Descriptive Analysis and Therapeutic Evaluation of Extranodal Diffuse Large B-Cell Lymphoma: An Eight-Year Monocentric Study

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of nonHodgkin lymphoma (NHL), representing 30–40% of adult cases. Extranodal involvement,
although less frequent, has significant implications for prognosis and management.
Objective: To describe the distribution, clinical features, treatment modalities, and
outcomes of extranodal DLBCL in a monocentric cohort.
Methods: A retrospective descriptive study was conducted over 8 years (2010–2017),
including 66 patients diagnosed with primary extranodal DLBCL. Sites included
gastrointestinal (33.5%), ENT (21.5%), bone (15%), endocrine (9%), cerebral (9%), and
others (12%). Diagnosis was based on histopathology and immunohistochemistry. All
patients underwent staging with Ann Arbor (or Musshoff for GI cases). Treatment involved
R-CHOP-based regimens, with CNS prophylaxis, radiotherapy, or surgery when indicated.
Results: Median age was 54 years (range: 20–84), with a male predominance (sex ratio 2:1).
Median diagnostic delay was 5 months. B symptoms were present in 26%. According to Ann
Arbor staging: I (64%), II (12%), III (4%), IV (20%). Treatment response in 48 evaluable
patients: CR (82%), PR (12%), failure (6%). Median follow-up: 23 months.
Conclusion: Extranodal DLBCL demonstrates significant heterogeneity in presentation and
outcomes. The gastrointestinal tract was the most common site. R-CHOP remains the gold
standard, but early diagnosis and site-specific management are critical. CNS prophylaxis
should be systematically considered for high-risk localizations.

1. Descriptive Analysis and Therapeutic
Evaluation of Extranodal Diffuse Large
B-Cell Lymphoma: An Eight-Year
Monocentric Study
M. Sid Ahmed, R. Abadi, L. Sahraoui, M. Djilali, Y. Ghassoul, S Baghdad, S.E. Belakehal
Department of Hematology, Constantine, Algeria
Department of Hematology, Central Hospital. Algiers, Algeria
Department of Hematology, Oran, Algeria
Abstract
Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-
Hodgkin lymphoma (NHL), representing 30–40% of adult cases. Extranodal involvement,
although less frequent, has significant implications for prognosis and management.
Objective: To describe the distribution, clinical features, treatment modalities, and
outcomes of extranodal DLBCL in a monocentric cohort.
Methods: A retrospective descriptive study was conducted over 8 years (2010–2017),
including 66 patients diagnosed with primary extranodal DLBCL. Sites included
gastrointestinal (33.5%), ENT (21.5%), bone (15%), endocrine (9%), cerebral (9%), and
others (12%). Diagnosis was based on histopathology and immunohistochemistry. All
patients underwent staging with Ann Arbor (or Musshoff for GI cases). Treatment involved
R-CHOP-based regimens, with CNS prophylaxis, radiotherapy, or surgery when indicated.
Results: Median age was 54 years (range: 20–84), with a male predominance (sex ratio 2:1).
Median diagnostic delay was 5 months. B symptoms were present in 26%. According to Ann
Arbor staging: I (64%), II (12%), III (4%), IV (20%). Treatment response in 48 evaluable
patients: CR (82%), PR (12%), failure (6%). Median follow-up: 23 months.
Conclusion: Extranodal DLBCL demonstrates significant heterogeneity in presentation and
outcomes. The gastrointestinal tract was the most common site. R-CHOP remains the gold
standard, but early diagnosis and site-specific management are critical. CNS prophylaxis
should be systematically considered for high-risk localizations.
Introduction
Diffuse large B-cell lymphoma (DLBCL) accounts for approximately one-third of all non-
Hodgkin lymphomas in adults. While nodal involvement is most common, up to 40% of
cases present with extranodal disease, which is often associated with distinctive biological

