Linfoma cutáneo primario difuso de células grandes-tipo pierna con regresión espontánea

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL LT) accounts for approximately 20% of all primary cutaneous B-cell lymphomas and tends to present as infiltrated nodules, tumors, and plaques on the legs in the elderly. Unlike other primary cutaneous large B-cell lymphomas, it has a poor prognosis and tends to require treatment with systemic chemotherapy.We present the case of an 82-year-old patient with a 1-year history of nodules and plaques on her right leg. Biopsy led to a diagnosis of PCLBCL LT and the lesions resolved without treatment within 1 month of the first visit. This is an atypical course of PCLBCL LT and we believe that it is the first such case to be reported in the literature.     

The applicability and prognostic value of the new TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sézary syndrome: results on a large cohort of primary cutaneous B-cell lymphomas and comparison with the system used by the Dutch Cutaneous Lymphoma Group

BACKGROUND: Recently, a consensus proposal was published for a TNM classification system for all primary cutaneous lymphomas other than mycosis fungoides and Sézary syndrome, meant to document extent of disease in a consistent manner. The applicability and the prognostic significance of this system have not been investigated thus far. OBJECTIVES: To test the applicability and prognostic relevance of the proposed TNM classification system on a cohort of primary cutaneous B-cell lymphomas (CBCL). METHODS: The study group included 71 primary cutaneous marginal zone lymphomas (PCMZL), 171 primary cutaneous follicle centre lymphomas (PCFCL) and 58 primary cutaneous diffuse large B-cell lymphomas, leg type (PCLBCL, LT). As only patients with primary cutaneous lymphoma were included (T1-3, N0M0), only the T-rating was scored. The results were compared with the scoring as applied by the Dutch Cutaneous Lymphoma Group. RESULTS: The system was easily applicable to all cases. In PCMZL and PCFCL no correlation was found between T-score and survival (5-year disease-specific survival: T1, 100% and 98%; T2, 94% and 93%; T3, 100% and 88%, respectively). In PCLBCL, LT there was a clear, although statistically not significant, association between increasing T-score and reduced survival (5-year disease-specific survival: T1, 75%; T2, 49%; T3, 0%; P = 0.077). Comparing the TNM system with the Dutch Cutaneous Lymphoma Group system, there was a discrepancy in the classification of 20 cases. CONCLUSIONS: The new TNM system is a useful tool to document disease extent in patients with CBCL and provides prognostic information in the group of patients with PCLBCL, LT.     

Aggressive primary cutaneous B‐cell lymphomas show increased Angiopoietin‐2‐induced angiogenesis

Primary cutaneous large B‐cell lymphomas, leg type (PCLBCL/LT) are primary cutaneous B‐cell lymphoma (PCBCL) with an intermediate prognosis. Therefore, antracycline‐based polychemotherapy combined with rituximab has been recommended as first‐line treatment. Yet, despite this regimen, the 5‐year survival rate remains 50–66% only. Angiogenesis, the formation of a vascular network, is essential for the pathogenesis of nodal lymphomas. So far, no study has analysed angiogenesis and its key factors in PCLBCL/LT. The present study was aimed at characterizing angiogenesis in PCLBCL/LT to identify the angiogenic molecules as potential therapeutic targets. The intra‐tumoral microvessel density (MVD) was assessed by immunohistochemical studies of CD20 and CD31. The MVD was higher in PCLBCL/LT compared with indolent PCBCL. Analyses of open‐source microarray data showed correlation between the angiogenic molecule angiopoietin‐2 (Ang‐2) and pan‐endothelial cell markers. ELISA studies determined a shift between Ang‐2 and Ang‐1 towards Ang‐2 in the peripheral blood of PCLBCL/LT patients. Immunofluorescence costainings against the Ang receptor Tie2/angiogenic integrins/CD34 revealed that the vasculature in both aggressive and indolent PCBCL tumors harbours an endothelial cell subpopulation with reduced expression of Tie2. In contrast, the alternative Ang‐2 binding partners, angiogenic integrins, are strongly expressed in PCBCL. In line with these findings, downstream targets of Ang‐2‐integrin signalling, that is phosphorylation of focal adhesion kinase at Tyr397, and sprouting angiogenesis are enhanced in PCLBCL/LT. Our data present Ang‐2 as a promising therapeutic target and anti‐angiogenic therapy as a new line in treatment of PCLBCL/LT as a hitherto intractable disease.     

