doi: 10.1111/1346-8138.12308
Journal of Dermatology 2014; 41: 63–67
CONCISE COMMUNICATION
Mycosis fungoides palmaris et plantaris successfully treated with radiotherapy: Case report and mini-review of the published work Noriaki NAKAI, Asami HAGURA, Shiho YAMAZATO, Norito KATOH Department of Dermatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kamigyo-ku, Kyoto, Japan
ABSTRACT Mycosis fungoides palmaris et plantaris (MFPP) is a rare variant of cutaneous T-cell lymphoma limited to the palms and soles that is not widely recognized because of its uncommon occurrence. We report a 73-year-old Japanese man who presented with an erosion on the left dorsal hand, a reddish tumor on the right palm, and hyperkeratotic erythematous plaques on the right sole. Skin biopsy showed histological features of mycosis fungoides (MF) with invasion into the deeper layers of skin. There was no visceral or lymph node invasion. We diagnosed this case as MFPP. External beam radiotherapy (EBRT) was performed to treat the hand lesions. Combination treatment with topical steroids and topical psoralen plus ultraviolet light therapy was performed to treat the right sole lesion, but was ineffective. Therefore, sequential EBRT was performed. Complete remission of all lesions was obtained. This is the first report of MFPP with a locally advanced tumor for which the efficacy of radiotherapy is described in detail. MFPP lesions occur on the dorsal aspect of hand or foot, and here we propose a classification of MFPP as hand and foot MF. The pathogenesis of MFPP is still unclear and further accumulation of data is required.
Key words: case report, complete remission, mini-review, mycosis fungoides palmaris et plantaris, radiotherapy.
INTRODUCTION Involvement of mycosis fungoides (MF) limited to the palms and/or soles was first designated as MF palmaris et plantaris (MFPP) by Resnik et al.1 in 1995. There have been nine reports of 23 MFPP cases in the English-language published work.1–9 Herein, we report a case of MFPP that was successfully treated with radiotherapy and we describe the clinicopathological characteristics of MFPP based on a review of published cases from September 1995 to April 2013.
CASE REPORT A 73-year-old Japanese man was referred to our department for diagnosis and treatment of eruptions that had been present on his foot and hands for 1 year. At another hospital, cutaneous T-cell lymphoma had been suspected based on histological findings in a skin biopsy from the dorsal aspect of his left hand. At his first visit to our department, an erosion measuring 60 mm 9 50 mm on the dorsal aspect of the left hand, a reddish tumor measuring 40 mm 9 25 mm on the right palm, and
hyperkeratotic erythematous plaques on the right sole were seen (Fig. 1a–c). There was no eruption except for those on the hand and foot. He had no history including other skin diseases such as psoriasis or palmoplantar pustulosis and an immunosuppressant use such as methotrexate and cyclosporin A. Laboratory tests were within normal limits. Abnormal peripheral blood lymphocytes were not detected and the patient was negative for serum antihuman T-lymphotropic virus type-I antibody. The serum soluble interleukin-2 receptor level was within the normal limit. Positron emission tomography and computed tomography showed slightly swollen lymph nodes in the axilla, but no systemic involvement. The skin biopsy was performed from the erosion on the dorsal aspect of the left hand and the hyperkeratotic erythematous plaques on the right sole, respectively. Histopathology of the left hand showed an eroded lesion with dense infiltration of hematoxylin-stained cells in the whole dermis (Fig. 2a). At higher magnification, large convoluted lymphocytes predominated in the dermal neoplastic infiltrate (Fig. 2b). A lymphocytic infiltrate with convoluted nuclei was present around the secretory portion of eccrine sweat glands. Immunohistochemically, the convoluted lymphocytes were positive for CD3, CD4 (Fig. 2c) and CD5, and negative for CD20. More
Correspondence: Noriaki Nakai M.D., Ph.D., Department of Dermatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. Email: [email protected] Received 22 July 2013; accepted 5 September 2013.
© 2014 Japanese Dermatological Association
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(a)
(b)
(c)
(d)
(e)
(f)
Figure 1. (a–c) Clinical findings at the first visit and (d–f) after radiotherapy. (a) An erosion measuring 60 mm 9 50 mm on the left dorsal hand. (b) A reddish tumor measuring 40 mm 9 25 mm on the right palm. (c) Hyperkeratotic erythematous plaques on the right sole. (d) The left dorsal hand at 3 months after radiotherapy. (e) The right palm at 3 months. (f) The right sole at 3 months.
