Skin nonmelanocytic tumor

Lymphoma and related disorders (see also Lymphoma chapter)

B cell neoplasms

Primary cutaneous follicle center lymphoma



Topic Completed: 5 August 2021

Minor changes: 5 August 2021

Copyright: 2003-2021, PathologyOutlines.com, Inc.

PubMed Search: Primary cutaneous follicle center lymphoma[title]


Mahsa Khanlari, M.D.
Beenu Thakral, M.D.
Page views in 2020: 2,447
Page views in 2021 to date: 3,288
Cite this page: Khanlari M, Thakral B. Primary cutaneous follicle center lymphoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomafollicularcutaneous.html. Accessed December 3rd, 2021.
Definition / general
  • Low grade B cell lymphoma arising in skin composed of follicular center B cells without evidence of systemic / nodal involvement at the time of diagnosis
Essential features
  • Mainly centrocytes; predominantly large centrocytes
  • Follicular, diffuse or follicular and diffuse growth pattern
  • Presence of monoclonal B cells in the right clinical and pathologic context can support a diagnosis of primary cutaneous follicle center lymphoma (PCFCL)
  • Diffuse growth of centroblasts and immunoblasts excludes this diagnosis
  • Clinically and genetically distinct from nodal follicular lymphoma
Terminology
ICD coding
  • ICD-O: 9597/3 - primary cutaneous follicle centre lymphoma
  • ICD-10: C86.6 - primary cutaneous CD30 positive T cell proliferations
Epidemiology
  • ~10% of all primary cutaneous lymphomas
  • Most common (~50%) type of primary cutaneous B cell lymphomas
  • Middle aged adults (i.e. 50 - 60 years)
  • M:F = ~1.5:1
  • Reference: Blood 2005;105:3768
Pathophysiology
Etiology
Diagrams / tables

Table 1: differential diagnosis of primary cutaneous follicle center B cell lymphoma
Criteria Primary cutaneous follicle center lymphoma (PCFCL) Secondary follicular lymphoma Primary cutaneous marginal zone lymphoma Primary cutaneous diffuse large B cell lymphoma, leg type
Age 50 - 60 years ~60 years ~55 years 70 years
Gender M > F M > F M > F F > M
Stage Low (I - II) High (III - IV) in majority of cases Low, limited to skin Low to high
Most common location Head and neck Variable Trunk, arms or head Lower leg(s)
Extracutaneous spread Absent Present, variable Rare (< 10%) Present, ~30%
Histology Mixture of centrocytes and centroblasts (no grading required) in follicular, follicular and diffuse or diffuse growth patterns; background fibrosis and sclerosis with stromal reaction present Mixture of centrocytes and centroblasts in follicles (grading based on number of centroblasts); background fibrosis and sclerosis with stromal reaction present Polymorphous: small lymphocytes, small to medium sized marginal zone (centrocyte-like) cells with pale cytoplasm, lymphoplasmacytic cells, plasma cells and occasional large, transformed lymphoid cells Centroblasts or immunoblasts (large noncleaved cells) in diffuse growth pattern; no background stromal reaction
BCL2 (IHC) Negative to weak positive Usually positive Usually positive Positive
CD10 Positive in follicular pattern (< 25%); negative in diffuse pattern Positive (usually) Negative Negative
BCL6 (IHC) Positive (~100%) Positive (usually) Negative Positive or negative
Ki67 Variable, usually > 30% Low (except for high grade)
BCL2 rearrangement / t(14;18) Absent (10 - 40% can be positive) Positive (~85%) Absent Present (~50%)
BCL6 or MYC rearrangements Absent Variably present Rare cases with BCL6 rearrangement BCL6 (30%), MYC (30%)
Cytogenetic findings Deletion of 14q32.33; c-REL amplifications (~60%) Complex
  • t(14;18)(q32;q21);IGH-MALT1
  • t(11;18)(q21;q21);BIRC3-MALT1
  • t(3;14)(p14.1;q32);IGH-FOXP1
Inactivation / deletion of CDKN2a (9p21.3) & CDKN2B genes, deletion of 6q arm (BLIMP1; 60%)
Molecular findings Mutations in any chromatin modifying genes (CREBBP, EZH2, KMT2D, EP300) are seen in < 10% of cases; gene expression profiling similar to germinal center B cell-like type DLBCL Mutations in any chromatin modifying genes (CREBBP, EZH2, KMT2D, EP300) are common MYD88 (6%), FAS (63%), SLAMF1 (24%), SPEN (18%) and NCOR2 (13%) MYD88 (60%), CD79B (20%), CARD11 (10%), TNFAIP3 / A20 (40%); gene expression profiling similar to activated B cell-like type
Prognosis Favorable, 95% at 5 years (disease free survival) Variable, 20 - 75% at 5 years 95 - 100% at 5 years Variable, ~50% at 5 years
References: Blood Adv 2021;5:649, Front Oncol 2020;10:651, Am J Clin Pathol 2020;154:428
Clinical features
Diagnosis
  • Diagnosis made by:
    • Histology and immunohistochemical evaluation of a skin biopsy
      • Lymphoma involving the dermis, with follicular to diffuse growth pattern
      • Mixture of centrocytes and centroblasts
  • Diagnosis is supported by:
    • Flow cytometry immunophenotyping, if performed
    • Immunoglobulin heavy / light chain gene rearrangement studies, if performed
  • Reference: StatPearls: Primary Cutaneous Follicle Center Lymphoma [Accessed 7 June 2021]
Radiology description
  • PET / CT: negative for lymphadenopathy
  • Dissemination to extracutaneous sites is uncommon (< 10% of patients) (J Clin Oncol 2006;24:1376)
Prognostic factors
Case reports
Treatment
  • Single cutaneous lesion
    • Local therapy with:
      • Either surgical excision or local radiation
      • In case of cutaneous relapse: radiotherapy
    • Generalized skin lesions:
      • Systemic intralesional administration of rituximab or systemic rituximab
  • Reference: Blood 2008;11:1600
Clinical images

