Solitary primary cutaneous CD30+ large cell lymphoma of natural killer cell phenotype bearing the t(2;5)(p23;q35) translocation and presenting in a child

Primary cutaneous CD30+ large cell lymphoma is an unusual tumor most commonly seen in adults. Most of these lymphomas are of T-cell origin and carry a good prognosis. We present the case of a 4-year-old girl with stage IEA CD30+ large cell lymphoma with a CD56+ natural killer cell phenotype and the t(2;5)(p23;q35) translocation. After excision, the patient has been free of disease for 44 months. Primary cutaneous CD30+ large cell lymphoma is uncommon in children. To our knowledge, primary cutaneous CD30+ natural killer type lymphoma has not been reported previously. The indolent behavior of this tumor indicates its similarity to other primary cutaneous CD30+ large cell lymphomas and its difference from other CD56+ lymphomas involving the skin, which often exhibit an aggressive clinical course. Cases such as this one illustrate why the use of a single, or even a few, immunohistochemical stains can be misleading in regard to lymphoma classification and prognostication.     

Unlikely role of Epstein-Barr virus in the pathogenesis of primary cutaneous CD30+ anaplastic large cell lymphoma

BACKGROUND: Primary cutaneous CD30+ anaplastic large cell lymphoma (ALCL) is a rare subset of cutaneous lymphoma, with a much better prognosis than its nodal counterpart. The pathogenesis of both nodal and primary cutaneous CD30+ ALCL is largely unknown but experimental data support the hypothesis that the Epstein-Barr virus could play a role in the nodal subset. OBJECTIVE: To evaluate the involvement of Epstein-Barr Virus (EBV) in primary cutaneous CD30+ ALCL by searching for both nucleic acids and EBV proteins in cutaneous lesions. SETTING: Two University Hospitals in Southern France (secondary referral hospitals). PATIENTS: Eight consecutive patients with typical primary cutaneous CD30+ anaplastic large cell lymphoma were studied. METHODS: Search for the presence of DNA, RNA and EBV proteins in cutaneous lesions by PCR, in situ hybridization and immunohistochemistry. RESULTS: EBV DNA and RNA was identified in only one lesion of primary cutaneous CD30+ ALCL and in none of the normal adjacent skin samples. In situ hybridization and immunohistological studies were consistently negative in all samples. Conclusion: These results do not support an early role of EBV in the oncogenetic pathogenesis of primary cutaneous CD30+ ALCL.     

原发性皮肤CD30阳性大细胞淋巴瘤1例

报告1例原发性皮肤恶性淋巴瘤。患者，女，14岁，左侧面部进行性肿胀3年余。病理报告为原发性皮肤CD30阳性大细胞淋巴瘤（PCCD30^ -LCL)。免疫组化染色示瘤细胞CD30阳性、CD45RO、CD20阴性。采用COP方案及CHOP-R方案化疗各1次后，效果较好，后失访。     

Disseminated CD8‐positive,CD30‐positive cutaneous lymphoproliferative eruption with overlapping features of mycosis fungoides and primary cutaneous anaplastic large cell lymphoma following remote solitary lesional presentation

CD8‐positive, CD30‐positive cutaneous lymphoproliferative disorders constitute a rare subset of T‐cell lymphoproliferative conditions, including variants of primary cutaneous anaplastic large cell lymphoma (ALCL), mycosis fungoides, lymphomatoid papulosis type D, cutaneous gamma‐delta T‐cell lymphoma and cutaneous peripheral T‐cell lymphoma. These entities share overlapping clinical, histopathologic and immunophenotypic features, presenting both a clinical and pathological diagnostic challenge. Presented here is a 73‐year‐old man with a disseminated, indolent CD30+, CD8+ cutaneous lymphoproliferative disorder with overlapping clinical and histopathological features of both mycosis fungoides and primary cutaneous ALCL, as well as features of lymphomatoid papulosis. To our knowledge, this is the first case of a generalized CD8+, CD30+ eruption with features of both mycosis fungoides and primary cutaneous ALCL arising following an episode of solitary primary cutaneous CD8‐positive ALCL.     