than 25% of the infiltrate cells were CD30-positive large convoluted lymphocytes (Fig. 2d). Histopathology of the right sole showed hyperkeratosis and epidermotropism with dense infiltration of atypical lymphocytes in the superficial dermis. The epidermotropic lymphocytes formed Pautrier’s microabscess (Fig. 2e). The atypical lymphocytes were partially positive for CD30 (Fig. 2f). T-cell receptor Cb1- and Jb2-chain gene rearrangements were confirmed in biopsy specimens from the hand lesion. Axillary lymph node biopsy was performed, but no atypical lymphocytic infiltrate was found. We diagnosed this case as MFPP T3N0M0 stage IIB according to the European Organization for Research and Treatment of Cancer (EORTC) classification. Because the lymphoma cells invaded the deep layers of the skin and the patient was thought to have large-cell transformation based on the immunohistological findings,10 external beam radiotherapy (EBRT) with total doses of 30 Gy and 40 Gy was performed to treat the erosion on the dorsal aspect of the left hand and the reddish nodule on the right palm, respectively. Three months after completion of radiotherapy, local clinical and histological remission of the lesions of the hands was obtained (Fig. 1d,e). Combined treatment with topical steroids and topical psoralen plus ultraviolet A therapy (PUVA) was performed to treat the hyperkeratotic erythematous plaques on the right sole because the lymphoma cells were limited to the superficial dermis in histological findings. The lesion was irradiated with increasing doses of ultraviolet A, starting with 0.3 J/cm2. This therapy was performed three times a week up to a total of 65 treatments (total, 87.1 J/cm2). However, the local remission was not obtained. Therefore, sequential EBRT with a total dose
64
of 36 Gy was performed and complete remission of all lesions was obtained (Fig. 1f). After treatment, the patient has shown no evidence of tumor recurrence on his hands and foot for over 1 year and for 6 months, respectively.
DISCUSSION The patient noticed the tumor development within a year after the skin lesions first appeared, which may suggest rapid tumor growth compared to common clinical course of MF. Therefore, our case required the differential diagnosis of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). PTCL-NOS is a heterogeneous group of nodal and extranodal mature T-cell lymphomas, and primary presentation in the skin is uncommon. The diagnosis can only be made by excluding other specifically defined categories of mature T-cell lymphoma.11 Our case did not show lymph node or internal organ involvement. Further, Pautrier’s microabscess, which is a histological feature of MF, was seen. Therefore, we diagnosed this case as MFPP. Including our case, there have been 10 reports of MFPP (24 patients) in the English-language published work (Table 1).1–9 The patients (16 males, seven females, and one patient of unidentified sex) had an age range of 11–83 years old (mean, 51.8; median, 52.0). The tumor mostly presented as erythematous hyperkeratotic patches and plaques with or without itch, fissure or scales. Only our case showed severe skin erosion and tumor. In 20 evaluable cases, epidermotropism was seen. In 13 of 18 evaluable cases, formation of Pautrier’s microabscess was detected. In seven of nine evaluable cases, the predominance of CD4 over CD8 cells was seen. Large-cell
© 2014 Japanese Dermatological Association
Mycosis fungoides palmaris et plantaris
(a)
(d)
(b)
(c)
(e)
(f)
Figure 2. (a–d) Histopathological findings for the erosion on the left dorsal hand and (e,f) for the hyperkeratotic erythematous plaques on the right sole. (a) An eroded lesion with dense infiltration of hematoxylin-stained cells in the whole dermis (hematoxylin– eosin [HE], original magnification 940). (b) The lesion consisted of aggregates of large convoluted lymphocytes (HE, 9400). (c) The atypical lymphocytes were almost all CD4-positive (9400). (d) More than 25% of the infiltrate cells were CD30-positive large convoluted lymphocytes (9400). (e) Pautrier’s microabscess was seen (HE, 9400). (f) The atypical lymphocytes were partially positive for CD30 (9400).
transformation was seen in two cases. Only our case showed CD30-positive atypical lymphocytes. The duration of the tumor ranged from 3 months to 25 years (mean, 4.2 years; median, 3 years). In 18 of 19 evaluable cases, T-cell receptor gene rearrangement was observed. In 14 evaluable cases, 13 were stage IA and one was stage IIB. Eleven patients received monotherapy, eight received combination therapy and four received no therapy. Ultraviolet light therapy (n = 9), topical corticosteroids (n = 4), systemic or local administration of an anticancer agent or immunosuppressant (n = 4), radiotherapy (n = 3), a vitamin A (n = 3) or vitamin D (n = 2) preparation, or CO2 laser therapy (n = 1) was performed. The response rate (complete plus partial response) was 95%. Follow-up information was available in 18 patients (mean follow up, 34.6 months; median follow up, 24.0 months). Tumor recurrence occurred in four patients after a mean period of 9.3 months, but the lesions were well controlled with additional treatment.1,2,6 No patients died of disease progression. Lesions were located in the palm and sole (n = 8, 33.3%), other regions in addition to the palm and sole (n = 9, 37.5%), palm alone (n = 4, 16.7%), sole alone (n = 1, 4.2%) and heel alone (n = 1, 4.2%). Only 13 patients (54.2%) met the definition of MFPP. One of the four patients reported by Resnik et al.1 was diagnosed with MFPP for an arm lesion that appeared
