HAEM5:Primary cutaneous follicle centre lymphoma

Haematolymphoid Tumours (WHO Classification, 5th ed.)

editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification

This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Primary Cutaneous Follicle Centre Lymphoma.

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Primary Author(s)*

Linlin Gao, MD, PhD and Shivani Golem, PhD, FACMG

WHO Classification of Disease

Structure	Disease
Book	Haematolymphoid Tumours (5th ed.)
Category	B-cell lymphoid proliferations and lymphomas
Family	Mature B-cell neoplasms
Type	Cutaneous follicle centre lymphoma
Subtype(s)	Primary cutaneous follicle centre lymphoma

Definition / Description of Disease

Primary cutaneous follicle center lymphoma (PCFCL) is a tumor arising in skin composed of germinal center B cells, including centrocytes and centroblasts.

Synonyms / Terminology

• Reticulohistiocytoma of the dorsum
• Crosti lymphoma

Epidemiology / Prevalence

• It accounts for about 50% of primary cutaneous B-cell lymphomas with an incidence of 0.1-0.2 per 100,000 persons per year
• It mainly occurs in middle-aged adults
• Male: female ratio is approximately 1.5:1

Clinical Features

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Signs and Symptoms	EXAMPLE: Asymptomatic (incidental finding on complete blood counts) EXAMPLE: B-symptoms (weight loss, fever, night sweats) EXAMPLE: Fatigue EXAMPLE: Lymphadenopathy (uncommon)
Laboratory Findings	EXAMPLE: Cytopenias EXAMPLE: Lymphocytosis (low level)

editv4:Clinical Features

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• Usually solitary, firm, and erythematous to violaceous plaques, nodules or tumors of variable size
• Multifocal in 15% of patients
• Lesions on the trunk may be surrounded by erythematous papules
• The skin surface is usually smooth and rarely ulcerated

Sites of Involvement

• Head
• Trunk

Morphologic Features

• Perivascular, periadnexal, or diffuse infiltrates with sparing of the epidermis
• The growth patterns include follicular, follicular and diffuse, and diffuse patterns
• The tumor is composed of centrocytes and variable numbers of centroblasts
• In a tumor with follicular growth pattern, follicles are poorly defined and composed of monotonous follicle center cells with no polarization
  • A follicular dendritic cell meshwork is present
  • Tingible body macrophages are usually absent
  • Mantle zones are attenuated or absent
  • Proliferation rate is low
• In a tumor with diffuse growth pattern, tumor cells are mainly large centrocytes, some of which are multilobated or spindle-shaped
  • Variable numbers of large centroblasts
  • Follicular dendritic cell meshwork may be lost
  • Proliferation rate is generally high

Immunophenotype

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Finding	Marker
Positive (universal)	EXAMPLE: CD1
Positive (subset)	EXAMPLE: CD2
Negative (universal)	EXAMPLE: CD3
Negative (subset)	EXAMPLE: CD4

editv4:Immunophenotype

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Finding	Marker
Positive (universal)	CD20, CD79a, BCL6
Positive (tumor with a follicular growth pattern)	CD10
Negative (universal)	CD5, CD43
Negative (most cases)	BCL2, MUM1, FOXP1

Chromosomal Rearrangements (Gene Fusions)

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Chromosomal Rearrangement	Genes in Fusion (5’ or 3’ Segments)	Pathogenic Derivative	Prevalence	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE: t(9;22)(q34;q11.2)	EXAMPLE: 3'ABL1 / 5'BCR	EXAMPLE: der(22)	EXAMPLE: 20% (COSMIC) EXAMPLE: 30% (add reference)	Yes	No	Yes	EXAMPLE: The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).

editv4:Chromosomal Rearrangements (Gene Fusions)

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The t(14;18)(q32;q21), IGH/BCL2 translocation, the genetic hallmark of nodal follicular lymphoma, is rare in primary cutaneous follicle center lymphoma.

Chromosomal Rearrangement	Genes in Fusion (5’ or 3’ Segments)	Pathogenic Derivative	Prevalence
t(14;18)(q32;q21)	5'BCL2/3'IGH	der(14)	7%
t(14;18)(q32;q21)	5'MALT1/3'IGH	der(14)	2%

editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).

