Corina Dommann-Scherrer

Clonal disease in extracutaneous compartments in cutaneous T-cell lymphomas. A comparative study between cutaneous T-cell lymphomas and pseudo lymphomas

Extracutaneous involvement is a sign of poor prognosis in cutaneous T-cell lymphomas (CTCL). Unfortunately it becomes clinically and histologically manifest only late in the course of the disease. It was the purpose of this study to detect clonality in peripheral blood, lymph nodes and bone marrow samples at times when extracutaneous involvement cannot other-wise be demonstrated. In addition to skin biopsies, peripheral blood, lymph node and bone marrow samples from a total of 25 patients were analysed by Southern blotting for clonal gene rearrangement of the T-cell receptor β-chain. Six of the patients were suffering from mycosis fungoides (MF), four from non-MF CTCL (pleomorphic T-cell lymphomas), seven from Sézary syndrome (SS), eight from pseudolymphoma (insect bites) (PSL), and one from lymphomatoid papulosis (LP). Clonal TcR b gene rearrangements were found in patients with MF in four of five skin probes as well as in two of two lymph node samples and in one of two peripheral blood samples. In SS patients, all skin probes (seven of seven), lymph node samples (six of six), peripheral blood samples (six of six) and one bone marrow specimen had a clonal TcR β gene rearrangement. In patients with non-MF CTCL, two of four skin, zero of two peripheral blood and one of one bone marrow samples with clonal T cells were detected. All investigated patients showed exactly the same rearrangement pattern at extranodal sites and in the skin, which is proof for the same clone in all compartments. In contrast, no rearrangements were detected in LP and PSL (zero of eight skin probes, zero of two peripheral blood samples). Our results provide strong evidence for an early systemic spread of neoplastic cells in CTCL. However, an initial tumour burden has to be reached in order to lead to a clinically and prognostically relevant manifestation.

Primary cutaneous T-cell-rich B-cell lymphoma. A case report with a 13-year follow-up.

Cutaneous B-cell lymphomas constitute approximately 20% of primary cutaneous lymphomas. Most histologic subtypes of nodal B-cell lymphomas also occur primarily in the skin. The recently described T-cell-rich B-cell lymphomas (TCRBCLs) manifest mainly in the lymph nodes. This article presents a case of TCRBCL arising primarily in the skin, the origin of which could be traced back 13 years. The patient is a 59-year-old man. Plaque-like and nodular skin infiltrates had first appeared in the left preauricular region. Repeated examinations never found any extracutaneous involvement. A skin biopsy and a retrospectively studied 10-year-old skin specimen showed identical histologic features. Immunohistochemistry identified the TCRBCL previously considered as cutaneous Hodgkins disease or a diffuse centroblastic centrocytic non-Hodgkins lymphoma. A clonal B-cell population was detected by polymerase chain reaction, showing a rearrangement of IgH gene. The case of this patient shows that primary cutaneous TCRBCLs, similarly to other B-cell lymphomas in the skin, may have a good prognosis, in contrast to their nodal counterparts.

Long-term outcome of idiopathic hypereosinophilic syndrome - transition to eosinophilic gastroenteritis and clonal expansion of T-cells

We describe a patient with idiopathic hypereosinophilic syndrome, without initial gastrointestinal symptoms, and their transition to eosinophilic gastroenteritis. This patient, a 65-year-old man, presented with fever, constitutional symptoms, peripheral and bone marrow eosinophilia 20 years ago. During the course of the disease, diarrhoea and malabsorption became prominent, whereas bone marrow eosinophilia regressed completely and blood eosinophilia regressed partially. Biopsies showed a severe eosinophilic gastroenteritis of the mucosal type involving the stomach, small bowel and colon. During the final years of the patients disease, mucosal eosinophilia became less intense and a mucosal infiltration with T-cells dominated. At autopsy, immunopathological studies of small intestines and colon specimens showed a clonal expansion of morphologically normal T-cells in the intestinal mucosa, which expressed the abnormal phenotype CD2+CD3+CD4-CD5-CD8-. Flow cytometry examination of peripheral blood revealed a corresponding abnormal population of CD3+CD4-CD8- T-cells, indicating a systemic spread of the process. The patient eventually died of non-obstructive small bowel infarction with peritonitis 20 years after the onset of the first symptoms. We postulate that the destructive eosinophilic/lymphocytic inflammation is caused by a clonal proliferation of T-lymphocytes with probable secretion of Type 2 T(helper) cell cytokines and consecutive stimulation of eosinophils.