© 2014 Japanese Dermatological Association
before palmar and plantar lesions, suggesting that this case was not MFPP, but MF. Sandwich et al.2 and Topf et al.7 also diagnosed MFPP in patients with axilla lesions or elbow and knee lesions, respectively, as well as palmar and plantar lesions. Kim et al.6 reported that palmar and plantar plaques recurred after 7 months of re-PUVA therapy and that additional lesions appeared on the trunk and face. In these cases, the lesions first appeared on the hand and foot, followed by other sites, suggesting that MFPP might also have been MF that began in the hand or foot and progressed to other sites. Therefore, we note that the lesions are confined to the palms and/or soles, or may extend to the other parts of the body. Our case and those in other studies4,5,7,8 were diagnosed as MFPP in patients with lesions in the dorsal aspect of hand, foot or finger. In our case, lesions were observed on the dorsal aspect of the hand and the palm and sole, but not on other parts of the body. Furthermore, the hand lesions corresponded to the tumor stage in the EORTC classification. MF lesions classically progress from patch to plaque to tumor stages over years to decades and the common sites are areas that are not sun-exposed, such as the buttocks, trunk and limbs.12 Therefore, the clinical course in our case was inconsistent with MF due to the presence of erosion and a tumor in the locally advanced stage that were limited to the hand and foot. Lesions
65
66
2006 2006
2006
2006 2006
2006
14 15
16
17 18
19
2006
2006 2006 2006
9
6
2004
11 12 13
8
5
1998
2006
7
4
1997
10
6
3
1995
4
1996
1995
3
5
1995
2
2
1995
1
1
Year
No.
Refs
80
47 51
11
59 61
63 44 51
36
37
62
45
56
53
50
56
50
57
Age
M
M M
M
M F
M M M
F
M
M
M
M
M
F
F
F
F
Sex
Palm Palm, sole Palm, sole
Arm, palm, sole Heel, palm, sole Palm, sole Axilla, palm, sole Foot‡, hand‡ Hand*, sole Finger, nail bed, palm, sole Face, palm, sole, trunk Palm, sole Palm Palm Palm, sole Heel Palm, sole Palm, sole
Sole
Eruption sites
CD4 = CD8
CD4 > CD8
–
–
nw
Plaque
Plaque
Plaque Plaque
Plaque
Plaque Patch, plaque
Plaque Plaque Patch, plaque
Plaque
Plaque, pustule, scale, crust, SC-nodule vesicle Plaque
Patch, plaque
Plaque
Blister, fissure Lichenification, plaque
+ nw
+(9 out of 12
+ +
+
nw nw nw nw nw nw
nw nw nw
+ + +
+ + +
nw
nw
CD4 > CD8
CD4 < CD8
nw
+ + +
cases)
nw
+
+
nw
nw
nw
CD4 > CD8
+
+
Plaque
nw
CD4 > CD8
+
nw
Patch
CD4/8 ratio
EDT
Histological feature PM
Clinical feature
Table 1. Summary of cases of mycosis fungoides palmaris et plantaris
nw
nw nw
nw
nw nw
nw nw nw
nw
nw
–
–
nw
nw
nw
nw
nw
nw
CD30
nw
nw nw
nw
nw nw
nw nw nw
nw
nw
nw
nw
nw
nw
nw
nw
nw
nw
LCT
5 years
5 years 6 years
3 years
3 years 2 years
9 months 3 years 1 year
1 year
7 years
5 years
>14 years
3 years
12 months
>3 years
7 months
6 months
5 months
Duration of disease
IA
IA IA
– TCR-c TCR-c
IA
IA IA
IA IA IA
IA
IA
nw
nw
nw
nw
nw
nw
nw
nw
TNM stage
TCR-c
TCR-c TCR-c
TCR-c TCR-c TCR-c
ND
TCR-c
TCR-Cb1
TCR-b, -c
nw
nw
TCR-c
TCR-c
TCR-c
TCR-c
Monoclonality
ND
S-Vitamin A, T-keratolytic agent S-Vitamin A ND
T-Vitamin D T-Vitamin D
UV-A1 UV-A1 S-methotrexate
Re-PUVA
Re-PUVA
nw
ND
T-keratolytic agent, T-NM, T-steroid CO2 laser
RT, T-PUVA
O-PUVA
RT, T-steroid, T-Vitamin A Methotrexate, O-PUVA
Treatment
nw
CR nw
PR
PR PR
CR CR CR
CR
CR
nw
NC
CR
PR
PR
CR
CR
PR
Response
Unknown
+ Unknown
LR
LR LR
– – –
–
+
nw
–
–
41 –
10
73 70
29 2 15
122
67
nw
24
60
18
+
–
nw
>24
7
40
Follow up (m)
+
–
-
nw
Recurrence
N. Nakai et al.
© 2014 Japanese Dermatological Association
M 2013 24 Our case
73
F 2010 23 9
40
M 83 2007 22 8
© 2014 Japanese Dermatological Association
*Palms and dorsae. †Soles and dorsae. ‡A lack of detailed information on the affected part. CR, complete regression; EDT, epidermotropism; F, female; LCT, large-cell transformation; LR, lesions remained; M, male; m, months; NC, no change; NM, nitrogen mustard; No., number; nw, not written; O, oral; PM, Pautrier’s microabscess; PR, partial regression; PUVA, psoralen plus ultraviolet A therapy; Ref., reference; RT, radiotherapy; S, systemic; SC, subcutaneous; T, topical; TCR, T-cell receptor; TNM, tumor–node–metastasis; UV, ultraviolet; y, year.
