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 (PTCLs) 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 anaplastic lymphoma kinase (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 rearrangements involving the TP63 gene on 3q28 have been described in PTCL. In one series of 190 PTCLs of various subtypes, TP63 rearrangements 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 rearrangements. In 63.6% of cases with TP63 rearrangements, the translocation partner gene was identified to be TBL1XR1. Other partners also exist.
TP63 rearrangements have been shown to encode fusion transcripts that give rise to fusion proteins homologous to delta-N isoforms of wild-type p63. TP63 rearrangements have been associated with inferior overall survival in a study comparing them with PTCL without TP63 rearrangements overall, and in a study limited to systemic ALK-negative ALCL. The clinical significance of the presence of a variant (non-TBL1XR1) partner is not known. The clinical significance of the presence of a TP63 rearrangement in cutaneous T-cell lymphomas and lymphoproliferative disorders also has not been established. Immunohistochemical staining for p63 protein with the 4A4 clone can be seen in cases either with or without TP63 rearrangements. Immunostaining for p63 has not demonstrated prognostic significance in 2 studies, and should not be considered a surrogate for TP63 rearrangement testing.
TP63 rearrangements also have been identified in some B-cell non-Hodgkin lymphomas. Thus, the presence of a TP63 rearrangement 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.
For other FISH testing for T-cell disorders in tissues, see:
-60506 / Cutaneous Anaplastic Large Cell Lymphoma, 6p25.3 (IRF4) Rearrangement, FISH, Tissue
-89041 / T-Cell Lymphoma, FISH, Tissue
Providing potential prognostic information in patients with systemic anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, and possibly other peripheral T-cell lymphomas
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, and particularly among systemic anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCLs), rearrangements involving TP63 have been associated with aggressive clinical behavior. B-cell lymphomas also may demonstrate this rearrangement. Clinical and pathologic correlation is recommended.
A negative result suggests that a TP63 rearrangement is not present, but does not exclude the diagnosis of ALCL or other peripheral T-cell lymphoma. Among systemic ALK-negative ALCLs lacking TP63 rearrangements, interpretation in the context of FISH testing for rearrangements of the DUSP22/IRF4 locus on 6p25.3 may yield additional potential prognostic information.
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 US 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
1. 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
2. Parilla Castellar ER, Jaffe ES, Said JW, et al: ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. Blood 2014: Aug 28;124(9):1473-1480; Epub ahead of print (June 3)