Lymphomatoid papulosis and FK 506
Authors: Siddiqui Mohammed A. , Sullivan Stephan , Al‐Mofadhi Ali M. 
Published: August 2010

A 53‐year‐old woman underwent an orthotopic liver transplant in Pittsburgh in October 1990. She had been suffering from chronic hepatitis C that had evolved into cirrhosis with ascites, jaundice, and encephalopathy. In April 1991 she required reconstruction of the biliary anastomosis because of stricture, and in October 1991 she underwent a liver biopsy because of mild elevation of alkaline phosphatase. The biopsy revealed mild chronic rejection and changes consistent with viral hepatitis. She was on oral FK 506, 4 mg b.i.d. In November 1992 she developed recurrent self‐healing erythematous, papulonodular lesions on the chest and shoulders (Pig. 1). The lesions were purplish red, mildly pruritic, 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 healing with hypopigmented scars. The lesions gradually increased in number and size.A trephine biopsy specimen was obtained from the lesional 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 February 1993, a papulonodular lesion near the left axilla enlarged to a size of 10 × 10 cm; it was ulcerated and necrotic. A biopsy was taken and sent for histopathology and immunohistochemistry. The patient continued 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 to appear.A decision about modification of the patient's immunosuppressive medication was left to the Transplant Team; however, there was concern that her lymphomatoid papulosis may be a side‐effect of her PK 506 treatment.Laboratory investigation revealed a normal peripheral blood film. Liver enzymes and a renal profile were within normal limits. The results of a bone marrow study, liver and spleen scan, and endoscopic examination of the gastrointestinal tract were normal. A skin biopsy revealed a nodular and wedge‐shaped dermal infiltrate involving the entire dermis. The pleomorphic epidermotropic infiltrate in the upper one‐third of the dermis was composed of many round or oval cells with 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 thickened walls with prominent endothelial cells.The second biopsy from the ulcerated axillary lesion showed a dense superficial and deep wedge‐shaped infiltrate, abnormal pleomorphic cells, and a few large lymphoid cells (Fig. 2) infiltrating the dermis and extending to the subcutaneous 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 extravasated red blood cells and edema in the dermis. The epidermis was necrotic 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 renal 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 levels of FK 506 which were never communicated to us were sent for the first 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 disappeared leaving a hyperpigmented scar, the small lesions of lymphatoid papulosis continued to come and go.