AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Classification
• Nosologic Entities of CBCL
• Differential Diagnoses of CBCL
• Workup in CBCL
• Treatment
• Follow Up
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Classification
• Nosologic Entities of CBCL
• Differential Diagnoses of CBCL
• Workup in CBCL
• Treatment
• Follow Up
• Multimedia
• References

Background

Cutaneous lymphomas (CLs) represent a unique group of lymphomas and are the second most frequent extranodal lymphomas.¹ They can be defined as unwarranted lymphoproliferative skin infiltrates of T-cell, B-cell, or natural killer cell lineage, which primarily occur in and remain confined to the skin, without detectable extracutaneous manifestations at diagnosis.

B-cell lymphomas account for the majority of nodal lymphomas, whereas in the skin, primary cutaneous B-cell lymphomas (CBCLs) represent 20-25% of all CLs. Because CBCLs have an overall favorable prognosis, proper recognition is vital for appropriate therapy and to avoid overtreatment in most cases. The tumor type and the extent of cutaneous involvement are the 2 most relevant prognostic factors in primary CBCL.²

Pathophysiology

The etiology and the exact steps in the pathogenesis of CLs are only partially understood. Most probably, lymphomagenesis of CL represents a multifactorial and multistep process, owing to the impact of various etiologic factors occurring over a long period. The disease likely begins as a hyperreactive inflammatory process. Deficits in cell proliferation regulation and defective oncogene and/or suppressor gene expression later promote transition from preneoplastic conditions to neoplasia. The most important factors initiating CBCLs are immunodeficiency disorders, infections with oncogenic viruses (eg, Epstein-Barr virus [EBV], human herpesvirus type 8/Kaposi sarcoma–associated herpesvirus, HIV), and bacteria (eg, Helicobacter pylori in mucosa-associated lymphoid tissue [MALT] lymphomas, Borrelia burgdorferi in CBCLs).

Demographic features

The frequency of CLs is 0.3 case per 100,000 population per year, with 10% (in the United States) to 20% (in Europe) being CBCLs, marginal zone lymphomas, or follicle center lymphoma (FCL) in most cases

The 5-year overall survival rate for most cases of CBCL is greater than 90%, except in diffuse large B-cell lymphoma (DLBCL), for which the 5-year survival rate is 20-50%.

No significant statistical data are available for CBCL with regard to any predisposition based on race. However, with regard to sex and age, DLBCL is predominantly seen in elderly women.

CLASSIFICATION

Section 3 of 10  

• Authors and Editors
• Introduction
• Classification
• Nosologic Entities of CBCL
• Differential Diagnoses of CBCL
• Workup in CBCL
• Treatment
• Follow Up
• Multimedia
• References

Diseases formerly designated as reticulosis or reticulosarcomatosis today are classified according to the World Health Organization (WHO)/European Organization for Research and Treatment of Cancer (EORTC) classification (WHO-EORTC classification) for primary CLs.^{3, 4 5, 6}

Cutaneous T-cell lymphomas (CTCLs) can be stratified in prognostically relevant clinical stages, but no generally accepted staging classification exists for primary CBCL. In 2007, a new TNM staging system for non–mycosis fungoides/Sézary syndrome has been developed.⁷ However, the value of this scheme still must be proven by clinicopathological studies.

WHO/EORTC classification of CBCLs^{3, 4, 5, 6} is as follows:

Cutaneous marginal zone B-cell lymphoma (MALT-type)

Variant

• Immunocytoma
• Primary cutaneous plasmacytoma

Primary cutaneous follicle centre lymphoma

Variants (according to growth pattern)

• Follicular
• Follicular and diffuse
• Diffuse

Cutaneous DLBCL

Variants

• Leg type
• Others

Intravascular large B-cell lymphoma

Lymphomatoid granulomatosis*

Chronic lymphocytic leukemia*

Mantle cell lymphoma*

Burkitt lymphoma*

*Not primarily in the skin; only secondary skin involvement.

NOSOLOGIC ENTITIES OF CBCL

Section 4 of 10  

• Authors and Editors
• Introduction
• Classification
• Nosologic Entities of CBCL
• Differential Diagnoses of CBCL
• Workup in CBCL
• Treatment
• Follow Up
• Multimedia
• References

Primary cutaneous marginal zone B-cell lymphoma (MALT-type)

Marginal zone B-cell lymphoma (MZL) (MALT-type) is an indolent CL, accounting for approximately 10% of all CLs. The prognosis is excellent, with a 5-year survival rate of greater than 95%.

