Pleomorphic Cutaneous T-cell Lymphoma Research Articles

Primary cutaneous CD8+ small/medium-sized pleomorphic T-cell lymphoma, ear-type: a unique cutaneous T-cell lymphoma with a favourable prognosis

Funding sources: none. Conflicts of interest: none declared. Madam, Compared with CD4+ primary cutaneous T‐cell lymphomas (CTCLs), CD8+ CTCLs occur infrequently. Among CD8+ CTCLs, CD8+ variants of CD4+ CTCL predominate; these display clinical features and prognosis similar to their CD4+ counterparts. According to the World Health Organization (WHO)–European Organisation for Research and Treatment of Cancer (EORTC) classification for cutaneous lymphomas, CD8+ variants of CD4+ CTCL occur in mycosis fungoides and its variant pagetoid reticulosis, Sézary syndrome (SS), CD30+ lymphoproliferative disorders, subcutaneous panniculitis‐like T‐cell lymphoma and nasal‐type natural killer/T‐cell lymphoma.1 Among the provisional entities in the WHO–EORTC classification, primary cutaneous aggressive epidermotropic CD8+ cytotoxic T‐cell lymphoma is defined by CD8 expression and is almost invariably associated with a fatal clinical outcome. In contrast, the provisional entity of small/medium‐sized pleomorphic CTCL was defined by the expression of CD4 to exclude the few CD8 cases that could not be lumped together by clinical presentation, histomorphology and course of disease.2 Recently, several groups have reported on an indolent CD8+ lymphoid proliferation on the ear with highly characteristic clinical and pathological features in a total of 10 patients.3–6 Here we describe another patient with this condition and suggest classifying this novel entity as primary cutaneous CD8+ small/medium‐sized pleomorphic T‐cell lymphoma, ear‐type.

Indolent CD8+ lymphoid proliferation of the ear: A phenotypic variant of the small-medium pleomorphic cutaneous T-cell lymphoma?

Indolent CD8+ lymphoid proliferation of the ear: A phenotypic variant of the small-medium pleomorphic cutaneous T-cell lymphoma?

Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Indolent CD8+ lymphoid proliferation of the ear: A phenotypic variant of the small‐medium pleomorphic cutaneous T‐cell lymphoma?

Recently, Petrella et al. described four patients with an unusual CD8+ lymphoid proliferation arising on the ear. These cases do not correspond clearly to any recognized category of cutaneous T-cell lymphoma (CTCL) described in the World Health Organization (WHO)/European Organization for Research and Treatment of Cancer (EORTC) 2005 classification. Three patients (all men; median age 64; range: 61-69) presented with plaques or small tumors localized on the ears. All lesions showed histopathologically a dense, diffuse infiltration of lymphocytes within the entire dermis without epidermotropism. Cytomorphology revealed predominance of medium-sized pleomorphic lymphocytes. Immunohistochemistry showed a cytotoxic phenotype (CD3 + /CD4 -/CD8 +). Polymerase chain reaction (PCR) analysis of the T-cell receptor (TCR)-gamma gene revealed a monoclonal rearrangement in two of three patients. Follow-up data of two patients were available; one is alive without skin or systemic manifestations of the disease after 28 months, whereas the other is alive with persistent skin disease after 7 months. Our observation confirms that some patients present with a peculiar lymphoid proliferation of small-medium pleomorphic cytotoxic lymphocytes located on the ear, probably representing a phenotypic variant of the cutaneous small/medium pleomorphic T-cell lymphoma (CSMPTCL). These cases should not be misinterpreted as a high-grade cytotoxic lymphoma.

Cutaneous lymphomas showing prominent granulomatous component: clinicopathological features in a series of 16 cases

