Cutaneous T-cell lymphoma
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Cutaneous T-cell lymphoma (CTCL) is a type of non-Hodgkin lymphoma of the skin in which T-cells (part of the immune system) grow in an uncontrolled way. Mycosis fungoides is the most common type of CTCL and tends to be slow growing and usually only affects the skin. Sezary syndrome is a less common but more advanced type of CTCL characterised by redness (erythroderma) in large areas of the skin, swollen lymph nodes, and abnormal lymphocytes circulating in the blood.

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Information for Health Professionals / Researchers (9 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Sarantopoulos GP, Palla B, Said J, et al.
Mimics of cutaneous lymphoma: report of the 2011 Society for Hematopathology/European Association for Haematopathology workshop.
Am J Clin Pathol. 2013; 139(4):536-51 [PubMed]
The Society for Hematopathology and European Association for Haematopathology workshop, from October 27 to 29, 2011, in Los Angeles, CA, exhibited many exemplary skin biopsy specimens with interesting inflammatory changes mimicking features of cutaneous lymphoma. This article reviews features observed in cutaneous lymphoid hyperplasia, cutaneous drug reactions, lupus-associated panniculitis, pityriasis lichenoides, hypereosinophilic syndrome, histiocytic necrotizing lymphadenitis, traumatic ulcerative granuloma with stromal eosinophils, and pigmented purpuric dermatosis, as well as a brief review of the pertinent literature and discussion of submitted conference cases. For the pathologist, it is important to be aware of diagnostic pitfalls as well as the limitations of ancillary testing (eg, clonality studies). Finally, correlation with total clinical information, good communication with clinical colleagues, close clinical follow-up with rebiopsy, and prudent use of laboratory studies are vital and will likely offer the best path toward a correct diagnosis.


Quintanilla-Martinez L, Jansen PM, Kinney MC, et al.
Non-mycosis fungoides cutaneous T-cell lymphomas: report of the 2011 Society for Hematopathology/European Association for Haematopathology workshop.
Am J Clin Pathol. 2013; 139(4):491-514 [PubMed]
Primary cutaneous T-cell lymphomas (CTCL) excluding mycosis fungoides (MF) were discussed in 2 sessions of the 2011 Society for Hematopathology/ European Association of Haematopathology Workshop, Los Angeles, CA. Session 2 focused on primary cutaneous CD30+ T-cell lymphoproliferative disorders and their differential diagnosis, including systemic CD30+ T-cell lymphoma secondarily infiltrating the skin. Interesting features like special morphologic variants and atypical phenotypes were presented. In addition, the possibility of rare ALK+ primary cutaneous lymphomas was discussed. Session 3 examined other more uncommon non-MF CTCLs, including subcutaneous panniculitis-like T-cell lymphoma, extranodal NK/T-cell lymphoma, hydroa vacciniforme-like T-cell lymphoma, and rare subtypes of primary cutaneous peripheral T-cell lymphoma, not otherwise specified. In addition, systemic T-cell lymphomas involving the skin secondarily, such as angioimmunoblastic T-cell lymphoma, were included in this session. In this report, novel findings, areas of special interest, and diagnostic challenges emerging from the cases submitted to the workshop will be highlighted. The necessity to integrate histologic, immunophenotypical, genetic, and in particular, clinical data to arrive at the correct diagnosis, and subsequently provide adequate treatment, is emphasized.


Song SX, Willemze R, Swerdlow SH, et al.
Mycosis fungoides: report of the 2011 Society for Hematopathology/European Association for Haematopathology workshop.
Am J Clin Pathol. 2013; 139(4):466-90 [PubMed]
Session 1 of the 2011 Workshop of the Society for Hematopathology and European Association for Haematopathology focused on mycosis fungoides (MF), the most common cutaneous lymphoma. The 62 cases in this case group demonstrated a wide spectrum of clinicopathologic features, including those seen in typical cases as well as those, by contrast, with atypical clinical history, morphology, immunophenotype, and/or genotype. Of the 62 cases, 27 (44%) were presented at the workshop and highlighted diagnostic challenges plus related issues. This report summarizes the approach recommended for making a confident diagnosis of MF and its clinically significant variants; emphasizes pitfalls in evaluating early MF, assessing nodal involvement, and diagnosing transformed MF; and discusses the relationship between MF and primary cutaneous CD30+ T-cell lymphoproliferative disorders. Last, Sézary syndrome is discussed, with concentration on those features distinct from MF.


Yao Y, Mark LA
Woringer-Kolopp disease mimicking foot dermatitis.
Cutis. 2012; 90(6):307-9, 316 [PubMed]
Woringer-Kolopp disease, also known as localized pagetoid reticulosis, is a rare cutaneous lymphoproliferative disorder classified as a solitary variant of mycosis fungoides (MF). Despite the indolent and benign nature of the disease, misdiagnosis and inappropriate treatment may result in years of debilitating symptoms and even loss of function. We present the case of a patient with long-standing Woringer-Kolopp disease that mimicked foot dermatitis. Histopathologic examination demonstrated epidermotropic infiltration of atypical lymphocytes that were CD3+ CD4- CD8-. The patient was successfully treated with topical keratolytics and bexarotene gel 1% with minimal residual lesions after 8 years of follow-up. We discuss the characteristics of this rare disease in contrast with localized MF as well as more aggressive forms of epidermotropic T-cell lymphoma.


