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H Stein

Publications and source records attributed to H Stein.

At least 19 recordsLinked to original sources
PubMed2007

[The morphologic variants of KSHV/HHV 8-associated lymphoproliferations].

KSHV/HHV 8 infection is associated with primary effusion lymphoma, multicentric Castleman disease (MCD) and MCD-associated plasmablastic lymphoma. We report the case of an HIV-infected male with Kaposi sarcoma, MCD in the lymph node and development of a KSHV/HHV 8-associated plasmablastic lymphoma in the liver. Immunohistochemistry revealed an HHV 8 infection of plasmablasts showing cytoplasmic IgM/lambda expression. To the best of our knowledge, liver infiltration by a MCD-associated HHV 8 positive plasmablastic lymphoma has not been documented previously. The differential diagnosis is discussed.

Adult↗
PubMed2007

[Burkitt's and Burkitt-like lymphoma. Molecular definition and value of the World Health Organisation's diagnostic criteria].

Among aggressive mature B-cell lymphomas, a reproducible morphological and immunohistological distinction between Burkitt's lymphoma and diffuse large B-cell lymphoma (centroblastic variant) is impossible in a substantial number of cases. The German reference centres for hematopathology collected 220 retrospective cases of aggressive mature B-cell lymphoma whose classification according to the current World Health Organisation criteria was reviewed. Gene expression analysis (Affymetrix) was performed in all cases and chromosomal translocations were determined using fluorescence in situ hybridization. Chromosomal losses and gains were analysed by matrix comparative genomic hybridisation and clinical data were successfully collected for most patients. The application of a novel bioinformatics method led to the identification of a stable and reproducible gene expression signature specific for Burkitt's lymphoma. A total of 44 cases were identified by this molecular signature [designated molecular Burkitt's lymphoma (mBL)]. These molecular Burkitt's lymphomas showed the morphology and immunohistology of classical or atypical Burkitt's lymphoma cases in 29 instances. However, 15 of the molecular Burkitt's lymphoma cases had the morphology of diffuse large B-cell lymphoma or could not be further specified. All molecular Burkitt's lymphomas showed an expression of BCL-6 and CD10, but a MYC translocation was not demonstrable in more than 10% of cases. Of significance is that more than 20% of the molecular Burkitt's lymphomas expressed BCL-2, although weakly in most instances. Our data demonstrate that: (1) the morphological, immunophenotypical and genetic spectrum of Burkitt's lymphoma is broader than previously expected, and (2) our molecular Burkitt's lymphoma signature enables a more precise and extended definition this lymphoma.

Burkitt Lymphoma↗
PubMed2006

Wotherspoon criteria combined with B cell clonality analysis by advanced polymerase chain reaction technology discriminates covert gastric marginal zone lymphoma from chronic gastritis.

BACKGROUND AND AIMS: Gastric mucosa associated lymphoid tissue lymphoma is a well defined B cell lymphoma yet often impossible to distinguish from severe chronic gastritis on morphological grounds alone. Therefore, it was suggested to use the clonality of the immunoglobulin (Ig) heavy chain (H) genes, as detected by polymerase chain reaction (PCR), as a decisive criterion. However, there is controversy as to whether B cell clonality also exists in chronic gastritis, hence rendering this approach futile at present. METHODS: An expert panel re-examined the histology and immunohistochemistry of a total of 97 cases of gastric biopsies, including clearcut marginal zone lymphoma, chronic gastritis, and ambiguous cases, applying the Wotherspoon criteria on the basis of haematoxylin-eosin and CD20 immunostainings. In addition, a new and advanced PCR system for detection of clonal IgH gene rearrangements was independently applied in two institutions in each case. RESULTS: The overall IgH clonality assessments of both institutions were in total agreement. Overt lymphoma (Wotherspoon score 5) was clonal in 24/26 cases. Chronic gastritis (Wotherspoon scores 1 and 2) was not clonal in 52/53 cases; the clonal case being Wotherspoon score 2. Of 18 cases with ambiguous histology (Wotherspoon scores 3 and 4) four were clonal. CONCLUSIONS: Using advanced PCR technology, clonal gastritis is extremely rare, if it exists at all. Thus B cell clonality in Wotherspoon 3 and 4 cases is regarded as suitable for definitively diagnosing gastric marginal zone lymphoma.

Algorithms↗
PubMed2006

[Malignant lymphomas of the liver: new diagnostic algorithms].

