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1.  Primary pleural lymphoma: a rare case and a synopsis of the literature 
Journal of Thoracic Disease  2013;5(4):E121-E123.
We report a case of a 74-year-old woman with no history of HIV infection or pyothorax who presented with progressive dyspnoea. Computed tomography (CT) showed bulky pleural mass and pleural effusion associated with the right-sided pleural disease. Thoracoscopic pleural biopsy was performed and revealed the diagnosis of primary pleural malignant lymphoma. Histopathological and immunohistochemical examinations revealed that it was small B-cell lymphoma with neoplastic cells that expressed the CD-20 antigen. This case is thought to be a very rare case of primary malignant lymphoma arising in the pleura of a patient with no history of pyothorax.
PMCID: PMC3755660  PMID: 23991319
Primary pleural lymphoma; thoracoscopic pleural biopsy
2.  Primary Effusion Lymphoma in an Elderly HIV-Negative Patient with Hemodialysis: Importance of Evaluation for Pleural Effusion in Patients Receiving Hemodialysis 
Pleural effusion is a ubiquitous complication in hemodialysis (HD) patients. Common etiologies of pleural effusion in this patient group are heart failure, volume overload, parapneumonic effusion, tuberculotic pleuritis, and uremic pleuritis. Although thoracentesis is a useful diagnostic method of pleural effusion, empirical reduction of the dry weight is often attempted without thoracentesis because pleural effusion is commonly caused by volume overload and responds to the dry-weight reduction. However, this empiricism has a risk of overlooking or delaying the diagnosis of potentially fatal etiologies that need specific treatments. We report an 86-year-old human immunodeficiency virus (HIV)-negative male on HD with primary effusion lymphoma (PEL), a large-cell non-Hodgkin lymphoma presenting with characteristic lymphomatous effusions in the absence of solid tumor masses, which is in association with human herpes virus 8 (HHV8) infection in immunocompromised individuals. The patient presented with left-sided pleural effusion. This is the first case report of PEL developing in a patient receiving HD. Thoracentesis and cytological analysis of the effusion was key to the diagnosis. We also review the literature regarding pleural effusion in HD patients. Further, we examine Kaposi's sarcoma herpes virus/HHV8-negative effusion-based lymphoma, a newly proposed distinct lymphoma that clinically and cytomorphologically resembles PEL, because it can be cured without chemotherapy. This report may arouse clinicians’ attention regarding the importance of evaluation for pleural effusion in HD patients, especially when the effusion or symptoms associated with pleural effusion are refractory to volume control.
PMCID: PMC4067712  PMID: 24987405
Primary effusion lymphoma; Thoracentesis; Kaposi's sarcoma herpes virus/human herpes virus 8-negative effusion-based lymphoma; Primary effusion lymphoma-like lymphoma; Hemodialysis; Human herpes virus 8
3.  Clinical history of HIV infection may be misleading in cytopathology 
CytoJournal  2010;7:7.
Human immunodeficiency virus (HIV)-infected patients are at an increased risk for developing opportunistic infections, reactive conditions and neoplasms. As a result, a broad range of conditions are frequently included in the differential diagnosis of HIV-related lesions. The clinical history of HIV infection may, however, be misleading in some cases. Illustrative cases are presented in which knowledge of a patient's HIV status proved to be misleading and increased the degree of complexity of the cytologic evaluation. Case 1 involved the fine needle aspiration (FNA) of a painful 3 cm unilateral neck mass in a 38-year-old female with generalized lymphadenopathy. Her aspirate revealed a spindle cell proliferation devoid of mycobacteria that was immunoreactive for S-100 and macrophage markers (KP-1, PGM1). Multiple noncontributory repeat procedures were performed until a final excision revealed a schwannoma. Case 2 was a CT-guided FNA of a positron emission tomography positive lung mass in a 53-year-old man. The acellular aspirate in this case contained structures resembling fungal spore forms that were negative for mucicarmine and GMS stains, as well as cryptococcal antigen immunocytochemistry. A Von Kossa stain confirmed that these pseudo-fungal structures were calcified debris. Follow up revealed multiple calcified lung and hilar node based granulomata. Case 3 involved the cytologic evaluation of pleural fluid from a 47-year-old man with Kaposi sarcoma and recurrent chylous pleural effusions. Large atypical cells identified in his effusion were concerning for primary effusion lymphoma. Subsequent pleural biopsy revealed extramedullary hematopoiesis, documenting these atypical cells as megakaryocytes. These cases demonstrate that knowledge of a patient's HIV status can be misleading in the evaluation of cytology specimens, with potential for misdiagnosis and/or multiple procedures. To avoid this pitfall in the setting of HIV infection, common entities unrelated to HIV infection and artifacts should always be included in the differential diagnosis.
PMCID: PMC2895884  PMID: 20607096
AIDS; cytology; HIV; misleading
4.  Thymic mucosa-associated lymphoid tissue lymphoma involving lymph nodes 
Thymic mucosa-associated lymphoid tissue (MALT) lymphoma involving lymph nodes is quite rare with only 13 previous cases reported in the literature.