Chromosomal translocations t(4;14), t(11;14) and proliferation rate stratify patients with mature plasma cell myelomas into groups with different survival probabilities: a molecular epidemiologic study on tissue microarrays.

Plasma cell myelomas (PMs) exhibit clinical and molecular heterogeneity. To date, morphology and immunohistochemistry on bone marrow trephines are of limited value to stratify patients into different prognostic categories. However, some chromosomal translocations are of prognostic and/or of predictive importance in PMs. In this study, the prognostic significance of morphology, CyclinD1 expression, proliferation index (Mib1) and presence of the translocations FGFR3/IgH [t(4;14)] and CCND1/IgH [t(11;14)] are compared in 119 patients with PM. Immunohistochemistry and fluorescence in situ hybridization analysis were carried out on a tissue microarray containing bone marrow trephines. Hundred and one PMs showed a mature morphology whereas 10 were immature. All but one PM carrying a translocation showed a mature morphology. Patients with a t(4;14) (12%) had a statistically significant shorter 1-year survival (P=0.004), whereas those with a t(11;14) (21%) had a trend towards a better clinical outcome. CyclinD1 protein expression was not significantly associated with survival. Besides the t(4;14), an immature morphology (P<0.001) and a proliferation index (Mib1) of more than 10% (P=0.002) were associated with a significantly worse outcome. A high occurrence of strong CyclinD1 protein expression in the tumor cells was predictive of either a t(11;14) or of a low level amplification of the CCND1 gene, suggesting that different molecular mechanisms may have lead to an over-expression of the CyclinD1 protein in PMs. These findings demonstrate that a high proliferation rate and translocations involving the IgH locus can stratify mature PMs into groups with distinct survival probabilities.

Expression of intercellular adhesion molecule 3 (CDw50) on endothelial cells in cutaneous lymphomas: A comparative study between nodal and cutaneous lymphomas

Advances in the molecular definition of surface proteins (adhesion molecules) involved in tumor metastasis may help to explain the invasive behavior of malignant tumors, that is, the migration of tumor cells involving reversible adhesive contacts, their release in the circulation, and their extravasation into distant sites. Intercellular adhesion molecule-3 (ICAM-3), the third receptor for the lymphocyte function-associated antigen molecule-1 (LFA-1) was recently characterized. We investigated fresh frozen skin biopsies from 10 patients with mycosis fungoides, four with pleomorphic T-cell lymphoma, six with Sézary syndrome, 10 with primary cutaneous B-cell lymphoma, and 10 with eczematous lesions as controls. The biopsies were compared with lymph node biopsies of five patients with known cutaneous T-cell lymphoma (CTCL), 10 with primary nodal B-cell lymphoma, and 11 with lymph-node specimens showing dermatopathic lymphadenopathy as controls. The specimens were stained with ICAM-3 antibody (Bender Medical Science) using the alkaline phosphatase antialkaline phosphatase method. Using cytomorphologic criteria, neoplastic lymphocytes could be differentiated from smaller reactive cells. Staining intensities were classified semiquantitatively as follows: 4, strong expression in 75 to 100% of the tumor cells; 3, 50 to 75%; 2, 25 to 50%; 1, 5 to 25%; and 0 fewer than 5% of the tumor cells. The endothelial cells in skin biopsies of seven of 30 primary cutaneous lymphomas expressed ICAM-3. In contrast, no expression of ICAM-3 could be demonstrated on endothelial cells in lymph nodes infiltrated with tumor cells of CTCL. Finally, endothelial cells of lymph nodes infiltrated with primary nodal B-cell lymphomas showed expression of ICAM-3 in three of 10 patients. The endothelial cells in the 11 control patients presenting with both eczematous lesions and dermatopathic lymphadenopathy showed no staining for ICAM-3. Every patient who expressed ICAM-3 on endothelial cells showed systemic spread of this disease. The findings suggest that ICAM-3 expression may be induced on endothelial cells in late-stage cutaneous lymphomas, probably by a cytokine-mediated mechanism.

