This rare lymphoma arises in the setting of a long-standing pyothorax or chronic inflammation of the pleura. It is a non-Hodgkin's extra-nodal lymphoma.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis and Treatment Commonly Used Terms
EPIDEMIOLOGY CHARACTERIZATION GEOGRAPHY More common in Japanese
Pyothorax-associated lymphoma: description of the first two cases detected in Italy.
Ascani S, Piccioli M, Poggi S, Briskomatis A, Bolis GB, Liberati F, Frongillo R, Caramatti C, Fraternali-Orcioni G, Gamberi B, Zinzani PL, Lazzi S, Leoncini L, O'Leary J, Piccaluga PP, Pileri SA.
Service of Pathologic Anatomy and Haematopathology, Institute of Haematology and Clinical Oncology L.& A. Seragnoli, Bologna University School of Medicine, Italy.
Ann Oncol 1997 Nov;8(11):1133-8 Abstract quote
BACKGROUND: Pyothorax-associated lymphoma (PAL) is a rare, but distinct, clinico-pathologic entity which occurs most often in Japanese people; to the best of our knowledge, only six cases of it have been reported in Western countries. The tumour develops several decades following artificial pneumothorax or chronic pleuritis due to tuberculous infection, produces pleural effusion associated with extensive local lymphomatous infiltrates, and is sustained by a polymorphic large B-cell clonal proliferation showing EBV integration in the genoma of the neoplastic cells.
PATIENTS AND METHODS: Herein we describe two cases of PAL observed in Italian patients, both extensively studied on the clinical, pathological, phenotypic, virological, and molecular levels.
RESULTS: The two cases occurred, respectively, 45 and 50 years after therapeutic pneumothorax because of tuberculous pleuritis and were characterized by a pleural mass extending to the thoracic wall, which on histological examination were seen to consist of large elements with immunoblastic morphology. Immunohistochemistry show monotypic restriction of Ig light chains, as well as the expression of CD45, B-cell markers (CD20, CD79a, CD45RA), bcl-2 oncogene product, EBNA-2 and, partially, LMP-1. The ratio of cycling cells was extremely high as was the number of mitotic figures. In situ hybridization displayed the presence in the neoplastic cells of the EBV-related small RNAs EBER 1 and 2, which in turn, along with the positivity for EBNA-2 and LMP-1, further strengthened the close relationships between PAL and latent viral infection. Molecular studies revealed, on one hand, clonal rearrangement of the Ig heavy chain J region genes, and on the other, negativity for HHV8 in one case and positivity in the other.
CONCLUSIONS: These cases of PAL are the first to be documented in Italy; they serve to direct attention to the fact that this condition is not confined to Japanese people, and that its occurrence in Western countries might be underestimated.
DISEASE ASSOCIATIONS CHARACTERIZATION EMPYEMA Tuberculosis, chronic pleuritis
PATHOGENESIS CHARACTERIZATION EPSTEIN-BARR VIRUS
Pyothorax-associated pleural lymphoma. A case evolving from T-cell-rich lymphoid infiltration to overt B-cell lymphoma in association with Epstein-Barr virus.
Ibuka T, Fukayama M, Hayashi Y, Funata N, Koike M, Ikeda T, Mizutani S.
Department of Chemotherapy, Tokyo Metropolitan Komagome Hospital, Japan.
Cancer 1994 Feb 1;73(3):738-44 Abstract quote
BACKGROUND. Pyothorax-associated pleural lymphomas (PAPL) occur in patients with long-standing pyothorax. Epstein-Barr virus (EBV) plays an important role in its development.
METHODS. An atypical case of PAPL is reported and its clinical features are compared with those of five cases of ordinary PAPL.
