Primary cutaneous anaplastic CD30+ large cell lymphoma

Primary cutaneous anaplastic CD30+ large cell lymphoma (PCALCL) is part of the spectrum of primary cutaneous CD30+ lymphoproliferative disorders together with lymphomatoid papulosis. It affects mainly elderly patients and presents as skin nodules that tend to ulcerate. Histological and immunohistochemical study show the expression of CD30 antigen in more than 75 % of neoplastic cells. Currently it is considered a low grade lymphoma with favourable prognosis and good response to treatments such as local radiotherapy, methotrexate or surgery. We report a 93-year-old patient with ulcerated nodules in her right leg. Histological and immunohistochemical study confirmed the diagnosis of PCALCL, of non-B, non-T origin. The patient was treated with local radiotherapy with progressive resolution of skin nodules and absence of relapse at 6 months follow-up.     

Expression of chemokines and chemokine receptors in cutaneous CD30+ lymphoproliferative disorders

BACKGROUND: Little is known about the mechanisms involved in skin-specific homing in CD30+ cutaneous lymphoproliferative disorders (CLPD). Chemokine/chemokine receptor interactions have been implicated in the homing of lymphoma cells to various tissue sites. OBJECTIVES: To investigate tissue samples from patients with CD30+ CLPD for the expression of the chemokine receptors CXCR3, CCR4 and CCR3 and their ligands MIG, TARC and RANTES. METHODS: Tissue samples from patients with primary cutaneous anaplastic large cell lymphoma (PCALCL, n=12) and lymphomatoid papulosis (LyP, n=13) were studied by immunohistochemistry on paraffin-embedded sections. Immunohistochemical analysis was also performed for CD20 (for B cells), CD45RO and CD3 (for T cells), CD30 and ALK-1. A portion of each skin specimen was stored at -80 degrees C and later examined using monoclonal antibodies against CD2, CD3, CD4, CD5, CD8, CD15, CD19, CD20 and CD30. RESULTS: CD30+ atypical lymphoid cells were frequently seen in PCALCL, and to a variable degree in LyP. In both disorders there were scattered CD3+ and CD45RO+ atypical lymphoid cells, but CD2, CD5, CD15, CD19, CD20 and ALK-1 showed negative reactivity. In addition, CD4+, but not CD8+, atypical lymphoid cells were occasionally seen in both disorders. CCR3 was expressed by atypical lymphoid cells in 10 of 12 (83%) cases of PCALCL, but in only five of 13 (38%) cases of LyP. CXCR3 was expressed in 11 of 13 (85%) cases of LyP, but in only one of 12 (8%) cases of PCALCL. CCR4 was expressed in 11 of 12 (92%) cases of PCALCL, but in only two of 13 (15%) cases of LyP. RANTES was strongly expressed by lymphoma cells in PCALCL (11 of 12: 92%), but was weak or sporadic in LyP (seven of 13: 54%). TARC showed weak or sporadic reactivity in both LyP and PCALCL, and MIG did not show a distinctive expression pattern in either disorder. CONCLUSIONS: We speculate that CCR3 is associated with the autocrine function in PCALCL, as evidenced by CCR3 coexpression with its ligand RANTES. We also found that LyP cells expressed CXCR3, which might support their migration towards the CXCR3 ligand MIG, which is expressed in stromal cells of the skin.     

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.     

原发性皮肤CD30阳性淋巴组织增生性疾病临床病理分析

目的 探讨原发性皮肤CD30阳性淋巴组织增生性疾病的临床及病理学特征。方法 对4例淋巴瘤样丘疹病及5例原发性皮肤间变性大细胞淋巴瘤的临床、病理学特征及免疫组化表达进行分析。结果 淋巴瘤样丘疹病分为A、B、C三型,组织学上形成一个连续的谱系,A型见多形性间变性大细胞或Sternberg-Reed样细胞散在分布或小片状分布在多量炎性细胞背景中;B型类似蕈样肉芽肿病变,表现为真皮层较宽的淋巴细胞浸润带,其中散在少量小至中等异形脑回样淋巴细胞;C型以间变性大细胞弥漫分布为特征,但临床上可自行消退。原发性皮肤间变性大细胞以皮下结节或皮肤丘疹就诊,瘤细胞体积大,呈多形性、圆形或椭圆形,胞质丰富,嗜酸或呈双色性,核大,核仁明显。两组病变中的大细胞均特征性表达CD30,预后均较好。结论 原发性皮肤CD30阳性淋巴组织增生性疾病是一组预后较好的皮肤T细胞性淋巴瘤谱系,综合临床表现、组织病理改变、免疫组化有助于本病的诊断。     

