Primary Cutaneous Follicle Center Lymphoma Research Articles

Long-Term Evolution of an Untreated Primary Cutaneous Follicle Center Lymphoma of the Scalp

Among primary cutaneous B-cell lymphomas, follicle center lymphomas represent, according to the World Health Organization-European Organisation For Research and Treatment of Cancer classification, a subgroup with a favorable prognosis. We describe the case of a 45-year-old man who presented with large infiltrated tumors and nodules coalescing into a wide ulcerated plaque of the scalp, extending from the frontal to the occipital region. At the vertex, 2 large ulcerations were present, reaching the subcutaneous tissues and the underlying bone structures with osseus infiltration and erosion and consequent meningeal exposure. A left retroauricular lymphadenopathy was also present. Histology and immunohystochemistry diagnosed a relapse of primary cutaneous follicle center lymphoma with multilobated histomorphology and lymph node involvement. The histological picture was unchanged from the first sample of 1989. Due to a refusal to treatment, the lesion progressively grew until now. After 6 courses of chemotherapy (cyclophosphamide, vincristine, liposomal doxorubicin, prednisone-Rituximab), the tumor displayed an impressive complete regression with the persistence of a 4-cm occipital ulceration and underlying bone erosion. The adenopathy disappeared as well. This case gave us the opportunity to observe the natural development of the disease, leading to local mutilating and destroying lesions but with low tendency to systemic spread and an impressive response to chemotherapy.

Cutaneous Presentation of Mantle Cell Lymphoma

© 2010 The Authors. doi: 10.2340/00015555-0886 Journal Compilation © 2010 Acta Dermato-Venereologica. ISSN 0001-5555 Mantle cell lymphoma (MCL) is a lymphoid malignancy of B-cells of the mantle zone or primary lymphoid follicle of lymph nodes. It is a moderately aggressive B-cell non-Hodgkin’s lymphoma (NHL). MCL represents only 6% of all NHL (1). MCL is listed in the new World Health Organization (WHO) European Organization for Research and Treatment for Cancer (EORTC) classification of cutaneous lymphomas that can secondarily involve the skin (2). According to this classification, “primary cutaneous lymphoma” refers to cutaneous T-cell lymphomas (CTCLs) and cutaneous B-cell lymphomas (CBCLs) that present in the skin with no evidence of extracutaneous disease at the time of diagnosis (2). The current WHO guidelines for the diagnosis of MCL rely on morphological examination and immunophenotyping with demonstration of cyclin D1 protein overexpression and/or the t(11;14)(q13;q32) translocation for confirmation (3). There are two primary B-cell lymphomas that are more common than MCL; cutaneous marginal zone Bcell lymphoma, and primary cutaneous follicle centre lymphoma. The former is an indolent cutaneous B-cell lymphoma derived from post-germinal centre cells and characterized by a proliferation of small lymphocytes, lymphoplasmo cytoid cells and plasma cells with monotypic cytoplasmic immunoglobulin. Follicle centre cell lymphoma is derived from follicle centre cells, consisting of a mixture of centrocytes and centroblasts (2, 4). Immunophenotyping assists in the differential diagnosis of these cutaneous lymphomas. Skin involvement in MCL is very rare (1). We describe here a case of MCL involving the skin as the first manifestation of the disease, and we review the clinical features of reported cases of MCL with skin lesions. CASE REpORT

Transformation of a Cutaneous Follicle Center Lymphoma to a Diffuse Large B-Cell Lymphoma—An Unusual Presentation

Primary cutaneous follicle center lymphoma (PCFCL) is characterized by a proliferation of follicle center cells in the skin. A definitive diagnosis is frequently delayed because of difficulties in interpretation of the histopathologic findings. It has an excellent prognosis with a 5-year survival over 95% and its risk of transformation has not been established. We describe a case report of man with a gastric diffuse large B-cell lymphoma (DLBCL) referred to our clinic because of nodules in the back that had gradually developed over a period of 10 years. A biopsy performed 3 years before was interpreted as reactive follicular hyperplasia. A new skin biopsy revealed a diffuse large B-cell lymphoma and immunoglobulin heavy chain gene rearrangements from the initial skin biopsy (PCBCL) and the DLBCL gastric biopsy were studied by polymerase chain reaction and an identical clonal rearrangement was detected which was highly suggestive of a transformation lymphoma.