Synonyms based on classification are as follows:

• WHO/EORTC classification (2005) - Primary cutaneous MZL
• WHO classification (2001) - Extranodal marginal zone lymphoma of MALT type
• Revised European American Lymphoma (REAL) classification (1997) - Extranodal MZL
• EORTC classification (1997) - Primary cutaneous MZL

Extranodal low-grade B-cell lymphoma of the MALT type and FCL are the most frequent types of peripheral B-cell neoplasms seen primarily in the skin.^{8, 9, 10}

Extranodal MZL may develop from reactive infiltrates that represent immune responses to external factors or autoantigens.¹¹ An etiopathological relationship to B burgdorferi has been demonstrated in some cases.^{12, 13}

Clinically, MZL manifests as solitary or multiple reddish, dome-shaped papules, nodules, or erythematous plaques, frequently located on the trunk and extremities and, to a lesser extent, on the head and neck area.

Histologic findings include a nodular or diffuse nonepidermotropic infiltrate composed of small to medium-sized lymphoid cells with indented nuclei and abundant, pale cytoplasm (marginal zone cells, monocytoid B-cells) or lymphoplasmacytoid cells.¹⁴ Darker chromatin-rich cells are surrounded by pale-staining cells, resulting in a characteristic inverse pattern.

The tumor cells express the following immunophenotype: CD19⁺, CD20⁺, CD22⁺, CD43⁺, CD79a⁺, CD5^-, CD10^-, CD23^-, bcl-6^-, bcl-2⁺, KiM1p⁺ (monocytoid B-cell–related antibody) and show monotypic expression of immunoglobulin light chain kappa more frequently than lambda. Plasmacytoid cells may be present in confluent aggregates. In the periphery of the infiltrate, a variable number of reactive CD3⁺ T cells  and reactive germinal centers are present, colonized by tumor cells and reactive T cells.

Molecular analysis has shown that immunoglobulin H (IgH) genes are clonally rearranged in most cases.¹⁵ Translocation of t(11;18), as is seen in the nodal counterpart, is not found in primary cutaneous MZL.

Primary cutaneous MZL with high numbers of monotypic plasma cells and lymphoplasmacytoid cells showing intranuclear periodic acid-Schiff–positive globular inclusions (Dutcher bodies) was previously referred to as cutaneous immunocytoma.^{12, 16}

Primary cutaneous FCL

Primary cutaneous FCL is an indolent lymphoma of follicle center cells (centrocytes and centroblasts). The prevalence rate is approximately 12%, and the 5-year survival rate is greater than 90-95%, indicating the excellent prognosis in comparison to its nodal counterpart.

Synonyms based on classification are as follows:

• WHO/EORTC classification (2005) - Primary cutaneous FCL
• WHO classification (2001) - Cutaneous FCL
• REAL classification (1997) - FCL, follicular
• EORTC classification (1997) - Primary cutaneous follicle center cell lymphoma

Clinically, nodules and tumors are found most frequently in the head and neck area, but they are also found in other locations of the body.¹⁷ A firm consistency without ulceration is very typical.

Histologically, 3 growth patterns can be differentiated: follicular, follicular and diffuse, and diffuse. The infiltrates are composed mainly of centrocytelike cells with intermingled centroblasts and immunoblasts. A subepidermal grenz zone is present in most cases. Mitoses, tingible body macrophages, and starry-sky features, typically found in reactive lymph follicles,¹⁸ are rare or absent in FCL.

Immunophenotypically, the cells in FCL express CD19⁺, CD20⁺, CD22⁺, CD43⁺, CD79a⁺, CD5^-, CD23^+/-, CD43, bcl-6⁺, bcl-2^-, CD10⁺ (in cases with a follicular growth pattern). Follicular dendritic cells (CD21⁺) are arranged in an irregular network, sometimes with a ringlike pattern. The MUM/IRF4 antigen, which is positive in DLBCL, is not expressed in FCL and may be helpful in differentiating FCL with a diffuse growth pattern from DLBCL.

