Management of primary cutaneous CD4⁺ small and medium pleomorphic T-cell lymphoma: A retrospective study

To the Editor:

Primary cutaneous small and medium CD4⁺T-cell lymphoma (CD4⁺ PCSM-TCL) is a rare variant of T-cell lymphoproliferative disorder accounting for 2% of all primary cutaneous lymphomas.¹ Clinically, this lymphoma is generally indolent and presents as a solitary papule, plaque, or nodule predominantly on the face, neck, or upper trunk.¹ On histologic analysis, it is characterized by a dense, nodular or diffuse lymphocytic infiltrate in the dermis. In the 2016 World Health Organization (WHO) classification, CD4⁺ PCSM-TCL is categorized as a primary cutaneous small- or medium-sized T-cell lympho-proliferative disorder given its indolent behavior and favorable outcomes.² However, no standard of care was established due to its rarity.

We retrospectively reviewed a cohort of 684 patients with a diagnosis of cutaneous lymphoma during 2008–2015 under an institutional review board—approved protocol. By using the 2005 WHO and European Organisation for Research and Treatment of Cancer (WHO-EORTC) criteria and 2008 WHO criteria¹ (a predominant small-to-medium—sized CD4⁺ pleomorphic T-cell phenotype without clinical features of mycosis fungoides), 11 patients were confirmed to have CD4⁺ PCSM-TCL. These patients (6 men and 5 women) had a median age of 70 (range 44–81) years at diagnosis (Table I). All tumors were CD3⁺ and CD4⁺ and had the clonal T-cell receptor (TCR). Patients were primarily white. The median follow-up time was 25 (range 8–93) months. Seven patients had solitary lesions. Six patients presented with lesions in the head and neck area. Five patients had disease in extremities and trunk. Four patients had multifocal lesions. No patient had systemic disease.

Table I.

Patient, tumor, and treatment characteristics of patients with primary cutaneous small and medium CD4⁺ T-cell lymphoma

Pt no.	Age at diagnosis, y	Sex	Distribution	Location	TCR	CD3	CD4	CD8	Treatment	RT dose	Follow- up, mo	Outcome	Recurrence
1	80	F	Multifocal	Left frontal, parietal area	Clonal	+	+	NA	Excision		32	CR	-
2	80	M	Multifocal	Left posterior thigh and right forearm	Clonal	+	+		RT	36 Gy in 20 fractions	93	CR	-
3	78	M	Multifocal	Left popliteal, left thigh, left arm, and left abdomen	Clonal	+	+		Excision, RT	30 Gy in 10 fractions	26	CR	-
4	68	M	Solitary	Right upper mid-back	Clonal	+	+	-	Excision		19	CR	-
5	72	F	Solitary	Right face	Clonal	+	+	-	Excision		41	CR	-
6	70	F	Solitary	Right upper chest	Clonal	+	+	-	Excision		25	CR	-
7	44	F	Solitary	Left cheek	Clonal	+	+	-	RT	36 Gy in 20 fractions	25	CR	-
8	67	F	Solitary	Right lateral nasal wall	Clonal	+	+	-	Excision		9	CR	-
9	81	M	Solitary	Right upper back	Clonal	+	+	-	Excision		8	CR	-
10	65	M	Solitary	Right anterior scalp	Clonal	+	+	-	Excision		25	CR	-
11	45	M	Multifocal	Bilateral cheek, bilateral temple	Clonal	+	+		RT	22.50 Gy in 10 fractions	17	CR	-

Electron RT was used.

CR, Complete response; NA, not available; Pt, patient; RT, radiation therapy; TCR, T-cell receptor.

Seven patients were treated with local excision alone. Three patients received electron radiation therapy (RT) alone, and 1 patient with 4 lesions was treated with both excision and RT. The median RT dose administered was 33 (range 22.5–36) Gy in 1.8–3 Gy/fraction. All patients achieved complete remission. These findings are similar to 2 previously published case series, highlighting that local failure is not frequently observed in daily practice.^3,4 Our data confirmed that surgical excision and RT can be used as primary treatment modalities for CD4⁺ PCSM-TCL.

In the present series, 2 patients with 4 lesions and 2 patients with 2 lesions achieved complete remission after local treatments targeted to each individual lesion site. Previously, it was suggested that multifocal disease might have a different clinical behavior from that of solitary lesions.³ Our data suggests that irrespective of multiple lesions localized treatment modalities are also suitable for this group of patients.

Selected studies with available treatment approaches and clinical outcomes were reviewed using PubMed (Table II). In total, 135 patients were identified; 41 patients were treated with localized RT alone, and 53 patients received local excision alone. Other treatment approaches (eg, administration of steroids, combination of RT and excision, and chemotherapy) are described in Table II. Overall, at a median follow-up of 24 months, 109 patients (80.7%) obtained complete remission.

Table II.

Selected literature review for management of primary cutaneous small and medium CD4⁺ T-cell lymphoma

Reference	Patients, N	Treatment approaches	Median follow-up, mo	Outcomes	Comments
Garcia-Herrera et al,  J Clin Oncol 2008;  26(20):3364–3371	24	6 RT, 8 excision,  5 chemotherapy,  5 other	24	16 complete remission,  4 partial remission,  2 no response,  2 progressive disease
Grogg et al,  Mod Pathol  2008;21(6):708–715	15	4 RT, 6 excision,  1 no treatment,  4 unknown	9	9 complete remission,  1 local recurrence,  1 systemic development,  4 unknown
Baum et al, J Am  Acad Dematol  2011;65(4):739–748	10	3 RT, 4 excision,  2 excision + steroids,  1 steroids + doxycycline	25	7 complete remission,  1 regional recurrence,  2 persistent nodule
James et al,  Leuk Lymphoma  2015;56:951–957	23	6 RT, 11 excision, 2 NA,  2 excision + RT,  1 CHOP + RT, 1 ILS	29	19 complete remission,  3 unknown, 1 other	Other: no local recurrence, possible persistent systemic disease, refused chemotherapy
Alberti-Violetti et al,  J Cutan Pathol  2016;43(12):  1121–1130	62	21 RT, 23 excision, 14 TS,  5 phototherapy,  1 ILS, 4 other	14	57 complete remission,  1 partial remission,  1 stable disease,  1 progressive disease,  2 W&W	Other: including cyclophosphamide, methotrexate, topical nitrogen mustard, systemic steroids
Topal et al, J Dtsch  Dermatol Ges  2016;14(5):522–524	1	RT 200 cGy × 15 fractions	NA	Complete remission

CHOP, Cyclophosphamide, doxorubicin, vincristine, prednisone; ILS, intralesional steroids; NA, not available; RT, radiation therapy; TS, topical steroids; W&W, waxing and waning.

Because CD4⁺ PCSM-TCL is most often indolent with rare systemic involvement, the condition should be primarily managed with localized treatment. This clinical course is different from that of mycosis fungoides, of which ~1 in 3 cases is associated with extracutaneous dissemination requiring more aggressive treatment regimens.⁵