The 33-years-old female was referred to our department for the investigation of abnormalities on computed tomographic (CT) scans. CT scans showed a 9-cm × 3-cm mass composed of a mixture of soft tissue and fat at the anterior mediastinum with lymphadenopathy in the neck, axillary and mediastinal regions. She was underwent complete surgical resection of the mass with regional lymph node dissection through a median sternotomy. Histological examination of the surgical specimens confirmed the diagnosis of MALT lymphoma arising in the thymus with nodal metastasis. She achieved complete remission after postoperative rituximab combined chemotherapy.
Thymic MALT lymphoma occurs most frequently in Asian female aged 40–60 years and commonly appears anterior mediastinal masses on CT scans. The excised tissue is necessary to confirm the accurate histological diagnosis. The disease usually remains localized for a long time, making local surgical resection highly effective. However, when the lymph nodes are involved, effective treatment approaches of the disease is still undefined.
We report a case of thymic MALT lymphoma involving lymph nodes, in which the patient was successfully treated with primary site resection with regional lymph node dissection followed by rituximab combined chemotherapy. Surgery provided not only a useful approach for collecting tissue for an accurate histological diagnosis, but also an effective local treatment, even in the case of advanced-stage thymic MALT lymphoma.
PMCID: PMC3604650  PMID: 23333805
Mucosa-associated lymphoid tissue lymphoma; Thymus; Thymectomy; Rituximab
5.  Pleural effusions in patients with AIDS 
Sexually Transmitted Infections  2000;76(2):122-125.
Objective: To describe the range of pathology causing pleural effusions in HIV infected patients with acute respiratory episodes and to attempt to identify whether any associated radiological abnormalities enabled aetiological discrimination.
Methods: Prospective study of chest radiographs of 58 consecutive HIV infected patients with pleural effusion and their microbiological, cytological, and histopathological diagnoses.
Results: A specific diagnosis was made in all cases. Diagnoses were Kaposi's sarcoma, 19 patients; parapneumonic effusion, 16 patients; tuberculosis, eight patients; Pneumocystis carinii pneumonia, six patients; lymphoma, four patients; pulmonary embolus, two patients; and heart failure, aspergillus/leishmaniasis, and Cryptococcus neoformans, one case each. Most effusions (50/58) were small. Bilateral effusions were commoner in Kaposi's sarcoma (12/19) and lymphoma (3/4) than in parapneumonic effusion (3/16). Concomitant interstitial parenchymal shadowing did not aid discrimination. A combination of bilateral effusions, focal air space consolidation, intrapulmonary nodules, and/or hilar lymphadenopathy suggests Kaposi's sarcoma. Unilateral effusion with focal air space consolidation suggests parapneumonic effusion if intrapulmonary nodules are absent: if miliary nodules and/or mediastinal lymphadenopathy are detected, this suggests tuberculosis.
Conclusions: A wide variety of infectious and malignant conditions cause pleural effusions in HIV infected patients, the most common cause in this group was Kaposi's sarcoma. The presence of additional radiological abnormalities such as focal air space consolidation, intrapulmonary nodules, and mediastinal lymphadenopathy aids aetiological discrimination.
Key Words: pleural effusion; Kaposi's sarcoma; bacterial pneumonia; chest radiograph
PMCID: PMC1758298  PMID: 10858714
6.  Primary peritoneal adenocarcinoma causes pleural effusion 
The most common malignancies associated with malignant pleural effusions are carcinomas of the breast, lung, gastrointestinal tract, ovary and lymphomas. Primary peritoneal adenocarcinoma is a very rare cause of malignant pleural effusion.
Case Report:
A 72-year old female patient presented to us with shortness of breath for the last 2 months. A contrast-enhanced computed tomography (CECT) scan of her-thorax revealed only bilateral pleural effusion with absence of any mass lesion or any mediastinal lymphadenopathy. A cytologic examination of pleural fluid revealed adenocarcinoma cells. A CECT of her abdomen and pelvis revealed heterogenous thickening of omentum with nodular appearances and small amount of ascites. Her ovaries were normal and no other mass lesion was detected. A histological examination of a peritoneal lesion was suggestive of adenocarcinoma.
The patient was diagnosed with a rare case of primary peritoneal adenocarcinoma with bilateral pleural effusion.
PMCID: PMC3347636  PMID: 22574304
Malignant pleural effusion; primary peritoneal adenocarcinoma
7.  Usefulness of 18F-FDG positron emission tomography/computed tomography for the diagnosis of pyothorax-associated lymphoma: A report of three cases 
Oncology Letters  2010;1(5):833-836.
