Maligne und benigne Lymphome des Auges,der Lid- und Orbitalregion

Zusammenfassung In der vorliegenden Studie wurden 23 Lymphome der Augen-, Lid- und Orbitalregion ausgewertet. Sie stammten aus einem nicht ausgewählten bioptischen Untersuchungsgut des Pathologischen Instituts der Universität Kiel und des Lymphknotenregisters bei der Deutschen Gesellschaft für Pathologie. Es handelte sich dabei um 12 maligne und 11 benigne Lymphome. Die malignen Lymphome stellten jeweils Non-Hodgkin-Lymphome dar. Unter den letzteren fanden wir elfmal ein Immunocytom, ein malignes Lymphom mit niedrigem Malignitätsgrad — dagegen nur einen Fall eines malignen Lymphoms mit hohem Malignitätsgrad, ein centroblastisches Lymphom. Die Diagnose eines benignen Lymphoms wurde jeweils durch die von uns erhobenen katamnestischen Angaben bestätigt.Während sich das benigne Lymphom in 7 von 11 Fällen in der Conjunctiva entwickelt hatte, war dies bei nur 2 von 11 Fällen mit Immunocytom zu beobachten. Das Immunocytom stellt einen Tumor dar, der aus Lymphocyten und Plasmazellen oder plasmocytoiden Zellen besteht und meist PAS-positive globuläre Einschlüsse in Kern und/oder Cytoplasma der Plasma- oder plasmocytoiden Zellen aufweist.

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Malignant and benign lymphomas of the eye, eyelid, and orbit

Summary Twenty-three lymphomas of the eye, eyelid, and orbit were chosen for study from biopsy material of the Department of Pathology, University of Kiel, and the Lymph Node Registry in Kiel. There were 12 malignant non-Hodgkin's lymphomas and 11 benign lymphomas. Catamnestic examination confirmed the histologic diagnosis in all 11 cases of benign lymphoma. Eleven of the malignant lymphomas represented immunocytomas and were therefore of low-grade malignancy. In contrast, there was only one case of malignant lymphoma of high-grade malignancy, which was diagnosed as centroblastic lymphoma. The immunocytoma was retrobulbar in one third of our cases and conjunctival in only 2 cases, whereas benign lymphoma had developed in the conjunctiva in 7 of 11 cases. Immunocytoma represents a tumor composed of lymphocytes and plasma cells or plasmacytoid cells. PAS-positive globular inclusions are usually found in the nucleus and/or cytoplasm of the plasma cells or plasmacytoid cells.

Herrn Prof. Dr. med. Dr. med. vet. h. c. W. Bargmann zum 70. Geburtstag gewidmet.     

Dysplastic follicular dendritic cells in hyaline‐vascular Castleman disease: a rare occurrence creating diagnostic difficulty

Follicular dendritic cell (FDC) proliferations and dysplastic FDCs can be seen in Hyaline‐vascular Castleman disease (HVCD). The association between HVCD and FDC sarcoma is well‐documented; dysplastic FDCs may be precursors to FDC sarcoma. Herein, we describe a case of HVCD with strikingly large and dysplastic FDCs, which raised the differential of Hodgkin lymphoma and other neoplasms. Scattered dysplastic FDCs were predominantly in germinal centers and mantle zones, and rarely in interfollicular areas. Although occasional germinal centers contained increased FDCs, no mass forming proliferations were present to suggest FDC sarcoma. Immunostaining demonstrated that the atypical FDCs expressed CD21, clusterin and CXCL13, but not CD23, S100, pankeratin or CD30; they aberrantly expressed epidermal growth factor receptor (EGFR). The present case demonstrates that dysplastic FDCs may be present as isolated cells that require immunophenotyping to distinguish them from malignant entities with similar morphologic features. A variety of FDC markers is required to confirm their origin as the expression of any single marker is not assured, as occurred in this case. Pathologists need be aware of FDC proliferations in HVCD because of their association with FDC sarcoma. Aberrant EGFR expression by dysplastic FDCs may indicate that they are pre‐neoplastic and necessitate long‐term patient follow‐up.     

