Torsades de pointes episode in a woman with high-grade fever and inflammatory activation: A case report.

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.

Primary cutaneous mantle cell lymphoma: Report of a rare case.

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.

EBV-positive T/NK lymphoproliferative diseases: analysis of prognostic factors for patients in China.

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.

Infectious mononucleosis caused by EBV infection with clonal cytotoxic T cells in an infant patient.

Infectious mononucleosis (IM) is a self-limiting lymphoproliferative disease usually caused by Epstein-Barr virus (EBV) infection, which predominantly infects B lymphocytes in adults. IM that occurs in T cells infected with EBV is rare and only a few cases have been reported worldwide. We describe a rare case of IM in an infant with an EBV infection predominantly in clonal cytotoxic T cells. A cervical node taken from a 10-month-old male infant was retrospectively analyzed. The architecture of the lymph node was effaced mostly with focal to extensive coagulative necrosis. In some areas, numerous infiltrating lymphocytes were detected, expressing CD2, CD3, and granzyme B, but lacked CD5 and CD56. EBV-encoded small RNAs were detected in the majority of lymphocytes. Furthermore, the T cell presented with T-cell receptor rearrangements. The patient did not do any radiation and chemotherapy. Thirty-two months follow up showed that the patient was well. We speculate IM can occur in infants through EBV infection of clonal cytotoxic T cells.

Epstein-Barr Virus-Positive T/NK-Cell Lymphoproliferative Disorders Manifested as Gastrointestinal Perforations and Skin Lesions: A Case Report.

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.

Aberrant phenotypes in Kikuchi's disease.

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.

Langerhans cell sarcoma in the cervical lymph node: a case report and literature review.

Langerhans cell sarcoma (LCS) is extremely rare, with only 36 cases reported in English literature. In this report we represent the case of a 77-year-old woman with a 1-month history of left neck swelling and pain. A diagnosis of LCS was rendered from pathological findings of the cervical lymph node biopsy. The patient's condition deteriorated rapidly and she died 2 days after diagnosis. A literature review in the context of the present case was performed to better enhance understanding of the early diagnosis and treatment of this unusual lesion.

[Clinicopathologic analysis of intestinal follicular lymphoma first presenting with gastrointestinal symptoms].

OBJECTIVE: To study the clinical features, endoscopic findings, pathologic diagnosis and treatment options of intestinal follicular lymphoma first presenting with gastrointestinal symptoms. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Clinicopathologic features of systemic EBV-positive T/NK-cell lymphoproliferative disease in adults].

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.