Primary Cutaneous CD4+ Small/Medium T-Cell Lymphoproliferative Disorders

Abstract

Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (PCSMLPD) is a recently recognized entity in the 2017 World Health Organization (WHO) classification. It belongs to the T-follicular helper (TFH) lymphoproliferations. The clinical, pathologic, and molecular features of this localized disease are underresearched. We conducted a retrospective multicentric study of 60 patients with a PCSMLPD that presented as a single cutaneous lesion. Clinical, pathologic, and targeted molecular analyses were performed. PCSMLPD presented mostly as a nodule (45%), located on the head and neck area (50%) in adults (mean age: 59 y [43.3 to 75.2]). All patients had an indolent disease course, either at initial staging or during follow-up (mean: 16.6 mo [1.3 to 31.9]). Spontaneous regression was reported in 31.9% of cases. The infiltrates were most often nodular and/or diffuse, expanding in the whole dermis (78%, Pattern 1), rather than subepidermal band-like in the superficial dermis (22%, Pattern 2). Epidermotropism, folliculotropism, and capillary hyperplasia were common. The expression of TFH lineage markers was more extensive in lesions with Pattern 2, but a substantial B-cell infiltrate was seen in both types of lesions. A clonal rearrangement of the TCR genes was identified in 68% of cases. One sample of the 13 tested revealed a mutation in the DNMT3A gene among the 9 genes studied (TET2, DNMT3A, IDH2, RHOA, SETD2, PLCG1, STAT3, STAT5B, and CD28). PCSMLPD follows a benign clinical course and can spontaneously regress after biopsy. Although PCSMLPD expresses TFH lineage markers, mutations usually found in angioimmunoblastic T-cell lymphomas are uncommon.

The Clinical Spectrum of Primary Cutaneous CD4+ Small/Medium-Sized Pleomorphic T-Cell Lymphoproliferative Disorder: An Updated Systematic Literature Review and Case Series

“…Most lesions were asymptomatic, although 4 cases described accompanying pruritus. The most common initial clinical diagnoses reported prior to biopsy were reactive lymphoid hyperplasia ( n = 24), basal cell carcinoma (BCC; n = 12), lymphoma unspecified ( n = 8), and insect bite reaction ( n = 6) [9].…”

“…Finally, the same patient achieved lasting complete resolution after just 3 weeks of local low-dose radiotherapy. Two other patients were treated with systemic corticosteroids and achieved only clinical improvement [11], compared to the 15 described cases managed with topical corticosteroids who completely resolved [9]. One case was treated with oral doxycycline without resolution [12].…”

Primary cutaneous peripheral T-cell lymphomas with a T-follicular helper phenotype: an integrative clinical, pathological and molecular case series study

“…A retrospective series published by our group showed a presentation with isolated self‐limited lesions, with a tendency for spontaneous regression after skin biopsy. 12 The lesions of pcTFH‐PTCL, taken individually, sometimes have the appearance of solitary dome‐shaped erythematous nodules, similar to the nodular variants of pcSMLPD. Nevertheless, these patients received chronic and even aggressive courses of treatment and were resistant to therapy, and few had nodal or systemic involvement during the evolution of the disease, making a diagnosis of pcSMLPD for such patients inappropriate and misleading in terms of clinical management.…”

“…6,7 Primary cutaneous CD4 + small-/medium-sized cell lymphoproliferative disorder (pcSMLPD), a disease generally presenting as solitary, self-contained lesions with distinctly indolent behaviour, is also considered to belong to the TFH lineage, [8][9][10][11] although it does not share the genetic mutations reported in systemic TFH-PTCL. 12 A subset of lymphoma with predominant or primary cutaneous presentation bearing a TFH phenotype (pcTFH-PTCL) cannot be reliably classified into any of the recognized entities of the current WHO classification. They are likely to differ from MF, SS and pcSMLPD by clinical presentation of lesions (multiple, with varied appearances, not restricted to patches/plaques), their histology and their outcomes (protracted disease with sometimes aggressive evolution), and, in contrast with other PTCLs, are defined by the absence of systemic disease and nodal involvement.…”

“… 6 , 7 Primary cutaneous CD4 + small‐/medium‐sized cell lymphoproliferative disorder (pcSMLPD), a disease generally presenting as solitary, self‐contained lesions with distinctly indolent behaviour, is also considered to belong to the TFH lineage, 8 , 9 , 10 , 11 although it does not share the genetic mutations reported in systemic TFH‐PTCL. 12 …”