Molecular analysis shows clonal rearrangement of immunoglobulin genes. In contrast to secondary skin involvement in FCL, chromosomal translocation of t(14;18) and BCL2 gene rearrangement are absent in most cases of primary cutaneous FCL.^{19, 20}

Studies on gene expression profiles have shown distinct patterns in various types of B-cell lymphoma of the skin.^{21, 22}

Reticulohistiocytoma of the back, or Crosti lymphoma, is a variant of cutaneous FCL.²³

Diffuse large B-cell lymphoma

Primary cutaneous DLBCL is an aggressive CBCL, accounting for approximately 6% of all CLs. It is associated with a relatively poor prognosis compared with other primary CBCLs, with a 5-year survival rate of 20-55%, and tends to spread to lymph nodes and extracutaneous sites.

Two groups have been differentiated. The first is the leg type and the second is DLBCL, other. The leg type usually occurs on the lower legs of elderly women. The term is similar to terms used in the classification of other extranodal lymphomas (eg, nasal type). It manifests with a distinct phenotype and can also be present in other locations of the body (with a similar bad prognosis). DLBCL, others, includes T-cell/histiocyte-rich DLBCL, plasmablastic lymphoma, and other types that do not fulfill the criteria for a DLBCL, leg type.

Synonyms based on classification are as follows:

• WHO/EORTC classification (2005) - Primary cutaneous DLBCL
• • DLBCL, leg type
  • DLBCL, other
• WHO classification (2001) - DLBCL
• REAL classification (1997) - DLBCL
• EORTC classification (1997) - Primary cutaneous large B-cell lymphoma of the leg

Clinically, these lymphomas usually manifest as a solitary nodule or as multiple tumors restricted to one anatomic area. They have a strong tendency for extracutaneous spread into regional lymph nodes and other extracutaneous sites.

The histological features are characterized by a diffuse infiltrate sparing a thin subepidermal grenz zone in most cases, covering the entire dermis, destroying adnexal structures, and extending into the subcutaneous tissue. The tumor cells are large B cells, formally referred to as centroblasts and immunoblasts.²⁴ Centrocytes, which are typically seen in FCL, are minimal or absent in DLBCL. 

The immunophenotype of the neoplastic cells is CD19⁺, CD20⁺, CD22⁺, CD5^-, CD10^-, CD79a⁺, bcl-2⁺⁺, bcl-6^-/+, MUM1⁺, CD138^-, cyclin D1^-. The strong positivity for Bcl-2 protein and MUM-1/IRF-4²⁵ allows differentiation of FCL with a diffuse growth pattern from DLBCL.

Molecular analysis shows clonal rearrangement of immunoglobulin genes. In primary cutaneous DLBCL, t(14; 18) and the bcl-2/JH translocation cannot be detected.²⁶ Gene expression profiles of DLBCL and FCL with a diffuse growth pattern are different.^{21, 22, 27}

DLBCL, other

The DLBCL, other subcategory includes large B-cell lymphomas with distinct growth patterns, such as T-cell rich/histiocytic DLBCL²⁸ and intravascular large B-cell lymphoma.^{29, 30}

B-cell lymphomas with common secondary cutaneous involvement

Skin involvement in mantle cell lymphoma is rare and usually secondary.³¹ Cyclin D1 is a useful marker for the small tumor cells derived from mantle cells.

Lymphomatoid granulomatosis is a rare multisystemic, angiocentric, and angiodestructive B-cell lymphoproliferative disease that involves extranodal sites, especially the lungs, skin, and nervous system. It is associated with EBV infection and may progress to DLBCL.

Burkitt lymphoma occurs endemically in children in the so-called lymphoma belt of Central Africa and is associated with EBV infection in most cases. Sporadic EBV-negative cases may be seen in association with HIV-induced immunodeficiency.³²

Waldenström macroglobulinemia is characterized by a clonal expansion of lymphocytes with plasmacytoid features that produce a monoclonal immunoglobulin M protein and infiltrate bone marrow, lymph nodes, and the spleen. Cutaneous involvement usually is nonspecific, showing urticarial and purpuric eruptions, ulcers, bullous lesions, and vasculitis.

