894 Correspondence 3 Lo SK, Wang CC, Fang W. Physical interpersonal relationships and social anxiety among online game players. Cyberpsychol Behav 2005; 8:15–20. 4 Bonis J. Acute Wiiitis. N Engl J Med 2007; 356:2431–2. 5 Rushing ME, Sheehan DJ, Davis LS. Video game induced knuckle pad. Pediatr Dermatol 2006; 23:455–7.
(a)
Key words: console gaming, palmar eccrine hidradenitis Conflicts of interest: none declared.
CD20+ primary cutaneous T-cell lymphoma presenting as a solitary extensive plaque
(b)
DOI: 10.1111/j.1365-2133.2009.09045.x SIR, CD20, a transmembrane protein mainly expressed in B cells, has been used to identify the subtypes of malignant lymphoma as a B-cell marker with CD79a.1 However, recent studies indicated that peripheral T-cell lymphomas rarely express CD20 antigen.2–6 We report a primary cutaneous peripheral T-cell lymphoma (PCPTL) that strongly expressed CD20. A 73-year-old man presented with an 8-month history of a progressive erythematous plaque on the left side of the abdomen. Physical examination revealed an oval, soft, welldemarcated reddish plaque measuring 13 · 5 cm, with a dark-red appearance in the centre (Fig. 1a). The border was slightly elevated. There were no palpable lymph nodes in the cervical, inguinal and axillary areas. The patient appeared to be in good health, and routine laboratory investigations showed no abnormalities. An incisional biopsy specimen was obtained from the lesion. Histopathological examination showed a dense diffuse infiltrate of atypical lymphocytes in the upper dermis and a nodular infiltrate in the deep dermis and subcutaneous tissue, and slight hyperkeratosis and atrophy of the overlying epidermis (Fig. 1b,c). There was little epidermotropism. A massive dermal infiltrate effaced the dermal architecture. Medium-tolarge atypical lymphocytes with hyperchromatic nuclei had a largely pleomorphic appearance including masses of mitoses. Immunohistological evaluation showed strong staining of atypical cells for CD3, CD4, CD5 and CD20, and partial positivity for CD8 and CD79a in the intermixed reactive cells (Fig. 2). There was no staining for CD7, CD30, CD56 or latent membrane protein 1 of the Epstein–Barr virus. Almost all tumour cells were immunoreactive for MIB-1, indicating a very high proliferative rate. Molecular genetic studies were performed using genomic DNA from the skin biopsy sample. Southern blot analysis demonstrated T-cell receptor b and c chain gene rearrangement and no clonal rearrangement of the immunoglobulin heavy chain. General examination by a computed tomographic scan, gallium-67 scintigraphy and bone marrow biopsy revealed no evidence of extracutaneous involvement. We made a diagnosis of
(c)
Fig 1. (a) Physical examination revealed a 13 · 5 cm, well-demarcated reddish plaque on the left side of the abdomen. (b) Histopathological examination showed a dense diffuse infiltrate of atypical lymphocytes in the upper dermis and a nodular infiltrate in the deep dermis. A massive dermal infiltrate effaced the dermal architecture. (c) Atypical lymphocytes had a largely pleomorphic appearance including masses of mitoses. There was little epidermotropism. Haematoxylin and eosin; original magnification: (b) · 40, (c) · 400.
PCPTL, unspecified (T1N0M0, stage IA). After excision of the solitary erythematous plaque with a 1-cm margin, electron beam therapy, total radiation dose 30 Gy, was given around the wound margins in 15 fractions over 3 weeks. There was no recurrence for a follow-up period of 1 year after the radiation therapy. As a specific B-cell marker, CD20 has been used to distinguish B-cell from T-cell lymphoma.1 CD20 has been 2009 The Authors
Journal Compilation 2009 British Association of Dermatologists • British Journal of Dermatology 2009 160, pp881–898
Correspondence 895
Fig 2. Immunohistological evaluation showed strong staining of atypical cells for CD3, CD4 and CD20, and partial positivity for CD8 and CD79a in the intermixed reactive cells. There was no staining for CD30 (original magnification · 100).
