There have been many inconsistencies in the naming, classifying, and diagnosing of malignant histiocytosis [1]. The original description of the disease was based on visual inspection and then on light microscopy. Later, as immunological and molecular techniques became available, many cases that were originally diagnosed as malignant histiocytosis were shown to be T cell or B cell lymphomas [2]. Therefore, the 2001 World Health Organization guidelines required the demonstration that there was no T or B cell specific gene rearrangements; however, in the 2008 guideline, this stipulation was abandoned [3] [4].

The classification and naming of malignant histiocytosis are also somewhat controversial. The disease has been referred to, among others, as atypical Hodgkin’s disease, histiocytic lymphoma, histiocytic medullary reticulosis [1], histiocytic sarcoma, [3] [5], or true histiocytic lymphoma.

The disease is very rare, and sometimes coexists with B or T cell neoplasms, or appears subsequently. It can present in various organs, mainly the lymph nodes, skin, gastrointestinal tract, and spleen, but many other sites can harbor malignant histiocytosis. Systemic symptoms, such as fever, fatigue, night sweats, and weight loss are often observed. Lymphadenopathy, splenomegaly, hepatomegaly, skin conditions such as rashes and multiple tumors, as well as gastrointestinal and other problems, are also encountered.

• Splenomegaly

  The long duration of massive splenomegaly suggests that this patient could represent a chronic form of MH. [ncbi.nlm.nih.gov]

  Lymphadenopathy, splenomegaly, hepatomegaly, skin conditions such as rashes and multiple tumors, as well as gastrointestinal and other problems, are also encountered. Anemia, thrombocytopenia, and leukopenia are frequent. [symptoma.com]

  Fever, splenomegaly and hepatomegaly are the most common early findings; b. Lymph node enlargement, skin rash, and neurologic abnormali¬ties may also occur. [hopkinsmedicine.org]

• Generalized Lymphadenopathy

  All had localized or generalized lymphadenopathy and three had hepatosplenomegaly at initial presentation. [ncbi.nlm.nih.gov]

  […] with generalized adenopathy. [medtextfree.wordpress.com]

• Fever

  Fever, hepatosplenomegaly and elevation of LDH levels all disappeared spontaneously, and presumptive diagnosis of benign reticulosis with haemophagocytosis was made. [ncbi.nlm.nih.gov]

• Weight Loss

  The patient also suffered from general fatigue, arthralgia, and weight loss. She was anemic and thrombocytopenic and had progressive impairment of liver function with coagulation defect. [ncbi.nlm.nih.gov]

  Monocytic leukaemia Monocytic leukaemia presents either with unexpected abnormalities found on blood tests or with generalised symptoms of fatigue, weight loss, easy bruising, recurrent infections, skin lumps ( leukaemia cutis ) and swelling of the gums [dermnetnz.org]

  Systemic symptoms, such as fever, fatigue, night sweats, and weight loss are often observed. [symptoma.com]

• Anemia

  The clinical features included fever, anemia, and marked hepatosplenomegaly without lymphadenopathy. [ncbi.nlm.nih.gov]

  […] reticulosis [ rĕ-tik″u-lo´sis ] an abnormal increase in cells derived from or related to the reticuloendothelial cells. familial histiocytic reticulosis ( histiocytic medullary reticulosis ) a fatal hereditary disorder marked by anemia, granulocytopenia [medical-dictionary.thefreedictionary.com]

  Anemia, thrombocytopenia, and leukopenia are frequent. The tumor cells are large, oval-shaped or round, with eosinophilic cytoplasm that can look foamy because of elevated lipid levels. The cells do not adhere to each other. [symptoma.com]

• Precocious Puberty

  A 10-year-old boy with precocious puberty of 2 1/2 years' duration presented with a malignant thoracic teratoma with elevated levels of beta human chorionic gonadotropin (beta-HCG) and alpha fetoprotein (alpha FP). [ncbi.nlm.nih.gov]

• Fishing

  FISH analysis confirmed the presence of IgH/BCL2 rearrangement in both the low grade follicular lymphoma (FL) and transformed Langerhans cells sarcoma (LCS) samples, demonstrating a clonal relationship. [ncbi.nlm.nih.gov]

• Rectal Bleeding

  The patient's symptoms and radiologic features improved dramatically with steroid therapy, and the patient remained free of severe symptoms for five years; at this stage, massive rectal bleeding occurred and segmental ileal resection was performed. [ncbi.nlm.nih.gov]

• Chest Pain

  Primary pulmonary involvement, which is rare in children, is seen predominately in male adults.135,136 Chronic nonproductive cough, chest pain, shortness of breath, and wheezing are the most common symptoms. [medtextfree.wordpress.com]

