Intravascular large B-cell lymphoma of the cutaneous variant in Korea

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of diffuse large B-cell lymphoma. It is characterized by proliferation of malignant lymphoid cells within the small vessels of various organs. The skin and central nervous system are commonly involved although it occurs in other organs such as the kidneys, adrenals, lung and liver. In Western patients, there is a cutaneous variant of IVLBCL, which involves only the skin. However, the Asian variant, which rarely involves the skin, is associated with hemophagocytosis. It was reported in the majority of Japanese patients. Here, we report a case of the cutaneous variant of IVLBCL in a Korean individual.     

Richter syndrome first manifesting as cutaneous B-cell lymphoma clonally distinct from primary B-cell chronic lymphocytic leukaemia

Richter syndrome (RS) is a transformation to high-grade non-Hodgkin lymphoma in patients with chronic lymphocytic leukaemia (CLL). RS may develop in lymph nodes or rarely extranodally. Skin localization of RS has been described in only a few cases. We present a 77-year-old woman who developed isolated diffuse large B-cell lymphoma (LBCL) in the skin of the nose without any other symptoms of RS. The LBCL in the skin was clonally distinct from the original bone marrow CLL cells. Moreover, LBCL cells were positive for LMP-1 segment of Epstein-Barr virus and overexpressed p53 protein. The patient was successfully treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) and adjuvant local radiotherapy.     

血管内大B细胞淋巴瘤4例临床病理分析

目的:分析4例血管内大B细胞淋巴瘤（IVLBCL）的临床病理特点。方法:回顾北京协和医院皮肤科2020年1-11月行皮肤组织病理确诊的4例IVLBCL患者的临床及病理资料。结果:4例患者年龄57~76岁,男2例,女2例。4例出现神经系统症状,3例发热,3例运动耐量下降、憋气,3例躯体凹陷性水肿。例1背部出现0.2 cm...     

Intravascular large B-cell lymphoma with cutaneous manifestations: a clinicopathologic, immunophenotypic and molecular study of three cases

Background:  Intravascular large B-cell lymphoma (IVLBCL) is an extremely rare type of malignant lymphoma characterized by exclusive or predominant growth of neoplastic cells within the lumen of blood vessels. Cases in the literature predominantly involve the skin and central nervous system, with special emphasis on the 'cutaneous variant'.
Methods:  Three cases of IVLBCL with cutaneous manifestations, including two systemic IVLBCL and one cutaneous variant, were described in this study. In all cases, clinical presentation and follow-up data were meticulously evaluated and immunophenotypic and molecular studies were performed.
Results:  All three cases displayed the B-cell phenotype and showed monoclonality with immunoglobulin heavy chain gene rearrangement. Bcl2 was expressed in the two systemic IVLBCL cases with fatal outcomes. The third patient with the 'cutaneous variant' achieved complete remission and a longer survival time of 15 months after chemotherapy.
Conclusions:  Skin manifestations and neurological findings, although to different degrees, are important clues to the diagnosis of IVLBCL. As most IVLBCL are grouped into the post-germinal center B-cell subtype of diffuse large B-cell lymphoma, Bcl2 expression may be correlated with a worse prognosis in IVLBCL. The cutaneous variant of IVLBCL has a significantly better outcome than that of systemic IVLBCL.     

Cutaneous spindled follicle center cell lymphoma with abundant mucin: A diagnostic pitfall

Primary cutaneous follicle center cell lymphoma is the most prevalent type of primary cutaneous B-cell lymphoma and usually portends a favorable prognosis. Typically, the diagnosis can be rendered based on characteristic histopathologic features and immunohistochemical profile. Rarely, a diagnostically challenging variant with a predominant spindle morphology mimicking other malignant spindle cell neoplasms may be encountered. Even more unusual is the presence of a prominent myxoid stroma in this rare sarcomatoid variant of follicle center cell lymphoma. Herein, we present a case of a 52-year-old man with a slowly enlarging cyst-like lesion on the chin with histopathologic examination revealing a malignant, predominantly spindled neoplasm within an abundant myxoid stroma. Following a broad panel of immunohistochemical stains, the strong positive staining of the spindle cells for LCA (CD45), CD20, and Bcl-6 confirmed the diagnosis of follicle center cell lymphoma. We present this distinctive rare subtype of cutaneous follicle center cell lymphoma to increase awareness of this variant and to discuss challenging histopathologic mimics to consider while highlighting the utility of immunohistochemistry stains to avoid misdiagnosis.     

