Diagnosis Of Cutaneous B-cell Lymphoma Research Articles

Primary Cutaneous B-Cell Lymphomas: Recent Advances in Diagnosis and Management

Primary cutaneous B-cell lymphoma (PCBCL) is a heterogeneous group of rare clonal B-cell lymphoproliferative disorders with distinct clinicopathologic features from more common nodal B-cell lymphomas. We performed a systematic review of the relevant literature in the MEDLINE database and analyzed laboratory and clinical data. This review discusses the three most common types of PCBCL: primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle-center lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT). Skin biopsies with histology, immunohistochemistry, and molecular clonality studies are essential for a correct diagnosis of cutaneous B-cell lymphoma. Comprehensive lymphoma staging with laboratory and imaging studies and bone marrow aspiration and biopsy are important for determining the prognosis and differentiation of PCBCL from secondary skin involvement with systemic B-cell lymphomas. PCMZL and PCFCL are low-grade PCBCLs, with an estimated 5-year disease-specific survival rate of greater than 95%. Surgical excision or focal radiation therapy is sufficient to control stages T1 and T2 disease. Rituximab monotherapy is frequently used for patients with stage T3 disease. PCDLBCL, LT is an intermediate-grade B-cell lymphoma, with a 5-year disease-specific survival rate of approximately 50%. An anthracycline-based chemotherapy regimen with rituximab is usually required as initial therapy to improve outcomes. In less than a decade, significant progress has been made in our understanding of PCBCL. Novel classification, staging, and prognostic systems have resulted in more accurate diagnosis and prognosis. Although no randomized prospective studies have been conducted in PCBCL, therapies derived from systemic B-cell lymphomas have shown promising results.

Confirmation of the prognostic value of the EORTC/WHO classification of primary cutaneous B-cell lymphoma in the United States: The Stanford University experience

8028 Background: Primary cutaneous B cell lymphoma (CBCL) represent distinct clinicopathologic entities with superior prognosis compared to their nodal counterparts. In the new WHO/EORTC Classification of Cutaneous Lymphomas (WHOc), CBCL are classified as either Marginal Zone (MZ), Follicle center lymphoma (FC) or diffuse large cell-leg type (DLBCL leg-type). WHOc combined previous FL and DLBCL into the category of FC. Only DLBCL leg-type was considered to be aggressive and thus separately categorized. In order to confirm the utility of the WHOc categories, we reclassified our cases. Methods: Records of 154 CBCL patients (pts) managed at Stanford University were reviewed. A diagnosis of CBCL was made based on H&E evaluation, immunohistochemistry including CD20 staining, along with a negative systemic staging evaluation. All pts were reclassified according to the WHO/EORTC classification of CBCL. Overall Survival (OS), disease specific survival (DSS) and freedom from progression (FFP) were analyzed according to the method of Kaplan and Meier. Prognostic factors were evaluated by multivariate regression model and included initial therapy, histology, LDH, stage, IPI, extent of disease and anatomic location. Results: 154 cases were reclassified as follows: 87 FC, 58 MZ, and 9 DLBCL leg-type. The median follow-up was 46 months. The 5 year OS and DSS were 86 and 95% respectively. For the MZ and FC subtypes the % 10 year OS/DSS was: 93/100, and 86/97 respectively. For DLBCL leg-type the % 5 year OS/DSS was 17/33 respectively. There were 22 deaths, seven of which were disease specific (4 DLBCL-leg type and 3 were FC). FFP was unaffected by the type of therapy given (chemotherapy or skin-directed). Conclusions: Our series is the largest single center experience in CBCL. We confirm the utility of the WHOc in distinguishing categories with differing prognosis. The indolent histologies have an excellent outcome and can be managed with local skin-directed therapy. The outcome of pt with DLBCL leg-type is significantly worse than the FC or MZ types and warrants a more aggressive approach in management. No significant financial relationships to disclose.

Primary cutaneous B-cell lymphoma (marginal zone) with prominent T-cell component and aberrant dual (T and B) genotype; diagnostic usefulness of laser-capture microdissection

The presence of a dominant B- or T-cell clone is an important diagnostic criterion for distinguishing cutaneous lymphomas from lymphoid reactive infiltrates. Rarely, a combined B- and T-cell rearrangement can be detected from a single sample. In such instances, genotypic analysis does not permit differentiation of the coexistence of a T- and B-cell lymphoma from a single clone harbouring a monoclonal rearrangement for both immunoglobulin heavy chain and T-cell receptor genes. We herein report a case of a skin tumour consistent with a dense cutaneous lymphoid infiltrate showing a double prominent B- and T-cell component. A dual B- and T-cell clonality was detected by polymerase chain reaction from whole-tissue DNA sample. Genotypic analysis with DNA, obtained after laser-assisted microdissection from the B-cell population, again showed both T- and B-cell monoclonal rearrangements. Conversely, the microdissected T-cell population did not reveal a clonal pattern. The diagnosis of cutaneous B-cell lymphoma with a dual B- and T-cell genotype was established. This description illustrates the diagnostic usefulness of laser-capture microdissection in cutaneous lymphomas presenting dual genotype.

