Rare macrophage diseases in adults

Diseases of macrophages are rare entities characterized by the accumulation of macrophages, dendritic cells or monocyte-derived cells in various tissues and organs. This article focuses on macrophage disorders which can be present in adult patients. The review highlights pathogenesis, signs and symptoms, diagnostic criteria and principles of therapy in the most frequent macrophage diseases in adults: hemophagocytic lymphohistiocytosis, Rosai-Dorfman disease, Gaucher disease, Niemann-Pick disease, and Langerhans cell histiocytosis. Since macrophage disorders can be encountered by various medical specialists, basic knowledge of these entities and their diagnostic criteria should be familiar to all physicians, including hematologists

Rituximab-associated progressive multifocal leukoencephalopathy after a single cycle of R-CHOP for T-cell/histiocyte-rich large B-cell lymphoma

Progressive multifocal leukoencephalopathy (PML) is a disease of immunocompromised patients caused by reactivation of the John Cunningham polyomavirus (JCV). A monoclonal anti-CD20 antibody rituximab is widely used as an important part of therapy for B-cell non-Hodgkin lymphomas and various autoimmune diseases. It is not fully explained how rituximab reactivates JCV.In this report, we present the case of a 61-year-old man with T-cell/histiocyte-rich large B-cell lymphoma who was treated with R-CHOP and intrathecal methotrexate. Two weeks after the first R-CHOP course he developed dysarthria, diplopia, and disturbances in motor coordination. Based on CT/MRI results showing 3cm×2cm large hypodense white matter lesion in left cerebellar hemisphere, and detection of JCV in the cerebrospinal fluid (14300viral copies/mL), the patient was diagnosed with PML. Despite treatment attempt with cidofovir and IVIG, the patient's neurological status continued to worsen. He developed progressive motor neuron deficits but retained intact cognitive functions. The patient deceased nearly three months after onset of rituximab treatment.Rituximab is a milestone in treatment of many hematological and autoimmune diseases. Considering how widespread has the use of rituximab become, the overall risk of developing PML is relatively low. Nevertheless, since the end of 1990s several reports were published on PML development in association with usage of rituximab. The authors would like to emphasize that although the total risk of PML occurrence in patients treated with rituximab is low, it is important that physicians administrating rituximab therapy are aware of this serious complication

Atypical cytomorphology of Gaucher cells is frequently seen in bone marrow smears from untreated patients with Gaucher disease type 1

Introduction. Gaucher cells (GCs), the lipid-laden storage macrophages, are the pathologic hallmark of Gaucher disease (GD). They are typically 20–100 μm in diameter with eccentrically placed nuclei and cytoplasm with characteristic crinkles and striations. A few previous observations have indicated that sometimes GD patients may display morphology of GCs which is different from this classical description. The aim of our study was to explore the morphological polymorphism of GCs in patients with untreated GD type 1 (GD1). Material and methods. May-Grünwald Giemsa stained bone marrow smears (BM-S) from 6 patients with sporadic GD1 were analysed; each patient sample consisted of two slides where all GCs and non-Gaucher cell macrophages were counted. We have defined for the study purposes and examined the following features of GCs which were considered as atypical: (1) foamy cytoplasm, (2) centrally placed nucleus, (3) cell diameter > 100 μm, (4) multinuclearity, (5) syncytial morphology, (6) unusually large cytoplasmic projections, and (7) apparent haemophagocytosis. Results. All analysed patients showed 22–40% GCs with atypical cytomorphology (median 29%). The median number of atypical features of GCs was 10 per patient (range 6–13). Multinuclearity was the most common atypical feature of GCs, followed by erythrophagocytosis and foamy cytoplasm. There was a strong positive correlation between erythrophagocytosis and foamy cytoplasm in GCs (Spearman’s rank correlation coefficient: 0.9). Although majority of atypical GCs had one atypical feature, there was a considerable amount of GCs presenting ≥ 2 atypical features. Conclusions. Untreated patients with GD1 often show a considerable proportion of GCs with atypical cytomorphology. The knowledge of possible atypical variant forms of GCs can contribute to a quicker and accurate diagnosis of GD, and minimize the risk for misdiagnosis. To the best of our knowledge, this is the first published report on atypical cytomorphology of GCs in untreated patients with GD1.