A prospective study of risk-adapted therapy for large cell non-Hodgkin's lymphoma with VACOP-B followed by high-dose CBV and autologous progenitor cell transplantation for high-risk patients in remission

Several centres reported a favourable outcome after high‐dose chemotherapy with autologous progenitor cell transplantation in selected patients with high‐risk large cell non‐Hodkgins lymphoma in first remission. Based on these observations, we wanted to prospectively determine the outcome of a risk‐adapted therapy for patients with large cell lymphoma. Patients aged 60 years or less received 12 weeks of VACOP‐B chemotherapy. For high‐risk patients in remission this was immediately followed by high‐dose chemotherapy with cyclophosphamide, carmustine and etoposide and autologous progenitor cell transplantation. High‐risk criteria were defined before the establishment of the International Index and included large cell lymphoma stage III or IV or mediastinal large lymphoma with sclerosis stage II or higher, and the presence of bulky tumours and/or an elevated LDH. 89 patients fulfilled the clinical selection criteria and were entered onto this multicentre study. 82 patients were evaluable after confirmation of large cell histology by pathology review. Of these, 51 were considered to be in the low‐risk group and 31 in the high‐risk group. The 3‐year event‐free survival for all patients was 68%. The 3‐year event‐free survival was 76% for the low‐risk and 55% for the high‐risk group (P = 0.061). Only 22/31 high‐risk patients were able to receive the high‐dose chemotherapy in first remission as intended. In conclusion, although our study demonstrated that a risk‐adapted therapy for large cell lymphoma could be safely administered, the potential impact on outcome of the strategy chosen here is likely to be small.

Mycetoma of the upper arm following infection by Actinobacillus actinomycetemcomitans

Mycetomas are subacute or chronic infections usually localized on unprotected skin areas and caused by fungi or Actinomyces. We report the case of a patient who suffered a splinter injury on his wrist after a motor accident. Six months later a cutaneous abscess with Actinobacillus acinomycetemcomitans developed on his wrist. Complete healing was obtained within 1 month after administration of ceftriaxon and doxycycline. The therapeutic management will be discussed.Zusammenfassung. Myzetome sind subakute oder chronische Infektionen, die gewöhnlich an unbedeckten Körperstellen lokalisiert sind und durch verschiedene Erreger, in der Regel durch Fadenpilze oder Aktinomyzeten, verursacht werden. Wir berichten über einen Patienten, der nach einem Autounfall sich eine Splitterverletzung im Bereich des rechten Handgelenkes zugezogen hatte. Ein halbes Jahr später bekam er an der Eintrittsstelle eine abszedierende Hautinfektion, welche sich histologisch als Myzetom herausstellte. Die Besonderheit dieses Falles liegt im kulturellen Nachweis von Actinobacillus actinomycetemcomitans, der wahrscheinlich zu einer chronisch-rezidivierenden subkutanen Infektion mit Myzetombildung bei einem Europäer geführt hat. Wir berichten über die therapeutischen Erfahrungen mit Ceftriaxon und Doxycyclin, welche diese Infektion binnen eines Monats zur Abheilung gebracht haben.Abstract. Mycetomas are subacute or chronic infections usually localized on unprotected skin areas and caused by fungi or Actinomyces. We report the case of a patient who suffered a splinter injury on his wrist after a motor accident. Six months later a cutaneous abscess with Actinobacillus acinomycetemcomitans developed on his wrist. Complete healing was obtained within 1 month after administration of ceftriaxon and doxycycline. The therapeutic management will be discussed.