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Malignant Histiocytosis

Polymorphic Reticulosis

Malignant histiocytosis is a rare neoplasm composed of cells with morphological and immunological characteristics similar to those of mature tissue histiocytes. The neoplasm may be disseminated or localized. An aggressive disease, it is often diagnosed at an advanced stage.


Presentation

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]
  • The major clinical findings included panhemocytopenia, splenomegaly, and signs of liver dysfunction with severe jaundice. During life, a definite diagnosis could not be established.[ncbi.nlm.nih.gov]
  • 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]
  • The dogs present with prominent progressive anemia and splenomegaly. With increasing involvement of the liver the hepatic enzymes become more elevated. Histology and immunophenotyping --LHS and DHS present with identical histiocytic features.[vin.com]
Generalized Lymphadenopathy
  • All had localized or generalized lymphadenopathy and three had hepatosplenomegaly at initial presentation.[ncbi.nlm.nih.gov]
  • Malignant histiocytosis (MH: sinusoidal hematolymphoid malignancy) is a rare lymphoreticular disorder characterized by an aggressive clinical course in younger patients with weight loss, hepatosplenomegaly, generalized lymphadenopathy and pancytopenia[ncbi.nlm.nih.gov]
Massive Splenomegaly
  • The long duration of massive splenomegaly suggests that this patient could represent a chronic form of MH.[ncbi.nlm.nih.gov]
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]
  • This is clearly seen in the seven patients we report where the initial diagnoses were that of viral fever or hepatitis.[ncbi.nlm.nih.gov]
  • 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]
  • The terminal event was characterized by fever, hepatosplenomegaly, thrombocytopenia, and a leukemic blood picture. The pathogenesis of this terminal transformation and proposed future studies are discussed.[ncbi.nlm.nih.gov]
  • A 10-year-old boy with malignant histiocytosis presented with fever, hepatosplenomegaly, and diffuse pancreatic enlargement, mimicking acute pancreatitis.[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]
  • Malignant histiocytosis (MH: sinusoidal hematolymphoid malignancy) is a rare lymphoreticular disorder characterized by an aggressive clinical course in younger patients with weight loss, hepatosplenomegaly, generalized lymphadenopathy and pancytopenia[ncbi.nlm.nih.gov]
  • Systemic symptoms, such as fever, fatigue, night sweats, and weight loss are often observed.[symptoma.com]
  • 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]
  • Characteristic symptoms are malaise, weight loss, abdominal pain, and diarrhea followed, after a period of weeks or months, by acute small intestinal obstruction, perforation, or bleeding.[link.springer.com]
Anemia
  • The clinical features included fever, anemia, and marked hepatosplenomegaly without lymphadenopathy.[ncbi.nlm.nih.gov]
  • Thus, based on analysis of the clinical findings of these 34 cases, the diagnostic criteria for AIVL consists primarily of cytopenia (anemia and/or thrombocytopenia), hepatosplenomegaly, absence of peripheral lymphadenopathy and tumor formation, and erythrocyte-hemophagocytosis[ncbi.nlm.nih.gov]
  • These features were usually accompanied by fever, deterioration of general condition, and hematological abnormalities including anemia, thrombocytopenia, and occasionally fibrinopenia.[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.[symptoma.com]
  • […] 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]
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]
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]
Hepatosplenomegaly
  • Fever, hepatosplenomegaly and elevation of LDH levels all disappeared spontaneously, and presumptive diagnosis of benign reticulosis with haemophagocytosis was made.[ncbi.nlm.nih.gov]
  • A 10-year-old boy with malignant histiocytosis presented with fever, hepatosplenomegaly, and diffuse pancreatic enlargement, mimicking acute pancreatitis.[ncbi.nlm.nih.gov]
  • The terminal event was characterized by fever, hepatosplenomegaly, thrombocytopenia, and a leukemic blood picture. The pathogenesis of this terminal transformation and proposed future studies are discussed.[ncbi.nlm.nih.gov]
  • Bilateral cervical and axillary lymphadenopathy was present along with hepatosplenomegaly. The haematological, cytological and histopathological features are described.[ncbi.nlm.nih.gov]
  • Abstract A patient with acquired immunodeficiency syndrome-related complex was examined for fever and hepatosplenomegaly. During his hospitalization, liver failure developed in the patient, and he became infected with Pseudomonas and Staphylococcus.[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]
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]
Exanthema
  • Polymorphic maculopapular exanthema with hemorrhaging, ulceration and formation of crusts are observed. Additionally, hair may often be thinning and the children may suffer from fever.[lecturio.com]
Hyperpigmentation
  • She was diagnosed as having malignant histiocytosis and treated with cyclophosphamide, vincristine, and prednisolone which she responded well; her fever subsided and the lesions healed with hyperpigmentation.[ncbi.nlm.nih.gov]

Workup

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].

