HAEM4Backup:Primary Cutaneous Follicle Centre Lymphoma

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Primary Author(s)*

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

Cancer Category/Type

Cancer Sub-Classification / Subtype

  • Primary Cutaneous Follicle Center 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[1].

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[2]

Clinical Features

  • 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[2]

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[3]
  • The tumor is composed of centrocytes and variable numbers of centroblasts[1]
  • 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[2]
    • Variable numbers of large centroblasts
    • Follicular dendritic cell meshwork may be lost
    • Proliferation rate is generally high

Immunophenotype

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)

The t(14;18)(q32;q21), IGH/BCL2 translocation, the genetic hallmark of nodal follicular lymphoma, is rare in primary cutaneous follicle center lymphoma[4][5].

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%

Characteristic Chromosomal Aberrations / Patterns

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[4]. 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[6]. In a case report of an aggressive PCFCL, c-MYC translocation and CDKN2A (9p21) deletion were detected[7].

Genomic Gain/Loss/LOH

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

Gene Mutations (SNV/INDEL)

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%

Epigenomics (Methylation)

  • Not known in this specific subgroup.

Genes and Main Pathways Involved

BCL2-mediated apoptosis pathway and NF-κB pathway

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

Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

  • Chromosomal abnormalities in PCFCL involving BCL2 or MALT1 do not correlate with a poor prognosis[2].

Familial Forms

  • Not known in this specific subgroup.

Other Information

Prognosis: Excellent prognosis with a 5-year survival rate >90%[8].

Links

  • None

References

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  1. ↑ 1.0 1.1 Gulia, Andrea; et al. (2011-11). "Clinicopathologic features of early lesions of primary cutaneous follicle center lymphoma, diffuse type: Implications for early diagnosis and treatment". Journal of the American Academy of Dermatology. 65 (5): 991–1000.e7. doi:10.1016/j.jaad.2010.06.059. ISSN 0190-9622. Check date values in: |date= (help)
  2. ↑ 2.0 2.1 2.2 2.3 World health organization classification of tumours of haematopoietic and lymphoid tissues, revised 4th edition, Swerdlow SH, Campo E, Harris NL, et al. (Eds), IARC, Lyon 2017.
  3. ↑ Senff, Nancy J.; et al. (2007-04-20). "Reclassification of 300 primary cutaneous B-Cell lymphomas according to the new WHO-EORTC classification for cutaneous lymphomas: comparison with previous classifications and identification of prognostic markers". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 25 (12): 1581–1587. doi:10.1200/JCO.2006.09.6396. ISSN 1527-7755. PMID 17353548.
  4. ↑ 4.0 4.1 Gángó, Ambrus; et al. (2018-10). "Concomitant 1p36 deletion and TNFRSF14 mutations in primary cutaneous follicle center lymphoma frequently expressing high levels of EZH2 protein". Virchows Archiv: An International Journal of Pathology. 473 (4): 453–462. doi:10.1007/s00428-018-2384-3. ISSN 1432-2307. PMID 29858685. Check date values in: |date= (help)
  5. ↑ Goodlad, John R.; et al. (2003-12). "Primary cutaneous diffuse large B-cell lymphoma: prognostic significance of clinicopathological subtypes". The American Journal of Surgical Pathology. 27 (12): 1538–1545. doi:10.1097/00000478-200312000-00006. ISSN 0147-5185. PMID 14657713. Check date values in: |date= (help)
  6. ↑ Abdul-Wahab, Alya; et al. (2014-06). "Chromosomal anomalies in primary cutaneous follicle center cell lymphoma do not portend a poor prognosis". Journal of the American Academy of Dermatology. 70 (6): 1010–1020. doi:10.1016/j.jaad.2014.01.862. ISSN 0190-9622. Check date values in: |date= (help)
  7. ↑ Tsang, Hamilton C.; et al. (2017-03). "An Aggressive Primary Cutaneous Follicle Center Lymphoma With c-MYC Translocation and CDKN2A (9p21) Deletion: A Case Report and Review of the Literature". The American Journal of Dermatopathology. 39 (3): e44–e49. doi:10.1097/DAD.0000000000000738. ISSN 1533-0311. PMID 27759694. Check date values in: |date= (help)
  8. ↑ Lucioni, Marco; et al. (2016-10). "Primary cutaneous B-cell lymphoma other than marginal zone: clinicopathologic analysis of 161 cases: Comparison with current classification and definition of prognostic markers". Cancer Medicine. 5 (10): 2740–2755. doi:10.1002/cam4.865. ISSN 2045-7634. PMC 5083727. PMID 27665744. Check date values in: |date= (help)
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