Primary hepatic lymphomas represent rare neoplasms, which are partly observed in association with chronic viral hepatitis, immunosuppression and autoimmune diseases. In contrast, secondary hepatic lymphomas are much more frequent and represent disseminated disease. Lymphomas involving the liver include, with decreasing frequency, diffuse large B-cell lymphoma, small lymphocytic lymphoma, Hodgkin's lymphoma, peripheral T-cell lymphoma, follicular lymphoma and extranodal marginal zone B-cell lymphoma. Many B-cell lymphomas in the liver reveal a characteristic infiltration pattern allowing a rapid and cost-effective diagnosis based on focused immunohistochemical analyses. In contrast, most T-cell lymphomas show a more diverse morphology, which is sometimes difficult to differentiate from a reactive condition. Therefore, additional molecular analyses are frequently necessary. The differential diagnosis includes hepatitis and inflammatory bile duct diseases, undifferentiated carcinoma, inflammatory myofibroblastic tumor as well as histiocytic and dendritic cell neoplasms.

Algorithms↗
PubMed2006

[Oral EBV-associated diffuse large B-cell lymphomas in HIV-negative immunocompromised patients].

BACKGROUND: Diffuse large B-cell lymphomas (DLBCL) are non-Hodgkin's lymphomas (NHL) and with a prevalence of 30-40% they comprise the most frequent NHL in adults. Although their etiology is still unknown, a virus induction, especially by the Epstein-Barr-virus (EBV), is the subject of discussion. Patients with congenital or acquired immunodeficiency are primarily afflicted. PATIENT 1: A 39-year-old female patient developed an EBV-associated DLBCL of the plasmablastic subtype in the maxillary alveolar ridge in the region of teeth 11 and 21 after 24 years of immunosuppressive therapy with azathioprine due to myasthenia gravis. Clinically the lesion presented as a localized acute necrotizing periodontitis that was resistant to symptomatic therapy. After polychemotherapy the disease is in complete remission until today. PATIENT 2: A 56-year-old male patient developed an EBV-associated DLBCL of immunoblastic variant of the right maxillary edentulous alveolar ridge in the posterior region 7 weeks after heart transplantation and immunosuppressive therapy with azathioprine and cyclosporine A. Clinically, a soft, nonpainful, swelling measuring 1.5x0.5x0.5 cm with a central ulceration was evident. The tumor was excised followed by local radiation therapy. No recurrence was noted during a 15-year-follow-up. DISCUSSION: The presented clinical cases demonstrate the increased risk of occurrence of oral malignant B-cell lymphomas as adverse effects of immunosuppressive therapy. The demonstration of EBV in the tumor cells in both cases underlines the involvement of this virus in the pathogenesis of oral DLBCL arising in the setting of an immunodeficiency as has been shown previously in patients with HIV. CONCLUSIONS: Due to the varying and often nonspecific clinical appearance of oral DLBCL, an early biopsy and work-up by an institute specialized in hematopathology is essential for diagnosis, because these tumors may disseminate in early stages.

Adult↗
PubMed2006

Histopathology in the light of molecular profiling.

The 2001 WHO classification distinguishes five variants (centroblastic, immunoblastic, plasmablastic, anaplastic and T-cell rich) and three subtypes (primary mediastinal, intravascular and primary effusion large B-cell lymphoma) of diffuse large B-cell lymphomas (DLBCLs).The recognition of the three subtypes as distinct disease entities can be considered as an advance in our understanding of these tumours. However, the variants of DLBCLs, which significantly outnumber the subtypes in frequency, represent an unresolved area. Gene expression profiling (GEP) of the variants led to a discrepancy in results and produced more questions than answers. The authors, therefore, initiated a multi-institutional collaborative research project in Germany aimed at a subtle morphologic, genomic and transcriptional characterisation of DLBCLs and Burkitt lymphoma (BL). We included BL in our study for two reasons: (1) it belongs to aggressive B-NHLs; and (2) at present, there are no reliable criteria that can be applied to distinguish BL from DLBCL. The GEPs derived from 200 patient samples were correlated with reviewed histology, the degree of genetic imbalances and clinical features. The results of this approach show that: (i) the DLBCL can be divided into more than four molecular groups; and (ii) the BL cases, identified by the consensus of five out of six lymphoma expert pathologists, displayed a genomic and gene expression profile that was clearly distinct from those of most DLBCLs. The group of DLBCLs that resembled BL in their GEP had a remarkably good prognosis, whereas those that differed in their GEP from the consensus BLs had unfavourable survival rates. In conclusion, combined application of genomic and gene expression profiling in conjunction with consensus reviewed histology and clinical features, appears to be a reliable approach that enables a reproducible and clinically meaningful characterisation of mature aggressive B-NHLs.