Pyothorax-associated lymphoma (PAL) is a unique and rare non-Hodgkin's lymphoma developing in the pleural cavity following a long-standing history of chronic pyothorax (CP). The development of F-18 2′-deoxy-2fluoro-D-glucose (FDG) positron emission tomography combined with computed tomography (PET/CT) has contributed to the evaluation of lymphoma staging. However, only a few studies describing FDG-PET/CT findings in PAL have been published. This study reported three cases of PAL; all 3 patients had previously undergone artificial collapse therapy for pulmonary tuberculosis. Both the first case (an 84-year-old male) and second case (an 83-year-old male) complained of abdominal pain. An ultrasound scan revealed a mass shadow in the left chest wall without abnormal findings in the abdomen, and the CT and magnetic resonance imaging scans suggested malignant lymphoma of the left chest. FDG-PET/CT imaging showed extremely intense FDG uptake only in the left pleura and chest wall. Diagnosis was CP in the two patients, showing a high maximum standardized uptake value (SUVmax: early, 14.8 and delayed, 19.4 in the first case; early, 20.8 and delayed, 27.3 in the second case, respectively). Histopathological analysis of the specimens obtained by biopsy of the PET/CT-positive pleural mass showed non-Hodgkin's, diffuse large B cell lymphoma in the two cases. The third case was a 79-year-old male with relapse after right pleuropneumonectomy for PAL (diffuse large B cell lymphoma) 4 years earlier. PET/CT showed intense FDG uptake (SUVmax: early, 19.9 and delayed, 35.7) in the right pleura and chest wall. Diagnosis was CP, suggesting the recurrence of PAL. Furthermore, abnormal intense FDG uptake was noted in the hilar, mediastinal and supraclavicular lymph nodes, as well as in the spleen. In conclusion, FDG-PET/CT imaging is useful in the evaluation of the area of invasion in PAL.
PMCID: PMC3436407  PMID: 22966389
pyothorax-associated lymphoma; positron emission tomography combined with computed tomography; F-18 2′-deoxy-2fluoro-D-glucose; pulmonary tuberculosis; non-Hodgkin's lymphoma
8.  Primary Spinal Marginal Zone Lymphoma Relapse at a Different Spinal Level after Remission of the Primary Lesion 
Global Spine Journal  2013;3(4):261-264.
Study Design Case report.
Objective Most spinal lymphomas occur in the context of systematic lymphomas. Marginal zone lymphoma (MZL) is a type of B-cell lymphoma originating from the marginal zone of B-cell follicles. Mucosa-associated lymphoid tissue (MALT) lymphoma is a type of extranodal MZL and rarely occurs in the central nervous system. To date, there has been only one case report of primary spinal MALT lymphoma and there are no case reports of relapsed MALT lymphoma at a different location of the spine.
Results A 58-year-old man complained of gait disturbance and urinary dysfunction. Magnetic resonance images showed an abnormal lesion in the epidural space at T11–L1 compressing the conus medullaris. The patient underwent laminectomy and partial resection of the tumor. Histopathologic and immunohistochemical findings were consistent with MALT lymphoma. Following postoperative radiotherapy, the epidural mass disappeared completely. Three years later, epidural MALT lymphoma at a different location in the thoracic spine (T8–T10) occurred and caused myelopathy again. Histologic diagnosis of the relapsed tumor was the same as had been seen 3 years previously.
Conclusions This is the first case report of relapsed spinal MALT lymphoma at a different location of the thoracic spine. Though the prognosis of MALT lymphoma is fairly good, careful follow-up is needed to screen any relapse or transformation to a high-grade lymphoma.
PMCID: PMC3854575  PMID: 24436880
spinal tumors; epidural tumor; spinal marginal cell lymphoma; MALT lymphoma; thoracic spine
9.  Primary effusion lymphoma associated with Human Herpes Virus-8 and Epstein Barr virus in an HIV-infected woman from Kampala, Uganda: a case report 
Primary effusion lymphoma is a recently recognized entity of AIDS related non-Hodgkin lymphomas. Despite Africa being greatly affected by the HIV/AIDS pandemic, an extensive MEDLINE/PubMed search failed to find any report of primary effusion lymphoma in sub-Saharan Africa. To our knowledge this is the first report of primary effusion lymphoma in sub-Saharan Africa. We report the clinical, cytomorphologic and immunohistochemical findings of a patient with primary effusion lymphoma.
Case presentation
A 70-year-old newly diagnosed HIV-positive Ugandan African woman presented with a three-month history of cough, fever, weight loss and drenching night sweats. Three weeks prior to admission she developed right sided chest pain and difficulty in breathing. On examination she had bilateral pleural effusions.
Haematoxylin and eosin stained cytologic sections of the formalin-fixed paraffin-embedded cell block made from the pleural fluid were processed in the Department of Pathology, Makerere University, College of Health Sciences, Kampala, Uganda. Immunohistochemistry was done at the Institute of Haematology and Oncology "L and A Seragnoli", Bologna University School of Medicine, Bologna, Italy, using alkaline phosphatase anti-alkaline phosphatase method. In situ hybridization was used for detection of Epstein-Barr virus.
The tumor cells were CD45+, CD30+, CD38+, HHV-8 LANA-1+; but were negative for CD3-, CD20-, CD19-, and CD79a- and EBV RNA+ on in situ hybridization. CD138 and Ki-67 were not evaluable. Our patient tested HIV positive and her CD4 cell count was 127/μL.
A definitive diagnosis of primary effusion lymphoma rests on finding a proliferation of large immunoblastic, plasmacytoid and anaplastic cells; HHV-8 in the tumor cells, an immunophenotype that is CD45+, pan B-cell marker negative and lymphocyte activated marker positive. It is essential for clinicians and pathologists to have a high index of suspicion of primary effusion lymphoma when handling HIV positive patients who have effusions without palpable tumor masses. Basic immunohistochemistry is essential for definitive diagnosis.
PMCID: PMC3048476  PMID: 21320326
10.  Malignant lymphoma of the urinary bladder: a clinicopathological study of 11 cases 
Journal of Clinical Pathology  2000;53(6):458-461.
Aim—To report the clinical and histological features and outcome of primary and secondary malignant lymphomas of the urinary bladder.