Comparative genomic hybridization analysis of cutaneous large B-cell lymphomas

The aim of the present study was to identify genetic aberrations in a series of patients with cutaneous large B-cell lymphoma (LBCL) using comparative genomic hybridization (CGH). Eighteen consecutive patients with primary (13 patients) (PCLBCL) and secondary (five patients) (SCLBCL) cutaneous large B-cell lymphoma were included in the study. Nine cases corresponded to PCLBCL leg type and four cases primary cutaneous follicle centre-cell lymphoma (PCFCL). Chromosomal imbalances (CIs) were detected in 14 of 18 samples (77.8%). All of nine cases with PCLBCL leg type and two of four cases with PCFCL showed CIs (100% and 50%, respectively). Regarding SCLBCL, in three of five cases (60%), CIs were detected. The most frequently detected gains involved 2q, 5q, 3 and 7q and amplifications affected 18, 12 and 13. Frequent losses were found in 17p. In PCLBCL leg type, the most frequent gains involved 2q and 7q, amplifications were localized in chromosomes 12, 13 and 18 and losses affected chromosomes 17p and 19. In PCFCL, gains located in 3q, 4 and 7q were found. Our study seems to confirm clear-cut differences between primary cutaneous LBCL and nodal diffuse LBCL, and it suggests the presence of genotypic differences between cases of PCLBCL leg type and cases of PCFCL.     

Simultaneous aberrations of single CDKN2A network components and a high Rb phosphorylation status can differentiate subgroups of primary cutaneous B-cell lymphomas

The cyclin-dependent kinase inhibitor 2A (CDKN2A) gene on chromosome 9p21 encodes p16 (INK4A), the inhibitor of the CDK4/retinoblastoma (Rb) cell proliferation pathway, as well as p14 (ARF), which controls p53-dependent pathways. Inactivation of p16 has previously been associated with the prognostically unfavourable primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL, LT). In this work, we analysed 22 tumors [nine primary cutaneous follicle centre lymphomas (PCFCL), seven primary cutaneous marginal zone lymphomas (PCMZL) and six PCLBCL, LT] not only for alterations of the p16 gene but also for p14, p53 and Rb by fluorescence in situ hybridization (FISH) and immunohistochemistry. In most PCLBCL, LT (4/6) alterations of CDKN2A (two biallelic deletions, one monoallelic deletion and one trisomy 9) and in addition the highest frequency of deletions of p53 (3/6) and Rb (3/6) were detected. p16 was not expressed but very high levels of phosphorylated Rb, indicating a functional effect of genomic CDKN2A alterations on the protein level in PCLBCL, LT. Regarding the p14/p53 axis, PCLBCL, LT showed a variable expression. Neither PCFCL nor PCMZL showed alterations of CDKN2A and also deletions of p53 or Rb were extremely rare in these subtypes. Exclusively in PCMZL, p53 protein was consistently lacking. In conclusion, only PCLBCL, LT is characterized by a high frequency of aberrations of the CDKN2A network components in both important tumor suppressor pathways regulated by the CDKN2A gene. Moreover, PCLBCL, LT appears to be distinguishable from PCMZL not only by its level of p53 expression but also by its stage of Rb phosphorylation. The latter may also apply to a subgroup of PCFCL.     