Distinct effects of CD30 and Fas signaling in cutaneous anaplastic lymphomas: a possible mechanism for disease progression

Lymphomatoid papulosis is part of a spectrum of CD30+ cutaneous lymphoproliferative disorders characterized by spontaneous tumor regression. The mechanism(s) of regression is unknown. In a recent study, a selective increase in CD30 ligand expression in regressing lesions of lymphomatoid papulosis and cutaneous CD30+ anaplastic large cell lymphoma was shown, suggesting that activation of the CD30 signaling pathway may be responsible for tumor regression, whereas no difference in Fas/Fas ligand expression was found between regressing and nonregressing lesions. Therefore we tested the effects of CD30 and Fas activation on three CD30+ cutaneous lymphoma cell lines (Mac-1, Mac-2 A, JK) derived from nonregressing tumors of two patients who had progressed from lymphomatoid papulosis to systemic anaplastic large cell lymphoma. To evaluate the effects of CD30 signaling, the cell lines were incubated with a CD30 agonistic antibody, HeFi-1. Proliferative responses, mitogen-activated protein kinase, and nuclear factor kappa B activities were determined with and without CD30 activation. Mac-1 and Mac-2 A showed increased proliferative responses to incubation with CD30 activating antibody, HeFi-1. Inhibition of the mitogen-activated protein kinase activity caused growth inhibition of the Mac-1, Mac-2 A, and JK cell lines. Activation of the Fas pathway induced apoptosis in all three cell lines. Taken together, these findings suggest that resistance to CD30-mediated growth inhibition provides a possible mechanism for escape of cutaneous anaplastic large cell lymphoma from tumor regression. Mitogen-activated protein kinase inhibitors are potential therapeutic agents for the treatment of advanced cutaneous anaplastic large cell lymphoma. J Invest Dermatol 115:1034-1040, 2000     

T cell receptor-gamma gene analysis of CD30+ large atypical individual cells in CD30+ large primary cutaneous T cell lymphomas

The hallmark of primary cutaneous CD30+ large T cell lymphoma are large lymphoid tumor cells, at least 75% of which, by definition, must be positive for CD30. The relatively benign clinical course of this lymphoma type has been explained with CD30-induced apoptosis, on the assumption that expression of CD30 defines the tumor clone; however, this hypothesis has not been tested on the molecular level to date. In this study we analyzed CD30+ cells in four patients with primary cutaneous CD30+ large T cell lymphoma by single cell polymerase chain reaction of T cell receptor-gamma genes followed by sequencing. Here, we demonstrate that most of the large CD30+ atypical cells possessed identical T cell receptor-gamma gene rearrangements, indicative of clonal proliferation. Nevertheless, polyclonally rearranged T cells were present in all CD30+ samples studied. In addition, one patient showed a second clone in a separate biopsy and three of four patients showed chromosomal imbalances as revealed by comparative genomic hybridization. Taken together, our data suggest that the CD30+ population in primary cutaneous CD30+ large T cell lymphoma indeed contains the tumor clone, thus providing molecular support for a link between clinical course and CD30-related signaling. Importantly, however, CD30 expression does not define the tumor clone as bystander T cells, as well as occasional additional clones, are also present in this population.     

CD56 expression in a case of primary cutaneous CD30+ anaplastic large cell lymphoma

We describe clinicopathological features of an unusual case of CD30+/CD56+ T-cell lymphoma in a 58-year-old Korean man who presented with disseminated nodules, papules and hyperpigmented patches. Coexpression of CD30 and CD56 in T-cell lymphoma is very rare. Our patient did not respond to an intensive chemotherapy regimen, in contrast to the previously reported cases of primary cutaneous CD30+ anaplastic large cell lymphoma. Coexpression of CD56 might therefore identify a subset of CD30+ lymphomas with more aggressive features.     

Lymphoma- and leukemia-associated cutaneous atypical CD30+ T-cell reactions

Cutaneous CD30+ lymphoid infiltrates appear cytologically atypical and occasionally may be misinterpreted as recurrent disease when they occur in patients treated for other primary hematologic malignancies. We recently encountered two such cases and present our findings. One patient with B-cell lymphoma and another with myeloid leukemia developed cutaneous eruptions after chemotherapy displaying highly atypical perivascular lymphoid cells on histology that mimicked recurrent disease. In both cases, the lymphocytes were CD30+ T cells by immunohistochemistry. The skin lesions spontaneously resolved and have not recurred. Because one case was initially misinterpreted as recurrent leukemia, we conclude that close clinical correlation and immunophenotypic confirmation should be done for atypical cutaneous lymphoid infiltrates in patients with primary hematologic malignancies. We discuss the differential diagnosis of atypical CD30+ infiltrates in this setting, which include recurrent lymphoma or myeloid leukemia, primary cutaneous anaplastic large cell lymphoma (ALCL), lymphomatoid papulosis (LyP), carbamazepine-induced CD30+ pseudolymphoma, viral infection and an atypical eruption of lymphocyte recovery.     