Please incorporate this section into the relevant tables found in:

• Chromosomal Rearrangements (Gene Fusions)
• Individual Region Genomic Gain/Loss/LOH
• Characteristic Chromosomal Patterns
• Gene Mutations (SNV/INDEL)

• Chromosomal abnormalities in PCFCL involving BCL2 or MALT1 do not correlate with a poor prognosis.

Individual Region Genomic Gain / Loss / LOH

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Chr #	Gain / Loss / Amp / LOH	Minimal Region Genomic Coordinates [Genome Build]	Minimal Region Cytoband	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE: 7	EXAMPLE: Loss	EXAMPLE: chr7:1- 159,335,973 [hg38]	EXAMPLE: chr7	Yes	Yes	No	EXAMPLE: Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
EXAMPLE: 8	EXAMPLE: Gain	EXAMPLE: chr8:1-145,138,636 [hg38]	EXAMPLE: chr8	No	No	No	EXAMPLE: Common recurrent secondary finding for t(8;21) (add reference).

editv4:Genomic Gain/Loss/LOH

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Chromosome Number	Gain/Loss/Amp/LOH	Region
1	Loss	chr 1p36
18	Amplification	chr 18q21.33

Characteristic Chromosomal Patterns

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Chromosomal Pattern	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE: Co-deletion of 1p and 18q	Yes	No	No	EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

editv4:Characteristic Chromosomal Aberrations / Patterns

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In a study of the genetic abnormalities of primary cutaneous follicle center lymphoma, 1p36 deletion was reported to occur in 22% (5/21) and BCL2 gene break in 10% (2/20) of the cases. TNFRSF14 nonsense and missense mutations were detected in 4/17 (23.5%) cases with concomitant 1p36 deletion in 2 cases. In 43% (9/21) of the cases, high EZH2 protein expression with a BCL2 negative phenotype was detected. In another study that investigated 57 patients with PCFCL, 1 case was found to have BCL2 chromosomal amplification, 4 cases had IGH/BCL2 translocation, and 1 case had IGH/MALT1 translocation. In a case report of an aggressive PCFCL, c-MYC translocation and CDKN2A (9p21) deletion were detected.

Gene Mutations (SNV / INDEL)

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Gene; Genetic Alteration	Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)	Prevalence (COSMIC / TCGA / Other)	Concomitant Mutations	Mutually Exclusive Mutations	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE: TP53; Variable LOF mutations EXAMPLE: EGFR; Exon 20 mutations EXAMPLE: BRAF; Activating mutations	EXAMPLE: TSG	EXAMPLE: 20% (COSMIC) EXAMPLE: 30% (add Reference)	EXAMPLE: IDH1 R123H	EXAMPLE: EGFR amplification				EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).

Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

editv4:Gene Mutations (SNV/INDEL)

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Gene	Mutation	Oncogene/Tumor Suppressor/Other	Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)	Prevalence (COSMIC/TCGA/Other)
TNFRSF14	W12Ter	Tumor suppressor	LOF	17.6%
TNFRSF14	C53G	Tumor suppressor	LOF	6%

Epigenomic Alterations

• Not known in this specific subgroup.

Genes and Main Pathways Involved

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Gene; Genetic Alteration	Pathway	Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations	EXAMPLE: MAPK signaling	EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations	EXAMPLE: Cell cycle regulation	EXAMPLE: Unregulated cell division
EXAMPLE:  KMT2C and ARID1A; Inactivating mutations	EXAMPLE:  Histone modification, chromatin remodeling	EXAMPLE:  Abnormal gene expression program

editv4:Genes and Main Pathways Involved

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BCL2-mediated apoptosis pathway and NF-κB pathway

Genetic Diagnostic Testing Methods

• Fluorescence in situ hybridization with BCL2 break apart and 1p36/1q25 dual color probes
• Polymerase chain reaction for IGH rearrangements
• Chromosomal microarray or karyotype analysis for 1p36 deletion
• DNA sequencing for TNFRSF14 mutations

Familial Forms

• Not known in this specific subgroup.

Additional Information

Prognosis: Excellent prognosis with a 5-year survival rate >90%.

Links

• None

References

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Notes

*Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome. *Citation of this Page: “Primary cutaneous follicle centre lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/6/2024, https://ccga.io/index.php/HAEM5:Primary_cutaneous_follicle_centre_lymphoma.