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.     

Early diagnosis of recurrent diffuse large B-cell lymphoma showing intravascular lymphoma by random skin biopsy

A 66-year-old man was admitted to our hospital presenting 2 weeks' history of fever of unknown origin with elevated levels of lactate dehydrogenase and C-reactive protein. Six years before this episode, he had developed diffuse large B-cell lymphoma, which had been successfully treated with chemoradiation. While recurrence of diffuse large B-cell lymphoma was suspected, there was neither lymphadenopathy nor tumor formation by the imaging study. Random biopsy from normal-appearing abdominal skin showed extensive infiltration of CD20(+), CD79a(+), CD3(-) atypical lymphoid cells in the lumen of vessels in subcutaneous tissues. These findings led us to the diagnosis of intravascular B-cell lymphoma. Following rituximab plus cyclophosphamide, adriamycin, vincristine and prednisolone therapy, high fever subsided, and lactate dehydrogenase and C-reactive protein levels returned to the normal range. In conclusion, random skin biopsy is useful for the early diagnosis of intravascular B-cell lymphoma.     

Concurrent mycosis fungoides and intravascular large B-cell lymphoma in a single patient

Mycosis fungoides (MF) is an indolent, uncommon, non-Hodgkin T-cell lymphoma of the skin. It classically presents with patches, plaques, and tumors and may rarely show spread to internal organs or bone marrow. Up to 7.5% of MF patients may be diagnosed with a second malignancy. Intravascular large B-cell lymphoma (IVLBCL) is an exceedingly rare non-Hodgkin B-cell lymphoma characterized by predominant growth of large neoplastic cells in the lumina of blood vessels. This case presents with an unusual confluence of two rare diagnoses, MF and IVLBCL, made more remarkable by the presence of both diagnoses on a single skin biopsy sample.     

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.     

The use of blind skin biopsy in the diagnosis of intravascular B-cell lymphoma

Intravascular B-cell lymphoma is a rare type of non-Hodgkin's lymphoma that is characterized by a clonal proliferation of lymphoblasts within small blood vessels. Patients present with nonspecific symptoms and are often only given a diagnosis at autopsy. We report a case of intravascular B-cell lymphoma, characterized by pyrexia, anemia, thrombocytopenia, and mental status decline, without obvious cutaneous manifestations, that was diagnosed with blind skin biopsy.     

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.     

原发性皮肤弥漫性大B细胞淋巴瘤（腿型）二例并文献复习

弥漫性大B细胞淋巴瘤（腿型）是皮肤B细胞淋巴瘤的一个罕见亚型，具有特征性的临床、病理、免疫组化及演变特征。本文报道2例原发性皮肤弥漫性大B细胞淋巴瘤（腿型）并复习相关文献。     

A case of intravascular large B-cell lymphoma mimicking erythema nodosum: the importance of multiple skin biopsies

BACKGROUND: Intravascular lymphoma is a rare disease characterized by the proliferation of neoplastic monuclear cells within the lumens of small blood vessels. The neoplastic cells are usually of B-cell origin, and rarely of T-cell or histiocytic origin. Although this clinicopathological entity of lymphoma has not been listed in general pathological classifications such as REAL classification or the Working Formulation, it is recently in the WHO classification scheme, which is essentially an updated REAL scheme, and the EORTC classification scheme. METHODS: In this report, a 62-year-old woman with intravascular large B-cell lymphoma was observed by clinical, histopathological, immunohistochemical and molecular methods. RESULTS: A 62-year-old woman presented with large erythematous macules on the bilateral thighs and lower legs. The lesions were accompanied with hard, tender, intradermal or subcutaneous nodules mimicking erythema nodosum. Histopathological examination in the first biopsy revealed non-specific panniculitis compatible with erythema nodosum. The second biopsy revealed emboli of atypical lymphocytes within many of the dilated and proliferated vessels in the deep dermis and subcutaneous tissue. These cells were positive for L-26 and kappa light chain, and negative for lambda light chain, factor VIII-related antigen, CD30, CD34, CD68 and UCHL-1. These findings confirmed the diagnosis of intravascular large B-cell lymphoma. A laboratory examination showed a high level of LDH and abnormal cells in the bone marrow. An MRI of the brain and computed tomographic (CT) scans of the chest and abdomen revealed no evidence of malignancy. Before the treatment, the size of the nodules decreased spontaneously by about 50% in one month and significantly in two months. Although combination chemotherapy, which consisted of CHOP, brought her partial remission, she experienced neurological symptoms 6 months after the initial treatment and died of brain metastasis 9 months after the treatment. CONCLUSIONS: This is a unique case for two following reasons: 1) the first biopsy revealed non-specific findings compatible with erythema nodosum; and 2) before the treatment, the nodules regressed spontaneously. Dermatologists should take multiple skin biopsies for EN lesions with the non-specific histopathological findings not to refute the existence of this disease.     

