Lynn D. Wilson MD, MPH, FASTRO

Professor of Therapeutic Radiology and of Dermatology; Vice Chairman, Therapeutic Radiology; Clinical Director, Therapeutic Radiology; Clinical Program Leader, Therapeutic Radiology, Yale Cancer Center

Research Interests

Cutaneous Lymphoma; Lung Cancer; Total Skin Electron Beam Therapy


Research Summary

The T-cell receptor is encoded by a gamma-delta and an alpha-beta gene complex. As the T-cell matures, the first rearrangement occurs in the gamma-delta gene complex. If this initial rearrangement is successful in producing a non-host reactive protein, such cells develop into mature CD3+, gamma-delta+, CD4-, CD8-, lymphocytes. Some of these cells migrate to the skin and others circulate within the peripheral blood. When this primary rearrangement is unproductive, the alpha-beta T-cell receptor gene complexes then undergo rearrangement, to produce CD3+, alpha-beta+, CD4+, CD8+ cells. Such cells circulate in the blood in a ratio of approximately 2-3:1, and constitute approximately 70% of all lymphocytes. After exit from the thymus to the circulation, T-cells undergo further maturation; skin is one site where maturation occurs in the presence of a variety of cytokines and skin-specific cell adhesion molecules. Not all T-cells migrate to and differentiate in the skin, as only those with homing receptors for cutaneous vascular adressins will do so.

Several theories have been proposed to explain the pathogenesis of the disorder known as cutaneous T-cell lymphoma (CTCL), or mycosis fungoides (MF). The first of two leading hypothesis proposes that MF is a disorder of malignant helper CD4+ T-cells, with a single neoplastic clone present at the very start of the disease process. The second hypothesis postulates a two stage process: a phase of chronic antigenic stimulation which results in a benign polyclonal proliferation of T lymphocytes, in which one clone is mutated (by polymerase errors, exposure to endogenous oxygenating agents, or an exogenous mutagen) and dominates the T-cell infiltrate. Cells are stimulated to develop "malignant potential," and to proliferate freely in the skin subsequently producing lesions clinically consistent with CTCL.

Weiss et. al. clearly demonstrated that cutaneous T-cell lymphoma (Mycosis Fungoides) is a disorder resulting from an expansion of a neoplastic clone of T-cells with characteristic rearrangements in T-cell receptor genes. Therefore, it should be possible to determine whether a "clinical recurrence" derives from the original neoplastic clone or represents a different neoplastic clonal T-cell expansion (which would reveal a second primary) by comparing the T-cell receptors (and/or the genes which have been rearranged to produce the receptor) in the primary lesion and the recurrence. This is an example of one area of research which our group has pursued.

Girardi M, Heald P.W., Wilson L.D.: The Pathogenesis of Mycosis Fungoides. New England Journal of Medicine 350:1978, 2004)

Extensive Research Description

The T-cell receptor is encoded by a gamma-delta and an alpha-beta gene complex. As the T-cell matures, the first rearrangement occurs in the gamma-delta gene complex. If this initial rearrangement is successful in producing a non-host reactive protein, such cells develop into mature CD3+, gamma-delta+, CD4-, CD8-, lymphocytes. Some of these cells migrate to the skin and others circulate within the peripheral blood. When this primary rearrangement is unproductive, the alpha-beta T-cell receptor gene complexes then undergo rearrangement, to produce CD3+, alpha-beta+, CD4+, CD8+ cells. Such cells circulate in the blood in a ratio of approximately 2-3:1, and constitute approximately 70% of all lymphocytes. After exit from the thymus to the circulation, T-cells undergo further maturation; skin is one site where maturation occurs in the presence of a variety of cytokines and skin-specific cell adhesion molecules. Not all T-cells migrate to and differentiate in the skin, as only those with homing receptors for cutaneous vascular adressins will do so.

Several theories have been proposed to explain the pathogenesis of the disorder known as cutaneous T-cell lymphoma (CTCL), or mycosis fungoides (MF). The first of two leading hypothesis proposes that MF is a disorder of malignant helper CD4+ T-cells, with a single neoplastic clone present at the very start of the disease process. The second hypothesis postulates a two stage process: a phase of chronic antigenic stimulation which results in a benign polyclonal proliferation of T lymphocytes, in which one clone is mutated (by polymerase errors, exposure to endogenous oxygenating agents, or an exogenous mutagen) and dominates the T-cell infiltrate. Cells are stimulated to develop "malignant potential," and to proliferate freely in the skin subsequently producing lesions clinically consistent with CTCL.

Weiss et. al. clearly demonstrated that cutaneous T-cell lymphoma (Mycosis Fungoides) is a disorder resulting from an expansion of a neoplastic clone of T-cells with characteristic rearrangements in T-cell receptor genes. Therefore, it should be possible to determine whether a "clinical recurrence" derives from the original neoplastic clone or represents a different neoplastic clonal T-cell expansion (which would reveal a second primary) by comparing the T-cell receptors (and/or the genes which have been rearranged to produce the receptor) in the primary lesion and the recurrence. This is an example of one area of research which our group has pursued.

Girardi M, Heald P.W., Wilson L.D.: The Pathogenesis of Mycosis Fungoides. New England Journal of Medicine 350:1978, 2004)


Selected Publications

  • Lloyd S, Chen Z, Foss FM, Girardi M, Wilson LD. Acute toxicity and risk of infection during total skin electron beam therapy for mycosis fungoides. J Am Acad Dermatol. 2013 Jul 9. [Epub ahead of print]
  • Wilson L.D., Detterbeck F.C., Yahalom J.: Clinical Practice: Superior vena cava syndrome with malignant causes. The New England Journal of Medicine 356:1862-1869, 2007.
  • Girardi M., Heald P.W., Wilson L.D.: Medical Progress: Pathogenesis of Mycosis Fungoides. The New England Journal of Medicine 350:1978-1988, 2004.
  • Lally B.E., Zelterman D., Colasanto J.M., Haffty B.G., Detterbeck F.C., Wilson L.D.: The impact of post operative radiotherapy for patients with stage II or III non-small cell lung cancer utilizing the Surveillance, Epidemiology and End Results Database. Journal of Clinical Oncology 24;2998-3006, 2006.
  • Yu J.B., Blitzblau R.C., Decker R.H., Housman D.M., and Wilson L.D.: Analysis of primaryCD30+ cutaneous lymphoproliferative disease and survival from the Surveillance, Epidemiology, and End Results (SEER) Database. Journal of Clinical Oncology 26;1483-1488, 2007.
  • Smith B.D., Smith G.L., Cooper D.L., Wilson L.D.: The cutaneous B-cell lymphoma prognostic index: A novel prognostic index derived from a population-based registry. Journal of Clinical Oncology 23;3390-3395, 2005.
  • Yu JB, Blitzblau RC, Patel SC, Decker RH, Wilson LD. Surveillance, Epidemiology, and End Results (SEER) Database Analysis of Microcystic Adnexal Carcinoma (Sclerosing Sweat Duct Carcinoma) of the Skin. Am J Clin Oncol. 2009 Aug 11.
  • Yu JB, Gross CP, Wilson LD, Smith BD. NCI SEER public-use data: applications and limitations in oncology research. Oncology (Williston Park). 2009 Mar23(3):288-95.
  • Lloyd S, Yu JB, Ross DA, Wilson LD, Decker RH. A Prognostic Index for Predicting Lymph Node Metastasis in Minor Salivary Gland Cancer. Int J Radiat Oncol Biol Phys. 2009 Apr 20. [Epub ahead of print]

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