Primary cutaneous CD8+ cytotoxic T‐cell lymphoma involving the epidermis and subcutis in a young child

CD8+ cytotoxic T‐cell lymphoma involving the skin represents a heterogeneous group of diseases that include subcutaneous panniculitis‐like T‐cell lymphoma, primary cutaneous aggressive epidermotropic CD8+ cytotoxic T‐cell lymphoma, and ‘type D’ lymphomatoid papulosis. In this report, we describe a case of CD8+ cytotoxic T‐cell lymphoma involving both the epidermis and subcutis. The patient was a 6‐year‐old girl who presented with a 3‐year history of multiple plaques on her trunk and legs. The lesions had relapsed twice but responded well to prednisone. Histopathologic examination showed the proliferation of atypical lymphocytes in the epidermis, dermis and subcutaneous tissue. On immunohistochemical analysis, the atypical lymphocytes were positive for βF1, CD3, CD8, perforin, granzyme B and TIA‐1, but negative for T‐cell receptor (TCR) γ, CD4, CD30 and CD56. It was difficult to classify this tumor in terms of the known types of cutaneous lymphoma, and this case should be differentiated with subcutaneous panniculitis‐like T‐cell lymphoma and primary cutaneous aggressive epidermotropic CD8+ T‐cell lymphoma.     

Primary cutaneous anaplastic large cell lymphoma

Primary cutaneous anaplastic large cell lymphoma (PC‐ALCL) is a CD30+ lymphoproliferative disorder (LPD) of the skin with a relatively good prognosis in the absence of high‐stage disease. CD30+ LPDs comprise approximately 25%‐30% of primary cutaneous lymphomas and as a group represent the second most common clonal T‐cell neoplasm of the skin behind mycosis fungoides. Diagnosis of PC‐ALCL relies strongly on clinicopathologic correlation given the potential morphologic, clinical and molecular overlap with the other cutaneous CD30+ LPD, lymphomatoid papulosis, and more aggressive hematolymphoid neoplasms.     

Primary cutaneous CD30+ large T-cell lymphoma in a patient with psoriasis treated with cyclosporine

We report the case of a 61-year-old woman who developed an anaplastic CD30+ cutaneous T-cell lymphoma during oral cyclosporine (CsA) therapy for recalcitrant psoriasis. Two months after CsA discontinuation, clinical and histological resolution of the lymphoma was observed. However, 3 years later extracutaneous involvement of the lymphoma could be detected. The association between CsA administration and the occurrence of the lymphoma may be casual, but a relationship with immunosuppression may also be hypothesized. We have reviewed all relevant data in the literature. To our knowledge, this is the first case of primary cutaneous CD30+ anaplastic large T-cell lymphoma in a patient treated with CsA for psoriasis.     

Topical imiquimod as treatment for different kinds of cutaneous lymphoma

Imiquimod as a topical immune response modifier leads to a localized production of interferon and other cytokines. Apart from its use for genital warts it has therefore been used as treatment for different cutaneous neoplasms, including a few cases of cutaneous T-cell lymphoma. We treated 8 patients (4 with mycosis fungoides, 1 with CD30+ anaplastic large cell lymphoma and 3 with primary cutaneous B-cell lymphoma) with topical imiquimod. Therapy was started three times per week, in cases without response, the frequency was increased to a daily application. Two patients with mycosis fungoides and the patient with the CD30+ anaplastic large cell lymphoma had a complete clinical remission, the other two patients with mycosis fungoides did not show a response to imiquimod. Of the patients with cutaneous B-cell lymphoma, two reached a partial remission, one did not respond to therapy. Two patients had side effects such as erythema and pruritus which disappeared when the frequency of therapy was reduced. Our preliminary data show that imiquimod might be effective in some cases with therapy resistant lesions of cutaneous T-cell lymphoma as well as of cutaneous B-cell lymphoma, but more controlled studies are needed.     