• Hepatosplenomegaly

  A 10-year-old boy with malignant histiocytosis presented with fever, hepatosplenomegaly, and diffuse pancreatic enlargement, mimicking acute pancreatitis. [ncbi.nlm.nih.gov]

• Hepatomegaly

  Most patients presented with systemic symptoms and lymphadenopathy (92%), splenomegaly (100%) and hepatomegaly (67%). Neurologic symptoms were present in three patients, while involvement of other organs was present in five patients. [ncbi.nlm.nih.gov]

  Lymphadenopathy, splenomegaly, hepatomegaly, skin conditions such as rashes and multiple tumors, as well as gastrointestinal and other problems, are also encountered. Anemia, thrombocytopenia, and leukopenia are frequent. [symptoma.com]

  Bone lesion, hyperprolactinemia, diabetes insipidus Skin invasion of Langerhans cells, exophthalmos, diabetes mellitus Skin invasion of Langerhans cells, hepatomegaly, enophthalmus Bone lesion, exophthalmos, diabetes insipidus Diabetes insipidus, hepatomegaly [lecturio.com]

  Fever, splenomegaly and hepatomegaly are the most common early findings; b. Lymph node enlargement, skin rash, and neurologic abnormali¬ties may also occur. [hopkinsmedicine.org]

  The disease occurs more often in men than in women.216,219,221 SIGNS AND SYMPTOMS Fever, headache, weakness, weight loss, dyspnea, and sweating occur commonly in most patients who have generalized disease.219,221,222 Splenomegaly, hepatomegaly, and lymphadenopathy [medtextfree.wordpress.com]

• Long Arm

  The malignant cells had a deletion of the long arm of chromosome #7, 46,XX,del(7)(q22). [ncbi.nlm.nih.gov]

• Purpura

  In case 2 the diagnosis was initially idiopathic thrombocytopenia purpura but he deteriorated on steroids, and was subsequently unsuccessfully treated with chemotherapy and gamma globulin infusions. [ncbi.nlm.nih.gov]

  Haug Browse recently published Learning/CME Learning/CME View all learning/CME CME Case 3-2019: A 70-Year-Old Woman with Fever, Headache, and Progressive Encephalopathy Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura Randomized [nejm.org]

• Skin Rash

  Lymph node enlargement, skin rash, and neurologic abnormali¬ties may also occur. [hopkinsmedicine.org]

• Subcutaneous Nodule

  A 32-year-old woman presented with recurrent erythematous plaques, subcutaneous nodules, and ulcers on the trunk and the extremities and intermittent fever for 7 months. [ncbi.nlm.nih.gov]

Anemia, thrombocytopenia, and leukopenia are frequent.

The tumor cells are large, oval-shaped or round, with eosinophilic cytoplasm that can look foamy because of elevated lipid levels. The cells do not adhere to each other. Bi- or multinucleated cells are not uncommon, and the nuclei can have multiple lobes. Mitoses and phagocytic activity are often observed. Lysosomes are seen in the cytoplasm in substantial numbers, but not Birbeck granules, which are cytoplasmic inclusions characteristic of Langerhans cells [6]. Various benign immune cells are also present - lymphocytes, neutrophils, eosinophils, and non-malignant histiocytes.

Immunological methods are used extensively for the diagnosis of malignant histiocytosis; a large number of histiocytic and other markers are available. Except for the extremely rare cases of transdifferentiation, an immunological examination should show the reaction with macrophage markers and lack of reaction with markers for myeloid cells, dendritic and Langerhans cells, B cells, T cells, and epithelial cells. Histiocytic markers are CD163 and CD 68, the latter being used regularly, although it is known to react with other types of cancer cells in addition to those of monocytic/macrophage origin [3]. CD163, which is a hemoglobin scavenger receptor, is essentially specific for macrophages or histiocytes [7]. Among other macrophage specific markers are CD11c, CD14, and CD31. No immunochemical staining with myeloid markers (myeloperoxidase, CD33 and CD34), dendritic cell markers (CD1a, CD21 and CD35), or T or B cell markers should be observed [6] [8] [9] [10], although, as mentioned above, a few examples of transdifferentiation have been described. Similarly, in most cases, immunoglobulin or T cell receptor gene rearrangements are not detected.

Benign and malignant histiocytes carry similar markers, therefore distinguishing them has to be based on cell morphology. Distinction from Langerhans cell neoplasms is by immunological markers, in addition to an absence of the characteristic Birbeck granules of Langerhans cells. Anaplastic large cell lymphoma, the cells of which are morphologically similar to malignant histiocytes, is most easily mistaken for malignant histiocytosis. However, anaplastic lymphoma cells express CD30, ALK-1, and other markers. Moreover, they harbor a characteristic chromosomal translocation, and T cell receptor gene rearrangements [3].

