Shutaku Kim

Comparative study of cutaneous T-cell lymphoma and adult T-cell leukemia/lymphoma: Clinical, histopathologic, and immunohistochemical analyses

An important disease entity distinct from cutaneous T‐cell lymphoma (CTCL) in Japan is adult T‐cell leukemia/lymphoma (ATL), which usually shows the same phenotype as CTCL, i.e., a helper/inducer T‐cell phenotype (CD4+CD8‐), and usually involves the skin. Clinically, both CTCL and ATL are heterogeneous in nature. in this study, we demonstrated differences between CTCL and ATL in terms of clinical and immunopathologic cell surface features. in patients with ATL, the predominant clinical findings were peripheral lymph node involvement, skin lesions, hepatosplenomegaly, leukemic manifestations, and an aggressive course. in patients with CTCL, by contrast, only skin lesions predominated at the onset of the disease and a relatively good prognosis was demonstrated. Phenotypic heterogeneity of ATL in the skin, i.e., CD4‐CD8‐, CD4+CD8‐, and CD4‐CD8+, was demonstrated. Expression of Leu8, CD7 (Leu9), and CD45RA (2H4) was high in both the skin‐infiltrating ATL cells and peripheral blood and lymph node ATL cells compared with that in the skin‐infiltrating CTCL cells. Expression of CD25 (IL‐2R), CD71 (OKT9), HLA‐DR, and HLA‐DQ was higher in the skin‐infiltrating ATL cells than in CTCL cells. Expression of CD29 (4B4) was high, and that of CD45RA (2H4) was low in both the skin‐infiltrating ATL and CTCL cells compared with the peripheral blood and lymph node ATL cells. Expression of CD45RO (UCHL‐1) was not significantly high in the skin‐infiltrating CTCL cells compared with that in ATL cells. the most significant phenotypic difference between ATL cells and CTCL cells was the expression of Leu8 (lymph node homing receptor), CD7 and CD25 antigens on the cell surface, and the main phenotypic difference between skin‐infiltrating ATL and CTCL cells and peripheral blood and lymph node ATL cells was the expression of CD29 and CD45RA. These findings confirm that the difference in antigen expression on the cell surface might reflect the clinical features of ATL and CTCL, and suggest that the predominant phenotype of peripheral blood and lymph node ATL cells is that of naive, relatively immature or activated T‐cells, and that CTCL cells are previously activated (memory) T‐cells. in other words, CTCL cells do not share the same origin as ATL cells. These observations support the concept that ATL is a disease distinct from CTCL.

Adult T-cell leukemia/lymphoma (ATL) –clinical, histopathological, immunological and immunohistochemical characteristics

Abstract Twenty‐one patients with ATL were assessed. The predominant physical findings were lymph node and bone marrow involvement, skin involvement, hepatosplenomegaly and leukemic manifestations. The predominant histopathological findings in both skin and lymph node specimens were the diffuse medium‐sized cell type and the diffuse mixed cell type. Some phenotypic discrepancy was found between the neoplastic cells in the peripheral blood, lymph nodes and skin of patients with ATL with respect to CD45RA and CD45RO, and CD7, CD29, CD25 and HLA‐DR. That is, the predominant neoplastic cell phenotype was the helper T‐cell, which was CD3+, CD4+, CD7+, CD25+, CD45RA+ and HLA‐DR+, and CD29− and CD45RO− in peripheral blood and lymph nodes, and CD3+, CD4+, CD7+, CD29+, CD45RO+ and HLA‐DR+, and CD45RA− in the skin. In other words, we have described the phenotypic heterogeneity of ATL cells and demonstrated the heterogeneity of CD45R isoform expression on ATL cells in different organs – the skin, peripheral blood and lymph nodes – of the same patient.

Phenotypic heterogeneity of lymphoma of the skin.