The histomorphologic spectrum of primary cutaneous diffuse large B-cell lymphoma: a study of 79 cases

Primary cutaneous large B-cell lymphomas (PCLBCL) have historically been a matter of debate in the literature. The 2005 World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification scheme segregated cutaneous B-cell lymphomas into 3 groups: primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicle center cell lymphoma, and primary cutaneous diffuse large B-cell lymphoma (PCDLBCL), "leg type" (PCDLBCL-LT). Additionally, the WHO-EORTC classification scheme utilized the term PCLBCL "other" not otherwise specified (NOS) type for rare cases of PCLBCL not belonging to either the "leg type" or the primary cutaneous follicle center cell lymphoma group. In this study, we retrospectively assessed the histomorphologic features of 79 cases of PCDLBCLs, including those of "leg type" and "other" NOS type, to further categorize the histologic spectrum of these unusual cutaneous neoplasms. The histologic diagnosis of PCLBCL usually poses little diagnostic difficulty; however, some cases may adopt unusual or unfamiliar appearances mimicking other lymphoproliferative disorders or other malignant neoplasms. Seventy-nine cases, occurring in 37 men and 42 women, aged 34-94 years, were analyzed. Fifty-three cases were classified as "leg type" and 26 cases were classified as "other" NOS type using the WHO-EORTC classification. Of the 53 cases classified as "leg type," 33 were women and 20 were men; of the 26 cases of "other" NOS type, 9 were women and 17 were men. In the "leg type" category, 31 cases were located on the lower extremities, 5 cases on the face, 5 cases on the arm, 3 cases on the chest, 2 cases on the shoulder, 2 cases on the back, 1 case on the trunk, 1 case on the buttock, 1 case on the supraclavicular area, 1 case on the head, and 1 case on the flank. Of the "other" NOS type category, 8 cases were located on the face, 5 cases on the shoulder, 3 cases on the head, 2 cases on the abdomen, 2 cases on the chest, 1 case on the trunk, 1 on the vulva, 1 on the axilla, 1 on the back, 1 on the neck, and 1 on the hip. Most cases assessed showed the classic morphologic appearance of PCDLBCL, but cases mimicking Burkitt lymphoma (starry-sky pattern), natural killer-cell (NK) lymphoma, mycosis fungoides (epidermotropism), low-grade B-cell lymphomas, epithelial malignancies, and Merkel cell carcinoma were encountered in this series. The high frequency of these rare histologic patterns can be explained by a bias associated with consultation practice. Careful histologic examination and immunohistochemical stains were used to establish the correct diagnosis. The differential diagnosis of PCDLBCL is broad and difficult to define histologically. Knowledge of these rare histologic variants is necessary to avoid misinterpretation of these cases as nonlymphoid malignancies.     

Expression of the T-cell regulatory marker FOXP3 in primary cutaneous large B-cell lymphoma tumour cells

Background Primary cutaneous B‐cell lymphomas (PCBCL) are subdivided into the aggressive form, primary cutaneous diffuse large B‐cell lymphoma, leg type (PCLBCL, LT) and two subtypes of indolent behaviour (primary cutaneous follicle centre lymphoma and primary cutaneous marginal zone B‐cell lymphoma). The difference in clinical behaviour can be explained by the tumour cell itself, or the lymphoma microenvironment including the antitumour immune response. Objectives To investigate the presence of regulatory T cells (Treg), CD4+CD25+FOXP3+, in the microenvironment of PCBCL in correlation with clinical outcome. Methods Tumour specimens of 55 consecutive cases of PCBCL were blinded and analysed for FOXP3, CD4 and CD25 expression by immunohistochemistry. Confocal images were taken with a Leica SP5. Statistical analyses were performed to determine significance. The test was considered significant when P < 0·05. Results The CD4 and FOXP3 expression as well as the CD4/FOXP3 ratio were significantly increased in PCBCL of indolent behaviour in contrast to PCLBCL, LT (P = 0·0002 for CD4, P < 0·0001 for FOXP3 and P = 0·0345 for FOXP3/CD4 ratio). CD25 expression did not differ in the three groups (P = 0·9414). Within the group of patients with PCLBCL, LT we identified a subgroup with FOXP3+ tumour cells as demonstrated by CD20/FOXP3 double stainings. Patients with FOXP3+ PCLBCL, LT tumour cells showed a better prognosis on Kaplan–Meier analysis. Conclusion High numbers of Treg in the lymphoma microenvironment correlate with a better prognosis in PCBCL. In PCLBCL, LT the presence of FOXP3+ tumour cells is beneficial for prognosis suggesting that FOXP3 expression of PCLBCL, LT tumour cells might serve as a tumour suppressor.     