原发性皮肤CD30+淋巴细胞增殖性疾病进展

原发性皮肤CD30^＋淋巴细胞增殖性疾病包括原发性皮肤间变性大细胞淋巴瘤、淋巴瘤样丘疹病和一些临界性肿瘤，构成疾病谱系。这些疾病的共同特点是肿瘤细胞表达CD30抗原。这类疾病预后较好．故选择治疗方法时需权衡积极治疗的短期疗效与潜在副作用间的利弊关系。CD30^＋细胞也可在其他疾病中见到，CD30^＋免疫组化结果应结合临床综合分析。     

Primary Cutaneous CD8+ CD30+ Anaplastic Large Cell Lymphoma: An Unusual Case with a High Ki-67 index—A Short Review

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a part of the spectrum of CD30⁺ cutaneous lymphoproliferative disorder, characterized by variable degrees of CD2, CD3, CD4 and CD5 expression by lymphoid cells. PCALCLs with an expression of cytotoxic phenotype (CD8⁺) and cytotoxic proteins are uncommon. Cutaneous CD8⁺ CD30⁺ lymphoproliferative lesions are difficult to classify, diagnose and may be the cause of misdiagnose. CD8⁺ PCALCL must be distinguished from CD8⁺ mycosis fungoides, lymphomatoid papulosis type D and primary cutaneous aggressive epidermotropic CD8⁺ T-cell lymphoma. Usually CD8⁺ PCALCL is an indolent disease with a favorable prognosis, except few cases can show poor outcomes. The high Ki-67 index points toward advanced PCALCL. Treatment modalities include surgical excision, radiotherapy and clinical monitoring. Chemotherapy is reserved for disseminated disease. We report a 59-year-old male presented with rapid development of multiple painful reddish-brown plaques and nodular ulcerative skin lesions over the left thigh region since 2 months. A diagnosis of CD8⁺ PCALCL with a high Ki-67 index was made on the basis of histology and immunohistochemistry, in co-relation with clinical presentation.     

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.     

Lymphomatoid papulosis associated with mycosis fungoides: clinicopathological and molecular studies of 12 cases

The association of mycosis fungoides and a primary cutaneous CD30+ lymphoproliferative disorder has been reported and probably represents different clinical aspects of a unique T-cell monoclonal expansion. In this study, 12 patients (6 men and 6 women) presented with lymphomatoid papulosis and mycosis fungoides. A TCRgamma gene rearrangement study was performed by an automated high-resolution PCR fragment analysis method on skin biopsy specimens taken from the different clinical lesions in each patient. An indolent clinical course was observed in the majority of patients. T-cell clonality was identified in 7 of 12 lymphomatoid papulosis lesions (58%) and in 6 skin biopsies of plaque stage mycosis fungoides (50%). In each individual case, where T-cell clonality was detected, both mycosis fungoides and lymphomatoid papulosis specimens exhibited an identical peak pattern by automated high-resolution PCR fragment analysis, confirming a common clonal origin. Only one case showed a clonal TCRgamma rearrangement from the lymphomatoid papulosis lesion, which could not be demonstrated in the mycosis fungoides specimen. The demonstration of an identical clone seems to confirm that both disorders are different clinical manifestations of a unique T-cell monoclonal proliferation. Our results also seem to confirm that the association of mycosis fungoides with a primary cutaneous CD30+ lymphoproliferative disorder usually carries a favourable prognosis.     

Primary cutaneous T-cell lymphoma occurring after organ transplantation

Lymphoma occurring after organ transplantation has been well described. The majority of cases are B-cell lymphomas and are usually associated with Epstein-Barr virus. Only a minority of posttransplant lymphomas are of T-cell origin, and primary cutaneous T-cell lymphoma (CTCL) is extremely rare. In this article, we report a case of cutaneous peripheral T-cell lymphoma, pleomorphic CD30+ large-cell type, and review the literature relating to posttransplant primary CTCL. Of the 23 cases of posttransplant primary CTCL, 5 patients had erythrodermic disease, and 8 had primary cutaneous anaplastic large cell lymphoma. In addition, there are two cases of mycosis fungoides, one case of subcutaneous panniculitis-like T-cell lymphoma, one case of CD30+ lymphomatoid papulosis, and 6 cases of peripheral T-cell lymphoma, of which 3 were CD30+ large cell lymphomas. Seventeen cases had renal transplants and the majority received both cyclosporine and azathioprine. No consistent viral association was noted among these cases. The sex ratio was 18:5 (male/female), and the mean age at diagnosis was 53 years. Mean time from transplantation to diagnosis is 6.4 years and mean survival time from diagnosis is 14.5 months. The prognoses normally associated with particular subsets of CTCL do not apply in the posttransplant setting.     

