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ALCL, ALK-; TP63 rearranged

Author:  Naoki Oishi, MD PhD; Andrew L Feldman, MD, 11/03/2018
Category: Lymphoma: Mature T and NK cell lymphoproliferations > Mature T-cell Lymphomas > Anaplastic Large Cell Lymphoma, ALK negative
Published Date: 11/03/2018
     
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A 72 year-old male presented with left inguinal lymphadenopathy and lymph node biopsy was performed.  A diagnosis of ALK-negative anaplastic large cell lymphoma (ALCL) was made and the patient was treated with combination anthracycline-based chemotherapy.  His disease progressed with increasing adenopathy and liver, bone, and skin involvement.  He underwent autologous stem cell transplant but died shortly thereafter, 18 months after initial diagnosis.

 

This is a representative case of ALK-negative ALCL with TP63 gene rearrangement.  ALK-negative ALCL shows significant clinical and genetic heterogeneity.  TP63 rearrangements are seen in 5-8% of cases and have been associated with an aggressive clinical course and very poor prognosis.  TP63 rearrangements can be detected by fluorescence in situ hybridization (FISH).  Immunohistochemistry for p63 is positive but is not specific for the rearrangement.  TP63 rearrangements also have been reported in peripheral T-cell lymphoma, not otherwise specified; other T-cell neoplasms; and diffuse large B-cell lymphoma.

 

Learning points from the case

1.      Rearrangements of TP63 are seen in 5-8% of ALK-negative ALCLs.

2.      ALK-negative ALCL with TP63 rearrangement is associated with an aggressive clinical course and poor prognosis.

3.      Immunohistochemistry for p63 is sensitive but not specific for TP63 rearrangement; confirmation requires FISH or another genetic methodology.

Figure 1: H&E images of ALK-negative ALCL with TP63 rearrangement

The low power image (left) shows effacement of the lymph node architecture by a monotonous population of cells.  At higher power (right) the cells are seen to be large, with abundant cytoplasm, vesicular chromatin, and small nucleoli.  Tumor cells with horseshoe-shaped nuclei, designated “hallmark” cells, are occasionally identified (inset).  

ALCLTP63R
#00061995
 
Figure 2: Immunohistochemical images of ALCL with TP63 rearrangement

Tumor cells are negative for CD45, CD20, CD3, CD4, and CD8 (so-called “null-cell” phenotype).  They show strong, uniform staining for CD30 with a membranous and Golgi pattern of staining.  Immunohistochemistry for ALK, a surrogate for the presence of an ALK rearrangement, is negative.  Immunohistochemistry for p63 is strongly and diffusely positive, the typical staining pattern in ALCL with TP63 rearrangement.  However, some ALCLs without TP63 rearrangement also may be positive for p63 by immunohistochemistry, and thus FISH or another genetic methodology is required to confirm the presence of the rearrangement.

ALCLTP63R
#00061996
 
Figure 3: FISH in ALCL with TP63 rearrangement

Dual-fusion FISH for fusion of TBL1XR1 (green) and TP63 (red), both on chromosome 3q, demonstrates two abnormal fusion signals (arrows), confirming a TP63 rearrangement.  While TBL1XR1 is the most common fusion partner, other TP63 fusions have been reported and FISH using a breakapart probe for the TP63 locus is also useful in the evaluation of TP63 rearrangements. 

ALCLTP63R
#00061997