- Email: [email protected]
Cutaneous involvement with marginal zone lymphoma
CASE
& REVIEW
Cutaneous involvement with marginal zone lymphoma Pedram Gerami, MD,a,c Scott C. Wickless, DO,a Christiane Querfeld, MD,b Steven T. Rosen, MD,b,c Timothy M. Kuzel, MD,b,c and Joan Guitart, MDa,c Chicago, Illinois Background: Cutaneous marginal zone lymphoma (MZL) may be a primary cutaneous condition or the result of secondary involvement from noncutaneous MZL. Distinguishing primary cutaneous MZL (PCMZL) from secondary cutaneous MZL (SCMZL) is of utmost importance for prognostic and therapeutic approach. Objective: We describe the clinical and histologic features of 4 cases of SCMZL (3 cases of nodal MZL and one case of orbital extranodal MZL), compare them with a cohort of 30 cases of PCMZL, and describe distinctive features of SCMZL. Methods: Thirty cases of PCMZL and 4 cases of non-PCMZL with secondary skin involvement were identified in our cutaneous lymphoma and dermatopathology databases. The medical records were reviewed regarding clinical, histologic, laboratory, and radiologic findings; disease course; response to treatment; and follow-up. All cases were reviewed by 3 dermatopathologists. Results: The histopathological and immunohistochemical features of SCMZL were indistinguishable from our cases with PCMZL. However, the clinical presentation in SCMZL appeared to be distinct. We observed these lesions in an older patient population and in 3 of 4 cases the lesions predominantly involved the head/neck area. Limitations: As PCMZL and SCMZLs are exceedingly rare, only 34 patients were identified in this singleinstitution study. Conclusions: The histologic and immunophenotypic changes in skin lesions from SCMZL may be indistinguishable from those in PCMZL. However, there may be some differences in the typical clinical presentation. PCMZL may be seen in younger patients and favors the trunk and extremities whereas MZL secondarily involving the skin favors the head/neck regions and is limited to older patients. Because there may be considerable overlap in the clinical presentations for patients with primary and secondary cutaneous disease, it is not unreasonable to perform a systemic evaluation for all patients. ( J Am Acad Dermatol 2010;63:142-5.) Key words: lymphoma; marginal zone lymphoma; mucosa-associated lymphoid tissue.
T
here are differences in clinical behavior of primary cutaneous marginal zone lymphoma (PCMZL) relative to other forms of marginal
From the Department of Dermatologya and Division of Hematology/Oncology,b Northwestern University Feinberg School of Medicine; and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.c Funding sources: None. Conflicts of interest: None declared. Reprint requests: Pedram Gerami, MD, Northwestern University, 676 N St Clair St, Suite 1600, Chicago, IL 60611. E-mail: [email protected]. Published online May 12, 2010. 0190-9622/$36.00 ª 2009 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2009.07.047
142
Abbreviations used: MZL: marginal zone lymphoma PCMZL: primary cutaneous marginal zone lymphoma SCMZL: secondary cutaneous marginal zone lymphoma
zone lymphoma (MZL). PCMZL tends to follow an extremely indolent course.1 We are unaware of any definitive cases of PCMZL resulting in death of the patient. Conversely, nodal MZL has a median survival of only 5 years.2 Also, there have been definitive cases of death of disease in other forms MZL such as gastric extranodal MZL and splenic MZL.3-5 Hence, when evaluating patients with cutaneous lesions of
Gerami et al 143
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MZL, it is important to determine whether the lesions As part of the histologic evaluation the T- to B-cell are primary or secondary. ratio was evaluated in all cases in which both T- and Staging is a critical part of management, treatment, B-cell markers were available. The ratio was graded and study of patients with lymphoma. Recently a by a semiquantitative method as greater than 1:1 new TNM staging system for primary cutaneous when B cells outnumbered T cells, 1:1 when T and B lymphomas other than mycosis fungoides and cells were nearly equal, and less than 1:1 when T Se´zary syndrome has been proposed. Therefore, cells outnumbered B cells. Patients were classified proper staging also requires according to the new TNM distinguishing PCMZL from classification proposed for CAPSULE SUMMARY secondary cutaneous MZL cutaneous lymphomas other (SCMZL) disease. than mycosis fungoides and We compared the clinical and histologic Disease associations in MZL Se´zary syndrome from the features of 30 patients with primary may vary based on the organ International