Methods—Eleven cases of malignant lymphoma of the urinary bladder were obtained from the registry of cases at St Bartholomews and the Royal London Hospitals. The lymphomas were classified on the basis of their morphology and immunophenotype, and the clinical records were reviewed.
Results—There were six primary lymphomas: three extranodal marginal zone lymphomas of mucosa associated lymphoid tissue (MALT) type and three diffuse large B cell lymphomas. Of the five secondary cases, four were diffuse large B cell lymphomas, one secondary to a systemic follicular follicle centre lymphoma, and one nodular sclerosis Hodgkins disease. Four patients with secondary lymphoma for whom follow up was available had died of disease within 13 months of diagnosis. Primary lymphomas followed a more indolent course. In one case, there was evidence of transformation from low grade MALT-type to diffuse large B cell lymphoma. The most common presenting symptom was haematuria. Cystoscopic appearances were of solid, sometimes necrotic tumours resembling transitional cell carcinoma, and in one case the tumours were multiple. These cases represented 0.2% of all bladder neoplasms.
Conclusions—Diffuse large B cell lymphoma and MALT-type lymphoma are the most common primary malignant lymphomas of the bladder. Lymphoepithelial lesions in MALT-type lymphoma involve transitional epithelium, and their presence in high grade lymphoma suggests a primary origin owing to transformation of low grade MALT-type lymphoma. Primary and secondary diffuse large B cell lymphomas of the bladder are histologically similar, but the prognosis of the former is favourable.
Key Words: bladder • lymphoma • mucosa associated lymphoid tissue lymphoma
PMCID: PMC1731210  PMID: 10911804
11.  A distinctive colour associated with high iodine content in malignant pleural effusion from metastatic papillary thyroid cancer: a case report 
Pleural effusions are a common clinical problem and affect about one million people in the United States and United Kingdom each year. Over 60 causes of pleural effusion have been identified; establishing the definitive aetiology can be difficult, and often requires invasive procedures. Guidelines state that macroscopic examination of the fluid should be the first step in determining the aetiology of a pleural effusion. Papillary thyroid carcinoma is an uncommon cause of malignant pleural effusion, with only 10 cases reported in the literature, their physical characteristics and composition having been rarely described. We describe for the first time a distinctive brown colour of the malignant effusion (despite centrifugation) from a rare case of metastatic papillary thyroid cancer to the pleura, associated with a high pleural fluid iodine content. Such a characteristic may be useful in expediting diagnosis of a malignant pleural effusion in the appropriate clinical context.
Case presentation
We present the case of a 71-year-old Caucasian man with metastatic papillary thyroid cancer; a large, long-standing, right-sided pleural effusion and a 83-fold higher pleural thyroglobulin level compared to corresponding serum, supporting this malignancy as the cause of the patient’s effusion. The pleural fluid had a distinctive pigmentation similar to iodine-containing antiseptic preparations. Biopsy during medical thoracoscopy confirmed metastatic papillary thyroid carcinoma. Analysis of pleural fluid showed a pleural thyroglobulin level over 80 times that of serum levels (29,000μg/L versus 350ug/L). Pleural fluid iodine content was 23,000ug/L and may account for the fluid’s distinctive pigment, as iodine is an essential component in thyroglobulin and thyroid hormone synthesis.
Pleural fluid pigmentation may aid diagnosis in the appropriate clinical setting. A distinctive iodine-like brown colour of pleural fluid may represent elevated iodine content and should raise consideration of metastatic thyroid cancer as a cause for a pleural effusion.
PMCID: PMC3680221  PMID: 23724969
Pleural effusion; Iodine; Thyroglobulin; Diagnosis; Thyroid; Carcinoma; Colour
12.  Somatostatin-receptor scintigraphy for staging and follow-up of patients with extraintestinal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT)-type 
British Journal of Cancer  2001;85(10):1462-1466.