Deriving health utility values from a randomized,double-blind,placebo-controlled trial of siltuximab in subjects with multicentric Castleman’s disease

Purpose: To estimate health utility values, explore predictors of utility values, and estimate the quality-adjusted life years (Q.A.L.Y.s) gained by treatment in multicentric Castleman’s disease (M.C.D.). Methods: The SF-36 was administered to 79 patients enrolled in a randomized, double-blind, placebo-controlled, multi-national study to determine the safety and efficacy of siltuximab plus best supportive care (B.S.C.) compared with B.S.C., in subjects with symptomatic M.C.D. Utility (SF-6D) scores were derived from the SF-36. Sensitivity analyses using utilities obtained by mapping the SF-36 to the EQ-5D were also conducted. Repeated measures, mixed effects models were conducted to estimate effects of treatment, responder status and?≥?Grade 3 adverse events (A.E.s) on changes in utility values over time, controlling for baseline utility value. Additionally, differential Q.A.L.Y. gain was assessed in the trial using multiple regression. Results: Patients on siltuximab and those who experienced a complete or partial response had higher mean utility values over time than those on placebo or those with stable disease. After an initial response to treatment, the mean utility remained relatively stable for patients on siltuximab and those who experienced a complete or partial response during the period when most patients were on study. A significantly different Q.A.L.Y. gain was found for patients on siltuximab (versus placebo) as calculated by SF-6D (0.070 Q.A.L.Y.s, p?<?.05) scores at 6 months (EQ-5D 0.096 Q.A.L.Y.s, p?<?0.05). Conclusions: Siltuximab demonstrated improved, durable health utility gains in this rare disease over B.S.C. The main SF-6D results were supported by EQ-5D sensitivity analysis. These findings are limited by the small study sample size and substantial missing data caused predominantly by crossover. A longitudinal, multisite international observational study capturing clinical, safety and health-related quality of life (H.R.Q.L.) endpoints are needed to confirm these findings.     

Human herpesvirus 8-associated multicentric Castleman disease in a patient with advanced HIV infection: A case report

Rational:Multicentric Castleman disease (MCD) is a nonclonal lymphoproliferative disorder that is rarely reported from Southeast Asian countries. Here, we report a case of human herpesvirus 8 (HHV-8)-associated MCD in a patient with advanced human immunodeficiency virus (HIV) infection who presented with prolonged intermittent fever, urticarial rash, hepatosplenomegaly, and generalized lymphadenopathy.Patient concerns:A 34-year-old man with advanced HIV infection who was in good compliance with his antiretroviral treatment regimen presented with intermittent fever, weight loss, marked hepatosplenomegaly, and generalized lymphadenopathy. Recurrent symptoms of high-grade fever, abdominal discomfort, pancytopenia, and high C-reactive protein level occurred for 16 months.Diagnoses:Histopathological findings of left inguinal lymph node revealed diffuse effacement of lymph node architecture with coexpression of HHV-8 latency-associated nuclear antigen 1 from immunohistochemical staining. The HHV-8 viral load was 335,391 copies/mL.Interventions:The patient was treated initially with one dose of intravenous rituximab (375 mg/m²) followed by subcutaneous rituximab (1400 mg) weekly for 5 weeks.Outcomes:The patient''s recurrent systemic symptoms subsided dramatically, and he has now been in remission for almost two years.Lessons:HHV8-associated MCD remains a diagnostic challenge in advanced HIV disease and should be suspected in those with recurrent flares of systemic inflammatory symptoms. Lymph node histopathology is essential for diagnosis and for excluding clonal malignancy. HHV-8 viral load is also useful for diagnosis and for monitoring disease activity.     