Somatostatin receptor scintigraphy in primary cutaneous T‐ and B‐cell lymphomas

Monitoring and repeated staging is of substantial importance in many patients with primary cutaneous T-cell lymphomas (CTCL). For primary cutaneous B-cell lymphomas (CBCL), extensive initial staging is the mainstay for correct diagnosis. To evaluate the value of somatostatin receptor scintigraphy using the radiolabeled somatostatin analog (111)In-pentetreotide in comparison to conventional imaging methods for the staging of patients with primary CTCL and primary CBCL. Twenty-two patients (15 patients with histologically verified CTCL and 7 patients with histologically verified CBCL) were included. Stage of disease was established by physical examination, laboratory screening, skin inspection, palpation of superficial lymph nodes, sonography and computed tomography (CT) in patients with advanced clinical stage. Focally elevated tracer uptake of (111)In-pentetreotide was compared to common imaging modalities, physical aspect and digital photographs of the respective skin lesions. Of the 15 patients with CTCL, only 4 (27%) showed positive scintigraphic results, but not in all sites of lymphomatous involvement. None of the five patients with mycosis fungoides in stage I, nor any of the four patients with Sézary syndrome, had a positive (111)In- pentetreotide scan. Of the seven patients with CBCL three positive scintigraphic results (43%) could be obtained: in two patients with a follicular center lymphoma and one patient with a diffuse large B-cell lymphoma - leg type, but again not in all apparent sites of lymphoma. Based on our results, we do not recommend the use of somatostatin receptor scintigraphy for routine staging of patients with CTCL and CBCL. As our series includes only 22 patients, and the number of patients with rarer variants of CTCL was rather small, it might be too premature to abandon SST-R in the staging of patients with cutaneous lymphomas.

Primary Cutaneous Follicle Center Lymphoma in An HTLV-1 Carrier.

Abstract 5032 BackgroundHuman T-lymphotropic virus type 1 (HTLV-1) is an oncogenic retrovirus associated with adult T-cell leukemia/lymphoma (ATLL), an aggressive neoplasm of mature CD4+ T-lymphocytes which always shows monoclonal integration of HTLV-1 provirus DNA. HTLV is not associated with B-cell non-Hodgkin's lymphoma (B-NHL); however rare cases of B-NHL have been reported in HTLV-1 carriers, leading some to hypothesize a role for HTLV-1 in B-cell lymphogenesis. We report a case of a Jamaican male HTLV-1 carrier with primary cutaneous follicle center lymphoma of B-cell origin and explore the link between HTLV-1 and B-NHL. Case ReportA 55 year old Jamaican male was seen in our hematology clinic for evaluation of multiple scalp masses progressive over six months. The lesions were painful, pruritic, but not associated with other constitutional symptoms. He had been in good health prior to the onset of these symptoms, and denied toxic habits or exposures. Physical examination revealed multiple firm, non-tender scalp masses, the largest measuring 3.0 × 2.0 cm; the overlying skin was nodular and erythematous but without breakdown or discharge. His complete blood count, basic metabolic profile, hepatic function and lactate dehydrogenase were all within normal limits. On excisional biopsy, the dermis showed a dense lymphoid infiltrate of medium to large sized cells, with a nodular and trabecular pattern of growth from the superficial dermis to the aponeurosis. Numerous large centroblast-like cells were present. Immunohistochemical stains demonstrated the following phenotype: CD45+, CD20+, CD79a+, BCL2+/-, BCL6+/-, CD10+, and MUM-/+. A stain for CD21 highlighted compact and fused/contiguous follicular dendritic cell meshworks in association with the neoplastic B-cell infiltrate. Staining with Ki-67 highlighted a variable but high proliferation rate (80%). A moderate infiltrate of small-sized T-cells (CD3+, CD5+) was also present. These features were diagnostic of a primary cutaneous follicle center lymphoma. Evaluation with the MYC breakapart probe showed no evidence of rearrangement; RT in-situ PCR for HTLV-1 showed a signal in many of the infiltrating T-cells. He was seropositive for positive HTLV-1 and negative for HIV and EBV infection. Bone marrow biopsy and aspiration and additional staging CTs were unremarkable. The patient received 4 cycles of R-CHOP chemotherapy and has been in a complete remission for 2 years. DiscussionWe report a case of a Jamaican male HTLV-1 carrier with cutaneous lymphoma of B-cell origin with detection of HTLV-1 proviral DNA in the neoplastic cells by RT in-situ PCR. Our findings lead us to speculate that HTLV-1 infected T-cells and/or an immunodeficient state in certain HTLV-1 carriers might allow for the development of B-cell lymphoma. Further research on the pathogenesis of HTLV-1 in B cell lymphomagenesis needs to be explored. DisclosuresNo relevant conflicts of interest to declare.