The presence of a prominent granulomatous tissue reaction in skin biopsies from primary cutaneous or systemic malignant lymphomas with secondary cutaneous involvement is a rare but well-known phenomenon. This paper aims to characterize and study a series of cutaneous lymphomas showing a prominent granulomatous component. The clinical, histopathological and evolutive features of granulomatous variants of mycosis fungoides (5 patients, 2 of them associating 'granulomatous slack skin' features), Sézary syndrome (1 patient), CD30(+) cutaneous T-cell lymphoma (2 patients), CD4(+) small/medium pleomorphic cutaneous T-cell lymphoma (1 patient), primary cutaneous B-cell lymphoma (3 patients) and peripheral T-cell lymphoma with secondary epithelioid granulomatous cutaneous involvement (4 patients) were reviewed. The observed features were clinically non-distinctive. Only those cases presenting with granulomatous slack skin features were clinically suspected (2 patients). Non-necrotizing granulomata (11 patients) and granuloma annulare-like (4 patients) were the most frequently observed histopathological patterns. In five cases, no diagnostic lymphomatous involvement was initially observed. From our series, no definite conclusions regarding prognosis could be established. The diagnosis of cutaneous lymphoma may be difficult when a prominent cutaneous granulomatous inflammatory infiltrate obscures the true neoplastic nature of the condition. However, the presence of concomitant lymphoid atypia may help to suspect the diagnosis. In doubtful cases, the clinical evolution and the demonstration of a monoclonal lymphoid B- or T-cell population may lead to a definite diagnosis.

Peripheral T-cell lymphomas unspecified presenting in the skin: analysis of prognostic factors in a group of 82 patients

AbstractIn the present study the clinicopathologic and immunophenotypic features of 82 patients with a CD30– peripheral T-cell lymphoma, unspecified, presenting in the skin were evaluated. The purpose of this study was to find out whether subdivision of these lymphomas on the basis of cell size, phenotype, or presentation with only skin lesions is clinically relevant. The study group included 46 primary cutaneous CD30– large cell lymphomas and 17 small/medium-sized T-cell lymphomas as well as 17 peripheral T-cell lymphomas with both skin and extracutaneous disease at the time of diagnosis. Patients with primary cutaneous small- or medium-sized T-cell lymphomas had a significantly better prognosis (5-year-overall survival, 45%) than patients with primary cutaneous CD30– large T-cell lymphomas (12%) and patients presenting with concurrent extracutaneous disease (12%). The favorable prognosis in this group with primary cutaneous small- or medium-sized T-cell lymphomas was particularly found in patients presenting with localized skin lesions expressing a CD3+CD4+CD8– phenotype. In the primary cutaneous T-cell lymphoma (CTCL) group and in the concurrent group, neither extent of skin lesions nor phenotype had any effect on survival. Our results indicate that peripheral T-cell lymphomas, unspecified, presenting in the skin have an unfavorable prognosis, irrespective of the presence or absence of extracutaneous disease at the time of diagnosis, cell size, and expression of a CD4+ or CD8+ phenotype. The only exception was a group of primary cutaneous small- or medium-sized pleomorphic CTCLs with a CD3+CD4+CD8– phenotype and presenting with localized skin lesions.

Killer cell immunoglobulin-like receptor expression delineates in situ Sézary syndrome lymphocytes.

p140/KIR3DL2 has been identified in malignant cell lines isolated from the skin and blood of patients with transformed mycosis fungoides (MF) and Sézary's syndrome (SS). For the first time, the expression of a cell membrane structure appeared to be able to distinguish CD4+ tumour lymphocytes from reactive lymphocytes in these small cutaneous T-cell lymphomas (CTCLs). This study has examined the in vivo expression of this receptor in various CTCL subtypes, which constituted a heterogeneous group. Tumour cells diffusely expressed KIR in SS, in lymphomatoid papulosis (LyP) and in CD4+CD30+ as well as CD8+ large cell pleomorphic CTCL. In contrast, the infiltrating lymphocytes did not express KIR in MF at the patch/plaque stage or in CD4+CD30- large cell pleomorphic CTCL, except for scattered small cells. One quarter of the transformed MF tested exhibited KIR+ tumour cells, suggesting heterogeneity in this subtype. KIR expression was also examined in inflammatory lesions characterized by a dense infiltrate of T cells, such as lupus erythematosus and lichen planus. Only scattered CD8+ cells in lichen planus expressed a significant amount of KIR3DL2. Taken together, these results show for the first time that KIR molecules are expressed in distinct subtypes of malignant CTCL. It is also shown for the first time that SS and MF, which are frequent variants of CTCL with similar histological features, can be distinguished by their KIR3DL2 expression analysis. The identification of this KIR also differentiates between lupus erythematosus and lichen planus, which are both diseases with dense benign lymphocytic infiltrates.

Localized cutaneous small to medium-sized pleomorphic T-cell lymphoma: A report of 3 cases stable for years

Small to medium-sized pleomorphic cutaneous T-cell lymphomas represent a provisional entity in the new European Organization for Research and Treatment of Cancer classification. We describe 3 patients with a localized and outstanding stable variant of this tumor. A median follow-up period of 50 months did not reveal any spread into regional lymph nodes or to distant sites in any patient. (J Am Acad Dermatol 2002;46:531-5.)