Treatment

  • 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]
  • Treatment with prednisolone, doxorubicin and irradiation controlled the tracheal compression.[ncbi.nlm.nih.gov]
  • Abstract We investigated the responses of patients with malignant histiocytosis (MH) to the treatment of epotoside-based regimen.[ncbi.nlm.nih.gov]
  • Satisfactory response to treatment was observed only in the responder group. Similarity of histopathology, cytology and immunophenotype was observed in these two groups.[ncbi.nlm.nih.gov]
  • Treatment of DEL cells with 33 nM 12-O-tetradecanoylphorbol-13-acetate for 6-24 h resulted in cell surface attachment (up to 80%), decrease in dividing ability, enhancement of nitro blue tetrazolium reducing capacity (from 8 to 42%), occurrence of a limited[ncbi.nlm.nih.gov]

Prognosis

  • 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]
  • Despite modest treatment success with a combination of cyclophosphamide, Adriamycin (doxorubicin), vincristine and prednisone, the overall prognosis remains poor. There are only a few reports of prolonged complete remissions in pediatric patients.[ncbi.nlm.nih.gov]
  • The PT is the most important prognosis factor. Early diagnosis and treatment led to improved survival in an otherwise aggressive and rapidly fatal condition.[ncbi.nlm.nih.gov]
  • The findings suggest that the prognosis in childhood MH remains guarded but not hopeless with aggressive combination chemotherapy.[ncbi.nlm.nih.gov]
  • It usually affects children or young adults and has a poor prognosis … Medical dictionary Histiocytosis — Classification and external resources ICD 10 C96.1, D76.0 ICD 9 … Wikipedia Histiocytosis, malignant — Histiocytosis in which the histiocytes actually[translate.academic.ru]

Etiology

  • A thorough work-up revealed no obvious etiology. At autopsy, malignant histiocytosis of the liver and bone marrow was diagnosed.[ncbi.nlm.nih.gov]
  • 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]
  • The DEL cell line is appropriate for studying the role of the 5q localized c-fms oncogene and of the genes of the mononuclear phagocyte growth factor (CSFI) and of their receptors in the dynamics and etiology of malignant hemopathies associated with a[ncbi.nlm.nih.gov]
  • Etiology of histiocytic sarcomas is unknown.[vin.com]
  • Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology.[icd10coded.com]

Epidemiology

  • 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]
  • Broadbent, V, Egeler, RM, Nesbit, ME: Langerhans cell histiocytosis—clinical and epidemiological aspects. Br J Cancer Suppl 23: 11 – 16, 1994 Google Scholar 4. Bucsky, P, Egeler, RM: Malignant histiocytic disorders in children.[dx.doi.org]
Sex distribution
Age distribution

Pathophysiology

  • 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]

Prevention

  • 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]
  • 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]
  • 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]

References

Article

  1. Low SE, Stafford JS. Malignant histiocytosis: a case report of a rare tumour presenting with spontaneous splenic rupture. J Clin Pathol. 2006;59(7):770-772
  2. Wilson MS, Weiss LM, Gatter KC, Mason DY, Dorfman RF, Warnke RA. Malignant histiocytosis. A reassessment of cases previously reported in 1975 based on paraffin section immunophenotyping studies. Cancer. 1990;66(3):530-536.
  3. Takahashi E, Nakamura S. Histiocytic sarcoma : an updated literature review based on the 2008 WHO classification. J Clin Exp Hematop. 2013;53(1):1-8.
  4. Wetzler M, Kurzrock R, Goodacre AM, McLaughlin P, Ku S, Talpaz M. Transformation of chronic lymphocytic leukemia to lymphoma of true histiocytic type. Cancer. 1995;76(4):609-617.
  5. Mathé G, Gerard-Marchant R, Texier JL, Schlumberger JR, Berumen L, Paintrand M. The two varieties of lymphoid tissue "reticulosarcomas", histiocytic and histioblastic types. Br J Cancer. 1970;24(4):687-695.
  6. Pileri SA, Grogan TM, Harris NL, et al. Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology. 2002;41(1):1-29.
  7. Nguyen TT, Schwartz EJ, West RB, Warnke RA, Arber DA, Natkunam Y. Expression of CD163 (hemoglobin scavenger receptor) in normal tissues, lymphomas, carcinomas, and sarcomas is largely restricted to the monocyte/macrophage lineage. Am J Surg Pathol. 2005;29(5):617-624.
  8. Sun W, Nordberg ML, Fowler MR. Histiocytic sarcoma involving the central nervous system: clinical, immunohistochemical, and molecular genetic studies of a case with review of the literature. Am J Surg Pathol. 2003;27(2):258-265.
  9. Ralfkiaer E, Delsol G, O'Connor NT, et al. Malignant lymphomas of true histiocytic origin. A clinical, histological, immunophenotypic and genotypic study. J Pathol. 1990;160(1):9-17.
  10. Hornick JL, Jaffe ES, Fletcher CD. Extranodal histiocytic sarcoma: clinicopathologic analysis of 14 cases of a rare epithelioid malignancy. Am J Surg Pathol. 2004;28(9):1133-1144.

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Last updated: 2019-07-11 20:44