Follicular mycosis fungoides mimicking a cutaneous B‐cell lymphoproliferative disorder

Follicular mycosis fungoides (MF) is an uncommon histological variant of MF characterized by infiltrates of atypical lymphocytes around and within the epithelium of the hair follicles (folliculotropism). Here we report a patient with rapidly progressive follicular MF on the face, associated with concurrent typical MF lesions elsewhere. The histology was unusual, as apart from dense lymphoid infiltrates showing folliculotropism and epidermotropism, there was a prominent B-cell component with germinal centres, leading to an initial diagnosis of cutaneous B-cell lymphoma. The final diagnosis of follicular MF was established on demonstration of clonal T-cell receptor gene arrangements and lack of clonality for heavy chain gene rearrangements. This case illustrates a variant of MF that has a more rapid progression than the otherwise indolent course of classical MF over many years, and the diagnostic pitfalls, whereby the histology can mimic a B-cell proliferative disorder.

Diagnosis of cutaneous B-cell lymphomas

Skin is the second most common site of extranodal lymphoma. The significance of cutaneous B-cell lymphomas has been underestimated due to the lack of monoclonal antibodies and molecular genetics in former years. Cutaneous B-cell lymphomas represent a heterogeneous group of entities which show variation in histology, immunophenotype and in prognosis. The most common entities presenting in skin are follicular lymphomas, marginal zone B-cell lymphomas, and diffuse large B-cell lymphomas. The majority of primary cutaneous B-cell lymphomas have an excellent prognosis. Whereas in B-cell lymphomas with secondary spread to the skin the clinical course is dependent on the prognosis of the primary lymphoma. It is evident that primary cutaneous lymphomas are distinct from nodal lymphomas and not extranodal manifestations of their lymph-node-based counterparts. In the current review the morphologic spectrum of cutaneous B-cell lymphomas comprising primary and secondary cutaneous B-cell lymphomas is discussed according to the WHO classification scheme.

Laser beam microdissection in the diagnosis of cutaneous B-cell lymphoma

Laser beam microdissection in the diagnosis of cutaneous B-cell lymphoma

Laser beam microdissection in the diagnosis of cutaneous B-cell lymphoma

Interpretation of molecular analyses of cutaneous lymphoid infiltrates may be difficult because a heterogeneous group of cells in usually present within the neoplasms. Extraction of DNA from tissue sections does not provide exact information about which cell population has been analysed. We present a laser microscope system that allows selective molecular analysis of single cells or small groups of cells in cases of cutaneous lymphoma. An ultraviolet (UV)-laser microscope system (PALM, Wolfratshausen, Germany) was used to isolate particular populations of cells from a routinely processed specimen of a cutaneous follicular lymphoid proliferation. Using the UV-laser beam, a circle was cut around a target germinal centre in order to separate it from neighbouring tissues and to isolate a pure population of germinal centre cells. Isolated cells were scraped off with a micromanipulator and placed in a proteinase-K solution. DNA was extracted and amplified by the polymerase chain reaction (PCR) technique. Analysis of immunoglobulin JH gene rearrangement showed a distinct monoclonal band. In a second phase, using the same procedure in the same specimen, mantle zone cells around a germinal centre and single interfollicular B lymphocytes were isolated for PCR analysis of immunoglobulin JH gene rearrangement. In this population of cells, no clonality could be detected. This new technique allows the selective elimination of undesired cells and tissue from cutaneous neoplasms. By destruction of unwanted tissues with laser-beam energy a contamination-free sample is obtained. Analysis of isolated cells in our case demonstrated a clonal rearrangement derived from germinal centre cells and not from other B lymphocytes in the specimen, confirming the diagnosis of cutaneous follicle centre lymphoma. The method described has exciting implications for dermatology and dermatopathology, allowing precise correlation of morphological features with findings by molecular genetics.

Histomorphology and cytomorphology of cutaneous B-cell lymphomas.

This article summarizes the conceptual and morphologic background for the diagnosis of cutaneous B-cell lymphomas (CBCL). The architectural pattern of the infiltrate and cytomorphology can indicate the B-cell nature of a skin lymphoma. Virtually all types of B-cell lymphomas, including pre-B-cell lymphoma; Burkitt-like lymphoma; malignant lymphoma, small lymphocytic; the many forms of germinal center cell-derived lymphomas; immunocytoma; plasmacytoma; and immunoblastic lymphoma (B type)-may involve the skin and can be classified according to modern lymphoma classifications.