6 – + Erosion, plaque, tumor
+
CD4 > CD8
+
+
1 year
TCR-Cb1, -Jb2
IIB
RT, T-PUVA, T-steroid
CR
9 – CR nw Patch
+
nw
nw
nw
3 months
nw
nw
nw LR PR
Bexarotene, S-doxorubicin S-gemcitabine, T-NM Excimer laser nw Plaque
+
CD4 > CD8
nw
+
5 years
nw
nw
0.5 Unknown nw nw PR ND T-PUVA, T-steroid IA IA TCR-c TCR-c 25 years 5 years nw nw nw – nw CD4 > CD8 nw 2006 2006 20 21 7
60 18
M nw
Palm Elbow, hand,* knee, sole Finger, foot†, hand*, heel Palm, sole Hand*, sole
Patch Papule, plaque
+ +
CD4/8 ratio PM EDT Age Year No. Refs
Table 1. (continued)
Sex
Eruption sites
Clinical feature
Histological feature
CD30
LCT
Duration of disease
Monoclonality
TNM stage
Recurrence Response Treatment
Follow up (m)
Mycosis fungoides palmaris et plantaris
of MFPP are also known to occur on the dorsal aspect of the hands or feet.4,7,8 Therefore, we propose here a definition of MFPP as hand and foot MF. In the current report, we have described a case of MFPP that was successfully treated with radiotherapy. To the best of our knowledge, this is the first report of MFPP with a locally advanced tumor in which the effectiveness of radiotherapy has been described in detail. The pathogenesis of MFPP is unclear and the number of reported cases of MFPP is insufficient to establish a clear explanation. Therefore, further accumulation of data and careful observation of the clinical course are required to improve the understanding of MFPP.
CONFLICT OF INTEREST:
The authors have no conflict of
interest to disclose.
REFERENCES 1 Resnik KS, Kantor GR, Lessin SR et al. Mycosis fungoides palmaris et plantaris. Arch Dermatol 1995; 131: 1052–1056. 2 Sandwich JT, Davis LS. Mycosis fungoides palmaris et plantaris. Arch Dermatol 1996; 132: 971. 3 Goldberg DJ, Stampien TM, Schwartz RA. Mycosis fungoides palmaris et plantaris: successful treatment with the carbon dioxide laser. Br J Dermatol 1997; 136: 617–619. 4 McNiff JM, Schechner JS, Crotty PL, Glusac EJ. Mycosis fungoides palmaris et plantaris or acral pagetoid reticulosis? Am J Dermatopathol 1998; 20: 271–275. 5 Toritsugi M, Satoh T, Higuchi T, Yokozeki H, Nishioka K. A vesiculopustular variant of mycosis fungoides palmaris et plantaris masquerading as palmoplantar pustulosis with nail involvement. J Am Acad Dermatol 2004; 51: 139–141. 6 Kim ST, Jeon YS, Sim HJ et al. Clinicopathologic features and T-cell receptor gene rearrangement findings of mycosis fungoides palmaris et plantaris. J Am Acad Dermatol 2006; 54: 466–471. 7 Topf S, Luftl M, Neisius U et al. Mycosis fungoides palmaris et plantaris–an unusual variant of cutaneous T-cell lymphoma. Eur J Dermatol 2006; 16: 84–86. 8 Lambert TJ, Prieto VG, Duvic M. Multiple plaques on the hands and feet. Mycosis fungoides (MF) palmaris et plantaris (MFPP). Arch Dermatol 2007; 143: 109–114. 9 Jin SP, Jeon YK, Cho KH, Chung JH. Excimer laser therapy (308 nm) for mycosis fungoides palmaris et plantaris: a skin-directed and anatomically feasible treatment. Br J Dermatol 2010; 163: 651–653. 10 Herrmann JL, Hughey LC. Recognizing large-cell transformation of mycosis fungoides. J Am Acad Dermatol 2012; 67: 665–672. 11 Quintanilla-Martinez L, Jansen PM, Kinney MC, Swerdlow SH, Willemze R. Non-mycosis fungoides cutaneous T-cell lymphomas: report of the 2011 Society for Hematopathology/European Association for Haematopathology workshop. Am J Clin Pathol 2013; 139: 491–514. 12 Wilcox RA. Cutaneous T-cell lymphoma: 2011 update on diagnosis, risk-stratification, and management. Am J Hematol 2011; 86: 928–948.
