Rubinstein-Taybi syndrome (RSTS) is a rare genetic disorder primarily attributed to mutations in the CREBBP gene, which plays a pivotal role in the syndrome's pathogenesis. Notably, individuals with RSTS are predisposed to malignancies due to the same genetic aberration. In this exceptional case, we have delved into the intricate relationship between RSTS and its association with a high-risk variant of Diffuse Large B-Cell Lymphoma (DLBCL), further shedding light on targeted treatment possibilities. It is known that CREBBP encoded transcriptional co-regulatory protein interacts with other transcription factors and controls gene expression. Alteration in the CREBBP gene as seen in this case can disrupt its function and expression.
We are reporting the patient's excellent response to treatment despite classic unfavorable prognostic markers like high Ki-67, high LDH, and unfavorable genomic aberrations like the presence of CREBBP, BRAF K601N, CREBBP R1319, FOX01 MV, and TNFRSF14 alterations. The observed complete remission on PET scans following EPOCH chemotherapy encourages the consideration for escalated treatment strategies such as R-EPOCH in cases involving CREBBP gene mutations. Moreover, recognizing the presence of both somatic and germline CREBBP mutations adds weight to the potential pathogenic role of these alterations in the context of this rare syndrome.
Intriguingly, the findings from this case have broader implications for other sporadic diffuse large B-cell lymphomas. For instance, the presence of CREBBP or BRAFK601N gene alterations in conjunction with the need for intensified therapies like R-EPOCH suggests a shared rationale for escalated treatment regimens across certain molecular subsets. This implies that a more personalized therapeutic approach, tailored to the genetic landscape of the malignancy, might be a pivotal factor in achieving comprehensive remission.
It is imperative to acknowledge the limitations of this study. One notable limitation pertains to the initial treatment approach of R-EPOCH rather than R-CHOP, which is considered standard of care. However, this choice was made initially by the patient's high Ki-67 and suspicion for Double HIT lymphoma. Whether the patient would have gotten a similar complete response if R-CHOP chemo was initiated is unknown.
In conclusion, this case not only contributes to the understanding of the intricate relationship between Rubinstein-Taybi syndrome and its association with high-risk DLBCL but also acts as a prototype for exploring innovative treatment approaches. The distinct response observed in this case warrants further investigation into the potential benefits of intensified therapies in diffuse large B-cell lymphoma patients harboring specific genetic alterations like CREBBP and BRAF. Ultimately, this study encourages continued research into the complex interplay between genetic mutations, syndrome-related predispositions, and effective therapeutic strategies for patients with rare syndromes and associated malignancies.