Primary cutaneous diffuse large B‐cell lymphoma,leg‐type,treated with a modified R‐CHOP immunochemotherapy – diagnostic and therapeutic challenges

Background: Primary cutaneous diffuse large B‐cell lymphoma (PCLBCL) represents a rare subtype among primary cutaneous B‐cell lymphoma exhibiting a characteristic genetic background, an aggressive clinical course and a high relapse rate under different therapeutic regimen. Therefore, PCLBCL has a rather restricted prognosis. Patients and methods: Four patients with PCLBCL were treated at our institution with age‐ and toxicity‐adapted first‐line immunochemotherapy with rituximab and modified CHOP (cyclophosphamid, vincristin, liposomal doxorubicin, prednisolon). On relapse, the same regimen with R‐CHOP or different antineoplastic strategies (radiation, polychemotherapy, immunotherapy, stem cell transplantation) were applied. Toxicity, clinical response and overall survival was documented. Results: Under this regimen, clinical response to modified R‐CHOP was achieved in all patients with tolerable toxicity – however, being characterized by a rapid disease progression with inconsistent response towards the subsequent therapeutic armentarium and unsecure impact on overall survival. Conclusions: So far, it is still unknown, if an extensive multimodal therapy for PBLBCL improves overall survival. Immunochemotherapy with R‐CHOP currently represents the most effective treatment.     

原发性皮肤弥漫大B细胞淋巴瘤(腿型)3例

 报道3例原发性皮肤弥漫大B细胞淋巴瘤(腿型)。患者2女1男,年龄分别为77、57和77岁,分别表现为下肢、上肢及背部单发的无痛性肿块。皮损组织病理表现为真皮弥漫浸润的肿瘤细胞,体积大,异型性明显;免疫组化显示肿瘤细胞表达CD79a及Mum-1,而Bcl-6及Bcl-2呈阳性或阴性。诊断为原发性皮肤弥漫大B细胞淋巴瘤(腿型)。3例患者经过利妥昔单抗联合化疗后临床症状完全缓解,其中1例发生皮肤外扩散。     

Primary Cutaneous Diffuse Large B-Cell Lymphoma of the Upper Limb: A Fascinating Entity

Primary cutaneous lymphomas are defined as lymphoid neoplasms that present themselves clinically on the skin and do not have extra-cutaneous disease, when the diagnosis is made or even after 6 months of the diagnosis. Primary cutaneous lymphomas of B-cells are less frequent than lymphomas of T-cells. Primary B-cell lymphomas have a better prognosis than secondary B-cell lymphomas. Primary B-cell cutaneous lymphomas are classified into five types according to the World Health Organization and European Organization for Research and Treatment of Cancer classification. The primary diffuse large B-cell cutaneous lymphoma – leg type corresponds to approximately 5-10% of the B-cell cutaneous lymphomas. It is predominantly seen in elderly people and has a female preponderance. Skin lesions can be single, multiple, and even grouped. A 5-year survival rate ranges from 36 to 100% of the cases. The expression of Bcl-2, presence of multiple lesions, and involvement of both the upper limbs lead to a worse prognosis. Very few cases have been described in the literature.     

