Peripheral T-Cell Lymphoma (PTCL), TP63 (3q28) Rearrangement, FISH, Tissue
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Peripheral T-cell lymphomas (PTCL) are malignant neoplasms of mature T lymphocyte origin that account for 10% to 15% of all non-Hodgkin lymphomas. Most subtypes have a slight male predominance and occur in older individuals (>50 years). Some subtypes, particularly ALK-positive anaplastic large cell lymphoma (ALCL), are seen in younger patients. Over 15 subtypes of PTCL are recognized in the World Health Organization classification system. These types differ in their clinical presentation, morphologic appearance, immunophenotype, genetics, and, in some cases, prognostic and therapeutic implications. The relative distribution of subtypes varies geographically. In the United States, the most common types of systemic PTCL are PTCL, not otherwise specified (NOS); angioimmunoblastic T-cell lymphoma (AITL); and ALCL (both ALK-positive and ALK-negative types).
In diagnostic practice, PTCL must be distinguished from reactive T-cell proliferations as well as from hematopoietic neoplasms of non-T-cell lineage and nonhematopoietic tumors. In addition, PTCL must be subclassified to the extent possible. The designation PTCL, NOS, is reserved for PTCL that do not meet criteria for inclusion in one of the other, more specific categories, which occurs in a significant fraction of PTCL.
Recurrent translocations involving the TP63 gene on 3q28 have been described in PTCL. In one series of 190 PTCL of various subtypes, TP63 translocations were seen in 5.8%. However, these were not distributed equally among PTCL subtypes, occurring in 9.4% of PTCL, NOS; 12.5% of ALK-negative ALCL; and 10.5% of primary cutaneous ALCL. No cases of ALK-positive ALCL, AITL, or other PTCL subtypes were found to have TP63 translocations. In 63.6% of cases with TP63 translocations, the translocation partner gene was identified to be TBL1XR1. Other partners also exist.
TP63 translocations have been shown to encode fusion transcripts that give rise to fusion proteins homologous to delta-N isoforms of wild-type p63. In 1 study, the presence of TP63 translocations among PTCL was associated with inferior overall survival compared with PTCL without TP63 translocations (median survival: 17.9 months vs. 33.4 months, respectively; p<0.05). The clinical significance of the presence of a variant (non-TBL1XR1) partner is not known. Immunohistochemical staining for p63 protein with the 4A4 clone can be seen in cases without TP63 translocations, did not demonstrate prognostic significance in 1 study, and should not be considered a surrogate for TP63 translocation testing.
TP63 translocations also have been identified in some B-cell non-Hodgkin lymphomas. Thus, the presence of a TP63 translocation should not be considered diagnostic for PTCL, and this result should be interpreted in the context of other pathologic, immunophenotypic, genetic, and clinical data. The clinical utility of TP63 testing in B-cell lymphomas has not been established.
Supporting the diagnosis of peripheral T-cell lymphoma when coordinated with a consultation by anatomic pathology.
A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal cutoff of the TP63 probe sets.
Among peripheral T-cell lymphomas, translocations involving TP63 have been associated with aggressive clinical behavior. B-cell lymphomas also may demonstrate this finding. Clinical and pathologic correlation is recommended.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is not approved by the U.S. Food and Drug Administration and it is best used as an adjunct to existing clinical and pathologic information.
Fixatives other than formalin (eg Prefer, Bouin) may not be successful for FISH assays.
Although FISH testing will not be rejected due to nonformalin fixation, results may be compromised.
Paraffin-embedded tissues that have been decalcified are generally unsuccessful for FISH analysis. The pathologist reviewing the hematoxylin and eosin-stained slide may find it necessary to cancel testing.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretative report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
Vasmatzis G, Johnson SH, Knudson RA, et al: Genome-wide analysis reveals recurrent structural abnormalities of TP63 and other p53-related genes in peripheral T-cell lymphomas. Blood 2012 Sep 13;120(11):2280-2289