Pegylated Liposomal Doxorubicin, Bleomycin, Vinblastine and Dacarbazine (CBVD) in the Treatment of Advanced Primary Cutaneous Lymphomas.

Abstract 3717Poster Board III-653 IntroductionPrimary cutaneous lymphomas (PCL) present in the majority of histologic variants an indolent behaviour and a good prognosis with a prolonged survival. In a very small number of patients (pts), PCL is aggressive at the onset while in pts who are resistant or have relapsed after repeated topic or systemic therapies an advanced disease is more frequently observed. In these patients no therapy is capable of inducing a stable remission of the disease. The efficacy and low toxicity of Pegylated Liposomal Doxorubicin (PLD) as a single agent in second-line therapy of PCL was recently demonstrated. In our study we tested the safety and efficacy of PLD (Caelyx®) (C) in association with three drugs of proven effectiveness in nodal lymphoprolipherative and other primary cutaneous neoplastic disorders: Bleomycin (B), Vinblastine (B) and Dacarbazine (D) (CBVD). Patients and MethodsFrom February 2003 to December 2008 we observed 37 consecutive pts with advanced PCL: 19 Cutaneous T-Cell Lymphomas (CTCL) and 18 cutaneous B-Cell Lymphomas (CBCL). The CTCL pts were: 15 males and 4 females, with median age 59 (27-86) years, of which 7 pts with Anaplastic Large Cell Lymphoma (ALCL) CD30 positive, 7 pts with transformed Mycosis Fungoides (tMF), 3 pts with CD30 negative ALCL, 1pt with Panniculitis-like (Pl) Lymphoma and 1 pt with transformed Sezary Syndrome (tSS), according to the WHO-EORTC consensus classification. Nine pts presented with a nodal involvement and 10 pts were resistant or relapsed after 1 or more systemic treatments. Among the CBCL pts there were: 8 males and 10 females, with median age 61 (42-84) years, 12 pts had a Follicular Centre Lymphoma (FCL), 3 a Marginal Zone Lymphoma (MZL) and 3 a Diffuse Large B-Cell Lymphoma Leg Type (LT). Five pts presented a nodal involvement and 11 pts had received 1 or more previous systemic therapy. All 37 pts received CBVD therapy at following dosage: C: 20 mg/m2, B: 10 mg/m2, V: 6 mg/m2, D: 325 mg/m2 at days 1 and 15, administered intravenously every 4 weeks for a maximum of 6 cycles. Rituximab (R) at dosage of 375 mg/m2 was administered to CBCL pts at 1st day of each cycle. Before the treatment, pts were submitted to a complete staging of disease including TC-scan, bone marrow biopsy, and immunophenotyping of peripheral blood cells. ResultsIn the CTCL group 4 pts received 4 CBVD cycles, 14 pts received 6 CBVD cycles and 1 pt presented a progressive disease after the 1st cycle. Overall Response Rate (ORR) was 94.7% (18/19 pts). Sixteen out of 18 pts (88.8%) had a Complete Remission (CR) with disappearance of nodal involvement and cutaneous lesions, 2/18 pts obtained a Partial Remission (PR) with disappearance of nodal involvement and 75% of cutaneous lesions. In the CBCL group 3 pts received 2 R-CBVD cycles, 3 pts 4 cycles and 11 pts 6 cycles: ORR was 100% and all pts obtained a CR. The occurrence of palmoplantar erytrodisesthesia in 5 pts and grade 2-3 granulocytopenia in 12 pts did not modify the therapy program. Two CTCL pts (1 tSS, 1Pl) and 1 CBCL (LT) pt in CR after therapy received an allogeneic Hemopoietic Stem Cells (HCS) transplant and 1 CBCL(FCL) pt a syngeneic HCS transplant. In CTCL group 11 (61%) pts maintained their response after a median follow up of 15.5 (9-71) months. Among CBCL pts 14 (77.7%) pts are still in CR after a median follow up of 15 (4-36) months. ConclusionsOur experience demonstrates that the CBVD association is an effective and safe therapy for advanced PCL in inducing an important tumour burden reduction with a high CR rate. The assessment of response duration requires a longer observation. A larger number of patients in a multicentric trial are needed to confirm our promising results. Disclosures:Off Label Use: liposomial doxorubicin has a peculiar cutaneous tropism and low cardiac toxicity compared with other anthracyclines.

