Intralymphatic Spread is a Rare Finding Associated With Poor Prognosis in Diffuse Large B-Cell Lymphoma With Extranodal Involvements

Abstract

Intralymphatic spread is common in solid cancers, but has been rarely studied in lymphomas. Review of 635 extranodal specimens from 475 diffuse large B-cell lymphoma (DLBCL) patients revealed intralymphatic spread in 10 surgical resection specimens from 10 patients including 9 de novo DLBCLs and 1 Richter transformation. The prevalence in de novo DLBCL with extranodal involvements was 1.65%. The most common involved site of intralymphatic spread was the gastrointestinal tract, followed by the female genital tract and breasts. Lymphatic vessels, lined by D2-40-positive endothelial cells, were expanded by lymphoma cells, reminiscent of intravascular lymphoma or tumor emboli. None of the involved lymphatic vessels were located in the mucosa. Patients with intralymphatic spread had a trend of lower overall response rate and a trend of higher progressive disease than those without intralymphatic spread. Compared with patients without intralymphatic spread, those patients with intralymphatic spread had a shorter median overall survival (14.3 vs. 96.2 mo; P=0.004) and a shorter median progression-free survival (11.2 vs. 64.2 mo; P=0.01), respectively. Multivariate analyses showed that intralymphatic spread was an independent poor prognostic factor for overall survival (hazard ratio, 3.029; 95% confidence interval, 1.315-6.978; P=0.009), irrespective of the National Comprehensive Cancer Network-International Prognostic Index, B symptoms, and serum albumin levels. Among patients who underwent surgical resection, intralymphatic spread was still an independent prognostic factor. In conclusion, our study demonstrated extranodal intralymphatic spread in DLBCL. Inspiringly, this rare morphologic finding may serve as a new negative prognostic indicator in DLBCL with extranodal involvements.

Mucosal intralymphatic spread in a relapsed diffuse large B cell lymphoma

“…Regarding morphology, we previously observed that intralymphatic spread is a rare finding and is associated with poor prognosis in DLBCL [6]. In extranodal organs (for example, the gastrointestinal tract, breast, and female genital tract), we observed peritumoral lymphatic vessels were distended with lymphoma cells, reminiscent of tumor emboli of solid cancers [6]. In the previous case series, we found intralymphatic spread in various histological structures, but mucosa was generally spared.…”

“…Fluorescence in situ hybridization (FISH) has demonstrated that MYC rearrangement correlates with poor prognosis [5]. Regarding morphology, we previously observed that intralymphatic spread is a rare finding and is associated with poor prognosis in DLBCL [6]. In extranodal organs (for example, the gastrointestinal tract, breast, and female genital tract), we observed peritumoral lymphatic vessels were distended with lymphoma cells, reminiscent of tumor emboli of solid cancers [6].…”

“…In the previous case series, we found intralymphatic spread in various histological structures, but mucosa was generally spared. Correspondingly, the involved lymphatic vessels were observed exclusively in surgical resection specimens and not in any mucosal biopsy [6].…”

Calcium Independent Effect of Orai1 and STIM1 in Non-Hodgkin B Cell Lymphoma Dissemination

“…Although surprising, these results could account for specific properties of extra-nodal DLBCL which exhibit an initial confinement to a single anatomical site and less propensity to disseminate [ 42 ]. Interestingly, a recent study has shown that, in contrast to solid cancers, intra-lymphatic spread of extra-nodal DLBCL lymphoma cells was a rare event [ 43 ] which might explain the lesser propensity of these tumors to disseminate. Thus, the down-expression of STIM1 or Orai1 could impair cell migration and/or intralymphatic spread, promoting homing of tumor B cells to extra-nodal sites.…”

Diffuse Large B-Cell Lymphoma With Striking Intrasinusoidal Pseudoglandular Growth Pattern as a Diagnostic Dilemma Mimicking Metastatic Poorly Differentiated Pancreatic Adenocarcinoma in an Intraabdominal Lymph Node

“…3,4 This striking intrasinusoidal pattern in a lymph node with DLBCL is highly unusual, 5 although sinusoidal involvement at extranodal sites has been reported. 6 On imaging, lymphomas may present in a pattern resembling a widely metastatic pancreatic carcinoma, 7 making the clinical differentiation difficult. Sinusoidal involvement by lymphoma cells as illustrated by this case can be a diagnostic pitfall, particularly in this setting.…”