Primary Histiocytic Sarcoma of Bone with Disseminated Involvement - Initial Presentation Mimicking Multiple Myeloma: The Atypical Face of a Rare Neoplasm

Case Presentation

Ann Hematol Oncol. 2019; 6(9): 1270.

Primary Histiocytic Sarcoma of Bone with Disseminated Involvement - Initial Presentation Mimicking Multiple Myeloma: The Atypical Face of a Rare Neoplasm

Lage LAPC1*, Albuquerque VJ1, Moraes RDR2, Couto SCF1, Culler HF2, Rocha V1 and Pereira J1

¹Department of Hematology, Hemotherapy and Cell Therapy, School of Medicine, University of São Paulo (FMUSP), UK

²Department of Pathology, School of Medicine, University of São Paulo (FMUSP), UK

*Corresponding author: Lage LAPC, Department of Hematology, Hemotherapy and Cell Therapy, School of Medicine, University of São Paulo (FMUSP), Av. Dr. Enéas Carvalho de Aguiar, 155 - Cerqueira César, São Paulo - SP, Brazil

Received: September 16, 2019; Accepted: November 12, 2019; Published: November 19, 2019


Histiocytic Sarcoma (HS) is an uncommon malignancy derived from macrophage/dendritic lineage cells and accounts for less than 1% of hematologic tumors. Due to its rarity, little is known about its clinical-biological behavior and therapeutic recommendations have not been standardized so far. In addition to lymph node enlargement most cases present extranodal involvement, especially in the gastrointestinal tract, skin and soft tissues. Bone involvement is usually described in association with systemic disease and in advanced stages. Here we describe a case of patient with HS with primary bone involvement and multiple osteolytic lesions and bone fractures in the absence of another organs involvement. A male patient presented with an aggressive disease with rapid progression and his disease was unresponsive to standard therapy. Although rare, this kind of HS presentation should fall within the scope of differential diagnosis of other neoplasms with widespread bone involvement such as multiple myeloma and bone metastasis from solid tumors as the prostate, breast and lungs.

Keywords: Histiocytic sarcoma; Cortical bone; Lytic lesions; Multiple myeloma; BRAFV600E


HS: Histiocytic Sarcoma; CD: Cluster Designation; KMT2D: histone-lysine N-methyltransferase 2D; MAP kinase: Mitogen- Activated Protein Kinase; MAP2K1: Mitogen-Activated Protein Kinase 1; Hb: Hemoglobin; Ht: Hematocrit; MCV: Mean Cell Volume; MCH: Mean Cell Hemoglobin; MCHC: Mean Corpuscular Hemoglobin Concentration; RDW: Red Cell Distribution Width; WBC: White Blood Count; TIBC: Total Iron-Binding Capacity; ESR: Erythroid Sedimentation Rate; CRP: C-Reactive Protein; Ca: Calcium; HIV: Human Immunodeficiency Virus; MRI: Magnetic Resonance Imaging; CT: Computerized Tomography; H&E: Haematoxyline & Eosin staining; TdT: Terminal Deoxynucleotidyl Transferase; 18-FDGPETCT: 18-Fluorodeoxyglucose-Computerized Tomography With Positron Emission; Max: Maximum; SUV: Standardized Up- Take Value; CHOEP: Cyclophosphamide, doxorubicin, Oncovin, Etoposide and Prednisone; G-CSF: Granulocyte Colony Stimulating Factor; OS: Overall Survival; ICE: Ifosfamide, Carboplatin and Etoposide


Histiocytic Sarcoma (HS) is an extremely rare neoplasm responsible for less than 1% of all hematologic malignancies [1]. Although its biological behavior resembles that of lymphomas, its cell line is histiocytic and non-lymphoid. Thereafter, the malignant cell of the HS exhibits morphological and immunophenotypic characteristics of the mature histiocyte. In the most recent 2016 revision of the World Health Organization Classification, histiocytic sarcoma was classified inside the macrophage/dendritic tumors along with others histiocytosis and stroma-derived dendritic cell tumors [2,3].

In the immunohistochemical analysis HS malignant cells shown positivity for one or more histiocytic lineage markers including CD68 (KP1, PGM1), CD163 and lysozyme. CD45, CD45RO and HLA-DR are often positive and it is typically negative for Langerhans cell markers and other dendritic cell markers such as CD1a, langherin, CD21 and CD35 as well as for myeloid, B-lymphoid and T-lymphoid markers. S-100 protein may be positive but usually it expression is weak or focal and Ki67 has a variable expression [4].

Gene expression studies have shown that a subset of HS has clonal rearrangement of the immunoglobulin gene, especially in cases associated with low-grade B-cell lymphomas [5]. BRAF V600E mutation has been also described in some cases. In a recent study 5 of 8 cases of HS presented the BRAF V600E mutation, making this information a promising option for target therapy [6]. In addition, recurrent mutations involving the KMT2D gene and MAP kinase pathway genes including KRAS, NRAS and MAP2K1 have been described [7,8]. Despite the progress made in the molecular field, its etiology still remains unknown.

