Primary cutaneous indolent B-cell lymphomas – a retrospective multicenter analysis and a review of literature

Figures & data

Table 1. Patients’ characteristics and clinical manifestations in indolent Primary Cutaneous B-cell Lymphomas.

Characteristic	PCBCL* No (%) or median (range)	PCFCL No (%) or median (range)	PCMZL No (%) or median (range)
Age [years]	61 (21–84)	57 (21–84)	62,5 (29–83)
Histopathology	52	25 (48)	26 (52)
Clinical suspicion
Solid cancer	9 (17)	5 (20)	4 (15)
Lymphoma	24 (46)	10 (40)	14 (54)
Reactive/inflammation	16 (31)	10 (40)	6 (23)
Missing data	3 (6)	–	2 (8)
Localization
Trunk	26 (52)	13 (52)	12 (46)
Head	21(40)	13 (52)	8 (31)
Upper extremities	13 (25)	7 (28)	6 (23)
Lower extremities	6 (11)	1 (16)	4 (15)
Number of lesions
One on one part	3 (6)	1 (4)	2 (7)
Multiple on one part	21 (40)	15 (60)	6 (23)
Solitary	28 (54)	9 (36)	18 (70)
Biggest lesion size [cm]
	2 (0.8–10)	2 (0.2–8)	2 (1–10)
Lesion character:
Nodules	28 (54)	14 (56)	14 (54)
Other	14 (27)	5 (20)	8 (31)
Missing data	10 (19)	6 (24)	4 (15)
Time from first symptoms to diagnosis [months]	6 (1–120)	9 (2–50)	6 (1–120)
Symptoms:
Pruritus	21 (40)	11 (44)	10 (38)
Pain	3 (6)	2 (8)	1 (4)
No symptoms	29 (56)	14 (56)	15 (58)

PCBCL: primary cutaneous B-cell lymphoma; PCFCL: primary cutaneous follicle center lymphoma; PCMZL: primary marginal zone lymphoma.

*One patient with undefined PCBCL was included in the general group only, thus the numbers may not add up.

Table 2. Diagnostic tests and procedures used in indolent primary cutaneous B-cell lymphomas.

Diagnostic test/procedure	General No (%)	PCFCLNo (%)	PCMZLNo (%)
Bcl-2 and Bcl-6 status (IHC)
Data available	38/52 (73)	19/25 (76)	19/26 (73)
Bcl-2 positive	27/38 (71)	10/19 (52)	17/19 (89)
Bcl-6 positive	17/38 (45)	15/19 (79)	2/19 (10)
Bone marrow examination
Data available	35/52 (67)	16/25 (64)	19/26 (73)
BM Biopsy	33/52 (63)	14/16 (87)	19/19 (100)
BM cytological and cytometric evaluation	2/52 (4)	2/16 (12)	0
BM involvement	1/35 (3)	0 (0)	1/19 (5)
Imaging studies
Data available	47/52 (90)	23/25 (92)	23/26 (88)
Conventional X-ray and ultrasonography	5/47 (11)	3/23 (13)	2/23 (9)
CT	25/47 (53)	12/23 (52)	13/23 (57)
PET CT – Data available	17/47 (36)	8/23 (35)	9/23 (39)
PET CT positive	9/17 (53)	4/8 (50)	5/9 (56)
LDH
Data available	33/52 (63)	19/25 (76)	14/26 (54)
Elevated	11/33 (33)	5/19 (26)	5/14 (36)

Bcl-2: B-cell lymphoma 2 gene; Bcl-6: B cell lymphoma 6 gene; BM: bone marrow; CT: computed tomography; IHC: immunochemistry; LDH: lactate dehydrogenase; PCFCL: primary cutaneous follicle center lymphoma; PCMZL: primary marginal zone lymphoma; PET-CT: positron-emission tomography/computed tomography.

The numbers may not add up, since one undefined PCBCL case was only included in the general column.

Table 3. Overview of publications of retrospective studies with at least 20 patients with primary cutaneous follicular lymphoma or primary marginal zone lymphoma, of which at least some were patients with multifocal disease.