皮下血管内大B细胞淋巴瘤

报告1例皮下血管内大B细胞淋巴瘤.患者男,73岁.因双侧大腿皮下结节,于2007年2月初就诊.皮损组织病理检查见血管腔内有大量肿瘤细胞聚集,免疫组化染色结果示肿瘤细胞CD20阳性,诊断为皮下血管内大B细胞淋巴瘤(IVLBCL).予环磷酰胺、长春新碱、泼尼松(COP方案)化疗后皮损缩小.IVLBCL恶性程度较高,临床表现无特异性,预后较差,皮损组织病理检查有助于诊断.     

Primary cutaneous marginal zone B-cell lymphoma: a clinical,histopathological, immunophenotypic and molecular genetic study of 22 cases

BACKGROUND: Primary cutaneous marginal zone B-cell lymphoma (MZCL) has recently been described. Differentiation from follicular centre cell lymphomas and lymphocytomas is often difficult due to insufficient experience and a lack of large series of patients. OBJECTIVES: To characterize primary cutaneous MZCL better, we report clinical, histopathological, immunophenotypic and molecular genetics features in a series of 22 patients. METHODS: All patients were treated and followed up at the same institution. Diagnosis of MZCL was based on the World Health Organization classification criteria. All samples were routinely tested with a wide panel of monoclonal antibodies. DNA was extracted from every sample following standard methods. IgH rearrangement and t(14;18)(q32;q21) studies were performed in all samples. RESULTS: Twenty-two patients (20 men, two women; mean age 50 years, range 24-77) were included. The mean follow-up was 43 months. Seventy per cent of patients presented with characteristic skin lesions on the trunk or extremities, consisting of deep red to violaceous infiltrated plaques, nodules or tumours frequently surrounded by diffuse or annular erythema. Four patients presented with lesions on the head and neck area. Two patients had disseminated skin lesions. The main histopathological features were non-epidermotropic, dense lymphocytic infiltrates mainly distributed in a nodular pattern. Adnexal involvement was usually present, with eventual formation of lymphoepithelial complexes. Cytologically, the infiltrate was polymorphous with marginal zone B cells and B-monocytoid cells. Blastoid CD30+ cells were often observed. Colonized reactive germinal centres and lymphoplasmocytoid differentiation were frequently present. Neoplastic cells were CD20+, CD79a+, CD5- and CD10-. Monotypic expression of light chains was observed in 18 cases (13 kappa; five lambda). Clonal IgH rearrangements were detected in 14 cases. The bcl-2 mutation t(14;18)(q32;q21) was demonstrated in two cases. Most patients were treated with local radiotherapy. Complete response rate with this approach was 100%. Six patients (27%) had skin recurrences from 6 months to 8 years after first treatment. Five patients (23%) had extracutaneous involvement. Two of them had a large cell transformation and one died of lymphoma. Three of four patients with head and neck presentation developed extracutaneous disease. CONCLUSIONS: MZCL appears to be a well recognizable entity, clinically, histologically and immunophenotypically. Although prognosis is generally good, the disease has potential for skin as well as extracutaneous recurrences. Large cell transformation and head and neck presentation may be associated with a worse prognosis.     