Gene Expression Profiling↗
PubMed2006

Different T-bet expression patterns characterize particular reactive lymphoid tissue lesions.

AIMS: To investigate T-bet expression profiles in various lymphoid tissue diseases caused by intracellular pathogens and to compare them in disorders without an infective aetiology. Murine and in vitro experiments have shown that the expression/induction of T-bet, the master regulator of Th1 differentiation, can be achieved by obligate intracellular pathogens and high interferon (IFN)-gamma levels. METHODS: Lymph node biopsies were analysed immunohistochemically employing single and double labelling for T-bet and CD20, CD4, CD8 and CD30 detection. RESULTS: In disorders associated with high IFN-gamma levels and intracellular pathogens (infectious mononucleosis, HIV-associated lymphadenopathy, cat-scratch disease, and toxoplasmic lymphadenitis), T-bet-expressing CD4 cells were accompanied by significant numbers of T-bet-positive CD8 and B cells. A similar profile was also found in histiocytic necrotizing (Kikuchi) lymphadenitis, a disease of unknown cause. In contrast, T-bet expression in disorders without an infective aetiology was observed in only a small portion of lymphocytes. CONCLUSIONS: Increased T-bet expression does not only identify intracellular infections in lymphoid tissue associated with high IFN-gamma levels, but also implies that, under these conditions, it becomes induced in B cells, which apparently support the Th1 response. T-bet expression in Kikuchi lymphadenitis underscores the hypothesis that it is caused by an intracellular microorganism.

Antigens, CD20↗
PubMed2006

Update on extranodal lymphomas. Conclusions of the Workshop held by the EAHP and the SH in Thessaloniki, Greece.

Classification and proper treatment of extranodal lymphoma is hindered by the diversity of lymphoma types and the relative rarity of many of these tumour types. In order to review controversial issues in extranodal lymphoma diagnosis, a joint Workshop of the European Haematopathology Association (EAHP) and the Society for Hematopathology (SH) was held, where 99 selected cases were reviewed and discussed. This Workshop summary is focused on the most controversial aspect of cutaneous B-cell lymphoma, other extranodal B-cell lymphomas, plasmablastic lymphoma and anaplastic large-cell lymphoma in extranodal sites, and makes practical recommendations about diagnosis and therapeutic approaches.

Diagnosis, Differential↗
PubMed2006

Three coexisting lymphomas in one patient: genetically related or only a coincidence?

The simultaneous manifestation of different lymphomas in the same patient or even in the same tissue, defined as composite lymphoma, is very rare. The exceptional case of a patient who, presented with simultaneous manifestation of three different lymphomas after 30 years of successful treatment of a nodal T cell lymphoma is reported here. The three lymphomas were: (1) primary cutaneous marginal zone B cell lymphoma (MZBL); (2) nodal Epstein-Barr virus (EBV)-associated classic Hodgkin's lymphoma (cHL) of the B cell type; and (3) peripheral T cell lymphoma coexisting in the skin and cervical lymph node. Immunohistochemical and molecular analyses showed different clonal origins of EBV-negative cutaneous MZBL and EBV-positive B cell cHL and, in addition, the presence of the same clonal T cell population in the skin and lymph node. The simultaneous occurrence of three different, clonally unrelated lymphomas in one patient at the same time has not been reported yet.

Aged↗
PubMed2005

Primary neuroendocrine carcinoma of inguinal lymph node.

Ninety-seven percent of neuroendocrine carcinomas are located in the gastrointestinal tract or in the bronchopulmonary tree. Inguinal lymph nodes as the primary tumor site for neuroendocrine carcinoma represent a very unusual location, and have only been described in 2 patient series in the literature. A 64-year-old, previously healthy, Caucasian female presented with a 2-month history of an enlarged inguinal lymph node on the right side. The removed lymph node showed histological and immunohistochemical characteristics of neuroendocrine differentiation (positive for synaptophysin, cytokeratin 20, neuron-specific enolase and chromogranin A). Although extensive investigations including repeated CT and NMR scans, classical endoscopy, wireless capsule endoscopy of the small intestine, octreotide- and MIBG scintigraphy were performed, no other primary tumor was found. Furthermore, there was no evidence of Merkel cell carcinoma on dermatological examinations. A possible explanation for the presence of neuroendocrine carcinomas within the lymph nodes is malignant transformation of preexisting intranodal epithelial nests, which have previously been described in lymph nodes located close to the salivary glands, thyroid gland, breast tissue and pancreas. Since the surgical removal of the affected lymph node, the patient has now been disease-free for 42 months. We therefore consider our case to represent a primary undifferentiated neuroendocrine carcinoma in an inguinal lymph node.