2. behavior and therapeutic challenges. Extranodal DLBCL can arise in nearly any organ, with
the gastrointestinal tract, ENT sites, and bone being the most frequent. Rare presentations
in the CNS, endocrine glands, or reproductive organs carry unique diagnostic and
therapeutic implications. The management of extranodal DLBCL remains based on R-CHOP
immunochemotherapy, often complemented by radiotherapy or surgery, and CNS
prophylaxis when indicated. This study aimed to characterize the clinical features,
treatment approaches, and therapeutic outcomes of patients with extranodal DLBCL treated
at our institution over an eight-year period.
Materials and Methods
This retrospective descriptive study included patients with histologically confirmed de novo
extranodal DLBCL diagnosed between January 2010 and December 2017 at the Hematology
Department, Central Army Hospital, Algiers. A total of 66 cases were analyzed. Histological
diagnosis was established through biopsy of the extranodal lesion and confirmed by
immunohistochemistry. All patients underwent full staging assessments including clinical,
radiological, and biological evaluation. Staging was performed using Ann Arbor for most
cases, while gastrointestinal cases were staged with the Musshoff system. The International
Prognostic Index (IPI) was calculated for each patient. Treatment consisted of R-CHOP-
based immunochemotherapy with CNS prophylaxis when appropriate. Additional
modalities such as surgery and radiotherapy were applied based on disease site and
extension. Treatment response was assessed clinically and radiologically after therapy
completion.
Results
The median age of the cohort was 54 years (range: 20–84), with a male-to-female ratio of
2:1. The median diagnostic delay was 5 months (range: 1–36). Distribution of primary sites
was as follows: gastrointestinal (33.5%), ENT (21.5%), bone (15%), cerebral (9%),
endocrine (9%), and others (12%). Endocrine cases involved thyroid (n=4), adrenal (n=1),
and testis (n=1). Other rare localizations included cutaneous, vaginal, hepatic, pulmonary,
muscular, and lacrimal sites. B symptoms were reported in 26% of patients. Common site-
specific symptoms included abdominal pain for gastrointestinal cases (28%), dysphagia for
ENT involvement (57%), bone pain (60%), and headaches for cerebral cases (50%).
Staging according to Ann Arbor: I (64%), II (12%), III (4%), IV (20%). For gastrointestinal
cases (Musshoff): I (28%), II (36%), III (4%), IV (32%).
Therapy: All patients received R-CHOP-based regimens. Radiotherapy or surgery was added
in selected cases. CNS prophylaxis was systematically applied when indicated. Among 48
evaluable patients, the overall response rate was 94% (CR 82%, PR 12%). Six percent had
refractory disease. The median follow-up duration was 23 months (range: 1–76).

3. Discussion
This study confirms the clinical heterogeneity of extranodal DLBCL and highlights site-
specific differences in presentation, diagnostic delay, and therapeutic outcomes. Our data
align with international reports identifying the gastrointestinal tract as the predominant
extranodal site, representing one-third of cases (Ferreri et al., 2019; Castillo et al., 2020).
ENT and bone localizations were also frequent, while endocrine and CNS presentations
were rare but clinically challenging due to delayed diagnosis and poorer outcomes.
The high proportion of early-stage disease in our cohort (76% stage I–II) may explain the
favorable response rates observed, with 82% achieving complete remission. This result is
consistent with pivotal trials demonstrating CR rates of 70–85% in extranodal DLBCL
treated with R-CHOP (Coiffier et al., 2002; Vitolo et al., 2017).
Nevertheless, survival outcomes are not uniform across extranodal sites. Primary CNS
DLBCL, testicular lymphoma, and adrenal involvement have been consistently associated
with inferior prognosis (Martinez-Calle et al., 2020; Chamoun et al., 2022). These entities
require tailored strategies, including intensified CNS prophylaxis, site-directed
radiotherapy, or high-dose methotrexate-based regimens.
The delayed diagnosis observed in endocrine localizations (median 15 months) reflects
both the rarity of the disease and the nonspecific clinical presentation. Such delay may
contribute to advanced staging and worse prognosis. Our findings highlight the need for
heightened clinical suspicion and timely biopsy of suspicious extranodal lesions.
Limitations of our study include its retrospective monocentric design, potential referral
bias, and relatively short median follow-up of 23 months, which restricts long-term survival
analysis. However, the systematic staging and uniform treatment approach strengthen the
reliability of our response data.
Future directions should include multicenter prospective studies with molecular profiling,
as emerging genomic classifications (e.g., cell-of-origin subtypes, MYC/BCL2 double-hit
status) may refine prognostic stratification and therapeutic personalization in extranodal
DLBCL (Schmitz et al., 2018; Wright et al., 2020).
Conclusion
Extranodal DLBCL is a clinically heterogeneous entity, most frequently involving the
gastrointestinal tract and ENT regions. Presentation and prognosis are strongly influenced
by the site of involvement, staging, and IPI risk category. R-CHOP remains the cornerstone
of therapy, but site-directed strategies and CNS prophylaxis are essential in high-risk
localizations. Early diagnosis and integration of molecular prognostic tools will be key to
improving survival in extranodal DLBCL.
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