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BACKGROUND QT interval prolongation can induce torsades de pointes (TdP), a potentially fatal ventricular arrhythmia. Recently, an increasing number of non-cardiac drugs have been found to cause QT prolongation and/or TdP onset. Moreover, recent findings have demonstrated the key roles of systemic inflammatory activation and fever in promoting long-QT syndrome (LQTS) and TdP development. CASE SUMMARY A 30-year-old woman was admitted with a moderate to high-grade episodic fever for two weeks. The patient was administered with multiple antibiotics after hospitalization but still had repeating fever and markedly elevated C-reactive protein. Once after a high fever, the patient suddenly lost consciousness, and electrocardiogram (ECG) showed transient TdP onset after frequent premature ventricular contraction. The patient recovered sinus rhythm and consciousness spontaneously, and post-TdP ECG revealed a prolonged QTc interval of 560 ms. The patient’s clinical manifestations and unresponsiveness to the antibiotics led to the final diagnosis of adult-onset Still’s disease (AOSD). There was no evidence of cardiac involvement. After the AOSD diagnosis, discontinuation of antibiotics and immediate initiation of intravenous dexamethasone administration resulted in the normal temperature and QTc interval. The genetic analysis identified that the patient and her father had heterozygous mutations in KCNH2 (c.1370C>T) and AKAP9 (c.7725A>C). During the 2-year follow-up period, the patient had no recurrence of any arrhythmia and maintained normal QTc interval. CONCLUSION This case study highlights the risk of systemic inflammatory activation and antibiotic-induced TdP/LQTS onset. Genetic analysis should be considered to identify individuals at high risk of developing TdP.

Background We describe the case of a 74-year-old man diagnosed with primary cutaneous mantle cell lymphoma (MCL), an extremely rare and controversial condition that is not included in the World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas. Case summary The patient presented diffuse cutaneous erythematous plaques and nodules throughout the body. Skin lesions were biopsied and histopathological examination showed diffuse monomorphic lymphocyte infiltration in the dermal and subcutaneous layers, sparing the epidermis. Immunohistochemical staining revealed CD20, cyclin-D1, CD5, and SOX-11 expression. Fluorescence in situ hybridization showed CCND1/IGH gene rearrangement. Correct diagnosis of primary cutaneous MCL requires ensuring that no other parts are involved; these cases require close follow-up to monitor their possible progression to systemic disease and for treating relapsed cutaneous disease. In this case, positron emission tomography scanning and clinical staging revealed no systemic involvement, and follow-up examination at 20 mo after diagnosis showed no evidence of systemic disease. The prognosis of primary cutaneous MCL is relatively good. Our patient received six cycles of chemotherapy, and the cutaneous manifestations presented almost complete remission. Conclusion Primary cutaneous MCL is rare, and its prognosis is relatively favorable. However, correct diagnosis is a prerequisite for proper treatment.

Objective This study aimed to investigate the diagnostic utility of immunohistochemistry (IHC) analysis (FNA) and Epstein-Barr virus- (EBV) encoded small RNAs (EBERs) in situ hybridisation analyses of cell block (CB) sections obtained using fine needle aspiration in nasopharyngeal carcinoma (NPC) with lymph node metastasis. Methods A total of 38 FNA biopsies were collected using a Youyi aspirator. The cytomorphology, CB-based histomorphology, IHC, and EBERs in situ hybridisation were observed and the sensitivity/final diagnostic rates were compared with those of simple smears and a combination of smears and CBs. Results The 38 cases of metastatic lymph nodes from NPC displayed the morphological characteristics of non-keratinising carcinoma in cell smears and CB sections. The tumour cells showed high expression of CK5/6, P63, Ki-67, and EBERs (94.7%, 36/38 cases) in the CB sections. The sensitivity and the final diagnostic rates were lowest with the simple cell smears (86.8%, 33/38 and 71.1%, 27/38 cases), moderate with the smears combined with CB sections (92.1%, 35/38 cases and 81.6%, 31/38 cases), and the highest with IHC and EBERs in situ hybridisation (94.7%, 36/38 and 94.7%, 36/38 cases). Conclusions FNA has great value in the diagnosis of NPC with lymph node metastases, and using cell smears combined with IHC and EBERs in situ hybridisation of CB sections could help clinical doctors promptly identify the primary lesions.

Background To evaluate the clinical utility of LIM Domain Only 2 (LMO2) negative and CD38 positive in diagnosis of Burkitt lymphoma (BL). Methods LMO2 and CD38 expression determined by immunohistochemistry in 75 BL, 12 High-grade B-cell lymphoma, NOS (HGBL,NOS) and 3 Burkitt-like lymphomas with the 11q aberration. Results The sensitivity and specificity of LMO2 negative for detecting BL were 98.67 and 100%, respectively; those of CD38 positive were 98.67 and 66.67%, respectively. The sensitivity and specificity of a combination of both for detecting BL were 97.33 and 100%, respectively. In our study, the combined LMO2 negative and CD38 positive results had a higher area under the curve than either LMO2 negative or CD38 positive alone. Conclusions A combination of LMO2 negative and CD38 positive is useful for the diagnosis of Burkitt lymphoma.

The Epstein-Barr virus (EBV) is a ubiquitous lymphotropic herpesvirus that infects the human body through the respiratory tract. Usually, primary infection with EBV is asymptomatic and occurs early in life, however adolescents or young adults are more likely to develop a self-limited symptomatic infection, which manifests as acute infectious mononucleosis (IM). Systemic EBV-positive lymphoproliferative disease (EBV + T/NK-LPD) has been described as a disease related to chronic or persistent EBV infection after acute EBV infection, with severe IM-like symptoms. EBV + T/NK-LPD is associated with high mortality and morbidity with life-threatening complications. Information on its prognostic factors remains limited, therefore in this study, we aimed to evaluate the association between prognostic factors and mortality and complications of EBV + T/NK-LPD in China by retrospectively reviewing 173 EBV + T/NK-LPD cases. We observed that the high mortality rate of EBV + T/NK-LPD was mainly due to serious and fatal complications. Fever, lymphadenopathy, hepatosplenomegaly, EBV-encoded RNA (EBER) > 50/HPF, Ki-67 > 30%, and other visible complications were closely associated with EBV + T/NK-LPD prognosis. In addition, fever, hepatosplenomegaly, decreased WBC count, and a Ki-67 index of > 30% were risk factors for complications. Thus, disease prognosis should be based on a comprehensive analysis of pathological and clinical data. Such data will help pathologists and clinicians to pay close attention to the changes in the clinical condition of the patients as well as take precautionary measures against the occurrence of fatal complications.

