CASE REPORT
Multiple Primary Cutaneous Plasmacytomas: An Unusual Presentation Derya Ugmak, Zeynep Meltem Akkurt, GUI Tiirkgu, Mehmet Harman, Mehmet Sinan Dal, and Feyzullah Ufmak
B a c k g ro u n d : E x tra m e d u lla ry p la s m a c y to m a o f th e skin , a rare ty p e o f c u ta n e o u s B-cell ly m p h o m a , is ch a ra cte rize d b y clo n a l
p ro life ra tio n o f pla sm a cells p rim a rily in th e skin w ith o u t evid e n ce o f m u ltip le m y e lo m a . O n ly a b o u t 30 cases w ith e x tra m e d u lla ry p la s m a c y to m a o f th e sk in are re p o rte d in th e lite ra tu re . C ase R e p o rt: A n 8 2 -y e a r-o ld m a le p a tie n t p re s e n te d to o u r c lin ic w ith c o m p la in ts o f a s y m p to m a tic red n o d u la r s w e llin g an d
p a in in th e a n te rio r c h e s t w a ll. A d e rm a to lo g ic e x a m in a tio n re ve a le d m u ltip le n o d u la r le s io n s o f v a ry in g size s w it h a ha rd s m o o th su rfa c e a n d v iv id red c o lo r. S e ru m p ro te in an d im m u n o g lo b u lin e le c tro p h o re s is , s k e le ta l ra d io g ra p h y , a n d b o n e m a rro w b io p s y s h o w e d n o rm a l re s u lts in th is p a tie n t. Here a rare case o f m u ltip le p rim a ry p la s m a c y to m a lo c a liz in g in th e s k in is
C o n te x te : Le p la s m o c y to m e e x tra m e d u lla ire de la peau, un ty p e rare de ly m p h o m e cu ta n e a ly m p h o c y te s B, se ca ra cte rise par
une p ro life ra tio n c lo n a le des p la sm o cyte s, q u i to u c h e p rin c ip a le m e n t la peau m a is q u i ne p re se n te pas de sig n e de m y e lo m e m u ltip le . La d o c u m e n ta tio n m e d ica le ne f a it e ta t qu e d 'u n e tre n ta in e de cas de p la s m o c y to m e e x tra m e d u lla ire de la peau. Ex p o s e
de
c a s: Un
h o m m e de 82 ans e st ve n u c o n s u lte r au c e n tre m e d ica l p o u r un e tu m e fa c tio n
n o d u la ire ro u g e
a s y m p to m a tiq u e e t de la d o u le u r a la p a ro i th o ra c iq u e a n te rie u re . Un e xa m en d e rm a to lo g iq u e a reve le de n o m b re u se s le sio n s n o d u la ire s de d iffe re n te s gro sseu rs, a su rfa ce d u re e t lisse e t de c o u le u r ro u g e v if. T o u te fo is , I'e le c tro p h o re s e des p ro te in e s seriqu es e t des im m u n o g lo b u lin e s , la ra d io g ra p h ie du s q u e le tte , e t un e b io p s ie de la m o e lle osseuse o n t d o n n e des re s u lta ts n o rm a u x. Sera do ne exp o se ici un cas rare de p la s m o c y to m e m u ltip le p r im itif, to u c h a n t la peau.
LASMACYTOMAS can be classified into two groups
P according to their location, namely solitary plasma cytoma of bone and extramedullary plasmacytoma (EMP).1 Solitary plasmacytoma of bone is most com monly found in the upper head and neck region in the axial skeleton. On the other hand, 80% of all EMPs occur in the respiratory tract and nasal cavity2,3; they rarely occur in the genitourinary tract, lymph nodes, breast, thyroid, stomach, brain, and skin.2,4 EMPs of the skin may present in two forms: metastatic cutaneous plasma cytoma (MCP) and primary cutaneous plasmacytoma
From the Departments o f Dermatology, Pathology, and Hematology, Dicle University, and the Department o f Gastroenterology, Diyarbakir Education and Research Hospital, Diyarbakir, Turkey. Address reprint requests to: Derya Ucmak, Department o f Dermatology, Dicle University, Diyarbakir 21280, Turkey; e-mail: ucmakderya@ gmail.com. D O I 1 0 .2 31 0/77 50 .2 01 3.131 03
© 2014 Canadian Dermatology Association
(PCP). In this report, we present a case with primary skin involvement.