Carcinoma, Neuroendocrine↗
PubMed2005

Complications encountered while using thin-wire-hybrid-external fixation modular frames for fracture fixation. A retrospective clinical analysis and possible support for "Damage Control Orthopaedic Surgery".

One hundred ninety eight adult patients who had sustained long bone fractures were treated by external fixation from admission to bone healing and consolidation. Of these, 135 had sustained high-energy injuries, 39 of them had suffered multi-system injuries. Superficial pin track infection was the most common complication, occurring predominantly in pins located in the femur, upper tibia and upper humerus. There were no cases of deep infection or osteomyelitis. One patient with a femoral shaft fracture developed a DVT although he was on preventive low molecular weight heparin, i.e. sc Clexane 40 mg daily. There were no cases of PE or ARDS. External fixation systems are a minimal invasive surgical modality, which allow three-dimensional fracture fixation after closed or minimal open reduction. They require a good command of surgical anatomy, but provide an optimal preservation of the fracture's soft tissue envelope, the critical biological factor for new bone formation and fracture healing. Recent publications have suggested that in the critically ill patient, minimally invasive fracture fixation surgery may prevent the perpetuation of a reactive, life threatening inflammatory reaction (the "second hit") which may induce the development of multiple organ dysfunction (MODS).

Adult↗
PubMed2005

Aggressive B-cell lymphomas: a review based on the workshop of the XI Meeting of the European Association for Haematopathology.

The generic term aggressive B-cell lymphoma includes a variety of entities, each with particular diagnostic and therapeutic issues. To define these entities better and to help confront such issues, a workshop was organized by the European Association of Haematopathology (EAHP) and the Society of Haematology during the XI Meeting of the EAHP, held in Italy in May 2002. Participants were asked to submit cases under various categories and all cases submitted were examined and reviewed by the panel members. The panel's diagnoses formed the basis for discussion at the workshop and a limited number of cases were selected to be presented in more detail and discussed during the workshop. After the workshop the panel met again to discuss the outcome, summarized in this report, which describes the panel's proposals regarding diagnostic criteria, terminology, the definition of new entities and evaluation of biological differential and new prognostic parameters.

Biomarkers, Tumor↗
PubMed2005

T-bet expression patterns in coeliac disease, cryptic and overt enteropathy-type T-cell lymphoma.

AIMS: To clarify the distribution and lineage allocation of T-bet-expressing cells in coeliac disease (CD) and in enteropathy-type T-cell lymphoma (ETTCL). The detection of elevated levels of interferon-gamma, interleukin-18 and the key regulator of Th1 helper immune response T-bet in CD biopsies led to the view that CD is the result of a Th1 response to gluten. It remains unknown whether T-bet is expressed in cryptic and overt ETTCL. METHODS: Specimens from 20 patients with CD, five patients with cryptic and 10 patients with overt ETTCL were analysed by immunohistology employing single and double labellings for T-bet and CD4 or CD8 antigens. RESULTS: In CD specimens nearly all intraepithelial CD8 cells and many CD4 cells in the lamina propria expressed T-bet. Cryptic ETTCL showed T-bet expression in the intraepithelial neoplastic cells while T-bet+ CD4 cells in the lamina propria were rare. Overt ETTCL showed T-bet expression in cases with non-anaplastic morphology. In addition, a proportion of bystander T cells expressed T-bet. CONCLUSIONS: Morphological evidence proves that while T-bet orchestrates a CD4- and CD8-based Th1 reaction in CD, its expression shifts to the neoplastic intraepithelial compartment of cryptic ETTCL and becomes absent or lost in anaplastic overt ETTCL.

CD4 Antigens↗
PubMed2005

Plasmacellular differentiation in extranodal marginal zone B cell lymphomas of the ocular adnexa: an analysis of the neoplastic plasma cell phenotype and its prognostic significance in 136 cases.

