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)
- Wang EH, Corso CD, Rutter CE, Park HS, Chen AB, Kim AW, Wilson LD, Decker RH, Yu JB: Postoperative Radiation Therapy Is Associated With Improved Overall Survival in Incompletely Resected Stage II and III Non-Small-Cell Lung Cancer. J Clin Oncol. 2015 Jun 22. pii: JCO.2015.61.1517
- Nath SK, Yu JB, Wilson LD. Poorer prognosis of African-American patients with mycosis fungoides: an analysis of the SEER dataset, 1988 to 2008. Clin Lymphoma Myeloma Leuk 14:419-23, 2014
- Lloyd S, Chen Z, Foss FM, Girardi M, Wilson LD. Acute toxicity and risk of infection during total skin electron beam therapy for mycosis fungicides. J Am Acad Dermatol 69:537-43, 2013.
- Wilson LD, Hinds GA, Yu JB: Age, race, sex, stage, and incidence of cutaneous lymphoma. Clin Lymphoma Myeloma Leuk 12:291-6, 2012.
- Yu JB, Blitzblau RC, Decker RH, Housman DM, Wilson LD. Analysis of primary CD30+ cutaneous lymphoproliferative disease and survival from the Surveillance, Epidemiology, and End Results database. J Clin Oncol 26:1483-8, 2008.
- Wilson LD, Detterbeck FC, Yahalom J: Clinical Practice: Superior vena cava syndrome with malignant causes. The New England Journal of Medicine 356:1862-1869, 2007.
- Lally BE, Zelterman D, Colasanto JM, Haffty BG, Detterbeck FC, Wilson LD: 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. J Clin Oncol 24:2998-3006, 2006.
- Smith BD, Smith GL, Cooper DL, Wilson LD: The cutaneous B-cell lymphoma prognostic index: A novel prognostic index derived from a population-based registry. J Clin Oncol 23:3390-3395, 2005.
- Smith BD, Glusac EJ, McNiff JM, Smith GL, Heald PW, Cooper DL, Wilson LD. Primary cutaneous B-cell lymphoma treated with radiotherapy: a comparison of the European Organization for Research and Treatment of Cancer and the WHO classification systems. J Clin Oncol 22:634-9, 2004.
- Girardi M, Heald PW, Wilson LD: Medical Progress: Pathogenesis of Mycosis Fungoides. The New England Journal of Medicine 350:1978-1988, 2004.