Introduction
The classification of primary cutaneous B-cell lymphomas (CBCL) in the new WHO-EORTC classification
scheme significantly differs from the REAL/WHO approach. If validated in large multicenter studies this
new system will result in significant changes in the clinical management of patients with CBLC. The
WHO-EORTC recognizes four types of primary cutaneous B-cell lymphomas:
 | primary cutaneous marginal zone B-cell lymphoma |
| primary cutaneous follicle center lymphoma |
| primary cutaneous large B-cell lymphoma, leg type |
| primary cutaneous diffuse large B-cell lymphoma, other |
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Clinical
PCLBCLleg affects eldery patients, with a female predominance. Clinically, patients present with
rapidly growing tumor nodules that most often affect one or both lower legs, but rarely may be located
elsewhere on the body. Dissemination to extracutaneous sites is more common than in primary cutaneous
follicle center cell lymphoma (PCFCCL). In European studies the 5-year survival is 55%. Patients with a
solitary tumor do better than those with multiple nodules on one or both legs.
Case 7 - Figure 4 - Large lymphocytes, some with features of immunoblasts, others with features of centroblasts.
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Case 7 - Figure 5 - CD20. Staining with the CD20 antibody reveals a B-cell phenotype.
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Case 7 - Figure 6 - Large lymphocytes, some with features of immunoblasts, others with features of centroblasts. bcl-2: The tumor cells are strongly and uniformly bcl-2 positive.
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Case 7 - Figure 7 - Ki-67: The proliferative rate as measured by staining with Ki-67 is in excess of 80%.
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Morphology
Histologically, the tumor consists of a dense, deep, diffuse and monotonous infiltrate that often
extends deep into the fat. The tumor is comprised almost exclusively of centroblasts and immunoblasts.
Only few small cells of B- or T-cell phenotype are admixed. Centroblasts correspond to the large
noncleaved follicular center cells in the Lukes and Collins classification. They have vesicular nuclei
with dispersed chromatin, one to three prominent nucleoli and a small amount of basophilic cytoplasm.
Immunoblasts have a centrally located single nucleolus and a moderate amount of basophilic cytoplasm.
Mitotic figures are easily found in PCLBCL-leg and the tumor does not elicit a stromal response..
Immunophenotype
CD20+++, CD79A+++, bcl-2+++, bcl-6++, MUM-1++. CD10-, . Monotypic surface or cytoplasmic
immunoglobulins.
Genetics/molecular
No consistent chromosomal translocation. EBV negative. Activated B-cell gene expression profile.
Treatment
The aggressive clinical behavior necessitates treatment as a systemic diffuse large B-cell lymphoma
with multiagent chemotherapy (anthracycline based) or newer agents such as rituximab.
Comment
PCLBCL-leg was included in the original EORTC classification as a CBCL of intermediate malignancy,
with a more aggressive clinical course than PCFCCL. This subclassification has caused much controversy
and skepticism, but it now appears that recent clinicopathologic and molecular studies support this
approach. The difference between WHO-EORTC and WHO classification schemes centers on diffuse large cell
lymphomas. In the WHO this diagnosis depends on growth pattern only. In the absence of a follicular
component lymphomas with a diffuse growth pattern are classified as diffuse large cell lymphoma,
independent of the cell type of lesional cells. Accordingly, the subgroup of diffuse large cell lymphoma
in the WHO includes lymphomas with a predominance of centrocytes as well as lymphomas composed almost
exclusively of centroblasts or immunoblasts. The WHO-EORTC groups diffuse large cell lymphomas with
centrocytes together with the follicular center cell lymphomas. The category of PCBCL-leg is reserved
for tumors with a diffuse growth pattern, composed of centroblast or immunoblasts and with a bcl-2
positive phenotype. This difference in grouping has implications for therapy. By including diffuse
large cell lymphomas with centrocytes in the diffuse large cell category (WHO) these tumors were
generally treated more aggressively, i.e. with systemic chemotherapy. Inclusion in the category of
PCFCCL allows for localized treatment of these neoplasms, either with excision, radiation or
intralesional rituximab.
Practical Considerations
An appropriate antibody panel for work-up of CBCL should contain at a minimum: CD20 or CD79a, bcl-2,
bcl-6, CD10, Ki-67, CD3, kappa, lambda
| Diagnosis | Primary cutaneous FCL | Primary cutaneous LBCL, leg-type |
| Morphology | Predominance of centrocytes, that are often large, especially in diffuse lesions
Centroblasts may be present, but not in confluent sheets
Pattern may be follicular, follicular and diffuse, or diffuse
A continuum without distinct categories or grades | Predominance of large to medium sized B cells with round nuclei, prominent nucleoli, and coarse chromatin
Cells may resemble centroblasts and immunoblasts
Little stromal reaction, confluent destructive growth pattern |
| Immunophenotype | Bcl-2: +/-, staining is weak when present
Bcl-6: +
CD10: +/-, diffuse lesions more often CD10 negative
MUM-1: usually - | Bcl-2: ++, staining is typically strong and in most neoplastic cells
Bcl-6:+/-
CD10:-/+, usually negative
MUM-1: usually + |
| Clinical features | Middle aged adults
Most commonly involving head or trunk
Tumor nodules, sometimes with satellite lesionsRarely multifocal | Most commonly elderly, especially women
Usually localized on leg, most often below knee
May uncommonly occur in other locations |
References
- WHO-EORTC classification for cutaneous lymphomas. Blood (in press)
- Grange F, Bekkenk MW, Wechsler J, et al. Prognostic factors in primary cutaneous large B-cell lymphomas: A European multicenter study. J Clin Oncol. 2001;19:3601-10.
- Goodlad JR, Krajewski AS, Batsone PJ, et al. Primary cutaneous diffuse large B-cell lymphoma. Prognostic significance and clinicopathologic subtypes. Am J Surg Pathol 2003;27:1495-1502.
- Hoefnagel JJ, Dijkman R, Basso K, et al. Distinct types of primary cutaneous large B-cell lymphoma identified by gene expression profiling. Blood (in press)