This study concerning mantle cell lymphoma (MCL) investigated retrospectively an association between patient prognosis and the percentage of the total number of lymphoma cells found in the follicular dendritic cell (FDC) meshwork, that is, the degree of overlap of lymphoma cells. Two hundred and nine MCL patients were apportioned to grades I-III, in which the CD21-positive FDC meshwork covered ≤50%, 51%-89%, and ≥90% of the tumor area, respectively. Significant differences among the grades (all, P 0.01) were found in the following: duration of disease (from onset of clinical manifestation to diagnosis); clinical staging; extranodal involvement (non-lymphoid organs); histological subtype; and Ki-67 proliferation index (PI). After removing the aggressive variants, the overall survival rates of grade I (n = 92) and II (n = 57) patients were similar. The overall survival rates of grade III (n = 46) patients differed from that of grade I + II patients (P 0.01). The grades negatively correlated with the Ki-67 PI value (r = -0.234, P = 0.001). At each grade the OSR of patients with Ki-67 PI ≤30% was similar to that of patients with Ki-6730%. In the Ki-67 PI ≤30% group, the OSRs of the patients differed significantly among the grades. In the Ki-6730% group the OSRs of the grades were similar. The results of multivariate Cox regression analysis showed that the degree of overlap, age and Ki-67 PI was the independent prognostic factors of the OSRs of MCL patients. Our data suggests that MCL patients in whom there was a high degree of overlap between the FDC meshwork and tumor area have a better clinical prognosis. The degree of overlap correlates well with the Ki-67 PI, which can be used to predict the prognosis of patients.

Intravascular lymphoma (IVL) is a rare neoplasm characterized by proliferation of malignant cells within the small vessel lumina, particularly capillaries. Cases of IVL almost always occur in extra...

// Guangyong Chen 1 , Rui Xu 1 , Bing Yue 1 , Xue Mei 1 , Peng Li 2 , Xiaoge Zhou 1 , Shoufang Huang 1 , Liping Gong 3 , Shutian Zhang 2 1 Department of Pathology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, 10050 China 2 Department of Gastroenterology and Hepatology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, 10050 China 3 Department of Pathology, Basic Medical College, Capital Medical University, Beijing, 100069 China Correspondence to: Shutian Zhang, email: zhangst@ccmu.Edu.cn Keywords: podoplanin, esophageal squamous cell carcinoma Received: October 24, 2016 Accepted: October 28, 2016 Published: January 11, 2017 ABSTRACT The esophageal squamous cell carcinoma (ESCC) is usually develped from low-grade intraepithelial neoplasia (LGIEN) and high-grade intraepithelial neoplasia (HGIEN) to infiltrative squamous cell carcinoma. Till now, it remains hard to screen for infiltration at earlier stages, especially the differentiation between HGEIN and early infiltrative carcinoma. The purpose of this study is to determine a role of podoplanin in differentiating between HGEIN and early infiltrative squamous cell carcinoma. Totally 133 patients pathologically diagnosed with early ESCC and/or precancerous lesions were enrolled.The EnVision two-step IHC staining technique was applied using the monoclonal mouse anti-human Podoplanin antibody (clone number: D2-40). The expressions of PDPN protein on the basal layer of squamous epithelium lesions could be divided into three different patterns: complete type, incomplete (non-continuous) type, or missing type. A diagnosis of HGEIN can be made if the basal layer showed non-continuous or complete expression of PDPN and a diagnosis of early infiltration can be made if the expression of PDPN is completely missing. Our study confirmed that PDPN was a potential biomarker to identify the presence of early infiltrative squamous cell carcinoma.

Systemic Epstein–Barr virus (EBV)-positive T-cell lymphoproliferative disorders (LPDs) of childhood is a highly aggressive EBV-positive T/natural killer (NK)-cell LPD, which emerges in the background of chronic active EBV infection (CAEBV) or shortly after primary acute EBV infection. The clinical presentations of CAEBV are varied; patients with atypical manifestations are easily misdiagnosed. We described a 14-year-old boy suffering from digestive disorders and intermittent fever for 1 year and 9 months, whose conditions worsened and skin lesions occurred 2 months before hospitalization. He was diagnosed as inflammatory bowel diseases (IBD) and treated accordingly. His other clinical features, hepatosplenomegaly, lymphadenopathy, anemia, hypoalbuminemia, and elevated inflammatory marks, were found in hospitalization. The boy suffered from repeatedly spontaneous intestinal perforations shortly after hospitalization and died of intestinal hemorrhea. The pathological results of intestine and skin both showed EBV-positive T/NK-cell LPD (lymphoma stage). There are rare studies reporting gastrointestinal perforations in EBV-positive T/NK-cell LPD, let alone repeatedly spontaneous perforations. Based on the clinical features and pathological results of this patient, the disease progressed from CAEBV (T-cell type) to systemic EBV-positive T-cell LPD of childhood (lymphoma). Not all the patients with CAEBV could have unusual patterns of anti-EBV antibodies. However, the presence of high EBV loads (EBV-encoded early small ribonucleic acid (RNA) (EBER) in affected tissues and/or EBV deoxyribonucleic acid (DNA) in peripheral blood) is essential for diagnosing CAEBV. Maybe because of his less common clinical features for CAEBV and negative anti-EBV antibodies, the boy was not diagnosed correctly. We should have emphasized the test for EBER or EBV-DNA. Meanwhile, for the IBD patients whose manifestations were not typical, and whose conditions were not improved by suitable therapies against IBD, infectious and malignant diseases should be considered.

