ALK-negative Anaplastic Large Cell Lymphoma

OVERVIEW

ALK-negative (ALK?) anaplastic large cell lymphoma (ALCL) is a CD30+ T-cell neoplasm that is morphologically similar to ALK-positive (ALK+) ALCL but lacks rearrangements of the ALK gene or expression of the ALK protein. Approximately 30% of ALK? ALCL have a DUSP22 rearrangement, and 8% have a rearrangement involving TP63. These rearrangements have not been reported in ALK+ ALCL. Generally ALK? ALCL has a poorer clinical outcome than ALK+ ALCL, with a 5-year overall survival rate of 42% as compared to 85%. However, ALK? ALCL with DUSP22 rearrangements have a favourable prognosis and are associated with a 5-year overall survival rate of 90%. Conversely, TP63 rearrangements are associated with a poor prognosis and a 5-year overall survival rate of 17%.

TEST REQUIREMENTS

  • Completed CGL Lymphoid Testing requisition form
  • FFPE Tumour specimen (see Specimen GuidelinesCytogenetics FISH FFPE test type)
    • An H&E stained slide with the tumour region circled, and the estimated % tumour content written in the Tumour Content field of the requisition.  NOTE: A minimum of 10% tumour and at least 200 nuclei is required.
    • Specimen block and/or at least one unstained slide for each probe requested.
    • See our FFPE Guidelines for additional details.

RESULT REPORTING

  • Specimens are reported as Positive for a DUSP22 or TP63 rearrangement, or Negative for a DUSP22 or TP63 rearrangement
  • Cases with DUSP22 rearrangements are associated with a favourable prognosis while cases with TP63 rearrangements are associated with a poor prognosis.

TURN-AROUND TIME

Results are reported within fourteen days from receipt of specimen and completed requisition form.  

METHOD

FISH analysis is performed on the provided FFPE specimen using the TP63 (3q28) dual-colour, break apart probe (Empire Genomics), and the tri-colour, break-apart probe (Cytocell) for DUSP22 (6p25.3) and centromere 6.

REFERENCES

  1. Parrilla Castellar et al. Blood (2014) PMID: 24894770