Multiple cutaneous lymphoproliferative disorders showing a retained tumor clone by <scp>T</scp>‐cell receptor gene rearrangement analysis: a case series of four patients and review of the literature

Stowman, Anne M.; Hsia, Ling-Lun Bob; Kanner, William A.; Mahadevan, Mani S.; Bullock, Grant C.; Patterson, James W.

doi:10.1111/ijd.12847

Cited by 15 publications

(7 citation statements)

References 20 publications

(56 reference statements)

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“…Importantly, with an exception of patient RG12, who during observation period developed S ezary syndrome (leukemic form of CTCL), none of the patients had any detectable leukemic blood involvement. The origin of the lymphoma TCR clonotypes in blood is unclear, though clinical observations of genetically related neoplasms in the same patient and multiple skin lesions often occurring simultaneously as an initial symptom (43)(44)(45)(46)(47) suggest that premalignant or malignant clones are circulating in peripheral blood and potentially seeding the skin, a situation that reminds the well-documented "clonal hematopoiesis" described for hematologic malignancies (48). The puzzling emergence and disappearance of T-cell clones during a course of mycosis fungoides may reflect clonal evolution of the tumor (49).…”

Section: Discussionmentioning

confidence: 99%

Clonotypic Diversity of the T-cell Receptor Corroborates the Immature Precursor Origin of Cutaneous T-cell Lymphoma

Hamrouni

Fogh

Zak

et al. 2019

Clinical Cancer Research

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Purpose: Mycosis fungoides is one of the most common types of extranodal T-cell lymphomas, considered to be caused by malignant transformation of the mature T cells residing in the skin. However, some clinical observations such as the multifocal distribution of mycosis fungoides lesions or patterns of relapse after radiotherapy are not readily explainable by the mature T-cell origin theory.Experimental Design: We have performed a detailed analysis of T-cell receptor (TCR) rearrangements in single malignant cells and in biopsies from mycosis fungoides tumors composed of >80% of malignant cells using next-generation sequencing (NGS) to pinpoint the relationship between neoplastic cells in mycosis fungoides. We have also aimed to detect malignant, circulating T-cell by whole blood TCR sequencing.Results: We found a substantial clonal heterogeneity in the mycosis fungoides samples with regards to TCR, and we demonstrated that lymphoma cells harboring identical TCRg sequences may harbor different TCRa and b sequences. Lack of absolute TCRa, -b, -g monoclonality was further confirmed by TCR amplification and sequencing from microdissected lymphoma cells. We have also found the TCR rearrangements characteristic for lymphoma cells in patients' peripheral blood despite the lack of leukemic blood involvement; however, the circulating TCRg clonotype did not always represent the dominant cutaneous clonotype.Conclusions: These findings can be explained by a model where malignant transformation takes place during early T-cell development giving rise to circulating premalignant clones, which home to the skin producing clinically apparent lesions of cutaneous lymphoma. Therapeutic strategies in T-cell lymphoma should therefore target those early lymphoma precursor cells.

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Section: Discussionmentioning

confidence: 99%

Clonotypic Diversity of the T-cell Receptor Corroborates the Immature Precursor Origin of Cutaneous T-cell Lymphoma

Hamrouni

Fogh

Zak

et al. 2019

Clinical Cancer Research

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“…The finding of a clonal TCR gene rearrangement may be helpful if present and can be seen in 60% to 100% of cases . Patients with multiple diagnoses of cutaneous T‐cell‐lymphoma including PC‐ALCL, MF and LyP can show shared clonal TCR gene rearrangements . Transient dominant T‐cell clones can also be seen in patients with recurrent disease …”

Section: Histology Immunohistochemistry and Clonalitymentioning

confidence: 99%

Primary cutaneous anaplastic large cell lymphoma

2017

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Primary cutaneous anaplastic large cell lymphoma (PC-ALCL) is a CD30+ lymphoproliferative disorder (LPD) of the skin with a relatively good prognosis in the absence of high-stage disease.CD30+ LPDs comprise approximately 25%-30% of primary cutaneous lymphomas and as a group represent the second most common clonal T-cell neoplasm of the skin behind mycosis fungoides. Diagnosis of PC-ALCL relies strongly on clinicopathologic correlation given the potential morphologic, clinical and molecular overlap with the other cutaneous CD30+ LPD, lymphomatoid papulosis, and more aggressive hematolymphoid neoplasms. K E Y W O R D SCD30+ lymphoproliferative disorder, primary cutaneous anaplastic large cell lymphoma

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“…This methodology provides a full spectrum of clones in the sample making it easy to follow a particular clone for identification of minimal residual disease, including malignant cells in lymph nodes missed by traditional histopathological analysis . The utility of TCR analysis as a stand‐alone biomarker of MF/SzS is limited as other T‐cell lymphoproliferative conditions and cutaneous lymphoid dyscrasias also demonstrate clonal rearrangement of TCR genes; however, TCR analysis has been successfully combined with other markers to improve identification of SzS …”

Section: Cell Surface Markersmentioning

confidence: 99%

The biomarker landscape in mycosis fungoides and Sézary syndrome

Dulmage

Geskin

Guitart

et al. 2017

Experimental Dermatology

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The practice of pre-emptive individualized medicine is predicated on the discovery, development and application of biomarkers in specific clinical settings. Mycosis fungoides and Sézary syndrome are the two most common type of cutaneous T-cell lymphoma, yet diagnosis, prognosis and disease monitoring remain a challenge. In this review, we discuss the current state of biomarker discovery in mycosis fungoides and Sézary syndrome, highlighting the most promising molecules in different compartments. Further, we emphasize the need for continued multicentre efforts to validate available and new biomarkers and to develop prospective combinatorial panels of already discovered molecules.

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Multiple cutaneous lymphoproliferative disorders showing a retained tumor clone by T‐cell receptor gene rearrangement analysis: a case series of four patients and review of the literature

Abstract: We report a series of four cases of individual patients with coexisting diagnoses of some combination of MF, LyP, and pcALCL, whose lesions presented in nontraditional sequence and demonstrated a retained clone by gene rearrangement analysis.

Cited by 15 publications

References 20 publications

Clonotypic Diversity of the T-cell Receptor Corroborates the Immature Precursor Origin of Cutaneous T-cell Lymphoma

Clonotypic Diversity of the T-cell Receptor Corroborates the Immature Precursor Origin of Cutaneous T-cell Lymphoma

Primary cutaneous anaplastic large cell lymphoma

The biomarker landscape in mycosis fungoides and Sézary syndrome

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