Name

ICD-O-1 Morphology

9612/3: Malignant lymphoma, immunoblastic type
9632/3: Malignant lymphoma, centroblastic type, NOS

ICD-O-2 Morphology

9680/3: Malignant lymphoma, large B-cell, diffuse, NOS
9682/3: Malignant lymphoma, large cell, noncleaved, diffuse
9712/3: Angioendotheliomatosis
Effective 1992 - 2000

ICD-O-3 Morphology

9680/3: Malignant lymphoma, large B-cell, diffuse, NOS
Effective 2001 and later

Reportable

for cases diagnosed 1992 and later

Primary Site(s)

See Abstractor Notes and Module 7

Grade

Not Applicable

Module Rule

Module 6: PH11, PH13

Alternate Names

Activated B-cell subtype
B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma
Burkitt-like lymphoma
Diffuse large B-cell lymphoma, NOS centroblastic variant
Diffuse large B-cell lymphoma, NOS immunoblastic variant
Diffuse large B-cell lymphoma/Intravascular large B-cell lymphoma
DLBCL
DLBCL/BL (Gray zone lymphoma)
DLBCL associated with chronic inflammation
Double hit lymphoma
EBV Positive DLBCL of the elderly
EBV-associated B-cell lymphoproliferative disorder of the elderly
Fibrin-associated diffuse large B-cell lymphoma
Germinal centre B-cell-like GCB
Germinal centre B-cell subtype
High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements
Lymphomatoid granulomatosis grade 3
Malignant lymphoma, centroblastic, diffuse
Malignant lymphoma, centroblastic, NOS
Malignant lymphoma, histiocytic, diffuse
Malignant lymphoma, histiocytic, NOS [OBS]
Malignant lymphoma, large B-cell, diffuse, centroblastic, NOS
Malignant lymphoma, large cell, cleaved, NOS [OBS]
Malignant lymphoma, large cell, cleaved and non cleaved [OBS]
Malignant lymphoma, large cell, diffuse, NOS [OBS]
Malignant lymphoma, large cell, non cleaved, NOS
Malignant lymphoma, large cell, noncleaved, diffuse
Malignant lymphoma, large cell, NOS
Malignant lymphoma, large cleaved cell, NOS [OBS]
Malignant lymphoma, noncleaved, diffuse, NOS [OBS]
Malignant lymphoma, noncleaved, NOS
Non-germinal centre B-cell-like; non-GCB
PCLBCL leg type
PCNSL
PIOL
Primary CNS lymphoma
Primary cutaneous DLBCL, leg type
Primary DLBCL of the CNS
Pyothorax-associated lymphoma
Richter syndrome
Splenic EBV-associated B-cell lymphoproliferative disorder
Triple hit lymphoma

Definition

Diffuse large B-cell lymphoma (DLBCL) is a neoplasm of medium or large B lymphoid cells whose nuclei are the same size as, or larger than, those of normal macrophages, or more than twice the size of those of normal lymphocytes, with a diffuse growth pattern.

Morphological, biological, and clinical studies have divided DLBCLs into morphological variants, molecular subtypes, and distinct disease entities.

Diffuse large B-cell lymphoma associated with chronic inflammation is a lymphoid neoplasm occurring in the setting of longstanding chronic inflammation and showing association with EBV. Most cases involve body cavities or narrow spaces. Pyothorax-associated lymphoma (PAL) is the protypical form, developing in the pleural cavity of patients with longstanding pyothorax.

EBV-positive diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), is an EBV-positive clonal B-cell lymphoid proliferation. Excluded from this category are cases of lymphomatoid granulomatosis, cases with evidence of acute or recent EBV infection, other well-defined lymphomas that may be EBV-positive (such as plasmablastic lymphoma and DLBCL associated with chronic inflammation), and EBV-positive mucocutaneous ulcer. This disease was formerly designated as EBV-positive DLBCL of the elderly. The elderly designation has been removed.

Fibrin-associated diffuse large B-cell lymphoma is an unusual form of diffuse large B-cell lymphoma associated with chronic inflammation. It is not mass forming and does not directly produce symptoms, but is discovered incidentally on histological examination of surgical pathology specific excised for various pathologies other than lymphomas.

