LYMPHOMATOID PAPULOSIS AND FK-506

A 53-year-old woman underwent an orthotopic liver transplant in Pittsb urgh in October 1990. She had been suffering from chronic hepatitis C that had evolved into cirrhosis with ascites, jaundice, and encephalop athy. In April 1991 she required reconstruction oi the biliary anastom osis because of stricture, and in October 1991 she underwent a liver b iopsy because of mild elevation of alkaline phosphatase. The biopsy re vealed mild chronic rejection and changes consistent with viral hepati tis, She was on oral FK 506, 4 mg b.i.d. In November 1992 she develope d recurrent self-healing erythematous, papulanodular lesions on the ch est and shoulders (Fig. 1), The lesions were purplish red, mildly prur itic, and undergoing vesiculation on the top. The lesions ranged from 3 to 5 mm in size, and a few showed ulceration and necrosis and were h ealing with hypopigmented scars. The Lesions gradually increased in nu mber and size. A trephine biopsy specimen was obtained from the lesion al skin. The tissue was prepared for light microscopic study by fixing in 10% formaldehyde solution and staining with hematoxylin and eosin, Immunohistochemistry was carried out for lymphoid markers, In Februar y 1993, a papulonodular lesion near the left axilla enlarged to a size of 10 x 10 cm; it was ulcerated and necrotic, A biopsy was taken and sent for histopathology and immunohistochemistry. The patient continue d on FK 506, 4 mg b.i.d. Many of the early lesions had become purpuric , eroded, and healed with scarring; however, fresh lesions continued t o appear. A decision about modification of the patient's immunosuppres sive medication was left to the Transplant Team; however, there was co ncern that her lymphomatoid papulosis may be a side-effect of her FK 5 06 treatment. Laboratory investigation revealed a normal peripheral bl ood film. Liver enzymes and a renal profile were within normal limits. The results of a bone marrow study, liver and spleen scan, and endosc opic examination of the gastrointestinal tract were normal. A skin bio psy revealed a nodular and wedge-shaped dermal infiltrate involving th e entire dermis. The pleomorphic epidermotropic infiltrate in the uppe r one-third of the dermis was composed of many round or oval cells wit h hyperchromatic nuclei, A few nuclei were indented or kidney-shaped. Mild mitotic activity was seen. The larger immunoblast-like cells were mixed with normal lymphoctyes and histiocytes. The capillaries had th ickened walls with prominent endothelial cells. The second biopsy from the ulcerated axillary lesion showed a dense superficial and deep wed ge-shaped infiltrate, abnormal pleomorphic cells, and a few large lymp hoid cells (Fig. 2) infiltrating the dermis and extending to the subcu taneous tissue. There were scanty histiocytes, neutrophils, and a few eosinophils. Some of the large abnormal cells had kidney-shaped nuclei but most had irregularly shaped nuclei with abundant cytoplasm (Fig. 3). There were many abnormal mitoses, and there were also numerous ext ravasated red blood cells and edema in the dermis. The epidermis was n ecrotic and ulcerated. The results of immunohistochemical tests showed a strong reaction for LCA and CD8, but a negative reaction for CD20. The patient's general condition and laboratory tests of hepatic and re nal functions remained normal. The results of all hematologic studies, including bone marrow smear, lymph node biopsy, and liver-spleen scan , were normal. The patient continued on FK 506, 4 mg b.i.d. Serum leve ls of FK 506 which were never communicated to us were sent for the fir st time in May 1993 and showed a serum level of 39 ng/mL (normal 0.5-2 ng/mL)(1) with an instruction to repeat the test. The dose of FK 506 was immediately reduced to 4 mg/day. The patient revisited the clinic for routine check-up on June 26, 1993. The axillary lesion had disappe ared leaving a hyperpigmented scar, the small lesions of lymphatoid pa pulosis continued to come and go.