74 Year‐Old Woman with Progressive Weakness

Clinical History

A 74‐year‐old woman suffered from progressive weakness, paresis of the right hemisphere and occasional headache during the last three months. The patient denied having had nausea, vomiting, fever or weight loss. Nuclear magnetic resonance showed round lobular lesions involving the frontal lobe and corpus callosum, protruding into the lateral ventricle. Lesions were enhanced with the contrast medium exhibiting a ring‐like appearance (Fig. 1a, 1b, 1c). A stereotactic brain biopsy was performed using VarioGuide system.

Figure 1.

Microscopic Pathology

Microscopically, the lesion infiltrated the brain and was composed of large, atypical cells with hyper‐chromatic nuclei and abundant cytoplasm (Fig. 1d). Mitoses were observed as well as focal necrosis without formation of secondary structures; endothelial hyperplasia and vascular proliferation forming glomeruli were absent. Immunohistochemical staining showed negativity for GFAP, S‐100, CD1a, CD20, CD3, CD8, CD34, CD117, MPO and CD15. Cells were positive for LCA (CD45) (Fig. 1e), CD163 (Fig. 1f), CD4 and CD68 (Fig. 1g). Proliferation index measured by Ki67 expression was 60% (Fig. 1h).

Diagnosis

Histiocytic sarcoma.

Discussion

Histiocytic sarcoma is a rare malignant neoplasm of the lympho‐hematopoietic system. Lymphadenopathy can be a clinical presentation but the majority of cases present with 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. 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 within the brain as 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. Hemophagocytosis 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). 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.