Angiomatoid fibrous histiocytoma is an uncommon soft tissue tumor most frequently affecting the deep dermis and subcutis of the extremities in children and young adults. We report the first case presenting as a primary pulmonary tumor in a 46-year-old man. Histologically, the tumor was composed of multiple cellular nodules surrounded by a fibrous pseudocapsule and peritumoral lymphoplasmacytic infiltrates. The nodules were composed of histiocytoid cells with a diffuse, whorled, or vague storiform pattern, with the intervening areas densely packed with plasma cells and lymphocytes. The tumor cells were immunoreactive for epithelial membrane antigen, and focally desmin, CD68, and CD163. Fluorescence in-situ hybridization revealed EWS gene translocation, which was further confirmed on polymerase chain reaction to result from EWS/ATF1 gene fusion. It is important to recognize that angiomatoid fibrous histiocytoma can occur in the lung because its histologic features are rather nondescript and thus can be mistaken for other tumors such as meningioma, inflammatory myofibroblastic tumor, and follicular dendritic cell sarcoma.

Initial reports emphasized the immunophenotypic similarities between benign and malignant T cell populations, while some previous studies indicating that aberrant T-cell antigen loss is a good marker for detecting malignant T-cell proliferation. Recently, we found a very interesting and thought-provoking phenomenon: In benign disease-28 of 38 (73.7%) cases of Kikuchi’s disease also showed aberrant phenotypes with loss of pan-T cell antigens, which makes the differential diagnosis between Kikuchi’s disease and T cell lymphoma more challenging. In our study, 38 cases of Kikuchi’s disease and 30 cases of reactive lymphoid hyperplasia (RLH) were studied by EliVision immunohistochemical staining. As well as TCR gene rearrangement using PCR was negative in 10 tested cases of the Kikuchi’s disease. Among these cases, the most common antigen deficiency was CD5 (22 cases), then CD7 (11 cases), CD2 (8 cases) and CD3 (2 cases). Compared with proliferative and xanthomatous types of Kikuchi’s disease, antigens tended to be lost in necrotizing type. Based on follow-up data, a correlation was not found between the occurrence of aberrant phenotypes and prognosis. In RLH, obvious pan-T cell antigen loss was also not found. In conclusion, this is the first study to demonstrate distinct patterns of antigen loss in Kikuchi’s disease, suggesting that T cell antigen loss is not reliable as an auxiliary diagnostic standard for T cell lymphoma.

BACKGROUND The Epstein-Barr virus (EBV) is thought to be involved in the pathogenesis of some Hodgkin disease (HD) cases. EBV may be associated particularly with childhood HD, a disease rare in the West compared with developing countries. In this study, a large series of Chinese pediatric HD cases has been examined to determine the age-specific prevalence of EBV. METHODS Paraffin sections from 104 pediatric and 52 adult Chinese HD cases were examined for EBV-RNA (EBERs) and EBV latent membrane protein-1. RESULTS Most pediatric cases arose in boys and showed an histology of mixed cellularity. Prominent interfollicular involvement was seen frequently in the childhood cases. EBV was identified in tumor cells in 113 of 156 (72%) HD cases but was more frequent in pediatric cases (93 of 104; 89%) compared with adult cases (20 of 52; 38%) (P 0.05; chi-square test). Pediatric HD was associated with EBV irrespective of histologic subtype. In adults, EBV was associated more frequently with mixed cellularity than with other subtypes. CONCLUSION To the authors' knowledge, this is to date the largest series of pediatric HD cases studied for EBV. Study findings provided further evidence that HD is etiologically heterogenous. The authors believe that pediatric HD now should be regarded as a distinctive EBV-related lymphoma. Cancer 2001;92:1621–31. © 2001 American Cancer Society.

Aims—To study the distribution of Epstein-Barr virus (EBV) variants containing mutations in the latent membrane protein 1 (LMP-1) oncogene and promoter in EBV associated Hodgkin's disease and infectious mononucleosis compared with previous findings in asymptomatic EBV carriers. Methods—Sequence analysis of the EBV LMP-1 promoter and gene in isolates from Danish patients with Hodgkin's disease (n = 61) and infectious mononucleosis (n = 10). Results—Viruses (previously designated group D) that contain two mutations in the activating transcription factor/cAMP response element (ATF/CRE) in the LMP-1 promoter, which are known to decrease promoter activity greatly, were significantly less frequent in Hodgkin's disease than in both infectious mononucleosis (p = 0.0081) and asymptomatic EBV carriers (p = 0.0084). In some cases, the LMP-1 gene contained mutations in a recently identified cytotoxic T cell (CTL) epitope. Most viral isolates contained mutations shown to increase nuclear factor κB (NF-κB) activation and had one of two newly identified C-terminal activation regions 3 (CTAR-3) deleted. The exon 1 Xho-I restriction site in the LMP-1 gene could be lost through a range of different mutations. Conclusions—These findings indicate selection pressure against EBV strains with weak LMP-1 promoter activity in Hodgkin's disease and thus provide further strong circumstantial evidence for the pathogenic role of EBV (and LMP-1) in this disease. Mutation of the CTL epitope suggests immune selection of EBV strains. Many EBV isolates contain functionally important mutations in the LMP-1 gene. Loss of the Xho-I restriction site should not be used as a marker of specific LMP-1 variants.

The clinicopathological features of human immunodeficiency virus (HIV)-associated lymphoma were investigated in a retrospective study of 85 adult patients in eastern Denmark diagnosed during the period 1990-1996. The possible pathogenetic role of Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8) in these tumours was also studied. Seventy patients (82%) presented with extranodal disease and 26 (31%) had CNS involvement at diagnosis. Diffuse large cell B-cell lymphoma was the most frequent histological subtype, comprising 65 of 79 cases available for microscopic re-evaluation (82%) and including 20 of 23 evaluable patients with CNS lymphoma (87%). EBV RNA was demonstrated by in situ hybridization in 51 of 65 evaluable tumours (79%) and in 14 of 16 cases (88%) with CNS-lymphoma. Three cases showed a T-cell phenotype. The presence of HHV-8 DNA was analysed by PCR in 32 cases. A strong band consistent with tumour cell infection was detected in only one case, weaker bands being seen in 4 cases. None of these patients had primary effusion lymphomas. In conclusion, Danish AIDS-related lymphomas are of predominantly high-grade B-cell type with extranodal localization and atypical presentation. Our results provide further evidence that EBV plays a major role in the pathogenesis of large cell AIDS-related lymphoma, whereas HHV-8 does not appear to contribute significantly to the development of solid lymphomas in this group of patients.

