Bone Marrow
Wojciech Gorczyca in Atlas of Differential Diagnosis in Neoplastic Hematopathology, 2014
Hemophagocytic syndrome (hemophagocytic lymphohistiocytosis) is characterized by fever, hepatosplenomegaly, cytopenia, and systemic macrophage activation with hemophagocytosis [4,5]. Blood smear or BM aspirate shows benign histiocytes (macrophages) with phagocytized erythrocytes, platelets, and occasionally granulocytes and lymphocytes (Figure 2.8J). Although it is most commonly associated with inherited or acquired immune deficiencies and viral infections [especially Epstein–Barr virus (EBV)], it can also complicate patients with malignancies. A special form of hemophagocytic syndrome in rheumatic diseases is called macrophage activation syndrome. Among hematopoietic tumors, hemophagocytic syndrome is typical for subcutaneous panniculitis-like T-cell lymphoma, but may also be seen in anaplastic large cell lymphoma (ALCL); extranodal NK/T-cell lymphoma, nasal type; aggressive NK/T-cell lymphoma/leukemia; intravascular large B-cell lymphoma (IVLBCL); plasmablastic lymphoma; and rarely Hodgkin lymphoma (HL).
Primary immunodeficiency diseases
Gabriel Virella in Medical Immunology, 2019
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder due to impaired lymphocyte cytotoxic activity due to defective formation of the immunologic cell-to-cell synapse that enables cytotoxic T cells and NK cells to kill an infected cellular target. The result is massive abnormal activation of T cells and macrophages, overproduction of γ-interferon, and infiltration of activated macrophages in the liver, bone marrow, spleen, and the central nervous system with massive hemophagocytosis. Clinical criteria include high fever with splenomegaly, autoimmune thrombocytopenia, neutropenia, and hemolytic anemia, and histologic evidence of hemophagocytosis in the tissues. Immune activation markers such as very high ferritin levels, hypofibrinogenemia, hyperlipidemia, and elevated plasma levels of soluble IL-2 receptor (sCD25) are usually found. Low NK numbers and activity are common. Familial forms can first appear in infancy or later in life and enable infection with human herpes viruses, particularly EBV. Mutations in Perforin, Syntaxin 11, and Munc 18 are the most common known genetic forms as all of these proteins play a critical role in tethering and formation of the immunologic synapse.
SARS-CoV Infections in Humans
Sunit K. Singh in Human Respiratory Viral Infections, 2014
Some of the clinical features of SARS suggested that exaggerated immune responses might be responsible for tissue damage. A fall in viral load when IgG sero-conversion occurred could be associated with clinical deterioration. The BOOP pattern was observed in the radiological imaging of some patients and confirmed in autopsies in some lethal cases. Hemophagocytosis had been also observed in the lung in autopsy series.
Clinical Characteristics and Outcomes of 101 Children with Hemophagocytic Lymphohistiocytosis: A Four-Year Single-Center Experience from Egypt
Published in Pediatric Hematology and Oncology, 2020
Asmaa Elsharkawy, Hala Assem, Mostafa Salama, Neveen Mikhael, Maha Y. Zeid, Yasmine El Chazli
Bicytopenia was reported in only 83% of our patients studied, as compared to 92% of the patients reported by Bergsten et al21 and 100% in many studies,6,22,30 this may be explained by the presence of pHLH not presenting with a full-blown picture in the present study. Tissue hemophagocytosis, which is not essential for the diagnosis of HLH,14 was observed in 33 patients, corresponding to 43% of those biopsied, almost exclusively from the BM. Gupta et al31 and Sasan et al32 observed hemophagocytosis in 57% and less than 20% of their patients, respectively. In contrast, the results of the HLH-2004 study showed hemophagocytosis in 82% of the available examinations.21 The considerable variation seen in different studies might be explained by the different timing and procedure for sampling. In our center, patients had a BM examination (aspirate and/or biopsy) only at diagnosis and it was not repeated if negative.
Etoposide-containing regimens for the treatment of critically ill patients with hematological malignancy-related hemophagocytic lymphohistiocytosis
Published in Acta Oncologica, 2022
Clara Vigneron, Valentine Le Stang, Justine Decroocq, Edwige Péju, Barbara Burroni, Nicolas Chapuis, Julien Charpentier, Frédéric Pène
Twenty-four patients were included in the study (Table 1). Sixteen patients fulfilled at least five HLH-2004 diagnostic criteria. The H-score was computed at high values of 253 [226.3–287.0], corresponding to HLH probability higher than 99% [98–>99]. Eight patients had less than five HLH-2004 criteria but with a median H score of 226 [178.3–243.5] resulting in a HLH probability of 98%. Figures of hemophagocytosis were found in 13 patients (56.5%). Hematological malignancies were generally related to mature T and B lymphoma (n = 17, 70.8%), and were often recently diagnosed (n = 20, 83.3%). Supports for organ failures were frequently initiated, including invasive mechanical ventilation (n = 13, 54.2%), vasopressors (n = 17, 70.8%), or renal replacement therapy (n = 13, 54.2%). Etoposide (median dose of 97.7 mg/m2 [86.5–105.5] per day for one or two injections) was administered early (median 0.5 d [0–2.25]) after the diagnosis of HLH was set, and was combined with high-dose steroids in 21 patients (87.5%). Four patients died rapidly before receiving additional chemotherapy. Disease-directed chemotherapy was initiated in 16 patients (58.3%) within one month following ICU admission (median of 4 d [1.5–7.0] from etoposide) and was initiated after one month in four patients.
Hemophagocytic lymphohistiocytosis mimicking neonatal hemochromatosis
Published in Pediatric Hematology and Oncology, 2019
Larisa Broglie, Bernadette Vitola, Monica S. Thakar, Donald Basel, Sara Szabo, Rashmi Agni, Julie-An Talano
Following admission, the family history prompted concern for neonatal hemochromatosis and work up was performed to assess for iron deposition to confirm this diagnosis. A liver MRI revealed low signal throughout the liver in all pulse sequences especially with T2-weighed and FISP images. The pancreas, spleen, and bone marrow were unremarkable. Given that there was no evidence of extrahepatic iron deposition, salivary gland biopsy was pursued but two attempts were inconclusive, without definitive evidence of iron deposition. Hepatology was consulted due to worsening clinical status of the patient with poor feeding, hepatitis, coagulopathy, abdominal distention and respiratory distress requiring intubation, and the differential diagnosis was then broadened; labs assessing for HLH were sent. Soluble IL-2 receptor levels were significantly elevated, NK cell and B cell counts were undetectable, and there was an absence of perforin production (Table 1). The absence of NK cells notably limited the assessment of NK cell function and perforin production, and CD107a degranulation was unable to be performed. A bone marrow biopsy was performed that showed hemophagocytosis. An HLH gene panel was then sent and the patient was found to be a compound heterozygote with previously described mutations in UNC13D – a missense mutation and a frameshift mutation (UNC13Dc.2346_2349 del GGAG; UNC13D:c.2672 T > C), confirming the diagnosis of familial HLH.4 After our patient was diagnosed with HLH, testing on the stillborn sibling identified the same pathogenic variants in UNC13D.
Related Knowledge Centers
- Hemophagocytic Lymphohistiocytosis
- Histiocyte
- Macrophage Activation Syndrome
- White Blood Cell
- Platelet
- Bone Marrow
- Red Blood Cell
- Phagocytosis
- Autopsy
- Covid-19