A 91-year-old man presented with a 9.0 x 7.0 cm exophytic mass on the dorsum of the right foot, surrounded by a scaling hyperkeratotic plaque-like lesion that had been present for many years. He had similar long-standing hyperkeratotic plaque-like lesions on both legs. Histopathologic examination of the exophytic mass revealed a well-differentiated squamous cell carcinoma surrounded by an eccrine syringofibroadenoma (ESFA). Histochemistry, immunohistochemistry and electron microscopy support this diagnosis. To our knowledge, this is the only reported case of ESFA being intimately associated with a malignant neoplasm.

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We reported recently the isolation of a macromolecular factor in macrophage culture supernatant which was able to inhibit the proliferation of mouse lymphoma cells and various immune reactions of mouse spleen cells in vitro (1). Shortly afterward Kung et al. (2) presented evidence that macrophages inhibited in vitro immune responses by depleting arginine from the culture medium, and arginase activity was demonstrated in macrophage lysate. However, in the report arginase activity in the culture medium was only slightly increased above background, and the products of arginine degradation were not identified. Hence there was uncertainty over whether this or another enzyme was responsible for arginine depletion. Arginine deiminase has been shown to cause similar growth inhibition in other culture systems (3). Furthermore, the macrophage arginase was not characterized; its mode of action and its relation to liver arginase, which have been extensively studied, were not shown. In the present paper these points have been investigated. Our inhibitor proved to be arginase (EC 3.5.3.1.), since it converted the arginine in the medium to urea and ornithine. The amount of enzyme activity found in the supernatants is quantitatively sufficient to account for the depletion of arginine to below a growth permissive level for lymphoma cells. The enzyme has a relatively low affinity for its substrate ( K , 1.0 x lo-, M) and has properties very similar to those of bovine liver arginase as reported by previous workers. Materials and methods. Mouse macrophage culture supernatant (MCS).This was prepared as in the previous report (1).The authors wish to thank Ms. Myra Lederman for secretarial assistance.Briefly, peritoneal cells were collected from DBN2 mice 4 days after ip injection of 2 ml thioglycollate medium. The cells, comprising more than 80% macrophages as judged by latex particle ingestion, were washed and cultured in Dulbecco's medium without serum for 48 hr at 1 x lo7 celldml. The viability at 48 hr culture was 80-92%. The culture fluid was then collected, centrifuged at 20,000 rpm for 20 min to remove cells, and (unless specified) dialyzed against Dulbecco's medium. The fluid was then filtered and stored at -20°C.Mouse lymphoma cells. L1210A was maintained in c u l t u r e in Dulbecco's medium and 10% fetal calf serum (FCS) as described previously (1). For inhibition assay, 2 x lo5 cells were inoculated in 1 ml of test fluid, cultured for 48 hr, and the viable cells were counted by trypan blue exclusion. R e a g e n t s . [ g u a n i d o -1 4 C ] -o r [ U -14C]arginine HCl and [14C]urea, all used at 50 mCi/mmole, were purchased from Amersham Corporation. Ingredients for c u l t u r e medium w e r e o b t a i n e d f r o m GIBCO, chromatographic reagents and salts were from Fisher, and other chemicals were from Sigma. Identification and measurement of products of arginine degradation in media treated with macrophage supernatant. One microcurie of C14 [ g~a n i d o -'~C ] -or [U-''C]arginine and unlabeled arginine at a final con...