Final Diagnosis -- Histiocytic Sarcoma


Histiocytic Sarcoma.


Histiocytic sarcoma is a rare malignant neoplasm of the lympho-hematopoietic system. Lymphadenopathy can be a clinical presentation but the majority of cases present extra-nodal involvement most commonly of the intestinal tract, skin and soft tissues. The brain, spinal cord, leptomeninges and eyes can also be involved. Primary presentation in the central nervous system is uncommon (5). Rarely, patients have a systemic presentation, with multiple sites of involvement sometimes referred to as malignant histiocytosis (1). The protocol for the examination of specimens from patients with Non-Hodgkin Lymphoma/Lymphoid Neoplasms of the American College of Pathologists lists histiocytic sarcoma among histiocytic and dendritic cell neoplasms along with Langerhans cell histiocytosis, Langerhans cell sarcoma, interdigitating dendritic cell sarcoma, follicular dendritic cell sarcoma, fibroblastic reticular cell tumor, indeterminate dendritic cell tumor and disseminated juvenile xanthogranuloma (3). Differential diagnoses of histiocytic disorders include diffuse large cell lymphoma, metastatic carcinoma, reactive histiocytosis and various storage diseases (4). The World Health Organization classification of histiocytic disorders distinguishes: (i) storage diseases, including Erdheim Chester disease (ECD); (ii) histiocytic disorders of varied biological behavior, which are benign and divided into dendritic cell and macrophage lineage; and (iii) malignant disorders such as histiocytic sarcoma (2).

Histiocytic sarcoma arises from abnormal reticuloendothelial system cell proliferation of histiocytes which in the brain are represented by microglia and dendritic cells. The individual neoplastic cells are usually large and round or oval; the cytoplasm is abundant and eosinophilic, and can be foamy. Haemophagocytosis is occasionally observed in neoplastic cells. The nuclei are generally large, round or oval and often eccentrically placed; large multinucleated forms are not uncommon. The chromatin pattern is usually vesicular, and nuclear atypia varies from mild to pleomorphic. Mitoses are common and there is a concomitant high DNA replication index. A variable number of reactive cells can be seen, including small lymphocytes, plasma cells, benign histiocytes and eosinophils (4). Characteristically, neoplastic cells are immunoreactive to CD45, CD68 and CD163 (a recently-characterized hemoglobin scavenger receptor which appears to be a specific marker of histiocytic lineage and a promising diagnostic tool for evaluating histiocytic neoplasms) (6). CD1a, CD20, CD3, CD8, CD34, CD117, MPO and CD15 are typically negative.

Histiocytic sarcoma is usually aggressive with a poor response to therapy, although some exceptions have been reported. Patients with clinically localized disease and small primary tumors have a more favorable long-term outcome. Regarding involvement of the central nervous system, there is no consensus on the most appropriate treatment because of the limited number of reported cases.


  1. Devic P, Androdias-Condemine G, Streichenberger N, Berger F, Honnorat J, Broussolle E and Thobois S. (2012) Histiocytic sarcoma of the central nervous system: a challenging diagnosis. Q J Med 105:77-79
  2. Campo E, Swerdlow S, Harris N, Pileri S, Stein H and Jaffe E. (2011) The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood 117:5019-5032
  3. Hussong JW, Arber DA et al. (2013) Protocol for the examination of specimens from patients with Non-Hodgkin Lymphoma/Lymphoid Neoplasms. College of American Pathologists 4-6
  4. Favara BE, Feller AC, Pauli M, Jaffe ES, Weiss LM, Arico M, Bucsky P, Egeler RM, Elinder G, Gadner H, Gresik M. (1997) Contemporary classification of histiocytic disorders. The WHO Committee On Histiocytic/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocyte Society. 29:157-66.
  5. Hornick J.L., Jaffe E.S., and Fletcher C.D. (2004) Extranodal histiocytic sarcoma: clinicopathologic analysis of 14 cases of a rare epithelioid malignancy. Am J Surg Pathol. 28: 1133-1144.
  6. Vos JA, Abbondanzo SL, Barekman CL, Andriko JW, Miettinen M, Aguilera NS. (2005) Histiocytic sarcoma: a study of five cases including the histiocyte marker CD163. Mod Pathol. 2005 May; 18:693-704.

Contributed by Isidro Ferrer; Fina Climent; Noemi Vidal; Luis Alberto Escobar; Juan José Sánchez; Alejandro Fernandez-Coello

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