A 74‐Year‐Old Female with a Well Circumscribed Parietal Lobe Mass

Clinical History and Imaging

This 74‐year‐old woman was admitted to the ER and subsequently our department due to craniocerebral traumata following involvement in a road accident. Brain computed tomography showed right parieto‐occipital fracture, left parietal and right occipital subdural hematomas, subarachnoid hemorrhage and diffuse cerebral edema. Brain magnetic resonance T2 weighted imaging revealed a left parietal, space‐occupying lesion (Figure 1A) with contrast enhancement in T1 weighted imaging (Figure 1B and C). Brain magnetic resonance angiography offered normal findings. In view of the radiologic findings with the identification of the space‐occupying mass, the patient underwent excisional surgery to confirm the nature of the lesion.

Figure 1.

Gross and Microscopic Pathology

The resected tumor measured 2.8 × 1.5 × 1.2 cm and was fairly well circumscribed, whitish in color and fibro‐elastic in consistency. Light microscopy showed alternating areas of various stromal consistency and variable cellularity, moderate at most (Figure 1D). At high power, the mildly atypical tumor cells were fusiform or spindle‐shaped, arranged in fascicles, vague whorls or swirls (Figure 1E), with pale eosinophilic cytoplasm and with mostly vesicular ovoid or angulated nuclei and distinct nucleoli, showing mild nuclear polymorphism and scarce mitotic figures. There were also isolated multinuclear cells as well as lymphoplasmacytic perivascular infiltrations to be seen. The brain parenchyma was regionally infiltrated by neoplastic tongues, while neuroglial islets were present within the tumor (Figure 1F). Areas with curvilinear vascular network could also be discerned (Figure 1G) as well as scant foci of necrosis and phagocytosis of the adjacent brain tissue. IHC revealed the following immunophenotype: Vimentin+ (Figure 1H), EMA–/+ (Figure 1I), GFAP− [only the above described neuroglial islets were strong positive for this marker; (Figure 1J)], CD34−, S100−, CK−, SMA− and Desmin−. The MIB1/Ki67 labeling index showed a variable immune‐positivity which ranged from 5% in the areas with low cellularity and reached values even up to 30% in the more cellular regions. What is your diagnosis?

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+).