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     

Pathobiology of CD30+ cutaneous T-cell lymphomas

Abstract:  CD30+ cutaneous lymphoproliferative disorders include lymphomatoid papulosis (LyP) and anaplastic large cell lymphoma (ALCL). LyP is associated with development of lymphoma in nearly 20% of patients. Herein is reviewed the clonal relationship of LyP to malignant lymphoma, the concept of a common stem cell for LyP and associated lymphomas, and the role of genetic instability in lymphomagenesis. The possible role of the CD30+ cell as a regulatory T‐cell is introduced and a model for progression of LyP to ALCL is illustrated.     

CD30-positive cutaneous T-cell lymphoma with concurrent solid tumour

Extranodal CD30+ T-cell lymphomas seldom carry classical t(2;5) translocation and are usually anaplastic large cell lymphoma kinase protein negative. They cover a wide spectrum of histological and clinical behaviour. The prognosis of CD30+ cutaneous T-cell lymphoma (CTCL) is good in the absence of nodal primary or disseminated disease. These lesions can undergo spontaneous regression, and overlap with the group of lesions of lymphomatoid papulosis. Although an increased incidence of solid tumours has been reported in patients with CD30+ non-Hodgkin lymphoma of the skin, reports of concurrent malignancies are rare in CD30+ CTCL. We report two patients with CD30+ CTCL who, respectively, had concurrent disseminated gastric carcinoma and bilateral ovarian teratoma. Despite an aggressive clinical and histological appearance, both cases ran favourable clinical courses. The CTCL responded completely to chemotherapy in one patient, who eventually succumbed to gastric cancer. In the other patient, lesions regressed spontaneously after bilateral oophorectomy. A possible relationship between the lymphoma and the solid tumours is discussed.     

Primary cutaneous CD30+ anaplastic large-cell lymphoma with generalized skin involvement and involvement of one peripheral lymph node, successfully treated with low-dose oral etoposide

Primary cutaneous CD30+ anaplastic large-cell lymphoma (PCALCL) in adults is rare, and the prognosis is generally excellent. Multifocal PCALCL tends to relapse after multiagent chemotherapy and is generally considered more prone to progress to extracutaneous involvement than is the localized disease. We report a 43-year-old woman with PCALCL who had generalized skin involvement accompanied by involvement of one peripheral draining lymph-node region. Although the disease relapsed after multiagent chemotherapy regimens, the disease was successfully treated with low-dose etoposide. We reviewed the previously reported cases of PCALCL treated with low-dose etoposide. We suggest that oral etoposide might be a useful effective treatment for treatment of relapsed multifocal PCALCL.     

Mucosal involvement in lymphomatoid papulosis: four cases

BACKGROUND: Lymphomatoid papulosis is a form of CD30+ cutaneous lymphoproliferation characterized by a benign chronic papulonodular eruption that regresses spontaneously. The clinical features contrast with the malignant histological aspect of lesions. Mucosal lesions are rare, with less than 10 published cases. We report four new cases and we highlight characteristic features of lesions at this particular site. PATIENTS AND METHODS: We report four cases of mucous lymphomatoid papulosis in three women aged 37, 38, and 71 years and one 66-year-old man. These cases were collated from three different hospitals: Orléans, Rouen and Caen. Mucosal lesions occurred after cutaneous eruption in two cases but remained isolated or preceded cutaneous lesions in the other two cases. The main site was the mouth in all four cases but one case also involved genital lesions. Two cases involved type A pathological features and two had type C features. Association with lymphoma was excluded on clinical, laboratory and radiological examination. One patient was treated with methotrexate (>7.5mg/week) and did not relapse. Of the three other untreated patients only one did not relapse (short 14-month follow-up). DISCUSSION: Recurrent oral ulcerations may be mucosal manifestations of lymphomatoid papulosis. This site does not appear to have any bearing on prognosis.     

Neutrophilenreiches, CD30+ anaplastisches T-Zell-Lymphom in Assoziation mit einer lymphomatoiden Papulose

The 2005 EORTC / WHO classification includes three CD30+ lymphoproliferative disorders: 1) primary cutaneous anaplastic large cell lymphoma, 2) lymphomatoid papulosis and 3) borderline cases. These entities may present with many different clinical appearances. Therefore, a precise differentiation among them often is impossible. We present a 40-year-old female who initially presented with a neutrophil-rich, anaplastic CD30+ T cell lymphoma followed by lymphomatoid papulosis.     

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 anaplastic large-cell lymphoma

Primary cutaneous anaplastic large-cell lymphoma (ALCL) is a form of cutaneous T-cell lymphoma that is characterized by solitary or localized nodules or plaques. Histopathologic features include a diffuse, non-epidermotropic infiltrate with cohesive sheets of large anaplastic CD30+ tumor cells. This entity must be distinguished from systemic ALCL with cutaneous involvement and lymphomatoid papulosis. Treatment modalities include clinical monitoring, radiation therapy, and surgical excision, with systemic chemotherapy reserved for disseminated or extracutaneous disease.     