The new World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas: a practical marriage of two giants

Following consensus meetings of the two parent organizations, a new World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification for primary cutaneous lymphomas has recently been published. This important development will now end the ongoing debate as to which of these was the preferred classification. The new classification will facilitate more uniformity in diagnosis, management and treatment of cutaneous lymphomas. In particular, it provides a useful distinction between indolent and more aggressive types of primary cutaneous lymphoma and provides practical advice on preferred management and treatment regimens. This will thereby prevent patients receiving high-grade treatment for low-grade biological disease. This review focuses on those diseases which have found new consensus agreement compared with the original WHO and EORTC classifications. In cutaneous T-cell lymphomas, these include folliculotropic mycosis fungoides, defining features of Sézary syndrome, primary cutaneous CD30+ lymphoproliferative disorders (primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis and borderline lesions) and subcutaneous panniculitis-like T-cell lymphoma. Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma, primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma and cutaneous gamma/delta T-cell lymphoma are allocated provisional entry status and thereby afford better definitions for some cases of currently unspecified primary cutaneous peripheral T-cell lymphoma. In cutaneous B-cell lymphomas, diseases which have found new consensus agreement include primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicular centre lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type and primary cutaneous diffuse large B-cell lymphoma, other. CD4+/CD56+ haematodermic neoplasm (early plasmacytoid dendritic cell leukaemia/lymphoma) now appears as a precursor haematological neoplasm and replaces the previous terminology of blastic NK-cell lymphoma. Other haematopoietic and lymphoid tumours involving the skin, as part of systemic disease, will appear in the forthcoming WHO publication Tumours of the Skin. The new classification raises interesting new problems and questions about primary cutaneous lymphoma and some of these are discussed in this article. It is, however, a splendid signpost indicating the direction in which research in cutaneous lymphoma needs to go. In the interim, we have an international consensus classification which is clinically meaningful.     

累及中枢神经系统的皮肤CD30~+间变性大细胞淋巴瘤1例

患者男,75岁,反复皮肤肿块11年。1个月前第3次复发伴语言、记忆和生活自理能力减退。头颅MRI示:左额叶,右顶叶多发占位,颅内淋巴瘤浸润。左大腿肿块组织病理示:真皮内大量异型细胞,体积较大,形态不规则,核扭曲,核分裂相可见;免疫组化:CD3(+),UCHL-1(+),CD30(+),ALK(-),MIB-1>90%。诊断:皮肤CD30+间变性大细胞淋巴瘤。中枢神经系统(central nerve system,CNS)累及可以是皮肤间变性大细胞淋巴瘤发生皮外累及的唯一部位,患者的意识改变是进行CNS筛查的重要提示。     

Progressive epidermotropic CD8+/CD4- primary cutaneous CD30+ lymphoproliferative disorder in a patient with sarcoidosis

We describe a patient with a CD8+/CD4- primary cutaneous CD30(+) lymphoproliferative disorder with striking epidermotropic histology and coincident cutaneous and systemic sarcoidosis. This patient illustrates the spectrum of clinical and histologic features of CD30+ lymphoproliferative disorders and the need for adequate staging in such cases. This patient's CD30/CD8 coexpression is rare and has clinical and prognostic implications, including mucosally and acrally accentuated lesions and a potentially more aggressive course. Primary cutaneous CD30+ lymphoproliferative disorders have an excellent prognosis; therefore multiagent chemotherapy modalities are generally not indicated. The combination of T-cell lymphoma and sarcoidosis is also rare and may limit treatment options.     

Primary cutaneous CD30+ T-cell lymphoproliferative disorder presenting as paraphimosis: a case report and review of the literature

Primary cutaneous CD30+ T-cell lymphoproliferative disorders (PC-CD30+ LPD) as a group are one of the more common types of T-cell lymphoma. More specifically primary cutaneous anaplastic lymphoma (PC-ALCL), one of these lymphoproliferative disorders, is the second most common cutaneous T-cell lymphoma. We report an unusual presentation of PC-ALCL. A 90-year-old, uncircumcised male presented with a 3-week history of painful penile swelling and discharge. The patient was treated with cephalexin and underwent emergent circumcision for paraphimosis. The diagnosis of ALCL was made on microscopic evaluation of the foreskin along with follow-up staging studies. A literature review revealed 31 previously reported cases of penile lymphoma, one of which reported a primary penile CD30+ T-cell lymphoma similar to ours. Only one case report described a lymphoma presenting as paraphimosis. Our case is the second reported case of PC-ALCL of the penis and the first of its kind to present as paraphimosis. Lymphomas must be included in the differential diagnosis of penile lesions and paraphimosis. When present, clinicians should be able to differentiate primary cutaneous lymphoma from lymphomas with secondary skin involvement. All foreskins should be submitted to pathology for proper evaluation of penile lesions.     