Society of cutaneous marginal zone lymphoma site of origin. For example, Cutaneous Lymphomas/ (PCMZL) with 4 patients with secondary gastric mucosa-associated European Organization for cutaneous marginal zone lymphoma lymphoid tissue is most Research and Treatment of (SCMZL). frequently associated with Cancer.6 Patients with PCMZL tended to be Helicobacter pylori infection younger and had a distribution favoring whereas salivary mucosaRESULTS the trunk and extremities. associated lymphoid tissue is Clinical findings mostly associated with hepaWe evaluated 30 patients Patients with SCMZL were older and titis C infection or Sjo¨gren with PCMZL, and 4 patients more commonly had head and neck disease. In European cases, with systemic lymphoma (3 involvement. PCMZL has been associated nodal MZL and one noncutaHistopathologic features of PCMZL and with Borrelia infection in 20% neous extranodal MZL) with SCMZL were virtually indistinguishable. of cases. Therefore, a more secondary cutaneous inBoth types of marginal zone lymphoma selective approach toward volvement. The average age showed a CD10 , BCLG , BCL21, CD431 evaluating possible disease of patients with PCMZL was immunophenotype. associations can be per50 years (15-80 years). There formed with knowledge of were 18 male and 12 female SCMZL less frequently displayed the organ site of origin for patients. Eight of the 30 pagerminal centers. the lymphoma. In this study, tients with PCMZL (27%) we examined the clinical prewere younger than 30 years sentation and histologic findings in 4 cases of MZL at the time of diagnosis. Among patients with secwith secondary cutaneous involvement and comondary cutaneous involvement, the average age was pared them with those of 30 cases of PCMZL. 57 years (49-65) with two men and two women. In the group with secondary skin involvement, the METHODS scalp was the most common site of presentation. After approval from the cancer center and instituThree of 4 patients (75%) presented with a predomtional review board of our university, the cutaneous inance of lesions in the head/neck area (Fig 1, A). In lymphoma database and the dermatopathology daone of the 4 patients, the lesions were exclusively on tabases from our university were searched for cases the head/neck area whereas in the other two they of PCMZL and non-PCMZL with secondary skin primarily involved the head/neck area, with fewer involvement. PCMZL was defined by the presence lesions on the trunk. In one patient, the lesions of cutaneous lesions with typical histologic features predominantly involved the trunk (Fig 1, B). Hence, of MZL with evidence of clonality either by polythere is some overlap between the typical presentamerase chain reaction or light chain restriction and tions of primary and secondary cutaneous disease. no evidence of extracutaneous involvement at the All 4 patients with SCMZL had multiple lesions. Of 30 time of diagnosis. All cases were reviewed by 3 patients with PCMZL, 25 (83%) presented with deepdermatopathologists (J. G., S. C. W., P. G.). Thirty seated papules/nodules to occasionally more supercases of PCMZL and 4 cases of non-PCMZL with ficial papules exclusively involving the upper trunk, secondary skin involvement were identified. The extremities, or both (Fig 1, C). medical records were reviewed regarding clinical, In 22 of these 25 patients the lesions were histologic, laboratory, and radiologic findings; dismultiple, whereas in the remaining 3 patients the ease course; response to treatment; and follow-up. disease consisted of a single lesion. In the other 5 d
d
d
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144 Gerami et al
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Fig 2. A, Dense mononuclear periadnexal infiltrate in patient with primary cutaneous marginal zone lymphoma (MZL). Some areas take on very linear appearance. B, Tracing of adnexa commonly seen in patients with secondary cutaneous MZL. (A and B, Original magnifications: 3400.)
Fig 1. A, Poorly defined erythematous patches/plaques on head and neck area in patient with secondary cutaneous marginal zone lymphoma (SCMZL) and cervical lymphadenopathy. B, Solitary well-demarcated cherry-red papule within group of coalescing erythematous patches/plaques on abdomen of patient with SCMZL. C, Welldemarcated beefy-red plaques on lower extremity of patient with primary cutaneous marginal zone lymphoma.
patients (17%) with PCMZL who did not show this typical pattern of deep-seated papules on the trunk or upper extremities, lesions were seen on the scalp in two patients and legs in two patients, and one patient presented with an isolated patch on the trunk.
