Death caused by possible unrecognized (too Late Recognized) Mycobacterium gordonae infection in a patient with angioimmunoblastic T-cell lymphoma.

Here, we present possible death caused by Mycobacterium gordonae infection in a patient with angioimmunoblastic T-cell lymphoma. Our patient was severely immunocompromised in whom we suspect to an infection, but we did not have isolates until she died. After she died, we received a positive sputum culture of M. gordonae. We conclude that when having severely immunocompromised patients with suspicion of infection but without isolates we should always consider the saprophytic mycobacteria. These mycobacteria require a long period of isolation, but patients with these mycobacteria are potentially curable if appropriate treatment is applied for a sufficiently long period.

Therapeutic effects of Salmonella typhi in a mouse model of T-cell lymphoma.

In this study, we assessed the effectiveness of a live, attenuated Salmonella enterica serovar Typhi (S. Typhi) vaccine strain as a cancer immunotherapy in a mouse model of metastatic T-cell lymphoma. EL4 tumor-bearing C57BL/6J mice immunized with S. Typhi strain CVD 915, by injection into the tumor and the draining lymph node areas, displayed a significant decrease in tumor growth, a reduction in the mitotic index (MI) of tumors, a delayed development of palpable lymph node metastases and most importantly improved survival, compared to untreated mice. Besides, complete tumor regression was achieved in a small number of bacteria-treated mice. A successful therapeutic response associated with a significant reduction of tumor mass was evident as early as 5 days after treatment. The administration of Salmonella to tumor-bearing mice promoted early cellular infiltration (mainly neutrophils) within the tumor, and was accompanied by a decreased intratumoral interleukin 10 production as well as by leukocyte expansion in tumor draining lymph nodes. A tumor-specific memory immune response was induced in most of cured animals, as evidenced by the lack of tumor growth after a rechallenge with the same tumor. EL4 cells cultured with live Salmonella failed to proliferate and underwent apoptosis in a dose-dependent, time-dependent, and contact-dependent manner. To our knowledge, these results demonstrate for the first time the efficacy of a S. Typhi vaccine strain as an oncolytic and immunotherapeutic agent against a highly malignant tumor and support the use of S. Typhi-based vaccine strains in cancer therapy.

Paediatric T-cell lymphoma of the appendix: a case report.

A 7-year-old boy with no history of malnutrition or diarrhoea complained of acute abdominal pain, was diagnosed with acute appendicitis, and underwent appendectomy. Histologically, a diffuse infiltrate of large atypical lymphoid cells was found in the entire appendiceal wall. Immunohistochemical examination revealed that the tumour cells expressed T-cell receptor (TCR)-ßF1, CD3, CD4, CD25, cytotoxic-related protein TIA1 and granzyme-B, but were negative for CD8, Foxp3, CD20, CD30 and CD56. Polymerase chain reaction (PCR) revealed clonal bands of TCR-γ gene products in the tumour tissue. No anti-cytomegalovirus antibody-positive cells were detected. In situ hybridization revealed no nuclear signals of Epstein-Barr virus (EBV)-encoded RNA. Helicobacter pylori infection was detected in tumour tissue by anti-East Asian cytotoxin-associated gene (Cag) A antibody and PCR using its specific primers. The patient received chemotherapy and has remained in remission for 2 years. To the best of our knowledge, only two cases of appendiceal T-cell non-Hodgkin lymphoma (NHL) have been reported, both in elderly patients. We believe that this is the first reported case of childhood CD4- and TIA1-positive cytotoxic T (Th1)-cell NHL in the appendix or gastrointestinal tract. Helicobacter pylori infection might be an initiator of atypical cytotoxic T-cell proliferation. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1302380563830412.

Listeria monocytogenes in a young patient with non Hodgkins lymphoma: case report.

Listeria monocytogenes is an intracellular food-borne pathogen, widely distributed in the environment, which rarely causes clinical infection in healthy people, but may cause severe disease in immunocompromised patients. A case of listeriosis is certified in an immunocompromised patient, thus confirming this microorganism to be an opportunistic human pathogen.