Multiple myeloma with monoclonal gammopathy typically induces hyperkeratotic spicules, preferentially on the face.³³

DIFFERENTIAL DIAGNOSES OF CBCL

Section 5 of 10  

• Authors and Editors
• Introduction
• Classification
• Nosologic Entities of CBCL
• Differential Diagnoses of CBCL
• Workup in CBCL
• Treatment
• Follow Up
• Multimedia
• References

Differentiation of CBCL from CTCL

The history in CTCL usually is long with a prediagnostic-preneoplastic phase over several years, during which differentiation from dermatitis may be impossible. In contrast, CBCL lesions evolve quickly, usually within a few weeks.

Most CTCLs show typical clinical features. The prototype, mycosis fungoides, starts with eczematous patches, slowly developing into plaques over years or sometimes over decades, and finally evolving into exophytic tumors with ulceration.

The most significant discriminating histological feature between T- and B-cell lymphomas of the skin is the growth pattern,^{4, 34, 35} which is horizontal, disk-like, and epidermotropic in CTCL and is ball-like, spherical, and nonepidermotropic in CBCL. Moreover, infiltrating cells in CTCL tend to be small and irregularly shaped with convoluted and indented nuclei. Cells in CBCL usually are oval or roundish, reflecting the shapes of large follicular center cells, immunoblasts, or plasma cells.

The immunophenotypical features are clearly different and correspond to the T- or B-cell lineage from which they originate. Genotyping reveals clonal rearrangement of immunoglobulin genes and of T-cell receptor genes, respectively.

Differentiation of CBCL and B-cell pseudolymphoma

The most important differential diagnosis of CBCL is from B-cell pseudolymphoma (PSL) (lymphoid hyperplasia) of the skin.^{16, 36, 37, 38}

Clinically, PSL is usually located as a single nodule on the face, neck, mammillae, or scrotum following B burgdorferi infection through a tick bite, tattooing, or other mechanical or infectious irritants. The consistency is soft, in contrast to the nodules of CBCL, which are firm or even hard.

Histologically, the infiltrate in CBCL is usually dome shaped with a convex border of infiltrative nodules. In PSL, it is wedge shaped, showing concave borders of the infiltrate. The latter may show regular germinal center formation, as is seen in reactive lymph nodes, with many starry-sky macrophages carrying ingested nuclear dust. Eosinophils, polyclonal plasma cells, and many T cells are present in the periphery and within the follicular area.

Immunophenotypically, the expression presence of both kappa- and lambda-positive cells in the infiltrate argues in favor of PSL. The networks of CD21⁺ dendritic cells are regular, round, or oval in PSL but are irregular, ringlike, or bizarre in CBCL, if present at all.

Genotyping reveals clonal rearrangement of immunoglobulin genes in most cases of CBCL and lacks clonality in PSL.

Differentiation of various types of CBCL

In contrast to primary CTCLs, primary CBCLs appear very clinically similar. However, a few criteria are seen more frequently in one or the other type. Nodules and tumors of MZL and of FCL demonstrate a hard consistency and are seen more frequently in the head and neck area (FCL) and on the trunk or arms (MZL), whereas single or grouped tumors on the lower legs typically appear in DLBCL, leg type, in elderly patients.

The histological growth pattern is nodular with convex borders. The infiltrating cells correspond in morphology to their normal counterparts, which are small lymphocytes and large follicle center cells, immunoblasts, and smaller mantle cells or marginal zone monocytoid or plasmacytoid B cells.

The immunophenotypical pattern is most important in the differentiation of various entities of CBCL. The typical differential features are given in the Table.

Gene rearrangement studies are helpful adjunctive diagnostic markers in the differentiation of CBCL from CTCL and B-cell PSL, but they do not allow discrimination of CBCL subtypes.

Gene expression profiles may be helpful for discriminating DLBCL from FCL and other subtypes of CBCL.^{21, 22, 27}

WORKUP IN CBCL

Section 6 of 10  

• Authors and Editors
• Introduction
• Classification
• Nosologic Entities of CBCL
• Differential Diagnoses of CBCL
• Workup in CBCL
• Treatment
• Follow Up
• Multimedia
• References

Mycosis fungoides, the prototype of CTCL, usually evolves from erythematous patches, to plaques, and then to tumoral lesions over a period of years and decades, whereas CBCL has a relatively brief history of nodules and tumors growing within a few weeks or months, preferentially in the head and neck area or trunk; these nodules and tumors may be surrounded by monomorphous papules or dermal plaques.