Hara M, Nemoto T, Hijima T, et al.
A case of IgA nephropathy associated with mycosis fungoides that developed into rapidly progressive glomerulonephritis.
Clin Nephrol. 2013; 79(2):161-5 [PubMed]
A 53-year-old Japanese male was diagnosed with atopic dermatitis and initiated treatment with a local dermatologist in February 2001. A routine medical check-up revealed proteinuria, microscopic hematuria and slight elevation of serum creatinine level in spring 2006. He was referred to our hospital for nephrology consultation and followup.In December 2009, he developed a sudden high fever of greater than 39 °C with sore throat. In addition, his serum creatinine level greatly increased to 4.6 mg/dl. His prevalent renal illness was thought to be rapidly progressive glomerulonephritis (RPGN). Soon after admission, kidney and skin biopsies were performed. The kidney specimens showed that the glomeruli had proliferative mesangial cells strongly positive for anti-IgA antibody, 75% of which manifested fibrocellular crescentic formation surrounding the Bowman's capsules. His skin disease was pathologically proven to be mycosis fungoides(MF). It is likely that his kidney disease was exacerbated by the upper respiratory tract infection and converted to RPGN. Ash is kidney function rapidly declined, hemodialysis therapy was initiated and he remains on chronic dialysis therapy. This is a serious case of IgA nephropathy associated with MF,which developed into RPGN and subsequent end-stage renal disease.


Gregoriou S, Rigopoulos D, Stamou C, et al.
Treatment of mycosis fungoides with bexarotene results in remission of diffuse plane xanthomas.
J Cutan Med Surg. 2013 Jan-Feb; 17(1):52-4 [PubMed]
BACKGROUND: Cutaneous xanthomas develop as a result of intracellular and dermal deposition of lipids in either hyper- or normolipidemic patients. Plane xanthomas may signal the presence of an underlying monoclonal gammopathy, chronic myelomonocytic leukemia, or cutaneous T-cell lymphoma. Investigators have suggested that xanthomatized T cells may result in induction of plane xanthomas.
METHODS: We report the case of a patient with mycosis fungoides (MF) and plane xanthomas who was treated with bexarotene for his MF.
RESULTS: Significant improvement in the clinical signs of MF was observed within 3 months. We also observed a substantial regression of the xanthomas after 5 months of treatment. Complete clinical remission of both the MF and xanthomas was obtained after 6 months. The patient was still free of xanthomas after 3 years of follow-up.
CONCLUSION: Bexarotene led to the clearing of the cutaneous lesions of cutaneous T-cell lymphoma and plane xanthomas. This may be due to an effect of bexarotene on the aberrant T cells that may cause xanthomatization.


Rodríguez-Pinilla SM, Ortiz-Romero PL, Monsalvez V, et al.
TCR-γ expression in primary cutaneous T-cell lymphomas.
Am J Surg Pathol. 2013; 37(3):375-84 [PubMed]
Primary cutaneous γδ T-cell lymphomas (PCGD-TCLs) are considered a subgroup of aggressive cytotoxic T-cell lymphomas (CTCLs). We have taken advantage of a new, commercially available antibody that recognizes the T-cell receptor-γ (TCR-γ) subunit of the TCR in paraffin-embedded tissue. We have analyzed a series of 146 primary cutaneous T-cell lymphomas received for consultation or a second opinion in the CNIO Pathology Department. Cases were classified according to the World Health Organization 2008 classification as mycosis fungoides (MF; n=96), PCGD-TCLs (n=5), pagetoid reticulosis (n=6), CD30(+) primary cutaneous anaplastic large cell lymphomas (n=5), primary cutaneous CD8 aggressive epidermotropic CTCLs (n=3), primary cutaneous CTCL, not otherwise specified (n=4), and extranodal nasal-type NK/T-cell lymphomas primarily affecting the skin or subcutaneous tissue (n=11). Sixteen cases of the newly named lymphomatoid papulosis type D (LyP-D; n=16) were also included. In those cases positive for TCR-γ, a further panel of 13 antibodies was used for analysis, including TIA-1, granzyme B, and perforin. Clinical and follow-up data were recorded in all cases. Twelve cases (8.2%) were positive for TCR-γ, including 5 PCGD-TCLs, 2 MFs, and 5 LyP-Ds. All 5 PCGD-TCL patients and 1 MF patient died of the disease, whereas the other MF patient and all those with LyP-D were alive. All cases expressed cytotoxic markers, were frequently CD3(+)/CD8(+), and tended to lose CD5 and CD7 expressions. Eight of 12 and 5 of 11 cases were CD30(+) and CD56(+), respectively. Interestingly, 5/12 TCR-γ-positive cases also expressed TCR-BF1. All cases analyzed were negative for Epstein-Barr virus-encoded RNA. In conclusion, TCR-γ expression seems to be rare and is confined to cytotoxic primary cutaneous TCLs. Nevertheless, its expression is not exclusive to PCGD-TCLs, as TCR-γ protein can be found in other CTCLs. Moreover, its expression does not seem to be associated with bad prognosis by itself, as it can be found in cases with good and bad outcomes.