Expression of cancer/testis antigens in cutaneous T cell lymphomas

Cancer/testis-antigens (CTA), a novel and expanding family of immunogenic proteins detected by serological screening of recombinant cDNA expression libraries, encompass promising candidate targets for T-cell based immunotherapy. We screened kryo-preserved tissue of cutaneous T cell lymphoma (CTCL, n=36) such as mycosis fungoides (MF, n=17), pleomorphic cutaneous T-cell lymphoma (n=8) and Sezary's syndrome (SS, n= 11) as well as a non-malignant entity (small plaques parapsoriasis, SPP, n=5), for the expression of CTA by RT-PCR and Northern blot hybridization. From a panel of eleven CTA (MAGE-1, MAGE-C1, MAGE-3, BAGE, GAGE, SSX-1, SSX-2, SSX4, SCP-1, NY-ESO-1 and TS85) (HOM-Tes-85), mRNA expression could be detected for SCP-1 in 8/17 MF and 6/8 pleomorphic CTCL patients but was completely absent in small plaques parapsoriasis. SS patients had a more heterogeneous antigen expression pattern: Gage (1/11), MAGE-1 (3/11), MAGE-3 (6/11), MAGE-C1 (5/11), NY-ESO-1 (7/11) and TS85 (5/11), with expression of MAGE-3 confirmed by immunohistochemistry. CTA could provide defined targets for antigen-based vaccination in a high percentage of cases with CTCL. SCP-1 might serve as an additional diagnostic indicator in early and clinically indistinct lesions suspicious for cutaneous T-cell lymphoma. © 2001 Wiley-Liss, Inc.

Expression of cancer/testis antigens in cutaneous T cell lymphomas.

Cancer/testis-antigens (CTA), a novel and expanding family of immunogenic proteins detected by serological screening of recombinant cDNA expression libraries, encompass promising candidate targets for T-cell based immunotherapy. We screened kryo-preserved tissue of cutaneous T cell lymphoma (CTCL, n=36) such as mycosis fungoides (MF, n=17), pleomorphic cutaneous T-cell lymphoma (n=8) and Sezary's syndrome (SS, n= 11) as well as a non-malignant entity (small plaques parapsoriasis, SPP, n=5), for the expression of CTA by RT-PCR and Northern blot hybridization. From a panel of eleven CTA (MAGE-1, MAGE-C1, MAGE-3, BAGE, GAGE, SSX-1, SSX-2, SSX4, SCP-1, NY-ESO-1 and TS85) (HOM-Tes-85), mRNA expression could be detected for SCP-1 in 8/17 MF and 6/8 pleomorphic CTCL patients but was completely absent in small plaques parapsoriasis. SS patients had a more heterogeneous antigen expression pattern: Gage (1/11), MAGE-1 (3/11), MAGE-3 (6/11), MAGE-C1 (5/11), NY-ESO-1 (7/11) and TS85 (5/11), with expression of MAGE-3 confirmed by immunohistochemistry. CTA could provide defined targets for antigen-based vaccination in a high percentage of cases with CTCL. SCP-1 might serve as an additional diagnostic indicator in early and clinically indistinct lesions suspicious for cutaneous T-cell lymphoma.

Epidermal Interferon-γ Inducible Protein-10 (IP-10) and Monokine Induced by γ-Interferon (Mig) but not IL-8 mRNA Expression is Associated with Epidermotropism in Cutaneous T Cell Lymphomas