CD123-positive Plasmacytoid Dendritic Cells in Primary Cutaneous Marginal Zone B-cell Lymphoma

The histogenesis of primary cutaneous marginal zone B-cell lymphoma (PCMZL) has not yet been clarified. Plasma-cytoid dendritic cells (PDC) play a crucial role in the initiation of immune responses and activation of T-cells and B-cells. We analyzed the presence of PDC by immunohistochemistry in various forms of primary cutaneous B-cell lymphomas and in B-cell pseudolymphomas. Clusters of CD123+PDC were observed in all PCMZL (23 of 23 cases; 100%) and in two-thirds of cutaneous B-cell pseudolymphomas (14 of 22; 64%), but only in a minority of primary cutaneous follicle center lymphoma (4 of 31; 13%) and not in primary cutaneous diffuse large B-cell lymphoma, leg type. CD123+ PDC clusters were found in close proximity to monoclonal plasma cells and T-cells and were already present at high numbers in early lesions and initial recurrences of PCMZL. In conclusion, the detection of larger clusters of PDC in PCMZL provides a useful adjunctive diagnostic marker and suggests a pathogenetically relevant role of these cells in PCMZL. Furthermore, the occurrence of PDC could explain the high number of T-cells typically found in PCMZL. We propose considering PCMZL as a unique and potentially antigen-driven neoplasm with PDC, T-cells, and B-cells as the constitutive tumor components.

Bcl-xL Gene Expression Correlated with Lower Apoptotic Cell Numbers and Shorter Progression-Free Survival in PCFCL

The expression of bcl-x(L), an antiapoptotic member of the bcl-2 family, has been correlated with poor prognosis in nodal follicular lymphomas (NFLs). So far, it has not been studied in primary cutaneous follicle center lymphomas (PCFCLs), which, compared with NFLs, express less frequently t(14;18)(q32;q21) and bcl-2. Using real-time PCR we measured bcl-xL and bcl-2 gene expression levels in laser-microdissected lymphoma cells of 20 PCFCL frozen sections. Numbers of apoptotic cells labeled by TUNEL assay were negatively correlated with bcl-xL expression levels (r=-0.840, P<0.005). Bcl-xL expression was significantly higher in biopsies of patients who developed relapse or disease progression later compared with patients who did not (P=0.022), and higher levels of bcl-xL gene expression were significantly correlated with shorter progression-free survival (PFS) (P=0.017). None of these features was correlated with bcl-2 gene expression levels. Our findings indicate that bcl-xL overexpression is inversely correlated with PFS in PCFCL. Moreover, the inverse correlation between bcl-xL expression levels and apoptotic cell numbers suggests that bcl-xL, through its antiapoptotic effect, might contribute to tumor cell survival in PCFCL.