Author, Publication, Year	No. of analyzed patients: PCFCL	No. of analyzed patients: PCMZL	Treatment modality	Complete response rate (%)	Median follow up (months)	Treatment outcomes
Hoefnagel et al. Arch Dermatol 2005 [8]	–	50	Observation, Rth, Chth (no Imt), Surg	Rth: 16 Chth: 20	36	5-y RFS 51% Extracutaneous dissemination 1/50
de la Fouchardiere et al. Ann Pathol 2005 [10]	2	33	Observation, Rth, Chth (no Imt), Surg, Antibiotics	–	24	Extracutaneous dissemination 6/35 (PCMZL only) Transformation 2/35 (PCMZL only)
Lucioni et al. Cancer Medicine 2016 [9]	96	–	Rth: 47, Chth: 26, Surg: 20,	84 (majority unifocal)	47	RR: 43% Extracutaneous dissemination 5/81 MTR: 24 months
Senff et al. JCO 2007 [11]	171	71	Rth: 31 PCMZL, 111 PCFCL, Chth: 5 PCMZL, 35 PCFCL, Surg: 9 PCMZL, 11 PCFCL	81 PCMZL, 98,8 PCFCL	–	RR: 56% PCMZL, 30% PCFCL extracutaneous dissemination: 8,5% PCMZL, 10,5% PCFCL
Hamilton et al. IJRO 2013 [19]	44	59	Rth: 49 PCMZL, 34 PCFCL, Chth: 1 PCMZL, 2 PCFCL, Imt: 1 PCMZL, 2 PCFCL, Surg: 7 PCMZL, 3 PCFCL	95 PCMZL (88% unifocal), 80 PCFCL	46,8	RR: 36% PCMZL, 23% PCFCL
Golling et al. et al. Leukemia Lymphoma 2008 [18]	16	31	Rth: 2 PCMZL, 4 PCFCL, Surg: 11 PCMZL, 16 PCFCL, Antibiotics: 11 PCMZL, 4 PCFCL	Rth: 100 PCMZL, 75 PCFCL, Surg: 91 PCMZL, 67 PCFCL, Antibiotics: 0 PCMZL, 0 PCFCL	63	RR: 71% PCMZL, 43% PCFCL Extracutaneous dissemination − 0
Akhtari et al. Leukemia Lymphoma 2016 [21]	16	21	Rth	Rth: 100	29	RR: 10/42 lesions MTR: 10 months
Senff et al. Blood 2008 Metaanalysis of 92 articles [7]	–	–	Rth: 132 PCMZL, 460 PCFCL, Imt: 3 PCMZL, 28 PCFCL, Chth: 33 PCMZL, 104 PCFCL, Surg: 75 PCMZL, 93 PCFCL	Rth: 99 PCMZL, 99 PCFCL, Imt: 67 PCMZL, 75 PCFCL, Chth: 85 PCMZL, 85 PCFCL, Surg: 99 PCMZL, 98 PCFCL	–	RR: Rth: 46% PCMZL, 47% PCFCL, Chth: 57% PCMZL, 14% PCFCL, Surg: 43% PCMZL, 40% PCFCL
Muniesa et al. JAAD 2020 [25]	29	25	Imt (Rituximab x 4)	Imt: 72 PCFCL, 64 PCMZL	90	RR: 41% PCFCL, 48% PCMZL mPFS 62 months

Chth: chemotherapy; CR: complete remission; Imt: immunotherapy; MTR: median time to relapse; PCFCL: primary cutaneous follicle center lymphoma; PCMZL: primary marginal zone lymphoma; PR: partial remission; PFS: progression free survival, RFS: relapse free survival; RR: relapse rate; Rth: radiotherapy; Surg: surgical treatment.

Table 4. First-line therapy results in primary cutaneous indolent B-cell non-Hodgkin lymphoma patients.

	CR No (%)	PR No (%)	RD No (%)
Radiotherapy	10 (83)	2 (17)	0 (0)
Rituximab monotherapy	5 (50)	5 (50)	0 (0)
Rituximab plus chemotherapy	7 (70)	2 (20)	1 (10)
Surgery	15 (94)	1 (6)	0 (0)
Total	37 (77)	10 (21)	1 (2)

CR: complete remission; PR: partial remission; RD: refractory disease.

No: number.

Figure 1. DOR correlation with CLIPI at 5 years for indolent PCBCLs. DOR: duration of response; CLIPI: cutaneous lymphoma international prognostic index; PCBCL: primary cutaneous B cell lymphoma

Hoefnagel JJ, Vermeer MH, Jansen PM, et al. Primary cutaneous marginal zone B-cell lymphoma: clinical and therapeutic features in 50 cases. Arch Dermatol. 2005;141(9):1139–1145.

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de la Fouchardiere A, Balme B, Chouvet B, et al. Pathological and clinical correlations in primary cutaneous B-cell lymphomas: a series of 44 cases. Ann Pathol. 2005;25(1):8–17.

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Lucioni M, Berti E, Arcaini L, et al. Primary cutaneous B-cell lymphoma other than marginal zone: clinicopathologic analysis of 161 cases: comparison with current classification and definition of prognostic markers. Cancer Med. 2016;5(10):2740–2755.

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Senff NJ, Hoefnagel JJ, Jansen PM, et al. Reclassification of 300 primary cutaneous B-Cell lymphomas according to the new WHO-EORTC classification for cutaneous lymphomas: comparison with previous classifications and identification of prognostic markers. J Clin Oncol. 2007;25(12):1581–1587.

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Hamilton SN, Wai ES, Tan K, et al. Treatment and outcomes in patients with primary cutaneous B-cell lymphoma: the BC Cancer Agency experience. Int J Radiat Oncol Biol Phys. 2013;87(4):719–725.

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Golling P, Cozzio A, Dummer R, et al. Primary cutaneous B-cell lymphomas – clinicopathological, prognostic and therapeutic characterisation of 54 cases according to the WHO-EORTC classification and the ISCL/EORTC TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sezary syndrome. Leuk Lymphoma. 2008;49(6):1094–1103.

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Akhtari M, Reddy JR, Pinnix CC, et al. Primary cutaneous B-cell lymphoma (non-leg type) has excellent outcomes even after very low dose radiation as single-modality therapy. Leuk Lymphoma. 2016;57(1):34–38.

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Senff NJ, Noordijk EM, Kim YH, et al. European Organization for Research and Treatment of Cancer; International Society for Cutaneous Lymphoma. European Organization for Research and Treatment of Cancer and International Society for Cutaneous Lymphoma consensus recommendations for the management of cutaneous B-cell lymphomas. Blood. 2008;112(5):1600–1609.

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Muniesa C, Domingo-Domenech E, Fornons-Servent R, et al. Systemic rituximab for the treatment of the indolent forms of primary cutaneous B-cell lymphomas: data from the Spanish Primary Cutaneous Lymphoma Registry. J Am Acad Dermatol. 2020;83(5):1535–1538.

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