CCR4 and CCR5 expression in a case of subcutaneous panniculitis-like T-cell lymphoma

Kitayama, Naomi; Otsuka, Atsushi; Honda, Yuki; Matsumura, Yasuhiro; Honda, Tetsuya; Kabashima, Kenji

doi:10.1684/ejd.2017.3016

Cited by 5 publications

(7 citation statements)

References 10 publications

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“…The neoplastic cells have a mature CD3 + CD4 − CD8 + T-cell phenotype and express cytotoxic proteins, such as granzyme B, TIA-1, and perforin ( 194 ). Although the exact mechanisms that neoplastic cells utilize to migrate into the hypodermis are still mostly unknown, CCR5 expression on neoplastic cells and its ligands, CCL3, CCL4, and CCL5, which can be secreted from immunologically activated adipocytes, may contribute to the pathogenesis of SPTCL ( 197 , 198 ).…”

Section: Subcutaneous Panniculitis-like T-cell Lymphomamentioning

confidence: 99%

New Therapies and Immunological Findings in Cutaneous T-Cell Lymphoma

Fujii

2018

Front. Oncol.

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Primary cutaneous lymphomas comprise a group of lymphatic malignancies that occur primarily in the skin. They represent the second most common form of extranodal non-Hodgkin’s lymphoma and are characterized by heterogeneous clinical, histological, immunological, and molecular features. The most common type is mycosis fungoides and its leukemic variant, Sézary syndrome. Both diseases are considered T-helper cell type 2 (Th2) diseases. Not only the tumor cells but also the tumor microenvironment can promote Th2 differentiation, which is beneficial for the tumor cells because a Th1 environment enhances antitumor immune responses. This Th2-dominant milieu also underlies the infectious susceptibility of the patients. Many components, such as tumor-associated macrophages, cancer-associated fibroblasts, and dendritic cells, as well as humoral factors, such as chemokines and cytokines, establish the tumor microenvironment and can modify tumor cell migration and proliferation. Multiagent chemotherapy often induces immunosuppression, resulting in an increased risk of serious infection and poor tolerance. Therefore, overtreatment should be avoided for these types of lymphomas. Interferons have been shown to increase the time to next treatment to a greater degree than has chemotherapy. The pathogenesis and prognosis of cutaneous T-cell lymphoma (CTCL) differ markedly among the subtypes. In some aggressive subtypes of CTCLs, such as primary cutaneous gamma/delta T-cell lymphoma and primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, hematopoietic stem cell transplantation should be considered, whereas overtreatment should be avoided with other, favorable subtypes. Therefore, a solid understanding of the pathogenesis and immunological background of cutaneous lymphoma is required to better treat patients who are inflicted with this disease. This review summarizes the current knowledge in the field to attempt to achieve this objective.

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Section: Subcutaneous Panniculitis-like T-cell Lymphomamentioning

confidence: 99%

New Therapies and Immunological Findings in Cutaneous T-Cell Lymphoma

Fujii

2018

Front. Oncol.

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“…None of the seven SPTCL cases that we studied showed any CCR4‐positive cells, suggesting that CCR4 does not play a role in SPTCL pathogenesis. A single SPTCL case with CCR4 and CCR5 positivity has been previously reported, and it was suggested that CCR5 is related to the migration and proliferation of neoplastic cells into the subcutis instead of the epithelium …”

Section: Discussionmentioning

confidence: 99%

“…A single SPTCL case with CCR4 and CCR5 positivity has been previously reported, and it was suggested that CCR5 is related to the migration and proliferation of neoplastic cells into the subcutis instead of the epithelium. 27 GDTCL is another CTCL subtype that presents with a panniculitic pattern in many cases. Although it is typically CD4-/CD8-, some cases are CD8+.…”

