Almost 4% of sFL cases involve the skin.^2,3,4,5 Cutaneous dissemination invariably occurs after the diagnosis of nodal disease. The typical interval between the original diagnosis of lymphoma and skin involvement is 3 to 7 years. Most of the cutaneous lesions in sFL present on the head and neck.³ Rare cases with rosacea-like clinical presentation had been described.⁶ Cases of sFL with cutaneous recurrences had been reported.⁷ Bone marrow infiltration is usually present at the time of skin involvement. The prognosis of sFL depends on histologic grade: the 5-year survival is 60% in high-grade and 100% in low-grade disease.² Skin involvement does not appear to influence clinical outcome.

sFL needs to be distinguished from primary cutaneous follicle center lymphoma (PCFCL), as the latter carries a good prognosis and only rarely requires chemotherapy. sFL with cutaneous involvement is characterized by a dermal-based infiltrate with sparing of the epidermis (Fig. 30-1). The infiltrate shows a follicular and/or diffuse pattern (50%). Grading of lesions is mandatory, as this can determine the prognosis of the tumors. Grading of sFL is based on the number of centroblasts per high-power field (counting 10 hpf, 0.159 mm²). Grade 3 lesions reveal more than 15 centroblasts/hpf. Grading of PCFCL is of no value and should not be performed in any case. The morphologic pattern of PCFCL is similar to that of sFL. The so-called spindle cell variant is unique to PCFCL and not associated with sFL.

The immunophenotype of sFL is characterized by B-cell antigenic expression (CD20, CD19) and markers of germinal center differentiation (CD10, BCL-6, LMO-2) (Fig. 30-2). BCL-2 expression is considered the hallmark of the disease. However, BCL-2 and CD10 are often negative in high-grade cases.⁸ Cases with a follicular pattern can show retained follicular dendritic networks, demonstrated by CD21, CD23, or CD35. MUM1 is typically positive in high-grade lesions, and only stains background plasma cells in low-grade follicular lymphoma (FL). CD30 can be seen in approximately 30% of cases.⁹

Nearly all cases of low-grade FL and most higher-grade FL show the t(14;18) translocation affecting the IGH and BCL2 genes. This translocation is only seen in a small fraction of cases of PCFCL (10% to 20%).¹

As opposed to sFL, most cases of PCFCL are negative for BCL2. Additionally, CD10 can be negative in cases with a diffuse growth pattern. MUM1 is invariably negative in PCFCL. Follicular dendritic networks are retained in cases with a nodular growth, but lost in diffuse patterns. Ki67 can be markedly elevated in PCFCL, particularly those with a large number of centroblasts. Increased proliferation has no prognostic significance, as opposed to sFL.

The t(14;18)(q32;q21), IGH-BCL2 translocation is present in 90% of low-grade FL, but is less frequent in high-grade FL. Other common cytogenetic aberrations include loss of 1p, 6q, 10q, and 17p, and gains of chromosomes 1, 6p, 7, 8, 12q, 18, and X. Fluorescent in-situ hybridization (FISH) detects ∼85% of the IGH-BCL2 translocation. This translocation is only seen in a small fraction of cases of PCFCL (10% to 20%).¹ Rare cases of high-grade FL can show an MYC rearrangement.

Cutaneous involvement is present in approximately 12% of patients with systemic MZL.¹² Cutaneous lesions typically occur as multiple red nodules on the head and neck (Fig. 30-3). In contrast, primary cutaneous MZL (PCMZL) has a predilection for the trunk and extremities. Nearly 20% of PCMZL can show generalized skin lesions.¹³ MZL can occur more frequently in the setting of Hepatitis C virus (HCV) infection, and rarely may present as lipoatrophy.¹⁴