Primary histiocytic sarcoma of the central nervous system: a case report with platelet derived growth factor receptor mutation and PD-L1/PD-L2 expression and literature review

Abstract

BackgroundHistiocytic sarcoma (HS) is an aggressive malignant neoplasm. HS in the central nervous system is exceptionally rare and associated with a poor prognosis. This report documents a case of primary HS of the central nervous system with treatment including surgery, radiotherapy, and chemotherapy.Case presentationOur patient was a 47 year old female presenting with progressive ataxia, headaches, imbalance, nausea, vomiting, and diplopia. MRI showed a heterogeneously enhancing lesion approximately 2.9 × 3.0 × 2.3 cm centered upon the cerebellar vermis with mild surrounding vasogenic edema and abnormal enhancement of multiple cranial nerves. The patient underwent surgical debulking, which revealed histiocytic sarcoma with grossly purulent drainage. Staging revealed diffuse leptomeningeal involvement, primarily involving the brain and lower thoracic and lumbar spine. She underwent adjuvant radiotherapy to the brain and lower spine and was started on high dose methotrexate. However, she experienced progressive disease in the cervical and thoracic spine as well as pulmonary involvement. Genomic sequencing of her tumor showed a mutation in the platelet-derived growth factor receptor A (p.V0681) which could be targeted with Dasatinib. However, she did not tolerate Dasatinib and she succumbed to progressive disseminated disease eight months from original diagnosis. Our pathologic evaluation also revealed expression of PD-L1 and PD-L2 by tumor cells raising the potential therapeutic role for immune checkpoint inhibition.ConclusionsThis case provides an example of effective CNS control with resection and moderate doses of radiation therapy. A review of the literature confirms aggressive multidisciplinary treatment is the most effective treatment against this disease. In addition, genomic sequencing may play an important role in determining new therapeutic options. However, CNS histiocytic sarcoma remains an aggressive disease with a propensity for early widespread dissemination and few long term survivors.

Primary histiocytic sarcoma in the brain with renal metastasis causing internal ophthalmoparesis and external ophthalmoplegia in a Maine Coon cat

“…CNS HS in humans is extremely rare, 17,18 and metastatic-associated disease even more so, with only one unpublished report of spontaneous metastatic spread. 19 Disseminated forms of HS with CNS involvement have been described dogs, 20,21 with different associated sites, including the kidneys.…”

Clinicopathological characteristics of histiocytic sarcoma affecting the central nervous system in dogs

“…“Dedicated owner” effects are likely to have affected the definitively treated survival outcomes, but the maximum documented survival time still was <8 months in a dog with a primary intracranial HS treated with surgery and lomustine, and only 8 of 96 dogs had survival times >4 months. Primary CNS HS is an extremely rare tumor in humans and carries a similarly poor prognosis with survival after definitive therapy typically <1 year . Limited data are available to define the incidence of primary versus secondary CNS HS in humans, but most reports involve primary tumors.…”

“…Primary CNS HS is an extremely rare tumor in humans and carries a similarly poor prognosis with survival after definitive therapy typically <1 year. 44,45 Limited data are available to define the incidence of primary versus secondary CNS HS in humans, but most reports involve primary tumors. Interestingly, a marked inflammatory infiltrate also has been described for these primary tumors in humans similar to their counterparts in dogs, [46][47][48][49] suggesting that they may have some common underlying characteristics.…”

Primary Histiocytic Sarcoma Presenting as a Breast Mass: A Case Report

“…In case of an advanced stage tumor, chemotherapy and radiotherapy may be considered, but the number of cases was so small that it was difficult to predict the effect of this treatment on prognosis [615]. For instance, primary histiocytic sarcoma of the central nervous system is known to have a poor prognosis [4], that the tumor of systemic involvement shows a more aggressive clinical course, and that the localized masses show a better prognosis [14]. However, the prognosis is unclear for tumors in uncommon sites such as the one in our present case.…”

“…Only a limited number of histiocytic sarcoma cases have been reported, and its exact etiology is unknown. This tumor mainly occurs at extranodal sites rather than in lymph nodes [1], and according to the cases that have been reported so far, various extranodal sites, such as the skin, soft tissue, gastrointestinal tract, respiratory system, bone marrow, spleen, and central nervous system, can be affected [1234].…”