The Epstein–Barr virus (EBV) nuclear antigen (EBNA)-1 is consistently expressed in EBV-associated tumours. Recently, EBNA-1 carboxy (C)-terminal sequence variants have been described based on the amino acid signature at codon 487, and designated prototype (P)-ala (identical to prototype B95.8 strain), P-thr, variant (V)-val, V-leu, and V-pro. These studies suggest that certain EBNA-1 variants show selective cell tropism and may be preferentially associated with different EBV-positive malignancies; for example, in contrast to P-ala subtypes, V-val appeared to be restricted to the oral compartment and to be associated with undifferentiated nasopharyngeal carcinoma (NPC). To test the hypothesis that V-val subtypes are restricted in distribution, EBNA-1 variants were investigated in NPC and throat washings (TWs) from a low (Denmark) and a high (China) NPC risk area. For comparison, cases of Hodgkin's disease (HD) were also studied. V-val was found to be the dominant EBNA-1 subtype, not only in Chinese TWs and NPC biopsies, but also in Chinese HD. Furthermore, V-val was not detected in any of the Danish NPC biopsies or TW samples. These findings show that V-val is not associated with NPC, nor is it restricted to the oral compartment, but rather that it represents a dominant Asian EBNA-1 subtype, both in EBV-associated malignancies and in the general population. Copyright © 2000 John Wiley & Sons, Ltd.

Sequence variations in the Epstein-Barr virus (EBV) encoded latent membrane protein-1 (LMP-1) gene have been described in a Chinese nasopharyngeal carcinoma-derived isolate (CAO), and in viral isolates from various EBV-associated tumors. It has been suggested that these genetic changes, which include loss of a Xho I restriction site (position 169425) and a C-terminal 30-base pair (bp) deletion (position 168287-168256), define EBV genotypes associated with increased tumorigenicity or with disease among particular geographic populations. To determine the frequency of LMP-1 variations in European wild-type virus isolates, we sequenced the LMP1 promoter and gene in EBV from lymphoblastoid cell lines from healthy carriers and patients without EBV-associated disease. Sequence changes were often present, and defined at least four main groups of viral isolates, which we designate Groups A through D. The widespread prevalence of LMP-1 sequence variations, particularly the Xho I polymorphism and the 30-bp deletion, indicate that they cannot be used as simple markers for oncogenic viruses related to particular forms of EBV-associated tumor. Several of the structural changes detected occur, however, at sites where they may affect transcription, translation, or function of LMP-1. Future in vitro studies should aim to establish the functional importance of variations at these sites.

To study the clinical features, endoscopic findings, pathologic diagnosis and treatment options of intestinal follicular lymphoma first presenting with gastrointestinal symptoms.The clinical features, pathologic findings and follow-up data were retrospectively studied in 9 cases of intestinal follicular lymphoma. Immunohistochemical study for CD3, CD5, CD20, CD21, Ki-67, bcl-2, bcl-6, CD10 and cyclin D1 was carried out.Seven of the 9 patients were females and two were males. The age of patients ranged from 5 to 60 years (mean = 44 years). The clinical manifestations included abdominal pain (5 cases), blood in stool (3 cases) and abdominal distension (1 case). The commonest site of involvement was ileocecal region (6/9). Endoscopic examination had been carried out in 6 patients and all showed the presence of multiple polyps. Five cases had undergone endoscopic biopsy. Histologic examination of the endoscopic biopsies showed lymphoma cells located mainly in mucosal layer, forming vague nodules with ill-defined boundaries. Plasma cells and eosinophils were not conspicuous. Immunohistochemically, the tumor cells in all cases diffusely expressed CD20, CD10 and bcl-2. The staining for CD3, CD5 and cyclin D1 was negative. Lymphoid cells with weak CD10-positivity were identified in the interfollicular regions. Four cases were treated with surgical resection and chemotherapy. The other 3 cases received chemotherapy only and the remaining cases were treated conservatively. All of them were still alive on follow up.Primary intestinal follicular lymphoma affects predominantly elderly patients and has a female predilection. The commonest site of involvement is ileocecal region. Endoscopic examination shows polypoid changes. The disease often runs a relatively indolent clinical course. The prognosis is better than that of primary nodal follicular lymphoma.

Systemic anaplastic large cell lymphoma (ALCL) is subtyped into ALK-positive ALCL and ALK-negative ALCL based on the presence or absence of ALK protein expression. ALK-positive ALCL is characterized by t(2;5)(p23;q35)/ NPM-ALK or variant ALK -involved translocations, while little is known about the genetic changes in ALK-negative ALCL. We investigated the structural and numerical aberrations of the ALK gene using interphase fluorescence in situ hybridization (FISH) in 81 cases with ALCL and analyzed their association with clinical outcome of the patients. ALK gene rearrangement was found in 47 of 50 (94%) ALK-positive ALCLs but in none of 31 ALK-negative ALCLs. Extra copies of the ALK gene locus, representing mainly extra copies of chromosome 2, were seen in 19 ALK-positive (38%) and 15 ALK-negative (48%) cases ( P = 0.357). In 55 cases with follow-up information, the mean survival time of the 38 ALK positive cases (58 months) was significantly longer than that of 17 ALK-negative cases (22.5 months) ( P = 0.038). Interestingly, the cases with extra copies of ALK had a significantly longer mean survival time than those without (64.4 months vs 35.3 months) ( P = 0.023) and this difference was observed in both ALK-positive (72.3 vs 45.9 months) and ALK-negative (34.7 vs 9.9 months) cases. Multivariate analysis showed that both ALK protein expression and extra copies of ALK gene were independent predictors for better survival ( P = 0.008). Our results suggest that the extra copies of ALK gene locus are a frequent genetic aberration in both ALK-positive and ALK-negative ALCL and is a favorable prognostic marker for the patients.