Case Report An 82-year-old male patient presented to our clinic with well-demarcated red nodular lesions localizing in the upper part of the body that varied in size from 0.5 to 4.0 cm (Figure 1). His biography and family history were normal. Lesional skin biopsy showed diffuse proliferation of plasma cells in the dermis (Figure 2). Clonality was demonstrated by lambda immunohistochemical staining. CD20 was negative as expected, and CD 138 was all positive (Figure 3). The laboratory tests, including complete blood count, bone marrow biopsy, serum and urine protein electrophoresis, and skeletal radiography, showed normal results. Given the clinical data, nodular lesions, normal levels of calcium, and results of the renal function tests, the patient was diagnosed with multiple PCPs. Radiotherapy was recommended to the patient; however, the patient turned down the treatment. After 10
DECKER^ ^ 7 Canadian Dermatology Association I Journal of Cutaneous Medicine and Surgery, Vol 18, No 5 (September/October), 2014: pp 361-364
U ftn a k et a l
Figure 1. Disseminated erythematous-violaceous nodular lesions.
months, the follow-up demonstrated that the lesions remained unchanged and the patient did not have any additional complaints.
Discussion There are currently four known types of plasma cell neoplasms: classic multiple myeloma (MM), EMP without MM, solitary plasmacytoma of bone, and plasma cell leukemia. Cutaneous manifestations are observed in all types.5 The diagnostic criteria for PCP are as follows: (1) cytoplasmic expression of immunoglobulins is con fined to a single immunoglobulin chain immunohistochemically, demonstrating that the cells are monoclonal
and the disease is malignant, and (2) myeloma is ruled out by laboratory tests as well as radiologic and bone marrow examinations.3,6 Cutaneous plasmacytomas are smooth, dome-shaped, violaceous nodules that may be subcutaneous or dermal. Ulceration has been detected in a small number of cases.7 Lesions are generally located in the face, trunk, and extremities.6'8 Underlying bone lesions and vascular and lymphatic invasion of the tumor or, more often, direct extension may lead to secondary (metastatic) cutaneous involvement (MCP).5 PCP is characterized by monoclonal proliferation of plasma cells primarily in the skin without evidence of systemic diseases.5 A consensus has recently been reached on a new classification for this group of diseases by the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer (EORTC). A combination of clinical, histologic, and immunophenotypic criteria forms the basis of the EORTC classification for primary cutaneous lymphomas. This classification consists of well-described disease qualities instead of histologic subgroups. In addition, some temporary qualities are also included in this recent classification. These qualities may show characteristic histologic features; however, they are yet to be defined in .clinical terms. These temporary qualities account for less than 5% of all primary cutaneous lymphomas.9 PCP usually affects elderly and middle-aged people (mean age approximately 60 years, ranging from 22 to 88 years), with a predominance of males (male:female ratio 4:1).10 Only 29 cases were reported in a review that covered
Figure 2. Light microscopy with dif fuse proliferation of plasma cells in superficial and deep dermis (hematoxylin-eosin stain; left, X I00 original magnification; right, X400 original magnification).
