Primary cutaneous diffuse large B-cell lymphoma, leg type: A systematic review of morphological mimics and atypical anatomical presentations.

Abstract

e19078 Background: Primary Cutaneous Diffuse Large B-cell Lymphoma, Leg Type (PCDLBCL-LT) is characterized by an aggressive clinical course and a distinct molecular profile. While the Leg Type designation captures the most common clinical pattern, this creates a significant knowledge gap when the malignancy deviates from this expected pattern. When the disease manifests in atypical locations or adopts morphologies that overlap with common inflammatory conditions, the resulting diagnostic complexity can lead to a gap in timely intervention, which is critical given the subtype's poor ~50% five-year survival rate. With this we systematically analyze documented deviations from the classic clinical pattern of PCDLBCL-LT to better define the full clinical spectrum of the disease. Methods: A systematic review was conducted using the PubMed (MEDLINE) database to identify case reports related to Primary Cutaneous Diffuse Large B-cell Lymphoma, Leg Type (PCDLBCL-LT). The search strategy employed terms targeting atypical anatomical presentations and analogous words (n=70). Inclusion criteria focused on confirmed cases of PCDLBCL-LT (n=47). After exclusion of treatment-based cases, review papers, and non-English reports, the literature (n=22) revealed a consistent pattern of diagnostic camouflage across three domains: anatomical heterogeneity, morphological mimicry, and atypical systemic presentations. Results: Anatomical heterogeneity was noted in a significant subset of cases, with primary lesions appearing on the periorbital region, cheek, and trunk. Morphological mimicry created substantial overlap with benign or chronic conditions, such as verrucous stasis dermatitis, chronic venous ulcers, and erythema nodosa. Finally, atypical systemic presentations, including fever of unknown origin (FUO) and hematological precursors, highlight a gap where the disease may remain invisible or mimic systemic inflammatory syndromes before classic cutaneous tumors emerge. Conclusions: The clinical challenges associated with PCDLBCL-LT are largely driven by the tension between the disease’s name and its broad biological potential. This research is critical because it systematically organizes the scattered clinical knowledge on atypical PCDLBCL-LT, transforming rare extra-leg presentations and morphological mimics from diagnostic pitfalls into recognizable patterns for clinicians. The study empowers oncologists to facilitate appropriate and early diagnosis for patients who might otherwise face fatal delays. This early intervention is the only proven method to improve the poor survival rate associated with this aggressive subtype, as it ensures high-risk patients receive immediate systemic staging and treatment.