RESULTS. The histology of the lymphoma changed from prominent T-cell infiltration to an overt B-cell lymphoma of diffuse, large cell-type. DNA studies of the lymphoma at the first presentation demonstrated dual rearrangement in the T-cell receptor beta (TCR beta) and immunoglobulin heavy chain J region (IgJH) genes. EBV genome analysis demonstrated monoclonal expansion of EBV-infected cells. EBV gene products were present only in large lymphocytes with B-cell phenotype. The same rearranged band of the IgJH gene, but not clonal rearrangement of the TCR beta gene, was observed in the overt B-cell lymphoma at the relapse. The same EBV-infected clone was observed throughout the course of the disease. The tumor was localized at the pyothorax wall, and cell-mediated immunity, reflected by a positive tuberculin reaction, was preserved only in the current case.
CONCLUSIONS. T-cell-rich lymphoid infiltration in the current case is a variant of EBV-associated PAPL, which is infiltrated by reactive T-cells with clonal accentuation. This is the first documented case of EBV-associated PAPL evolving from T-cell-rich lymphoid infiltration.
Department of Pathology, Osaka University, School of Medicine, Japan.
Int J Hematol 1996 Dec;65(1):9-16 Abstract quote
In 1987, we reported three patients with pleural lymphoma developed after a 22-30 year history of pyothorax resulting from artificial pneumothorax for the treatment of pulmonary tuberculosis or tuberculous pleuritis.
Based on the pathologic and epidemiologic studies, we regarded the chronic pyothorax (CP) to be etiologically important in the development of pleural lymphoma. Through a nation-wide study in Japan, 37 cases of pleural lymphoma were collected. Pleural lymphoma had developed during the 20 year history of CP in all patients.
Histologically all were non-Hodgkin's lymphoma with the diffuse large cell type being the most common. Immunologic and immunohistochemical studies revealed that 32 out of 33 cases were of B-cell lymphoma. From these findings, we proposed the term pyothorax-associated lymphoma (PAL).
We examined the presence of Epstein-Barr virus (EBV) genome on the paraffin-embedded specimens in 34 PAL cases and 16 cases of CP alone. Combined polymerase chain reaction (PCR), in situ hybridization, and immunohistochemistry revealed that the EBV genome was detected in lymphoma cells in all PAL, but only one of the cases with CP alone.
These findings suggested the etiological role of EBV for the development of PAL. We also described here the character of cell lines established from PAL, association of PAL with Kaposi's sarcoma-associated herpes virus, results of a case-control study on risk factors for development of PAL, and p53 mutations.
Appearance of a different clone of Epstein-Barr virus genome in recurrent tumor of pyothorax-associated lymphoma (PAL) and a mini-review of PAL.
Kanno H, Ohsawa M, Iuchi K, Nakatsuka S, Yamamoto S, Nishioka M, Aozasa K.
Department of Pathology, Osaka University Medical School, Suita, Japan.
Leukemia 1998 Aug;12(8):1288-94 Abstract quote
A case of pyothorax-associated lymphoma (PAL) is reported. A 76-year-old Japanese man developed a lymphoma in the pleural cavity after 46 years duration of pyothorax due to pulmonary tuberculosis. The histologic diagnosis of biopsy specimen was diffuse large cell lymphoma of B cell type.
The lymphoma cells contained the monoclonal Epstein-Barr virus (EBV) determined by the analysis of terminal repeat of EBV genome and expressed EBV nuclear antigen 2 and latent membrane protein 1 (LMP1). He received antineoplastic chemotherapy and was induced to complete remission (CR). After 19 months of CR, the lymphoma developed again in the thoracic wall.
Histopathology and immunohistochemical phenotypes of recurrent tumor were almost the same as those of the primary tumor with the exception of a little more frequent expression of LMP1. The EBV genome in lymphoma cells was monoclonal, however, the clone was different from that of the primary tumor. After antineoplastic chemotherapy, minor EBV-positive clones in primary lymphoma might survive and develop into recurrent tumor.
These results suggest that the PAL starts as poly- or oligoclonal proliferation of B lineage cells. This poly- or oligoclonality of PAL at the initial stage may suggest underlying immunosuppressive conditions in the development of PAL.