Canadian Dermatology Association I Journal of Cutaneous Medicine and Surgery, Vol 18, No 5 (Septemher/Octoher), 2014. pp 361 364
Multiple Primary Cutaneous Plasmacytomas
the years until 2000 and brought together clinicopathologic features, prognostic factors, and treatment of PCP. In this study, 58.6% of the patients had solitary lesions, whereas 37.9% had multiple lesions, all localizing in the same region.8 In our literature search, we came across only two case reports: one about a 62-year-old patient and the other about a 55-year-old patient with multiple lesions localizing in the trunk. In these patients, the skin lesions showed nodular or diffuse dermal infiltrates that consisted almost entirely of mature plasma cells, including multinucleated plasma cells. Similarly in immunocytomas, coexistent clonal lymphocytes are deficient. The tumor cells are not positive for CD20 and leukocyte common antigen; however, they express monotypic clg+ and CD38+.9 The treatment of choice is usually surgical excision in patients with solitary or a small number of plasmacytomas. However, there are also patients who were treated by and benefited from radiotherapy.6’7 Chemotherapy is indicated in the presence of a considerable amount of multiple cutaneous plasmacytomas, where excision is not possible.6 Patients with multiple skin lesions have been reported to have a higher risk of death and a poorer prognosis compared to patients with solitary skin lesions.3,6,8 There is no description as to the clinical course of the disease, and it cannot be predicted. The neoplasm may progress rapidly by spreading systemically or locally in some patients or may follow a benign protracted course in others. In addition, complete staging may not be positive at the first presentation; however, the disease may act as a precursor of MM in some cases.10 The prevalence of transformation of EMP into MM has been reported to be
A
30 to 50% in a median time of 1.5 to 2.5 years.11 Therefore, close monitoring is recommended, especially in patients with PCP that involves multiple skin lesions.10 Our patient has been closely monitored as he has multiple lesions. Almost 10 months have passed since the diagnosis was established, and there is still no evidence of transformation into MM.
Acknowledgment Financial disclosure of authors and reviewers: None reported.
References 1. Kilciksiz S, Karakoyun-Celik O, Agaoglu FY, Haydaroglu A. A review for solitary plasmacytoma of bone and extramedullary plasmacytoma. Sci World ] 2012;2:6. 2. Galieni P, Cavo M, Pulsoni A, Awisati G, et al. Clinical outcome of extramedullary plasmacytoma. Haematologica 2000;85:47-51. 3. Tilting T, Bork K. Primary plasmacytoma of the skin. J Am Acad Dermatol 1996;34:386-90, doi:10.1016/S0190-9622(07)80014-4. 4. Lin B, Weiss LM. Primary plasmacytoma of lymph nodes. Hum Pathol 1997;28:1083-90, doi:10.1016/S0046-8177(97)90063-0. 5. Alvarez-Twose I, Vano-Galvan S, Calvo-Villas JM, et al. Metastatic cutaneous plasmacytoma presenting as a perianal giant mass. Dermatol Online I 2008;14:17. 6. Fitzhugh VA, Siegel D, Bhattacharyya PK. Multiple primary cutaneous plasmacytomas. I Clin Pathol 2008;61:782-3, doi:10. 1136/jcp.2008.056051. 7. Bluefarb SM. Cutaneous manifestations of multiple myeloma. AMA Arch Derm 1955;72:506-22, doi:10.1001/archderm.l955. 03730360012002.
< 7 Canadian Dermatology Association I Journal of Cutaneous Medicine and Surgery, Vol 18, No 5 (September/October), 2014: pp 361-364
3 63
8. Muscardin LM, Pulsoni A, Cerroni L. Primary cutaneous plasmacytoma: report of a case with review of the literature. J Am Acad Dermatol 2000;43:962-5, doi:10.1067/mid.200Q. 103997. 9. Willemze R, Kerl H, Sterry W, et al. EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer. Blood 1997;90:354-71.
364
10. Kazakov DV, Belousova IE, Muller B, et al. Primary cutaneous plasmacytoma: a clinicopathological study of two cases with a long-term follow-up and review of the literature. J Cutan Pathol 2002;29:244-8, doi:10.1034/i.l600-0560.2002.290408.x. 11. Weber DM. Solitary bone and extramedullary plasmacytoma. Hematology Am Soc Hematol Educ Program 2005;373-6, doi:10. 1182/asheducation-2005.1.373.