Histomorphology and cytomorphology

CBCL exhibits a typical growth pattern, referred to as a B-cell pattern.³⁴ It is characterized by a (often well-demarcated) nodular infiltrate of densely packed lymphoid cells in the dermis with convex margins, without significant interstitial infiltration and without epidermotropism. The subepidermal grenz zone is free of lymphoid cells. Whereas inflammatory infiltrates usually comprise a mixture of various cell types, lymphoproliferative disorders, especially FCL (diffuse type) and DLBCL, mostly show a predominance of one cell type.

Cytomorphologically, the infiltrating cells in CBCL correspond to small lymphocytes or to the cellular components of the lymph follicle (ie, centrocytes, centroblasts, mantle cells, monocytoid B cells of the marginal zone, plasma cells, or immunoblasts).

Immunohistochemistry and phenotypic features

Immunohistochemical identification of the tumor cell phenotype plays a crucial role in the diagnostic workup, especially of CBCLs. The most important antibodies for CBCL are CD5 (expressed in B-cell chronic lymphatic leukemia), CD20, CD79a, CD21 (marker for follicular dendritic cells), CD10, Mum-1/IRF4, bcl-2, bcl-6, and kappa- and lambda light chains. Classic T-cell markers (ie, CD2, CD3, CD4, CD8, CD7, CD43 [also stains blastic B cells and a variety of histiocytic cells], CD30) should be negative. However, be aware of aberrant expression of T-cell markers (ie, CD43, CD5) or of CD30 in CBCL.

Translocation of the BCL2 gene (t14;18),¹⁹ although regularly seen in nodal follicular lymphomas, is usually negative in CBCL and thus cannot be regarded as a helpful diagnostic tool in these cases.

Genotyping and cytogenetic studies in CBCLs

The tumor cells show clonal rearrangement of immunoglobulin genes in 60-70% of the cases in CBCL.  Cases of cutaneous lymphoid hyperplasia with monotypic plasma cells have been reported, which have been described to be a biologically distinct clinicopathological entity.³⁸

The genetic defects in CL are heterogeneous.⁴ Thus, to date, the detection of chromosomal abnormalities has limited diagnostic or prognostic value in CTCL and CBCL. Nodal follicular lymphoma is determined by the presence of a unique translocation between chromosomes 14 and 18, t(14;18)(q32;q21), BCL2-JH gene rearrangement that is not present in primary cutaneous FCL. Genetic alterations have been detected in intravascular lymphoma, possibly delineating the critical mutations associated with the initiation and progression of this disease, but without any diagnostic relevance.³⁹

Cytogenetic analysis using fluorescence in situ hybridization and other techniques has shown that recurrent chromosomal abnormalities known in systemic MZL of the MALT type and in nodal FCL rarely occur in primary CBCL of these types.⁴⁰ A reciprocal translocation between the long arms of chromosomes 12 and 21, t(12;21)(q13;q22), has been found in a patient with primary cutaneous FCL,⁴¹ which again is of some interest in view of the potential pathogenetic pathway of these tumors, but so far has no practical diagnostic relevance.

The modern standard procedure to elucidate and define the normal and pathologic state of a cell or tissue type is the analysis of tissue-specific gene expression and functional profiling by microarray technology.^{21, 22}

Blood tests, laboratory tests, and other investigations

A routine blood cell count is performed in order to exclude leukemic spread to tumor cells, which is unlikely if palpable enlargement of the lymph nodes is absent. In primary CBCL, abnormalities in routine laboratory investigations are not  expected.

The likelihood of significant node involvement in patients with nonpalpable nodes is low; therefore, blind lymph node biopsy is not indicated. However, a lymph node biopsy should be performed if lymph nodes are enlarged.

Additional investigations include chest radiography, ultrasonography, and CT scanning of the abdomen and peripheral lymph nodes. CT scanning of the abdomen and peripheral lymph nodes is useful in patients with advanced skin disease and palpable lymphadenopathy for an accurate baseline assessment and to document disease progression. A bone marrow biopsy should be considered in persons with DLBCL, in order to confirm the primary cutaneous origin and to exclude extracutaneous origin of the lymphoproliferative disorder.

