Papular mycosis fungoides: Six new cases and association with chronic lymphocytic leukemia

Table 1 Mycosis fungoides presenting as persistent papules in the literature

Case1	ARG; Dur	Distribution	Dermal infiltrate	Epidermal lymphocytes	Immunophenotype	PCR	Progression (time)2
Kodama1	57WM;	T	PV, F	Sm;	CD30-	ND	No
	NS			PMAs
Kodama2	58WF;	T, UE	Li, PV	Pleo Sm-med;	CD4+30-	Pos	No
	2 yr			No PMAs
Kodama3	57F;	T, UE, LE	Li, PV	NS;	CD30-	ND	Yes (3 yr)
	Few mo			No PMAs
Kodama4	41M;	LE	Li, PV	NS;	CD30-	ND	Yes (2 mo)
	NS			No PMAs
Kodama5	59WM;	T, UE, LE3	Li	NS;	CD30-	ND	No
	30 yr			PMAs
Kodama6	61M;	T	PV	NS;	CD4+8-30-	ND	No
	NS			PMAs
Uddin	31WF;	T, UE, LE	Li, PV, SC, VA	NS;	Mostly CD30-	ND	No
	2 yr			No PMAs
Martorell-Calatayud1	50WF;	T3	A, P, Li, PV, F	Pleo Med-lg;	CD4+30-	Pos	No
	2 yr			PMAs
Martorell- Calatayud2	55WF;	T, LE3	NS	Sm-med;	CD4+30-	Neg	No
	1.5 yr			No PMAs
Liu	27AM;	T3	Li	NS;	CD4+8-30-	ND	No
	NS			PMAs
Neri	47WF;	UE, LE	PV	Sm-med CL;	CD4-8+7+30-	Pos	No
	1 yr			PMAs
Noe1	83WF;	T, UE, LE	PV	NS;	CD4+30-	Pos	No
	3 yr			PMAs
Noe2	65WF; 1mo	T	Li, PV	NS	CD30-	ND	Yes (NS)
Brajon	63WM; 10 mo	T, UE, LE	Li, PV	CL;	CD4+8-30-	Pos	No
				NS
Santamarina– Albertos	55WM;	LE	Li	Sm-med CL;	CD4+30-	Pos	No
	1 yr			NS
Balta	35WM;	T, UE, LE	A, PV	NS;	CD4-8+30-	Pos	No (10 mo)
	2 yr			PMAs

¹References: [3-11];

²Time to progression of disease;

³Some grouping or clustering of lesions. ARG: Age, race, gender; Dur: Duration to disease; PCR: Polymerase chain reaction for rearrangement of T cell receptor gamma chain; NS: Not stated; T: Trunk; UE: Upper extremities; LE: Lower extremities; Li: Lichenoid; PV: Perivascular; A: Acanthosis; P: Parakeratosis; F: Fibrosis; VA: Vacuolar alteration; SC: Subcutaneous; Sm: Small sized; Med: Medium sized; Lg: Large sized; Pleo: Pleomorphic; PMA: Pautrier microabscess; CL: Lymphocyte with cerebriform or infolded nuclei.

Table 2 Six additional patients with papular mycosis fungoides

Pt	ARG; Dur1	Lesions and Size (mm)	Distribution	Dermal Infiltrate	Epidermal Lymphocytes	Immunophenotype2	TCR-γ(method)	Course and Status (Duration FU)
1	68WM; 15 mo	Pa (1-2)	T, UE, UE	PA, VA, F, PC, Eos, LVC	Focal basilar Ep, Med CLs; No PMAs	ED: NS D: CD4 > CD8, CD30 10%	Pos Sk + Bd (SSCP)3	Controlled on prednisone; developed pancytopenia; DwD (99 mo)
2	47 WM; 19 yr	Pa (3-5)	H/N, T	A, PV, F, Eos, PC, MtF, LVC	Focal basilar Ep, Med-lg CLs; PMAs	ED: CD4+8-7-62L-30- D: CD4 90%, CD8 < 10%, CD7< 10%, CD62L < 1%, CD30 5%-10%	Pos Sk + Bd (DGGE)3	Poor or partial response to PUVA, MTX, isotretinoin, XRT, IFNα; DwD (171 mo)
3	57 WF; 5 yr	Pa (2-5)	LE, UE	P, A, Li, PV, CLs	Basilar Ep, CLs; No PMAs	ED: CD4+8-7+62L+30+/- 4 D: CD4 80%, CD8 20%-30%, CD7 40%, CD62L 50%, CD30 1%-2%	Neg (DGGE)	PUVA/NBUVB: CR; breast CA; RA, HT; A, NED (156 mo)
4	68 WM; 6 mo	Pa (2-8)	T, LE	A, Li, F, EE, Neu (v), CLs	Diffuse Ep, Med CLs; No PMAs	ED: CD4+/-8-7+62L-30- D: CD4 60%-70%, CD8 20%, CD7 70%, CD62L 70%, CD30 1%-2%	Pos (DGGE)	PUVA: CR ; no progression; AwD (210 mo)
5	58 WM; 2 mo	PaNd (2-14)	T, LE	Sp, Li, F, FM, CLs	Basilar Ep, Med-lg CLs; PMAs	Not available	Neg (SSCP)5	TopHN2: CR; No progression; A, NED (171 mo)
6	81 WM; 15 mo	PaNd (5-15)	T, LE	Li, F, CLs, MtF	Diffuse Ep, Med-lg CLs; PMAs	ED: CD4+8-7-62L-30- D: CD4 99%, CD8 1%, CD7 10%, CD62L 99%, CD30 20%	Neg (DGGE)3,5	PUVA: PR; DwD/MI (12 mo)

