Lymphoid Aggregates as Positive Prognostic in Overall Survival for Melanoma

Because the prevalence and impact of immature precursor lymphoid structures known as lymphoid aggregates (LAs) remain unresolved in relation to metastatic cutaneous melanoma disease progression, researchers examined the characteristics and prognostic ability of LAs and tertiary lymphoid structures (TLSs) in histologic samples from patients with melanoma.

A research group led by Lilit Karapetyan, MD, assessed The Cancer Genomic Atlas-skin cutaneous melanoma digital slides and melanoma specimens from the University of Pittsburgh for the presence of LAs and TLSs with hematoxylin and eosin staining, multiple immunofluorescence (mIF), and transcriptomic analyses. Results were published in Journal of ImmunoTherapy of Cancer.

Cox proportional hazard regression models were used to assess the prognostic value associated with the presence of lymphoid structures in melanomas.

Samples (N=278) were analyzed and split into primary melanomas in skin (n=195) and metastatic melanomas involving skin/subcutaneous/soft tissue sites (n=83).

Seventy-two percent of tumor specimens contained histologically defined LAs located in the peritumoral (34%), intratumoral (5.6%), or stromal (6.1%), with the remaining samples (54.3%) exhibiting LAs in multiple locations.

Whereas LAs more commonly tended to form in primary melanoma samples, TLSs with germinal centers predominantly formed in peritumoral (45.2%) or stromal (35.5%) locations in metastatic melanomas (P=.02), with TLSs observed in 11% of all melanoma specimens evaluated.

mIF analyses revealed cellular heterogeneity of lymphoid structures, with CD20+ B cells present in nodule-shapes and stromal locations, where they exhibited a high degree of co-localization with CD4+ and CD8+ T cells.

A previously defined 12-chemokine gene expression score was significantly higher in samples with evidence of LAs versus none (P<.001). Samples without LAs/LTSs were enriched with pigmentation/neural network gene signatures. The presence of LAs was significantly associated with tumor-free regional lymph node status (P=.002).

In multivariable analysis, after adjusting for age, sex, sample type, and stage, the presence of LAs were associated with improved patient overall survival (hazard ratio, 0.52; 95% CI, 0.31-0.87; P=.01).