Histopathology We evaluated the histopathology and immunohistochemistry from all 30 patients with PCMZL and the 4 patients with SCMZL. The most common pattern identified in at least one biopsy specimen from 28 of 30 patients (93%) with PCMZL consisted of patchy or vertically oriented infiltrates tracing the adnexa (Fig 2, A). All 28 cases showed involvement of the hair follicle and 12 patients had prominent eccrine involvement. Occasional involvement of the arrector pili muscle was also noted. In 21 of these 28 patients, the infiltrate surrounding the follicle consisted of monotonous zones of monocytoid and plasmacytoid lymphocytes with some mature plasma cells. Plasma cell aggregates were identified at the peripheral aspect of the infiltrate. In 7 of the 28 patients, the periadnexal infiltrate was predominantly plasmacytic, resembling immunocytoma. Reactive germinal centers were seen in 12 patients. In 28 of 30 cases, T- and B-cell markers were both available. In 15 of the cases the T and B cells were approximately equal (1:1). In 8 cases T cells surpassed B cells (\1:1) and in only 5 cases there were significantly more B cells than T cells ([1:1). Nine of 30 cases showed the presence of germinal centers.
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Cases of MZL with secondary skin involvement demonstrated similar histologic features to cases of PCMZL. Three of 4 cases showed periadnexal tracing by the lymphoma with mixed populations of monocytoid and plasmacytoid lymphocytes as well as focal aggregates of mature plasma cells (Fig 2, B). None of the cases showed germinal centers. In 3 of the 4 cases B cells strongly outnumbered T cells ([1:1), whereas in one case they were approximately equal (1:1). Immunohistochemistry for CD43 was available in 13 cases of PCMZL and two cases of SCMZL and was positive in all cases tested. Cases of MZL secondarily involving the skin were histologically and immunophenotypically indistinguishable from those of PCMZL.
DISCUSSION It is important to distinguish primary cutaneous lymphomas from systemic lymphomas secondarily involving the skin because of the better prognosis, different disease associations, and alternative staging schemes and treatment options. Our study shows that there are some clinical features that may be helpful in distinguishing PCMZL and SCMZL. Patients with PCMZL tend to be younger than those with SCMZL, with the average age of PCMZL being 50 years versus 57 years in SCMZL. In addition, although 27% of patients with PCMZL were younger than 30 years, our youngest patient with secondary cutaneous involvement was 49 years old. This suggests that younger patients with cutaneous MZL are unlikely to have a site of origin outside of the skin. In addition, patients with SCMZL had a predominance of head/neck lesions in 3 of 4 cases (75%). Using Fisher exact test, P equals .033 comparing the 17% (5/30) of PCMZL versus the 75% (3/4) of SCMZL with the 2tailed test. This was an uncommon site of presentation seen in only 7% (2 of 30 patients) with PCMZL. Hence, older patients with head/neck lesions are the most likely to have a systemic source for their MZL and may require a more comprehensive workup and monitoring to exclude extracutaneous disease. Histologic features were highly similar in cases of PCMZL and SCMZL. Both types showed striking tropism for adnexal structures, primarily the hair follicle unit. Both types also have an identical immunophenotype being CD10e, BCL6e, and BCL21. Aberrant expression of CD43 was seen in all of our cases tested. The most significant histologic difference in our comparison was the difference in T- to B-cell ratio in primary and secondary cases and the number of cases with germinal centers. In general primary
