Acitretin combined with NB‐UVB in the treatment of cutaneous CD30‐positive anaplastic large cell lymphoma

Cutaneous CD30⁺ lymphoproliferative disorders represent a spectrum of skin lymphatic reticular proliferative diseases, including lymphomatoid papulosis (LYP), primary cutaneous anaplastic large cell lymphoma (PC‐ALCL), and borderline lesions between them. Although they all express CD30 as a phenotypic marker and share overlapping immunophenotypic features, they differ in clinical manifestations, pathological features, treatment, and prognosis. LYP is a kind of benign disease characterized by recurrent papules and nodules, and may spontaneously regress. PC‐ALCL presents with solitary tumor or local grouped nodules characterized by large T‐cells and may completely or partially resolve in fewer than half of cases. We reported a case of patient with clinical manifestation and pathologic features consistent with LYP in its early stages, which later turned into PC‐ALCL. This patient was treated with acitretin combined with NB‐UVB and had an obvious response.     

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.     

Epstein-Barr virus in CD30 anaplastic large cell lymphoma involving the skin and lymphomatoid papulosis in South Korea

BACKGROUND: Epstein-Barr virus (EBV)-associated cutaneous lymphoproliferative disorders are prevalent in Asia, and less frequent in Western countries. AIM: To elucidate the possible association of EBV with CD30+ anaplastic large cell lymphoma (ALCL) involving the skin and lymphomatoid papulosis (LyP) in South Korea. METHODS: In situ hybridization for EBV-encoded small RNA (EBER) and immunohistochemistry including viral latent membrane protein-1 (LMP-1) were performed on formalin-fixed, paraffin-embedded skin specimens of 26 cases of LyP and 16 cases of CD30+ ALCL involving the skin which were selected from six university hospital medical centers in South Korea. RESULTS: In situ hybridization studies showed positivity of the neoplastic cells for EBER in two of 16 cases of CD30+ ALCL and in none of the cases of LyP. One EBER-positive case was cutaneous CD30+ ALCL with concurrent lymph node involvement. The other was CD30+ ALCL involving the skin and other organs, including lymph nodes, bone, lung, and spleen. Immunostaining for LMP-1 was also positive only for the two cases of EBER-positive CD30+ ALCL. CONCLUSION: LyP and primary cutaneous CD30+ ALCL are very rarely associated with EBV in South Korea.     

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 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+ lymphoproliferative disorder: primary cutaneous anaplastic large cell lymphoma followed by lymphomatoid papulosis

CD30+ large anaplastic lymphoid cells are seen in anaplastic large cell lymphoma (ALCL), and also in lymphomatoid papulosis (LyP) and other lymphoproliferative disorders. It can be difficult precisely to categorize these disorders with CD30+ cells. We report a case of primary cutaneous CD30+ ALCL with systemic metastases in whom the clinical disease subsequently evolved into LyP. The patient was initially administered cisplatin and etoposide and made a good response. Eighteen months later, recurrent, self-healing cutaneous small nodules appeared around the original tumour site without any systemic involvement. Histopathological examination of the recurrent lesions revealed infiltration with a mixture of cells that included neutrophils, eosinophils and CD30+ large anaplastic cells cytologically identical with those in the primary lesion. The anaplastic cells in both the primary and recurrent lesions were positive for monoclonal antibodies CD30, CD25 and a monoclonal antibody directed against the chimeric protein p80(NPM-ALK). These observations suggest the possibility that the ALCL and the subsequent LyP represent different clinical manifestations of proliferation of the same clone.     

Skin involvement as the first symptom of rapidly progressive ALK‐positive systemic anaplastic large cell lymphoma

Systemic anaplastic large cell lymphomas (sALCLs) comprise a heterogeneous group of relatively rare T‐cell non‐Hodgkin lymphomas that are characterized by CD30 expression. Anaplastic lymphoma kinase (ALK)‐positive ALCL is a type of sALCL that commonly involves lymph nodes and extranodal sites. Skin involvement usually presents as tumours, nodules and ulcers. We describe an unusual case of ALK‐positive ALCL in an 11‐year‐old Chinese boy, who initially presented with skin eruption with rapid progression and poor prognosis. This case emphasizes the value of clinical factors to predict the prognosis of ALK‐positive sALCL, and we recommend close collaboration between dermatologists, pathologists and haematologists/oncologists to assure the correct diagnosis and treatment.     

Localized perineal cutaneous nodules: a case of recurrent systemic anaplastic large‐cell lymphoma

We report an unusual case of localized cutaneous nodules heralding the recurrence of systemic CD30+ anaplastic large‐cell lymphoma (ALCL). A 47‐year‐old woman developed numerous violaceous nodules in the perineal and upper thigh area 3 years after multimodal treatment and complete remission of primary anaplastic large‐cell CD30+ lymphoma. Using immunohistochemical and T‐cell gene rearrangement analysis, a recurrence of her anaplastic large‐cell lymphoma was diagnosed.     