Section: Discussionmentioning

confidence: 99%

C‐C chemokine receptor 4 expression in CD8+ cutaneous T‐cell lymphomas and lymphoproliferative disorders, and its implications for diagnosis and treatment

et al. 2019

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Aims Patients with aggressive CD8+ cutaneous T‐cell lymphomas (CTCLs) progress rapidly and respond poorly to therapy. Confounding treatment planning, there is clinicopathological overlap between aggressive CD8+ CTCLs and other lymphoproliferative disorders (LPDs). Hence, improved diagnostic methods and therapeutic options are needed. The aim of this study was to examine C‐C chemokine receptor 4 (CCR4) expression as a diagnostic and therapeutic biomarker in CD8+ CTCLs/LPDs. Methods and results Forty‐nine cases (41 patients) with CD8+ CTCLs/LPDs were examined, including CD8+ mycosis fungoides (MF) (n = 14), aggressive epidermotropic CD8+ cytotoxic T‐cell lymphoma (AETCL) (n = 8), subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) (n = 7), CD30+ LPDs (n = 6), primary cutaneous γδ T‐cell lymphoma (GDTCL) (n = 6), and others (n = 8). Immunohistochemical tissue staining was performed with a CCR4 monoclonal antibody on formalin‐fixed paraffin‐embedded tissue sections. CCR4 immunostaining was graded as percentage infiltrate, i.e. high (>25%) and low (≤25%), and the results were correlated with clinicopathological diagnoses. CCR4 expression was seen in 69% of the studied cases. Any CCR4 positivity was seen in all CD8+ MF cases, in 83% of CD30+ LPD cases, in 75% of AETCL cases, in 33% of GDTCL cases, and in none of the SPTCL cases. High CCR4 expression was seen in 79% of CD8+ MF cases versus 33% of CD30+ LPD cases, in 17% of GDTCL cases, and in 12.5% of AETCL cases. Patients with more advanced MF stage had higher CCR4 expression. Conclusions CCR4 immunohistochemistry may be an adjunct in distinguishing advanced CD8+ MF from other CD8+ CTCLs/LPDs. Although CCR4 expression may justify therapeutic targeting of this receptor in CD8+ MF, the role of such therapies in other CD8+ CTCLs/LPDs is not yet clear.

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“…11,12 SPTCL is a cytotoxic T-cell lymphoma derived from α/β T-cells within subcutaneous tissue and commonly CD8+ and CD56-. 10,[13][14][15][16] This is an important distinction, as cases of CTCL with ϒ/δ T-cell phenotype typically represent a more aggressive clinical course with distinctly different immunophenotypical and histological characteristics. Therefore, SPTCL has been reserved for cases with α/β phenotypes, whereas ϒ/δ phenotypes are now classified as primary cutaneous ϒ/δ Tcell lymphomas.…”

Section: Case Reportmentioning

confidence: 99%

Subcutaneous panniculitis-like T-Cell lymphoma: A mixed diagnostic approach to diagnosing a vague clinical picture

Hill¹,

Wang²,

Elewski

et al. 2019

J of Skin

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Subcutaneous panniculitis-like T-Cell lymphoma (SPTCL) is a rare subtype of cutaneous T-cell lymphoma, and it has been associated with a range of clinical symptoms from mild to severe. Most commonly, this disease is described as following a slowly progressing course, associated with vague constitutional symptoms and good prognosis. This case report describes the clinical presentation and findings of SPTCL in a 31 year old female and describes the challenges of recognizing and properly diagnosing this disease. SPTCL has been described as a mimicker of other, more common and nonmalignant diseases of the skin, such as lupus panniculitis. This report highlights a variety of specific tests including immunohistochemical and immunoperoxidase staining, as well as genotypic analysis of T-cell receptors, that were effective in combination in isolating this diagnosis. Moreover, choice of treatment for these patients can be challenging, as an array of interventions have been described in past cases to treat SPTCL. This report recognizes the efficacy of a treatment course that included a six-cycle course of combined chemotherapy (vincristine, doxurubicine, cyclophosphamide, and prednisone, also known as CHOP) followed by weekly methotrexate and PET scan surveillance for two years. With both initial and maintenance therapy, this patient showed excellence response evidenced by a progressive decrease in metabolic activity of malignant lesions, lack of new lesions, and remaining without symptoms. While this disease is rare, it is important to include SPTCL in the differential when considering patients with a panniculitic picture.

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CCR4 and CCR5 expression in a case of subcutaneous panniculitis-like T-cell lymphoma

Cited by 5 publications

References 10 publications

New Therapies and Immunological Findings in Cutaneous T-Cell Lymphoma

New Therapies and Immunological Findings in Cutaneous T-Cell Lymphoma

C‐C chemokine receptor 4 expression in CD8+ cutaneous T‐cell lymphomas and lymphoproliferative disorders, and its implications for diagnosis and treatment

Subcutaneous panniculitis-like T-Cell lymphoma: A mixed diagnostic approach to diagnosing a vague clinical picture

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