July 2014 - Presented by Jessica Rogers, M.D. & Pritesh Chaudhari, M.D.


Histiocytic Sarcoma


Histiocytic Sarcoma is a rare hematopoietic neoplasm representing less than 1 % of all non-Hodgkin’s lymphomas.  The diagnosis of HS relies primarily on verification of histiocytic lineage and the exclusion of other, poorly differentiated, large cell malignancies.  The recent characterization of CD163, a hemoglobin scavenger receptor protein, has offered a means of identifying histiocytic cells with a greater degree of specificity and is a promising marker in the diagnosis of true histiocytic malignancies.  Extranodal presentation is frequent and the clinical course is generally aggressive with poor prognosis.  Stage of disease and possibly tumor size appear to be prognostically significant.

Typical microscopic findings include Sinus expansion or nodal effacement with sparing of follicles by large cells with variable pleomorphism, abundant eosinophilic cytoplasm, irregular nuclei and prominent nucleoli.  In addition, finding may include giant cells, focal spindling, necrosis, mitotic figures and inflammatory background.  Erythrophagocytosis, a feature previously felt to be important in the diagnosis, may be present but is nonspecific and frequently is not prominent in bona fide cases.

The importance of immunophenotypic studies in the diagnosis has been emphasized.  However, markers once thought to be specific for histiocytic differentiation, such as alpha-1-antitrypsin, alpha-1-antichymotrypsin, lysozyme, and KP1, have been shown to have low specificity and may be positive in a wide variety of neoplasms.  Monoclonal antibodies, such as PG-M1, and more recently CD163, have demonstrated more restricted reactivity.  In particular CD163 has recently been studied in a variety of benign and malignant tissues and shows almost exclusive expression in cells of monocyte/macrophage lineage.  Genetic rearrangement studies remain a controversial issue but are probably not necessary to establish the diagnosis.

Suggested treatment options consist of tumor resection followed by administration of induction chemotherapy consisting of dose-escalated CHOP plus etoposide.  Clinical studies have shown no evidence of disease for 30 months post treatment.


1. Jeffery A Vos, Susan L Abbondanzo, Carol L Barekman, JoAnn W Andriko, Markku Miettinen and Nadine S Aguilera., Histiocytic Sarcoma: a study of five cases including the histiocyte marker CD163.  Modern Pathology, 2005 18: 693-704.

2.  Tsujimura H, Miyaki T, Yamada S, Sugawara T, Ise M, Iwata S, Yonemoto T, Ikebe D, Itami M, Kumagai K.  Successful treatment of histiocytic sarcoma with induction chemotherapy consisting of dose-escalated CHOP plus etoposide and upfront consolidation auto-transplantation.  Int J Hematol. 2014 Jul 26.

3. Oka K1, Nakamine H, Maeda K, Yamakawa M, Imai H, Tada K, Ito M, Watanabe Y, Suzuki H, Iwasa M, Tanaka I.  Primary histiocytic sarcoma of the spleen associated with hemophagocytosis. Int J Hematol. 2008 May;87(4):405-9. doi: 10.1007/s12185-008-0059-6.