Przydatność poszczególnych faz wielofazowej spiralnej tomografii komputerowej w wykrywaniu przerzutów nowotworowych do wątroby

Background: In view of the constant progress in methods of treating liver metastases, new standards for radiological examinations must be developed. The purpose o f this study was to evaluate the ability of sequential phases of multiphase spiral CT (sCT) to detect liver metastases and their segmental localization. Material/Methods: sCT was performed on 100 patients with hepatic metastases. sCT included unenhanced scans (NC) and those o f the hepatic arterial-dominant (HAP), portal venous-dominant (PVP), and equilibrium phases (EP). In each phase, the number, size o f detectable lesions, and the accuracy of the topographic report of lesion location in liver segments were evaluated. Patients with primary cancer of the gastrointestinal tract constituted almost 70% of the group. Results: A total of 354 liver metastases were detected by sCT. PVP revealed 346 (97.7%), HAP 298 (84.2%), and EP 241 (68.1%) secondary lesions. NC scans revealed 195 metastases (55.1%) when evaluated in the 'abdominal window'. The exact localization of metastases in liver segments was established in PVP in 88% o f cases, in HAP 76%, in EP 70%, and in the NC phase in 71% of cases. Lesion diameter ranged from 4 to 127 mm (median: 21 mm). Lesions of more than 30 mm in diameter were clearly detectable in each phase of the CT examination. Conclusions: PVP in sCT has the highest sensitivity in detecting liver metastases and contributes to the most adequate segmental localization. In the standard diagnosis of liver metastases, biphasic examination including HAP and PVP should be performed

Development of classical Hodgkin’s lymphoma in an adult with biallelic STXBP2 mutations

Experimental model systems have delineated an important role for cytotoxic lymphocytes in the immunosurveillance of cancer. In humans, perforin-deficiency has been associated with occurrence of hematologic malignancies. Here, we describe an Epstein-Barr virus-positive classical Hodgkin's lymphoma in a patient harboring biallelic mutations in STXBP2, a gene required for exocytosis of perforin-containing lytic granules and associated with familial hemophagocytic lymphohistocytosis. Cytotoxic T lymphocytes were found infiltrating the tumor, and a high frequency of Epstein-Barr virus-specific cytotoxic T lymphocytes were detected in peripheral blood. However, lytic granule exocytosis and cytotoxicity by cytotoxic T lymphocytes, as well as natural killer cells, were severely impaired in the patient. Thus, the data suggest a link between defective lymphocyte exocytosis and development of lymphoma in STXBP2-deficient patients. Therefore, with regards to treatment of familial hemophagocytic lymphohistocytosis patients with mutations in genes required for lymphocyte exocytosis, it is important to consider both the risks of hemophagocytic lymphohistocytosis and malignancy.Swedish Research CouncilSwedish Cancer FoundationSwedish Children’s Cancer FoundationHistiocytosis AssociationClas Groschinsky’s Memorial FundJeanssons FoundationÅke Olsson Foundation for Hematological ResearchÅke Wiberg FoundationKarolinska Institute Research FoundationStockholm County Council (ALF project)Publishe

Długotrwała pancytopenia po chemioterapii jako objaw demaskujący chorobę Gauchera u pacjentki z rakiem płuca

The diagnosis of congenital metabolic disease can be very difficult and often extends in time. This applies particularly to metabolic diseases of milder phenotype, such as an adult form (type 1) of Gaucher disease caused by the inherited (autosomal recessive) deficiency of the lysosomal enzyme glucocerebrosidase.In this work, we present a case of 48-year-old Polish patient (living in Sweden) with lung cancer, who developed a prolonged pancytopenia complicated by sepsis after each cycle of chemotherapy. These symptoms led to initiation of hematological diagnostic work-up and the assumption that the complications are caused by Gaucher disease. Definitive diagnosis of Gaucher disease was confirmed by results of enzymatic analyses, which revealed reduced activity of glucocerebrosidase in peripheral blood lymphocytes to 0.44μkat/kg protein (ref.: 2.1–3.8), increased activity of plasma chitotriosidase to 1241nkat/L (ref.: G (N370S), confirming diagnosis of type 1 Gaucher disease in the patient. The presence of the mutation c.604C>T has never been previously reported in a Polish patient with Gaucher disease. Administration of enzyme replacement therapy with imiglucerase (Cerezyme™) led to a rapid improvement of peripheral blood counts and enabled further continuation of intensive chemotherapy for lung cancer.In conclusion, the authors would like to emphasize that knowledge of the symptoms and the principles of diagnosis of Gaucher disease among hematologists is very important for efficient diagnostics of patients affected by this rare disease