A novel functional T cell hybridoma recognizes macrophage cell death induced by bacteria: a possible role for innate lymphocytes in bacterial infection.

We have established a novel TCRalphabeta (TCRVbeta6)(+)CD4(-)CD8(-) T cell hybridoma designated B6HO3. When the B6HO3 cells were cocultured with bacterial-infected J774 macrophage-like cells, IFN-gamma production by B6HO3 cells was triggered through direct cell-cell contact with dying J774 cells infected with Listeria monocytogenes (LM), Shigella flexneri, or Salmonella typhimurium that expressed the type III secretion system, but not with intact J774 cells infected with heat-killed LM, nonhemolytic lysteriolysin O-deficient (Hly(-)) LM, plasmid-cured Shigella, or stationary-phase Salmonella. However, the triggering of B6HO3 cells for IFN-gamma production involved neither dying hepatoma cells infected with LM nor dying J774 cells caused by gliotoxin treatment or freeze thawing. Cycloheximide and Abs to H-2K(d), H-2D(d), Ia(d), CD1d, TCRVbeta6, and IL-12 did not inhibit the contact-dependent IFN-gamma response, indicating that this IFN-gamma response did not require de novo protein synthesis in bacterial-infected J774 cells and was TCR and IL-12 independent. Thus, in an as yet undefined way, B6HO3 hybridoma recognizes a specialized form of macrophage cell death resulting from bacterial infection and consequently produces IFN-gamma. Moreover, contact-dependent interaction of minor subsets of splenic alphabeta T cells, including NKT cells with dying LM-infected J774 and bone marrow-derived macrophage (BMM) cells, proved to provide an IFN-gamma-productive stimulus for these minor T cell populations, to which the parental T cell of the B6HO3 hybridoma appeared to belong. Unexpectedly, subsets of gammadelta T and NK cells similarly responded to dying LM-infected macrophage cells. These results propose that innate lymphocytes may possess a recognition system sensing macrophage cell "danger" resulting from bacterial infection.

Infection by Rhodotorula sp. in children receiving treatment for malignant diseases.

Rhodotorula sp. are commensal yeasts that may cause opportunistic infections. There have been only a few case reports of Rhodotorula fungemia in children with cancer, and in all of them the patients had a central venous catheter inserted. The authors report three nonfatal cases of fungemia by Rhodotorula in patients with post-chemotherapy neutropenia. Two of three patients required catheter removal, and a response was achieved with systemic antifungal therapy. Aggressive therapy may be required for selected high-risk patients.

Clinical relevance of three subtypes of primary sinonasal lymphoma characterized by immunophenotypic analysis.