Whitling NA, Shanesmith RP, Jacob L, et al.
Composite lymphoma of mycosis fungoides and cutaneous small B-cell lymphoma in a 73-year-old male patient.
Hum Pathol. 2013; 44(4):670-5 [PubMed]
Composite lymphoma of T-cell and B-cell type is uncommon, and the one occurring primarily on skin is extremely rare. Herein, we report a unique case of composite lymphoma of mycosis fungoides and cutaneous small B-cell lymphoma in a 73-year-old male patient. The patient presented with multiple erythematous patches, plaques, and nodules on the upper arms, scalp, and trunk. Four punch biopsies of arm and scalp lesions demonstrated lymphoid infiltrate in superficial to deep dermis with a characteristic zone distribution of T-cell and B-cell components. T cells were distributed in papillary and perifollicular dermis and displayed a larger size with convoluted nuclei, whereas B cells were small sized, assuming nodular infiltrate in mid-deep dermis with coexpression of CD5. Molecular test detected clonal rearrangement of both TCRG and IGH/K genes with identical amplicons for each gene in all 4 biopsies. Clinical staging revealed no extracutaneous lesions. A multidisplinary approach is emphasized to establish a definitive diagnosis.


Mak G, Porter PC, Bandi V, et al.
Tracheobronchial mycosis in a retrospective case-series study of five status asthmaticus patients.
Clin Immunol. 2013; 146(2):77-83 [PubMed] Article available free on PMC after 01/02/2014
The etiology of status asthmaticus (SA), a complication of severe asthma, is unknown. Fungal exposure, as measured by fungal atopy, is a major risk factor for developing asthma, but the relationship of fungi in SA per se has not previously been reported. In this five patient retrospective case series study, lower respiratory tract cultures were performed on bronchoalveolar lavage or tracheal aspirate fluid, comparing standard clinical laboratory cultures with a specialized technique in which respiratory mucus was removed prior to culture. We show that mucolytic treatment allows an increased detection of fungal growth, especially yeast, from the lower airways of all SA patients. We also demonstrate that inhalation of the yeast Candida albicans readily induces asthma-like disease in mice. Our observations suggest that SA may represent a fungal infectious process, and support additional prospective studies utilizing anti-fungal therapy to supplement conventional therapy, broad-spectrum antibiotics and high-dose glucocorticoids, which can promote fungal overgrowth.


Thomas BR, Whittaker S
A practical approach to accurate classification and staging of mycosis fungoides and Sézary syndrome.
Skin Therapy Lett. 2012; 17(10):5-9 [PubMed]
Cutaneous T-cell lymphomas are rare, distinct forms of non-Hodgkin's lymphomas. Of which, mycosis fungoides (MF) and Sézary syndrome (SS) are two of the most common forms. Careful, clear classification and staging of these lymphomas allow dermatologists to commence appropriate therapy and allow correct prognostic stratification for those patients affected. Of note, patients with more advanced disease will require multi-disciplinary input in determining specialist therapy. Literature has been summarized into an outline for classification/staging of MF and SS with the aim to provide clinical dermatologists with a concise review.


Deonizio JM, Guitart J
The role of molecular analysis in cutaneous lymphomas.
Semin Cutan Med Surg. 2012; 31(4):234-40 [PubMed]
The purpose of this review is to summarize the most important molecular techniques for the diagnosis of cutaneous lymphomas. When making a diagnosis, we are looking for the solid clinicopathological correlation. Molecular analysis includes immunophenotyping and clonality analysis, and is important for 2 principal reasons: (1) to confirm the diagnosis in cases where the clinical and/or pathological presentations are nondiagnostic, and (2) to further characterize the nature of the lymphoma. More specifically, we are trying to discern whether the lymphoma is primarily cutaneous or systemic with secondary skin involvement, and we are also attempting to subclassify the tumor. Recently, many techniques have provided a more accurate diagnosis of cutaneous lymphomas and some prognostic implications, including polymerase chain reaction, fluorescence in situ hybridization, and flow cytometry. Fluorescence in situ hybridization is not routinely used in the diagnosis of cutaneous lymphoma, but many studies have shown potential future applications in various areas. Other techniques, such as comparative genomic hybridization, are still confined to the research arena, but have added some insight into the molecular pathogenesis of cutaneous T-cell lymphoma.


Litvinov IV, Kupper TS, Sasseville D
The role of AHI1 and CDKN1C in cutaneous T-cell lymphoma progression.
Exp Dermatol. 2012; 21(12):964-6 [PubMed]
Cutaneous T-cell lymphoma (CTCL) is the most common lymphoma of the skin. Recent reports suggest that AHI1 is overexpressed in a subset of CTCL-derived cell lines, where it downregulates the expression of CDKN1C tumor suppressor gene. In the current work, we test the expression of these genes in 60 patients with Mycosis Fungoides and Sezary Syndrome by RT-PCR and correlate our findings with 6 years of clinical follow-up. These findings reveal that AHI1 and CDKN1C exhibit opposite expression patterns, where AHI1 is expressed in poor and intermediate prognosis patients, while CDKN1C is expressed in favourable prognosis patients. Kaplan-Meier analysis documents that downregulation of CDKN1C is associated with poor disease outcome in patients with CTCL, while upregulation of AHI1 shows a weak association with aggressive disease course.


