Lymphoma & related disorders
Mature B cell neoplasms
Follicular lymphoma
Pediatric type
Authors: Mahsa Khanlari, M.D., Jennifer Chapman, M.D.
Editorial Board Member: Patricia Tsang, M.D., M.B.A.
Deputy Editor-in-Chief: Genevieve M. Crane, M.D., Ph.D.
Last author update: 14 October 2020
Last staff update: 14 October 2021
Copyright: 2001-2024, PathologyOutlines.com, Inc.
PubMed Search: Pediatric type follicular lymphoma
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Diagrams / tables | Clinical features | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Frozen section description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Khanlari M, Chapman JR. Pediatric type. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomafollicularchildhood.html. Accessed December 11th, 2024.
Definition / general
- Localized neoplasm of germinal center B cells
- Entirely follicular pattern
- Lymph nodes of children and young adults
Essential features
- At least partial effacement of nodal architecture
- Pure follicular proliferation
- Any component of diffuse large B cell lymphoma (DLBCL) excludes pediatric type follicular lymphoma (PTFL)
- Nodal disease
- Stage I - II
- BCL6 positivity
- BCL2 negativity or weak positivity
- High proliferative fraction (> 30%)
- No BCL2, BCL6, IRF4 or aberrant IG rearrangement
- No BCL2 amplification
Terminology
- Pediatric type nodal follicular lymphoma (PTNFL)
ICD coding
Epidemiology
- 1 - 2% of all pediatric non-Hodgkin lymphoma
- No upper age cutoff for diagnosis
- Majority 5 - 25 years (< 40 years)
- M:F = 10:1
- Reference: Virchows Arch 2019;475:771
Sites
- Head and neck lymph node, most frequent
- Inguinal and axillary nodes, less frequent
Diagrams / tables
Pediatric type follicular lymphoma versus follicular lymphoma usual type
| Pediatric type FL | Usual type FL | |
| Age | Young | Old age (sixth decade) |
| Stage | Low (I - II) | High (III - IV) in majority of cases |
| Location | Head and neck | Variable |
| Extranodal location | Absent | Present, variable |
| Histology | Grade 3 | Grade 1 - 3 |
| BCL2 (IHC) | Negative / dim | Usually positive |
| CD10 | Positive (~100%) | Positive (usually) |
| Ki67 | High | Low (except for high grade) |
| t(14;18) IGH-BCL2 | Absent | Present, up to 90% |
| Monotypic B cells by flow cytometry | Frequent | Frequent |
| Monoclonal IgH rearrangements | Frequent | Frequent |
| BCL6 or MYC rearrangements | Absent | Variably present |
| Genetic | 1p36 loss | Complex, variable |
| Mutations | TNFRSF14, MAP2K1, IRF8 (K66R) | CREBBP, EZH2, KMT2D |
| Prognosis | Favorable | Variable |
Clinical features
- Young patients
- Localized (stage I)
- Commonly involves lymph nodes of the head and neck
- Bone marrow involvement has not been reported
- B symptoms are absent
- Does not progress or recur after excision
- References: Am J Surg Pathol 2013;37:333, Haematologica 2010;95:253
Radiology description
- Localized nature of the disease
- Absence of mediastinal or intraabdominal lymph node involvement
Prognostic factors
- Excellent prognosis
- 5 year survival of over 95%
Case reports
- 13 year old boy presented with a slow growing mass on the right side of his neck (Medicine (Baltimore) 2019;98:e17567)
- 16 year old boy presented with asymptomatic and unilateral parotid swelling (Arch Craniofac Surg 2018;19:279)
Treatment
- Patients with localized disease: surgical excision
- Does not require radiation or chemotherapy (Ann Hematol 2013;92:1537, Blood 2016;128:1093)
- Note: majority of adult patients reported have received systemic chemotherapy or radiation therapy (Am J Surg Pathol 2013;37:333)
Gross description
- Lymph node: vaguely nodular pattern in cut section with bulging of node parenchyma
Frozen section description
- Avoid specific diagnosis on frozen section due to requirement to examine submitted tissue completely to exclude a diffuse component and to confirm the absence of BCL2, BCL6 and MYC rearrangements
- Cytogenetic analysis, flow cytometry, preparation of imprints should be considered
Microscopic (histologic) description
- At least partial effacement of nodal architecture
- Entirely follicular pattern
- Expansile or serpiginous follicles
- Absence of diffuse component
- Rim of residual normal lymph node architecture at the periphery
- So called node in node appearance
- No extracapsular extension
- Attenuated mantle zones
- Monotonous population of intermediate sized blastoid cells within neoplastic follicles imparting a high grade or starry sky histologic appearance
- Blastoid cells comprising the neoplastic follicles are morphologically distinct from both centrocytes and centroblasts
- Tingible body macrophages present
- Lack of polarization of germinal center
- Reference: Haematologica 2010;95:253
Microscopic (histologic) images
Contributed by L. Jeffrey Medeiros, M.D. and Mahsa Khanlari, M.D.