Epstein-Barr virus (EBV)-positive pyothorax-associated lymphoma (PAL): chromosomal integration of EBV in a novel CD2-positive PAL B-cell line.
Daibata M, Taguchi T, Nemoto Y, Saito T, Machida H, Imai S, Miyoshi I, Taguchi H.
Departments of Medicine, Anatomy and Microbiology, Kochi Medical School, Kochi, Japan.
Br J Haematol 2002 Jun;117(3):546-57 Abstract quote
Pyothorax-associated lymphoma (PAL) is a clinico-pathological entity arising in the pleural cavity of patients with long-standing inflammatory pyothorax. PAL is closely associated with Epstein-Barr virus (EBV), but how this virus contributes to the development of the lymphoma is unknown.
We have successfully obtained a novel EBV-infected PAL cell line, designated Pal-1. The cell line and its source coexpressed CD2 and CD20 molecules, but other representative B- and T-cell markers such as CD1, CD3, CD5, CD7, CD10 and CD19 were not found. The B-cell origin of Pal-1 cells was proven by rearrangement of the immunoglobulin heavy- and light-chain genes without rearranged T-cell receptor genes. Both the cell line and primary tumour cells carried monoclonal EBV genome. Although EBV genome is known to be maintained as circular extrachromosomal DNA, neither circular nor linear extrachromosomal EBV DNA was detectable in Pal-1 cells by in situ lysis gel analysis. Fluorescence in situ hybridization demonstrated viral integration at a marker chromosome mostly consisting of the centromere region of chromosome 1.
The viral integration event may enhance a chromosomal instability at the insertion site. This cell line represents the first example of EBV integration in PAL and could enable the study of the potential role of integrated viral infection in the development of PAL as well as mechanism of the aberrant phenotype expression.
HUMAN HERPES VIRUS-8
Expression profile of human herpesvirus 8 (HHV-8) in pyothorax associated lymphoma and in effusion lymphoma.
O'Donovan M, Silva I, Uhlmann V, Bermingham N, Luttich K, Martin C, Sheils O, Killalea A, Kenny C, Pileri S, O'Leary JJ.
Department of Histopathology, The Coombe Women's Hospital and Trinity College, Dublin, Ireland.
Mol Pathol 2001 Apr;54(2):80-5 Abstract quote
AIMS: Pyothorax associated lymphoma (PAL) occurs in a clinical setting of longstanding pyothorax or chronic inflammation of the pleura. Like primary effusion lymphoma, it has an association with Epstein-Barr virus (EBV), and is confined to the pleural cavity, but has differing morphological and phenotypic features. Human herpesvirus 8 (HHV-8) has been consistently reported in primary effusion lymphoma. This study examines the immunophenotype of two European cases of PAL, investigates the presence of HHV-8 and its expression profile, and assesses whether PAL is similar to other effusion lymphomas.
METHODS: Material was obtained from two European cases of PAL. Immunocytochemical analysis was performed using antibodies against CD45, CD20, CD79a, CD45RAA, CD3, CD43, CD45RO (UCHL1), CD30, BCL-2, CD68, epithelial membrane antigen (EMA), BCL-6, p53, Ki-67, kappa light chain, lambda light chain, and the EBV antigens latent membrane protein 1 (LMP-1) and EBV encoded nuclear antigen 2 (EBNA-2). The cases were examined for HHV-8 by means of polymerase chain reaction in situ hybridisation (PCR-ISH), solution phase PCR, in situ hybridisation (ISH), and real time quantitative TaqMan PCR to HHV-8 open reading frame 26 (ORF-26) and viral (v) cyclin encoding regions. The expression profile of HHV-8 in PAL and in BC-1 and BC-3 cells was assessed by RNA TaqMan PCR to the HHV-8 genes encoding v-cyclin, v-IL-6, and G protein coupled receptor (GPCR).