BCL2 and JUNB abnormalities in primary cutaneous lymphomas

BACKGROUND: BCL2 is upregulated in nodal and extranodal B-cell non-Hodgkin's lymphomas, with a consequent antiapoptotic effect. However, loss of BCL2 has also been noted in some malignancies, suggesting a different molecular pathogenesis. OBJECTIVES: To investigate genomic and protein expression status of BCL2 and to compare the results with that of JUNB in primary cutaneous lymphomas (PCLs). METHODS: We analysed gene copy number of BCL2 and JUNB in 88 DNA samples from 80 patients with PCL consisting of Sézary syndrome/mycosis fungoides (SS/MF), primary cutaneous B-cell lymphoma (PCBCL) and primary cutaneous CD30+ anaplastic large cell lymphoma (C-ALCL) by the use of real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC). Real-time PCR and IHC findings were subsequently compared with the results of additional fluorescent in situ hybridization (FISH) analysis of 23 cases of SS and Affymetrix cDNA expression microarray study of two primary cutaneous T-cell lymphoma (CTCL) cell lines. RESULTS: Real-time PCR analysis showed loss of BCL2 gene copy number in 22 of 80 PCL cases (28%), including 17 of 42 SS/MF, three of 13 C-ALCL and two of 33 PCBCL samples, and gain of BCL2 in four PCBCL samples. Gain of JUNB was identified in 18 of 71 PCL cases (25%), including nine of 35 SS/MF, seven of 13 C-ALCL and two of 31 PCBCL samples. IHC analysis revealed absent nuclear expression of BCL2 protein in 47 of 73 PCL cases, comprising 28 of 36 SS/MF, eight of eight C-ALCL and 11 of 29 PCBCL cases. In contrast, BCL2 protein expression was detected in 26 of 73 PCL cases, consisting of 18 of 29 PCBCL and eight of 36 SS/MF cases. JUNB protein expression was present in tumour cells from 30 of 33 of SS/MF and eight of eight C-ALCL, and was absent in tumour cells from 18 of 27 PCBCL cases. A comparison between BCL2 and JUNB revealed loss of BCL2 and gain of JUNB in five of 35 SS/MF samples, and expression of JUNB protein and absent BCL2 expression in 25 SS/MF and eight of eight C-ALCL cases. In contrast, expression of BCL2 and absent JUNB expression were detected in 67% of PCBCL cases. Additional FISH analysis revealed deletion of BCL2 in 19 of 23 SS cases (83%), including eight cases with BCL2 loss shown by real-time PCR. Furthermore, Affymetrix expression microarray demonstrated decreased expression of proapoptotic and antiapoptotic genes involved in BCL2 signalling pathways such as BOK, BIM, HRK, RASA1 and STAT2 in two CTCL cell lines with BCL2 loss and absent BCL2 expression. Increased expression of JUNB was also identified in the MF cell line. CONCLUSIONS: These findings provide a comprehensive assessment of BCL2 and JUNB status in PCL, and suggest that there is a selection pressure in a subset of CTCL cases for tumour cells showing BCL2 loss and upregulation of JUNB primarily through chromosomal deletion and amplification, respectively.     

Unilesional follicular mycosis fungoides: report of two cases with progression to tumor stage and review of the literature

Mycosis fungoides (MF) is the most common type of cutaneous lymphoma and has protean clinicopathological manifestations. Follicular or folliculotropic MF (FMF) is a rare variant, which histopathologically is characterized by pronounced folliculotropism of neoplastic T cells, with or without follicular mucinosis, and clinically by an impaired prognosis compared to classic MF. In contrast, unilesional MF is a very rare variant with an excellent prognosis, with a single case of large-cell transformation reported to date. The combination of folliculotropic and unilesional MF is very unusual, with only two cases reported to date. Here we report two patients with unilesional folliculotropic MF with progression to tumor stage in both patients. To the best of our knowledge, this is the first report on the disease evolution with large-cell transformation and progression of unilesional FMF. Complete remission was achieved by local radiation therapy in both patients. The differential diagnoses, classification and implications for the treatment of unilesional FMF as well as the pertinent literature are discussed.     

