Multifocal histiocytic sarcoma of the CNS (primary or metastatic?)
POST MORTEM FINDINGS
The formalin fixed brain weighed 1490g. Coronal sections showed scattered grayish tumors up to 2cm in diameter, located in the body of both lateral ventricles attached to the ependymal surface. Smaller tumors were present in the fourth ventricle, infiltrating the cerebellum and medulla (Figures 3A and 3B, respectively). The aqueduct and fourth ventricle were filled with blood due to secondary hemorrhages in the brainstem. The spinal cord was macroscopically unremarkable but, on microscopic examination, the spinal roots were infiltrated by tumor cells, which focally entered the spinal cord parenchyma as well as subarachnoid space, which was also infiltrated by tumors cells intracranially. The feature of erythrophagocytosis by tumor cells was frequently evident (Figures 3C and 4A). The right oculomotor nerve was thicker than the left one due to tumor cell infiltration (Figure 3D). Severe tumor cell infiltration was present in the reminder of the intracranial part of the left trigeminal nerve, as well. Extra axial spread of the tumor cells was evident only in the liver, with disseminated tumor cells creating only two macroscopically visible foci, and pituitary gland (Figures 4A and 4B, respectively). All tumors described showed the same microscopic features as those in the biopsy specimen.
First described by Mathe et al in 1970, histiocytic sarcoma (HS) is a rare neoplasm that usually arises in the lymph nodes, skin and intestinal tract (5). HS is usually a disease of adults, with a peak incidence in the fifth decade (4). According to the World Health Organization, HS is defined as a neoplastic proliferation of cells, with morphological and immunophenotypic characteristics of mature tissue histiocytes (8). A diagnosis of HS requires verification of the histiocytic lineage and exclusion of other hematopoietic and non-hematopoietic malignancies. Immunohistochemistry should include histiocytic markers (CD68, lysozyme, CD11c, CD14, and CD163, the last named being regarded as a specific HS marker), which confirm the diagnosis, as well as markers that exclude possible differential diagnoses of anaplastic large cell lymphoma, diffuse large cell B-cell lymphoma, peripheral T cell lymphoma, Langerhans cell histiocytosis, carcinoma, melanoma and glial tumors.
Primary HS of the brain is extremely rare, with only 16 cases reported in the literature, of which eleven presented as a single lesion and five with multifocal lesions (1-4,6,7,9,10). The age of presentation in these cases ranged from 20 months to 69 years, without a gender predominance. The clinical symptoms were non-specific (weakness, dizziness, headache, vomiting) and also depended on the localization of the tumor (9). Of the 6 reported cases with multifocal lesions (including the current case), there were 4 females, ranging in age from 37 to 55 years and 2 males of age 11 and 44 years, with a short survival time of 3 weeks to 8 months, in spite of aggressive treatment (1,2,4,9). Most cases of HS were treated with combined surgery, chemotherapy and radiation therapy. All the cases had an aggressive course, with a survival time up to 10 months, except a case with primary leptomeningeal HS with disease-free survival longer than 3 years following treatment with surgery, radiotherapy and chemotherapy (6).
There is a little data about the metastatic potential of primary CNS HS. Our case is the first described case of primary CNS HS with spontaneous extra axial metastasis to the liver and pituitary gland. In 2003, Sun et al. described a case of a 13 year old boy with focal left occipital HS who underwent resection of the lesion and placement of a ventriculoperitoneal shunt (7). The patient died 3 months after surgery and a superficial lesion on the rectal serosa was found at autopsy, which had probably been seeded from the ventriculoperitoneal shunt (according to the hypothesis of the authors). Autopsy also showed extensive meningeal and ventricular involvement by HS and focal brain infiltration. Our case is the second reported case of primary CNS HS with autopsy that revealed multifocal intraventricular HS with extensive infiltration of the subarachnoid space, right oculomotorius and trigeminus nerves, spinal nerve roots, in particular the roots of the cauda equina and brain parenchyma of cerebrum, cerebellum and medulla at the sites of the tumor ependymal attachments.
In conclusion, primary CNS HS is a very rare neoplasm and difficult to diagnose without biopsy and immunohistochemistry. The presence of large, polymorphic histiocytes with polymorphic nuclei and occasional multinucleated cells should raise suspicion of HS but a wide panel of immunostainings is necessary to achieve a correct diagnosis. HS expresses one or more histiocytic markers and does not express markers of other cell lineages. The disease is extremely aggressive with a poor prognosis. There is no agreement on the most appropriate treatment because the disease is rare and the number of reported cases is limited.
We are grateful to Dr. Christopher DM Fletcher from Brigham and Women's Hospital in Boston for performing CD163 and PU1, and confirming our diagnosis. Thanks to Mr. Miha Juvan for his valuable technical assistance.
Contributed by Danijela Oštrić, MD; Marija Todosijević, MD; Anja Jeričević, MD; Saša Šega Jazbec MD, PhD; Mara Popović, MD, PhD