Delfino C, Grandi V, Pileri A, et al.
Combination treatment in CTCL: the current role of bexarotene.
G Ital Dermatol Venereol. 2012; 147(6):573-80 [PubMed]
Primary cutaneous T-cell lymphomas are a heterogeneous group of extranodal NH lymphomas primarily presenting in the skin without extracutaneos involvement at diagnosis. Treatment choices closely depend on clinic-pathologic entity and disease stage. Among available choices, oral bexarotene has shown efficacy and safety both in monotherapy and in association with other treatments, by virtue of its versatility and high synergism with alpha-interferon, photochemotherapy (PUVA), and chemotherapy. Moreover, when associated with a wise management of its side effects, bexarotene is well tolerated if used in long-term administration, and it is therefore a good candidate to maintenance treatment after different induction therapies. Recently, the Gruppo Italiano Linfomi Cutanei (GILC) has started some pilot studies, with the aim to investigate bexarotene potential in association with PUVA and single agent chemotherapy (as pegylated liposomal doxorubicin and gemcitabine), and as consolidation/maintenance treatment. The preliminary results of GILC pilot studies confirm the good tolerability and safety of low-intermediate dose bexarotene, and its potential synergism with PUVA and chemotherapy. In addition, its use in consolidation/maintenance has proven efficacy in improving overall response rate.


Zinzani PL
Advanced/aggressive CTCL: improving the efficacy of treatment.
G Ital Dermatol Venereol. 2012; 147(6):563-72 [PubMed]
Treatment regimens of patients with cutaneous T-cell lymphoma (CTCL) vary widely based on clinician preference and patient tolerance. Skin directed therapies are recommended for patients with early stage IA and IB MF, with combinations used in refractory cases. While no regimen has been proven to prolong survival in advanced stages, immunomodulatory regimens should be used initially to reduce the need for cytotoxic therapies. In more advanced stages of disease, treatment efforts should strive for palliation and improvement of quality of life. With many new therapies and strategies on the horizon, the future looks promising for CTCL patients.


Kempf W, Rozati S, Kerl K, et al.
Cutaneous peripheral T-cell lymphomas, unspecified/NOS and rare subtypes: a heterogeneous group of challenging cutaneous lymphomas.
G Ital Dermatol Venereol. 2012; 147(6):553-62 [PubMed]
Cutaneous peripheral T-cell lymphoma, unspecified/not otherwise specified (PTL NOS) represents a phenotypically and prognostically heterogenous group of cutaneous T-cell lymphomas (CTCL) that do not fit into any of well defined defined CTCL subtypes. In the WHO-EORTC classification as well as the WHO classification, three entities have been delineated as provisional rare subtypes of PTL based on their characteristic clinico-pathological, immunophenotypic and prognostic features and have been separated out from PTL, NOS: Primary cutaneous CD4-positive small/medium T-cell lymphoma (CD4+ SMTL), primary cutaneous CD8-positive aggressive epidermotropic T-cell lymphoma (CD8+ AECTCL), and primary cutaneous gamma/delta T-cell lymphoma (CGD-TCL). CD4+ SMTL manifests in most patients with a solitary nodule in the head and neck area and nodular infiltrates of CD4+ small to medium-sized lymphocytes with nuclear pleomorphism. The prognosis of this lymphoproliferation is excellent in patients with a solitary lesion, but may be impaired in patients with multifocal disease. Rapidly evolving erosive or necrotic plaques and nodules with an epidermotropic infiltrate of CD8+ atypical lymphocytes are the hallmark of CD8+ AECTCL, which exhibits a poor prognosis. CGD-TCL displays a broad spectrum of clinical and histological manifestations with expression of the T-cell receptor gamma/delta chain as the common denominator and diagnostic marker. As most of other forms of PTL, CGD-TCL carries a poor prognosis. Despite the rarity of PTL NOS, clinicians as well as dermatopathologists and pathologists should be familiar with these rare CTC, especially since most of these lymphomas exhibit an unfavourable prognosis. Immediate intense treatment with multiagent chemotherapy and hematopoietic stem cell transplantation is indicated in patients with PTL NOS. This review focuses on the clinicopathological aspects, the diagnostic criteria and the classification of the rare subtypes of PTL and PTL NOS.