To study the possible loss of pan-T cell antigens CD2, CD3, CD5 and CD7 in Kikuchi's disease and to evaluate the role of T cell antigen loss in distinguishing benign from malignant T-cell lymphoid lesions.Formalin-fixed and paraffin-embedded tissues of 33 cases of Kikuchi's disease and 15 cases of reactive lymphoid hyperplasia were studied by EliVision immunohistochemical staining for CD2, CD3, CD5 and CD7.Twenty-four of the 33 (72.7%) cases of Kikuchi's disease lost one or more of the pan-T cell antigens, including the loss of CD5 only (13 cases), CD7 only (1 case), CD2 only (1 case), CD2 and CD7 (2 cases), CD5 and CD7 (4 cases), CD2 and CD5 (2 cases), and CD2, CD7 and CD5 (1 case). Amongst these cases, the commonest antigen loss was CD5 (20 cases, 60.6%), followed by CD7 (8 cases, 24.2%) and CD2 (6 cases, 18.2%). Compared with the xanthomatous subtype of Kikuchi's disease, the loss of antigens was more commonly seen in the proliferative and necrotizing subtypes. Analysis of follow-up data showed that the loss of antigens in Kikuchi's disease was not significantly associated with the prognosis. In reactive lymphoid hyperplasia, the expression of CD2, CD3, CD5 and CD7 was seen in all cases with similar intensity, with no obvious pan-T cell antigen loss.Loss of one or more pan-T cell antigens in Kikuchi's disease is demonstrated in present study, suggesting that the immunophenotypic pattern is not unique in T cell lymphoma.

To study the clinicopathologic features and disease outcome of intravascular natural killer-cell lymphoma (IVNKL).The histologic features, immunohistochemical findings and results of in-situ hybridization for Epstein-Barr virus-encoded RNA (EBER) were analyzed in 2 novel cases of IVNKL. Seven cases of IVNKL previously reported in the literature were reviewed.The patients were a 68-year-old woman and a 22-year-old man. They both presented with erythematous patches and nodules on their trunk and extremities. Skin biopsies confirmed the diagnosis of IVNKL. The tumor cells were positive for CD3, CD56, granzyme B and EBER. Both patients died 2 months after the diagnosis. Amongst the 9 reported cases, including those from the literature, the male was 4 cases, the female was 5 cases. The mean age of the patients was 45.7 years and the median age was 47 years. Skin lesions represented the commonest clinical manifestations. Multiple organ involvement was found in 7 cases and central nervous system was involved in 3 cases. Six patients died during 2 to 17 months of follow-up. The median survival was 9 months and the one-year survival rate was (35.6±18.6)%. The clinical outcome of the patients with multiple organ involvement was worse than that with skin manifestations only. The difference however was not statistically significant (P=0.083).IVNKL is a rare disease. Diagnosis should be made according to typical histologic findings, immunophenotype and EBER in-situ hybridization results. The overall prognosis of IVNKL is poor. Early diagnosis and treatment before multiorgan involvement may be helpful in improving the clinical outcome.

Mesenchymal cystic hamartoma (MHC) of the lung is a very rare disease with an indolent clinical course and might be easily misdiagnosed as pleuropulmonary blastoma and other uncommon cystic lung lesions. We present a case of a 43-year-old woman who had sudden dyspnea resulting from a spontaneous right-sided pneumothorax. Computed tomography revealed multiple bilateral nodules and cysts of the right lung. Pathologically, the cysts and nodules were composed of primitive mesenchymal cells. The walls of the cysts were lined with normal respiratory epithelium and the nodules were permeated by scattered airways that were also lined with normal respiratory epithelium. Based on the combination of pathologic and clinical features, we made the diagnosis of MHC. One and one-half years after thoracotomy the patient is well without evidence of recurrence.

To study the clinicopathologic features, immunophenotype, clonality and Epstein-Barr virus (EBV) status of systemic EBV-positive T/NK-cell lymphoproliferative disease in adults (ASEBV(+)T/NK-LPD).Twenty cases of ASEBV(+)T/NK-LPD were analyzed retrospectively with histopathologic review, immunohistochemistry and in-situ hybridization for EBV-encoded RNA (EBER). The follow-up data were collected.There were altogether 15 males and 5 females. The median age of the patients was 34 years. The average duration from onset of symptoms to diagnosis was 8.7 months. Fever (18/20), hepatosplenomegaly (18/20) and lymphadenopathy (17/20) were the main clinical manifestations. Eleven of the 17 patients died during follow-up, with a mean survival of 2.9 months. Histologically, there was obvious expansion of T zone of the involved lymph nodes, associated with diminished lymphoid follicles. The interfollicular areas were widened and infiltrated by small to median-sized lymphoid cells which showed only mild atypia. Scattered large lymphoid cells were not uncommon. The nodal capsule was thickened in 6 cases. Focal necrosis was seen in 9 cases. Sinus histiocytic proliferation with erythrophagocytosis was observed in 3 cases. In addition, there were mild atypical lymphoid cells infiltrate into the liver, spleen, intestinal mucosa and bone marrow. Immunohistochemical study and in-situ hybridization showed that the EBER-positive cells were of T-cell lineage, with CD3 expression. They were also positive for cytotoxic molecules (granzyme B or TIA-1). Only 1 case was CD56 positive. A predominance of CD8-positive cells was demonstrated in 8 of the 14 cases studied, while CD4-positive cells predominated in the remaining 5 cases. One case showed similar proportion of CD8 and CD4-positive cells. The number of EBER-positive cells ranged from 30 to more than 300 per high-power fields. These EBER-positive cells were of small to large size and located mainly in the expanded T zone and occasionally in the germinal centers. Three of the 7 cases exhibited clonal rearrangement of T-cell receptor gamma gene, while the other 4 cases exhibited polyclonal rearrangement of T-cell receptor gamma gene.ASEBV(+)T/NK-LPD is a systemic disease with a subacute or chronic clinical course. Most patients suffer from relapsing fever, lymphadenopathy and hepatosplenomegaly. The disease is characterized by proliferation of EBV-infected cytotoxic T cells. The T zone of the involved lymph nodes shows expansion by mildly atypical lymphoid cells. The disease is associated with poor clinical outcome and can be life-threatening. The patients often die of multiorgan failure and bleeding.

