MUM1 expression in cutaneous CD30+ lymphoproliferative disorders: a valuable tool for the distinction between lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma

Kempf, Werner; Kutzner, Heinz; Cozzio, Antonio; Sander, Christian; Pfaltz, Monique C.; Müller, Beatrix

doi:10.1111/j.1365-2133.2008.08566.x

Cited by 40 publications

(20 citation statements)

References 40 publications

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“…Lymphomatoid papulosis is characterized by skin lesions that typically wax and wane; however, this history is not always available, depending on the practice setting. Immunohistochemical tests do not aid in this distinction: a single study suggested that IRF4 protein itself could be used to differentiate lymphomatoid papulosis from cutaneous anaplastic large cell lymphoma, 19 but there is no evidence for this in the present study or in several previous studies. 7, 13, 15, 20 Clusterin staining likewise has not been helpful.…”

Section: Discussioncontrasting

confidence: 81%

Specificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: a multicenter study of 204 skin biopsies

et al. 2011

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Current pathologic criteria cannot reliably distinguish cutaneous anaplastic large cell lymphoma from other CD30-positive T-cell lymphoproliferative disorders (lymphomatoid papulosis, systemic anaplastic large cell lymphoma with skin involvement, and transformed mycosis fungoides). We previously reported IRF4 (interferon regulatory factor-4) translocations in cutaneous anaplastic large cell lymphomas. Here, we investigated the clinical utility of detecting IRF4 translocations in skin biopsies. We performed fluorescence in situ hybridization for IRF4 in 204 biopsies involved by T-cell lymphoproliferative disorders from 182 patients at three institutions. Nine of forty-five (20%) cutaneous anaplastic large cell lymphomas and 1 of 32 (3%) cases of lymphomatoid papulosis with informative results demonstrated an IRF4 translocation. Remaining informative cases were negative for a translocation (7 systemic anaplastic large cell lymphomas; 44 cases of mycosis fungoides/Sézary syndrome (13 transformed); 24 peripheral T-cell lymphomas, not otherwise specified; 12 CD4-positive small/medium-sized pleomorphic T-cell lymphomas; 5 extranodal NK/T-cell lymphomas, nasal type; 4 gamma-delta T-cell lymphomas; and 5 other uncommon T-cell lymphoproliferative disorders). Among all cutaneous T-cell lymphoproliferative disorders, fluorescence in situ hybridization for IRF4 had a specificity and positive predictive value for cutaneous anaplastic large cell lymphoma of 99% and 90%, respectively (p=0.00002, Fisher’s exact test). Among anaplastic large cell lymphomas, lymphomatoid papulosis, and transformed mycosis fungoides, specificity and positive predictive value were 98% and 90%, respectively (p=0.005). Fluorescence in situ hybridization abnormalities other than translocations and IRF4 protein expression were seen in 13% and 65% of cases, respectively, but were non-specific with regard to T-cell lymphoproliferative disorder subtype. Our findings support the clinical utility of fluorescence in situ hybridization for IRF4 in the differential diagnosis of T-cell lymphoproliferative disorders in skin biopsies, with detection of a translocation favoring cutaneous anaplastic large cell lymphoma. Like all fluorescence in situ hybridization studies, IRF4 testing must be interpreted in the context of morphology, phenotype, and clinical features.

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Section: Discussioncontrasting

confidence: 81%

Specificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: a multicenter study of 204 skin biopsies

et al. 2011

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“…Since rare PTCL-Us and systemic ALK-negative ALCLs showed IRF4 translocations, the specificity of IRF4 translocations for C-ALCL in skin biopsies requires further study; identifying the IRF4 partner gene(s) may be helpful in this regard. Lymphomatoid papulosis and transformed MF also should be evaluated for IRF4 translocations, since these disorders express CD30 and MUM1/IRF443,45 but were not included in the present study. Finally, IRF4 translocations might be prognostic in C-ALCL, since lymph node involvement was more common in translocated C-ALCLs than in untranslocated C-ALCLs or in previous series 26…”