Clinical study of primary cutaneous B-cell lymphoma using both the European Organization for Research and Treatment of Cancer and World Health Organization classifications

Primary cutaneous B-cell lymphoma (PCBCL) is rare, with few series reported in the literature. Its classification and treatment remain controversial. Biopsy specimens of 13 patients with PCBCL were classified according to both the European Organization for Research and Treatment of Cancer (EORTC) and the new World Health Organization (WHO) classifications. Treatment and clinical outcomes were documented. Using the EORTC classification there were seven men and six women aged 32-85 years (mean = 51 years) with follicle centre cell (FCC) lymphoma (nine), immunocytoma (two) and primary cutaneous large B-cell lymphoma of the leg (PCLBCL-leg) (two). When the WHO classification was used, the nine patients with FCC were reclassified as follicle centre (five) and diffuse large B-cell lymphoma (four). Most patients had localized disease (12). Initial treatment consisted of radiotherapy alone (seven), combination chemotherapy alone (one), combined chemoradiotherapy (three) and surgery (two). Twelve patients achieved complete remission (median follow up 28 months, range 10-167 months). One patient with PCLBCL-leg died from progressive cutaneous disease. Most localized PCBCL lesions (except PCLBCL-leg) have a favourable prognosis. We recommend that clinicians be familiar with the important differences in the EORTC and WHO classifications. Further large prospective studies comparing the WHO and EORTC classifications are required to more clearly delineate the outcomes of the increasing number of patients who are classified as DLBCL by the WHO system.     

Absence of the t(14;18) chromosomal translocation in primary cutaneous B-cell lymphoma

BACKGROUND: The t(14;18)(q32;q21) chromosomal translocation is found in the majority of nodal follicular lymphomas and in a lower percentage of systemic high-grade diffuse large B-cell lymphomas. The translocation results in the juxtaposition of the bcl-2 gene on chromosome 18 with the immunoglobulin heavy chain joining region on chromosome 14. Bcl-2 protein prevents apoptosis and the translocation leads to overexpression of a functionally normal Bcl-2 protein that prevents apoptosis of neoplastic cells. OBJECTIVES: The purpose of our study was to analyse cases of primary cutaneous B-cell lymphoma (PCBCL) for the presence of the t(14;18) translocation and to correlate the results with Bcl-2 expression and histological subtype. METHODS: Forty-four cutaneous B-cell lymphoid proliferations (36 PCBCL, four follicular B-cell lymphomas with cutaneous presentation and four reactive B-cell infiltrates) were analysed by polymerase chain reaction amplification and polyacrylamide gel electrophoresis using consensus primers for the joining region on the immunoglobulin heavy chain gene in combination with either a primer for the major breakpoint region (MBR) or the minor cluster region (mcr) on chromosome 18. RESULTS: None of 36 PCBCL analysed demonstrated a t(14;18) translocation; however, three of four systemic follicular B-cell lymphomas presenting in the skin were found to have a translocation in the MBR, which was confirmed by sequence analysis. Correlation with Bcl-2 immunostaining showed that of seven patients with high-grade cutaneous diffuse large B-cell lymphoma, four were Bcl-2 positive but had no evidence of a t(14;18) translocation. In the five cases classified as primary cutaneous follicle centre cell lymphoma, the neoplastic cells within the germinal centres failed to express Bcl-2. However, Bcl-2-positive neoplastic cells were present in all four cases of systemic follicular lymphoma, including the case that did not show a t(14;18) translocation. In all cases of marginal zone lymphoma the marginal zone lymphocytes were Bcl-2 positive. CONCLUSIONS: These findings indicate that the t(14;18) translocation does not occur in PCBCL, which suggests the involvement of different pathogenetic mechanisms compared with their nodal counterparts. Furthermore, the detection of a t(14;18) translocation in cutaneous B-cell lymphoma should suggest the presence of systemic disease, which underlies the need for exhaustive staging procedures.     