Epstein-Barr virus (EBV) can be detected in Hodgkin and Reed-Sternberg (HRS) cells in about one-half of cases of Hodgkin's disease (HD) in Western countries. To determine whether EBV is also associated with HD in a developing country such as China, we studied paraffin sections from 28 Chinese cases of HD for expression of latent membrane protein-I (LMP-I) and EBV-encoded small RNA (EBER-I), using immuno-histology and RNA/RNA in situ hybridization respectively. The cases were selected from a large series of Chinese lymphomas following histological and immunophenotypical revision. EBV gene expression was found in HRS cells in 17/28 cases, and was related to histological sub-type, being present in 10/11 of mixed cellularity, 6/14 nodular sclerosis, 0/1 lymphocytic predominance, 0/1 lymphocytic depletion, and 1/1 unclassified HD. The 2 methods for detecting EBV gene expression gave similar results, except in one case of nodular sclerosis, in which HRS cells were negative for EBER-I, but weakly positive for LMP-I. In 5/12 cases with EBER-negative HRS cells, rare small or medium-sized lymphocytes expressed EBER-I but not LMP-I. These results suggest that (i) Chinese HD is frequently associated with EBV; (ii) the proportional frequency and sub-type distribution of EBV-positive HD are similar in China and in the West; (iii) both LMP-I immunohistology and EBER in situ hybridization reliably detect EBV in HRS cells in routine biopsies, but the former is simpler and less resource-consuming to perform.

To study the clinical and pathologic features of 4 cases of the so-called blastic natural killer (NK)-cell lymphoma, with reference to the 2008 WHO classification of tumours of haematopoietic and lymphoid tissues.The clinical, pathologic and immunohistochemical findings (EliVision method) of 4 cases of blastic NK-cell lymphoma (previously diagnosed according to the 2001 WHO classification) were retrospectively analyzed and reclassified with a special reference to the 2008 WHO classification.The 4 cases of hematologic malignancy studied were characterized by the presence of medium-sized blastic lymphoma cells, CD56 expression, and absence of lineage-specific B-cell, T-cell and myeloid cell markers. According to the 2001 WHO classification, they fell into the category of blastic NK-cell lymphoma. Three of the cases presented with primary cutaneous lesions and expression of CD56, CD4 and CD123. They are likely derived from the plasmacytoid dendritic cells rather than NK cells. They were then, according to the 2008 WHO classification, reclassified as the blastic plasmacytoid dendritic cell neoplasm. The remaining case showed lymph node involvement, positive for CD56 and CD4, negative for CD123, and not accompanied with the cutaneous lesions. This case was provisionally classified as a ambiguous lineage leukemia-NK cell lymphoblastic leukemia/lymphoma.The so-called blastic NK-cell lymphomas in the 2001 WHO classification are rare and represent a heterogeneous group of lymphoproliferative disorders, with different clinical, pathologic and immunohistochemical features. It's suggested to have a precise category when applying the 2008 WHO classification to this kind of lesion.

To clarify clinical and morphological features and immunophenotype of T lymphoblastic lymphoma/leukaemia (T-LBL/ALL) and to further improve the knowledge and diagnostic accuracy for T-ALL/LBL.128 cases of T-LBL/ALL were analyzed for the clinical features, morphology, immunophenotype and TCR gene rearrangement using routine eosin and haematoxylin stain, immunohistochemistry and polymerase chain reaction combining with the clinical findings.In 128 cases of T-LBL/ALL, there were 94 male and 34 female. The ratio of male/female was 2.8:1. The age of patients ranged from 4 to 88 years, with an average of 27 years and a median of 22 years. Lymph nodes and extranodal areas were involved in 58/128 and 27/128 cases of T-LBL/ALL, respectively. The other 43 cases had involvement of both nodal and extranodal areas. Cervical node and mediastinum were involved in 74 cases and 43 cases, respectively. Diffuse growth pattern of tumor cells was predominant. Nodular growth pattern was seen only in a few cases. Most cases composed of small to medium-sized lymphoblasts, and other 7 cases showed a composition of large lymphoblasts. Tumor cells expressed TdT in 121/128 (94.5%) cases, CD34 in 48/98 (49.0%) cases, CD3 in 78/108 (72.2%) cases, CD7 in 104/108 (96.3%) cases, CD43 in 56/63 (88.9%) cases, CD79a in 5/70 (7.1%) cases, CD10 in 25/76 (32.9%) cases, CD99 in 58/60 (96.7%) cases and Pax-5 in 4/91(4.4%) cases. All of the cases were negative for MPO. A follow up data, ranging from 1 to 53 months, was obtained in 51/128 (39.8%) patients. The over all survival rate was 68.6% and the median survival time was 12 months. Under a similar condition of carrying a positive staining result on CD3 in tumor cells, there was a statistically significant difference between patients in the group of over 30 of age and that with the age ranging from 11 to 30. Patients associating with a CD10 positive staining of tumor cells showed also a shorter survival period. In addition, there were 4 out of 5 cases showing the presence of TCR gene rearrangement.T-LBL/ALL are aggressive in behavior, associating mainly with enlarged cervical lymph nodes and masses in the mediastinum, occurring predominantly in children and young adults. Although small to medium-sized tumor cells with diffuse pattern were found in most cases, however, large-sized tumor cells and nodular pattern could also be obtained in a few cases. Immunohistochemistry staining particularly adoption of CD7, Pax-5, TdT, CD34 and Ki-67 stainings in combination are helpful of making a diagnosis for T-LBL/ALL. Analysis of TCR gene rearrangement will be helpful for the diagnosis of a few difficult cases.

To study the significance and differential diagnosis of intralymphatic accumulation of lymphocytes.The clinical and pathologic features of 4 cases of intralymphatic accumulation of lymphocytes were reviewed retrospectively. Immunohistochemical study was carried out and follow-up data were analyzed.The sites of involvement included tonsil (2 cases), pharynx (1 case) and appendix (1 case). The duration of disease ranged from 1 week to 3 months. Follow up of the patients (from 3 to 84 months) showed no evidence of disease recurrence. Gross examination of the tissues (except in the case of appendiceal involvement) showed polypoid changes. Histologically, the lymphatic channels were filled up with small lymphocytes and associated with fibrosis in the vicinity. Immunohistochemical study revealed a T-cell phenotype of the intralymphatic lymphoid cells.The accumulation of lymphocytes in lymphatic channels is associated with a benign clinical course. This phenomenon may be due to retention of lymphocytes secondary to the perilymphatic chronic inflammation and fibrosis. Although the lesion simulates intravascular lymphomatosis morphologically and shows a uniform T-cell phenotype, the lymphoid cells lack obvious cellular pleomorphism and mitotic activity. The solitary nature of the lesion, when coupled with the indolent clinical behavior, is also helpful in the differential diagnosis.