Section: Resultsmentioning

confidence: 99%

Recurrent translocations involving the IRF4 oncogene locus in peripheral T-cell lymphomas

et al. 2008

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Oncogenes involved in recurrent chromosomal translocations serve as diagnostic markers and therapeutic targets in hematopoietic tumors. In contrast to myeloid and B-cell neoplasms, translocations in peripheral T-cell lymphomas (PTCLs) are poorly understood. Here, we identified recurrent translocations involving the multiple myeloma oncogene-1/interferon regulatory factor-4 (IRF4) locus in PTCLs. IRF4 translocations exist in myeloma and some B-cell lymphomas, but have not been reported previously in PTCLs. We studied 169 PTCLs using fluorescence in situ hybridization and identified 12 cases with IRF4 translocations. Two cases with t(6;14)(p25;q11.2) had translocations between IRF4 and the T-cell receptor-alpha (TCRA) locus. Both were cytotoxic PTCLs, unspecified (PTCL-Us) involving bone marrow and skin. Eight of the remaining ten cases were cutaneous ALCLs without TCRA rearrangements (57% of cutaneous ALCLs tested). These findings identified IRF4 translocations as a novel recurrent genetic abnormality in PTCLs. Cytotoxic PTCL-Us involving bone marrow and skin and containing IRF4/TCRA translocations might represent a distinct clinicopathologic entity. Translocations involving IRF4 but not TCRA appear to occur predominantly in cutaneous ALCLs. Detecting these translocations may be useful in lymphoma diagnosis. Further, due to its involvement in translocations, MUM1/IRF4 protein may play an important biologic role in some PTCLs, and might represent a possible therapeutic target.

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“…It has been described in CD30 + T-cell lymphoproliferative disorders, including systemic anaplastic large cell lymphoma (ALCL) and LyP. 29 Although some report utility in this stain for differentiating between LyP and primary cutaneous ALCL, 30 other studies have reported that it does not distinguish between the two. 31,32 The presence of CD8 + CD30 + LyP and ALCL in 7 of 7 cases suggest that it may represent an adjunctive marker for CD8 + lymphoproliferative disease.…”

Section: Immunohistochemical and Molecular Featuresmentioning

confidence: 97%

Characterization of Primary Cutaneous CD8+/CD30+ Lymphoproliferative Disorders

Martires

Abdulla

et al. 2015

The American Journal of Dermatopathology

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CD30 primary cutaneous lymphoproliferative diseases include both lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (PCALCL). The neoplastic cell of most primary CD30 lymphoproliferative disorders is CD4 positive. The terminology LyP "type D" has been used to describe a growing number of cases of LyP with a predominantly CD8 infiltrate. PCALCL with a CD8 phenotype has also been described, which presents a particularly difficult diagnostic and management challenge, given the difficulty in distinguishing it histologically from other cytotoxic lymphomas such as primary cutaneous aggressive epidermotropic CD8 cytotoxic T-cell lymphoma and CD8 gamma/delta and natural killer/T-cell lymphoma. We report 7 additional cases of these rare cutaneous CD8/CD30 lymphoproliferative disorders. We also present a unique case of CD8/CD30 LyP with histologic similarities to LyP type B. In all 7 of our cases of CD8 LyP and CD8 anaplastic large cell lymphoma, we found focal to diffuse MUM-1 positivity. We propose that MUM-1 may represent an adjunctive marker for CD8 lymphoproliferative disease. Finally, we review the current literature on cases of CD8 LyP and PCALCL. For the 106 cases examined, we found similar clinical and histologic features to those reported for traditional CD4CD30 LyP and PCALCL.

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MUM1 expression in cutaneous CD30+ lymphoproliferative disorders: a valuable tool for the distinction between lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma

Abstract: MUM1 expression is a valuable tool for the distinction of LyP and ALCL and thus represents a novel adjunctive diagnostic marker in CD30+ lymphoproliferative disorders.

Cited by 40 publications

References 40 publications

Specificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: a multicenter study of 204 skin biopsies

Specificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: a multicenter study of 204 skin biopsies

Recurrent translocations involving the IRF4 oncogene locus in peripheral T-cell lymphomas

Characterization of Primary Cutaneous CD8+/CD30+ Lymphoproliferative Disorders

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