctional component. In common acquired and congenital nevi, the upper dermal component stained less than the junctional component of the lesion. The deepest components of these nevi were negative. Spitz nevi and cellular blue nevi had positive dermal cells, even without a junctional component. Additional staining for a proliferation marker, such as cyclin (PCNA) or Ki-67 (with the antibody MIB-1), can help further in distinguishing a nevoid MM from a Spitz's nevus. Melanoma has strong nuclear staining throughout the lesion. In contrast, Spitz's nevi have more staining at the top of the lesion than at the bottom. The patterns of HMB-45 and MIB-1 staining can be used along with standard histologic criteria for the diagnosis of nevoid MM. Clinicopathologic correlation is needed to distinguish some metastatic melanomas from primary nevoid MM.

Enhancement of glucose transport in clone 9 cells by exposure to alkaline pH: studies on potential mechanisms.

Incubation of a nontransformed rat liver cell line, Clone 9, at pH 8.5 resulted in an approximately 16-fold stimulation of cytochalasin B-inhibitable 3-O-methylglucose (3-OMG) transport, an effect that was independent of the presence of serum. Exposure to 100 ng/ml 12-O-tetradecanoylphorbol 13-acetate (TPA) stimulated 3-OMG uptake, and the enhancement was not additive to that produced by incubation at pH 8.5. In cells "depleted" of protein kinase C activity by a 20-hr exposure to TPA, however, the stimulation of 3-OMG transport in response to incubation at alkaline pH was still fully demonstrable. In control and alkaline pH-exposed cells, the inhibition of 3-OMG uptake by cytochalasin B was consistent with a single-site ligand binding model (K1 approximately 10(-7) M). Northern blot analysis demonstrated the presence of only the human erythrocyte/rat brain/HepG2 cell glucose transporter-mRNA isoform (EGT), and the abundance of this mRNA was unchanged following exposure to alkaline pH. Immunoblot analysis, using polyclonal antibodies directed against the carboxy-terminal dodecapeptide of EGT, demonstrated an approximately 2.0-fold increase in the abundance of transporters in partially purified plasma membrane fractions following incubation at pH 8.5, while EGT abundance was unchanged in whole-cell extracts. It is concluded that the stimulation of glucose transport in response to incubation of Clone 9 cells at alkaline pH does not require the presence of serum or activation of protein kinase C, and that the response is at least in part mediated by an increase in the number of glucose transporters in the plasma membrane.