TREATMENT

Section 7 of 10  

• Authors and Editors
• Introduction
• Classification
• Nosologic Entities of CBCL
• Differential Diagnoses of CBCL
• Workup in CBCL
• Treatment
• Follow Up
• Multimedia
• References

Overtreatment in FCL and MZL must be prevented because CBCLs have a much better prognosis than their nodal counterparts. Aggressive systemic treatment regimens are suitable only for DLBCL and for patients with extracutaneous spread. Treatment follows standard regimens for primary nodal lymphomas in these patients (see Lymphoma, B-Cell). 

The treatment of primary CLs associated with an excellent prognosis (ie, MZL [including immunocytoma] and FCL)^{42, 43, 44, 45, 46} is as follows:

• First-line treatments for solitary lesions
• • Surgical excision
  • Antibiotics - Doxycycline at 100 mg twice daily for 3 weeks⁴⁷ or pulse therapy with cefotaxime^{43, 48}
  • Radiotherapy - 20-100 kV Orthovolt therapy 1-4 times per week, to a total dose of up to 15-20 Gy⁴⁹; extended-field irradiation at 30 Gy (4 fractions of 2.5 Gy/wk); localized-field irradiation as either a boost after extended-field irradiation or as definitive treatment; energies of 45 kV x-ray filtered by 0.55 aluminium, for small depth lesions; higher energies (≤100 kV) for deeper lesions; radiation dose varies from 30-40 Gy (fractions of 2 Gy/wk)^{10, 50, 51, 52}
• Second-line treatments for solitary lesions
• • Intralesional glucocorticosteroids
  • Intralesional rituximab - Injections 2-3 times weekly; single doses of 1-3 mL of stock solution (10 mg mL-¹)⁵³ or 3 times a week with 3 mL of stem solution (at 10 mg/mL); therapy repeated 6 times every 26 days⁵⁴
  • Intralesional interferon alfa - 3 and 9 million U subcutaneously (weekly basis) or 9 million U 3 times a week^{48, 55}
• First-line treatments for multiple lesions
• • Antibiotics - Doxycycline at 100 mg twice daily for 3 weeks⁴⁷ or pulse therapy with cefotaxime^{43, 48}
  • Radiotherapy - 20-100 kV Orthovolt therapy 1-4 times per week, to a total dose of up to 15-20 Gy⁴⁹; extended-field irradiation at 30 Gy (4 fractions of 2.5 Gy/wk); localized-field irradiation as either a boost after extended-field irradiation or as definitive treatment; energies of 45 kV x-ray filtered by 0.55 aluminium, for small depth lesions; higher energies (≤100 kV) for deeper lesions; radiation dose varies from 30-40 Gy (fractions of 2 Gy/wk)^{10, 50, 51, 52}
• Second-line treatments for multiple lesions
• • Intralesional interferon alfa - 3 and 9 million U subcutaneously (weekly basis) or 9 million U 3 times a week^{55, 48}
  • Intralesional rituximab - Injections 2-3 times weekly; single doses of 1-3 mL of stock solution (10 mg mL-¹)⁵³ or 3 times a week with 3 mL of stem solution (at 10 mg/mL); therapy repeated 6 times every 26 days⁵⁴
  • Intravenous rituximab - 375 mg/m² weekly for 4 weeks^{56, 57}

The treatment of primary CLs associated with a poor prognosis (ie, DLBCL, intravascular lymphoma)⁴² is as follows (also see Lymphoma, B-Cell): 

• First-line treatment for isolated or grouped lesions
• • Radiotherapy - 20-100 kV Orthovolt therapy 1-4 times per week, to a total dose of up to 15-20 Gy⁴⁹; extended-field irradiation at 30 Gy (4 fractions of 2.5 Gy/wk); localized-field irradiation as either a boost after extended-field irradiation or as definitive treatment; energies of 45 kV x-ray filtered by 0.55 aluminium, for small depth lesions; higher energies (≤100 kV) for deeper lesions; radiation dose varies from 30-40 Gy (fractions of 2 Gy/wk)^{10, 50, 51, 52}
  • Surgical excisions
• First-line therapy for multiple lesions
• • Monochemotherapy - Liposomal doxorubicin⁵⁸ or pegylated liposomal doxorubicin at 20-40 mg/m² intravenously every 2-4 weeks⁵⁹
  • Polychemotherapy - CHOP regimen, ie, cyclophosphamide, hydroxydaunorubicin (Adriamycin), Oncovin (ie, vincristine), and prednisone
• Second-line therapy for multiple lesions - Polychemotherapy (as above) plus rituximab