Lymph node in 23 year old man
IHC for CD20
IHC for CD10
IHC for BCL6
IHC for BCL2
IHC for IgD; attenuated and focally absent mantle zone
Cytology description
- 2 types of cytology:
- Centroblastic cells
- Monotonous, medium sized blastoid cells
- Resemble centrocytes but are intermediate to large in size with more dispersed chromatin, high proliferative rate, frequent mitoses
- Small nucleoli as compared with centroblasts
- Reference: Am J Surg Pathol 2013;37:333
Positive stains
Negative stains
- BCL2 negative / weak
- MUM1 / IRF4 (usually negative)
Molecular / cytogenetics description
- Clonal immunoglobulin gene rearrangement by PCR
- Gains or amplifications of 6p24.3, including IRF4 (Haematologica 2013;98:1237)
- Loss of heterozygosity in 1p36 or mutations of TNFRSF14 (Haematologica 2013;98:1237)
- Negative for rearrangements of BCL2, BCL6 and IRF4 loci
- Presence of BCL2, BCL6 or IRF4 rearrangements excludes a diagnosis of pediatric type follicular lymphoma
- MAP2K1 mutations in approximately 40 - 50% of cases (Blood 2016;128:1093, Blood 2017;130:323)
- Hot spot mutation in IRF8 (K66R, p.L66A), 15 - 50% of cases (Blood 2017;130:323)
- Specific for pediatric type follicular lymphoma (Mod Pathol 2016;29:1212)
Sample pathology report
- Lymph node, left neck, excisional biopsy:
- Pediatric type follicular lymphoma (see comment)
- Comment: The patient is a 12 year old male presenting with isolated enlargement of left cervical lymph node. Other lymphadenopathy and extranodal masses as well as B symptoms are absent. Histologic sections show an excisional biopsy of lymph node demonstrating partial nodal architectural effacement. There is a rim of normal lymph node tissue in which reactive germinal centers are seen. Effaced areas of the lymph node are characterized by the presence of increased, irregularly shaped neoplastic follicles containing a monotonous population of intermediate sized lymphoid cells with blastic nuclear features. Mitotic activity is brisk and tingible body macrophages are present. A diffuse component is not identified. The lymph node is submitted entirely for histologic evaluation. By immunohistochemistry, the neoplastic cells are positive for CD20, CD10, BCL6 and HGAL and negative for CD3 and CD5. A subset of neoplastic cells express dim BCL2, but the majority are negative. The proliferative rate of lymphoid cells within neoplastic follicles is ~60%. FISH studies have been performed and are negative for the presence of BCL2, BCL6, MYC and IRF4 rearrangements. Next generation sequencing has been performed and has identified the presence of a TNFRSF14 mutation. The above histologic, immunophenotypic and cytogenetic features, in the appropriate clinical context, support the diagnosis of pediatric type follicular lymphoma.
Differential diagnosis
- Florid reactive follicular hyperplasia:
- Most lack monoclonality of B cells but a minor subset of cases can harbor clonal or monotypic populations of CD10 positive B cells
- Architectural effacement with node in node appearance supports a diagnosis of pediatric type follicular lymphoma (PTFL)
- Increased and expansile nature of the follicles, monotony of cells within follicles, lack of polarization and high grade histologic appearance of follicles supports PTFL
- Follicular lymphoma (FL), high grade:
- Usually older age
- Clinical findings support systemic disease (other lymphadenopathy, extranodal masses, B symptoms, staging)
- Presence of a diffuse component
- Rearrangements / amplification of BCL2, BCL6 or IG loci
- See table Pediatric type follicular lymphoma versus follicular lymphoma usual type
- Large B cell lymphoma (LBCL) with IRF4 rearrangement:
- Usually in Waldeyer ring
- Positive for MUM1 / IRF4 by immunohistochemistry
- IRF4 rearrangement
Additional references
Board review style question #1
Which of the following features is typical of pediatric type follicular lymphoma?
- High grade morphologic features indicating aggressive disease and poor prognosis
- Lack BCL2 gene rearrangements
- Lack monoclonal B cells
- Overexpress BCL2 protein
Board review style answer #1
B. PTFL, by definition, lack BCL2 gene rearrangements. These lymphoid proliferations do frequently contain monoclonal B cells and histologically appear high grade but they do not express BCL2 protein and are clinically low stage with excellent prognosis.
Comment Here
Reference: Pediatric type follicular lymphoma (PTFL)
Comment Here
Reference: Pediatric type follicular lymphoma (PTFL)
Board review style question #2
A 23 year old man presented with a right cervical lymph node enlargement. Cut section of the lymph node is provided in images. By immiunohistochemical stain, the cells are positive for BCL6 in the expanded follicles (image 1) while negative for BCL2. PCR is performed and clonal immunoglobulin gene rearrangement is detected. Which of the following is true?
- Chance of recurrence after resection is high
- Diagnosis requires integration of morphology with lymphoma staging findings
- Frequent CREBBP mutation
- Ki67 proliferative index is low in cells highlighted by BCL6 in immunohistochemistry
Board review style answer #2
B. Diagnosis requires integration of morphology with lymphoma staging findings (Am J Surg Pathol 2013;37:333).
Comment Here
Reference: Pediatric type follicular lymphoma (PTFL)
Comment Here
Reference: Pediatric type follicular lymphoma (PTFL)