cases tended to have dense T-cell infiltrates, with more B than T cells in 18%, approximately equal B and T cells in 54%, and more T than B cells in 28%. Contrastingly, SCMZL showed greater B than T cells in 75%. Furthermore, none of the cases of SCMZL in our cohort had germinal centers, although 30% of primary cutaneous cases had germinal centers. Overall, the histologic differences are subtle and in general insufficient to reliably distinguish primary from secondary disease. Hence, we believe the clinical clues that we have suggested may be helpful in distinguishing primary from secondary cutaneous disease. This is particularly helpful in younger patients with classic upper truncal and upper extremity distribution of lesions and may help establish appropriate follow-up and management and avoid excessive radiologic and other unnecessary ancillary testing to monitor disease. PCMZL may be seen in younger patients and favors the trunk and extremities whereas MZL secondarily involving the skin favors the head/neck regions and is limited to older patients. However, because there may be considerable overlap in the clinical presentations for patients with primary and secondary cutaneous disease, it is not unreasonable to perform a systemic evaluation for all patients. Further studies are necessary to better understand the diagnosis and treatment of this rare entity. REFERENCES 1. Gerami P, Wickless SC, Rosen S, Kuzel TM, Ciurea A, Havey J, Guitart J. Applying the new TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Se´zary syndrome in primary cutaneous marginal zone lymphoma. J Am Acad Dermatol 2008;59:245-54. 2. Arcaini L, Paulli M, Burcheri S, Rossi A, Spina M, Passamonti F, et al. Primary nodal marginal zone B-cell lymphoma: clinical features and prognostic assessment of a rare disease. Br J Haematol 2007;136:301-4. 3. Arcaini L, Lazzarino M, Colombo N, Burcheri S, Boveri E, Paulli M, et al. Splenic marginal zone lymphoma: a prognostic model for clinical use. Blood 2006;107:4643-9. 4. Jezersek NB, Vovk M, Juznic ST. A single-center study of treatment outcomes and survival in patients with primary gastric lymphomas between 1990 and 2003. Ann Hematol 2006;85:849-56. 5. Nakamura T, Seto M, Tajika M, Kawai H, Yokoi T, Yatabe Y, Nakamura S. Clinical features and prognosis of gastric MALT lymphoma with special reference to responsiveness to H pylori eradication and API2-MALT1 status. Am J Gastroenterol 2008; 103:62-70. 6. Kim YH, Willemze R, Pimpinelli N, Whittaker S, Olsen EA, Ranki A, et al. TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Se´zary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC). Blood 2007;110:479-84.
& REVIEW
Cutaneous involvement with marginal zone lymphoma Pedram Gerami, MD,a,c Scott C. Wickless, DO,a Christiane Querfeld, MD,b Steven T. Rosen, MD,b,c Timothy M. Kuzel, MD,b,c and Joan Guitart, MDa,c Chicago, Illinois Background: Cutaneous marginal zone lymphoma (MZL) may be a primary cutaneous condition or the result of secondary involvement from noncutaneous MZL. Distinguishing primary cutaneous MZL (PCMZL) from secondary cutaneous MZL (SCMZL) is of utmost importance for prognostic and therapeutic approach. Objective: We describe the clinical and histologic features of 4 cases of SCMZL (3 cases of nodal MZL and one case of orbital extranodal MZL), compare them with a cohort of 30 cases of PCMZL, and describe distinctive features of SCMZL. Methods: Thirty cases of PCMZL and 4 cases of non-PCMZL with secondary skin involvement were identified in our cutaneous lymphoma and dermatopathology databases. The medical records were reviewed regarding clinical, histologic, laboratory, and radiologic findings; disease course; response to treatment; and follow-up. All cases were reviewed by 3 dermatopathologists. Results: The histopathological and immunohistochemical features of SCMZL were indistinguishable from our cases with PCMZL. However, the clinical presentation in SCMZL appeared to be distinct. We observed these lesions in an older patient population and in 3 of 4 cases the lesions predominantly involved the head/neck area. Limitations: As PCMZL and SCMZLs are exceedingly rare, only 34 patients were identified in this singleinstitution study. Conclusions: The histologic and immunophenotypic changes in skin lesions from SCMZL may be indistinguishable from those in PCMZL. However, there may be some differences in the typical clinical presentation. PCMZL may be seen in younger patients and favors the trunk and extremities whereas MZL secondarily involving the skin favors the head/neck regions and is limited to older patients. Because there may be considerable overlap in the clinical presentations for patients with primary and secondary cutaneous disease, it is not unreasonable to perform a systemic evaluation for all patients. ( J Am Acad Dermatol 2010;63:142-5.) Key words: lymphoma; marginal zone lymphoma; mucosa-associated lymphoid tissue.