Bernengo MG, Quaglino P
Erythrodermic CTCL: updated clues to diagnosis and treatment.
G Ital Dermatol Venereol. 2012; 147(6):533-44 [PubMed]
Erythroderma is a rare but severe cutaneous condition characterized from a clinical point of view by a complete involvement (as per definition more than 80% body surface) of the skin surface. Pre-existing dermatoses account for about 70% of erythroderma cases, drug reactions are responsible for erythroderma in about 20%, whilst primary cutaneous T-cell lymphoma (CTCL) constitute less than 10% of and are represented by erythrodermic mycosis fungoides and Sézary syndrome. The challenge in these patients is represented by the identification of the etiological agents or conditions, which is clearly of overwhelming relevance in the clinical management and treatment strategies. In recent years, the development of multiparameter flow-cytometry, which allows to identify specific antigens expressed or not expressed on the surface of atypical lymphoid T-cells, and T-cell molecular biology techniques, which are aimed to identify the presence of a clonal T-cell population in the skin and blood on the basis of the finding of rearrangement of the T-cell receptor, have represented relevant useful tool in the differential diagnosis between benign and lymphomatous erythroderma. Moreover, a better understanding of the immunological and molecular pathways in CTCL disease evolution provided the identification of specific therapeutical targets, as well as the constant improvement in the laboratory techniques lead to the development of new and promising agents in CTCL.


Quaglino P, Pimpinelli N, Berti E, et al.
Mycosis fungoides: disease evolution of the "lion queen" revisited.
G Ital Dermatol Venereol. 2012; 147(6):523-31 [PubMed]
Mycosis fungoides (MF), which represents the most common subtype of primary cutaneous T-cell lymphoma (CTCL), is an epidermotropic lymphoma included as an indolent form in the recent WHO/EORTC classification. From a clinical point of view, the classic disease progression usually is slow and takes over years or even decades, and characterized by the evolution from patches to more infiltrated plaques and eventually to tumours or erythroderma. However, the analysis of the MF disease course has been greatly impaired by the rarity of the disease, thus data about the time course of disease progression and pattern of relapse during time are not well known. In this review, a summary of published data on MF large patients cohorts will be presented, together with the results obtained by a retrospective analysis of clinical features and follow-up data of 1,422 MF patients diagnosed and followed-up from 1975 to 2010 in 27 Italian Centres (Italian Study Group for Cutaneous Lymphoma). From a clinical perspective, the amount of data support the relevance of a stage-tailored, differentiated follow-up strategy, in as much as the TNMB staging appears not only to be associated with different progression rates, but also shows as a new finding a relationship with different patterns of disease progression. From a biological point of view, there is the need to understand the molecular basis of the different clinical pathways of disease progression, to be able to potentially identify at an earlier phase of disease evolution, the patients who are more likely to develop erythroderma or tumour-stage progression. In conclusion, if MF is indeed a true "lion queen", as dermatologists we need to be expert and wise tamers to keep it under control.


Willemze R
Thirty years of progress in cutaneous lymphoma research.
G Ital Dermatol Venereol. 2012; 147(6):515-21 [PubMed]
Primary cutaneous lymphomas are a heterogeneous group of T-cell and B-cell neoplasms that present in the skin without any evidence of extracutaneous disease at the time of diagnosis. In 1980 primary cutaneous lymphomas other than mycosis fungoides, Sezary syndrome and some related disorders, collectively termed cutaneous T-cell lymphoma had not yet been recognized. This historic review describes the history of cutaneous lymphoma research in Europe over the last thirty years. European collaborative studies by dermatologists and pathologists, often coordinated by the European Organization for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Group, resulted in the definition of new types of cutaneous T-cell lymphomas (CTCL) and cutaneous B-cell lymphomas (CBCL), and the development of consensus classifications for primary cutaneous lymphomas (EORTC classification; WHO-EORTC classification; WHO classification 2008), which resulted in better diagnosis and treatment of these diseases. More recent activities described herein are the development of guidelines for staging, treatment and the design of clinical trials, often in close collaboration with the International Society for Cutaneous Lymphomas, the formation of an EORTC CTCL trials platform and attempts to translate the results of molecular genetic studies into clinical practise. In this review the importance of a multidisciplinary approach and continued international collaboration not only in clinical trials and guideline development, but also in basic research is emphasized.


Damaj G, Gressin R, Bouabdallah K, et al.
Results from a prospective, open-label, phase II trial of bendamustine in refractory or relapsed T-cell lymphomas: the BENTLY trial.
J Clin Oncol. 2013; 31(1):104-10 [PubMed]
PURPOSE: To determine the efficacy and safety of bendamustine as a single agent in refractory or relapsed T-cell lymphomas.
PATIENTS AND METHODS: Patients with histologically confirmed peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma who progressed after one or more lines of prior chemotherapy received bendamustine at 120 mg/m(2) per day on days 1 through 2 every 3 weeks for six cycles. The primary end point was overall response rate (ORR). Secondary end points were duration of response (DOR), progression-free survival (PFS), and overall survival (OS).
RESULTS: Of the 60 patients included, 27 (45%) were refractory to their last prior chemotherapy, and the median duration of the best previous response was 6.6 months. Histology was predominantly angioimmunoblastic lymphadenopathy and PTCL not otherwise specified. The disease was disseminated in the majority of patients (87%). The median number of previous lines of chemotherapy was one (range, one to three). Twenty patients (33%) received fewer than three cycles of bendamustine, mostly because of disease progression. In the intent-to-treat population, the ORR was 50%, including complete response in 17 patients (28%) and partial response in 13 patients (22%). Bendamustine showed consistent efficacy independent of major disease characteristics. The median values for DoR, PFS, and OS were 3.5, 3.6, and 6.2 months, respectively. The most frequent grade 3 to 4 adverse events were neutropenia (30%), thrombocytopenia (24%), and infections (20%).
CONCLUSION: Bendamustine showed an encouraging high response rate across the two major PTCL subtypes, independent of age and prior treatment, with acceptable toxicity in refractory or relapsed T-cell lymphoma.