We studied surface markers present in 56 cases of lymphoma of the skin by immunohistochemical staining, using the ABC (avidin‐biotin‐peroxidase complex) and PAP (peroxidase‐antiperoxidase complex) methods. Of these cases, 49 were T‐cell lymphoma and 7 were B‐cell lymphoma. Ten of the 49 cases of T‐cell lymphoma were adult T‐cell leukemia/lymphoma (ATL). Twenty‐five of 31 cases of T‐cell lymphoma except ATL analyzed by the ABC method showed a helper/inducer phenotype (Leu2a−, Leu3a+), two cases showed a suppressor/cytotoxic phenotype (Leu2a+, Leu3a−), one case showed Leu2a+Leu3a+, one case showed an inducer phenotype (Leu2a−, Leu3a+, Leu9+), and one case showed OKT11+, Leu2a−, Leu3a−, Leu1−, Leu9+, CD25+, Leu10+, CD30+. One CD8+ lymphoma was Pagetoid reticulosis, and a CD4+, CD8+ lymphoma was lymphomatoid papulosis with erythematous plaque. Cutaneous T‐cell lymphoma (CTCL), previously described by Edelson et al., is defined as a helper T‐cell lymphoma with marked affinity for the skin. In our study, 5 cases of T‐cell lymphoma of the skin were not CTCL as described by Edelson et al. These results show that T‐cell lymphoma of the skin is heterogeneous in nature. In other words, CTCL is one type but represents a major proportion of T‐cell lymphomas of the skin.

Treatment of cutaneous T-cell lymphomas (CTCL) with extracorporeal photochemotherapy--preliminary report.

Since August of 1988, we have treated seven CTCL patients with extracorporeal photochemotherapy, including two with tumor‐stage mycosis fungoides (MF) showing mucinous degeneration, two with plaque‐stage MF, and two with erythrodermatous MF. One was withdrawn just after the first trial. For each patient, the phenotypes of peripheral blood lymphocytes were analyzed by flow cytometry in terms of the percentages of OKT11, OKT3, OKT4, Leu9, OKT8, B1, Tac, OKT9, OKIal, Leu7, Leu3a/4B4, and Leu3a/2H4 cells. These parameters were compared with the clinical responses according to skin score. The two patients with tumors died, but the five patients without tumors did not. Three of the 6 patients responded to the treatment. Side effects that are often associated with standard chemotherapy, such as bone marrow suppression, gastrointestinal symptoms and hair loss, were not observed. One cardiovascular event (1 patient) occurred. No significant changes in T‐cell subsets were seen during the course of therapy. These preliminary data suggest that extracorporeal photochemotherapy may be effective for CTCL other than tumor‐stage MF.

A case of cutaneous B-cell lymphoma treated successfully with MACOP-B.

A case of cutaneous B‐cell lymphoma successfully treated by MACOP‐B therapy is described. The patient was a 43‐year‐old man with reddish tumors measuring 3 to 7 cm in diameter on the right cheek and the post‐auricles. Histopathologically, massive infiltrations of medium‐sized atypical lymphoid cells were found in the reticular dermis and subcutis. A clear zone beneath the epidermis was also detected. The atypical lymphoid cells were positive for CD19, CD20, CD22 and HLA‐DR but negative for CD3, CD4, CD5, CD10, CD43, CD45RO and CDw75. The patient was treated successfully with the MACOP‐B protocol from March of 1990 to May of 1990. Since April of 1990, he has been free of disease.

A Case of Cutaneous B‐cell Lymphoma with a Storiform Stromal Reaction

A case of cutaneous B‐cell lymphoma is described. The patient was treated only by surgical excision of the skin tumors five times during a period of about two years from February of 1984 to October of 1986. After the last surgical excision, a continuous disease‐free period was achieved. Biopsy samples showed dense lymphocytic infiltrations with discrete masses in the dermis and subcutis; one of them showed a storiform pattern. At the time, the infiltrating cells were composed of medium and large lymphoid cells and spindle‐shaped cells. The medium and large lymphoid cells were positive for CD20, CD22 and HLA‐DR and negative for CD3, CD4, CD5, CD8, CD43, and kappa and lambda light chain. The spindle‐shaped cells were negative for CD20, CD43, kappa and lambda light chain, lysozyme, and S‐100 protein.