Low Stage Follicular Lymphoma: Biologic and Clinical Characterization According to Nodal or Extranodal Primary Origin

Studies suggest that primary extranodal follicular lymphoma (FL) is not infrequent but it remains poorly characterized with variable histologic, molecular, and clinical outcome findings. We compared 27 extranodal FL to 44 nodal FL using morphologic, immunohistochemical, and molecular genetic techniques and evaluated the clinical outcome of these 2 similarly staged groups. Eight cases of primary cutaneous follicle center lymphoma were also studied. In comparison to nodal FL, a greater number of extranodal FL contained a diffuse growth pattern (P=0.004) and lacked CD10 expression (P=0.014). Fifty-four percent of extranodal and 42% of nodal FL cases showed evidence of t(14;18), with minor breakpoints (icr, 3'BCL2, 5'mcr) more commonly found in extranodal cases (P=0.003). Outcome data showed no significant differences in overall survival (P=0.565) and progression-free survival (P=0.627) among extranodal, nodal, and primary cutaneous follicle center lymphoma cases. Analysis of all cases by t(14;18) status indicate that the translocation-negative group is characterized by a diffuse growth pattern (P=0.043) and lower BCL2 expression (P=0.018). The t(14;18)-positive group showed significantly better overall survival (P=0.019) and disease-specific survival (P=0.006) in comparison with the t(14;18)-negative group. In low stage FL, the status of t(14;18) seems to be more predictive of outcome than origin from an extranodal versus nodal site.

16 Diagnosis of Secondary Follicular Center Cell Lymphoma to Pancreas With Endoscopic Ultrasound–Guided Fine-Needle Aspiration Biopsy Cytopathology No. C 08-8 (C-410)

16 Diagnosis of Secondary Follicular Center Cell Lymphoma to Pancreas With Endoscopic Ultrasound–Guided Fine-Needle Aspiration Biopsy Cytopathology No. C 08-8 (C-410)

Primary Cutaneous CD4+ Small/Medium-sized Pleomorphic T-cell Lymphoma Expresses Follicular T-cell Markers

Cutaneous CD4 small/medium-sized pleomorphic T-cell lymphoma (CSTCL) is a cutaneous T-cell lymphoma defined by a predominance of small-to-medium-sized CD4 pleomorphic T cells, with a favorable clinical course. Cases are also characterized by the presence of a rich infiltrate of reactive B cells. Recently, it has been reported that follicular helper T cells (TFH cells) display a distinct gene expression profile, positive for PD-1, CXCL13, and BCL-6. We report for the first time the expression of PD-1 and other TFH cell markers in CSTCLs and discuss its biologic significance. Sixteen CSTCLs were included in this study, and also 20 reactive inflammatory conditions, 10 primary cutaneous marginal zone, 10 follicular center lymphomas, and 5 primary CD30 cutaneous lymphomas. They were immunohistochemically analyzed for a large panel of markers. Double immunoperoxidase labeling of paraffin sections was performed for PD-1, OCT-2, and BCL-6. Clonal Ig and T-cell receptor rearrangements and Epstein-Barr virus-encoded RNA expression were also evaluated. Morphologic and clinical data were reviewed. Histologic examination showed a dense polymorphic lymphoid infiltrate throughout the dermis. Atypical large CD4 cells were positive for PD-1, CXCL13, and BCL-6 in all cases, and were attached in small clusters, or formed rosettes around CD30/OCT-2+ B blast cells. Epstein-Barr virus was not apparent in any of the cases. A dominant T-cell clone was identified in 14 cases, whereas polymerase chain reaction IgH gene rearrangement studies showed that all cases were polyclonal. None of the patients had lymphadenopathy or showed any evidence of systemic disease, nor did they have any previous history of mycosis fungoides or drug reactions. FTH cell markers are not exclusive to angioimmunoblastic lymphadenopathy but may also be seen in neoplastic cells of CSTCLs. Moreover, these findings suggest that B-cell stimulation by FTH could also take place in some cutaneous T-cell lymphomas.