The majority of lymphomas of the mucosa-associated lymphoid tissue (MALT)-type arise in the stomach, but extragastric locations are also frequently encountered. Due to previous results indicating that somatostatin receptor (SSTR)-expression distinguishes between gastric and extragastric MALT-type lymphoma, we have initiated a study to evaluate the role of SSTR-scintigraphy for staging and follow-up of patients with extragastric manifestations of MALT-type lymphoma. A total of 30 consecutive patients, including 24 with primary extragastric MALT-type lymphoma, 5 patients with dissemination to extragastric sites (including colon, lung, parotid, ocular adnexa and breast) following an initial gastric MALT-lymphoma and one patient with spread to stomach, lung and lymph nodes following parotid lymphoma were prospectively studied. All patients had histologically verified MALT-type lymphoma: 2 patients had lymphoma presenting in the lung, 9 in the ocular adnexa, 7 had lymphomas in the parotid, 2 patients had disease located in the breast, 3 patients had lymph-node relapse following MALT-type lymphoma of the parotid, the lacrimal gland and the thyroid, and 1 had primary MALT-lymphoma of the liver. All patients underwent SSTR-scintigraphy using 111In-DTPA-D-Phe1-Octreotide (111In-OCT) before initiation of therapy, while 13 also had a second scan after treatment. The results of gamma camera imaging were compared to conventional staging. No positive scans could be obtained in patients with dissemination following gastric lymphoma, while all patients with primary extragastric lymphoma had positive scans at the site of histologically documented involvement before initiation of therapy. In addition, also the patient with secondary spread to stomach, lung and lymph nodes was positive in all documented lymphoma sites. In one patient, focal tracer uptake in projection to the maxillary sinus was documented, which was bioptically verified as inflammation. In the scans performed after therapy, focal tracer accumulation in the left orbit indicated persistance of disease following irradiation in one patient with otherwise negative work-up, which was verified by MRI and biopsy 6 months later. In another patient, a positive scan indicated disease relapse in the lacrimal gland 9 months before clinical verification by means of ultrasound. In one patient, a focus not present in the pretherapeutic scan was found in the ethmoidal sinus, corresponding to a hyperplastic polyp. Both SST-scan as well as CT indicated disease persistance in one case, while negative scans corresponding to complete remission as judged by conventional staging were obtained following therapy in the remaining patients, and absence of relapse has been confirmed for a median follow-up of 2 years. These results indicate that 111In-OCT is an excellent tool for staging and non-invasive therapy-monitoring in extragastric MALT-type lymphomas. These data further confirm our initial finding that gastric MALT-type lymphomas do not express relevant amounts of respective SSTR, and that SSTR-scanning is able to distinguish between gastric vs extragastric origin of MALT-type lymphoma irrespective of the site of presentation.© 2001 Cancer Research Campaign
PMCID: PMC2363931  PMID: 11720429
somatostatin; extraintestinal MALT-lymphoma; scintigraphy
13.  Thyroid Lymphoma: Recent Advances in Diagnosis and Optimal Management Strategies 
The Oncologist  2013;18(9):994-1003.
Primary thyroid lymphoma is rare, and there are limited numbers of randomized or prospective trials to guide management, thus controversy remains over optimal treatment. The aim of this paper is to discuss the changes in diagnostic modalities and to focus on the recent alterations in the management of this rare disease, including targeted therapies as well as the more limited role of the endocrine surgeon.
Learning Objectives
Explain the diagnostic modalities used to diagnose primary thyroid lymphoma.Describe the role of the endocrine surgeon in the diagnosis and treatment of thyroid lymphoma.Cite the recent advances in the treatment of primary thyroid lymphoma.
Primary thyroid lymphoma is rare, composing approximately 5% of all thyroid malignancies and less than 3% of all extranodal lymphomas. It typically presents as a rapidly enlarging goiter with associated compressive symptoms. Thyroid ultrasound and fine needle aspiration cytology, using flow cytometry and immunohistochemistry, remain the main modalities used to confirm the presence of lymphoma. The increasing use of an ultrasound-guided core biopsy to achieve an accurate diagnosis has further limited the role of surgery. An open surgical biopsy may still be required not only for definitive diagnosis but also to confirm the subtype of lymphoma. There are limited numbers of randomized or prospective trials to guide management, and controversy remains over optimal treatment. Treatment and prognosis of this disease can be dichotomized into two separate groups: pure mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL) or mixed subtypes. Early stage (stage IE) intrathyroidal MALT lymphomas typically have an indolent course and may be treated with single-modality surgery, radiotherapy, or a combination of both. DLBCLs are more aggressive, and survival outcomes are highest with multimodal therapy incorporating monoclonal antibodies, chemotherapy, and radiotherapy. The prognosis is generally excellent but can be varied because of the heterogeneous nature of thyroid lymphomas. The aim of this paper is to discuss the changes in diagnostic modalities and to focus on the recent alterations in the management of this rare disease, including targeted therapies as well as the more limited role of the endocrine surgeon.
PMCID: PMC3780647  PMID: 23881987
Primary thyroid lymphoma; Thyroid; Lymphoma; Thyroid surgery; Thyroid malignancy
14.  Expression profile of human herpesvirus 8 (HHV-8) in pyothorax associated lymphoma and in effusion lymphoma 
Molecular Pathology  2001;54(2):80-85.
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, κ light chain, λ 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/2000 cell genome equivalents (sensitivity of 1 viral genome in 106 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.
PMCID: PMC1187007  PMID: 11322168
pyothorax associated lymphoma; human herpesvirus 8; primary effusion lymphoma
15.  Role of percutaneous closed needle pleural biopsy among patients of undiagnosed exudative pleural effusion 
Sometimes etiological diagnosis of pleural effusion is difficult despite cytological, biochemical and microbiological tests and labeled as undiagnosed exudative pleural effusions.Aim of present study was to make an etiological diagnosis of pleural effusion.
Materials and Methods:
Study group included patients of exudative pleural effusion where etiological diagnosis could not be yielded by conventional cytological, biochemical and microbiological investigations. Pleural tissue was obtained by Cope’s pleural biopsy needle and or thoracoscopy. Pleural biopsy was subjected to histopathology, ZN staining and culture to find the mycobacterium tuberculosis.
