Primary Cutaneous Follicle Center Lymphoma

Aaron Auerbach, MD, PhD

Key Facts

Terminology

PCFCL
Mature B-cell lymphoma of follicle center cells, primary to skin and not originating in another anatomic site

Clinical Issues

Microscopic Pathology

Ancillary Tests

CD20(+), Bcl-6(+), CD10(+/−) (often negative in diffuse variant)
Bcl-2(−/+) and MUM1(−)
CD23, CD21, and CD35 positive in FDC meshworks
Usually CD43(−), unlike other B-cell lymphomas
CD5(−), Bcl-1(−)
Clonal Ig heavy chain (IgH) gene rearrangement
t(14;18), often not detected
Gene expression profiling findings akin to germinal center-like large B-cell lymphoma

Top Differential Diagnoses

There is a single large raised red nodule

on the scalp, 5 cm in largest dimension. Microscopically, the nodule was diagnosed as PCFCL. (Courtesy M. Tomaszewski, MD.)

Low-power magnification shows PCFCL with a multinodular

dermal infiltrate that is separated from the epidermis by a grenz zone

. (Courtesy M. Tomaszewski, MD.)

TERMINOLOGY

Abbreviations

Synonyms

Follicular lymphoma of skin
Crosti disease (reticulohistiocytoma of dorsum)
- Plaques/tumors surrounded by erythematous macules/papules

Definitions

Mature B-cell lymphoma of follicle center cells, primary in skin
- Disease limited to skin for 6 months after diagnosis
Distinct disease from systemic follicular lymphoma
- Better prognosis
- Fewer BCL2 rearrangements than systemic follicular lymphoma

CLINICAL ISSUES

Epidemiology

Incidence
- 0.1-0.2 cases per 100,000 people per year
- Most common primary cutaneous B-cell lymphoma
  - ˜ 20% of all skin lymphomas
  - ˜ 60% of all B-cell skin lymphomas
Age
- Usually adults
  - Median age: 60 years
  - But can also be seen in childhood
Gender
- Male:female = 1.5:1

Site

Presentation

Usually single lesion
- ˜ 15% multifocal
Plaques, nodules, or tumors of differing sizes
- From < 1 cm to > 40 cm in greatest dimension
Rarely ulcerates

Treatment

Prognosis

Good
- Much better than systemic follicular lymphoma
- Usually complete remission with treatment
- ˜ 95% 5-year survival
Not affected by
- Grade or growth pattern
- Bcl-2 expression or t(14;18) status
˜ 35% recurrence (often proximal to original lesion); extracutaneous spread ˜ 10%
˜ 10% disseminate to extracutaneous sites

MICROSCOPIC PATHOLOGY

Histologic Features

Dermal B-cell infiltrate, often extends into subcutis (˜ 75%)
- No overlying epidermotropism
Growth pattern
- Nodular, diffuse, or nodular and diffuse
- May be classified as follicular (> 75% follicular architecture), follicular and diffuse (25-75% follicular architecture), or diffuse (< 25% follicular architecture) growth pattern
Follicles
- Often not well-defined
- Usually seen in small lesions
- Lack mantle zones
- Lack tingible body macrophages
- Contain follicular dendritic cells
Tumor cells
- Mostly centrocytes (small to medium-sized, cleaved)
- Variable numbers of centroblasts (larger in size)
Cases with ↑ numbers of centroblasts
- Diagnose as PCFCL if nodular or nodular and diffuse growth pattern
- Diagnose as diffuse pattern PCFCL if large cells and only diffuse growth pattern
Grading of follicular lymphoma
- Not necessary or of prognostic value for PCFCL
- Is necessary for systemic follicular lymphoma
  - Grade 1: < 5 centroblasts per high-power field; grade 2: 6-15 centroblasts per high-power field; grade 3: > 15 centroblasts per high-power field
  - Grades 1 and 2 show minimal differences in long-term outcome
  - Thus, 2008 WHO classification lumps cases with few centroblasts as “follicular lymphoma grade 1-2 (low grade)” in systemic follicular lymphoma, and does not advise grading of PCFCL