T‐cell receptor gene rearrangement analysis of sequential biopsies in cutaneous T‐cell lymphomas with the Biomed‐2 PCR reveals transient T‐cell clones in addition to the tumor clone

Detection of a dominant T‐cell clone by T‐cell receptor (TCR) gene rearrangement analysis is often essential for the diagnosis of cutaneous T‐cell lymphomas (CTCL). The occurrence of T‐cell clones in addition to the diagnostic T‐cell clone during the course of CTCL has been reported, but the data of these studies have been contradictory. We retrospectively evaluated the data of 114 lesional skin biopsies from 26 patients with Mycosis fungoides and two patients with primary cutaneous anaplastic large cell lymphoma, which were analysed with the standardized Biomed‐2 PCR for the TCRγ and TCRβ locus. A dominant T‐cell clone was repetitively detected in 93% (26/28) of patients. Additional T‐cell clones appeared temporarily in 39% (11/28) of patients. Correlation with the clinical data did not show an association of the presence of additional T‐cell clones with age, number of treatments, progression of disease or survival. Our findings demonstrate that a persistent T‐cell clone, most likely the disease causing tumor clone, is detectable in almost all CTCL patients. In addition, transiently appearing T‐cell clones frequently occur during the course of disease. The biological relevance of these additional clones has still to be determined. However, it is important to take the possibility of additional T‐cell clones into account for diagnostic analyses.     

Hypopigmented interface T‐cell dyscrasia: A form of cutaneous T‐cell dyscrasia distinct from hypopigmented mycosis fungoides

Hypopigmentation in cutaneous T‐cell lymphoproliferative disease should not always be equated with hypopigmented mycosis fungoides (MF). A form of hypopigmented pre‐lymphomatous T‐cell dyscrasia falling under the designation of the so‐called hypopigmented interface variant of T‐cell dyscrasia has recently been proposed. The aim of the present study was to establish hypopigmented interface T‐cell dyscrasia as its own entity apart from other T‐cell dyscrasias and MF using a patient case series. Twenty four cases of hypopigmented interface T‐cell dyscrasia were identified in the dermatopathology database of Weill Medical College of Cornell University. There were 17 females and seven males (mean age, 36 years). In children and adolescents, the patients were most commonly of African American extraction. Truncal photo‐protected areas manifesting as large solitary patches or multiple smaller macules were characteristic; disease progression to MF occurred in only one patient. The lesions responded to topical steroids and light therapy. The pathology was defined by a cell poor interface associated with degeneration of keratinocytes and melanocytes, and by lymphocytes whose nuclei showed low‐grade cerebriform atypia, and which expressed a significant reduction in CD7 and CD62L expression. In 50% of the cases, the implicated cell type was of the CD8 subset. Clonality was not identified. Hypopigmented interface T‐cell dyscrasia is a distinct entity separate from and rarely progressive to MF.     

Indolent course of cutaneous gamma‐delta T‐cell lymphoma

Cutaneous gamma‐delta T‐cell lymphoma (γδTCL) is a rare malignancy that typically displays an aggressive clinical course. We present an unusual case of a 57‐year‐old woman with a 3‐year history of lower extremity nodules. Histopathologic, immunophenotypic and molecular genetic studies revealed a clonal, predominantly pannicular gamma‐delta T‐cell infiltrate, leading to a diagnosis of cutaneous γδTCL. The clinical course was characterized by rapid improvement within months of starting systemic corticosteroids, with relapse in ulcerations but no new lesions more than 3 years after onset of disease. Our case and seven previously reported patients with indolent and relatively localized cutaneous γδTCL provide evidence that not all cases of this entity carry a poor prognosis. This indolent subset adds complexity to treatment of cutaneous γδTCL.     

Primary cutaneous follicular helper T‐cell lymphoma

Follicular helper T‐cells (TFH) represent a specific subset of CD4‐positive helper T‐cells that help B‐cells to differentiate into long‐lived antibody‐secreting plasma cells or memory B‐cells. The expression of TFH markers in neoplastic T‐cells, traditionally related to the angioimmunoblastic (AITL) subgroup of peripheral T‐cell lymphomas, is nowadays well‐known to be more widespread than previously thought. We report hereby a case of cutaneous T‐cell lymphoma in a 75‐year‐old woman, whose morphological and immunophenotypical features raises the differential diagnosis between cutaneous involvement by AITL and the recently described primary cutaneous T‐cell lymphoma with follicular helper‐phenotype.     