Primary cutaneous spindle cell B‐cell lymphoma with multiple figurate erythema‐like manifestation

We report a 68-year-old Korean man presenting with asymptomatic erythematous polycyclic annular firm plaques on his back that spread to the right shoulder. Histopathologic examination showed dense, diffuse infiltrates involving the entire dermis, consisting of atypical lymphocytes with many centrocytes and a few centroblasts. Spindle-shaped cells with elongated, twisted nuclei containing dispersed chromatin were also seen. Immunohistochemical analysis showed that all of the cells were strongly positive for CD20, CD21, CD79a and CD45, while they were negative for CD3, CD5, CD10, CD23, CD35, CD43, CD45RO and CD68. The spindle cells were also negative for smooth-muscle actin, desmin, S-100 and CD34. They consistently expressed nuclear bcl-6, but did not express bcl-2, multiple myeloma-1 and p16. We diagnosed him with primary cutaneous spindle cell B-cell lymphoma (PCSBCL) and treated him with six cycles of cyclophosphamide, adriamycin, vincristine, prednisone and rituximab (R-CHOP) chemotherapy; his skin lesions disappeared completely. Immunohistochemical profiles suggest that PCSBCL is a variant of primary cutaneous follicle center lymphoma.

Coincidence of cutaneous follicle center lymphoma and diffuse large B‐cell lymphoma

Primary cutaneous follicle center lymphoma (PCFCL) is a neoplasm with differentiation of centrocytes and centroblasts presenting in the skin. At the time of initial manifestation, extracutaneous involvement is absent. PCFCL is considered as an indolent variant of primary cutaneous B-cell lymphomas since dissemination to extracutaneous sites is rare and the prognosis is favorable. Here we describe a 30-year-old man who was diagnosed with a cutaneous FCL and did not show extracutaneous affection at the time of occurrence. Six months later, however, he developed a diffuse large B-cell non-Hodgkin lymphoma localized in several lymph nodes of the neck that most likely reflects the occurrence of a second primary tumor in the same patient.

Low-Dose Palliative Radiotherapy for Cutaneous B- and T-Cell Lymphomas

To determine the efficacy of low-dose palliative radiotherapy for both low-grade malignant cutaneous B-cell lymphomas (CBCLs) and cutaneous T-cell lymphomas (mycosis fungoides). A total of 18 patients with low-grade CBCL (10 primary cutaneous marginal zone B-cell and 8 primary cutaneous follicle center lymphomas) with 44 symptomatic plaques and tumors underwent low-dose (4 Gy in two fractions) local radiotherapy. A total of 31 patients with mycosis fungoides were treated at 82 symptomatic sites, initially with 4 Gy and later with 8 Gy in two fractions. The complete response rate for CBCL lesions was 72%. Of the 44 B-cell lymphoma lesions, 13 were re-treated to the same site after a median of 6.3 months because of persistent (n = 8) or recurrent (n = 5) symptomatic disease. Of the mycosis fungoides patients treated with 4 Gy in two fractions (17 lesions), 70% failed to respond. Increasing the dose to 8 Gy in two fractions yielded a complete response rate of 92% (60 of 65 lesions). The patients in whom low-dose radiotherapy failed were retreated with 20 Gy in eight fractions. Our results have demonstrated that low-dose involved-field radiotherapy induces a high response rate in both CBCL and cutaneous T-cell lymphoma lesions without any toxicity. Therefore, this treatment is now our standard palliative treatment. At progression, it is safe and feasible to apply greater radiation doses.