BACKGROUND: The purpose of this study was to investigate the clinical relevance of subtypes categorized by immunophenotypic analysis in primary sinonasal lymphomas. METHODS: Eighty patients with localized non-Hodgkin's lymphoma involving the nasal cavity and/or paranasal sinuses were divided into three subtypes on the basis of their immunohistochemical findings: (A) B-cell lymphoma (n = 19), (B) T-cell lymphoma (n = 27), and (C) natural killer (NK)/T-cell lymphoma (n = 34). The clinicopathologic profiles, immunophenotypic data, patterns of treatment failure, and survival data among the three patient groups were retrospectively compared. RESULTS: The nasal cavity was the predominant site of involvement in T-cell and NK/T-cell lymphoma, whereas sinus involvement without nasal disease was common in B-cell lymphoma. Systemic B symptoms were frequently observed in NK/T-cell lymphoma. Almost all patients with NK/T-cell lymphoma showed a strong association with the Epstein-Barr virus by in situ hybridization studies. Sixty-five patients (81%) patients achieved complete remission after initial treatment, but 36 (55%) of these subsequently experienced treatment failure. Although there were no significant differences in locoregional failure rates among the patients of the three groups, distant failure was far more common in B-cell or NK/T-cell lymphoma than in T-cell lymphoma (p =.005). Most B-cell lymphoma cases showed a predilection for sites of systemic failure in the nodal and extranodal sites below the diaphragm, such as the paraaortic lymph nodes or the gastrointestinal (GI) tract, whereas patients with NK/T-cell lymphoma showed an increased risk of systemic dissemination to the skin, testes, or GI tract, including the development of hemophagocytic syndrome. The 5-year actuarial and disease-free survival rates for all patients were 57% and 51%, respectively. Of the three subtypes of primary sinonasal lymphomas, T-cell lymphoma seemed to carry the most favorable prognosis and NK/T-cell lymphoma the worst. (The 5-year actuarial survival rate was 57% for B-cell lymphoma, 80% for T-cell lymphoma, 37% for NK/T-cell lymphoma; p =.02, log-rank.) By univariate and multivariate analyses, immunophenotype was identified as the most important prognostic factor. CONCLUSIONS: Our data indicate that the three subtypes of primary sinonasal lymphomas classified by immunohistochemical studies exhibit different clinical profiles, different patterns of failure, and different treatment outcomes. Given these observations, it is concluded that the recognition of these distinct subsets, diagnosed on the basis of immunophenotypic study, is very important and clinically relevant in predicting their potential behavior and prognosis.

[Nasal NK/T lymphoma. A case report]. / Lymphome NK/T nasal. A propos d'un cas.

We report a case of nasal NK/T lymphoma occurring in a 42 year old man, after a 2 year history of nasal obstruction initially related to chronic sinusitis. A first superficial biopsy was not contributive. Twenty months later, a second nasal biopsy led to the diagnosis of nasal NK/T cell lymphoma in view of the presence of a pleomorphic lymphoid infiltrate associated with necrosis and angiocentric features. Extensive immunohistochemical studies performed on paraffin and frozen sections together with genotypic analysis supported the NK cell origin of the neoplastic cells. In addition, EBV infection was established by in situ hybridization which showed EBERs transcripts in the nuclei of virtually all neoplastic cells. The tumour rapidly progressed and the patient died six months after diagnosis.

Detection of epstein-barr virus in nasal T-cell lymphoma.

The close relationship between Epstein-Barr virus (EBV) and nasal T-cell lymphoma (NTL) has frequently been reported. However, the status of the infection, either lytic or latent, is obscure. This study involved 16 patients with NTL. Phenotypes of lymphoma cells were examined by immunohistochemical staining using CD3, CD4, CD8, CD20 and CD45RO monoclonal antibodies. EBV-encoded small nuclear RNA (EBER)-1 and EBV NotI tandem repeat region were detected by reverse transcription, using a rapid (< or = 60 min) in situ hybridization technique. Tumor cells expressed at least one T-cell marker, such as CD3, CD4, CD8 and CD45RO. CD20 was not detected in any of the cases. EBER-1 was identified in all cases; no Notl tandem DNA repeat was demonstrated. All cases demonstrated a T-cell phenotype. These data suggest that NTL is associated with EBV infection in the latent phase.

Cytotoxic T-cell lymphoma diffusely involving the entire gastrointestinal tract associated with Epstein-Barr virus and tubercle bacilli infection.

We describe a rare case of cytotoxic gastrointestinal T-cell lymphoma with protein-losing enteropathy. Initial examination revealed the coexistence of T-cell lymphoma and tuberculosis in the mesenteric lymph node and liver. Despite anti-tuberculosis and anti-cancer treatment, the patient experienced chronic diarrhea and malabsorption and died approximately 3 years after onset. Autopsy specimens revealed medium-sized lymphoma cells, with a phenotype of CD3+, CD4-, CD7+, CD8+, CD30-, CD56-, CD103 (HML-1)-, TIA-1+, and granzyme B+, proliferating primarily and consistently in the mucosa of the entire bowel tract from esophagus to rectum. Interestingly, Epstein-Barr virus (EBV)-encoded small nuclear RNAs were detected in the tumors by in situ hybridization. Southern blot analysis revealed monoclonal proliferation in the EBV-infected T cells. Although the present case can possibly be categorized as an intestinal T-cell lymphoma according to the Revised European-American Lymphoma Classification, the case showed a unique clinical course and distribution of lymphoma cells. We present here an interesting case of gastrointestinal cytotoxic T-cell lymphoma and examine the possible association with infectious agents.