Immunoglobulin G4-related lymph node disease with an orbital mass mimicking Castleman disease: A case report

BACKGROUNDImmunoglobulin (Ig) G4-associated diseases are a group of systemic diseases involving multiple organs and are also known as IgG4-associated sclerosing diseases. IgG4-associated lymphadenopathy occurring in the lymph nodes is characterized by a lack of specificity due to its clinicopathological characteristics and must be differentiated from a variety of lesions, such as Castleman disease, lymphatic follicular reactive hyperplasia, and lymphoma.CASE SUMMARYA 65-year-old male patient, with Guillain-Barre syndrome for 5 years, presented to our hospital complaining of bilateral orbital mass for 2 years. After hospitalization, the results of the patient’s laboratory tests showed that immunoglobulin subgroup IgG4 was 33.90 g/L and IgG was 30.30 g/L, but serum interleukin-6 was normal. The pathological morphology of orbital mass and cervical lymph node were consistent, which showed that a large number of plasma cells and eosinophils were observed in the lymphatic follicles, and the interstitial fibrous tissue was proliferative. Immunohistochemistry showed that CD20 (B cells) (+), CD3 (T cells) (+), CD38 (+), IgG (+), IgG4 positive cells > 100/high powered field, and IgG4/IgG > 40%. Combined with clinical and immunohistochemical results, lymphadenopathy was consistent with Castleman disease-like IgG4-associated sclerosing disease. Prednisone acetate treatment was given at 40 mg/d. After 2 wk, the superficial lymph nodes and orbital masses shrank, and the IgG4 level decreased. As prednisone acetate was regularly used at a reduced dosage, no recurrence of the disease has been observed.CONCLUSIONThis case suggested that it is necessary to proceed cautiously in clinical practice with such patients, and immunoglobulin, complement, interleukin-6, C-reactive protein, and other examinations should be performed to confirm the diagnosis.     

A multidisciplinary collaborative model based on single-port thoracoscopy for the treatment of giant mediastinal lymph node hyperplasia: a case report

Mediastinal unicentric Castleman disease (UCD) frequently manifests as a hyper-enhancing lymph node mass and is often surgically curable. However, because of excessive vascularisation and adhesion to important surrounding structures, surgery is often associated with severe haemorrhage that is often difficult to control thoracoscopically. Therefore, thoracotomy is often preferred, which increases the trauma to the patient and affects postoperative recovery. Here, we describe the case of a 30-year-old male patient with a large upper mediastinal lymph node (7 × 5 × 4 cm) that was compressing his superior vena cava. The distribution of nutritive arteries of the mass was analysed in detail, and the main branches were embolised prior to surgery. With the assistance of preoperative isovolumetric haemodilution, we achieved complete resection through single-port thoracoscopy, with only minor haemorrhage, which enabled the patient to recover rapidly. This multidisciplinary collaborative model, based on single-port thoracoscopic surgery, may be of wide practical use for the treatment of mediastinal UCD.     

Castleman disease: delineating the spectrum

Glanzmann thrombasthenia (GT) is caused by inherited defects of the α_IIbβ₃ platelet glycoprotein. This bleeding disorder can be treated with platelet transfusion therapy, but some patients will be immunized and begin to form anti‐human leucocyte antigen (HLA) and/or anti‐α_IIbβ₃ antibodies. These antibodies can bind and interfere with the function of the transfused platelets, rendering treatment ineffective. However, platelet transfusion refractoriness attributable to HLA antibodies may be managed by the selection of compatible donors, although they are not always readily available, particularly in an emergency. Thus, anti‐α_IIbβ₃ antibodies represent one of the most severe complications in GT. Both genetic and environmental factors may contribute to the risk of anti‐α_IIbβ₃ development, but the underlying pathogenic mechanisms are still unknown. This review will summarize the current knowledge of the risk factors for development of anti‐α_IIbβ₃ antibodies in patients with GT and discuss how these findings may influence the clinical management of patients.     

TAFRO syndrome successfully treated with tocilizumab: A case report and systematic review

Thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome is considered as a unique clinicopathologic variant of multicentric Castleman’s disease and is recently reported in Japan. This entity represents a severe inflammatory state leading to organ failures such as severe liver dysfunction seen in our case, and can be treated by immunosuppressive agents, steroids, and cyclosporine shown in several case reports. A systematic review and our case suggest the potential utility of tocilizumab as a treatment for TAFRO syndrome.