A giant apocrine hidrocystoma associated with elevated serum carcinoembryonic antigen levels: a case report.

BACKGROUND: Serum carcinoembryonic antigen levels are often elevated in patients with malignant diseases. However, the etiology of elevated serum carcinoembryonic antigen levels may be extremely difficult to determine considering that this finding may occasionally occur in patients with benign diseases. Apocrine hidrocystomas, which are typically small and found on the face, are benign cystic lesions of apocrine sweat glands. CASE PRESENTATION: A 58-year-old Japanese man was referred to us because of high serum carcinoembryonic antigen levels (15.9 ng/mL) found incidentally during a routine medical checkup. A physical examination revealed a hemispherical mass approximately 5 cm in diameter on his left thigh. Magnetic resonance imaging of the region showed a multilocular cystic mass with clear margins and a smooth surface, suggesting a cystic tumor. He underwent local mass resection. Pathological examination of the resected mass revealed an apocrine hidrocystoma with luminal cells, which tested immunohistochemically positive for carcinoembryonic antigen. Postoperatively, serum carcinoembryonic antigen levels returned to normal. This report is the first to describe an apocrine hidrocystoma associated with high serum carcinoembryonic antigen levels. CONCLUSIONS: An apocrine hidrocystoma can cause elevation of serum carcinoembryonic antigen levels. Despite its rarity, apocrine hidrocystoma should be considered in the differential diagnosis of conditions causing high serum carcinoembryonic antigen levels. In addition, skin diseases deserve more careful attention for patients with high serum carcinoembryonic antigen levels.

[Cutaneous angiosarcoma with difficulty in differential diagnosis of thrombocytopenia].

An 87-year-old man was referred to our hospital because of sustained bleeding from head skin lesions after trauma. Examination of peripheral blood showed severe thrombocytopenia, a nearly normal coagulation test, and elevated PAIgG. Based on the tentative diagnosis of immune thrombocytopenic purpura (ITP), immunosuppressive drugs and high-dose immunoglobulin were administered; however, the platelet count did not recover, and was followed by severe DIC, resulting in a fatal outcome due to massive bleeding from the scalp. Histopathological examination of autopsy samples of skin lesions revealed angiosarcoma, suggesting that Kasabach-Merritt syndrome (KMS) complicated with DIC, but not ITP, was the primary cause of thrombocytopenia. Although KMS is commonly accompanied with hemangioma in infants, it is extremely rare in patients with angiosarcoma, which is an uncommon malignant neoplasm. In this case, our correct diagnosis of thrombocytopenia was difficult because of the unusual clinical setting, indicating that careful interpretation of physical, laboratory and pathological examinations is mandatory for correct diagnosis of thrombocytopenia of unknown etiology.

Antitumor enediyne chromoprotein C-1027: mechanistic investigation of the chromophore-mediated self-decomposition pathway.

C-1027 is an extremely potent antitumor agent that causes double-stranded DNA cleavages. It is a unique small molecule-protein complex composed of a highly reactive enediyne chromophore, which upon binding reacts with its target molecule DNA through radical-mediated hydrogen abstraction and an apoprotein that encapsulates the chromophore serving as its carrier to reach DNA. Although C-1027 has favorable properties as an effective drug delivery system, it slowly self-decomposes due to the reactivity of the chromophore toward the apoprotein. Understanding how the C-1027 destroys itself may enable design of its analogues that overcome this limitation. In this paper, mechanistic insights into the self-reactivity of C-1027 that facilitates its own decomposition are described. We provide evidence that the formation of the Gly96 radical, which promotes the oxidative protein scission and the subsequent chromophore release, is the major pathway for the self-decomposition of C-1027. On the basis of the newly isolated products of the self-decomposition, we propose that the apoprotein effectively protects two different structural elements of the chromophore that are essential for its biological activity: the nine-membered enediyne moiety (necessary for DNA cleavage) and the benzoxazine moiety (necessary for DNA intercalation). Using an engineered apoprotein analogue kinetically more stable toward the chromophore radical, we show that enhanced overall properties can be achieved for the natural C-1027 with respect to stability and antitumor activities. The results present the first example of a rationally designed C-1027 analogue reported to display superior in vitro antitumor activity to the natural C-1027. Our findings may have implications for design of proteins that can stably encapsulate highly reactive small molecules.