Actinic granuloma occurring in an unusual association with cutaneous B-cell chronic lymphocytic leukemia

Granulomatous cutaneous reactions are well described in association with T-cell non-Hodgkin lymphoma and Hodgkin lymphoma, but are rarely seen in association with B-cell non-Hodgkin lymphoma or leukemia. We report a case of a 65-year-old woman with B-cell chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who presented with multiple, tender, firm pink papules on the face, upper trunk and upper extremities 6 years after diagnosis of CLL. Biopsy revealed both palisading granulomatous dermatitis consistent with actinic granuloma and a dense perivascular lymphocytic infiltrate consistent with the patient's known history of leukemia. This is an unusual manifestation of cutaneous B-cell CLL that is rarely seen.     

Malignant transformation of lymphadenosis benigna cutis: a possibly transformed case and B-cell lymphoma

This study presents a patient who had had a 10 year history of lymphadenosis benigna cutis (LABC) before malignant lymphoma of the skin subsequently developed. During the LABC stage, the lesion showed several foci of cavernous hemangioma-like nodules which disappeared spontaneously but reccurred repeatedly. These cutaneous nodules were finally diagnosed as malignant lymphoma of the skin with a histology of diffuse, mixed small and large cell type according to the classification of the Working Formulation. Among the subpopulations of tumor cells, B-cells were highly predominant. It is suggested that LABC may have the potential to transform into malignant lymphoma (probably B-cell lymphoma).     

A case report and literature review of cutaneous intravascular large B-cell lymphoma presenting clinically as panniculitis: a difficult diagnosis,but a good prognosis

Intravascular large B-cell lymphoma is a rare, non-mass-forming, extranodal large B-cell lymphoma subtype characterized by the presence of tumor cells in the lumens of vessels. It is divided into two major types: classical and Asian. Patients presenting only with skin involvement are mostly female, at a younger age than classical intravascular large B-cell lymphoma patients, and have a better prognosis. Since the diagnosis of cases with isolated skin involvement is difficult, keeping this entity in mind, performing a careful microscopic examination, and applying new, effective treatment regimens will make it possible to achieve better clinical outcomes in these cases.     

Cutaneous metastasis of primary diffuse large B-cell lymphoma of the central nervous system developing 4 years after complete remission: Diagnosis confirmed by comparison of clones

B-cell lymphoma of the central nervous system (CNS) is a rare malignancy with diffuse large B-cell lymphoma (DLBCL) variant being most common. Although DLBCL has a high propensity to relapse locally within the CNS, only a few cases of cutaneous metastasis have been described in the literature. We present a unique case of cutaneous metastasis of a primary DLBCL of the CNS in a 79-year-old man who was in clinical remission for 4 years until presenting with a lesion in the left adrenal gland and cutaneous nodules on the left flank. Skin biopsy specimen revealed a diffuse dermal infiltrate of atypical B-cell lymphocytes with expression of CD20, BCL-2, BCL-6, and MUM-1, suggestive of DLBCL. For differentiation between another primary or a recurrent process, immunoglobulin kappa (IgK) light chain gene rearrangement was performed and demonstrated that the DLBCL of the skin and CNS were of the same clonal origin. Restaging computerized tomography after initiating chemotherapy and daily ibrutinib showed complete resolution of the left adrenal mass and resolving cutaneous lesions. Our case demonstrates the rare, late cutaneous metastasis of DLBCL of the CNS and highlights the importance of genetic testing for the distinction between the primary and secondary lesions.     

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 marginal zone B-cell lymphoma in a patient with chronic lymphocytic leukaemia

Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is a low-grade malignant lymphoma that presents in the skin with no evidence of extracutaneous localization at diagnosis. We present an 80-year-old woman with B-cell chronic lymphocytic leukaemia (CLL) who developed multifocal PCMZL lesions 14 months after CLL diagnosis. PCMZL was clonally similar to the original bone marrow (BM) CLL cells. The specific translocation t(14;18) (q32;q21) with breakpoints in IGH and BCL2 loci was found in a skin specimen, but was absent in BM and peripheral blood (PB) cells. In contrast, a 13q deletion was found in BM and PB CLL cells. The patient was treated with chlorambucil and complete response of PCMZL was achieved. To our knowledge this is the first patient with CLL in whom PCMZL has been diagnosed.     

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.