Histiocytic sarcoma, also formerly known as “true histiocytic lymphoma”, is rare because of its prevalence rate less than 1% of all non-Hodgkin’s lymphomas . The differential diagnosis of HS involves various lymphomas, histiocytic and dendritic cell neoplasms, melanomas, metastatic carcinoma and pleomorphic sarcomas , which is confronted with challenges of misdiagnosis and requires proficient recognition of clinic features, the atypical-morphology of tumor cell, the expression of histiocyte-associated makers.
Microscopically, HS is characterized by large and pleomorphic cells with ‘‘Pac-Man’’-like nuclei and abundant vacuolated cytoplasm . Commonly, a predominant noncohesive proliferation diffused among HS neoplastic cells, no matter in solid nodules with reactive eosinophilic infiltration stroma  or in bone marrow with abundant phagocytes . Moreover, although the association of HS with other lymphocytic leukemia/lymphomas had been frequently reported in recent years, most of which still presented as the noncohesive or single diffuse proliferation cells in biopsy [9–11]. The atypical cohesive growth pattern of large neoplastic cells only appeared in several cases of B-cell lymphomas of plasma blastic lymphoma (PBL) [12, 13], T-cell lymphomas of anaplastic large cell lymphoma (ALCL) [14, 15], other metastatic carcinoma to bone marrow  and one case of classic Hodgkin lymphoma (CHL) . Interestingly, in this case, a rare sight that neoplastic cell in tightness cohesive clusters with symplasm morphological was distinctly observed on this bone marrow smear, even accompanying with the hemophagocytosis and EBV infection. Thus the mimic cohesive morphology of large neoplastic cells deserves additional attention in terms of differential diagnosis for this case.
The immunohistochemistry (IHC) helps to differentiate HS from other large neoplastic cells lymphomas of B cell type or T cell type. WHO classified PBL as an uncommon mature B-cell lymphoma, occurring most frequently in HIV-positive patients, but exceptions do exist, which was characterized by positive expression of the following postgerminal centre B cell associated and plasma cell associated markers: multiple melanoma oncogene (MUM1) epithelial membrane antigen (EMA) and CD138 . The ALCL is defined as a CD30 + peripheral T-cell neoplasm that is not reproducibly distinguishable on morphological grounds from ALCL-ALK+, but lacks the ALK protein and exists the case of ALCL-ALK- [18, 19]. This HS case is strictly profiled by the crucial marker of CD163, CD68 and CD4 [5, 20], differentiated with typical absence of CHL maker (CD15), myeloid maker (MPO), T cell of ALCL (CD30, ALK) and B cell (CD20, CD138, PAX-5).
Additionally, most studies have demonstrated that BRAF V600E mutations occur in nearly two-thirds of HS, while the tumor-suppressor gene CDKN2A was the frequently altered gene (46%) [21, 22]. A targeted next-generation sequencing (NGS) study recently demonstrated recurrent mutations activating the 57% mitogen-activated protein kinase (MAPK) pathway (MAP2K1, KRAS, NRAS, BRAF, PTPN11, NF1, CBL) and the 21% phosphoinositide 3-kinase (PI3K) pathway (PTEN, MTOR, PIK3R1, PIK3CA) in HS cases, respectively. Unfortunately, the death of our patient in this case terminated the gene-related determination. Anyway, these hadoop findings of gene mutation or arrangement should contribute to the diagnosis and treatment of HS.