Bone involvement in two cases of thoracic primary cutaneous diffuse large B-cell lymphoma, leg type

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT), is defined by a predominance of confluent sheets of centroblasts and immunoblasts, which strongly express Bcl-2 protein. This cutaneous lymphoma is mainly characterized by the development of skin lesions on the lower leg. Other localizations are possible (namely non-leg PCLBCL-LT) and usually affect younger patients. PCLBCL-LT is distinguished from the two other subtypes of primary cutaneous B-cell lymphomas by its immunohistopathological features, its aggressive clinical behaviour with a worse prognosis linked to skin recurrences, but also secondary extracutaneous spread. Bone involvement underlying skin lesions has been reported in few series and cases reports during PCLBCL-LT. We describe here two aggressive cases of PCLBCL-LT with high burden and infiltrative thoracic tumours, with localized bone involvement.     

Rituximab in cutaneous B-cell lymphoma: a report of two cases

We report two patients with primary cutaneous B-cell lymphoma who were treated with rituximab, a new anti-CD20 monoclonal antibody. The first patient, who had a diffuse large B-cell lymphoma of the lower leg, achieved an 85% improvement. The second patient, who had a primary cutaneous B-cell lymphoma, which had undergone high-grade transformation and systemic spread, achieved a minor response of approximately 30%. Both patients subsequently relapsed. The first patient achieved complete clearance with a second course of rituximab given with systemic chemotherapy, but again relapsed. Treatment with rituximab has been reported to produce response rates of 48% in relapsed systemic low-grade or follicular lymphoma, but there are no previous reports of the use of rituximab in primary cutaneous B-cell lymphoma.     

Cutaneous B‐cell lymphomas – pathogenesis,diagnostic workup,and therapy

Cutaneous B‐cell lymphomas (CBCLs) comprise a group of mature lymphoproliferative B‐cell disorders that primarily affect the skin. Characterized by great biological and clinical variability among its various subtypes, CBCLs fundamentally differ from primary nodal or systemic B‐cell lymphomas. Given their uncomplicated course and excellent prognosis, lymphoma classifications rank primary cutaneous marginal zone lymphoma (PCMZL) and primary cutaneous follicle center lymphoma (PCFCL) as indolent CBCLs. By contrast, diffuse large B‐cell lymphoma, leg type (DLBCL‐LT) in particular, represent more aggressive lymphoma variants associated with a poorer prognosis. Therapeutic decisions and diagnostic procedures are based on the exact histological and immunohistochemical classification as well as the exclusion of systemic involvement and thus differentiation from nodal and systemic lymphomas. In this context, the diagnostic workup should also include molecular biology methods. Primary therapeutic options for indolent CBCL lesions include surgery and radiation therapy, as well as systemic treatment with rituximab (anti‐CD20 antibody) in case of dissemination. More aggressive CBCLs usually require a combination of rituximab and polychemotherapy, primarily the CHOP regimen or modifications thereof. Given that the pathogenesis and biology of CBCLs has not been conclusively elucidated, and given the limited therapeutic armamentarium available, there is great need for comprehensive research, especially with respect to DLBCL‐LT.     

Treatment of radiation-relapsing primary cutaneous B-cell lymphoma with an anti-CD20 monoclonal antibody

Primary cutaneous B cell lymphomas have a high recurrence rate after treatment with surgery and/or local radiation therapy. Two men are described in whom radiotherapy-relapsing cutaneous B-cell lymphomas were successfully treated with the monoclonal anti-CD20 antibody rituximab. Both patients had a complete response with no recurrence at follow-up at 17 and 24 months for the large B-cell lymphoma of the leg and the follicle centre cell lymphoma, respectively. These are two of the few cases in the literature showing that rituximab is an effective and well-tolerated treatment for radiotherapy-relapsing primary cutaneous B cell lymphoma.     