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Journal of Dermatology 2014; 41: 63–67
CONCISE COMMUNICATION
Mycosis fungoides palmaris et plantaris successfully treated with radiotherapy: Case report and mini-review of the published work Noriaki NAKAI, Asami HAGURA, Shiho YAMAZATO, Norito KATOH Department of Dermatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kamigyo-ku, Kyoto, Japan
ABSTRACT Mycosis fungoides palmaris et plantaris (MFPP) is a rare variant of cutaneous T-cell lymphoma limited to the palms and soles that is not widely recognized because of its uncommon occurrence. We report a 73-year-old Japanese man who presented with an erosion on the left dorsal hand, a reddish tumor on the right palm, and hyperkeratotic erythematous plaques on the right sole. Skin biopsy showed histological features of mycosis fungoides (MF) with invasion into the deeper layers of skin. There was no visceral or lymph node invasion. We diagnosed this case as MFPP. External beam radiotherapy (EBRT) was performed to treat the hand lesions. Combination treatment with topical steroids and topical psoralen plus ultraviolet light therapy was performed to treat the right sole lesion, but was ineffective. Therefore, sequential EBRT was performed. Complete remission of all lesions was obtained. This is the first report of MFPP with a locally advanced tumor for which the efficacy of radiotherapy is described in detail. MFPP lesions occur on the dorsal aspect of hand or foot, and here we propose a classification of MFPP as hand and foot MF. The pathogenesis of MFPP is still unclear and further accumulation of data is required.
Key words: case report, complete remission, mini-review, mycosis fungoides palmaris et plantaris, radiotherapy.
INTRODUCTION Involvement of mycosis fungoides (MF) limited to the palms and/or soles was first designated as MF palmaris et plantaris (MFPP) by Resnik et al.1 in 1995. There have been nine reports of 23 MFPP cases in the English-language published work.1–9 Herein, we report a case of MFPP that was successfully treated with radiotherapy and we describe the clinicopathological characteristics of MFPP based on a review of published cases from September 1995 to April 2013.
CASE REPORT A 73-year-old Japanese man was referred to our department for diagnosis and treatment of eruptions that had been present on his foot and hands for 1 year. At another hospital, cutaneous T-cell lymphoma had been suspected based on histological findings in a skin biopsy from the dorsal aspect of his left hand. At his first visit to our department, an erosion measuring 60 mm 9 50 mm on the dorsal aspect of the left hand, a reddish tumor measuring 40 mm 9 25 mm on the right palm, and
hyperkeratotic erythematous plaques on the right sole were seen (Fig. 1a–c). There was no eruption except for those on the hand and foot. He had no history including other skin diseases such as psoriasis or palmoplantar pustulosis and an immunosuppressant use such as methotrexate and cyclosporin A. Laboratory tests were within normal limits. Abnormal peripheral blood lymphocytes were not detected and the patient was negative for serum antihuman T-lymphotropic virus type-I antibody. The serum soluble interleukin-2 receptor level was within the normal limit. Positron emission tomography and computed tomography showed slightly swollen lymph nodes in the axilla, but no systemic involvement. The skin biopsy was performed from the erosion on the dorsal aspect of the left hand and the hyperkeratotic erythematous plaques on the right sole, respectively. Histopathology of the left hand showed an eroded lesion with dense infiltration of hematoxylin-stained cells in the whole dermis (Fig. 2a). At higher magnification, large convoluted lymphocytes predominated in the dermal neoplastic infiltrate (Fig. 2b). A lymphocytic infiltrate with convoluted nuclei was present around the secretory portion of eccrine sweat glands. Immunohistochemically, the convoluted lymphocytes were positive for CD3, CD4 (Fig. 2c) and CD5, and negative for CD20. More
Correspondence: Noriaki Nakai M.D., Ph.D., Department of Dermatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. Email: [email protected] Received 22 July 2013; accepted 5 September 2013.
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(a)
(b)
(c)
(d)
(e)
(f)
Figure 1. (a–c) Clinical findings at the first visit and (d–f) after radiotherapy. (a) An erosion measuring 60 mm 9 50 mm on the left dorsal hand. (b) A reddish tumor measuring 40 mm 9 25 mm on the right palm. (c) Hyperkeratotic erythematous plaques on the right sole. (d) The left dorsal hand at 3 months after radiotherapy. (e) The right palm at 3 months. (f) The right sole at 3 months.