Anaplastic lymphoma kinase-positive primary cutaneous anaplastic large cell lymphoma--is it a new variant?

Anaplastic large cell cutaneous lymphomas are clinically and pathologically heterogeneous, CD30 + (Ki-1) lymphoproliferative disorders. The importance of anaplastic lymphoma kinase (ALK) positivity is well known in the prognosis of primary systemic anaplastic large cell cutaneous lymphomas; however, the same in primary cutaneous anaplastic large cell cutaneous lymphomas is not much clear. Herein we report a 65-year-old male with an 18-month history of minimally pruritic localized nodulo-plaque lesion over lower back. Histology revealed cutaneous large cell lymphoma and immunohistochemical staining showed positivity for CD30, CD3 and ALK. The role of ALK positivity in pcALCL is discussed in this article.     

Cutaneous CD30 positive lymphoproliferative disorders with coexistent epithelial neoplasms: Report of two cases

Primary cutaneous large cell anaplastic lymphoma (C‐ALCL) and lymphomatoid papulosis (LyP) are cutaneous CD30+ lymphoproliferative disorders (CD30+ LPD). An association with CD30+ LPD and pseudoepitheliomatous hyperplasia has been recognized. Additionally, rare reports of epithelial neoplasms such as keratoacanthomas and squamous cell carcinomas (SCC) occurring in association with both C‐ALCL and LyP have been reported. We report two cases of CD30+ LPD with associated epithelial neoplasms; one patient with a primary cutaneous CD30+ LPD and SCC identified within the same lesion, and the other with a keratoacanthoma arising in a lesion of LyP. The pathogenesis of this association is poorly understood although various hypotheses exist. Awareness of the coexistence of these entities will avoid misdiagnosis and incorrect treatment.     

Therapeutic hotline: Primary cutaneous CD4 + small/medium-sized pleomorphic T cell lymphoma coexisting with myelodysplastic syndrome transforming into chronic myelomonocytic leukemia successfully treated with cyclophosphamide

Cutaneous T cell lymphomas other than mycosis fungoides, Sezary syndrome, and primary cutaneous CD30+ lymphoproliferations constitute less than 10% of all cutaneous T cell lymphomas. Primary cutaneous small/medium CD4+ T cell lymphoma is a member of this third group of cutaneous lymphomas, separated out as provisional entity in the World Health Organization classification - European Organization for Research and Treatment of Cancer (WHO-EORTC) classification. It still awaits development of more precise diagnostic criteria and optimal therapy. We report a case of primary cutaneous CD4 + small/medium-sized pleomorphic T cell lymphoma accompanied with myelodysplastic syndrome successfully treated with cyclophosphamide. It seems that cyclophosphamide as a single-agent chemotherapy in patients with disseminated lesions might be safe and quite effective therapeutic option.     

Cutaneous CD30‐positive lymphoproliferative disorders with CD8 expression: a clinicopathologic study of 21 cases

Lymphomatoid papulosis (LyP) and cutaneous anaplastic large cell lymphoma (ALCL) belong to the spectrum of cutaneous CD30+ lymphoproliferative disorders, an indolent form of T‐cell lymphoproliferative disease. We reviewed 21 cases of CD30+ lymphoproliferative lesions expressing cytotoxic profile (CD8+). Seven cases of cutaneous ALCL, 2 cases of systemic ALCL involving the skin, and 12 cases of LyP. The cases of LyP were predominated by small lymphocytes exhibiting a prominent epidermotropic pattern consistent with either type B or type D LyP. Four cases showed co‐expression of CD56. The ALCL cases included myxoid features, pseudoepitheliomatous change, and an intravascular component. In all cases that were primary in the skin an indolent clinical course was seen while one patient with systemic myxoid ALCL is in remission following systemic multiagent chemotherapy. The paucity of other neutrophils and eosinophils and concomitant granulomatous inflammation were distinctive features in cases of type B and type D LyP. CD30 and CD45 Ro positivity and a clinical course typical of LyP were useful differentiating features from an aggressive cytotoxic CD8+ T cell lymphoma. In all cases that were primary in the skin an indolent clinical course was observed. CD30 and CD45 Ro positivity and a clinical course typical of LyP were useful in preventing a misdiagnosis of an aggressive cytotoxic CD8+ T cell lymphoma.