Guitart J, Weisenburger DD, Subtil A, et al.
Cutaneous γδ T-cell lymphomas: a spectrum of presentations with overlap with other cytotoxic lymphomas.
Am J Surg Pathol. 2012; 36(11):1656-65 [PubMed]
We reviewed our multicenter experience with gamma-delta (γδ) T-cell lymphomas first presenting in the skin. Fifty-three subjects with a median age of 61 years (range, 25 to 91 y) were diagnosed with this disorder. The median duration of the skin lesions at presentation was 1.25 years (range, 1 mo to 20 y). The most common presentation was deep plaques (38 cases) often resembling a panniculitis, followed by patches resembling psoriasis or mycosis fungoides (10 cases). These lesions tended to ulcerate overtime (27 cases). Single lesions or localized areas of involvement resembling cellulitis or pyoderma were reported in 8 cases. The most common anatomic site of involvement was the legs (40 cases), followed by the torso (30 cases) and arms (28 cases). Constitutional symptoms were reported in 54% (25/46) of the patients, including some with limited skin involvement. Significant comorbidities included autoimmunity (12 cases), other lymphoproliferative disorders (5 cases), internal carcinomas (4 cases), and viral hepatitis (2 cases). Lymphadenopathy (3/42 cases) and bone marrow involvement (5/28 cases) were uncommon, but serum lactose dehydrogenase (LDH) was elevated in 55% (22/39) of the patients. Abnormal positron emission tomography and/or computed tomography scans in 20/37 subjects mostly highlighted soft tissue or lymph nodes. Disease progression was associated with extensive ulcerated lesions resulting in 27 deaths including complications of hemophagocytic syndrome (4) and cerebral nervous system involvement (3). Median survival time from diagnosis was 31 months. Skin biopsies varied from a pagetoid pattern to purely dermal or panniculitic infiltrates composed of intermediate-sized lymphocytes with tissue evidence of cytotoxicity. The most common immunophenotype was CD3+/CD4+/CD5+/CD8+/BF1+/γ-M1+/TIA-1+/granzyme-B+/CD45RA-/CD7-, and 4 cases were Epstein-Barr virus positive. This is the largest study to date of cutaneous γδ T-cell lymphomas and demonstrates a variety of clinical and pathologic presentations with a predictable poor outcome.


Lessin SR, Duvic M, Guitart J, et al.
Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides.
JAMA Dermatol. 2013; 149(1):25-32 [PubMed]
OBJECTIVE: To evaluate the efficacy and safety of a novel mechlorethamine hydrochloride, 0.02%, gel in mycosis fungoides. DESIGN Randomized, controlled, observer-blinded, multicenter trial comparing mechlorethamine, 0.02%, gel with mechlorethamine, 0.02%, compounded ointment. Mechlorethamine was applied once daily for up to 12 months. Tumor response and adverse events were assessed every month between months 1 and 6 and every 2 months between months 7 and 12. Serum drug levels were evaluated in a subset of patients.
SETTING: Academic medical or cancer centers.
PATIENTS: In total, 260 patients with stage IA to IIA mycosis fungoides who had not used topical mechlorethamine within 2 years and were naive to prior use of topical carmustine therapy.
MAIN OUTCOME MEASURES: Response rates of all the patients based on a primary clinical end point (Composite Assessment of Index Lesion Severity) and secondary clinical end points (Modified Severity-Weighted Assessment Tool and time-to-response analyses).
RESULTS: Response rates for mechlorethamine gel vs ointment were 58.5% vs 47.7% by the Composite Assessment of Index Lesion Severity and 46.9% vs 46.2% by the Modified Severity-Weighted Assessment Tool. By the Composite Assessment of Index Lesion Severity, the ratio of gel response rate to ointment response rate was 1.23 (95% CI, 0.97-1.55), which met the prespecified criterion for noninferiority. Time-to-response analyses demonstrated superiority of mechlorethamine gel to ointment (P< .01). No drug-related serious adverse events were seen. Approximately 20.3% of enrolled patients in the gel treatment arm and 17.3% of enrolled patients in the ointment treatment arm withdrew because of drug-related skin irritation. No systemic absorption of the study medication was detected.
CONCLUSION: The use of a novel mechlorethamine, 0.02%, gel in the treatment of patients with mycosis fungoides is effective and safe.
TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00168064.