than 25% of the infiltrate cells were CD30-positive large convoluted lymphocytes (Fig. 2d). Histopathology of the right sole showed hyperkeratosis and epidermotropism with dense infiltration of atypical lymphocytes in the superficial dermis. The epidermotropic lymphocytes formed Pautrier’s microabscess (Fig. 2e). The atypical lymphocytes were partially positive for CD30 (Fig. 2f). T-cell receptor Cb1- and Jb2-chain gene rearrangements were confirmed in biopsy specimens from the hand lesion. Axillary lymph node biopsy was performed, but no atypical lymphocytic infiltrate was found. We diagnosed this case as MFPP T3N0M0 stage IIB according to the European Organization for Research and Treatment of Cancer (EORTC) classification. Because the lymphoma cells invaded the deep layers of the skin and the patient was thought to have large-cell transformation based on the immunohistological findings,10 external beam radiotherapy (EBRT) with total doses of 30 Gy and 40 Gy was performed to treat the erosion on the dorsal aspect of the left hand and the reddish nodule on the right palm, respectively. Three months after completion of radiotherapy, local clinical and histological remission of the lesions of the hands was obtained (Fig. 1d,e). Combined treatment with topical steroids and topical psoralen plus ultraviolet A therapy (PUVA) was performed to treat the hyperkeratotic erythematous plaques on the right sole because the lymphoma cells were limited to the superficial dermis in histological findings. The lesion was irradiated with increasing doses of ultraviolet A, starting with 0.3 J/cm2. This therapy was performed three times a week up to a total of 65 treatments (total, 87.1 J/cm2). However, the local remission was not obtained. Therefore, sequential EBRT with a total dose
64
of 36 Gy was performed and complete remission of all lesions was obtained (Fig. 1f). After treatment, the patient has shown no evidence of tumor recurrence on his hands and foot for over 1 year and for 6 months, respectively.
DISCUSSION The patient noticed the tumor development within a year after the skin lesions first appeared, which may suggest rapid tumor growth compared to common clinical course of MF. Therefore, our case required the differential diagnosis of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). PTCL-NOS is a heterogeneous group of nodal and extranodal mature T-cell lymphomas, and primary presentation in the skin is uncommon. The diagnosis can only be made by excluding other specifically defined categories of mature T-cell lymphoma.11 Our case did not show lymph node or internal organ involvement. Further, Pautrier’s microabscess, which is a histological feature of MF, was seen. Therefore, we diagnosed this case as MFPP. Including our case, there have been 10 reports of MFPP (24 patients) in the English-language published work (Table 1).1–9 The patients (16 males, seven females, and one patient of unidentified sex) had an age range of 11–83 years old (mean, 51.8; median, 52.0). The tumor mostly presented as erythematous hyperkeratotic patches and plaques with or without itch, fissure or scales. Only our case showed severe skin erosion and tumor. In 20 evaluable cases, epidermotropism was seen. In 13 of 18 evaluable cases, formation of Pautrier’s microabscess was detected. In seven of nine evaluable cases, the predominance of CD4 over CD8 cells was seen. Large-cell
© 2014 Japanese Dermatological Association
Mycosis fungoides palmaris et plantaris
(a)
(d)
(b)
(c)
(e)
(f)
Figure 2. (a–d) Histopathological findings for the erosion on the left dorsal hand and (e,f) for the hyperkeratotic erythematous plaques on the right sole. (a) An eroded lesion with dense infiltration of hematoxylin-stained cells in the whole dermis (hematoxylin– eosin [HE], original magnification 940). (b) The lesion consisted of aggregates of large convoluted lymphocytes (HE, 9400). (c) The atypical lymphocytes were almost all CD4-positive (9400). (d) More than 25% of the infiltrate cells were CD30-positive large convoluted lymphocytes (9400). (e) Pautrier’s microabscess was seen (HE, 9400). (f) The atypical lymphocytes were partially positive for CD30 (9400).
transformation was seen in two cases. Only our case showed CD30-positive atypical lymphocytes. The duration of the tumor ranged from 3 months to 25 years (mean, 4.2 years; median, 3 years). In 18 of 19 evaluable cases, T-cell receptor gene rearrangement was observed. In 14 evaluable cases, 13 were stage IA and one was stage IIB. Eleven patients received monotherapy, eight received combination therapy and four received no therapy. Ultraviolet light therapy (n = 9), topical corticosteroids (n = 4), systemic or local administration of an anticancer agent or immunosuppressant (n = 4), radiotherapy (n = 3), a vitamin A (n = 3) or vitamin D (n = 2) preparation, or CO2 laser therapy (n = 1) was performed. The response rate (complete plus partial response) was 95%. Follow-up information was available in 18 patients (mean follow up, 34.6 months; median follow up, 24.0 months). Tumor recurrence occurred in four patients after a mean period of 9.3 months, but the lesions were well controlled with additional treatment.1,2,6 No patients died of disease progression. Lesions were located in the palm and sole (n = 8, 33.3%), other regions in addition to the palm and sole (n = 9, 37.5%), palm alone (n = 4, 16.7%), sole alone (n = 1, 4.2%) and heel alone (n = 1, 4.2%). Only 13 patients (54.2%) met the definition of MFPP. One of the four patients reported by Resnik et al.1 was diagnosed with MFPP for an arm lesion that appeared