B-Cell Cutaneous Lymphoid Hyperplasia Representing Progressive Transformation of Germinal Center: A Report of 2 Cases

Cutaneous lymphoid hyperplasia (CLH) is a reactive polyclonal benign lymphoproliferative process predominantly composed of B cells or T cells, either localized or disseminated. The authors report histomorphologic, immunophenotypic, and genotypic findings of 2 cases of B-cell CLH demonstrating progressive transformation of germinal center (PTGC). Histologically, most of the lymphoid follicles were PTGCs with a few hyperplastic germinal centers. PTGC was characterized by enlarged but well-circumscribed follicles without clear demarcation of the germinal center and mantle zone, which contained a predominance of small lymphocytes and variable numbers of centrocytes, centroblasts, and immunoblasts. However, there were no centroblasts and immunoblasts resembling lymphocytic and/or histiocytic Reed-Sternberg cell variants in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in either lesion. These unusual CLHs should be differentiated from the primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicular lymphoma, particularly "floral variant," or NLPHL. To avoid overdiagnosis and overtreatment, immunophenotypic and genotypic studies are required along with careful morphologic examination.

Primary multifocal non-Hodgkin lymphoma of the colon successfully treated with chemotherapy

View Large Image Figure Viewer Download Hi-res image View Large Image Figure Viewer Download Hi-res image View Large Image Figure Viewer Download Hi-res image An asymptomatic 59-year-old woman was referred for colorectal cancer screening. She had no significant medical history and was taking no medications except multivitamins. Colonoscopy revealed multiple lesions, at 7 different locations (from the rectum to the proximal transverse colon), all of which appeared similar; they were polypoid, had a normal-appearing overlying mucosa, and measured 5 to 15 mm in size (A, B). Three of these lesions were removed by using a polypectomy snare, and the others were biopsied. Histology was similar for all of the lesions: non-Hodgkin lymphoma; follicular center cell lymphoma; Grade 2, follicular pattern (C, H&E, orig. mag. ×4, D, Bcl-2, orig. mag. ×10). CT scanning of the abdomen and pelvis showed retroperitoneal, iliac, and inguinal adenopathy. She was treated with 4 months of chemotherapy, which consisted of rituximab, cyclophosphamide, vincristine, and prednisone. Colonoscopy was repeated 2 months after completion of chemotherapy; all the lesions had disappeared, and the entire colon showed normal mucosa. Repeat CT scanning revealed resolution of the lymphadenopathy. View Large Image Figure Viewer Download Hi-res image View Large Image Figure Viewer Download Hi-res image

Expression of HGAL in primary cutaneous large B-cell lymphomas: evidence for germinal center derivation of primary cutaneous follicular lymphoma

The classification of primary cutaneous large B-cell lymphoma (PCLBCL) is based on standard morphology, immunohistochemistry, and clinical presentation. There are two major subtypes in the current WHO–EORTC classification: follicle center lymphoma and diffuse large B-cell lymphoma, leg-type (DLBCL-LT). The goals of this study were to examine a series of DLBCLs to determine (1) whether the immunohistochemical paradigm of germinal center B-cell and non-germinal center B-cell types of systemic DLBCL could be applied to PCLBCL; (2) whether application of the newly described germinal center B-cell marker, human germinal center-associated lymphoma (HGAL) also discriminates between these types as a further support for germinal center B-cell origin for primary cutaneous center lymphoma; and (3) whether any of these biologic markers were of prognostic significance. To this end, 32 cases of diffuse PCLBCL (22 primary cutaneous follicular center lymphomas and 10 DLBCL-LT) were classified based on the WHO–EORTC criteria and studied for expression of CD20, BCL2, BCL6, CD10, MUM-1, and HGAL by immunohistochemistry. Results were correlated with clinical features. HGAL and BCL6 expression and germinal center B-cell phenotype were associated with primary cutaneous follicular center lymphoma. The combination of HGAL and BCL6 positivity had the highest sensitivity (88%) and specificity (100%) for predicting subtype compared to either marker alone. Both HGAL and BCL6 were associated with the germinal center B-cell phenotype. The correlation of HGAL expression with the germinal center B-cell phenotype demonstrates the role of this marker in the classification of cutaneous large B-cell lymphomas. BCL6 expression was the only immunohistochemical marker associated with overall survival. Characterizing PCLBCLs with markers of B-cell maturation stage is a useful framework for studying, classifying, and clinically stratifying these lymphomas.

