Mycosis Fungoides and Sézary Syndrome. These tumors of neoplastic CD4+ T cells home to the skin; as a result, they often are referred to as cutaneous T cell lymphoma. Mycosis fungoides usually manifests as a nonspecific erythrodermic rash that progresses with time to a plaque phase and then to a tumor phase. Histologically, neoplastic T cells, often with a cerebriform appearance produced by marked infolding of the nuclear membranes, infiltrate the epidermis and upper dermis. With disease progression, both nodal and visceral dissemination appear. Sézary syndrome is a clinical variant characterized by (1) a generalized exfoliative erythroderma and (2) tumor cells (Sézary cells) in the peripheral blood. Circulating tumor cells also are present in as many as 25% of cases of plaqueor tumor-phase mycosis fungoides. Patients diagnosed with early-phase mycosis fungoides often survive for many years, whereas patients with tumor-phase disease, visceral disease, or Sézary syndrome survive on average for 1 to 3 years.
Adult T Cell Leukemia/Lymphoma. This neoplasm of CD4+ T cells is caused by a retrovirus, human T cell leukemia virus type 1 (HTLV-1). HTLV-1 infection is endemic in southern Japan, the Caribbean basin, and West Africa, and occurs sporadically elsewhere, including in the southeastern United States. The pathogenesis of this tumor is discussed in Chapter 6. In addition to lymphoid malignancies, HTLV-1 infection also can cause tropical spastic paraparesis, a progressive demyelinating disease affecting the central nervous system and the spinal cord.
Adult T cell leukemia/lymphoma commonly is associated with skin lesions, lymphadenopathy, hepatosplenomegaly, hypercalcemia, and variable lymphocytosis. In addition to CD4, the leukemic cells express high levels of CD25, the IL-2 receptor α chain. In most cases the tumor is very aggressive and responds poorly to treatment. The median survival time is about 8 months.
Peripheral T Cell Lymphoma. This heterogeneous group of tumors makes up about 10% of adult NHLs. Although several rare distinctive subtypes fall under this heading, most tumors in this group are unclassifiable. In general, these are aggressive tumors that respond poorly to therapy. Moreover, because these are tumors of functional T cells, patients often suffer from symptoms related to tumor-derived inflammatory products, even when the tumor burden is relatively low.
Before ending our review of lymphoid neoplasms, it is worthwhile pausing to summarize the manner in which common driver mutations in specific entities produce changes in cellular behavior that exemplify particular hallmarks of cancer (
Fig. 12.25 ). Such alterations not only highlight important pathogenic principles, but are increasingly the targets of effective therapies, such as antibodies that block PD-1 (Hodgkin lymphoma) and drugs that antagonize BCL2 (follicular lymphoma and other B cell tumors).
Highlyaggressivetumorsthatmanifestwithsignsandsymptomsofbonemarrowfailure,orasrapidlygrowingmasses
Tumorcellscontaingeneticlesionsthatblockdifferentiation,leadingtotheaccumulationofimmature,nonfunctionalblasts
Indolentcourse,commonlyassociatedwithimmuneabnormalities,includinganincreasedsusceptibilitytoinfectionandautoimmunedisorders http://ebooksmedicine.net
Mantle cell lymphoma Many examples Cyclin D1 translocations (e.g., loss of CDKN2A in ALL)
Germinal center B cell lymphomas Class-switching, somatic hypermutation
Relatively unimportant due to intrinsic ability of lymphoid cells to invade and circulate