Primary leptomeningeal sarcomatosis
Primary leptomeningeal sarcoma (PLS) is an extremely rare neoplasm of the central nervous system, representing 10% of all intracranial meningeal sarcomas. PLS presents either with diffuse leptomeningeal involvement or large discrete lesions, and it usually occurs in children and young adults.(1-6) Diffuse involvement of the meninges is present in approximately 10% of the cases and is classified under the heading of primary leptomeningeal sarcomatosis.(5, 6) PLSs are highly aggressive tumors with a poor outcome with 50% averaging only 1-year of survival after resection. It may therefore be important to diagnose meningeal sarcomas as early as possible.(4) Only a few cases have been reported to date.(1-6) The clinical history is usually short, and deterioration is rapid on account of either the intractable character of the lesion. Radiotherapy was performed to our patient with a 50 Gy by 25 fractions in 5 weeks. However, an MRI 6 months after onset demonstrated diffuse leptomeningeal contrast enhancing tumors over the brain and entire spinal cord, as well as ventriculomegaly of the lateral ventricle and the third ventricle. She died 7 months after the onset of the disease.
The CSF has been abnormal in all cases in which it was examined and it typically shows an elevated protein level, a low glucose content, and variable pleocytosis.(1, 2, 3, 5) Because these changes are nonspecific, cytological studies are necessary and in some cases highly suggestive of PLS.(1)
Due to the presence of diffuse leptomeningeal involvement, the clinical picture may resemble chronic infection, a metastatic tumor, a primary tumor or sarcoidosis. During the follow-up period, there was progressive decline in the cognitive functions of the patient and in addition to the cerebral and cerebellar involvement, signs of spinal cord dysfunction became evident.(2, 3, 5, 6) In most of the cases, the radiological examinations provide non-specific findings. MRI tends to reveal diffuse leptomeningeal thickening (DLT) and contrast enhancement with spinal cord involvement, which are non-specific findings.(2,4,6) Possible misinterpretations include neoplastic and inflammatory meningeal involvement, as seen in meningoencephalitis, leukemia, leptomeningeal melanosis and meningeal metastatic spreading. Nevertheless, isolated leptomeningeal involvement is sometimes present.(4)
One of the most important differential diagnoses is tuberculous meningitis, which often presents with a meningeal thickening and diffuse meningeal contrast enhancement.(2, 3)In contrast to other forms of meningitis, identification of the pathogenic organism can be difficult in for tuberculous meningitis.
The pathological findings detected DLT and multiple intraparenchymal lesions in the biopsy specimens of our case. Tuberculosis, sarcoidosis, syphilis, fungal infections and rheumatoid arthritis, which all could be the cause of a non-neoplastic meningeal thickening or pachymeningitis were excluded on the basis of clinical or laboratory findings.(6) Due to the similar morphological appearance, it can be difficult to distinguish neuroblastoma from meningeal sarcoma.(2) No infiltration suggesting lymphoma or leukemia that can lead to a diffuse meningeal thickening was detected. In PLS, immunohistochemical examinations reveal strong immunopositivity of the tumor cells for vimentin and focal immunopositivity for EMA and S-100.(2, 6) GFAP, actin, desmin, keratin, NSE, and anti-melanoma antigen were negative.(2) The determination of tumor proliferation activity showed a high number of positive tumor cells for PCNA and Ki-67.
The lesion in our case was diagnosed as PLS. The presence of S100 positivity with CD68 negativity and the absence of granuloma formation made the diagnosis of Langerhans cell granulomatosis unlikely which can also lead to similar pathological findings. The vimentin and S100 positivity and the areas showing increased mitotic activity all were consistent with PLS. The parenchymal cystic lesions detected in the biopsy specimens were thought to be the result of expanded perivascular spaces.(1)
In order to avoid misinterpretations and delays of therapy, early open brain biopsy or surgical resection of the lesion is necessary in cases of unclear brain masses, especially of unclear meningeal processes. Due to the low number of cases published so far, the biological behavior and clinical management (e.g. postoperative radiation or chemotherapy) of this tumor entity still awaits further investigation. When a mass lesion exists, radical tumor resection seems to afford the best prognosis(2), whereas the benefits of radiation therapy and chemotherapy are still not clear.
While radiation therapy has been the recommended treatment, the limited survival time of patients with PLS makes its efficacy difficult to assess.(5) In adults, however, these lesions have been documented to occasionally occur following radiation therapy of other brain tumors. In these cases, they typically arise 2-10 years after irradiation.(2)
Contributed by Takashi Mizowaki, Takashi Sasayama, Shuho Semba, Ryohei Sasaki, Kensaku Yasuo, Satoshi Nakamizo, Kazuhiro Tanaka, Katsu Mizukawa, Yoshito Uchihashi, Eiji Kohmura