A supraclavicular ALK-positive anaplastic large-cell lymphoma initially misdiagnosed and yet successfully treated with wide excision and adjuvant chemotherapy : a case report

Background ALK-positive Anaplastic Large-Cell Lymphomas (ALCL) are chemo-sensitive cancers; combination of histologic and immunophenotypic or genetic studies remains the main strategy to prevent their unnecessary surgical excision as they can mimic soft-tissues sarcomas in histology. In sub-Saharan Africa, however, availability and affordability of immunophenotypic studies, especially extended immunohistochemistry (IHC) tests, constitute major limitations for accurate diagnoses. The case presented herein is an example of a heavy surgical management resulting from an initially inaccurate diagnosis, but eventually treated successfully. Case presentation A 15-year-old female patient presented with a 5-month history of a painless right supraclavicular mass. The initial biopsies had conflicting histology reports. In view of its rapid growth, it was first managed surgically, as a high-grade sarcoma stage T4N1M0: a wide “en bloc resection” with primary flap covering was done. Post-operative histology with an extended IHC from the widely resected tissue finally revealed an ALK-positive ALCL, which proved to be sensitive to chemotherapy. An adjuvant chemotherapy of six cycles of CHOP regimen followed with a good response; the patient became clinically stable, and all the investigations that were done, including a PET-CT scan, could not detect any residual active disease. She was still disease-free at 2 years after completion of chemotherapy. Conclusions Although cost-effective, combined histologic and immunophenotypic studies, especially extended IHC tests, can reduce the incidence of misdiagnosed large-cell lymphoma. As exemplified in this present case, obtaining appropriate and sufficient tissue from the tumor could possibly increase the chance of finding an accurate diagnosis

Genetic subgroups inform on pathobiology in adult and pediatric Burkitt lymphoma

Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult BL (aBL) and other adult lymphomas not fully explored. We sought to more thoroughly identify the somatic changes that underlie lymphomagenesis in aBL and any molecular features that associate with clinical disparities within and between pBL and aBL. Through comprehensive whole-genome sequencing of 230 BL and 295 diffuse large B-cell lymphoma (DLBCL) tumors, we identified additional significantly mutated genes, including more genetic features that associate with tumor Epstein-Barr virus status, and unraveled new distinct subgroupings within BL and DLBCL with 3 predominantly comprising BLs: DGG-BL (DDX3X, GNA13, and GNAI2), IC-BL (ID3 and CCND3), and Q53-BL (quiet TP53). Each BL subgroup is characterized by combinations of common driver and noncoding mutations caused by aberrant somatic hypermutation. The largest subgroups of BL cases, IC-BL and DGG-BL, are further characterized by distinct biological and gene expression differences. IC-BL and DGG-BL and their prototypical genetic features (ID3 and TP53) had significant associations with patient outcomes that were different among aBL and pBL cohorts. These findings highlight shared pathogenesis between aBL and pBL, and establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiologic, diagnostic, and therapeutic strategies