T
here are differences in clinical behavior of primary cutaneous marginal zone lymphoma (PCMZL) relative to other forms of marginal
From the Department of Dermatologya and Division of Hematology/Oncology,b Northwestern University Feinberg School of Medicine; and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.c Funding sources: None. Conflicts of interest: None declared. Reprint requests: Pedram Gerami, MD, Northwestern University, 676 N St Clair St, Suite 1600, Chicago, IL 60611. E-mail: [email protected]. Published online May 12, 2010. 0190-9622/$36.00 ª 2009 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2009.07.047
142
Abbreviations used: MZL: marginal zone lymphoma PCMZL: primary cutaneous marginal zone lymphoma SCMZL: secondary cutaneous marginal zone lymphoma
zone lymphoma (MZL). PCMZL tends to follow an extremely indolent course.1 We are unaware of any definitive cases of PCMZL resulting in death of the patient. Conversely, nodal MZL has a median survival of only 5 years.2 Also, there have been definitive cases of death of disease in other forms MZL such as gastric extranodal MZL and splenic MZL.3-5 Hence, when evaluating patients with cutaneous lesions of
Gerami et al 143
J AM ACAD DERMATOL VOLUME 63, NUMBER 1
MZL, it is important to determine whether the lesions As part of the histologic evaluation the T- to B-cell are primary or secondary. ratio was evaluated in all cases in which both T- and Staging is a critical part of management, treatment, B-cell markers were available. The ratio was graded and study of patients with lymphoma. Recently a by a semiquantitative method as greater than 1:1 new TNM staging system for primary cutaneous when B cells outnumbered T cells, 1:1 when T and B lymphomas other than mycosis fungoides and cells were nearly equal, and less than 1:1 when T Se´zary syndrome has been proposed. Therefore, cells outnumbered B cells. Patients were classified proper staging also requires according to the new TNM distinguishing PCMZL from classification proposed for CAPSULE SUMMARY secondary cutaneous MZL cutaneous lymphomas other (SCMZL) disease. than mycosis fungoides and We compared the clinical and histologic Disease associations in MZL Se´zary syndrome from the features of 30 patients with primary may vary based on the organ International Society of cutaneous marginal zone lymphoma site of origin. For example, Cutaneous Lymphomas/ (PCMZL) with 4 patients with secondary gastric mucosa-associated European Organization for cutaneous marginal zone lymphoma lymphoid tissue is most Research and Treatment of (SCMZL). frequently associated with Cancer.6 Patients with PCMZL tended to be Helicobacter pylori infection younger and had a distribution favoring whereas salivary mucosaRESULTS the trunk and extremities. associated lymphoid tissue is Clinical findings mostly associated with hepaWe evaluated 30 patients Patients with SCMZL were older and titis C infection or Sjo¨gren with PCMZL, and 4 patients more commonly had head and neck disease. In European cases, with systemic lymphoma (3 involvement. PCMZL has been associated nodal MZL and one noncutaHistopathologic features of PCMZL and with Borrelia infection in 20% neous extranodal MZL) with SCMZL were virtually indistinguishable. of cases. Therefore, a more secondary cutaneous inBoth types of marginal zone lymphoma selective approach toward volvement. The average age showed a CD10 , BCLG , BCL21, CD431 evaluating possible disease of patients with PCMZL was immunophenotype. associations can be per50 years (15-80 years). There formed with knowledge of were 18 male and 12 female SCMZL less frequently displayed the organ site of origin for patients. Eight of the 30 pagerminal centers. the lymphoma. In this study, tients with PCMZL (27%) we examined the clinical prewere younger than 30 years sentation and histologic findings in 4 cases of MZL at the time of diagnosis. Among patients with secwith secondary cutaneous involvement and comondary cutaneous involvement, the average age was pared them with those of 30 cases of PCMZL. 