Rituximab for primary cutaneous diffuse large B-cell lymphoma-leg type

Primary cutaneous diffuse large B-cell lymphoma leg type (PCDLBCL-LT) is a rare type of lymphoma, of poor prognosis, which affects elderly people. Rituximab is an anti-CD20 monoclonal antibody and has demonstrated its efficiency in the treatment of nodal lymphomas. Rituximab with polychemotherapy has been reported in PCDLBCL-LT with a good response but many adverse effects. We evaluated the risk-benefit ratio of treatment with single-agent rituximab in a retrospective study on 8?patients with PCDLBCL-LT treated with rituximab. The main evaluation clinical endpoint was the rate of objective responses to the treatment. The secondary endpoints were the adverse effects, disease-free survival and overall survival. After 4?courses of single-agent rituximab, 75% of objective responses were achieved. 100% of patients relapsed (median disease-free survival: 5.25 months, median follow-up: 17.7 months). The tolerance was excellent with one adverse event (Grade I). Rituximab monotherapy induces a rate of objective responses which is less than rituximab with polychemotherapy, with no lasting therapeutic response. The tolerance of rituximab monotherapy is higher than rituximab with polychemotherapy. The risk-benefit ratio is a bit lower but rituximab is well tolerated and may be useful for short term palliative treatment.     

原发性皮肤弥漫大B细胞淋巴瘤（腿型）一例

报告1例原发性皮肤弥漫性大B细胞淋巴瘤（腿型）。患者男,51岁。右小腿出现多个红色结节5个月,组织病理检查：表皮和真皮之间见无细胞浸润带,真皮内淋巴样细胞浸润,细胞体积大,异形。肿瘤细胞CD20（++）,Bcl-6(+),Bcl-2(+),Pax-5(+),Ki-67 50％-75％(+),CD79a(+),MUM-1（+）,CD10（-）,诊断为原发性皮肤弥漫性大B细胞淋巴瘤（腿型）,给予CD20单克隆抗体加CHOP方案治疗,病情好转。     

Linfomas cutáneos. Parte II: otros linfomas cutáneos

Primary cutaneous T-cell lymphomas other than mycosis fungoides, Sézary syndrome, and lymphoproliferative CD30⁺ disorders are few, accounting for less than 5% of all cutaneous lymphomas. A cytotoxic phenotype is characteristic of these tumors, and their clinical behavior is usually aggressive. Patients often present with extracutaneous symptoms or develop them shortly after diagnosis. Management is usually multidisciplinary, and intensive systemic therapy and bone marrow transplantation should be considered. Cutaneous B-cell lymphomas account for approximately 30% of primary cutaneous lymphomas. They make up a heterogeneous group of tumors that have different clinical and pathological features. Clinical course also varies. Presenting as papules, nodules, or tumors of variable reddish–violaceous coloring, the lesions may be solitary or multiple and occasionally form clusters. There may also be generalized lesions, present at multiple sites on the trunk, head, or extremities. Three well-defined groups of primary cutaneous lymphoma have been reported: follicle center lymphoma; marginal zone lymphoma, which follows an indolent course; and a diffuse large B-cell lymphoma, leg type, which follows an aggressive course.     

Primary cutaneous B-cell lymphomas

Cutaneous B-cell lymphomas (CBCL) are the second most common form of primary cutaneous lymphomas. The cutaneous follicle center lymphoma and the cutaneous marginal zone lymphoma (extranodal MALT type lymphoma) account for the vast majority of CBCL and manifest with nodules. These two lymphoma entities have an indolent, slowly progressive course and an excellent prognosis despite a high rate of recurrences. In contrast, cutaneous diffuse large B-cell lymphoma, leg type, and other rare forms of CBCL display an impaired prognosis and therefore require to be treated with multiagent chemotherapy and anti-CD20 monoclonal antibodies in most cases. Clinico-pathologic correlation, histology with immunohistochemical profile and genotyping as well as staging examinations are crucial diagnostic elements in the work-up of CBCL.     