considered to be a 35-kDa transmembrane protein expressed from early pre-B-cell development until final differentiation into plasma cells.2 The binding of the antibodies against CD20 protein inhibited proliferation and differentiation of B cells, suggesting that CD20 protein might be involved in the regulation of B-cell growth.7 Indeed, anti-CD20 monoclonal antibodies have been used for the treatment of non-Hodgkin B-cell lymphoma and autoimmune diseases. Recently, rare cases have been reported in the literature that show T-cell lymphomas ⁄leukaemias expressing CD20.2–6 The existence of CD20+ T cells in the peripheral blood of healthy individuals has been shown using flow cytometry,8 and two-thirds of these normal CD3+ ⁄CD20+ T cells are CD8 positive and one-third is CD4 positive in the peripheral blood.2 These results raise the possibility that CD20+ lymphoma is not an aberrant expression of CD20 but rather one of malignant transformation of a small population of T cells that normally express CD20. To our knowledge, four cases of CD20+ cutaneous T-cell lymphoma have been reported before.3–6 One of them was mycosis fungoides diagnosed as tumour stage with lymph node involvement and skin nodules.3 The other three cases
were PCPTL presenting with solitary or localized plaques,4–6 and two of these showed an aggressive clinical course with repeated skin recurrence.5,6 In the present case, a solitary lesion grew to a bulky plaque measuring 13 · 5 cm during only 8 months, and pleomorphic atypical lymphoma cells showed CD20 antigen and a high MIB-1 index, indicating aggressive behaviour. Previous studies indicated that the CD20+ T cells in T-cell lymphoma expressed several activation antigens such as CD38, CD45RO and HLA-DR,9 and T cells derived from monkey lymph node expressed CD20 by antigenic stimulation.10 Although the significance of CD20 antigen expressed in T-cell lymphoma has been unclear, these results suggested that CD20 might be a marker of T-cell activation. Further studies are required to determine the prognostic significance of CD20+ T-cell lymphomas. Department of Dermatology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan Correspondence: Yasushi Matsuzaki. E-mail:
[email protected]
2009 The Authors Journal Compilation 2009 British Association of Dermatologists • British Journal of Dermatology 2009 160, pp881–898
H. OSHIMA Y. MATSUZAKI S. TAKEUCHI H. NAKANO D. SAWAMURA
896 Correspondence
References 1 Stashenko P, Nadler LM, Hardy R et al. Characterization of a human B lymphocyte-specific antigen. J Immunol 1980; 125:1678–85. 2 Quintanilla-Martinez L, Preffer F, Rubin D et al. CD20+ T-cell lymphoma: neoplastic transformation of a normal T-cell subset. Am J Clin Pathol 1994; 102:483–9. 3 Sen F, Kang S, Cangiarella J et al. CD20 positive mycosis fungoides: a case report. J Cutan Pathol 2008; 35:398–403. 4 Blakolmer K, Vesely M, Kummer JA et al. Immunoreactivity of B-cell markers (CD79a, L26) in rare cases of extranodal cytotoxic peripheral T- (NK ⁄ T-) cell lymphomas. Mod Pathol 2000; 13:766–72. 5 Magro CM, Seilstad KH, Porcu P et al. Primary CD20+CD10+CD8+ T-cell lymphoma of the skin with dual IgH and TCRb gene rearrangement. Am J Clin Pathol 2006; 126:14–22. 6 Garcia-Herrera A, Colomo L, Camo´s M et al. Primary cutaneous small ⁄ medium CD4+ T-cell lymphomas: a heterogeneous group of tumors with different clinicopathologic features and outcome. J Clin Oncol 2008; 26:3364–71. 7 Tedder TF, Forsgren A, Boyd AW et al. Antibodies reactive with the B1 molecule inhibit cell cycle progression but not activation of human B lymphocytes. Eur J Immunol 1986; 16:881– 7. 8 Hultin LE, Hausner MA, Hultin PM et al. CD20 (pan-B cell) antigen is expressed at a low level on a subpopulation of human T lymphocytes. Cytometry 1993; 14:196–204. 9 Takami A, Saito M, Nakao S et al. CD20-positive T-cell chronic lymphocytic leukaemia. Br J Haematol 1998; 102:1327–9. 10 Murayama Y, Mukai R, Sata T et al. Transient expression of CD20 antigen (pan B cell marker) in activated lymph node T cells. Microbiol Immunol 1996; 40:467–71. Key words: CD20, cutaneous T-cell lymphoma Conflicts of interest: none declared.