57 years (49-65) with two men and two women. In the group with secondary skin involvement, the METHODS scalp was the most common site of presentation. After approval from the cancer center and instituThree of 4 patients (75%) presented with a predomtional review board of our university, the cutaneous inance of lesions in the head/neck area (Fig 1, A). In lymphoma database and the dermatopathology daone of the 4 patients, the lesions were exclusively on tabases from our university were searched for cases the head/neck area whereas in the other two they of PCMZL and non-PCMZL with secondary skin primarily involved the head/neck area, with fewer involvement. PCMZL was defined by the presence lesions on the trunk. In one patient, the lesions of cutaneous lesions with typical histologic features predominantly involved the trunk (Fig 1, B). Hence, of MZL with evidence of clonality either by polythere is some overlap between the typical presentamerase chain reaction or light chain restriction and tions of primary and secondary cutaneous disease. no evidence of extracutaneous involvement at the All 4 patients with SCMZL had multiple lesions. Of 30 time of diagnosis. All cases were reviewed by 3 patients with PCMZL, 25 (83%) presented with deepdermatopathologists (J. G., S. C. W., P. G.). Thirty seated papules/nodules to occasionally more supercases of PCMZL and 4 cases of non-PCMZL with ficial papules exclusively involving the upper trunk, secondary skin involvement were identified. The extremities, or both (Fig 1, C). medical records were reviewed regarding clinical, In 22 of these 25 patients the lesions were histologic, laboratory, and radiologic findings; dismultiple, whereas in the remaining 3 patients the ease course; response to treatment; and follow-up. disease consisted of a single lesion. In the other 5 d
d
d
d
d
d
144 Gerami et al
J AM ACAD DERMATOL JULY 2010
Fig 2. A, Dense mononuclear periadnexal infiltrate in patient with primary cutaneous marginal zone lymphoma (MZL). Some areas take on very linear appearance. B, Tracing of adnexa commonly seen in patients with secondary cutaneous MZL. (A and B, Original magnifications: 3400.)
Fig 1. A, Poorly defined erythematous patches/plaques on head and neck area in patient with secondary cutaneous marginal zone lymphoma (SCMZL) and cervical lymphadenopathy. B, Solitary well-demarcated cherry-red papule within group of coalescing erythematous patches/plaques on abdomen of patient with SCMZL. C, Welldemarcated beefy-red plaques on lower extremity of patient with primary cutaneous marginal zone lymphoma.
patients (17%) with PCMZL who did not show this typical pattern of deep-seated papules on the trunk or upper extremities, lesions were seen on the scalp in two patients and legs in two patients, and one patient presented with an isolated patch on the trunk.
Histopathology We evaluated the histopathology and immunohistochemistry from all 30 patients with PCMZL and the 4 patients with SCMZL. The most common pattern identified in at least one biopsy specimen from 28 of 30 patients (93%) with PCMZL consisted of patchy or vertically oriented infiltrates tracing the adnexa (Fig 2, A). All 28 cases showed involvement of the hair follicle and 12 patients had prominent eccrine involvement. Occasional involvement of the arrector pili muscle was also noted. In 21 of these 28 patients, the infiltrate surrounding the follicle consisted of monotonous zones of monocytoid and plasmacytoid lymphocytes with some mature plasma cells. Plasma cell aggregates were identified at the peripheral aspect of the infiltrate. In 7 of the 28 patients, the periadnexal infiltrate was predominantly plasmacytic, resembling immunocytoma. Reactive germinal centers were seen in 12 patients. In 28 of 30 cases, T- and B-cell markers were both available. In 15 of the cases the T and B cells were approximately equal (1:1). In 8 cases T cells surpassed B cells (\1:1) and in only 5 cases there were significantly more B cells than T cells ([1:1). Nine of 30 cases showed the presence of germinal centers.
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Cases of MZL with secondary skin involvement demonstrated similar histologic features to cases of PCMZL. Three of 4 cases showed periadnexal tracing by the lymphoma with mixed populations of monocytoid and plasmacytoid lymphocytes as well as focal aggregates of mature plasma cells (Fig 2, B). None of the cases showed germinal centers. In 3 of the 4 cases B cells strongly outnumbered T cells ([1:1), whereas in one case they were approximately equal (1:1). Immunohistochemistry for CD43 was available in 13 cases of PCMZL and two cases of SCMZL and was positive in all cases tested. Cases of MZL secondarily involving the skin were histologically and immunophenotypically indistinguishable from those of PCMZL.