• Bilateral Pulmonary Infiltrates

  A 30-year-old previously healthy housewife presented with bilateral pulmonary infiltrates. She was treated with various antibiotics but died with disseminated intravascular coagulation. [ncbi.nlm.nih.gov]

The experience with the treatment of malignant histiocytosis has been disappointing. Despite modest treatment success with a combination of cyclophosphamide, Adriamycin (doxorubicin), vincristine and prednisone, the overall prognosis remains poor. [ncbi.nlm.nih.gov]

What is the treatment? Most patients with these cancerous forms of histiocytosis respond to treatment with chemotherapy or radiotherapy. Malignant histiocytosis progresses very quickly and treatment must be started as early as possible. [dermnetnz.org]

In MH patients, other parameters, such as coagulopathy and lactic dehydrogenase, ferritin and IL-1 levels, did not correlate with prognosis. [ncbi.nlm.nih.gov]

Treatment and prognosis The prognosis can be extremely variable with eosinophilic granuloma carrying the best and Letterer-Siwe disease-carrying the worst prognosis. [radiopaedia.org]

We think that reactive and malignant histiocytosis are not really two distinct entities with different etiologies, but a continuum of host responses to several insults with different degrees of aggressiveness depending on the host immune status. [ncbi.nlm.nih.gov]

Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology. [icd10coded.com]

Etiology of histiocytic sarcomas is unknown. [vin.com]

Bassuni, MB, BCh, MSc, and Osama Eid, MB, BCh, MSc pp. 342-345 Brucellosis in Saudi Arabia: Epidemiology in the Central Region Ibrahim Abdulkarim Al Mofleh, AFIM,, Abdulkarim Ibrahim Al Aska, AFIM, Mohammed Abdulaziz Al Sekait, PhD, Sulaiman Rashed Al [annsaudimed.net]

Introduction A rare malignant histiocytic lesion of the bone similar in presentation to osteosarcoma, but histologically different (lacks osteoid formation) also known as undifferentiated pleomorphic sarcoma Epidemiology incidence comprises < 2% of all [orthobullets.com]

Linguistic Variant - Portuguese, Brazil) 2015AB LNC-RU-RU (LOINC Linguistic Variant - Russian, Russia) 2015AB LNC-TR-TR (LOINC Linguistic Variant - Turkish, Turkey) 2015AB LNC-ZH-CN (LOINC Linguistic Variant - Chinese, China) 2015AB MCM (Glossary of Clinical Epidemiologic [doctor.am]

Epidemiology of Langerhans Cell Histiocytosis Prevalence of histiocytosis X The incidence is 0.4-1 in 100,000 with an age-based peak for a disseminated course of the disease in infants and toddlers. [lecturio.com]

Carstensen H, Ornvold K: The epidemiology of LCH in Denmark: 1975–1989. Med Pediatr Oncol 21:387, 1993. 115. Broadbent V, Egeler RM, Nesbit ME: Langerhans cell histiocytosis: Clinical and epidemiological aspects. [medtextfree.wordpress.com]

Etiology of Langerhans Cell Histiocytosis Causes of Langerhans cell histiocytosis A disturbed intercellular communication between effector cells, specifically T-cells and the antigen presenting Langerhans cells is assumed as pathophysiology. [lecturio.com]

Lungs: some patients are asymptomatic, diagnosed incidentally because of lung nodules on radiographs; others suffer from chronic cough and shortness of breath. [13] Less frequently gastrointestinal tract, central nervous system, and oral cavity. [14] Pathophysiology [en.wikipedia.org]

The former designation is favored for discussions of the cell biology and pathophysiology of the mature cell found in tissues in the monocyte-macrophage system. [medtextfree.wordpress.com]

Previously, the lack of monoclonal antibodies specific to histiocytes and the absence of techniques for performing molecular genetic studies on paraffin-embedded tissue prevented the study of such cases. [ncbi.nlm.nih.gov]

December 13, 2018 Kris Carter, DVM, MPVM, DACVPM, Epidemiologist, Center for Preparedness and Response, Centers for Disease Control and Prevention (CDC), and Matthew E. [merckvetmanual.com]

NCI_CTEP-SDC (Cancer Therapy Evaluation Program - Simple Disease Classification) 2015AB NCI_CareLex (Content Archive Resource Exchange Lexicon) 2015AB NCI_DCP (NCI Division of Cancer Prevention Program) 2015AB NCI_DICOM (Digital Imaging Communications [doctor.am]

Surgical excision may be successful for solitary lesions, but it does not prevent development of new lesions elsewhere. [vin.com]

The best way to manage cancer pain in pets is to prevent it, a term referred to as preemptive pain management. [petcancercenter.org]

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