A case of natural killer cell monoclonal expansion during efalizumab treatment in a patient with psoriasis DOI: 10.1111/j.1365-2133.2009.09059.x SIR, A 78-year-old man with a 10-year history of severe plaque psoriasis was seen in our department in March 2006 in order to begin efalizumab (Raptiva; Merck Serono, Geneva, Switzerland) therapy. Previously, several systemic therapies including acitretin, psoralen + ultraviolet A therapy, methotrexate and ciclosporin had yielded only moderate improvement, without achieving complete remission. At presentation he showed psoriatic plaques involving scalp, trunk and limbs. The Psoriasis Area and Severity Index (PASI) was 23Æ4 and the body surface area (BSA) affected was 38%. Serology for hepatitis and human immunodeficiency viruses, as well as tuberculin test (Quantiferon test), were negative. The patient was started on efalizumab at a dose of 0Æ7 mg kg)1 at week 1 and then 1 mg kg)1 subcutaneously per week thereafter, according to current protocols. On this single agent, psoriasis markedly improved over the following
3 months. At week 12, PASI had reduced to 9Æ5, accounting for < 50% of the initial score (PASI 50), and BSA was 6%. As recommended by standard follow-up protocols, the patient had full blood cell counts monthly for the first 3 months and quarterly thereafter. The patient maintained normal blood cell counts and had no systemic complaints for the first year of therapy. In September 2007 the patient developed peripheral lymphocytosis. Blood chemistry revealed a white blood cell (WBC) count of 9Æ3 · 109 L)1, haemoglobin 14Æ6 g dL)1, platelet count 225 · 109 L)1; differential count included 39% neutrophils, 54% lymphocytes, 6% monocytes, 0Æ8% eosinophils and 0Æ2% basophils. Circulating lymphocytes were morphologically atypical, big and granulomatous. Immunophenotype characterization revealed a normal CD3+ T-cell count, as opposed to an increase of natural killer (NK) cells (CD3) CD16+ CD56+) (1Æ72 · 109 L)1, 32%; normal 0Æ20–0Æ40 · 109 L)1, 8–20%) with prevalent monoclonal expression. The patient did not show lymphadenopathy or hepatosplenomegaly. An ultrasound examination of the abdomen was normal. Haematologists suggested to discontinue any immunosuppressive treatment in order to avoid malignant change into large granular lymphocytic leukaemia. However, while decreasing efalizumab, NK cells decreased rapidly and counts returned to within normal range in the following 2 months. Efalizumab was therefore maintained at a dose of 0Æ5 mg kg)1 weekly and then stopped after 2 weeks of complete remission; psoriasis did not relapse and the patient is still being monitored by monthly WBC counts. Efalizumab binds CD11a on the surface of T cells,1 affecting T-cell activation and trafficking, and is effective and safe for the treatment of severe psoriasis.2,3 Mild-to-moderate influenza-like symptoms can occur with the first treatments. Moreover, after approval of the drug it became evident that a few patients may develop thrombocytopenia or haemolytic anaemia,4 although the mechanism for the haematological toxicity is still unclear. To date, several papers have consistently reported the occurrence of elevated WBC counts during efalizumab therapy. Some authors define this increase as ‘relative leucocytosis’, as it seems primarily due to an increase in lymphocyte counts, while neutrophils and monocytes usually remain unchanged.5 An up to fourfold elevation in lymphocytes has been documented; this generally develops within 2–8 weeks from starting efalizumab administration and is gradually reversed upon discontinuation of the drug.6 It has been clarified that efalizumab-dependent lymphocytosis is mainly due to the recompartmentalization of T-cell subsets between affected tissue and peripheral blood.7 The interference of efalizumab in lymphocyte extravasation and homing into psoriatic plaques appears to be responsible for the T-cell depletion observed in affected skin, as well as for the increase in blood cells. Vugmeyster et al.5 demonstrated that during efalizumab therapy both CD4+ and CD8+ naı¨ve and memory circulating 2009 The Authors
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