Out of 25 patients, 17 (68%) and 8 (32%) were male and female, respectively. Age ranged from 15 to 65 years (mean 31.72). Mean value of serum and pleural fluid LDH was 170.56 U/L and 1080.28 U/L, respectively. Histopathology of 9 (36%) showed epitheloid granuloma with caseation necrosis. In other 9 (36%) patients, epitheloid granulomas (with or without giant cells) was reported. In 5 (20%) patients, histopathology report was of nonspecific chronic inflammation. Histopathology was reported as normal in one case; it turned out to be a case of malignancy. In two (8%) patients, pleural tissue obtained was inadequate for opinions; however, other tests revealed malignancy in one and tuberculosis in other. Ziehl-Neelsen (ZN) stain was positive for AFB in two patients and culture of pleural tissue showed presence of Mycobacterium tuberculosis in three patients.
The role of percutaneous closed needle biopsy of pleura among patients of undiagnosed exudative pleural effusion is still accepted as a diagnostic tool, as this may lead to a specific diagnosis among 76% of cases. This is of particular importance in a developing country like India where the facilities of thoracoscopy and imaging guided cutting needle biopsies are not easily available.
PMCID: PMC3109830  PMID: 21712918
Closed needle pleural biopsy; pleural biopsy; undiagnosed pleural effusion
16.  A Case of Human Herpes Virus-8 Unrelated Primary Effusion Lymphoma-Like Lymphoma Presented as Pleural Effusion 
Primary effusion lymphoma (PEL) is a rare type of lymphoma that arises in the body cavity without detectable masses. It is associated with human herpes virus-8 (HHV-8), Epstein-Barr virus (EBV), and human immunodeficiency virus (HIV). Recently, PEL unrelated to viral infection has been reported and it has been termed HHV-8 unrelated primary effusion lymphoma-like lymphoma (HHV-8 unrelated PEL-like lymphoma). Here, we report a case of HHV-8 unrelated PEL-like lymphoma in an 80-year-old woman. Chest X-ray and computed tomography revealed left-sided pleural effusion. Pleural effusion analysis and mediastinoscopic biopsy showed atypical cells that had originated from the B cells. The cells were positive for CD20 and bcl-2, but negative for CD3, CD5, CD21, CD30, CD138, epithelial membrane antigen, and HHV-8. Serological tests for HIV and EBV were negative. Considering the patient's age, further treatments were not performed. She has shown good prognosis without chemotherapy for more than 18 months.
PMCID: PMC3538188  PMID: 23319997
Lymphoma, Primary Effusion; Herpesvirus 8, Human; Pleural Effusion
17.  Kappa-chain gene rearrangement in an apparent T-lineage lymphoma. 
Journal of Clinical Investigation  1986;78(6):1439-1442.
We describe a 10-yr-old boy with T-lineage non-Hodgkin's lymphoma. He had a mediastinal mass, swollen supraclavicular lymph nodes, and pleural effusion. A supraclavicular lymph node biopsy under light microscopy showed a malignant lymphoma of diffuse lymphoblastic type. Most of the cells taken from the malignant pleural effusion expressed T cell-associated antigens such as Leu-1 and OKT 8. To confirm these antigens as T-lineage lymphoma, we examined genomic DNA from malignant cells obtained from the pleural effusion. As was expected, T cell receptor beta-chain gene rearrangements were demonstrated. However, when the immunoglobulin gene organization was analyzed, we detected rearrangements in both the heavy- and kappa-chain genes. To our knowledge, this is the first case in which kappa-chain gene rearrangement was detected in apparent T-lineage cells. These findings provide important information relating to determination of the cellular lineage of lymphoid malignancy.
PMCID: PMC423886  PMID: 3097073
18.  Endocytoscopic findings of lymphomas of the stomach 
BMC Gastroenterology  2013;13:174.
The gastric lesions of various lymphomas were observed at the cellular level using endocytoscopy.
Endocytoscopy and magnifying endoscopy with narrow band imaging (NBI) were performed in 17 patients with lymphomas of the stomach. The lesions consisted of 7 with low-grade mucosa-associated lymphoid tissue (MALT), 5 with gastric involvement by adult T-cell leukemia/lymphoma (ATLL), 4 with diffuse large B-cell lymphoma (DLBCL), and 1 with peripheral T-cell lymphoma.
On conventional endoscopy, 9 were classified as having superficial spreading type, 7 were mass-forming type, and 1 was diffuse infiltrating type. Anti-H. pylori treatment was given in the 7 MALT lymphoma cases. NBI magnification endoscopy invariably showed dilatation or ballooning and destruction of gastric pits and elongation and distortion in microvessels. Endocytoscopy showed mucosal aggregation of interstitial cellular elements in almost all gastric lymphoma cases. The nuclear diversity in size and configuration was exclusively seen in gastric lymphomas other than MALT lymphoma, whereas the nuclei of MALT lymphoma cells were regular and small to moderate in size. Inter-glandular infiltration by lymphomatous cell elements was frequently observed in MALT lymphoma and DLBCL, but it was uncommon in peripheral gastric T-cell malignancies. Endocytoscopy could identify the disease-specific histology, the lymphoepithelial origin, as inter-glandular infiltration of cellular components in MALT lymphoma and the possibly related DLBCL cases. Complete regression (CR) was observed in 2 of the 7 MALT lymphoma patients. In the 2 patients with CR who underwent repeat endocytoscopy, the ultra-high magnification abnormalities returned to normal, while they were unchanged in those without tumor regression.
