[The understanding of Epstein-Barr virus associated lymphoproliferative disorder].

In recent years, there are increasing articles concerning Epstein-Barr virus associated lymphoproliferative disorder (EBV+ LPD), and the name of EBV+ LPD is used widely. However, the meaning of EBV+ LPD used is not the same, which triggered confusion of the understanding and obstacles of the communication. In order to solve this problem. Literature was reviewed with combination of our cases to clarify the concept of EBV+ LPD and to expound our understanding about it. In general, it is currently accepted that EBV+ LPD refers to a spectrum of lymphoid tissue diseases with EBV infection, including hyperplasia, borderline lesions, and neoplastic diseases. According to this concept, EBV+ LPD should not include infectious mononucleosis (IM) and severe acute EBV infection (EBV+ hemophagocytic lymphohistiocytosis, fatal IM, fulminant IM, fulminant T-cell LPD), and should not include the explicitly named EBV+ lymphomas (such as extranodal NK/T cell lymphoma, aggressive NK cell leukemia, Burkitt lymphoma, and Hodgkin lymphoma, etc.) either. EBV+ LPD should currently include: (1) EBV+ B cell-LPD: lymphomatoid granulomatosis, EBV + immunodeficiency related LPD, chronic active EBV infection-B cell type, senile EBV+ LPD, etc. (2) EBV+ T/NK cell-LPD: CAEBV-T/NK cell type, hydroa vacciniforme, hypersensitivity of mosquito bite, etc. In addition, EBV+ LPD is classified, based on the disease process, pathological and molecular data, as 3 grades: grade1, hyperplasia (polymorphic lesions with polyclonal cells); grade 2, borderline (polymorphic lesions with clonality); grade 3, neoplasm (monomorphic lesions with clonality). There are overlaps between EBV+ LPD and typical hyperplasia, as well as EBV+ LPD and typical lymphomas. However, the most important tasks are clinical vigilance, early identification of potential severe complications, and treating the patients in a timely manner to avoid serious complications, as well as the active treatment to save lives when the complications happened.

[Lymphomatoid granulomatosis]. / Granulomatose lymphomatoïde.

Lymphomatoid granulomatosis, described in 1972 by Liebow, is a rare, Epstein-Barr virus (EBV)-associated lymphoproliferative disorder, involving the lung, and often the skin or the central nervous system. It could have a systemic course making its diagnosis difficult. Controversy still remains about precise taxonomy and lymphomatoid granulomatosis is classified as a lymphoma, whose severity extends from indolent forms to aggressive large B cell lymphomas. Histology is essential and shows characteristically an inflammatory angiocentric infiltrate, composed with polymorphous mononucleated cells containing a varying number of large atypical CD20-positive B-lymphocytes within a background of numerous small reactive CD3-positive T-lymphocytes, often associated with necrosis. In situ hybridization often shows EBV RNA within atypical B-cells. Atypical large B-lymphocytes proportion and to a lesser degree EBV-positive B-lymphocytes proportion allow to classify the disease (grade I to III) and have a prognostic value. An aggressive form of B lymphoma occurs in 7 to 47% of cases during lymphomatoid granulomatosis course. Moreover, grade III diseases share numerous characteristics of lymphoma and often require chemotherapy. Several conditions mimic lymphomatoid granulomatosis, and include various hematologic malignancies (large B-cells lymphomas, T/NK lymphomas, post-immunodepression lymphoproliferative disorders) or granulomatosis with polyangiitis. The objective of this article is to review the clinical, radiological, histological and therapeutic characteristics of this rare disorder.

Pulmonary vasculitis.

The granulomatous vasculitides frequently involve the lung. These syndromes include Wegener's granulomatosis, allergic angiitis and granulomatosis, and the polyangiitis overlap syndrome. Although not a true systemic vasculitis, necrotizing sarcoid granulomatosis also represents a type of pulmonary vasculitis. It is clear that many infectious agents can cause a picture in the lung that can be confused with granulomatous vasculitis and that an infectious process must be ruled out before a diagnosis of pulmonary vasculitis can be established. Pulmonary vasculitis can be associated with the hypersensitivity vasculitides, and pulmonary hemorrhage can be secondary to pulmonary capillaritis. Therapy of the hypersensitivity vasculitides consists of removing the offending antigen and instituting a limited course of corticosteroids. If the vasculitis is secondary to an underlying disease, such as lymphoma, therapy should be directed at the primary disease. Combination therapy with cyclophosphamide and corticosteroids is effective in the systemic vasculitides and the 5-yr survival rate is approximately 90%.

Peripheral T-cell lymphomas: histologic, immunohistologic, and clinical characterization.