Images hosted on other servers:

PCFCL in forehead and scalp

Microscopic (histologic) description
  • Infiltrate is based in the superficial dermis:
    • Lymphoma may involve the entire dermis
    • Often follicles of the tumor extending into the subcutis
    • Perivascular, periadnexal, nodular and diffuse infiltrates
    • Follicles are ill defined; lack tingible body macrophages and mantle zone
  • Intact grenz zone
  • Growth pattern varies:
    • Follicular (mainly head and neck)
    • Follicular and diffuse
    • Purely diffuse (primarily trunk)
  • Mixture of centrocytes and centroblasts
  • Large cells are variable and can be polylobated
  • Predominance of large centrocytes (large cleaved cells), may be spindle shaped
  • Variable numbers of centroblasts
  • T cells are abundant
  • No WHO grading of lymphoma required as in nodal / systemic follicular lymphoma
  • Reference: Arch Pathol Lab Med 2018;142:1313
Microscopic (histologic) images

Contributed by Beenu Thakral, M.D.

Panoramic view of skin biopsy

Neoplastic follicle

CD20

BCL6


BCL2

CD10

CD21

Ki67

Cytology description
  • Cells resembling centrocytes and centroblasts (Jaffe: Hematopathology, 2nd Edition, 2016)
  • Large centrocytes: dispersed chromatin and small nucleoli
  • Large noncleaved cells: prominent and paracentral nucleoli
Positive stains
Negative stains
Flow cytometry description
Molecular / cytogenetics description
Sample pathology report
  • Skin, left cheek, biopsy
    • Low grade follicular lymphoma involving skin (see comment)
    • Comment: Histologic sections demonstrate skin involved by lymphoma. The lymphoma has a vague nodular pattern and is composed of a mixture of large noncleaved and small cleaved lymphoid cells with predominance of small lymphoid cells. The epidermis is unremarkable. No epidermotropism noted. Plasma cells are not increased. Immunohistochemical studies performed demonstrate that the neoplastic cells are positive for CD10, CD20, PAX5, BCL6 and are negative for BCL2, cyclin D1 and MUM1. CD3 and CD5 highlight small reactive lymphocytes in the background. Ki67 demonstrates a proliferation index of ~20%.
    • In the appropriate clinical setting, this neoplasm involving the skin is consistent with primary cutaneous follicle center cell lymphoma. Clinical correlation and staging studies may help to confirm this diagnosis. If the neoplasm is systemic, this follicular lymphoma can be classified as low grade.
Differential diagnosis
Board review style question #1

CD20

BCL6

BCL2



A 50 year old man presented with a solitary and erythematous lesion on the scalp for ~3 weeks. He does not recall any similar lesion(s) in the past. On physical exam, no splenomegaly or lymphadenopathy is noted. A skin biopsy is performed and a diagnosis of primary cutaneous follicle center B cell lymphoma is rendered. Which of the following statements regarding this lesion is most accurate?

  1. Deletions of a small region on chromosome 9p21.3 containing CDKN2A and CDKN2B gene loci are frequently reported
  2. They are generally BCL2 negative, have a good prognosis and do not require grading for prognosis
  3. Majority of these lesions have t(14;18) translocation or BCL2 gene rearrangement
  4. MYD88 mutation is frequently reported in this lesion
Board review style answer #1
B. They are generally BCL2 negative, have a good prognosis and do not require grading for prognosis

Comment Here

Reference: Primary cutaneous follicle center lymphoma
Board review style question #2
Which of the following findings best matches with the diagnosis of primary cutaneous follicle center lymphoma (PCFCL)?

  1. CD20+, CD10-, BCL2+, BCL6+ with IGH-BCL2 gene rearrangement
  2. CD20+, CD10-, BCL2-, BCL6+with IGH-BCL2 gene rearrangement
  3. CD20+, CD10-, BCL2-, BCL6+ in the absence of IGH-BCL2 gene rearrangement
  4. CD20+, CD10+, BCL2+, BCL6+ with IGH-BCL2 gene rearrangement
  5. CD20+, CD10-, BCL2-, BCL6- in the absence of IGH-BCL2 gene rearrangement
Board review style answer #2
C. CD20+, CD10-, BCL2-, BCL6+ in the absence of IGH-BCL2 gene rearrangement (see Positive stains, Negative stains and Molecular / cytogenetics description)

Comment Here

Reference: Primary cutaneous follicle center lymphoma
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