HS is usually aggressive and present as advanced stages III and IV and with poor response to therapy, although exceptions have been reported. In fact, most patients die from disease progression [9]. Lymphadenopathy is common and most cases present extralymphonodal involvement, most commonly in the gastrointestinal tract, skin, superficial and deep soft tissues, lung and nasal cavity [10]. Few reports have shown neoplasia arising in the central nervous system, endocrine tissues and bone marrow [11,12]. Rarely, patients shown systemic disease with multiple disease sites referred to as malignant histiocytosis.

Secondary bone involvement is described in systemic disease as well as in advanced stages, but primary bone disease was not described in the literature yet. Here, we report the case of a 32-yearold man with primary bone HS presenting with disseminated bone involvement characterized by multiple lytic lesions and fractures mimicking multiple myeloma. This is the first case of primary bone HS reported to date, an extremely rare and aggressive form of this disease.

Case Report

A previously healthy 32-year-old Brazilian man has a 4-month history of weight loss of 33 kg, night sweats, intermittent fever, fatigue, intolerance to usual efforts, and solid tumors onset in the trunk and scalp. He evolved with significant bone pain in the scapula, sternum, ribs and lumbosacral spine. The patient denied perception of lymph node enlargement, pruritus, as well as a history of recurrent infections and hemorrhagic manifestations.

He was admitted in our emergency department complaining loss of strength and sensitivity in both lower limbs, associated with urinary retention and fecal incontinence with started 1 week ago. Physical and neurological examination revealed deep skin and mucous pallor, flaccid crural paraplegia and hardened tumors on the back, scalp, sternum and left costal gradient. There were no superficial lymphadenopathy or hepatosplenomegaly.

Initial laboratory tests showed: Hb 63 g/L, Ht 19%, MCV 82 fl, MCH 29 pg, MCHC 33%, RDW 15.4%, WBC 14.09 x 109/L (73.1% neutrophils, 4.0% eosinophils, 0.1% basophils, 15.7% lymphocytes and 7.1% monocytes) and platelet count of 722 x 109/L. Reticulocyte count 1.15% (30,000 reticulocytes/mm3) and inflammation-consistent iron profile (serum iron: 34 μg/dL, iron saturation 17%, ferritin 6,795 ng/mL, transferrin 158 mg/dL and TIBC = 202 μg/dL). Renal, hepatic and thyroid function within normal range but with increased lactic dehydrogenase (492 U/L) and significant increase of inflammatory tests (ESR = 140 mm/h and CRP = 252.3 mg/L). He also presented with hypercalcemia (ionic Ca++ 5.44 mg/dl) and polyclonal hypergammaglobulinemia. HIV, B and C hepatitis serologies were negative.

Upon clinical suspicion of complete spinal cord compression syndrome, the patient underwent thoracic and lumbosacral Magnetic Resonance Imaging (MRI), which showed multiple osteolytic lesions diffusely affecting the bone and vertebral bodies, some with cortical rupture and soft tissue component, as well as vertebral fractures compromising T4, T6 and T10 with evidence of compressive myelopathy. Chest, abdomen and pelvis CT scans revealed osteolytic lesions in pelvic bones and a large mass on the left tenth rib with a soft tissue component measuring 9.2 x 6.0 x 7.8 cm and a soft tissue component mass involving the iliac and sacrum bone with evidence of foraminal invasion, measuring 10.9 x 9.0 x 5.1 cm.

Bone biopsy showed undifferentiated malignant proliferation of mononuclear cells with high histological grade and necrosis (H&E - Figure 1A). Cell proliferation presented plasmacytoid/ cuboidal morphological differentiation in a solid and linear discoid arrangement, with some large bi or multinucleated atypical cells, with scarce cytoplasm and minimal inflammatory background. The neoplastic cells were immunohistochemically positive for vimentin, lysozyme, diffuse CD68, CD45, CD43, CD99 and ki67 in 50% of the cells and negative for myeloid, lymphoid B and T-associated markers, cytokeratin, CD15, CD30, CD34, CD56, CD1a, CD138, S-100, TdT, desmina and Melan-A (Figure 1 - B, C and D), allowing the HS diagnosis.

Citation: Lage LAPC, Albuquerque VJ, Moraes RDR, Couto SCF, Culler HF, Rocha V, et al. Primary Histiocytic Sarcoma of Bone with Disseminated Involvement - Initial Presentation Mimicking Multiple Myeloma: The Atypical Face of a Rare Neoplasm. Ann Hematol Oncol. 2019; 6(9): 1270.