CD30 antigen expression in cutaneous inflammatory infiltrates of scabies: a dynamic immunophenotypic pattern that should be distinguished from lymphomatoid papulosis

BACKGROUND: Expression of CD30 antigen is a distinct marker of lymphocyte activation that was originally described in the Reed-Sternberg cells of Hodgkin's disease. The observation of CD30+ cells has been considered a diagnostic feature of cutaneous CD30 lymphoid proliferations. However, CD30 expression has also been reported in some cutaneous benign inflammatory infiltrates. METHODS: Eleven skin biopsies from patients with scabies were double-blindly and retrospectively analysed. A panel of histopathological parameters and immunophenotypic expression of CD4, CD8, CD30 and S-100 antigens was studied. CD30 and S-100 antigens expression were related to clinical features. RESULTS: Large CD30+ cells were demonstrated in eight (8/11) biopsies, corresponding to patients with long-standing lesions (3 months or longer). However, no expression of the CD30 antigen was observed in all biopsy specimens (3/11) corresponding to early lesions (2 months or less). The presence of S-100 positive cells in the papillary dermis was an almost constant feature. CONCLUSIONS: CD30+ large cells seem to be a common feature in long-standing infiltrates of scabies. CD30 expression in scattered cells of a cutaneous lymphoid infiltrate cannot be assessed as a strong diagnostic argument of neoplastic cutaneous CD30+ lymphoid proliferation (lymphomatoid papulosis/cutaneous CD30+ lymphoma). Therefore, the possibility that large atypical CD30+ cells may be also present in several benign inflammatory diseases should be always considered.     

A comparison of clinical, morphological and immunohistochemical features of lymphomatoid papulosis and primary cutaneous CD30(Ki-1)-positive anaplastic large cell lymphoma

The advent of immunoperoxidase technique on paraffin embedded tissue has identified a number of shared immunologic markers present in various lymphoproliferative cutaneous disorders. Two such disorders are the recently described primary cutaneous CD30-positive anaplastic large cell lymphoma (ALCL) and lymphomatoid papulosis; both entities are characterized by CD30-positive large atypical cells predominantly of T cell origin. We have compared the clinical, morphological and immunohistochemical features of 50 patients with lymphomatoid papulosis to a group of 27 patients with cutaneous CD30-positive ALCL. There are clear differences between the clinical presentation in these two diseases, and although both are characterized by similar atypical cells, the histologic pattern and distribution of atypical cells is sufficiently different to allow distinction and specific diagnosis based on hematoxylin and eosin stained sections supported by the immunohistochemical stains. In addition, both diseases are characterized by a long benign course, rarely complicated by development of lymphoreticular malignancy and invariably demonstrate CDSO(Ki-I) antigen positive large atypical cells.     

Lymphomatoid papulosis: reappraisal of clinicopathologic presentation and classification into subtypes A, B, and C

OBJECTIVES: To analyze clinicopathologic features of lymphomatoid papulosis and delineate the characteristics of histopathologic variants (types A, B, and C). DESIGN: Retrospective nonrandomized study. SETTING: University-based dermatologic referral center. PATIENTS: Eighty-five patients with lymphomatoid papulosis. Clinical data and 1 or more biopsy specimens were available for review in all cases. When possible, immunophenotypic and molecular analyses were carried out. RESULTS: Of these patients, 78 presented only 1 histopathologic subtype of lymphomatoid papulosis (64 had type A, 3 had type B, and 11 had type C). The last 7 patients presented more than 1 subtype (1 had A and B, 5 had A and C, and 1 had A, B, and C). Two patients had regional lymphomatoid papulosis, an unusual clinical presentation characterized by groups of lesions localized to 1 anatomic region. We observed, we believe for the first time, that some histopathologic patterns, ie, follicular mucinosis (n = 1), syringotropic infiltrates (n = 1), epidermal vesicle formation (n = 2), and syringosquamous metaplasia (n = 1), were associated with lymphomatoid papulosis. A distribution along hair follicles, or follicular lymphomatoid papulosis, was observed in 5 biopsy specimens. A bandlike rather than a wedge distribution of the infiltrate was seen in 5 specimens from patients with lymphomatoid papulosis type A. Of 8 patients who had associated lymphoid malignancies, 4 had Hodgkin disease and 4 had mycosis fungoides. CONCLUSIONS: Lymphomatoid papulosis is a cutaneous disorder with multiple clinicopathologic features. Differentiating between mycosis fungoides and anaplastic large cell lymphoma may be very difficult and sometimes impossible. In the spectrum of CD30(+) cutaneous lymphoproliferative disorders, boundaries between these 2 entities are not clear-cut.