RESULTS: Both cases expressed CD24, CD20, CD79a, BCL-2, light chain restriction, and high Ki-67 staining. EBV was identified by EBER-ISH in one case. HHV-8 was not identified by solution phase PCR, but was detected by PCR-ISH (sensitivity of 1 viral genome copy/cell) in 35% of the cells and by TaqMan PCR, which showed 50-100 HHV-8 copies/2,000 cell genome equivalents (sensitivity of 1 viral genome in 10(6) contaminating sequences). HHV-8 v-IL-6, v-cyclin, and GPCR encoded transcripts were identified using RNA TaqMan PCR. v-IL-6 was high in PAL and in BC-1 and BC-3 cells.
CONCLUSION: The presence of HHV-8 in one of two patients with PAL raises interesting questions in relation to the pathobiology of the condition. Clearly, the results indicate that HHV-8 is not an obligate pathogen, necessary for the effusion phenotype, but might contribute to it by its secretion of specific cytokines.
CHARACTERIZATION RADIOLOGIC Chronic pleural effusion LABORATORY MARKERS
CHARACTERIZATION GENERAL Arise in the pleural
Adv Anat Pathol. 2005 Nov;12(6):324-31. Abstract quote
Pyothorax-associated lymphoma (PAL) is a non-Hodgkin lymphoma of exclusively B-cell phenotype developing in the pleural cavity of patients after more than 20-year history of pyothorax resulting from an artificial pneumothorax for the treatment of pulmonary tuberculosis or tuberculous pleuritis.
The most common symptoms on admission are chest pain and fever. Serum neuron-specific enolase level suggesting a diagnosis of small cell lung cancer is occasionally elevated. Histologically PAL usually shows a diffuse proliferation of large cells of B-cell type (diffuse large B-cell lymphoma [DLBL]). In PAL cells, representative B-cell markers other than CD20 are frequently negative with aberrant expression of T-cell markers such as CD2. A gene expression profile of PAL is distinct from nodal DLBL in its higher expression level of interferon-inducible genes. PAL is strongly associated with Epstein-Barr virus (EBV) infection with expression of EBV latent genes such as EBNA-2, LMP-1, together with EBNA-1. Taken together, PAL is a distinct entity both in its clinicopathologic presentation as well as its gene expression profile.
Use of an artificial pneumothorax, EBV infection, and cytokines and reactive oxygen species produced in longstanding pyothorax might be important factors for PAL development.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL Large cell lymphomas, often with plasmacytoid differentiation VARIANTS
CHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE
Pyothorax-associated lymphoma. An unusual case with biphenotypic character of T and B cells.
Mori N, Yatabe Y, Narita M, Kobayashi T, Asai J.
First Department of Pathology, Nagoya University School of Medicine, Japan.
Am J Surg Pathol 1996 Jun;20(6):760-6 Abstract quote
Pyothorax-associated lymphoma is known to develop in patients who received an artificial pneumothorax for pulmonary tuberculosis some 30 to 40 years previously. Such patients exhibit large, immunoblastic lymphoma cells and often have a B-cell phenotype.
We present a patient with an artificial pneumothorax and such a late developing lymphoma but with the unique finding of aberrant T- and B-cell phenotypes. Southern blot hybridization using immunoglobulin gene JH and T-cell receptor beta chain receptors revealed germline configurations. Lymphomas developing in immunocompromised patients, such as those with acquired immunodeficiency syndrome, may show such unusual phenotypes.
The unusual phenotypes found in this patient provide evidence that his pyothorax-associated lymphoma was related to an immunocompromised state.
Pyothorax-associated lymphoma: a peculiar clinicopathologic entity derived from B cells at late stage of differentiation and with occasional aberrant dual B- and T-cell phenotype.
Petitjean B, Jardin F, Joly B, Martin-Garcia N, Tilly H, Picquenot JM, Briere J, Danel C, Mehaut S, Abd-Al-Samad I, Copie-Bergman C, Delfau-Larue MH, Gaulard P.
Departement de Pathologie and EA2348, Hopital Henri Mondor, AP-HP, Creteil, France.