Canadian Dermatology Association I Journal of Cutaneous Medicine and Surgery, Vol 18, No 5 (September/October), 2014: pp 381-364
Copyright of Journal of Cutaneous Medicine & Surgery is the property of Decker Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Multiple Primary Cutaneous Plasmacytomas: An Unusual Presentation Derya Ugmak, Zeynep Meltem Akkurt, GUI Tiirkgu, Mehmet Harman, Mehmet Sinan Dal, and Feyzullah Ufmak
B a c k g ro u n d : E x tra m e d u lla ry p la s m a c y to m a o f th e skin , a rare ty p e o f c u ta n e o u s B-cell ly m p h o m a , is ch a ra cte rize d b y clo n a l
p ro life ra tio n o f pla sm a cells p rim a rily in th e skin w ith o u t evid e n ce o f m u ltip le m y e lo m a . O n ly a b o u t 30 cases w ith e x tra m e d u lla ry p la s m a c y to m a o f th e sk in are re p o rte d in th e lite ra tu re . C ase R e p o rt: A n 8 2 -y e a r-o ld m a le p a tie n t p re s e n te d to o u r c lin ic w ith c o m p la in ts o f a s y m p to m a tic red n o d u la r s w e llin g an d
p a in in th e a n te rio r c h e s t w a ll. A d e rm a to lo g ic e x a m in a tio n re ve a le d m u ltip le n o d u la r le s io n s o f v a ry in g size s w it h a ha rd s m o o th su rfa c e a n d v iv id red c o lo r. S e ru m p ro te in an d im m u n o g lo b u lin e le c tro p h o re s is , s k e le ta l ra d io g ra p h y , a n d b o n e m a rro w b io p s y s h o w e d n o rm a l re s u lts in th is p a tie n t. Here a rare case o f m u ltip le p rim a ry p la s m a c y to m a lo c a liz in g in th e s k in is
C o n te x te : Le p la s m o c y to m e e x tra m e d u lla ire de la peau, un ty p e rare de ly m p h o m e cu ta n e a ly m p h o c y te s B, se ca ra cte rise par
une p ro life ra tio n c lo n a le des p la sm o cyte s, q u i to u c h e p rin c ip a le m e n t la peau m a is q u i ne p re se n te pas de sig n e de m y e lo m e m u ltip le . La d o c u m e n ta tio n m e d ica le ne f a it e ta t qu e d 'u n e tre n ta in e de cas de p la s m o c y to m e e x tra m e d u lla ire de la peau. Ex p o s e
de
c a s: Un
h o m m e de 82 ans e st ve n u c o n s u lte r au c e n tre m e d ica l p o u r un e tu m e fa c tio n
n o d u la ire ro u g e
a s y m p to m a tiq u e e t de la d o u le u r a la p a ro i th o ra c iq u e a n te rie u re . Un e xa m en d e rm a to lo g iq u e a reve le de n o m b re u se s le sio n s n o d u la ire s de d iffe re n te s gro sseu rs, a su rfa ce d u re e t lisse e t de c o u le u r ro u g e v if. T o u te fo is , I'e le c tro p h o re s e des p ro te in e s seriqu es e t des im m u n o g lo b u lin e s , la ra d io g ra p h ie du s q u e le tte , e t un e b io p s ie de la m o e lle osseuse o n t d o n n e des re s u lta ts n o rm a u x. Sera do ne exp o se ici un cas rare de p la s m o c y to m e m u ltip le p r im itif, to u c h a n t la peau.
LASMACYTOMAS can be classified into two groups
P according to their location, namely solitary plasma cytoma of bone and extramedullary plasmacytoma (EMP).1 Solitary plasmacytoma of bone is most com monly found in the upper head and neck region in the axial skeleton. On the other hand, 80% of all EMPs occur in the respiratory tract and nasal cavity2,3; they rarely occur in the genitourinary tract, lymph nodes, breast, thyroid, stomach, brain, and skin.2,4 EMPs of the skin may present in two forms: metastatic cutaneous plasma cytoma (MCP) and primary cutaneous plasmacytoma
From the Departments o f Dermatology, Pathology, and Hematology, Dicle University, and the Department o f Gastroenterology, Diyarbakir Education and Research Hospital, Diyarbakir, Turkey. Address reprint requests to: Derya Ucmak, Department o f Dermatology, Dicle University, Diyarbakir 21280, Turkey; e-mail: ucmakderya@ gmail.com. D O I 1 0 .2 31 0/77 50 .2 01 3.131 03
© 2014 Canadian Dermatology Association
(PCP). In this report, we present a case with primary skin involvement.
