- Eric Jacobsen, MD
Eric Jacobsen, MD
- Assistant Professor of Medicine
- Harvard Medical School
Histiocytic sarcoma (HS) is an extremely rare non-Langerhans histiocyte disorder of unknown cause that most commonly presents with symptoms due to unifocal or multifocal extranodal tumors. HS may occur as a sporadic illness or may be clonally related to a separate synchronous or metachronous hematologic malignancy, such as follicular lymphoma or acute lymphoblastic leukemia.
Histocytic disorders are thought to be derived from mononuclear phagocytic cells (macrophages and dendritic cells) or histiocytes. This group has generally been divided into Langerhans cell histiocytosis and non-Langerhans histiocytosis. Langerhans cell histiocytosis is so named for its presumed derivation from the Langerhans cells, which are specialized dendritic cells found in the skin and mucosa. In contrast, non-Langerhans histiocytoses are thought to be derived from the monocyte-macrophage lineage.
The epidemiology, clinical manifestations, pathologic features, diagnosis, and management of HS will be presented here. The diagnosis and management of Langerhans cell histiocytosis and other non-Langerhans histiocytic disorders are presented separately. (See "Clinical manifestations, pathologic features, and diagnosis of Langerhans cell histiocytosis" and "Pulmonary Langerhans cell histiocytosis" and "Langerhans cell histiocytosis (eosinophilic granuloma) of bone in children and adolescents" and "Erdheim-Chester disease".)
HS is an extremely rare disease with only a few hundred cases reported in the literature. HS has been diagnosed in all age groups, but is most common in adults. In two case series, the median ages at diagnosis were 46 and 55 years [1,2]. There is no apparent gender difference.
There are no known environmental or hereditary genetic factors predisposing to the development of HS. HS can occur as an isolated disease or in the context of other hematologic neoplasms, such as follicular lymphoma, myelodysplasia, or acute lymphoblastic leukemia . When HS occurs in the context of another hematologic malignancy, the two entities are often clonally related [3,4]. Of importance, tumors with pathologic features consistent with HS occurring in the context of acute monocytic leukemia are not considered HS.
- Hornick JL, Jaffe ES, Fletcher CD. Extranodal histiocytic sarcoma: clinicopathologic analysis of 14 cases of a rare epithelioid malignancy. Am J Surg Pathol 2004; 28:1133.
- 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.
- Castro EC, Blazquez C, Boyd J, et al. Clinicopathologic features of histiocytic lesions following ALL, with a review of the literature. Pediatr Dev Pathol 2010; 13:225.
- Wang E, Hutchinson CB, Huang Q, et al. Histiocytic sarcoma arising in indolent small B-cell lymphoma: report of two cases with molecular/genetic evidence suggestive of a 'transdifferentiation' during the clonal evolution. Leuk Lymphoma 2010; 51:802.
- deMent SH. Association between mediastinal germ cell tumors and hematologic malignancies: an update. Hum Pathol 1990; 21:699.
- Feldman AL, Arber DA, Pittaluga S, et al. Clonally related follicular lymphomas and histiocytic/dendritic cell sarcomas: evidence for transdifferentiation of the follicular lymphoma clone. Blood 2008; 111:5433.
- Chen W, Lau SK, Fong D, et al. High frequency of clonal immunoglobulin receptor gene rearrangements in sporadic histiocytic/dendritic cell sarcomas. Am J Surg Pathol 2009; 33:863.
- Carrasco DR, Fenton T, Sukhdeo K, et al. The PTEN and INK4A/ARF tumor suppressors maintain myelolymphoid homeostasis and cooperate to constrain histiocytic sarcoma development in humans. Cancer Cell 2006; 9:379.
- Go H, Jeon YK, Huh J, et al. Frequent detection of BRAF(V600E) mutations in histiocytic and dendritic cell neoplasms. Histopathology 2014; 65:261.
- Haroche J, Charlotte F, Arnaud L, et al. High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses. Blood 2012; 120:2700.
- Swerdlow SH, Campo E, Harris NL, et al. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, IARC Press, Lyon 2008.
- Oka K, Nakamine H, Maeda K, et al. Primary histiocytic sarcoma of the spleen associated with hemophagocytosis. Int J Hematol 2008; 87:405.
- Vos JA, Abbondanzo SL, Barekman CL, et al. Histiocytic sarcoma: a study of five cases including the histiocyte marker CD163. Mod Pathol 2005; 18:693.
- Yoshida C, Takeuchi M. Histiocytic sarcoma: identification of its histiocytic origin using immunohistochemistry. Intern Med 2008; 47:165.
- Mikami M, Sadahira Y, Suetsugu Y, et al. Monocyte/Macrophage-specific marker CD163+ histiocytic sarcoma: case report with clinical, morphologic, immunohistochemical, and molecular genetic studies. Int J Hematol 2004; 80:365.
- Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127:2375.
- Yaman E, Ozturk B, Erdem O, et al. Histiocytic sarcoma: PET-CT evaluation of a rare entity. Ann Nucl Med 2008; 22:715.
- Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol 2010; 28:4184.
- Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002; 346:235.
- Haroche J, Cohen-Aubart F, Emile JF, et al. Reproducible and sustained efficacy of targeted therapy with vemurafenib in patients with BRAF(V600E)-mutated Erdheim-Chester disease. J Clin Oncol 2015; 33:411.
- Haroche J, Cohen-Aubart F, Emile JF, et al. Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation. Blood 2013; 121:1495.
- Idbaih A, Mokhtari K, Emile JF, et al. Dramatic response of a BRAF V600E-mutated primary CNS histiocytic sarcoma to vemurafenib. Neurology 2014; 83:1478.
- Mainardi C, D'Amore ES, Pillon M, et al. A case of resistant pediatric histiocytic sarcoma successfully treated with chemo-radiotherapy and autologous peripheral blood stem cell transplant. Leuk Lymphoma 2011; 52:1367.
- Gergis U, Dax H, Ritchie E, et al. Autologous hematopoietic stem-cell transplantation in combination with thalidomide as treatment for histiocytic sarcoma: a case report and review of the literature. J Clin Oncol 2011; 29:e251.
- Abidi MH, Tove I, Ibrahim RB, et al. Thalidomide for the treatment of histiocytic sarcoma after hematopoietic stem cell transplant. Am J Hematol 2007; 82:932.
- Shukla N, Kobos R, Renaud T, et al. Successful treatment of refractory metastatic histiocytic sarcoma with alemtuzumab. Cancer 2012; 118:3719.