On endocytoscopy, intra-glandular aggregation of cellular components was invariably identified in lymphomas of the stomach. Nuclear regularity in size and configuration may indicate the cytological grade, differentiating the indolent low-grade from aggressive lymphoproliferative diseases. The inter-glandular infiltration seen on endocytoscopy can indicate the lymphoepithelial lesions seen in MALT lymphoma and related DLBCL. Endocytoscopy would be applicable for virtual histopathological diagnosis of different lymphoproliferative disorders and their clinical assessment during ongoing endoscopy.
PMCID: PMC3877966  PMID: 24369830
ATLL; DLBCL; Endocytoscopy; Gastric low-grade MALT lymphoma; H. pylori; Narrow band imaging
19.  Epstein Barr virus DNA analysis in blood predicts disease progression in a rare case of plasmablastic lymphoma with effusion 
In HIV-1-infected patients a long lasting CD4+ cell decline influences the host-EBV balance and thereby increases the risk for EBV related malignancies. In spite of a world-wide access to combination antiretroviral therapy (cART) there are still a considerable number of HIV-1-infected patients who will develop severe immunodeficiency. These undiagnosed HIV-1 infected patients, so called late testers, demonstrate an increased lymphoma risk, compared to patients diagnosed early. Consecutive individual screening for EBV DNA-load in late testers might be a useful predictor of emerging EBV-malignancy.
Patient biopsies and ascites were analyzed morphologically, by immuncyto-histochemistry and in-situ hybridization. Viral DNA and RNA load were quantified by PCR. Cell lines from primary tumor and from ascites, were established in vitro and further analyzed.
We here report on a case of EBV-positive lymphoma in an AIDS patient, first presenting with pleural effusion and ascites and was thus initially considered a primary effusion lymphoma (PEL) but was later diagnosed as a plasmablastic lymphoma (PBL). The patient had responded to cART with undetectable HIV-RNA and increased CD4 cell count one year prior to lymphoma presentation. At the time of lymphoma diagnosis the HIV-RNA values were <50 RNA-copies per mL blood (undetectable) and the CD4-positive cell count 170 ×106/L. The lymphoma was CD45-negative and weakly CD22- and CD30-positive. The patient had a history of Kaposi sarcoma and HHV-8 seropositivity. The lymphoma biopsies, and three cell lines derived on different occasions from the tumor cell effusion, were all EBV-positive but HHV-8 negative.
A noticeable EBV-DNA load decline was observed during the remission of the lymphoma following CHOP-therapy. The EBV-DNA load increased dramatically at the time of recurrence.
EBV DNA load might be useful in monitoring the effect of lymphoma treatment as well as in estimating the risk of EBV-associated lymphoma in HIV-1 infected patients with pronounced immunosuppression.
PMCID: PMC3726497  PMID: 23880011
EBV; HIV-1; HHV-8; DNA load; Plasmablastic lymphoma
20.  T-cell lymphoblastic lymphoma presenting with pleural effusion: A case report 
Adult lymphoblastic lymphoma (LBL) is an aggressive form of non-Hodgkin lymphoma occurring in predominantly adolescent and young adult men, accounting for 1% to 2% of all non-Hodgkin's lymphomas. In contrast to B-LBL, T-cell LBL is much more common, accounting for up to 90% of disease in adults. Mediastinal mass, pleural and/or pericardial effusions are the major characteristics of T-LBL. We report an 18-year-old male with a pleural effusion, mediastinal mass, a light pericardial effusion, and a normal hemogram. The cytology of the pleural effusion initially suggested malignancy, but definitive diagnosis was unclear. After a medical thoracoscopy, the partial pleura was picked and immunophenotypic study revealed the following: CD3+, TdT+, CD99+, CD20−. The patient was finally diagnosed with T-LBL and died only 6 months after that. The case highlight the point that medical thoracoscopy is a safe and accurate diagnostic procedure for pleural diseases, and partial pleura biopsy with immunophenotyping was essential for achieving the correct diagnosis of LBL.
PMCID: PMC4061434
T-cell lymphoblastic lymphoma; Non-Hodgkin's lymphoma; Pleural effusion; Medical thoracoscopy
21.  Primary extranodal marginal zone lymphoma – Epididymis 
An elderly male presented with painful swelling in the right side of scrotum. He was treated with antibiotics for epididymoorchitis without any response. Ultrasound examination revealed a hypoechoic vascular mass in the tail of the epididymis. Fine needle aspirate cytology was inconclusive. Excision of the mass was done and biopsy revealed primary extranodal marginal zone lymphoma arising from mucosa associated lymphoid tissue (MALT) of epididymis. Marginal zone lymphoma arising from the MALT of epididymis is very rare. Lymphoma should be considered as a differential diagnosis of any epididymal swelling unresponsive to conservative treatment. We report a rare case of primary extranodal marginal lymphoma of MALT arising from epididymis.