Low Expression of Adhesion Molecules in a Case of Cutaneous T-cell Lymphoma

A case of cutaneous T‐cell lymphoma (CTCL) with low expression of the adhesion molecules lymphocyte function‐associated antigen‐1 (LFA‐1), intercellular adhesion molecule‐1 (ICAM‐1), and very late antigen‐4 (VLA‐4) is described. The patient was a 90‐year‐old man with red round homogeneous tumors on his scalp, trunk, and extremities. He had no history of definite erythema or plaque stage. A biopsy sample taken from a tumor revealed massive infiltration of atypical lymphocytes in the reticular dermis and subcutis with a definite clear zone. The atypical lymphocytes were medium‐sized with slightly convoluted nuclei. Immunohistochemically, the infiltrates showed the phenotype of so‐called memory T cells. On the basis of these features, the case was diagnosed as CTCL. Expression of LFA‐1, ICAM‐1 and VLA‐4 on the infiltrates was 9%, 13% and 11%, respectively, which is much lower than that in classic mycosis fungoides. This finding suggests that loss of these adhesion molecules may contribute to loss of epidermotropism in the advanced stage of CTCL.

Successful Treatment of Adult T‐cell Leukemia/Lymphoma with MACOP‐B, M‐FEPA and VEPP‐B Combination Chemotherapy

A 45‐year‐old man was referred to our department in March of 1989. Physical examination showed erythroderma, palmo‐plantar hyperkeratosis, generalized lymphadenopathy, hepatosplenomegaly, and leukemic manifestation. The lymphocyte count in the peripheral blood before treatment was 1.7 × 104 cells/mm3. Atypical lymphocytes such as flower cells and lobulated cells were seen in the peripheral blood. A sample excised from a lymph node showed immunoblastic, pleomorphic T cells by a modified classification scheme of the Working Formulation. A high level of serum LDH was detected (2.1 times the upper normal limit). Anti HTLV‐1 antibody was also detected in the serum. The atypical lymphocytes were positive for CD3, CD4, CD5, CD7 and HLA‐DR, and negative for CD8. Thus, the clinical, pathologic and immunologic features were those of typical acute‐type ATL.

Cutaneous B-cell lymphoma consisting of large cleaved cells with multilobated nuclei

A 65‐year‐old man was seen at the Ushioda Hospital in Au‐gust 1989, because of a 1‐month history of a tumor on the scalp. The tumor was excised and the diagnosis was malig‐nant lymphoma. The patient was then referred to our de‐partment in September 1989. Several nut‐sized lymph nodes wvepa‐b and m‐fepa for 2 months. Since then, the patient has been free of disease up to the time of writing, July 1992, a period of 2.5 years.

A case of malignant proliferative trichilemmoma.

At our clinic, we have encountered two patients with malignant proliferating trichilemmal cyst and 11 patients with malignant trichilemmoma in a 13-year period (1981-1993). We present a case of malignant proliferating trichilemmal cyst in a 72-year-old Japanese man, who had first noticed a coffee-bean sized skin tumor on the scalp about 5 years before presentation. This tumor was removed totally at a local clinic about 2 years later, but recurrence was noticed 6 months after surgery. In March 1992, 130 mg of CPT-11 was infused intravenously. The first course of the treatment consisted of one fusion per week for 4 weeks, and a minor response was obtained. However, a second course of treatment, 120 mg of CPT-11 per week for 4 weeks, could not reduce the size of the mass, and therefore sugery was carried out. Two years after surgery, there has been no evidence of recurrence.