Final Diagnosis -- Intracranial Low-grade Fibromyxoid Sarcoma (LGFMS)

FINAL DIAGNOSIS

Intracranial low-grade fibromyxoid sarcoma (LGFMS).

DISCUSSION

Low-grade fibromyxoid sarcoma (LGFMS) is among the rarest human neoplasms, a mesenchymal/fibroblastic, deceptively benign histologically, malignant tumor with a paradoxical potential for aggressive clinical behavior, recurrence and metastasis, with approximately 350 reported cases [2]. It may affect patients of any age, arises in the extremities or trunk, but may occur at unusual locations, including the brain. Only 6 cases of primary intracranial LGFMS have been reported in the literature, of which one with molecular/cytogenetic data [1] and one pediatric case [4]. The first case described in the series by Paulus et al. showed moderately dense spindle cells in a myxoid matrix, with rare mitoses and no necrosis, pleomorphism or storiform texture [3]. Histology was similar in our case, consistent with the classical subtype, as there were no giant collagen rosettes to be seen. Arcades of small blood vessels, a characteristic feature of this neoplasm, were however present, as well as alteration of fibrous and myxoid zones, fascicular and whorling growth patterns and bland cytology.

The neoplastic cells of LGFMS almost consistently present a FUS-CREB3L2 gene fusion and an immunohistochemically detectable MUC4 overexpression [1], phenotypes which unfortunately could not be investigated at our institutes. Our nonspecific IHC findings were consistent with the ones described in IHC studies of LGFMS, namely a strong positivity for the nonspecific marker vimentin and a focal positivity for EMA. The rarely reported focal expression of SMA was absent here.

There is a wide differential diagnostic spectrum for primary intracranial sarcomas. The cerebral metastasis of an extracranial sarcoma cannot be histologically distinguished, thus requiring clinical examination and follow-up, which were negative in our case. Also, intracranial extension from the skull or parameningeal sites must be considered. Regarding histopathology, sclerosing epithelioid fibrosarcoma, a seemingly related tumor to LGFMS, was excluded due to the absence of its typical histology (prominent hyalinized, sclerotic collagen matrix containing epithelioid cells arranged in cords and nests). The homogenous myxoid stroma and high nuclear polymorphism seen in myxofibrosarcoma were also absent, as were the storiform pattern, cellular polymorphism, abundant necrosis and pleomorphic/neoplastic glial cells within the neuroglial islands observed in malignant fibrous histiocytoma or gliosarcoma. Fibromatosis lesions lack the loose appearance and myxoid background, but offer nuclear β-catenin expression. Sarcomatous or chordoid/myxomatous meningioma may be excluded by IHC (strongly positive for EMA and CK with a high Ki67 index), as is the case with low-grade astrocytoma (GFAP+), solitary fibrous tumor (CD34+) and schwannoma (S100+).

REFERENCES

1. Chen N, Gong J, Nie L, Chen X, Xu M, Chen M et al (2015) Primary intracranial low-grade fibromyxoid sarcoma with FUS gene rearrangement. Neuropathology 35(4):348-353.
2. Folpe AL, Hornick JL, Mertens F (2013) Low-grade fibromyxoid sarcoma. In: WHO Classification of Tumours of Soft Tissue and Bone, Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (eds.), Chapter 3, pp. 95-96, IARC: Lyon.
3. Paulus W, Slowik F, Jellinger K (1991) Primary intracranial sarcomas: histopathological features of 19 cases. Histopathology 18(5):395-402.
4. White IK, Scherer AG, Baumanis MM, Abdulkader M, Fulkerson DH (2015) Rapidly enlarging low-grade fibromyxoid sarcoma with intracranial extension in a 5-year-old girl: case report. J Neurosurg Pediatr 16(4):372-376.

Contributed by Alexandros Iliadis, Elsa Pazarli, Charalampos-Chrysovalantis Chytoudis-Peroudis, Stella Chondromatidou, Ioannis Tsitouridis, Ioannis Efstratiou, Dimitrios Kanakis