Dermal xanthomatous infiltrates after brentuximab vedotin therapy in mycosis fungoides with large‐cell transformation: A novel histologic finding

Mycosis fungoides (MF) is the most common variant of cutaneous T‐cell lymphomas. Large‐cell transformation of MF has been associated with disease progression and overall poor outcome. The expression of CD30, which defines anaplastic large cell lymphoma (ALCL) and lymphomatoid papulosis, might also occur in a subset of patients with MF, with or without large‐cell transformation. Brentuximab vedotin is an anti‐CD30 monoclonal antibody which has been proven to be a safe and effective therapeutic agent in the treatment of CD30‐positive lymphomas, such as Hodgkin lymphoma and ALCL. Recently, brentuximab vedotin has been shown to have a significant clinical activity in treatment‐refractory or advanced MF or Sezary syndrome with a wide‐range of CD30 expression levels. We report a patient with MF tumor stage with large‐cell transformation and low CD30 expression with good response to brentuximab vedotin and unusual extensive xanthomatous changes in the follow‐up biopsy.     

Pediatric case of anaplastic lymphoma kinase‐positive anaplastic large cell lymphoma forming a solitary skin tumor on the forearm

A 5‐year‐old girl noticed a rapidly growing reddish nodule on her right forearm. Although oral antibiotics had been administrated for 2 weeks, the tumor enlarged. Skin biopsy revealed excessive infiltration of atypical neoplastic cells expressing CD4, CD30 and anaplastic lymphoma kinase (ALK). These histological and immunohistochemical findings were consistent with anaplastic large cell lymphoma (ALCL). Computed tomography showed multiple lymphadenopathy, but lymph node biopsy and bone marrow examination did not show any evidence of systemic dissemination. However, due to the positive results for ALK and multiple lymphadenopathy, we diagnosed ALK‐positive ALCL forming a solitary skin tumor on the forearm. The patient received chemotherapy and presented marked improvement. This paper discusses the difficulty of diagnosing pediatric ALK‐positive ALCL limited to the skin and reviews the medical published work.     

Oral involvement in lymphomatoid papulosis

Lymphomatoid papulosis is a cutaneous lymphoma with an indolent clinical behaviour characterized by chronic development of recurrent, self-limited lesions appearing as necrotic papules and with a pathology compatible with T cell lymphoma. Mucosal involvement by lymphomatoid papulosis is very rare but has been reported in the literature. It usually appears as ulcers in patients previously diagnosed of lymphomatoid papulosis. From a histological perspective it is characterized by an infiltrate of CD 30 positive atypical lymphocytes together with a mixed inflammatory infiltrate of eosinophils, neutrophils, histiocytes and plasma cells. We report the case of a man previously diagnosed of lymphomatoid papulosis that developed two ulcerated lesions in the tongue whose biopsy confirmed the diagnosis of oral involvement by lymphomatoid papulosis.     

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。     

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.     

Co-existent primary cutaneous anaplastic large cell lymphoma and lymphomatoid papulosis

We describe the case of a 37-year-old female with a history of psoriasiform dermatitis who presented with multicentric primary cutaneous CD30-positive anaplastic large T cell lymphoma (ALCL). Despite aggressive systemic therapy, the patient suffered multiple relapses and the lymphoma spread to cervical and inguinal lymph nodes. Later in her clinical course it was appreciated that she was also suffering from lymphomatoid papulosis (LyP). The case illustrates the overlapping clinical, histological and immunophenotypic features of ALCL and LyP, conditions which represent a spectrum of CD30-positive lymphoproliferative disease. A multidisciplinary approach between dermatologist, oncologist and pathologist is essential for the optimal management of these complex conditions.     

Coexistence of CD30-positive anaplastic large cell lymphoma and mycosis fungoides

Primary cutaneous T-cell lymphomas, including lymphomatoid papulosis, mycosis fungoides and CD30+ anaplastic large cell lymphoma (ALCL) overlap clinicopathologically and form part of a spectrum of lymphoproliferative disorders. There have been several case reports of these diseases coexisting. We describe a 59-year-old Korean man who presented with a recurrent, solitary CD30+ ALCL of 25 years' duration as well as patch stage mycosis fungoides of 11 years' duration. Such occurrences may represent different clinical manifestations of the same clonal T-cell abnormality, and provide further insight into the pathogenesis of these related disorders.     

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.     