DISCUSSION It is important to distinguish primary cutaneous lymphomas from systemic lymphomas secondarily involving the skin because of the better prognosis, different disease associations, and alternative staging schemes and treatment options. Our study shows that there are some clinical features that may be helpful in distinguishing PCMZL and SCMZL. Patients with PCMZL tend to be younger than those with SCMZL, with the average age of PCMZL being 50 years versus 57 years in SCMZL. In addition, although 27% of patients with PCMZL were younger than 30 years, our youngest patient with secondary cutaneous involvement was 49 years old. This suggests that younger patients with cutaneous MZL are unlikely to have a site of origin outside of the skin. In addition, patients with SCMZL had a predominance of head/neck lesions in 3 of 4 cases (75%). Using Fisher exact test, P equals .033 comparing the 17% (5/30) of PCMZL versus the 75% (3/4) of SCMZL with the 2tailed test. This was an uncommon site of presentation seen in only 7% (2 of 30 patients) with PCMZL. Hence, older patients with head/neck lesions are the most likely to have a systemic source for their MZL and may require a more comprehensive workup and monitoring to exclude extracutaneous disease. Histologic features were highly similar in cases of PCMZL and SCMZL. Both types showed striking tropism for adnexal structures, primarily the hair follicle unit. Both types also have an identical immunophenotype being CD10e, BCL6e, and BCL21. Aberrant expression of CD43 was seen in all of our cases tested. The most significant histologic difference in our comparison was the difference in T- to B-cell ratio in primary and secondary cases and the number of cases with germinal centers. In general primary
cases tended to have dense T-cell infiltrates, with more B than T cells in 18%, approximately equal B and T cells in 54%, and more T than B cells in 28%. Contrastingly, SCMZL showed greater B than T cells in 75%. Furthermore, none of the cases of SCMZL in our cohort had germinal centers, although 30% of primary cutaneous cases had germinal centers. Overall, the histologic differences are subtle and in general insufficient to reliably distinguish primary from secondary disease. Hence, we believe the clinical clues that we have suggested may be helpful in distinguishing primary from secondary cutaneous disease. This is particularly helpful in younger patients with classic upper truncal and upper extremity distribution of lesions and may help establish appropriate follow-up and management and avoid excessive radiologic and other unnecessary ancillary testing to monitor disease. PCMZL may be seen in younger patients and favors the trunk and extremities whereas MZL secondarily involving the skin favors the head/neck regions and is limited to older patients. However, because there may be considerable overlap in the clinical presentations for patients with primary and secondary cutaneous disease, it is not unreasonable to perform a systemic evaluation for all patients. Further studies are necessary to better understand the diagnosis and treatment of this rare entity. REFERENCES 1. Gerami P, Wickless SC, Rosen S, Kuzel TM, Ciurea A, Havey J, Guitart J. Applying the new TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Se´zary syndrome in primary cutaneous marginal zone lymphoma. J Am Acad Dermatol 2008;59:245-54. 2. Arcaini L, Paulli M, Burcheri S, Rossi A, Spina M, Passamonti F, et al. Primary nodal marginal zone B-cell lymphoma: clinical features and prognostic assessment of a rare disease. Br J Haematol 2007;136:301-4. 3. Arcaini L, Lazzarino M, Colombo N, Burcheri S, Boveri E, Paulli M, et al. Splenic marginal zone lymphoma: a prognostic model for clinical use. Blood 2006;107:4643-9. 4. Jezersek NB, Vovk M, Juznic ST. A single-center study of treatment outcomes and survival in patients with primary gastric lymphomas between 1990 and 2003. Ann Hematol 2006;85:849-56. 5. Nakamura T, Seto M, Tajika M, Kawai H, Yokoi T, Yatabe Y, Nakamura S. Clinical features and prognosis of gastric MALT lymphoma with special reference to responsiveness to H pylori eradication and API2-MALT1 status. Am J Gastroenterol 2008; 103:62-70. 6. Kim YH, Willemze R, Pimpinelli N, Whittaker S, Olsen EA, Ranki A, et al. TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Se´zary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC). Blood 2007;110:479-84.