Listeriosis in pediatric oncology patients.

BACKGROUND: Adult cancer patients are considered to be at an increased risk for Listeria monocytogenes infections, but, to the authors' knowledge, little information regarding this infection in the pediatric oncology population has been published. METHODS: The Memorial Sloan-Kettering Cancer Center microbiology laboratory's database was searched for cases of Listeria monocytogenes infection during the period from January 1981 to December 1996, and thorough chart reviews of the cases identified in patients age < 21 years were performed. RESULTS: Listerial infections occurred in 5 children (3 with leukemia, 1 with lymphoma, and 1 with a brain tumor) among 20,612 admissions to the pediatric department during this period. All five children were actively receiving therapy for their malignancy, and two also were receiving other potentially immunosuppressive therapies. None was receiving co-trimoxazole prophylaxis. All were treated successfully for the Listeria monocytogenes infection with ampicillin and gentamicin (four patients) or ampicillin alone (one patient). At last follow-up two patients were long term, event-free survivors, two had died of their underlying malignancy, and one patient had died of cytomegalovirus pneumonitis. CONCLUSIONS: Listeria monocytogenes infections in pediatric oncology patients can be treated successfully with ampicillin-containing antibiotic regimens.

Primary intestinal non-Hodgkin's lymphoma and Epstein-Barr virus: high frequency of EBV-infection in T-cell lymphomas of Mexican origin.

Epstein-Barr virus is universally associated with endemic Burkitt's lymphoma (BL) and undifferentiated nasopharyngeal carcinoma and can be detected in a significant proportion of cases of Hodgkin's disease (HD) and peripheral T-cell lymphoma, but only rarely in sporadic B-NHL. The frequency of EBV-positivity in certain neoplasms shows important geographic variations. Both HD and sporadic BL from Latin America have shown higher rates of EBV-association than cases from Western countries. In T-NHL, the frequency of EBV-positivity is influenced by the site of the primary tumor and the phenotype of the neoplastic cells. Nasal and nasal-type T-NHL, which show a T/NK-cell phenotype with expression of CD56 are virtually always EBV-associated, whereas only a proportion of nodal, gastrointestinal and pulmonary T-NHL are EBV-infected. A recent investigation of primary intestinal lymphomas of Mexican origin demonstrated EBV-positivity in all examined cases of T-NHL and BL and a proportion of other B-NHLs. The presence of EBV was independent of the presence or absence of enteropathy. Two of 6 cases studied showed CD56 expression. The high rate of EBV-positivity independent of histologic subtype is in contrast to the low to intermediate rates of EBV-positivity found in cases of intestinal T-NHL from Western countries and indicates that geographic differences in the frequency of EBV-association of lymphoid neoplasms might also extend to a fraction of peripheral T-cell lymphomas.

[Cytomegalovirus retinitis. Blindness in a patient with lymphoma]. / Cytomegalovirus-retinitis. Blindhed hos en lymfompatient.

We present a case of a 52 year-old female treated with high dose chemotherapy for a malignant lymphoma. After a six month period on maintenance chemotherapy the patient developed a cytomegalovirus induced retinitis which was first suspected to be a lymphoma relapse. She went blind, despite treatment with ganciclovir.

Coxiella burnetii in polymorphic lymphocytes in tissue and blood of patients with polymorphic reticulosis.