Case Report An 82-year-old male patient presented to our clinic with well-demarcated red nodular lesions localizing in the upper part of the body that varied in size from 0.5 to 4.0 cm (Figure 1). His biography and family history were normal. Lesional skin biopsy showed diffuse proliferation of plasma cells in the dermis (Figure 2). Clonality was demonstrated by lambda immunohistochemical staining. CD20 was negative as expected, and CD 138 was all positive (Figure 3). The laboratory tests, including complete blood count, bone marrow biopsy, serum and urine protein electrophoresis, and skeletal radiography, showed normal results. Given the clinical data, nodular lesions, normal levels of calcium, and results of the renal function tests, the patient was diagnosed with multiple PCPs. Radiotherapy was recommended to the patient; however, the patient turned down the treatment. After 10
DECKER^ ^ 7 Canadian Dermatology Association I Journal of Cutaneous Medicine and Surgery, Vol 18, No 5 (September/October), 2014: pp 361-364
U ftn a k et a l
Figure 1. Disseminated erythematous-violaceous nodular lesions.
months, the follow-up demonstrated that the lesions remained unchanged and the patient did not have any additional complaints.
Discussion There are currently four known types of plasma cell neoplasms: classic multiple myeloma (MM), EMP without MM, solitary plasmacytoma of bone, and plasma cell leukemia. Cutaneous manifestations are observed in all types.5 The diagnostic criteria for PCP are as follows: (1) cytoplasmic expression of immunoglobulins is con fined to a single immunoglobulin chain immunohistochemically, demonstrating that the cells are monoclonal
and the disease is malignant, and (2) myeloma is ruled out by laboratory tests as well as radiologic and bone marrow examinations.3,6 Cutaneous plasmacytomas are smooth, dome-shaped, violaceous nodules that may be subcutaneous or dermal. Ulceration has been detected in a small number of cases.7 Lesions are generally located in the face, trunk, and extremities.6'8 Underlying bone lesions and vascular and lymphatic invasion of the tumor or, more often, direct extension may lead to secondary (metastatic) cutaneous involvement (MCP).5 PCP is characterized by monoclonal proliferation of plasma cells primarily in the skin without evidence of systemic diseases.5 A consensus has recently been reached on a new classification for this group of diseases by the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer (EORTC). A combination of clinical, histologic, and immunophenotypic criteria forms the basis of the EORTC classification for primary cutaneous lymphomas. This classification consists of well-described disease qualities instead of histologic subgroups. In addition, some temporary qualities are also included in this recent classification. These qualities may show characteristic histologic features; however, they are yet to be defined in .clinical terms. These temporary qualities account for less than 5% of all primary cutaneous lymphomas.9 PCP usually affects elderly and middle-aged people (mean age approximately 60 years, ranging from 22 to 88 years), with a predominance of males (male:female ratio 4:1).10 Only 29 cases were reported in a review that covered
Figure 2. Light microscopy with dif fuse proliferation of plasma cells in superficial and deep dermis (hematoxylin-eosin stain; left, X I00 original magnification; right, X400 original magnification).
