Name

Follicular lymphoma, grade 3

ICD-O-1 Morphology

9615/3: Malignant lymphoma, follicular center cell, NOS
9633/3: Malignant lymphoma, follicular center cell, non-cleaved NOS
9693/3: Malignant lymphoma, lymphocytic, well differentiated, nodular
9697/3: Malignant lymphoma, centroblastic type, follicular
9698/3: Follicular lymphoma, grade 3
Effective 1978 - 1991

ICD-O-2 Morphology

9693/3: Malignant lymphoma, lymphocytic, well differentiated, nodular
9697/3: Malignant lymphoma, centroblastic type, follicular
9698/3: Follicular lymphoma, grade 3
Effective 1992 - 2000

ICD-O-3 Morphology

9698/3: Follicular lymphoma, grade 3
Effective 2001 and later

Reportable

for cases diagnosed 1978 and later

Primary Site(s)

See Module 7
Most common sites of involvement: lymph nodes, spleen, bone marrow (BM), peripheral blood (PB), and Waldeyer ring, skin, duodenum, ocular adnex, breast and testis

Grade

See Abstractor Notes

Module Rule

None

Alternate Names

Diffuse, follicular lymphoma, grade 3
Follicular lymphoma, diffuse, grade 3
Follicular lymphoma, grade 3A
Follicular lymphoma, grade 3B
Follicular lymphoma, high grade
Grade 3, follicular lymphoma, diffuse
Large B-cell lymphoma with IRF4 rearrangement
Malignant lymphoma, centroblastic, follicular
Malignant lymphoma, histiocytic, nodular [OBS]
Malignant lymphoma, large cell, follicular, NOS
Malignant lymphoma, large cell, noncleaved, follicular [OBS]
Malignant lymphoma, large cleaved cell, follicular [OBS]
Malignant lymphoma, lymphocytic, well differentiated, nodular [OBS]
Malignant lymphoma, noncleaved cell, follicular, NOS [OBS]
Testicular follicular lymphoma

Definition

Follicular lymphoma (FL) is a neoplasm composed of follicle centre (germinal center) B cells (typically both centrocytes and centroblasts/large transformed cells), which usually has at least a partially follicular pattern. Progression in cytological grade is common during the natural history of the disease.

There are several variants/subtypes of Follicular lymphoma

1) Diffuse variant of follicular lymphoma. See 9690/3.
2) Duodenal-type follicular lymphoma. See 9695/3.
3) In situ follicular neoplasia (formerly called FL in situ). See 9695/1.
4) Large B-cell lymphoma with IRF4 rearrangement. See below.
5) Pediatric-type follicular lymphoma. See 9695/3.
5) Testicular follicular lymphoma. See below.

Large B-cell lymphoma (LBCL) with IRF4 rearrangement is an uncommon subtype of LBCL that can be entirely diffuse, follicular and diffuse, or entirely follicular. It is characterized by strong expression of IRF4/MUM1, usually with IFR4 rearrangement. It occurs primarily in children and young adults, with predominantly Waldeyer ring or head and neck lymph node involvement.

Testicular follicular lymphoma is a distinctive variant of FL. They are reported with higher frequency in children, but area also seen rarely in adults. They differ biologically from fl in that they lack evidence of the BCL2 translocation. Cytologically they are of high cytological grade, usually grade 3A, but have a good prognosis, even without additional therapy beyond surgical resection.

Abstractor Notes

Follicular lymphoma, NOS (9690/3) histology is a generic disease description. DCO cases or path report only cases usually stay in this classification. The NOS histology may be the working diagnosis. Further review of the medical record should be done to look for the tests listed as definitive diagnosis.

The more specific follicular lymphomas are:
1. Follicular lymphoma, grade 1 (9695/3)
2. Follicular lymphoma, grade 2 (9691/3)
3. Follicular lymphoma, grade 3 [3A, 3B] (9698/3)

When a more specific diagnosis is identified, the histology should be changed to the more specific neoplasm name and code.

FL is graded according to the proportion of large cells (centroblasts). Studies suggest this histologic grading predicts clinical outcome, with more large cells behaving more aggressively and having a higher likelihood of transformation to diffuse large cell lymphoma.
1) Grade 1-2 (low grade): 0-15 centroblasts per HPF (9690/3)
1) Grade 1: 0-5 centroblasts per HPF (9695/3)
2) Grade 2: 6-15 centroblasts per HPF (9691/3)
3) Grade 3: > 15 centroblasts per HPF (9698/3)
4) Grade 3A: Centrocytes present (9698/3)
5) Grade 3B: Solid sheets of centroblasts (9698/3)

Most patients present with widespread disease, including peripheral and central (abdominal and thoracic) lymphadenopathy and splenomegaly. The BM is involved in 40-70%.

Only 1/3 of patients present with stage I or II at the time of diagnosis.

When any area of diffuse large-B-cell lymphoma (DLBCL) is present in a FL the disease should be reported as diffuse large B-cell lymphoma (9680/3) (See PH rules).

Definitive Diagnostic Methods

FISH
Genetic testing
Histologic confirmation
Immunophenotyping

Genetics Data

CREBBP mutation
EPHA7 mutation
KMT2D (MLL2) mutation
MEF2B mutation
MYC gain
TNFAIP3 (also called A20) deletion, mutation
TNFRSF14 deletion, mutation

Immunophenotyping

BCL2 expression
BCL6 expression
CD5 negative
CD10 expression and positive
CD19 expression
CD22 expression
CD23 expression
CD43 negative
CD79a expression and positive
GCET1 positive
GCET2 (HGAL) positive
IgD negative
IgM positive
LMO2 positive
PAX5 positive

Treatments

Chemotherapy
Hematologic Transplant and/or Endocrine Procedures
Immunotherapy
Radiation therapy

Transformations from

None

Corresponding ICD-9 Codes

202.0 Nodular lymphoma

Corresponding ICD-10 Codes

C82.2 Follicular non-Hodgkin's lymphomas, Large cell

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

C82.2 Follicular lymphoma grade III, unspecified (effective October 01, 2015)
C82.3 Follicular lymphoma grade IIIa (effective October 01, 2015)
C82.4 Follicular lymphoma grade IIIb (effective October 01, 2015)

Signs and Symptoms

Drenching night sweats
Fever (for no known reason)
Lymphadenopathy (abdominal and thoracic)
Pain in the chest, abdomen, or bones (for no known reason)
Painless swelling in the lymph nodes in the neck, underarm, groin or stomach
Skin rash or itchy skin
Weight loss (for no known reason)

Diagnostic Exams

Complete blood count (CBC)
Cytogenetics studies
CT (CAT) scan
Laparoscopy (rarely performed)
Laparotomy (rarely performed)
MRI (Magnetic resonance imaging)
PET scan (positron emission tomography scan)

Progression and Transformation

25-35% of patients transform to DLBCL

Epidemiology and Mortality

Age: 60 years median age (rare occurrence under 20 years of age)
Incidence: Follicular lymphomas account for 20% of all lymhpomas
Sex: slight female predominance
Survival: 8-15 years median survival, closely related to the extent of the disease at diagnosis

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: 266-281

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