To investigate the architectural and cytological variations of plasma cell neoplasms, and discuss the diagnosis and differential diagnosis.Histological and immunohistochemical examinations were used to study the morphologic and immunophenotypic features of 46 cases of plasma cell neoplasms.40 out of 46 cases were diffuse growth pattern. 3 cases had a nestlike architecture that can mimic neuroendocrine tumors and 3 cases had a prominent fibrous sclerosis background. Amyloid deposition, calcification or ossification and angiomatoid areas can be prominent and may obscure the neoplastic plasma cells. Cytologically, 30 cases were composed of relatively mature plasma cells and can be recognized without too much difficulty. Tumor cells resembled immunoblasts in 6 cases and small lymphocytes in 4 cases. In another 2 cases tumor cells were easily confused with Signet-ring cells or clear cells. Tumor cells were composed of anaplastic cells, histocytoid cells and spindle cells in each one case, respectively. Lastly, tumor cells can be polymorphous which composed of multilobated, monocytoid or multinucleated cells in one case. 93.1% (27/29) cases expressed CD79a while only 5.1% (2/39) cases expressed CD20.87.1% (27/31) cases expressed CD38 and 83.3% (25/30) cases expressed CD138, 96.8% (30/31) cases expressed MUM-1. Light chain restrictions were detected in 38 cases, that 27 cases expressed lambda and 11 for kappa.Except for the common architecture and cytology in plasma cell tumor, unusual morphology may appear. Thus, pay attention to distinguish from lymphoma such as small lymphocytic lymphoma and anaplastic large cell lymphoma, pooly differentiated carcinoma, clear cell carcinoma or Signet-ring cell carcinoma, sarcoma, etc. And immunohistochemistry is essential in the diagonosis.

To study the clinicopathologic features of 66 cases of primary systemic anaplastic large cell lymphoma (ALCL), with emphasis on the differences between ALK-positive and ALK-negative cases.The clinical data of 66 cases of ALCL was analyzed. The histologic features were reviewed. Immunohistochemical study for CD30, ALK protein, epithelial membrane antigen, CD2, CD3, granzyme B and TIA-1 was carried out. In-situ hybridization for small mRNA of Epstein-Barr virus (EBER) was also performed. The chromosomal abnormalities were studied by fluorescence in-situ hybridization (FISH). The differences between ALK-positive and ALK-negative cases were statistically analyzed.There were 48 cases of ALK-positive ALCL and 18 cases of ALK-negative ALCL. The patients with ALK-positive ALCL were younger than those with ALK-negative ALCL (P0.05), with the median age being 18 years and 36 years, respectively. Fever, especially hyperpyrexia, was more commonly observed in ALK-positive ALCL patients than in ALK-negative ALCL patients (33 cases versus 4 cases, P0.05). The overall survival rate and median duration of survival in patients with ALK-positive ALCL were higher and longer than those in patients with ALK-negative ALCL (80% versus 71%; 21 months versus 12.5 months, P0.05). There were however no significant differences in histology between ALK-positive ALCL and ALK-negative ALCL. Histologically, most cases showed diffuse growth pattern. Nodular pattern was demonstrated in a minority of cases. "Hallmark" cells were seen in most of the ALCL cases. Focal necrosis and myxomatous stroma were identified in a few cases. Most ALK-positive cases belonged to the common variant (35 cases). A small number represented lymphohistiocytic variant (8 cases). Small cell variant and sarcomatoid subtype were found only in few cases (3 cases and 2 cases, respectively).On the other hand, common variant (17 cases) constituted the majority of ALK-negative ALCL. Lymphohistiocytic variant was seen in only 1 case. Immunohistochemical study showed that ALK-positive ALCL always expressed CD30 and epithelial membrane antigen. ALK-positive ALCL more often expressed epithelial membrane antigen (100% versus 72%; P0.05) but less so for T-cell markers (including CD2, CD3, CD43 and CD45RO). Cytotoxic molecules were more commonly expressed in ALK-positive ALCL (P0.05). EBER was negative in all cases studied. FISH showed that in ALK-positive ALCL, 1 case had normal ALK gene, 1 had deletion and multicopy and 2 had deletion. On the other hand, 1 case of ALK-negative ALCL had normal ALK gene.While there are no significant morphologic differences between ALK-positive ALCL and ALK-negative ALCL, the clinical features, immunophenotypes and genetic features of both groups vary. These differences are helpful in guiding the differential diagnosis.

To investigate the clinicopathologic features and differential diagnostic methods for follicular dendritic cell sarcoma.Histological and immunohistochemical examinations and EBER in situ hybridization were used to investigate the pathological features of 5 cases of follicular dendritic cell sarcoma, and related literature was reviewed.There were 3 males and 2 females with a median age of 54 years (range, 28 - 75 years). The location of lesions included lymph node (2 cases), tonsil (1 case), stomach (1 case), and liver (1 case). The growth patterns were fascicular or whorls and/or diffuse. The neoplastic cells were spindle or ovoid in shape with indistinct border and slightly eosinophilic cytoplasm. The nuclei were round, oval or spindle in shape with small distinct nucleoli. Warthin-Finkeldey-like multinucleated giant cells were detected in two cases. Mitotic figures were found in 1-22/10 HPF. Immunohistochemical staining showed that CD21 and CD23 (3 of 5), CD35 (4 of 5), D2-40 (4 of 4), and CXCL13 (3 of 4) were positive in neoplastic cells. EBER was detected in one of five cases by in situ hybridization. Four cases were followed-up for 6 approximately 25 months and no recurrence or death was observed yet.Follicular dendritic cell sarcoma is an extremely rare and should be considered as a moderately malignant tumor, and may present histological polymorphism with certain distinctive features. Immunohistochemistry is necessary in differential diagnosis to distinguish from other tumors.

