PCFCL is the most common subtype of CBCL, accounting for one-third to one-half of all CBCLs.^1,2,5,6 PCFCL occurs primarily in adults, with an age range of 17 to 89 years (median 51 to 58 years) and a slight male predominance.^2,5 Since the adoption of the 2005 WHO/EORTC classification for CBCLs, many cases previously thought to be primary cutaneous diffuse large B-cell lymphoma (PCDLBCL) would now be reclassified as PCFCL,² a distinction that is critical because of prognostic implications and therapeutic approach.

The etiology of PCFCL is unknown. Borrelia burgdorferi DNA can be identified within tissue from a minority of PCFCL cases in endemic areas in Europe⁷; however, this finding has not been confirmed in nonendemic areas including the United States.⁸ Screening for B. burgdorferi is not currently recommended as part of the evaluation of patients with suspected PCFCL.⁴ Causal connection to oncogenic bacterial or viral infections has also not been established. Hepatitis C viral DNA can be demonstrated in as many as 30% of cases of PCFCL, though the clinical relevance is unknown⁹; a similar situation exists for human herpesvirus 8.¹⁰ Epstein–Barr virus (EBV) DNA has not been demonstrated in PCFCL.¹¹

The clinical presentation of PCFCL is of solitary or clustered smooth, erythematous to violaceous infiltrated papules, plaques, nodules, or tumors, usually on the head and neck or trunk^2,12 (Fig. 26-1). Widespread or multifocal involvement can occur. Ulceration is rare. PCFCL occurring on the scalp is a particularly common presentation and can demonstrate relatively subtle erythema (Fig. 26-2) and present with isolated telangiectasias.¹³ A few distinct clinical variants of PCFCL have been described: “Crosti lymphoma” or “reticulohistiocytoma of the dorsum” presents with figurate, annular erythematous plaques surrounding infiltrated central plaques on the trunk.¹⁴ A military or agminated presentation on the face and trunk can mimic benign entities such as rosacea, insect bites, or folliculitis^15,16 (Fig. 26-3). Regardless of the clinical variant or extent of involvement, PCFCL has an excellent prognosis, with a 5-year survival of ≥95%.^2,17 Recurrences are relatively common, occurring in 20% to 50% of patients,^1,5 but do not negatively impact the long-term outcome. Extracutaneous involvement is not typical, being observed in about 10% of cases in the largest case series.^2,5 An exception to the generally excellent prognosis is PCFCL occurring on the leg, which has been associated with a less favorable 5-year survival of 41%.²

PCFCLs are composed of a mixture of centrocytes, with smaller, cleaved nuclei, and centroblasts, with larger, noncleaved nuclei and visible nucleoli (Fig. 26-4). Follicular, diffuse and follicular, or diffuse growth patterns are seen, with variable mixtures sometimes present within the same lesion. The epidermis is spared, and a grenz zone is nearly always present^18,19 (Fig. 26-5A). Lymphoid infiltrates are perivascular and periadnexal, and can extend into the fat¹⁸ in what has been described as a “bottom heavy” appearance.²⁰ As opposed to systemic FL, grading of PCFCL according to the WHO classification is not reflective of the clinical behavior of the disease and is no longer routinely reported.

The follicular pattern of PCFCL demonstrates distorted, variably sized follicles throughout the dermis and sometimes into the subcutaneous fat (Fig. 26.5). The most reliable feature of neoplastic follicles in PCFCL is a lack of tingible body macrophages, found in the majority of cases.^20,21 Other features of neoplastic follicles are variable size, reduced or absent mantle zones, and a lack of polarization, without distinct dark and light zones²¹ (Fig. 26-6). Reactive lymphoid follicles at the periphery¹⁹ and T-cell infiltrates can be prominent, particularly in the interfollicular zone and stroma of early lesions.¹⁷ Other inflammatory cells, such as eosinophils and plasma cells, are less frequently seen.^20,21

The diffuse pattern is the first type of PCFCL recognized and is more frequently encountered than the follicular type.^2,17,20,22 The diffuse pattern is usually present in larger nodules and tumors of PCFCL, but can be seen in smaller, early lesions and, in contrast to nodal FL, is a distinct histologic type that does not represent progression from a follicular pattern.²³ Morphologically, diffuse PCFCL shows a proliferation of large centrocytes with variable centroblasts in a nodular or sheet-like pattern, extending throughout the dermis and often into the subcutaneous fat. Well-formed follicular structures are absent²³ (Figs. 26-7 and 26-8). The diffuse pattern of PCFCL can be difficult to distinguish from PCDLBCL, particularly when there is an abundance of centroblasts (see section “Differential Diagnosis”).

A spindle-cell or sarcomatoid variant of CBCL has also been described, with many of these cases demonstrating follicle center origin.^{24,25,26,27,28} Spindle-cell follicle center lymphoma shows nodules or fascicles of spindled cells, often admixed with areas of more typical-appearing centroblasts and centrocytes. The spindled cells can be monomorphic or take on pleomorphic shapes, including “boomerang” or “spermatozoa” morphology^24,25 (Fig. 26-9). Thickened collagen bundles can be present, and differentiation from other spindle-cell neoplasms can be challenging and requires immunohistochemical (IHC) stains.²⁵