Rituximab en el tratamiento de los linfomas cutáneos B primarios: revisión

Rituximab is a chimeric mouse-human antibody that targets the CD20 antigen, which is found in both normal and neoplastic B cells. In recent years, it has been increasingly used to treat cutaneous B-cell lymphoma and is now considered an alternative to classic treatment (radiotherapy and surgery) of 2 types of indolent lymphoma, namely, primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma. Rituximab is also administered as an alternative to polychemotherapy in the treatment of primary cutaneous large B-cell lymphoma, leg type. Its use as an alternative drug led to it being administered intralesionally, with beneficial effects. In the present article, we review the literature published on the use of rituximab to treat primary cutaneous B-cell lymphoma.     

Primary diffuse large B-cell lymphoma of the skin

B-cell lymphomas of the skin represent a wide spectrum of disorders. We present the microscopic and immunohistochemical features of a primary cutaneous B-cell lymphoma and classify it either as a diffuse large B-cell lymphoma or an indolent follicle-center-cell lymphoma according to the updated REAL/WHO system and the EORTC classification respectively. The former system is widely recommended; nevertheless, the EORTC system is also worth considering when planning management, because most data on long-term outcomes are based on it and it is considered to offer remarkable prognostic information.     

Cutaneous spindle-cell B-cell lymphoma: a morphologic variant of cutaneous large B-cell lymphoma

The morphologic spectrum of large B-cell lymphoma is broad. Several unusual variants have been described such as lymphoma with myxoid stroma, sclerosing B-cell lymphoma, signet ring-cell lymphoma, and multilobated B-cell lymphoma among others. We report on five cases of cutaneous large B-cell lymphoma in which the neoplastic cells were spindle-shaped. In two cases, the clinical features fulfilled those of a primary cutaneous lymphoma; in the three other cases, the lymphoma most likely arose primarily in the skin, but incomplete clinical workups precluded definite categorization. The patients ranged in age from 30 to 89 years and presented with solitary lesions on the trunk or head. Histopathologic examination revealed nodular or dense diffuse infiltrates involving the entire dermis as well as the subcutaneous fat in some cases. Thickened collagen bundles between the spindled cells were present in one case. Cytomorphologic analysis showed the presence of round or oval medium-sized and large-sized lymphocytes with features of centrocytes and centroblasts in some foci, with others dominated by cells with spindle-shaped, elongated, twisted nuclei with dispersed chromatin and scant cytoplasm. Immunohistologic analysis revealed that both round or oval and spindled cells were positive for CD20 in all cases; in all cases tested, these cells were also positive for MIB-1 and were negative for CD3, CD5, CD43, CD45RO, CD21, CD30, CD68, S-100, HMB-45, actin, smooth-muscle actin, and cytokeratin. Bcl-2 was expressed in one of three cases tested. Analysis of the rearrangement of the J(H) gene by polymerase chain reaction performed in one case showed a monoclonal pattern. Spindle-cell large B-cell lymphoma represents a distinctive rare subtype of the cutaneous large B-cell lymphoma and can arise primarily in the skin in some cases. Recognition of this variant is necessary to avoid misdiagnosis of other cutaneous malignant spindle-cell tumors.     

Primary cutaneous B-cell lymphoma

Primary cutaneous B-cell lymphomas include extranodal marginal zone B-cell lymphoma, follicular lymphoma, large B-cell lymphoma, and, rarely, mantle cell lymphoma. Our purpose in conducting this review was to determine the clinical and behavioral characteristics of primary cutaneous B-cell lymphomas, their relationship to infectious triggers, and therapeutic response. We conducted a retrospective chart review of 23 adult patients presenting to the dermatology clinic at M. D. Anderson Cancer Center with primary cutaneous B-cell lymphoma between January 1999 and May 2003. Primary cutaneous B-cell lymphomas generally present on the head and neck, with the trunk and extremities afflicted to a lesser extent. Patients were found to have serologic evidence of prior infection with Borrelia burgdorferi (n = 10), Helicobacter pylori (n = 5), and Epstein-Barr virus (n = 6). Overall, treatment of primary cutaneous B-cell lymphoma should involve multiple modalities; however, specific treatment aimed at concurrent or suspected infection, particularly B burgdorferi, is a helpful adjunct and may achieve complete remission in a small subset of patients.     

Use of an expanded immunohistochemical panel to distinguish cutaneous Hodgkin lymphoma from histopathologic imitators

In lymph nodes, classical Hodgkin lymphoma can typically be distinguished from non-Hodgkin lymphoma (NHL) by the presence of Hodgkin and Reed-Sternberg cells that co-express CD30 and CD15. However, anaplastic large cell lymphoma (ALCL) and diffuse large B-cell lymphoma (DLBCL) can show identical features, and some cases of classical Hodgkin lymphoma lack CD15 expression, rendering them difficult to differentiate from CD30-positive NHL. The differential diagnosis of cutaneous Hodgkin lymphoma similarly includes ALCL and DLBCL, and, additionally, tumors of mycosis fungoides. Recent studies have shown that classical Hodgkin lymphoma is of B-cell origin in virtually all cases, and shows at least focal weak expression of the B-cell marker PAX5 and often focal weak expression and no expression of the B-cell markers Oct-2 and BOB.1, respectively. All three of these markers are almost invariably absent in T-cell lymphomas and are strongly expressed in B-cell lymphomas. We report a 40-year-old man with classical Hodgkin lymphoma who developed cutaneous nodules. A biopsy from one revealed Hodgkin/Reed-Sternberg cells with a similar immunophenotype to the diagnostic lymph node biopsy, namely CD30+/CD15+, diffusely but weakly PAX5+, focally weakly Oct-2+ and lacking BOB.1 expression, thereby confirming a diagnosis of cutaneous Hodgkin lymphoma. To our knowledge, this is the first report of the expression pattern of the combination of PAX5, Oct-2 and BOB.1 in the context of cutaneous involvement by Hodgkin lymphoma.     