Ponciano A, de Muret A, Machet L, et al.
Epidermotropic secondary cutaneous involvement by relapsed angioimmunoblastic T-cell lymphoma mimicking mycosis fungoides: a case report.
J Cutan Pathol. 2012; 39(12):1119-24 [PubMed]
Angioimmunoblastic T-cell lymphoma (AITL) is frequently associated with skin lesions, but epidermotropic cutaneous involvement has never been described. A 37-year-old man presented with erythematous and pruriginous plaques, clinically suggestive of mycosis fungoides, distributed all over the body, 3 weeks after the last line of a polychemotherapy, given for an AITL diagnosed 1 year earlier on a lymph node biopsy. Skin biopsy showed an epidermotropic CD4(+) T-cell lymphoma, so that a diagnosis of mycosis fungoides was first proposed. Further investigations showed that atypical lymphocytes strongly expressed CD10 and markers of follicular helper T cells (T(FH) ) including PD1, BCL-6 and CXCL13. The diagnosis of an unusual epidermotropic cutaneous localization of the AITL was finally made, supported by the presence of the same T-cell clone in the initial lymph node biopsy and the skin. We therefore recommend performing markers of T(FH) cells in patients with unusual epidermotropic cutaneous T-cell lymphomas, particularly if they have any clinical features suggestive of AITL.


Dummer R, Quaglino P, Becker JC, et al.
Prospective international multicenter phase II trial of intravenous pegylated liposomal doxorubicin monochemotherapy in patients with stage IIB, IVA, or IVB advanced mycosis fungoides: final results from EORTC 21012.
J Clin Oncol. 2012; 30(33):4091-7 [PubMed]
PURPOSE: Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma. There is a need for multicenter trials involving defined patient populations using rigorous assessment criteria. We have investigated pegylated liposomal doxorubicin (PLD) in a clearly defined patient population with advanced MF.
PATIENTS AND METHODS: Eligible patients had stage IIB, IVA, or IVB MF, refractory or recurrent after at least two previous systemic therapies. Patients were registered to receive a maximum of six cycles of PLD 20 mg/m2 on days 1 and 15, every 28 days (one cycle). The primary end point was response rate (RR).
RESULTS: Nine centers recruited 49 eligible patients. The median number of chemotherapy cycles received was five. There were no grade 3 to 4 hematologic toxicities. Grade 3 or 4 nonhematologic/nonbiochemical toxicities included cardiac symptom (2%), allergy/hypersensitivity (2%), constitutional symptom (4%), hand and foot reaction (2%), other dermatologic toxicity (6%), other GI toxicity (4%), infection (4%), pulmonary embolism (2%), and cardiac ischemia (2%). Of 49 patients, 20 (40.8%) were responders (complete clinical response [CCR] or partial response [PR] as overall response): three (6.1%) experienced CCRs, and 17 (34.7%) experienced PRs. A 50% or greater reduction of cutaneous manifestations was observed in 26 (60.5%) of 43 assessable patients. Two early deaths were reported, resulting from related cardiovascular toxicity and disease progression. The lower limit of the one-sided 90% CI for RR was 31.2%. Median time to progression and median duration of response were 7.4 and 6 months, respectively.
CONCLUSION: PLD has an acceptable safety profile in patients with advanced MF. The efficacy of PLD seems promising.


Rausch T, Cairoli A, Benhattar J, et al.
EBV+ cutaneous B-cell lymphoproliferation of the leg in an elderly patient with mycosis fungoides and methotrexate treatment.
APMIS. 2013; 121(1):79-84 [PubMed]
A 77-year-old man with a 5-year history of mycosis fungoides (MF) who had received several lines of therapy, including intravenous courses of Methotrexate (MTX) for the past 2 years, went on to develop several ulcerated cutaneous nodules on the left leg. Biopsy revealed diffuse sheets of EBV-positive large B cells (CD20+ CD30 ± IgM Lambda), with an angiocentric distribution and a monoclonal IGH gene rearrangement. Although the pathological features were diagnostic for an EBV-positive diffuse large B-cell lymphoma (DLBCL), several possibilities could be considered for assignment to a specific entity: EBV-positive DLBCL of the elderly, methotrexate-induced lymphoproliferative disorder (LPD), lymphomatoid granulomatosis, or the more recently described EBV-positive mucocutaneous ulcer. The development of EBV+ lymphoproliferations has been reported in two other patients with MF under MTX, and occurred as skin lesions of the leg in one of these and in the current case, which may question the relatedness to primary cutaneous DLCBL, leg-type.


Kempf W, Kazakov DV, Schärer L, et al.
Angioinvasive lymphomatoid papulosis: a new variant simulating aggressive lymphomas.
Am J Surg Pathol. 2013; 37(1):1-13 [PubMed]
Lymphomatoid papulosis (LyP) belongs to the spectrum of primary cutaneous CD30-positive lymphoproliferative disorders. Clinically, LyP is characterized by a variable number of self-healing papulo-nodular lesions, with the typical waxing and waning course. Histologically, 4 types (A, B, C, and D) have been delineated. Angioinvasive growth and large ulcers are rare findings in LyP and simulate aggressive lymphoma. We retrospectively analyzed the clinicopathologic and molecular features of angioinvasive LyP in a series of 16 patients. This new form of LyP is characterized by oligolesional papules that rapidly ulcerate and evolve into large necrotic eschar-like lesions with a diameter of 1 to 4 cm and an angiocentric and angiodestructive infiltrate of small-sized to medium-sized atypical lymphocytes expressing CD30 and frequently CD8. As in other forms of LyP, the lesions underwent spontaneous regression after a few weeks. Recurrences were common, but the prognosis was excellent with no extracutaneous spread or disease-related deaths. Complete remission occurred in 9 of 16 patients (56%). This LyP variant should be distinguished from aggressive forms of angiocentric and angiodestructive and cytotoxic T-cell lymphomas. We propose the term LyP type E for this clinically and histologically unusual variant.