Epidermal infiltration by neoplastic CD4+ T cells is a characteristic histologic feature of early stage mycosis fungoides, the most common type of cutaneous T cell lymphoma (CTCL). The mechanisms involved in epidermotropism are unknown. It has been suggested that the CXC chemokines IL-8 and interferon-gamma inducible protein 10 (IP-10) may play a role, but evidence that these chemokines are produced within the epidermis in epidermotropic CTCL is lacking. In this study skin biopsies from 17 CTCL patients, including 12 mycosis fungoides, four pleomorphic CTCL, and one CD8+ CTCL, were investigated for epidermal IL-8 and IP-10 mRNA expression by RNA in situ hybridization. In addition, the expression of monokine induced by gamma-interferon (Mig) mRNA, a CXC chemokine closely related to IP-10, was studied as well. The expression of IL-8 receptors A and B (CXCR1 and CXCR2, respectively) was investigated by immunohistochemistry. The results were correlated with the number and phenotype of epidermotropic T cells. Epidermal expression of IP-10 and Mig mRNA was detected in 10 of 11 and seven of 11 epidermotropic CTCL, respectively, but not in five nonepidermotropic CTCL biopsies or normal human skin. Epidermal IP-10 and Mig mRNA expression correlated with epidermal infiltration of CD4+ T cells, but not of CD8+ T cells. IL-8 mRNA was demonstrated in the epidermis of only two of 15 CTCL biopsies, and was associated, in both cases, with accumulation of neutrophils. Consistently, immunostaining of the (intraepidermal) T cells with antibodies against CXCR1 and CXCR2 was not observed. In conclusion, the results of this study indicate that IP-10, and to a lesser extent Mig, but not IL-8 is involved in the preferential infiltration of neoplastic CD4+ T cells in CTCL.

Demonstration of Frequent Occurrence of Clonal T Cells in the Peripheral Blood of Patients With Primary Cutaneous T-Cell Lymphoma

AbstractClonal T cells have been demonstrated in skin lesions of all stages of cutaneous T-cell lymphomas (CTCLs). However, there are conflicting data regarding the CTCL stage at which dissemination of clonal cells into peripheral blood occurs. Although the multifocal occurrence of cutaneous CTCL lesions and T-cell recirculation suggest an early appearance of neoplastic cells in the blood, circulating clonal T cells have only been detected in advanced stages. We investigated their occurrence by a highly sensitive polymerase chain reaction (PCR) assay amplifying T-cell receptor γ rearrangements and subsequent heteroduplex temperature gradient gel electrophoresis (HD-TGGE) of the amplification products. Circulating clonal T cells were found in 26 of 45 patients with mycosis fungoides (MF ), six of seven with Sezary's syndrome (SS), 10 of 13 pleomorphic CTCLs, and three of four unclassified CTCLs. Corresponding skin specimens carried clonal T cells in 29 of 40 MF, three of four SS, 12 of 12 pleomorphic, and two of two unclassified CTCL patients. Except for the blood specimen of a psoriatic patient, all samples of 60 controls (psoriasis vulgaris, atopic dermatitis, and healthy volunteers) revealed polyclonal amplification products. In 30 of 32 CTCL patients carrying a clonal rearrangement in blood and skin, identity of both clones was indicated by HD-TGGE and confirmed by sequencing six of these cases. We found an unexpected high frequency of identical clonal T cells in peripheral blood and skin of CTCL patients, including early stages of MF. This supports the concept of an early systemic disease in CTCL and raises new questions concerning the pathogenesis.

Demonstration of Frequent Occurrence of Clonal T Cells in the Peripheral Blood of Patients With Primary Cutaneous T-Cell Lymphoma

Clonal T cells have been demonstrated in skin lesions of all stages of cutaneous T-cell lymphomas (CTCLs). However, there are conflicting data regarding the CTCL stage at which dissemination of clonal cells into peripheral blood occurs. Although the multifocal occurrence of cutaneous CTCL lesions and T-cell recirculation suggest an early appearance of neoplastic cells in the blood, circulating clonal T cells have only been detected in advanced stages. We investigated their occurrence by a highly sensitive polymerase chain reaction (PCR) assay amplifying T-cell receptor γ rearrangements and subsequent heteroduplex temperature gradient gel electrophoresis (HD-TGGE) of the amplification products. Circulating clonal T cells were found in 26 of 45 patients with mycosis fungoides (MF ), six of seven with Sezary's syndrome (SS), 10 of 13 pleomorphic CTCLs, and three of four unclassified CTCLs. Corresponding skin specimens carried clonal T cells in 29 of 40 MF, three of four SS, 12 of 12 pleomorphic, and two of two unclassified CTCL patients. Except for the blood specimen of a psoriatic patient, all samples of 60 controls (psoriasis vulgaris, atopic dermatitis, and healthy volunteers) revealed polyclonal amplification products. In 30 of 32 CTCL patients carrying a clonal rearrangement in blood and skin, identity of both clones was indicated by HD-TGGE and confirmed by sequencing six of these cases. We found an unexpected high frequency of identical clonal T cells in peripheral blood and skin of CTCL patients, including early stages of MF. This supports the concept of an early systemic disease in CTCL and raises new questions concerning the pathogenesis.