© 2014 Japanese Dermatological Association
before palmar and plantar lesions, suggesting that this case was not MFPP, but MF. Sandwich et al.2 and Topf et al.7 also diagnosed MFPP in patients with axilla lesions or elbow and knee lesions, respectively, as well as palmar and plantar lesions. Kim et al.6 reported that palmar and plantar plaques recurred after 7 months of re-PUVA therapy and that additional lesions appeared on the trunk and face. In these cases, the lesions first appeared on the hand and foot, followed by other sites, suggesting that MFPP might also have been MF that began in the hand or foot and progressed to other sites. Therefore, we note that the lesions are confined to the palms and/or soles, or may extend to the other parts of the body. Our case and those in other studies4,5,7,8 were diagnosed as MFPP in patients with lesions in the dorsal aspect of hand, foot or finger. In our case, lesions were observed on the dorsal aspect of the hand and the palm and sole, but not on other parts of the body. Furthermore, the hand lesions corresponded to the tumor stage in the EORTC classification. MF lesions classically progress from patch to plaque to tumor stages over years to decades and the common sites are areas that are not sun-exposed, such as the buttocks, trunk and limbs.12 Therefore, the clinical course in our case was inconsistent with MF due to the presence of erosion and a tumor in the locally advanced stage that were limited to the hand and foot. Lesions
65
66
2006 2006
2006
2006 2006
2006
14 15
16
17 18
19
2006
2006 2006 2006
9
6
2004
11 12 13
8
5
1998
2006
7
4
1997
10
6
3
1995
4
1996
1995
3
5
1995
2
2
1995
1
1
Year
No.
Refs
80
47 51
11
59 61
63 44 51
36
37
62
45
56
53
50
56
50
57
Age
M
M M
M
M F
M M M
F
M
M
M
M
M
F
F
F
F
Sex
Palm Palm, sole Palm, sole
Arm, palm, sole Heel, palm, sole Palm, sole Axilla, palm, sole Foot‡, hand‡ Hand*, sole Finger, nail bed, palm, sole Face, palm, sole, trunk Palm, sole Palm Palm Palm, sole Heel Palm, sole Palm, sole
Sole
Eruption sites
CD4 = CD8
CD4 > CD8
–
–
nw
Plaque
Plaque
Plaque Plaque
Plaque
Plaque Patch, plaque
Plaque Plaque Patch, plaque
Plaque
Plaque, pustule, scale, crust, SC-nodule vesicle Plaque
Patch, plaque
Plaque
Blister, fissure Lichenification, plaque
+ nw
+(9 out of 12
+ +
+
nw nw nw nw nw nw
nw nw nw
+ + +
+ + +
nw
nw
CD4 > CD8
CD4 < CD8
nw
+ + +
cases)
nw
+
+
nw
nw
nw
CD4 > CD8
+
+
Plaque
nw
CD4 > CD8
+
nw
Patch
CD4/8 ratio
EDT
Histological feature PM
Clinical feature
Table 1. Summary of cases of mycosis fungoides palmaris et plantaris
nw
nw nw
nw
nw nw
nw nw nw
nw
nw
–
–
nw
nw
nw
nw
nw
nw
CD30
nw
nw nw
nw
nw nw
nw nw nw
nw
nw
nw
nw
nw
nw
nw
nw
nw
nw
LCT
5 years
5 years 6 years
3 years
3 years 2 years
9 months 3 years 1 year
1 year
7 years
5 years
>14 years
3 years
12 months
>3 years
7 months
6 months
5 months
Duration of disease
IA
IA IA
– TCR-c TCR-c
IA
IA IA
IA IA IA
IA
IA
nw
nw
nw
nw
nw
nw
nw
nw
TNM stage
TCR-c
TCR-c TCR-c
TCR-c TCR-c TCR-c
ND
TCR-c
TCR-Cb1
TCR-b, -c
nw
nw
TCR-c
TCR-c
TCR-c
TCR-c
Monoclonality
ND
S-Vitamin A, T-keratolytic agent S-Vitamin A ND
T-Vitamin D T-Vitamin D
UV-A1 UV-A1 S-methotrexate
Re-PUVA
Re-PUVA
nw
ND
T-keratolytic agent, T-NM, T-steroid CO2 laser
RT, T-PUVA
O-PUVA
RT, T-steroid, T-Vitamin A Methotrexate, O-PUVA
Treatment
nw
CR nw
PR
PR PR
CR CR CR
CR
CR
nw
NC
CR
PR
PR
CR
CR
PR
Response
Unknown
+ Unknown
LR
LR LR
– – –
–
+
nw
–
–
41 –
10
73 70
29 2 15
122
67
nw
24
60
18
+
–
nw
>24
7
40
Follow up (m)
+
–
-
nw
Recurrence
N. Nakai et al.
© 2014 Japanese Dermatological Association
M 2013 24 Our case
73
F 2010 23 9
40
M 83 2007 22 8
© 2014 Japanese Dermatological Association
*Palms and dorsae. †Soles and dorsae. ‡A lack of detailed information on the affected part. CR, complete regression; EDT, epidermotropism; F, female; LCT, large-cell transformation; LR, lesions remained; M, male; m, months; NC, no change; NM, nitrogen mustard; No., number; nw, not written; O, oral; PM, Pautrier’s microabscess; PR, partial regression; PUVA, psoralen plus ultraviolet A therapy; Ref., reference; RT, radiotherapy; S, systemic; SC, subcutaneous; T, topical; TCR, T-cell receptor; TNM, tumor–node–metastasis; UV, ultraviolet; y, year.
