Lymphoma & related disorders

Mature B cell neoplasms

Follicular lymphoma

Follicular neoplasia in situ

Editorial Board Member: Genevieve M. Crane, M.D., Ph.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Neval Ozkaya, M.D.
Elaine S. Jaffe, M.D.

Last author update: 17 January 2019
Last staff update: 20 March 2023 (update in progress)

Copyright: 2019-2023,, Inc.

PubMed Search: Follicular neoplasia in situ

Neval Ozkaya, M.D.
Elaine S. Jaffe, M.D.
Page views in 2022: 2,779
Page views in 2023 to date: 967
Cite this page: Ozkaya N, Jaffe ES. Follicular neoplasia in situ. website. Accessed June 1st, 2023.
Definition / general
  • In situ follicular neoplasia is a monoclonal proliferation of BCL2 positive B cells confined to follicle centers
  • B cells are positive for t(14;18)(q32;q21) (Blood 2002;99:3376)
Essential features
  • Histopathologic and immunohistochemical evaluation are essential
  • Clinical and pathological evidence of usual follicular lymphoma is lacking in other sites
  • BCL2 intensity in germinal centers is strong, stronger than adjacent mantle cuff
  • CD10 is strongly positive
  • Variable number of germinal centers may be involved
  • Lymph node architecture is preserved
  • Formerly follicular lymphoma in situ
  • "In situ follicular lymphoma" terminology is discouraged, because risk for clinically significant lymphoma is small
ICD coding
  • ICD-10: D36.0 - benign neoplasm of lymph nodes
  • ICD-0: 9695/1 - in situ follicular neoplasia
  • Lymph node otherwise showing follicular hyperplasia
  • May be seen in secondary lymphoid follicles of tonsil, spleen and lymphoid tissue in extranodal sites
  • Precursor lesion of conventional follicular lymphoma but progresses to follicular lymphoma in fewer than 5% of cases
  • B cells with BCL2 rearrangement within germinal centers
  • Other than BCL2 rearrangement, low level of genetic aberrations is found
  • Very early step in lymphomagenesis (Blood 2018 Nov 6 [Epub ahead of print])
  • High environmental exposure to pesticides and herbicides associated with increase in cells carrying t(14;18)(q32;q21) (IGH / BCL2) translocation in the peripheral blood
Diagrams / tables

Images hosted on other servers:

Development of FL-like B cells

Clinical features
  • Always an incidental finding
  • Risk for clinically significant follicular lymphoma less than 5%
  • Low incidence of other lymphoma subtypes in affected patients, mainly mantle cell lymphoma, chronic lymphocytic leukemia, marginal zone lymphoma and diffuse large B cell lymphoma
Diagnostic criteria
  • BCL2 and CD10 strongly positive in lesional cells
  • Neoplastic cells confined to follicle centers of secondary follicles
  • Lymph node architecture is preserved
  • Lymph nodes may show other pathology or involvement by unrelated lymphoma, usually of B cell lineage
  • Low levels of B cells with the BCL2 rearrangement in the peripheral blood may be found by PCR
  • In blood, referred to as follicular lymphoma-like B cells (Haematologica 2013;98:1571)
Case reports
  • Clinical evaluation for follicular lymphoma at other sites recommended at diagnosis
  • No treatment indicated if only in situ follicular neoplasia is found
Gross description
  • No gross finding is evident
  • Involved lymph node may be enlarged secondary to lymphoid hyperplasia or other pathology
Microscopic (histologic) description
  • Lesion generally not evident on routine H&E stained sections
  • Lymph node architecture is intact
  • Involved follicles are generally normal in size
  • The neoplastic cells (BCL2 strong+, CD10 strong+) are exclusively centrocytes, confined to the follicle centers
  • Individual germinal centers show varying degrees of involvement
  • By definition, no interfollicular infiltration is seen
  • Involved follicles show low proliferation fraction with Ki67
Microscopic (histologic) images

Contributed by Elaine S. Jaffe, M.D.

H&E overview

BCL2 overview

CD10 overview

BCL2 neoplastic follicle

H&E neoplastic follicle

CD10 neoplastic follicle

H&E reactive follicle

BCL2 reactive follicle

CD10 reactive follicle

Positive stains
  • Strong expression of BCL2 and CD10
  • BCL6 is variably positive
  • B cell phenotype intact: CD20, CD19, CD79a, PAX5
  • Low proliferation index (Ki67 ~10%) in contrast to reactive germinal center
Negative stains
Flow cytometry description
Molecular / cytogenetics description
Differential diagnosis
Board review style question #1
Which of the following is characteristic of in situ follicular neoplasia?

  1. Bone marrow involvement is common at diagnosis
  2. Common in childhood
  3. Lymphocytosis is a common finding
  4. Tend to involve extranodal sites
  5. Typically an incidental finding
Board review style answer #1
E. It is typically an incidental finding.

Comment here

Reference: Follicular neoplasia in situ
Board review style question #2
Which of the following is true about in situ follicular neoplasia?

  1. Composed exclusively of centrocytes
  2. High mitotic rate
  3. Interfollicular infiltration of neoplastic B cells is common
  4. Positive for BCL6 rearrangement
  5. Positive for CCND1 rearrangement
Board review style answer #2
A. In situ follicular neoplasia has a monomorphic appearance and is composed exclusively of centrocytes.

Comment here

Reference: Follicular neoplasia in situ
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