High-grade B-cell lymphoma (HGBL) is a group of aggressive, mature B-cell lymphomas that for biological and clinical reasons should not be classified as diffuse large B-cell lymphoma (DLBCL), NOS, or as Burkitt lymphoma (BL). There are two categories of HGBL.
1) HGBL with MYC and BCL2 and/or BCL6 rearrangements, encompasses all B-cell lymphomas that have a MYC (8q24) rearrangement in combination with a BCL2 (18q21) and or a BCL6 (3q27) rearrangement, i.e. the so-called double-hit and triple-hit lymphomas.
2) HGBL, NOS encompasses cases that either have features intermediate between DLBCL and BL, or appear blastoid, but by definition do not harbor a genetic double hit.

Primary cutaneous diffuse large B-cell lymphoma (PCLBCL), leg type, is a PCLBCL composed exclusively of centroblasts and immunoblasts, most commonly arising within the leg.

Primary diffuse large B-cell lymphoma (DLBCL) of the CNS is defined as DLBCL arising within the brain, spinal cord, leptomeninges or eye. Excluded are lymphomas of the dura, intravascular large B-cell lymphomas, lymphomas with evidence of systemic disease or secondary lymphomas, and all immunodeficiency-associated lymphomas.

Abstractor Notes

Patients may present with nodal or extranodal disease. The most common extranodal site is the gastrointestinal site (stomach and ileocecal region). Other common sites of extranodal presentation include the bone, testes, spleen, Waldeyer ring, salivary glands, thyroid, liver, kidneys, and adrenal glands.

Patients usually present with a rapidly enlarging tumor mass at single or multiple nodal or extranodal sites. Many patients are asymptomatic, but B symptoms may be present. Specific localizing symptoms may be present and are highly dependent on the site of extranodal involvement.

For more information on lymphoma, see the NCI website: http://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq#section/_1 or http://www.cancer.gov/types/lymphoma/patient/adult-nhl-treatment-pdq#section/_129

Definitive Diagnostic Methods

Cytology (for primary CNS lymphoma only)
Genetic testing
Histologic confirmation
Immunophenotyping

Genetics Data

BCL2 (18q21.3 gain/amplification)
CARD11 mutation
CDKN2A (9p21 deletion)
CD274/PDCD1LG2 (9p24.1 gains/amplification )
CD79B mutation
CREBBP mutation
GNA13 mutation
KMT2D (also called MLL2) mutation
MEF2B mutation
MYD88 mutation
PRDM1 (6q21 deletion)
PTPN1 mutation
REL (2p16 gain/amplification)
SOCS1 mutation
STAT6 mutation
TNFRSF14 (1p36;32 deletion)
3q27 gain/amplication

Immunophenotyping

BCL2 expression
BCL6 positive
CD5 expression
CD10 positive
CD15 positive
CD19 expression
CD20 expression
CD22 expression
CD30 expression
CD79a expression
FOXP1 expression
IRF4/MUM1 positive
LMO2 expression
PAX5 expression

Treatments

Chemotherapy
Hematologic Transplant and/or Endocrine Procedures
Hormone therapy
Radiation therapy

Transformations to

None

Corresponding ICD-9 Codes

200.7 Large cell lymphoma

Corresponding ICD-10 Codes

C83.3 Diffuse non-Hodgkins lymphoma, large cell (diffuse)

Corresponding ICD-10-CM Codes (U.S. only)

C83.3 Diffuse large B-cell lymphoma (effective October 01, 2015)

Signs and Symptoms

Drenching night sweats
Fever (for no known reason)
Pain in the chest, abdomen, or bones (for no known reason)
Painless swelling in the lymph nodes
Rapidly enlarging mass at single or multiple nodal or extranodal sites
Skin rash or itchy skin
Weight loss (for no known reason)

Diagnostic Exams

CT (CAT) scan
Laparoscopy (rarely performed)
Laparotomy (rarely performed)
MRI (magnetic resonance imaging)
PET (positron emission tomography) scan

Progression and Transformation

None

Epidemiology and Mortality

Age: 70 years median age (occur in children and adults)
Incidence: 25-30% of adult NHL's (western countries)
Sex: slight male predominance
Survival: 5 year survival ~62% without bone marrow involvement; 5 year survival 10% with bone marrow involvement

Sources

Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds):
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition)
IARC: Lyon 2017
Section: Mature B-cell neoplasms
Pages: 291--297, 300-306, 309-311, 335-341

International Classification of Diseases for Oncology, Third Edition, First Revision. Geneva: World Health Organization, 2013.
Section: ICD-O-3.1 (2011) Morphological Codes
Pages: http://codes.iarc.fr/codegroup/2

National Cancer Institute
Section: General Information About Adult Non-Hodgkin Lymphoma (NHL)
Pages: https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq
Glossary