A review of 40 cases of peripheral T-cell lymphoma identified at our institution between March 1983 and December 1985 revealed a clinically, histologically, and immunologically diverse group of neoplasms that were difficult to classify by conventional histomorphologic criteria for non-Hodgkin's lymphomas. These lymphomas were frequently extranodal at the time of initial manifestation (52%), and their clinical aggressiveness correlated with three major histologic categories--small lymphocytic, diffuse mixed, and large cell. Of the 40 lymphomas, 18 exhibited distinctive histologic features that allowed assignment of these cases into one of four subgroups: (1) angioimmunoblastic lymphadenopathy, (2) lymphomatoid granulomatosis, (3) Hodgkin's-like disease, and (4) Lennert's lymphoma (lymphoepithelioid lymphoma). Study of all our cases that fulfilled the morphologic criteria for lymphomatoid granulomatosis or angioimmunoblastic lymphadenopathy by using immunologic methods for identification of B-cell and T-cell antigens has shown these neoplasms to be peripheral T-cell lymphomas. Therefore, we now consider these earlier proposed entities to be distinct histologic variants of peripheral T-cell lymphoma.

Pulmonary angiitis and granulomatosis revisited.

Re-examination of the pathologic and clinical features of the entities traditionally classified under the heading "pulmonary angiitis and granulomatosis" indicates that there is little advantage in retaining this artificial category and that these entities should be considered variants of diseases to which they are actually related. Wegener's granulomatosis and allergic angiitis and granulomatosis appear to be examples of true systemic vasculitides in which the lung is a predominant but not the only or even the most important site of involvement. Wegener's granulomatosis may manifest with involvement limited to lung, a form that has been called limited Wegener's; however, many or most such cases progress to classic disease involving kidney and often upper respiratory tract. Similarly, Wegener's granulomatosis may present with disease limited initially to the upper respiratory tract (a form of midline granuloma); this process may also spread to involve lung and kidney. It seems unlikely that limited Wegener's is truly a separate disease category. Evaluation of the pathologic and clinical features of necrotizing sarcoid granulomatosis indicate that it very much resembles ordinary sarcoid in most histologic features, in the nature of extrapulmonary involvement, and in its clinical course and that it probably corresponds to the clinical--radiographic entity of nodular sarcoid. Lymphomatoid granulomatosis appears to have little relationship to the other members of the angiitis and granulomatosis group; its behavior and histologic features are those of a lymphoproliferative disorder that in most cases is or becomes histiocytic lymphoma. Some cases of so-called benign lymphocytic angiitis also fall into this category; the remainder appear to represent a variety of completely unrelated pathologic processes. Last, bronchocentric granulomatosis is most commonly one of the histologic manifestations of allergic bronchopulmonary aspergillosis, although it is likely that other agents or processes produce the same histologic pattern. Although the presence of a common set of pathologic features makes the concept of angiitis and granulomatosis attractive from a morphologic point of view, there is minimal clinical similarity among them, and these diseases appear to be totally separate entities.

Pulmonary lymphomas: current concepts.

The shift from a clinical definition (aggressive behavior) to an immunologic definition (clonal proliferations of cells) of lymphomas has led to a reinterpretation of most pulmonary pseudolymphomas as indolent lymphomas. The recognition of the diverse histologic appearance of lymphomas and the acceptance of extranodal lymphomas support the view that most cases of lymphomatoid granulomatosis are malignant lymphomas. Criteria for the recognition and classification of pulmonary lymphoid lesions are discussed.

Midline granuloma syndrome: a clinicopathologic study of 13 patients.

Thirteen patients with the clinical features of the midline granuloma syndrome are reported. Seven of the patients were determined to have Wegener's granulomatosis and had segmental necrotizing glomerulonephritis in their renal biopsies. Eighteen upper aerodigestive trace mucosal biopsies were available for review from the seven patients, and nine of these biopsies had a granulomatous angiodestructive inflammatory cell infiltrate considered "diagnostic" of Wegener's granulomatosis. The remaining nine biopsies lacked the specific histologic features of Wegener's granulomatosis but were considered consistent with mucosal involvement by the disease. Five of the remaining six patients had upper aerodigestive tract biopsies that were characterized by lymphocytic infiltrates. Three of the five patients had appreciable numbers of "atypical" cells in their biopsies and presented with radiologic evidence of lung involvement. It is our impression that patients with "significant cellular atypia" in their lymphocytic infiltrates have a disease indistinguishable from lymphomatoid granulomatosis, and these patients have a high propensity for either the presence or development of systematic disease that may require chemotherapy. Two patients had lymphocytic infiltrates with only minor degrees of cytologic atypia and no evidence of multisystem disease, and both of these patients responded to local radiation therapy. The remaining patient had a nonspecific histologic pattern in her numerous biopsies and was diagnosed as idiopathic midline destructive disease. She also had an adequate response to radiation therapy.