Canadian Dermatology Association I Journal of Cutaneous Medicine and Surgery, Vol 18, No 5 (Septemher/Octoher), 2014. pp 361 364
Multiple Primary Cutaneous Plasmacytomas
the years until 2000 and brought together clinicopathologic features, prognostic factors, and treatment of PCP. In this study, 58.6% of the patients had solitary lesions, whereas 37.9% had multiple lesions, all localizing in the same region.8 In our literature search, we came across only two case reports: one about a 62-year-old patient and the other about a 55-year-old patient with multiple lesions localizing in the trunk. In these patients, the skin lesions showed nodular or diffuse dermal infiltrates that consisted almost entirely of mature plasma cells, including multinucleated plasma cells. Similarly in immunocytomas, coexistent clonal lymphocytes are deficient. The tumor cells are not positive for CD20 and leukocyte common antigen; however, they express monotypic clg+ and CD38+.9 The treatment of choice is usually surgical excision in patients with solitary or a small number of plasmacytomas. However, there are also patients who were treated by and benefited from radiotherapy.6’7 Chemotherapy is indicated in the presence of a considerable amount of multiple cutaneous plasmacytomas, where excision is not possible.6 Patients with multiple skin lesions have been reported to have a higher risk of death and a poorer prognosis compared to patients with solitary skin lesions.3,6,8 There is no description as to the clinical course of the disease, and it cannot be predicted. The neoplasm may progress rapidly by spreading systemically or locally in some patients or may follow a benign protracted course in others. In addition, complete staging may not be positive at the first presentation; however, the disease may act as a precursor of MM in some cases.10 The prevalence of transformation of EMP into MM has been reported to be
A
30 to 50% in a median time of 1.5 to 2.5 years.11 Therefore, close monitoring is recommended, especially in patients with PCP that involves multiple skin lesions.10 Our patient has been closely monitored as he has multiple lesions. Almost 10 months have passed since the diagnosis was established, and there is still no evidence of transformation into MM.
Acknowledgment Financial disclosure of authors and reviewers: None reported.
References 1. Kilciksiz S, Karakoyun-Celik O, Agaoglu FY, Haydaroglu A. A review for solitary plasmacytoma of bone and extramedullary plasmacytoma. Sci World ] 2012;2:6. 2. Galieni P, Cavo M, Pulsoni A, Awisati G, et al. Clinical outcome of extramedullary plasmacytoma. Haematologica 2000;85:47-51. 3. Tilting T, Bork K. Primary plasmacytoma of the skin. J Am Acad Dermatol 1996;34:386-90, doi:10.1016/S0190-9622(07)80014-4. 4. Lin B, Weiss LM. Primary plasmacytoma of lymph nodes. Hum Pathol 1997;28:1083-90, doi:10.1016/S0046-8177(97)90063-0. 5. Alvarez-Twose I, Vano-Galvan S, Calvo-Villas JM, et al. Metastatic cutaneous plasmacytoma presenting as a perianal giant mass. Dermatol Online I 2008;14:17. 6. Fitzhugh VA, Siegel D, Bhattacharyya PK. Multiple primary cutaneous plasmacytomas. I Clin Pathol 2008;61:782-3, doi:10. 1136/jcp.2008.056051. 7. Bluefarb SM. Cutaneous manifestations of multiple myeloma. AMA Arch Derm 1955;72:506-22, doi:10.1001/archderm.l955. 03730360012002.
< 7 Canadian Dermatology Association I Journal of Cutaneous Medicine and Surgery, Vol 18, No 5 (September/October), 2014: pp 361-364
3 63
8. Muscardin LM, Pulsoni A, Cerroni L. Primary cutaneous plasmacytoma: report of a case with review of the literature. J Am Acad Dermatol 2000;43:962-5, doi:10.1067/mid.200Q. 103997. 9. Willemze R, Kerl H, Sterry W, et al. EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer. Blood 1997;90:354-71.
364
10. Kazakov DV, Belousova IE, Muller B, et al. Primary cutaneous plasmacytoma: a clinicopathological study of two cases with a long-term follow-up and review of the literature. J Cutan Pathol 2002;29:244-8, doi:10.1034/i.l600-0560.2002.290408.x. 11. Weber DM. Solitary bone and extramedullary plasmacytoma. Hematology Am Soc Hematol Educ Program 2005;373-6, doi:10. 1182/asheducation-2005.1.373.
Canadian Dermatology Association I Journal of Cutaneous Medicine and Surgery, Vol 18, No 5 (September/October), 2014: pp 381-364
Copyright of Journal of Cutaneous Medicine & Surgery is the property of Decker Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