Diffuse large B-cell lymphoma associated with skin, muscle and cranial nerve involvement

The present case, a 75-year-old man with extranodal B-cell lymphoma showed facial hemiplegia, paresthesia and cutaneous manifestations. He was initially diagnosed as having a facial paralysis of unknown etiology. One month after the original diagnosis, erythematous indurated plaques developed on his left cheek and nose. A skin biopsy from the plaque on his cheek showed dense infiltrates of large lymphocytes with irregularly shaped nuclei and prominent nucleoli in the dermis and subcutaneous tissue. The lymphocytes were positive for L26 and CD79a. A diagnosis of diffuse large B-cell lymphoma was made. A muscle biopsy from facial muscle in the area of the erythematous plaque showed massive destruction of the muscle tissues by the lymphomatous infiltrates. Furthermore, electrodiagnostic study showed peripheral cranial nerve palsies, involving the left facial and trigeminal nerves. We conclude that diffuse large B-cell lymphoma may develop symptoms such as facial hemiplegia and paresthesia prior to cutaneous manifestations. Diffuse large B-cell lymphoma must be considered as one of the important causes of palsies of cranial nerves at the peripheral level.     

Immunochemotherapy for Bcl-2 and MUM-negative aggressive primary cutaneous B-cell non-Hodgkin’s lymphoma

The case of a 44-year-old man with a primary cutaneous large B-cell non-Hodgkin’s lymphoma of the scalp is reported. His mother died of gastric lymphoma and his sib brother is in a 20-year remission of T-cell lymphoma. The patient presented with a 16-year history of occipital and parietal alopecia and a recently worsening scalp rash. The histopathology and immunohistochemistry performed in April 2006 indicated a bcl-6+, MUM− and bcl-2−, primary cutaneous follicle center B-cell non-Hodgkin’s lymphoma, with an aggressive transformation to a diffuse large B-cell lymphoma. Bone marrow biopsy and CT chest, abdomen, and pelvis were negative for systemic lymphoma. The patient had an excellent clinical and histological resolution following 8 cycles of rituximab and CHOP protocol immunochemotherapy, and remains in complete remission until now. The protracted indolent phase of the disease, the familial history of lymphoma, the histological aggressive features and the patient’s excellent response to immunochemotherapy all contribute to a very unusual manifestation of this disease.     

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 involvement with Burkitt-like lymphoma

We report a case of a 27-year-old woman with a known history of Burkitt-like lymphoma (BLL), who presented with a rapidly enlarging nodule in the suprapubic area. Skin biopsy of the suprapubic nodule was consistent with cutaneous involvement of BLL. BLL is a highly aggressive B-cell lymphoma with a high proliferative rate. Like Burkitt lymphoma, BLL is characterized by a translocation of the c-MYC proto-oncogene. Histopathologic characteristics are considered borderline between those of classic Burkitt lymphoma and diffuse large B-cell lymphoma. Cutaneous involvement of BLL is rare and poorly documented in the literature.     

Diagnostic principles and new developments in primary cutaneous B-cell lymphomas

The most common subtypes of primary cutaneous B-cell lymphomas are marginal zone B-cell lymphoma/immunocytoma, follicle center cell lymphoma, and large B-cell lymphoma of the leg. Precise classification (European Organization for Research and Treatment of Cancer (EORTC) scheme) can be achieved only after a complete synthesis of clinical, histopathological, immunophenotypic, and molecular features. It is extremely important to emphasize that primary cutaneous B-cell lymphomas differ significantly from their nodal counterparts and are frequently characterized by an excellent prognosis. Awareness of this special clinical behavior should prevent the application of unnecessarily aggressive treatment protocols. Future definitions of primary cutaneous B-cell lymphomas will be based on their etiology and pathogenesis and especially on their molecular features. Some important areas are presented where exciting findings have been detected.     

New aspects in the biology of cutaneous B-cell lymphomas

Immunologic and molecular genetic studies greatly contributed to a better understanding and interpretation of the distinct clinico-pathologic features of primary cutaneous B-cell lymphomas (CBCL), which are the basis for the consensus WHO-EORTC classification. There is increasingly accumulating evidence that these well defined clinico-pathologic entities of CBCL have specific immunologic and molecular features, which further support their nosologic categorization as well as either interesting similarities with other extranodal B-cell lymphomas or definite peculiarities as compared to nodal B-cell lymphomas of similar histotype (specifically, follicle center lymphoma and diffuse large B-cell lymphoma).