Wang X, Magro CM
Human myxovirus resistance protein 1 (MxA) as a useful marker in the differential diagnosis of subcutaneous lymphoma vs. lupus erythematosus profundus.
Eur J Dermatol. 2012 Sep-Oct; 22(5):629-33 [PubMed]
BACKGROUND: Substantial clinicohistologic overlap exists between lupus erythematosus profundus (LEP) and lymphomas involving the subcutis, including subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and primary cutaneous gamma/delta T-cell lymphoma (GDTCL). Unequivocal markers separating the entities are not established.
OBJECTIVES: To explore the usefulness of interferon alpha (INF-α)-induced protein, myxovirus resistance protein 1 (MxA), in the differential diagnosis of these entities, as studies show that the expression pattern of MxA follows the distribution of the inflammatory infiltrate in cutaneous lupus, while INF- α is not known to operate in lymphoma.
MATERIALS AND METHODS: MxA immunohistochemistry was performed on skin biopsies from 5 patients with a clinical and histological diagnosis of SPTCL, 9 patients with GDTCL and 9 patients with LEP.
RESULTS: In SPTCL and GDTCL, MxA was primarily seen in macrophages and generally did not exceed 20% of the infiltrate. In contrast, a significant portion of the subcutaneous infiltrate was positive for MxA in LEP, with 50% of the infiltrate staining on average. A greater number of macrophages and lymphocytes stained with a greater intensity as well (P<0.001). Moreover, endothelial cell staining was uniquely identified in LEP but not in lymphoma.
CONCLUSION: Although specificity is not 100%, minimal staining of MxA is a predictor for SPTCL or GDTCL. Conversely, extensive staining for MxA both qualitatively and quantitatively is a feature of LEP. Endothelial staining also appears to be specific for LEP.


Kairouani M, Sekkate S, Ismaili N, et al.
A rare case of nephrotic syndrome revealing mycosis fungoide managed successfully with chemotherapy.
Pan Afr Med J. 2012; 12:67 [PubMed] Article available free on PMC after 01/02/2014
The occurrence of the nephrotic syndrome during mycosis fungoide is very unusual. We report a rare case of mycosis fungoide revealed by hydrops related to nephrotic syndrom in a 37-year old male patient. He has been admitted to intensive care unit because of a breathing distress and a hydrophobs. Whole body computed tomography scan revealed bilateral axillary, cervical lymph nodes, tumoral infiltration of the subcutaneous tissue in the cervicothoracic and abdominal regions, multiples bilateral pulmonary metastasis, bilateral pleural effusion, and abdominal effusion; the kidneys were normal. The patient was staged IVb (T3N3M1). He was treated with CHOP (cyclophosphamide, Doxorubicin, Vincristin and prednisone). Evolution after eight cycles of chemotherapy was spectacular. The development of nephrotic syndrom secondary to mycosis fungoide is rare. It requires a multidisciplinary approach with nephrologists and oncologists.


Deonizio JM, Guitart J
Current understanding of cutaneous lymphoma: selected topics.
Dermatol Clin. 2012; 30(4):749-61, vii-viii [PubMed]
Recent epidemiology studies have identified a steady increase in the incidence of cutaneous lymphomas over the past few decades. Although possible explanations for this increased incidence include heightened awareness of these conditions as well as a more refined diagnostic acuity by dermatologists and pathologists, an increase secondary to environmental factors cannot be discounted. Our understanding of cutaneous lymphomas keeps evolving. Consequently, our knowledge and understanding of cutaneous lymphomas requires reconsideration of past dogma and critical revision of the new proposals. In this article, some hot topics and important new findings in the field are reviewed.


Elston DM
What's new in the histologic evaluation of alopecia and hair-related disorders?
Dermatol Clin. 2012; 30(4):685-94, vii [PubMed]
The diagnosis of alopecia and other hair-related disorders can be challenging. An appreciation of the newest diagnostic techniques and newly described entities can help clinicians to provide the best care for patients. This article focuses on advances in the histologic evaluation of alopecia. Also discussed are recent advances in the understanding of hair-related disorders that do not result in alopecia. Advances in the understanding of disease mechanisms can help in treating hair disorders that proved refractory in the past.


Fung MA, Barr KL
Current knowledge in inflammatory dermatopathology.
Dermatol Clin. 2012; 30(4):667-84, vii [PubMed]
The complex and fascinating spectrum of inflammatory skin disease, and the comprehension of it, is ever expanding and evolving. During the first decade of the 21st century, numerous advances in the understanding of inflammatory disease mechanisms have occurred, particularly in psoriasis and atopic dermatitis. Continuation of this trend will assure a future in which molecular tests for biomarkers of immediate clinical relevance are used in routine patient care, not only for diagnosis but also for prognosis and management. This article focuses on selected recent or noteworthy developments that are clinically relevant for the histologic diagnosis of inflammatory skin diseases.


This page last updated: 22nd May 2013
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