FOLLOW UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Classification
• Nosologic Entities of CBCL
• Differential Diagnoses of CBCL
• Workup in CBCL
• Treatment
• Follow Up
• Multimedia
• References

Patients should be seen in an outpatient setting at least every 6 months for a clinical workup; they do not require any additional laboratory workup unless enlargement  of the regional lymph nodes has occurred.

The Medscape Dermatologic Surgery Resource Center and Chronic Leukemia Resource Center may be of interest.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Classification
• Nosologic Entities of CBCL
• Differential Diagnoses of CBCL
• Workup in CBCL
• Treatment
• Follow Up
• Multimedia
• References

Media file 1:  Solitary nodule in marginal zone lymphoma.
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Media file 2:  Monocytoid B cells and plasmacytoid cells in marginal zone lymphoma.
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Media file 3:  Marginal zone lymphoma, CD20.
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Media file 4:  Intranuclear periodic acid-Schiff–positive Dutcher bodies in immunocytoma (marginal zone lymphoma).
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Media file 5:  Follicle center lymphoma. Multiple skin tumors.
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Media file 6:  Small and large follicle center cells.
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Media file 7:  Follicle center cell lymphoma. Irregular pattern of CD21-positive dendritic cells.
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Media file 8:  Tumorous lesions on the legs in a patient with diffuse large B-cell lymphoma.
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Media file 9:  Large lymphoid cells of diffuse large B-cell lymphoma, sparing a subepidermal grenz zone.
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Media file 10:  Neoplastic cells in diffuse large B-cell lymphoma with strong positivity for bcl-2.
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REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Classification
• Nosologic Entities of CBCL
• Differential Diagnoses of CBCL
• Workup in CBCL
• Treatment
• Follow Up
• Multimedia
• References

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2. Zinzani PL, Quaglino P, Pimpinelli N, Berti E, Baliva G, Rupoli S, et al. Prognostic factors in primary cutaneous B-cell lymphoma: the Italian Study Group for Cutaneous Lymphomas. J Clin Oncol. Mar 20 2006;24(9):1376-82. [Medline].
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5. Burg G, Jaffe ES. WHO/EORTC Classification of Cutaneous Lymphomas. In: LeBoit P, Burg G, Weedon D, Sarasin A. Tumors of the Skin. 10. Lyon, France: WHO Books; 2006:166-8.
6. Willemze R, Jaffe ES, Burg G, Cerroni L, Berti E, Swerdlow SH, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. May 15 2005;105(10):3768-85. [Medline].
7. Olsen E, Vonderheid E, Pimpinelli N, Willemze R, Kim Y, Knobler R, et al. Revisions to the staging and classification of mycosis fungoides and Sezary 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. Sep 15 2007;110(6):1713-22. [Medline].
8. Cerroni L, Signoretti S, Hofler G, Annessi G, Putz B, Lackinger E, et al. Primary cutaneous marginal zone B-cell lymphoma: a recently described entity of low-grade malignant cutaneous B-cell lymphoma. Am J Surg Pathol. Nov 1997;21(11):1307-15. [Medline].
9. Bailey EM, Ferry JA, Harris NL, Mihm MC Jr, Jacobson JO, Duncan LM. Marginal zone lymphoma (low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type) of skin and subcutaneous tissue: a study of 15 patients. Am J Surg Pathol. Aug 1996;20(8):1011-23. [Medline].
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11. Bahler DW, Kim BK, Gao A, Swerdlow SH. Analysis of immunoglobulin V genes suggests cutaneous marginal zone B-cell lymphomas recognise similar antigens. Br J Haematol. Mar 2006;132(5):571-5. [Medline].
12. Braun-Falco O, Guggenberger K, Burg G, Fateh-Moghadam A. [Immunocytoma simulating chronic acrodermatitis atrophicans]. Hautarzt. Dec 1978;29(12):644-7. [Medline].
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Article Last Updated: Jun 13, 2008