Shonosuke Nagae

A case of CD56+ cutaneous aleukaemic granulocytic sarcoma with myelodysplastic syndrome

We describe a 70‐year‐old man with cutaneous granulocytic sarcoma who presented with numerous cutaneous nodules but without any leukaemic involvement of the peripheral blood. The tumour cells were positive for lysozyme, peroxidase, CD11a, CD11c, CD33 and HLA‐DR, and weakly positive for CD4 and CD14, suggesting granulocytic differentiation. The bone marrow at admission showed dysplasia of the erythrocytic and granulocytic lineage and complex chromosomal abnormalities in association with an increase in monocytes. The patient was diagnosed as having granulocytic sarcoma of monocytic lineage with concomitant myelodysplastic syndrome. In this case, tumour cells also expressed the neural cell adhesion molecule (CD56), which has been suggested as a possible risk factor for developing granulocytic sarcoma in acute myelogenous leukaemia.

Hyperthermic Isolated Limb Perfusion with Intra‐Arterial Administration of Carboplatin and/or Interferon‐β for the Treatment of Malignant Melanoma of the Leg

Our experiences of hyperthermic isolated limb perfusion with administration of carboplatin, interferon‐β or a combination of both are reported. Administration of high doses of these reagents was well tolerated by patients with melanoma without severe complications after the treatment. A total of 8 patients underwent this therapeutic modality. Remarkable clinical improvement was seen in the first patient, who was in Stage III at the time of the perfusion. Histopathological findings indicated severe damage to the melanoma cells after the operation. Prophylactic hyperthermic perfusion was performed in 6 other patients with Stage II–III melanoma of the lower limb. None of them have shown any signs of recurrence 1–10 months later. The activities of natural killer cells or T lymphocytes appeared to be increased when the perfusion was carried out with concomitant administration of both carboplatin and interferon‐β. These results suggest that hyperthermic isolated limb perfusion with carboplatin and/or interferon β administration is effective in patients with advanced stage melanoma.

Kinetics of immunological parameters in patients with malignant melanoma treated with hyperthermic isolated limb perfusion

Kinetics of immunological parameters such as natural killer (NK) cell activity and tritium-thymidine uptake rate of T lymphocytes by phytohemagglutinin stimulation were investigated using peripheral leukocyte fractions of melanoma patients treated with hyperthermic isolated limb perfusion (HILP). Also, serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) were quantified during and after HILP. It was found that NK cell activity was augmented during HILP, and T lymphocyte function was stimulated 24 h and 1 week after HILP with statistical significance. NK cell activities in the cells isolated from perfused and non-perfused circulations were equally augmented during HILP in two patients examined. Serum concentrations of sICAM-1 in the patients who received HILP also increased 24 h or even 1 week after HILP. The stimulation of these immune competent cells and upregulation of sICAM-1 by HILP were independent of the stages of melanoma patients at the time of HILP or the doses of agents which were used for the infusion during HILP. The origin of cells which shed sICAM-1 into the serum of the patients who received HILP remains to be further investigated.

STUDIES OF CELL AND ORGAN CULTURE OF PSORIATIC AND NORMAL EPIDERMIS IN VITRO

Involved and noninvolved epidermis from 15 psoriatic patients, and epidermis from 12 normal individuals were grown under various conditions in vitro as cell and organ cultures. In the organ cultures of normal or noninvolved psoriatic skin, epidermal cells migrated around the dermis and differentiated. In psoriatic organ cultures, progressive necrotic changes were observed in the spinous cells including gradual detachment of the spinous layer from the dermis. In spite of these necrotic changes, newly‐grown basal cells which appeared on the dermal tissue in the 9 to 12‐day psoriatic explants clearly incorporated 3H‐thymidine into nuclear DNA. By electron microscopy these cells were observed to have numerous ribosomes, a few mitochondria, tonofilament‐like structures in the cytoplasm, and no hemi‐desmosomes. Dissociated epidermal cells from the involved psoriatic skin failed to grow on plastic dishes. When these cells were plated on dishes coated with increasing amounts of collagen, the rate of cellular attachment was proportional to the thickness of the collagen coating, but they were unable to grow and form epidermal monolayers. In contrast, normal and noninvolved psoriatic epidermal cells attached to the dishes regardless of the presence of collagen and formed differentiated epidermal monolayers.

Two Cases of Metastatic Malignant Melanoma of the Lower Limb Treated with Hyperthermic Isolated Limb Perfusion and Concomitant Infusion of Either Carboplatin or β-Interferon

Two cases of metastatic malignant melanoma of the lower limb who were treated successfully with hyperthermic isolated limb perfusion are reported. One patient was infused with cis‐diammine (1.1‐cyclobutanedicarboxylate) platinum (II) (carboplatin, Paraplatin®, Bristol‐Myers Squibb Company, New Jersey, USA), and the other was infused with human natural β‐interferon (Feron®, Toray, Tokyo, Japan), via the external iliac artery. The first case showed a remarkable suppression of the growth of multiple metastatic melanoma nodules associated with numerous melanophage infiltrations, as shown histopathologically after the operation. The patients serum level of 5‐S‐cysteinyl dopa decreased for the two months following the treatment In the second case, new formation of metastatic melanoma nodules was completely suppressed for up to 12 months following the operation. Analysis of immunological parameters showed that the number of peripheral CD8+ lymphocytes gradually and constantly increased after the operation, while that of CD4+ lymphocytes transiently increased and then returned to the pre‐operative level. Natural killer activity transiently decreased to a slight degree 4 days after the operation and then returned to the pre‐operative level 21 days after the operation. Side effects, such as nausea, vomiting and leg discomfort, were seen in the patient (Case 1) treated with carboplatin, but were completely reversible. These results suggest that hyperthermic isolated limb perfusion with concomitant infusion of carboplatin or β‐interferon is effective in suppressing the growth of metastatic malignant melanomas of the lower limb.