PMCID: PMC3263232  PMID: 22279330
B-cells; epididymis; lymphoma; marginal zone
22.  Acute onset pyothorax-associated lymphoma (PAL) with inflammatory features 
Pyothorax-associated lymphoma (PAL) is a B-cell non-Hodgkin's lymphoma, and develops after 20-40 years of pyothorax or pleuritis including tuberculosis. An 88-year-old Japanese woman developed fever and right pleural effusion. No mycobacterium was recognized by Ziel-Neelsen stain, culture tests and PCR technique in the effusion. The patient was diagnosed as non-specific pleuritis. No tumor formations were seen in the right pleura by imaging modalities, and she was treated by antibiotics. Eight months later, she complained of severe back pain and fever. Imaging modalities revealed many tumors in the right pleura, and biopsy of the tumors was performed. The biopsy showed severe diffuse proliferation of lymphoid cells. The lymphoid cells consisted of atypical large lymphoid cells and small lymphoid cells. The large atypical cells were positive for CD45 and CD20 but negative for CD15 and CD30, thus confirming B cell neoplasm. Ki-67 labeling was 79%. The small cells were positive for CD45, CD20 and CD3, reflecting a mixture of mature B and T-cells. The small cells appeared non-neoplastic inflammatory cells. CD68-positive macrophages were also scattered. In situ hybridization for EB virus DNA showed positive signals in the large atypical B-cells and, to a lesser degree, in the small lymphocytes. The author thinks that this tumor is PAL with inflammatory reaction. The present case shows that the duration between PAL and pleuritis can be very short, and PAL may be associated with inflammatory reaction at the early neoplastic stage.
PMCID: PMC3294231  PMID: 22400078
Pyothorax-associated lymphoma; pathology; immunohistochemistry
23.  Primary intrathoracic malignant mesenchymal tumours: computed tomography features of a rare group of chest neoplasms 
Insights into Imaging  2014;5(2):237-244.
To describe the computed tomography (CT) features in a case series of primary intrathoracic extracardiac malignant mesenchymal tumours (sarcomas).
A 5-year retrospective research was conducted, and 18 patients were selected. CT exams were reviewed by two chest radiologists, blinded to tumour pathological type, origin and grade. Lesions were described in relation to location, size, shape, margins, enhancement, presence of cavitation, calcifications, ground glass component, intratumoural enhanced vessels, pleural effusion, pleural tags, lymphangitis, chest wall/rib involvement and pathological lymph nodes.
The readers described five pulmonary, six mediastinal and seven pleural/wall based lesions. Mean largest diameter was 103 mm. The most frequent shape was irregular (n = 12), most predominant margin was smooth (n = 12) and enhancement was mostly heterogeneous (n = 8). Intratumoural vessels and pleural effusion were seen in 11 patients. Pathological lymph nodes were present in four cases and calcifications in two cases.
Some frequent radiological features were described independently of tumour location and subtype. A sarcoma should be included as a major differential diagnosis when the radiologist faces an intrathoracic mass of large size (>70 mm) but with well defined smooth or lobulated margins, especially if presenting intratumoural vessels, associated pleural effusion but no significant lymphadenopathy.
Main messages
• Malignant mesenchymal tumours (sarcomas) are rare and can arise from any structure in the chest.
• Intrathoracic sarcomas show some frequent radiological features, independent of location and type.
• Some CT features may help the radiologist suspect for a sarcoma instead of other more common tumours.
PMCID: PMC3999366  PMID: 24407922
Neoplasm; Malignant mesenchymal tumour; Sarcoma; Thoracic cavity; Computed tomography
24.  Tracheal stenting for primary tracheal mucosa-associated lymphoid tissue lymphoma 
Primary tracheal mucosa-associated lymphoid tissue (MALT) lymphoma is extremely rare. We report a 49-year-old female patient with the complaint of dyspnea. Fiberoptic bronchoscopy showed polypoid, variable-sized and irregular nodules causing narrowing of the tracheal lumen from the proximal trachea to the left main bronchus. Because of severe stenosis in the airway and the severity of symptoms, this case was unresectable. The patient was then treated successfully with placement of an endobronchial stent through bronchofibroscopy. After the placement of the stent, bronchoscopic biopsy was performed. Pathological analysis confirms a diagnosis of MALT-associated malignant lymphoma. We performed systemic chemotherapy on the patient. The temporary stent was removed after the reduction of the stenosis. This is the first case in which tracheal MALT lymphoma was treated successfully following tracheal stent insertion guided by bronchofibroscopy. Temporary tracheal stenting can be a favorable choice for a patient with tracheal stenosis caused by primary tracheal MALT lymphoma.
PMCID: PMC3621548  PMID: 23547898
Lymphoma; Mucosa-associated lymphoid tissue (MALT); Trachea; Tracheal stent
25.  Spontaneous regression of primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) colliding with invasive ductal carcinoma of the breast: a case report 
Malignant lymphomas of the breast, whether they are primary or secondary, are rare diseases, constituting only around 0.1 to 0.15% of the primary neoplasm of the breast. Although the most prevalent histological subtype is diffuse large B-cell lymphoma, primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) also occurs in the breast as in other extranodal sites, comprising about 15% of malignant lymphomas of the breast. In many cases, primary MALT lymphoma of the breast is low grade lymphoma, localized in the breast with indolent behavior and good prognosis. Here we report a case of spontaneous regression of primary MALT lymphoma of the breast. The lymphoma collided with invasive ductal carcinoma in the breast. Both tumors were identified in the Vacora biopsy specimen before the operation. However, the lymphoma disappeared, while the carcinoma remained, in the resected mass. To our knowledge, this is the first case report of spontaneous regression of MALT lymphoma of the breast colliding with breast cancer.
PMCID: PMC4230083  PMID: 25400790
MALT lymphoma; invasive ductal carcinoma; breast; spontaneous regression

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