ABSTRACT
An 18-year-old female presented with a 4.5 cm abdominal mass. Biopsy showed sheet-like growth of large tumor cells with round to oval nuclei, 1-2 nucleoli, and abundant cytoplasm. Immunohistochemistry showed strong, uniform CD30 staining and cytoplasmic ALK staining. B-cell markers (CD20, CD79a, PAX5, kappa/lambda) and T-cell markers (CD2, CD3, CD4, CD5, CD43, granzyme B, T-cell receptor-ß) were negative. Other hematopoietic markers (CD45, CD34, CD117, CD56, CD163, EBV) were negative, but CD138 was positive. Non-hematopoietic markers showed desmin positivity and negativity for S100, melan A, HBM45, PAX8, PAX2, WT1, MYO-D1, myogenin, pancytokeratin, and CAM5.2. Sequencing identified PRRC2B::ALK fusion. A diagnosis of epithelioid inflammatory myofibroblastic sarcoma (EIMS) was made. EIMS is a rare, aggressive form of inflammatory myofibroblastic tumor typically presenting in children and young adults. The tumor comprises large epithelioid cells that express ALK and often CD30. ALK-positive ALCL has a similar age range and also is a large-cell tumor expressing CD30 and ALK. Other ALK-positive neoplasms (e.g., carcinomas, ALK-positive large B-cell lymphoma, ALK-positive histiocytosis) typically lack CD30 and have distinct clinicopathologic features that aid diagnosis. Hematopathologists need to distinguish EIMS from ALK-positive ALCL, which frequently shows loss of pan-T-cell antigens. Careful morphologic evaluation for the hallmark cells of ALCL and comprehensive phenotyping are critical to avoid this diagnostic pitfall. If known, the ALK rearrangement partner gene may also provide diagnostic clues; for example PRRC2B::ALK and RANBP2::ALK occur in EIMS but not ALCL.
ABSTRACT
Anaplastic large cell lymphoma (ALCL), one of the most common T-cell lymphomas, shows unifying pathological features but is clinically and genetically heterogeneous. One genetic subgroup, characterized by recurrent DUSP22 rearrangements (R), has distinct morphologic, immunophenotypic, and molecular features and can be identified in routine pathology practice using a breakapart (BAP) fluorescence in situ hybridization (FISH) probe. However, some cases show equivocal BAP-FISH findings (BAP-FISHEQ) and the features of these cases are poorly understood. Here, we sought to characterize DUSP22 BAP-FISHEQ ALCLs further. First, we applied an immunohistochemistry (IHC) algorithm using TIA1, pSTAT3Y705, and LEF1, which can predict DUSP22-R with high accuracy. Among 37 BAP-FISHEQ ALCLs, 18 (49%) were IHC-algorithm positive (IHCPOS), 8 (21%) were IHC-algorithm negative (IHCNEG), and 11 (30%) were IHCEQ. In 32 BAP-FISHEQ cases, we also applied a dual-color, dual-fusion (D-FISH) probe for t(6;7)(p25.3;q32.3), which accounts for 45% of DUSP22-R ALCLs. Among BAP-FISHEQ cases, D-FISH was positive in 10/18 IHCPOS cases (56%), 0/9 IHCEQ cases (0%), and 0/5 IHCNEG cases (0%). Median survival in BAP-FISHEQ ALCLs was 105 months, intermediate between BAP-FISHPOS ALCLs (median survival not reached) and BAP-FISHNEG ALCLs (19 months). Thus, DUSP22 BAP-FISHEQ ALCLs are clinicopathologically heterogeneous, likely due to an admixture of cases with an unbalanced DUSP22-R and cases with focal deletions without rearrangement. For clinical reporting, we recommend that DUSP22 BAP-FISHEQ ALCLs be reported as equivocal, and not be grouped with BAP-FISHPOS ALCLs. Clinical adoption of an IHC algorithm, possibly supplemented by t(6; 7) D-FISH, could facilitate genetic subtyping in about two-thirds of BAP-FISHEQ ALCLs.