Primary cutaneous follicular lymphoma C82.6

Most common primary cutaneous B-cell lymphoma (indolent, low malignant character), originating from neoplastic follicular centres. The lymphoma generally consists of a mixture of centrocytes (small and medium-sized cells with a notched nucleus) and centroblasts (large cells with large bright, non-notched nuclei and prominent corpuscles), which may have a follicular, mixed follicular/diffuse or diffuse growth pattern.

In absolute terms, primary cutaneous follicular B-cell lymphomas (PCBCL) are rare, although they are by far the largest group among primary cutaneous B-cell lymphomas (PCBCL) (40-70% of this group).

An incidence of 4/100,000/year is reported for the total number of primary cutaneous and non-cutaneous follicular B-cell lymphomas (see Follicular Lymphoma below). The proportion of primary cutaneous B-cell lymphomas is about 1% in larger B-cell lymphoma collectives (Kim et al. 2015).

The origin of follicular lymphoma lies in the B cells of the germinal centers. In about 90% of patients, a balanced translocation between the immunoglobulin heavy chain gene on chromosome 14 and the Bcl-2 gene on chromosome 18 is detectable. The t(14;18)(q32;q21) leads to overexpression of the intact Bcl-2 protein and thus to inhibition of apoptosis. This constellation conditions a longer survival time of transformed cells and their slow accumulation in lymphoid tissues.

About 70% of the known t(14;18)(q32;q21) translocations are found in the major breakpoint region (MBR) of the Bcl-2 locus, 10-15% in the minor breakpoint region (mbr) of the Bcl-2 locus ((Huet S et al. 2018). Note: Bcl-2 translocations are characteristic but not specific to follicular lymphoma. They can also be detected at low frequency in healthy individuals (bone marrow, lymph nodes). Furthermore, this translocation is a feature of diffuse large B-cell lymphoma (DLBCL) detected in bone marrow and lymphoid tissue.

Middle-aged adults (40-60 years). m:w=1:1

Trunk, capillitium, face (> 90%), rarely on the extremities (DD: cutaneous marginal zone lymphoma).

Mostly solitary, rarely multiple, diffusely arranged or grouped, 3.0-5.0 cm (in diameter), red or brown-red, asymptomatic plaques or nodules with a smooth surface. No tendency to ulceration.

A special variant is the so-called "Crosti-lymphoma". Here there are large plaques on the back.

Dense nodular or diffuse infiltration of dermis and subcutis. Clear orientation to the adnexal structures with subepidermal free zone (free border zone). No epidermotropy. A distinct follicular pattern is observed especially when localized on the head. Cytomorphologically, smaller cells with clearly notched nuclei and numerous granules (characteristics of centrocytes) as well as larger cells with large round nuclei and one or more prominent nucleoli (characteristics of centroblasts) are found. The infiltrate is supplemented by immunoblasts (large nuclei with central nucleolus), small lymphocytes, histiocytes, rarely eosinophilic granulocytes and plasma cells. Especially in early lesions, numerous reactive T cells are found.

With the progression of the tumor, follicular structures are expressed less frequently, and the number of reactive T cells is relatively reduced. Monomorphic populations of large germinal center cells tend to predominate.

Immunohistology: expression of B-cell associated antigens: CD19, CD20, CD79a. In follicular structures: expression of CD10; also BCL6, CD21 (dendritic reticulum cells).

PCR: in about 70% of cases, detection of clonal tumor cell population with monoclonal rearrangement of immunoglobulin heavy chain genes.

Cytogenetic feature of systemic follicular lymphoma is chromosomal translocation t(14;18) (q32;q21) in up to 90% of cases. This translocation is found in a minority of primary cutaneous follicular lymphomas (!). The chromosomal translocation leads to an overexpression of Bcl-2, an anti-apoptotic oncogene.

Clinical differential diagnoses: S.u. lymphoma, cutaneous B-cell lymphoma.

Histological differential diagnoses:

• Lymphoma, cutaneous B-cell lymphoma, marginal zone l ymphoma: The histopathologic pattern shows reactive germinal centers surrounded by neoplastic marginal zone cells (centrocyte-like cells), lymphoplasmacytoid cells, and plasma cells.
• Non-follicular nodular (cytic) mantle cell lymphoma.
• Pseudolymphoma ( lymphadenosis cutis benigna type).

Basically, follicular lymphomas are considered lymphomas with an excellent prognosis.

• In patients with "low burden follicular lymphoma", i.e. only few HV and no other clinical symptoms, a "wait and see" strategy can be pursued in coordination with the patient. Chemotherapy at this stage is not recommended.
  • Alternative: In a large study with 384 patients (RESORT) it could be shown that the early application of Rituximab was superior to the "wait and see" group (time to treatment failure).
  • Alternative: Patients with solitary or few (< 10) lesions can be treated either surgically or (locally) radiotherapeutically.
• Recurrences are not always a sign of tumor progression. In this respect they can also be treated locally.
• For patients with advanced follicular lymphomas, standard chemotherapy according to the CHOP scheme or R-CHOP scheme ( rituximab + CHOP) is recommended. R-CHOP can significantly increase the time to therapy failure (TTF) according to studies.
• Alternatively: CVP (cyclophosphamide, vincristine, prednisone) or R-CVP (rituximab + CVP). The combination R-CVP is also superior here, the time to progression (TTP) is extended by 20 months according to studies.
• In patients with multiple lesions, good results were achieved with systemically or intralesionally applied anti-CD20-Ak(rituximab).

Negative bone marrow infiltration results in an excellent prognosis with a 5-year survival rate of 95%. With detectable bone marrow infiltration the 5-year survival rate drops to 63%. Remarkably, the prognosis worsens significantly with localization on the leg (5-year survival rate of only 40% - mustard 2007-). The reason for this is unclear.

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