To study the morphologic features, immunophenotypes, differential diagnoses and prognosis of histiocytic sarcoma (HS).The clinical and pathologic findings of 6 cases of HS were reviewed. Immunohistochemical assay (Elivision staining) was also performed. Follow-up information was available in 4 patients.There were altogether 3 males and 3 females. The age of patients ranged from 12 to 81 years old (median = 54.6 years). The sites of involvement included lymph node (number = 2 cases) and skin or soft tissue (number = 4 cases). The tumor was composed of sheets of large epithelioid cells with abundant eosinophilic cytoplasm, oval to irregular nuclei, vesicular chromatin and large nucleoli. Binucleated form was not uncommon. Two of the cases showed increased pleomorphism with multinucleated tumor giant cell formation. Focal cytoplasmic with foamy appearance was identified in 3 cases. One case demonstrated foci of spindly sarcomatoid appearance. Hemophagocytosis was identified in 2 cases. Mitotic figures were readily identified. The tumor cells were often accompanied by various numbers of inflammatory cells. Immunohistochemical study showed that all cases were diffusely positive for leukocyte common antigen, CD4, CD68 and CD163. Four of the 5 cases studied also expressed lysozyme. Amongst the 4 patients with follow-up information available, 3 died of the disease at 6 to 11 months interval after diagnosis. One patient, whose lesion was localized at the skin and soft tissue, survived for 3 years, with no evidence of tumor recurrence.Accurate diagnosis of the HS is based on the combination of morphologic examination and immunohistochemical assay. HS often presents with clinically advanced disease and pursues an aggressive clinical course, with a poor response to therapy. However, a subset of cases presenting with clinically localized lesion may carry a relatively favorable long-term outcome.

To study the value of loss of CD10 expression in the diagnosis and differential diagnosis of follicular lymphoma (FL).One hundred and twenty-six cases of FL and 31 cases of reactive follicular hyperplasia (RFH) were studied with routine microscopy and immunohistochemistry.Loss of CD10 expression was observed in 37 cases (29.4%) of FL. Three patterns of CD10 loss were demonstrated, as follows: diffuse CD10 loss in all of the neoplastic follicles (33/37, 89%), CD10 loss in most follicles (3/37, 8%) and CD10 loss in only a few follicles (1/37, 3%). In general, loss of CD10 was frequently seen in higher-grade FL. Morphologically, the cases with CD10 loss showed follicular architecture. The neoplastic follicles in high-grade FL were of various sizes and showed irregular margins, while those in low-grade FL were relatively uniform in size with regular margin. Sometimes, the CD10-negative FL cells contained a clear cytoplasm, mimicking monocytoid B cells. On the other hand, CD10 expression was found in all of the 31 cases of RFH studied, with the exception of occasional individual or regressed follicles.The expression of CD10 differs in FL and RFH. Loss of CD10 expression is seen mainly in FL. It is thus considered as a valuable parameter in differentiating between FL and RFH.

To study the clinicopathologic features, diagnosis and differential diagnosis of systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease of childhood (CSEBV(+)T-LPD).Thirty cases of CSEBV(+)T-LPD were retrospectively studied by light microscopy, immunohistochemistry and in-situ hybridization for EBV-encoded RNA (EBER). The clinical information and follow-up data were analyzed.Nineteen of the 30 patients were males and 11 females. The median age of disease onset was 9 years (range = 1.5 to 32 years). The average duration between disease onset and diagnosis was 14 months. The major clinical manifestations were fever (96.7%), lymphadenopathy (83.3%) and hepatosplenomegaly (66.7%). Cutaneous manifestations were not uncommon, which included hypersensitivity to mosquito bite (13.3%) and skin rash (20.0%). Six of the 20 patients died on follow up. Histologically, the lymph nodes showed expansion of T zone, with diminished or effaced lymphoid follicles. The lymphoid cells were of small to medium size. Scattered large lymphoid cells were also identified in the expanded T zone. Furthermore, the liver and spleen showed mild to marked sinusoidal infiltration. In some cases, various degrees of sinus histiocytosis with erythrophagocytosis were present. Skin biopsies showed mild to marked degree of lymphocytes infiltration in dermis. Immunohistochemical study and in-situ hybridization showed that the EBER-positive cells were of T lineage and CD3 positive. They also expressed cytotoxic molecules granzyme B and TIA-1. Seven of the 8 cases examined were CD8 positive, while the remaining case was mainly CD4 positive. Thirteen of 15 cases were shown to be CD56 negative. The number of EBER-positive cells ranged from 5 to more than 500 per high-power field. These cells included small to large lymphoid cells located mostly in the expanded T zone and sometimes in the germinal centers. Nine of the 30 cases, which consisted mainly of medium to large-sized lymphoid cells, were also EBER positive.Systemic EBV-positive T-cell lymphoproliferative disease of childhood occurs most often in children and young adults, with a median age of 9 years. It has a subacute or chronic clinical course. Most of the patients have evidence of systemic disease, often with lymph node, liver, spleen and skin involvement. It carries a poor clinical outcome and can be life-threatening. The disease is characterized by a clonal proliferation of EBV-infected T cells with cytotoxic immunophenotype. Definitive diagnosis requires correlation between clinical, pathologic and ancillary investigation findings.

To evaluate the efficiency of the BIOMED-2 PCR assay and its implication in the diagnosis of mature B-cell non-Hodgkin's lymphomas.Clinical, morphological and immunohistochemical features of 72 cases of non-Hodgkin's lymphomas were studied, including 25 reactive lymphoid hyperplasia, 37 diffuse large B cell lymphomas (DLBCL) and 35 extranodal marginal zone lymphomas of mucosa associated lymphoid tissues (MALT lymphoma and in addition, 25 cases of reactive lymphoid hyperplasia were used as the controls). DNA was exacted from the paraffin embedded formalin fixed tissue blocks and the quality of DNA was assessed using the BIOMED-2 specimen control reaction. Adequate samples were then analyzed by BIOMED-2 for immunoglobulin heavy and kappa light chain rearrangements.Adequate DNA was obtained in 83 of 97 samples, including 60 mature B cell lymphomas and 23 reactive lymphoid hyperplasia. Clonal B-cell gene rearrangements were detected in 57 of 60 (95%) lymphomas. In contrast, clonal Ig gene rearrangements were not detected in any of the 23 cases of reactive lymphoid hyperplasia.BIOMED-2 assay is highly sensitive and specific for the detection of clonal B cell gene rearrangement using routine paraffin embedded formalin fixed specimens.