¹Duration: Time from onset of disease to evaluation;

²Estimated percentage of positively labeled cells in dermal infiltrate (frozen sections). CD2, CD3, and CD5 expressed by all cases (data not shown);

³Clonal B-cell population detected by flow cytometry for patients 1, 2 and 6 and confirmed by PCR for patients 1 and 2 (see text for details);

⁴30% of epidermotropic T cells expressed CD30;

⁵Blood sample also negative for T cell clone. Pt: Patient; ARG: Age, race, gender; TCR-γ: T-cell receptor gamma chain rearrangement; FU: Follow up; Pa: Papule; Nd: Nodule; T: Trunk; UE: Upper extremity; LE: Lower extremity; A: Acanthosis; Sp: Spongiosis; P: Parakeratosis; VA: Vacuolar alteration; Ep: Epidermotropism; Li: Lichenoid (band-like); PV: Perivascular; PA: Periadnexal; PDE: Papillary dermal edema; F: Fibrosis; FM: Follicular mucinosis; Neu (v): Neutrophils in vessels; PC: Plasma cells; Eos: Eosinophils; EE: Extravasated erythrocytes; CL: Lymphocytes with cerebriform or infolded nuclei (mycosis cells); MtF: Mitotic figures; LVC: Lymphocytes with vesiculated nuclei and prominent nucleoli; PMA: Pautrier microabscess; Sm-med: CLs with small-medium sized nuclei (5 to 7 µm in diameter); Med-lg: CLs with medium-large sized nuclei (7 to 9 µm in diameter); ED: Epidermis; D: Dermis; >: Greater than; <: Less than; NS: Not stated; Sk: Skin; Bd: Blood; DGGE: Denaturing gradient gel electrophoresis; SSCP: Single-stranded conformation polymorphism; MTX: Methotrexate; XRT: Local field radiation therapy, IFNα: Interferon alfa; PUVA: Methoxsalen-ultraviolet A photochemotherapy; NBUVB: Narrow band ultraviolet B phototherapy; TopHN2: Topical mechlorethamine; CA: Carcinoma; RA: Rheumatoid arthritis; HT: Hashimoto’s thyroiditis; MI: Mycocardial infarction; AwD: Alive with active disease; DwD: Dead with active disease; A: NED, alive, no evidence disease; LTF: Lost to follow up.

Table 3 Frequency of B-cell chronic lymphocytic leukemia occurring after a diagnosis of cutaneous T cell lymphoma

Ref.	Cohort	No. patients (Dx)	No. secondary B-CLL (%)
Olsen et al[27]	One institution	63 (CTCL)	0 (0)
Kantor et al[28]	One institution	519 (MF)	2 (0.39)
Väkevä et al[29]	Finnish cancer registry	319 (MF/SS)	1 (0.3)
Barzilai et al[24]	Two institutions	398 (MF)	2 (0.50)1
Huang et al[30]	One institution	429 (MF/SS)	1 (0.23)
Huang et al[30]	SEER-9 registry	1798 (MF/SS)	0 or 4 (0 or 0.22)2
Hallerman et al[31]	One institution	62 (CTCL)	0 (0)
Brownell et al[32]	One institution	672 (CTCL)	0 (0)
Hodak et al[33]	One institution	343 (MF)	2 (0.59)
Hodak et al[33]	Israeli population registry	683 (MF)	1 (0.15)
Lindahl et al[34]	Population-based	386 (MF)	0 (0)3
Current study	SEER-9 registry	3,977 (MF)	10 (0.25)

¹One case with B-CLL preceding MF was excluded;

²Surveillance, Epidemiology, and End Results (SEER)-9 Cohort between 1984 through 2001 included 4 cases of leukemia, not defined;

³The 2 cases of hematologic cancer exclusive of non-Hodgkin lymphoma in this cohort were not B-CLL (Lindahl, personal communication, 2016). MF: Mycosis fungoides; SS: Sézary syndrome; CTCL: Cutaneous T cell lymphoma; B-CLL: B cell chronic lymphocytic leukemia; Dx: Diagnostic groups in cohort.