Oral bexarotene for post‐transplant cutaneous T‐cell lymphoma

Organ transplant recipients receiving immunosuppression have an increased risk of developing post‐transplant lymphoproliferative diseases (PTLDs). Traditionally, PTLDs refer to Epstein‐Barr virus (EBV)‐induced B‐cell lymphoma. However, post‐transplant T‐cell lymphoma may also occur and tends to have a poorer response to reduced immunosuppressive therapy. As such, additional therapy is often needed for post‐transplant T‐cell lymphoma, including post‐transplant cutaneous T‐cell lymphoma (PT‐CTCL). We present only the third case of PT‐CTCL occurring after liver transplantation. The patient was diagnosed with stage IB mycosis fungoides (MF). His lesions were refractory to multiple skin‐directed therapies, and so he was given oral bexarotene 150 mg daily and his oral tacrolimus dose was decreased to 2 mg daily. Remarkably, his MF patches have demonstrated a complete response to oral bexarotene 75 mg daily without recurrence over 11 years of follow‐up. He developed hypertriglyceridemia with bexarotene 150 mg, so his dose was decreased to 75 mg, without loss of response. Our report is the second to describe PT‐CTCL demonstrating a long‐term complete response to oral bexarotene. Given its anti‐carcinogenic properties and favorable toxicity profile, oral bexarotene represents an appealing treatment option for PT‐CTCL refractory to skin‐directed therapies.     

Cutaneous gamma/delta T‐cell lymphoma

Only 40 cases of primary cutaneous gamma/delta T‐cell lymphoma (GD‐TCL) have been described. GD‐TCL was included as a provisional entity in the WHO‐EORTC classification of cutaneous lymphomas in 2005. GD‐TCL often failed to respond to polychemotherapy and radiation therapy and have a poor prognosis with a mean survival of only 15 months. We present a patient treated with surgery, immunomodulatory therapy, and polychemotherapy. He then received hematopoietic stem cell transplantation and has been in complete remission since. Allogeneic stem cell transplantation appears to be a promising therapeutic option for aggressive and generally fatal lymphomas like GD‐TCL.     

Primary cutaneous T‐cell lymphoma presenting as mycosis fungoides with a T‐/null‐cell phenotype: report of two cases

Variations in the clinical and histological presentation of cutaneous T‐cell lymphoma (CTCL) can hamper diagnosis. We report two cases of a novel presentation of CTCL characterized by an aberrant immunophenotype with complete loss of pan T‐cell antigens including T‐cell receptor β chain and showing the clinical and histopathological appearance of erythrodermic and plaque‐stage mycosis fungoides.     

Hematopoietic stem cell transplantation in advanced cutaneous T‐cell lymphoma

We retrospectively reviewed data pertaining to five patients with cutaneous T‐cell lymphoma (CTCL) who had received hematopoietic stem cell transplantation (HSCT) between 2004 and 2015 at Kurume University Hospital, along with their clinical data until March 2016. For patients with advanced CTCL eligible for HSCT, autologous HSCT was performed when they responded well to chemotherapy, and allogeneic HSCT was selected for patients with advanced mycosis fungoides (MF)/Sézary syndrome (SS) and CTCL other than MF/SS with poor chemosensitivity. Two patients (primary cutaneous anaplastic large cell lymphoma and primary cutaneous CD8⁺ aggressive epidermotropic cytotoxic T‐cell lymphoma) who responded well to chemotherapy received autologous HSCT: one patient was alive in partial remission and the other died due to therapy‐related acute myeloid leukemia without disease relapse. In the remaining three patients with MF or SS, allogeneic HSCT was performed. Although one patient with MF died due to disease progression, the remaining two patients were alive in complete remission. Although there were two deaths in this study, the outcomes were considered satisfactory.