Immune thrombocytopenia due to Tranilast (Rizaben): detection of drug-dependent platelet-associated IgG.

Tranilast (Rizaben®)‐induced thrombocytopenia occurring in a 17‐year‐old man was reported. After withdrawal of the drug, he recovered within a week with oral prednisolone administration. Serological examination revealed no anti‐platelet antibody, but platelet‐associated IgG (PAIgG) was found. After incubation of peripheral blood of the patient with the drug in vitro, the level of PAIgG was significantly increased. These findings suggest the presence of a drug‐dependent anti‐platelet IgG in the patients serum. This is the first report of immune thrombocytopenia caused by Tranilast. Our method for detecting drug‐dependent platelet antibody in vitro is safe and useful for diagnosing drug‐induced thrombocytopenia.

Factor XIIIa expression in pseudo-Kaposi sarcoma.

A 39‐year‐old man had pseudo‐Kaposi sarcoma on his left foot. A biopsy specimen obtained from a cutaneous lesion showed increased numbers of vascular spaces, proliferation of fibroblast‐like spindle cells, and deposition of hemosiderin in the dermis. Immunohistochemically, proliferative fibroblast‐like spindle cells around the vessels were positive for anti‐factor XIIIa antibody. Excessive heat radiation was detected from the skin lesions by thermography.

Delayed Tissue Necrosis Associated with Mitomycin‐C Administration

To the Editor: Mitomycin C (MMC), an antitumor antibiotic, is active in numerous tumors and has been well used for cutaneous squamous cell carcinoma in association with peplomycin. Although extravasation of MMC to the tissues at the time of administration is a well-known cause of ulceration and tissue necrosis, there have been only infrequent previous case reports of an unexplained, delayed cutaneous ulceration (1-5). Cutaneous ulceration from extravasation of MMC generally occurs one to two weeks after treatment and persists for one to four months (6). We report a case of a patient who developed cutaneous ulceration seven weeks after intravenous MMC infusion without symptoms of tissue injury. Case Report: A 71-year-old woman underwent a resection for perianal squamous cell carcinoma developed from Bowens disease (Bowen-carcinoma) onJune 20th, 1997. She underwent left inguinal lymph node dissection for metastasis in November of 1998 and following local radiation and chemotherapy including MMC and peplomycin in December. Peplomycin was intramuscularly used on the bilateral deltoid muscle from December 1 to December 9. On December 10, she received MMC injection into th left volar antebrachial region adjacent to anticubital fossa. The patient did not notice any pain or incongruity while receiving this MMC infusion. There was no evidence of erythema or infiltration noted at that time. Four days later, the infusion site on her left forearm was slightly inflamed. The symptoms disappeared in several days without any specific treatment. However, seven weeks after the MMC injection, she noted slight induration and burning just on the left anticuboital Letters to the Editor

Properties of Partially Purified Mouse Epidermal Transglutaminase

Mouse epidermal transglutaminase was partially purified from the epidermis of newborn BALB/c mice. The epidermal homogenate was subjected to CM‐cellulose chromatography and then to gel filtration on Sephadex G‐150. Two separate peaks with enzyme activity were reproducibly observed in CM‐cellulose chromatography. Gel filtration on Sephadex G‐150 of the peak fractions in CM‐cellulose chromatography gave a single enzyme activity peak (molecular weight about 55,000). Native polyacrylamide gel electrophoresis at pH 4.5 showed two major bands with enzyme activity. The final enzyme preparation (Sephadex G‐150 fraction) had a pH optimum of 10.0 in glycine‐NaOH buffer. Calcium ion and SH‐protecting agent (dithiothreitol) were essential for enzyme activity. The enzyme was not inactivated by heating at 56°C for 45 min in the presence of calcium. Trypsin treatment of the enzyme enhanced the activity about threefold; this enhancement was blocked by trypsin inhibitor. The enzyme bound to lysine‐Sepharose 4B in the presence of casein in Tris‐acetate buffer, pH 6.0, at 37°C; 40% of the enzyme activity was eluted from this enzyme‐lysine‐Sepharose complex with 1 M NaCl.

Increase in the peripheral lymphocyte populations expressing CD54 (ICAM-1) after hyperthermic isolated limb perfusion in patients with malignant melanoma: an analysis of four cases

The lymphocytes isolated from perfused or non-perfused circulations before, during, and after hyperthermic isolated limb perfusion (HILP) in the four patients with malignant melanoma were analysed for the expression of CD54 (ICAM-1), CD58 (LFA-3), CD4, CD8, HLA class I and class II in order to investigate the mechanism(s) of the activation of such immunocompetent cells as natural killer (NK)-cells or T-lymphocytes by HILP. It was thus found that the lymphocyte populations expressing CD54 increased significantly 1 day after HILP in the four patients examined. The lymphocyte populations expressing CD58 apparently increased. It was also found that the NK-cell and T-lymphocyte activities increased during or after HILP in the present four cases as observed previously in the other melanoma patients. These results indicate that our HILP system may augment the immunological activities through the mechanisms of the induction of CD54 or CD58 expression in the peripheral lymphocytes of the melanoma patients who receive HILP.