AIM: To determine (a) the expression of plasma cell related antigens in extranodal marginal zone B cell lymphomas (EMZL) of the ocular adnexa; and (b) the prognostic value of plasmacellular differentiation in these tumours. METHODS: A consecutive case series of 136 ocular adnexal EMZL obtained from three ocular pathology centres over 20 years was analysed retrospectively. An extensive immunohistochemical panel, including the plasma cell related antigens VS38c, CD38, CD138, multiple myeloma oncogene-1-protein (MUM1/IRF4), and CREB binding protein (CBP) was performed. EMZL were defined as "plasmacellular differentiated" on the basis of morphological features, evidence of cytoplasmic immunoglobulin, negativity for BSAP/PAX5, and expression of at least one of the investigated plasma cell related antigens. Controls included normal or hyperplastic lymphatic tissues. Detailed clinical data were collected for most patients, and compared with the results of immunohistochemistry. The end points considered for statistical analysis were development of local tumour recurrence, development of systemic disease, and lymphoma related death. RESULTS: 57 (42%) of the 136 ocular adnexal EMZL showed a plasmacellular differentiation; 45 of these plasmacytoid cases were primary tumours. In contrast with most admixed normal plasma cells, which displayed co-expression of MUM1/IRF4, Vs38c, CD38, CD138, and CBP, the plasmacellular differentiated EMZL tumour cells demonstrated co-expression of all five plasma cell related antigens in only six of 57 (11%) plasmacellular differentiated ocular adnexal EMZL. The most commonly expressed plasma cell related antigen was MUM1/IRF4, immunoreactivity being seen in 56/57 (98%) plasmacellular differentiated EMZL examined. Although the association of plasmacellular differentiation in primary ocular adnexal EMZL and disseminated disease was statistically significant on univariate analysis (p = 0.042), this was weaker on multivariate analysis. CONCLUSION: Plasmacellular differentiated tumour cells in EMZL demonstrate an aberrant immune profile for plasma cell related antigens when compared with normal plasma cells. On multivariate analysis, plasmacellular differentiation in ocular adnexal EMZL was not significantly associated with local recurrence, the development of systemic disease, or with lymphoma related death.

ADP-ribosyl Cyclase↗
PubMed2004

Totally endoscopic coronary artery bypass graft: initial experience with an additional instrument arm and an advanced camera system.

BACKGROUND: Robotically enhanced telemanipulation for totally endoscopic coronary artery bypass does not provide adequate tactile feedback, traction, or countertraction. The exposition of coronary target sites is difficult, the visual field is limited, and the epicardial stabilization may be troublesome. A fourth robotic arm for endothoracic instrumentation has been added to the da Vinci surgical system to facilitate totally endoscopic operations. The stereoendoscope was upgraded with a wide-angle feature. METHODS: The procedure was performed in five patients. Four of these patients had left internal thoracic artery (LITA) to left anterior descending artery (LAD) grafting on the beating heart and the fifth had sequential bypass grafting (LITA to diagonal branch and LAD) on an arrested heart. The additional effector arm of the da Vinci surgical system was brought into the operative field beneath the operating table and used as a second right arm. The wide-angle view was activated by either the console or the patient side surgeon. RESULTS: The mean operative, port placement, and anastomotic times for a beating-heart totally endoscopic coronary artery bypass were 195 +/- 58, 25 +/- 10, and 18 +/- 5 min, respectively. All procedures were free of morbidity and mortality, with satisfactory angiographic control. The sequential arterial bypass grafting procedure was fully completed in totally endoscopic technique. CONCLUSIONS: The additional instrumentation arm and wide-angle visualization are useful technical improvements of the da Vinci surgical system, solving the problem of traction, countertraction, and facilitated exposition of target sites as well as visualization of the surgical field. They provide potential for wider acceptance of totally endoscopic coronary artery bypass grafting in a larger surgical community.

Aged↗
PubMed2004

[Clear cell chondrosarcoma (CCCS) of the nasal septum].

INTRODUCTION: Chondrosarcomas belong to the most common malignomas of the skeletal system. The vast majority is located at the epiphysis of the long bones or in the pelvis. Less than 10% of chondrosarcomas are located in the head and neck area, most common in the bony viscerocranium and the larynx. Five histological variants can be differentiated: conventional, mesenchymal, myxoid, dedifferentiated and in less than 5% clear cell chondrosarcomas (CCCS). This case report gives the first description of a CCCS originating from the nasal septum. CASE REPORT: A 79 year old female complaining about a 6 month history of nasal obstruction revealed a huge ballooning of the basal septum in anterior rhinoscopy. Computed tomography exhibited a septal tumor with amorphous calcification. Histology of the tumor resected via lateral rhinotomy confirmed a diagnosis of CCCS. Because of clear surgical margins no radiation therapy was performed. The patient stayed free of recurrence during follow-up of sixteen months. DISCUSSION: The patient presented with typical symptoms of nasoseptal tumors as well as representative CT-scans and histologic findings of CCCS. Because of the complete resection and the CCCS-subtype, the patient is expected to have a positive prognosis.

Aged↗