Profiling of apoptosis genes identifies distinct types of primary cutaneous large B cell lymphoma

Two distinct primary cutaneous large B cell lymphomas are recognized: primary cutaneous follicle centre lymphoma (PCFCL), characterized by an excellent prognosis, and primary cutaneous large B cell lymphoma, leg-type (PCLBCL leg-type), with an unfavourable prognosis. To determine whether inhibition of the apoptosis pathways may underlie the difference in clinical outcome between PCFCL and PCLBCL leg-type, we investigated the expression of only apoptosis-related genes by microarray expression profiling. Unsupervised cluster analysis was carried out using 169 genes involved in apoptosis on a group of 21 previously untreated patients diagnosed with primary cutaneous large B cell lymphoma. Cluster analysis resulted in two separate groups which showed large overlap with the PCFCL and PCLBCL leg-type. One group was characterized by high expression levels of pro- and anti-apoptotic genes. The other group was characterized by high expression levels of apoptosis-inducing cytotoxic effector genes, possibly reflecting a cellular cytotoxic immune response. Our results suggest that the clinically favourable PCFCLs are characterized by a relatively intense cellular cytotoxic immune response and that PCLBCL leg-types are characterized by constitutive activation of the intrinsic mediated apoptosis pathway, with concomitant downstream inhibition of this apoptosis pathway. Thus, strategies neutralizing the function of apoptosis-inhibiting proteins might be effective in PCLBCL leg-type.

Abnormal AP-1 protein expression in primary cutaneous B-cell lymphomas

Primary cutaneous B-cell lymphoma (PCBCL) consists mainly of primary cutaneous marginal zone B-cell lymphoma (PCMZL), primary cutaneous follicle centre lymphoma (PCFCL) and primary cutaneous large B-cell lymphoma, leg type (PCLBCL-LT). The activator protein 1 (AP-1) transcription factor includes JUN, FOS and other family members. To assess the expression pattern of AP-1 transcription factors in PCBCL. We analysed paraffin tissue sections from nine cases of PCMZL, seven PCFCL, six PCLBCL-LT and two unspecified PCBCL cases by using immunohistochemistry with antibodies against c-JUN, JUNB, JUND, c-FOS, RAF1, alphaPAK, CD30 and CCND1. A positive staining for JUND (++) was observed in six cases of PCFCL (86%), five PCLBCL-LT (83%) and five PCMZL (56%). Positive CCND1 protein expression was present in four cases of PCLBCL-LT (67%), four PCFCL (57%) and four PCMZL (44%), and the two unspecified PCBCL cases. Expression of alphaPAK protein was seen in three cases of PCLBCL-LT (50%), two PCMZL (22%) and one PCFCL. However, c-JUN, c-FOS and RAF1 protein were rarely expressed in the PCBCL cases analysed; JUNB and CD30 protein expression was absent in these cases. These findings suggest that the presence of abnormal AP-1 protein expression is associated with upregulation of JUND, CCND1 and alphaPAK and downregulation of JUNB in PCBCL.

Primary Cutaneous Follicle Center Lymphoma Associated with Alopecia Areata

We report a patient who presented simultaneously with primary cutaneous follicle center lymphoma (PCFCL) of the face and scalp and alopecia areata of the scalp and beard bearing a clonal T-cell receptor gene rearrangement. To our knowledge, alopecia areata has not been previously reported in association with PCFCL. Both lesions regressed with topical imiquimod and systemic steroids, which suggests an inter-relationship in this case between the clonal B-cell and T-cell populations in driving outgrowth of these lesions.