6 – + Erosion, plaque, tumor
+
CD4 > CD8
+
+
1 year
TCR-Cb1, -Jb2
IIB
RT, T-PUVA, T-steroid
CR
9 – CR nw Patch
+
nw
nw
nw
3 months
nw
nw
nw LR PR
Bexarotene, S-doxorubicin S-gemcitabine, T-NM Excimer laser nw Plaque
+
CD4 > CD8
nw
+
5 years
nw
nw
0.5 Unknown nw nw PR ND T-PUVA, T-steroid IA IA TCR-c TCR-c 25 years 5 years nw nw nw – nw CD4 > CD8 nw 2006 2006 20 21 7
60 18
M nw
Palm Elbow, hand,* knee, sole Finger, foot†, hand*, heel Palm, sole Hand*, sole
Patch Papule, plaque
+ +
CD4/8 ratio PM EDT Age Year No. Refs
Table 1. (continued)
Sex
Eruption sites
Clinical feature
Histological feature
CD30
LCT
Duration of disease
Monoclonality
TNM stage
Recurrence Response Treatment
Follow up (m)
Mycosis fungoides palmaris et plantaris
of MFPP are also known to occur on the dorsal aspect of the hands or feet.4,7,8 Therefore, we propose here a definition of MFPP as hand and foot MF. In the current report, we have described a case of MFPP that was successfully treated with radiotherapy. To the best of our knowledge, this is the first report of MFPP with a locally advanced tumor in which the effectiveness of radiotherapy has been described in detail. The pathogenesis of MFPP is unclear and the number of reported cases of MFPP is insufficient to establish a clear explanation. Therefore, further accumulation of data and careful observation of the clinical course are required to improve the understanding of MFPP.
CONFLICT OF INTEREST:
The authors have no conflict of
interest to disclose.
REFERENCES 1 Resnik KS, Kantor GR, Lessin SR et al. Mycosis fungoides palmaris et plantaris. Arch Dermatol 1995; 131: 1052–1056. 2 Sandwich JT, Davis LS. Mycosis fungoides palmaris et plantaris. Arch Dermatol 1996; 132: 971. 3 Goldberg DJ, Stampien TM, Schwartz RA. Mycosis fungoides palmaris et plantaris: successful treatment with the carbon dioxide laser. Br J Dermatol 1997; 136: 617–619. 4 McNiff JM, Schechner JS, Crotty PL, Glusac EJ. Mycosis fungoides palmaris et plantaris or acral pagetoid reticulosis? Am J Dermatopathol 1998; 20: 271–275. 5 Toritsugi M, Satoh T, Higuchi T, Yokozeki H, Nishioka K. A vesiculopustular variant of mycosis fungoides palmaris et plantaris masquerading as palmoplantar pustulosis with nail involvement. J Am Acad Dermatol 2004; 51: 139–141. 6 Kim ST, Jeon YS, Sim HJ et al. Clinicopathologic features and T-cell receptor gene rearrangement findings of mycosis fungoides palmaris et plantaris. J Am Acad Dermatol 2006; 54: 466–471. 7 Topf S, Luftl M, Neisius U et al. Mycosis fungoides palmaris et plantaris–an unusual variant of cutaneous T-cell lymphoma. Eur J Dermatol 2006; 16: 84–86. 8 Lambert TJ, Prieto VG, Duvic M. Multiple plaques on the hands and feet. Mycosis fungoides (MF) palmaris et plantaris (MFPP). Arch Dermatol 2007; 143: 109–114. 9 Jin SP, Jeon YK, Cho KH, Chung JH. Excimer laser therapy (308 nm) for mycosis fungoides palmaris et plantaris: a skin-directed and anatomically feasible treatment. Br J Dermatol 2010; 163: 651–653. 10 Herrmann JL, Hughey LC. Recognizing large-cell transformation of mycosis fungoides. J Am Acad Dermatol 2012; 67: 665–672. 11 Quintanilla-Martinez L, Jansen PM, Kinney MC, Swerdlow SH, Willemze R. Non-mycosis fungoides cutaneous T-cell lymphomas: report of the 2011 Society for Hematopathology/European Association for Haematopathology workshop. Am J Clin Pathol 2013; 139: 491–514. 12 Wilcox RA. Cutaneous T-cell lymphoma: 2011 update on diagnosis, risk-stratification, and management. Am J Hematol 2011; 86: 928–948.
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