Bcl-2, Bcl-6 and CD10 expression in cutaneous B-cell lymphoma: further support for a follicle centre cell origin and differential diagnostic significance

BACKGROUND: Primary cutaneous follicle centre cell lymphomas (PCFCCLs) are the most common type of cutaneous B-cell lymphoma. There is ongoing discussion on the origin of the neoplastic B cells in these PCFCCLs, and consequently on their relation to the groups of primary cutaneous marginal zone B-cell lymphomas (PCMZLs) and nodal follicular lymphomas. OBJECTIVES: To define better the neoplastic B cells in PCFCCLs, and to find out if differences in the expression of the antiapoptopic protein Bcl-2, and Bcl-6 and CD10, molecules which are normally expressed by the neoplastic B cells in nodal follicular lymphomas, might have diagnostic or prognostic significance in cutaneous B-cell lymphoproliferative disorders. METHODS: Pretreatment biopsies of well-defined groups of PCFCCL (n = 24), PCMZL (n = 14), primary cutaneous large B-cell lymphoma of the leg (PCLBCL-leg; n = 19), secondary cutaneous follicular lymphoma (n = 3) and cutaneous pseudo-B-cell lymphoma (n = 6) were investigated by immunohistochemistry for expression of Bcl-2, Bcl-6 and CD10. RESULTS: The PCFCCLs consistently expressed Bcl-6, whereas CD10 and Bcl-2 were expressed in only one and two of 24 cases, respectively. In contrast, PCMZLs were always negative for Bcl-6 and CD10, but were Bcl-2 positive, whereas skin and lymph node localizations of secondary cutaneous follicular lymphomas consistently expressed all of Bcl-2, Bcl-6 and CD10. Reactive follicle centre cells in pseudo-B-cell lymphomas expressed Bcl-6 (six of six cases) and CD10 (five of six cases), but not Bcl-2. PCLBCL-leg was Bcl-6 positive and CD10 negative in all cases, irrespective of clinical outcome, and strongly expressed Bcl-2 protein in all but two cases. CONCLUSIONS: The results of the present study provide further support for the follicle centre cell origin of both PCFCCL and PCLBCL-leg, and indicate that staining for Bcl-2, Bcl-6 and CD10 can serve as an important adjunct in the differential diagnosis of cutaneous B-cell lymphoproliferative disorders.     

Primary cutaneous B‐cell lymphoma in Nottinghamshire U.K.: prognosis of subtypes defined in the WHO‐EORTC classification

Background Primary cutaneous B‐cell lymphomas (PCBCL), with the exception of large B‐cell lymphoma of leg type and intravascular large B‐cell lymphoma, are associated with an excellent prognosis. These lymphomas have become much better understood in recent years leading to the publication in 2005 of the World Health Organization–European Organisation for Research and Treatment of Cancer classification. Objectives To determine the relative frequency of occurrence of subtypes of PCBCL in a defined population, and the survival of patients with these subtypes. Methods During the period 1987–2009, 61 consecutive patients with PCBCL were identified from the Nottingham Lymphoma Registry (population 1·1 million). After histological review, the number of patients with each subtype was as follows: marginal zone, 18; follicle centre, 14; diffuse large B cell, leg type, 16; diffuse large B cell, other sites, 12; and intravascular large B cell, one. Results The 5‐ and 10‐year lymphoma‐specific survival for patients with marginal zone lymphoma was 100%. The only patient with intravascular large B‐cell lymphoma died from widespread disease in spite of chemotherapy. The 4‐year lymphoma‐specific survival for follicle centre cell lymphoma was 90%. Patients with the other subtypes had the following 5‐year lymphoma‐specific survival rates: diffuse large B cell, leg type, 61% and diffuse large B cell, other, 40%. The median age at diagnosis for patients with diffuse large B‐cell lymphoma, leg type was 82 years and as a consequence the 5‐year overall survival was only 15%. There was a 3·4‐fold increase in the incidence of PCBCL from the period 1987–1997 to the period 1998–2009. Conclusions PCBCL is a rare disease (incidence around three per million population per year). It is, in our view, essential that it is diagnosed by a pathologist with an interest in cutaneous lymphoma and that the very different prognosis of the individual subtypes is appreciated by the treating clinician.