Relapsing ulcerative papules over bilateral hands and scrotum in an Asian man: an atypical manifestation of primary cutaneous CD30-positive lymphoma

A 33-year-old Taiwanese man presented at our clinic with multiple erythematous ulcerated papules over his bilateral hands. CD30-positive anaplastic large cell lymphoma (CD30+ ALCL) was diagnosed by an incisional biopsy. After a thorough survey for extracutaneous involvement, the diagnosis of primary cutaneous CD30+ ALCL was established. Due to spontaneous regression of some skin lesions, the patient refused therapeutic intervention. Subsequently, an ulcerative nodule arose over the scrotum. It spontaneously regressed 5 weeks later. Although histologically alarming, this particular lymphoma bears favorable prognosis. Thus, recognition of this entity is of great importance, because it may prevent patients from undergoing unnecessary aggressive treatment. To our knowledge, CD30+ ALCL has not been reported to evolve in the pattern similar as observed in our patient. Thus, this Asian man presents a rare presentation of CD30+ ALCL.     

CD30 positive anaplastic large‐cell lymphoma mimicking Langerhans cell histiocytosis

The presence of CD 1a+ dendritic cells (DC) has been well described in T‐cell lymphoproliferative disorders, and the presence of large numbers of DCs has rarely been reported as a mimicker of Langerhans cell histiocytsis (LCH). We present the case of a 56‐year‐old female with a solitary nodule on the chin whose case was referred to our institution for confirmation of the diagnosis of LCH. Skin biopsy showed an ulcerated nodule containing a wedge‐shaped infiltrate comprised of large atypical cells and cells with prominent grooved nuclei. The constellation of histologic and immunologic features favored a CD30 lymphoproliferative disorder of T‐cell lineage even though there were accompanying numerous dendritic histiocytes and CD1a positive Langerhans cells. The sheets of CD30 positive atypical lymphoid cells which express T‐cell markers were consistent with CD30 positive lymphoproliferative disease and favor CD30 positive anaplastic large‐cell lymphoma (ALCL) over Langerhans histiocytosis. The absence of Anaplastic Lymphoma Kinase (ALK) staining favored a primary cutaneous origin. This case signifies a CD 30+ ALCL of the skin which histopathologically mimics a LCH. Ezra N, Van Dyke GS, Binder SW. CD30 positive anaplastic large‐cell lymphoma (ALCL) mimicking Langerhans cell histiocytosis (LCH).     

Contribution of longitudinal follow up and clinical pathological correlation in the diagnosis CD30‐positive skin infiltrates

The diagnosis of a CD30+ cutaneous infiltrate is often difficult and requires clinicopathologic correlation. To further evaluate this challenge, initial clinical and histopathologic diagnoses were correlated with final clinicopathologic diagnosis in 44 cases with CD30 immunopositivity. Dermatopathologic evaluation confirmed the initial clinical diagnosis in 65% of the suspected benign cases, all cases of suspected lymphomatoid papulosis (LyP), and 72% of clinically malignant cases. In the 25 patients with clinical suspicion for lymphoma, the histopathologic diagnoses included lymphoma in 18, LyP in 2, CD30+ lymphoproliferative disorder (CD30 LPD) in 3 and hypersensitivity reaction in 2 patients. Clinicopathologic correlation led to a change in three cases diagnosed histopathologically as anaplastic large cell lymphoma (ALCL) reclassified as LyP type C, and one patient diagnosed as CD30 LPD clinically evolved as herpes virus infection. Furthermore, five cases reported as CD30 LPD received more specific diagnoses after clinicopathologic correlation (LyP type C in three, and ALCL in two patients). Clinicopathologic correlation is essential in establishing the correct diagnosis of CD30 LPD, in particular the distinction of ALCL from LyP type C. In this setting, the histopathologic diagnosis of CD30 LPD is advisable in the absence of clinical data.     

Relapsing lymphomatoid papulosis after allogenic bone‐marrow transplant

Lymphomatoid papulosis (LyP) is a rare cutaneous lymphoproliferative disorder in children, which can rarely be associated with a cutaneous or systemic lymphoma. We report a 13‐year‐old girl who presented with typical LyP and pathological features of subtype A. Six months later, the patient presented with rapidly progressive peripheral and systemic lymphadenopathy. On examination of a lymph‐node biopsy, a lymphoid infiltrate negative for anaplastic lymphoma kinase (ALK) and positive for CD30 was found, suggestive of systemic anaplastic large T‐cell lymphoma (S‐ALCL). The patient was treated with chemotherapy, followed by allogeneic bone‐marrow transplant (BMT). Over the following 6 years, she presented with biopsy‐confirmed LyP relapses with complete cutaneous, peripheral‐blood and bone‐marrow chimerism. This is only the third reported paediatric association of S‐ALCL with LyP to our knowledge, and seems to be the first paediatric case of recurrent relapses of LyP after bone‐marrow allograft for S‐ALCL with total (100%) cutaneous and bone‐marrow chimerism. LyP occurring after allogenic BMT does not appear to be donor‐derived.