Coxiella burnetii is a well-known causative agent of granulomatous inflammation and an inducer of morphological changes and transformation of human B lymphocytes in vitro. An association of the organism with polymorphic reticulosis (PMR), a malignant granulomatous inflammation characterized by polymorphic lymphocytes, was examined. The infection of C. burnetii was demonstrated in all cases tested, especially in polymorphic lymphocytes. Also the presence of morphologically transformed peripheral blood lymphocytes (PBLs) infected with C. burnetii was demonstrated. In cultures of blood lymphocytes, C. burnetii-infected polymorphic cells identified as B cells became immortalized in vitro. These findings implicate the role of C. burnetii in the process of PMR.

Immunoblastic transformation of a Sezary syndrome in a black Caribbean patient without evidence of HTLV-I.

We describe an unusual case of Sezary syndrome which transformed into a large T-cell non Hodgkin's lymphoma (immunoblastic) in a black man of Caribbean descent with negative HTLV-I serology and no evidence of HTLV-I infection by DNA analysis using sensitive techniques. The disease presented as a small-cell Sezary syndrome and transformed in an inguinal lymph node one year from diagnosis. Immunological markers in the small and large cells showed a mature T-cell phenotype CD4+, CD8- with expression of T-cell activation markers and a high proliferative rate. Ultrastructural analysis confirmed small Sezary cells with serpentine nucleus in the peripheral blood and immunoblasts in the lymph node. Cytogenetics demonstrated complex clonal chromosome abnormalities with involvement of 7q35, the locus for the beta chain of the T-cell receptor (TCR). Southern-blot analysis showed the same rearrangement of the TCR beta, gamma, delta chain genes in lymph node and peripheral blood cells. Antibodies to HTLV-I were not detected in the serum by ELISA and particle agglutination (PA) nor HTLV-I specific sequences were demonstrated by nested polymerase chain reaction with primers to the envelope proteins, LTR and tax/rex of HTLV-I in both tissues, blood and lymph node. The disease had an aggressive course and was refractory to therapy; the patient died of progressive disease 28 months from presentation. Two unusual features characterised this patient's illness: immunoblastic transformation of a Sezary syndrome in a patient of Afro-Caribbean origin without evidence of HTLV-I DNA sequences and negative HTLV-I serology and the atypical lymph node histology resembling ATLL.

Epstein-Barr virus is localized in the tumour cells of nasal lymphomas of NK, T or B cell type.

Seven cases of nasal lymphoma were studied to identify the lineage of Epstein-Barr virus (EBV)+ cells using dual-labelling methods. Five cases were phenotypically and genotypically of natural killer cell (NK) type with germ-line configuration of T-cell receptor (TcR) beta-chain gene and immunoglobulin heavy-chain joining region (IgJH) gene, with one case each of T- and B-cell type showing rearranged TcR beta or IgJH and lambda-light chain genes respectively. EBV genome was clonal in all these cases except in the B-cell case where its clonality was undeterminable. Using in situ hybridization (ISH) for EBV-encoded small nuclear RNA 1 and 2 (EBER), signal was detected in 45% to 88% of nucleated cells in the tumours. Immunostaining for EBV latent membrane protein-I (LMP) also revealed numerous LMP+ cells in 3/5 NK-type cases and the T- and B-cell cases. Using ISH for EBER combined with immunostaining for CD markers and double immunohistochemistry for LMP and CD markers, the predominant lineage of the EBV+ cells was identified as: CD2+CD3-CD19-CD20- CD45R0 +/- CD56+CD68- in the NK-type cases, CD2+CD3 +/- CD19-CD20- CD45R0+CD56-CD68- in the T-cell case and CD20+CD45R0-CD68- in the B-cell case, in agreement with the genotype and phenotype of each tumour. These results show that, in EBV+ nasal lymphomas of NK, T- or B-cell lineage, EBV was consistently associated with the tumour-cell population and support the view that EBV serves a promoting role in the pathogenesis of different types of EBV+ nasal lymphoma.