Am J Surg Pathol 2002 Jun;26(6):724-32 Abstract quote
We report 12 European cases of pyothorax-associated lymphomas occurring 30-67 years following artificial pneumothorax for pleuropulmonar tuberculosis.
Eleven patients presented with a localized pleural tumor mass, whereas one patient also had liver involvement. Histologic examination showed a diffuse proliferation of large lymphoid cells with frequent plasmacytoid differentiation (n = 8), expressing CD20 (n = 10), CD79a (n = 11), and/or CD138 (n = 5) B-cell antigens. Aberrant expression of T-cell markers (CD2, CD3, CD4) was noted in five cases. The B-cell origin of lymphoma cells was confirmed by the demonstration of immunoglobulin light chain restriction or clonal B cell population in six cases. In 11 of 12 cases in situ hybridization disclosed Epstein-Barr virus genome in most tumor cells and immunohistochemistry a type III LMP-1+/ EBNA-2+ latency profile. HHV-8/ORF73 antigen was not detected in all tested cases (n = 11). All investigated cases (10 of 10) disclosed a uniform CD10-/BCL-6-/MUM1+/CD138+/- phenotype, consistent with a derivation from late germinal center (GC)/post-GC B cells. Clinical outcome was poor with a median survival time of 5 months. Only one patient was in complete remission after 34 months.
This study further confirms that pyothorax-associated lymphoma represents a distinct clinicopathologic entity among diffuse large B-cell lymphoma, which is characterized by a peculiar clinical presentation, frequent plasmacytoid features, and a strong association with EBV. Moreover, we show that this lymphoma entity likely originates from B cells at a late stage of differentiation and occasionally shares an aberrant dual B/T phenotype.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES T-CELL RICH B-CELL LYMPHOMA
T-cell-rich large B-cell lymphoma. A study of 30 cases, supporting its histologic heterogeneity and lack of clinical distinctiveness.
Krishnan J, Wallberg K, Frizzera G.
Department of Hematopathology, Armed Forces Institute of Pathology, Washington, D.C.
Am J Surg Pathol 1994 May;18(5):455-65 Abstract quote
To determine whether correlations existed between morphologic and immunophenotypic findings and clinical characteristics, 30 cases of T-cell-rich large B-cell lymphomas (TBL) were evaluated by histopathology, immunostaining, and polymerase chain reaction on paraffin-embedded material.
All were characterized by a polymorphic cell composition, including a variable mixture of small and large lymphoid cells and reactive cell. Most cases (87%) fitted into one of three main histologic types of non-Hodgkin's lymphoma (diffuse, mixed cell; diffuse, large cell; follicular and diffuse, mixed cell), and one group of eight cases had the prototypic features described by Ramsay et al. (17). All cases showed a component of large CD20(L26)+ MB2+ B cells in a predominant back-ground of reactive T cells (> 50% of the total lymphoid forms). Clonality was demonstrated by light chain restriction in 67% of cases and by rearrangement of the immunoglobulin heavy chain gene and bcl-2 gene in 64% and 28% of cases, respectively. The patients were predominantly men (70%), ages 18-83 years (median of 62.5), and were initially seen predominantly with nodal disease (and extranodal involvement in 20%) at advanced stages (III-IV: 77%). Treatment was mostly aggressive chemotherapy, and the outcomes were favorable (84% alive and well).
These features are not distinctive as compared with those of typical large-cell lymphoma, nor did subgroups within the series (prototypic cases versus others; cases with less [< or = 70%] or more [> 70%] T-cell infiltration) significantly differ in clinical presentation or outcome. Thus, this study confirms that TBL, while useful as a diagnostic variant to be distinguished from both peripheral T-cell lymphoma and Hodgkin's disease, is a heterogeneous assortment of diverse histopathologic categories rather than a clinicopathologic entity. The term "T-cell rich" might, however, be usefully retained as a morphologic specification to be added to recognized histologic categories of lymphoma.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSTIC FACTORS TREATMENT Therapy for a large B-cell lymphoma
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