47‐YEAR‐OLD MAN WITH FRONTAL LOBE TUMOR

CLINICAL HISTORY

A 47 year‐old man presented with left extremity weakness for 1 year, which had worsened significantly over the past 40 days. 23 years ago he suffered head trauma with loss of consciousness for 30 minutes and was diagnosed with a concussion. Two weeks later he had his first generalized seizure, and continued to have about one seizure per week. His seizures were not well‐controlled on phenytoin. Fifteen years ago, the patient underwent brain CT scan, revealing right frontal encephalomalacia (Figure 1c). Epilepsy surgery was performed and silver clips were deployed for hemostasis. Following the surgery and change of medications to carbamazepine he continued to suffer seizures about one or twice a month. At this current presentation for left extremity weakness, the neurological examination discovered decreased muscle strength of the left side. CT scan revealed a huge hypodense lesion in the right frontal lobe with remarkable mass effect (Figure 1a), but without distinct contrast‐enhancement (Figure 1b). Hyperdense foci could be seen within the mass, which were ascertained to be the silver clips used in his surgery. MRI scan could not be performed due to these clips. A right frontal craniotomy was performed and a large tumor was removed and submitted for pathology.

Figure 1.

PATHOLOGY

Grossly, the tumor was about 8cm in diameter, hard in texture, surrounded by gliosis and partial infiltration into the cerebral cortex and invasion of the overlying bone flap. Upon sectioning, the silver clips were found within the compact tumor parenchyma, surrounded by a halo of dark‐stained tissue (0.5–1 cm in diameter). Histologically, the tumor was composed of spindle‐shaped cells arranged in fascicles with discernible collagenous matrix in between (2, 3); The fusiform and tapered nuclei were moderately hyperchromatic and exhibited pleomorphism; Mitotic activity was common but atypical mitoses were rarely seen; There were occasionally bizarre and multi‐nucleated tumor cells; The tumor invaded the brain with an ill‐defined border, and reactive gliosis at the edges. The tumor cells revealed a strong positive reaction for a‐SMA (Figure 4), but negative for vimentin, pan‐cytokeratin, EMA (Epithelial Membrane Antigen) and CD34. Ki‐67 labeling index was <30%. Ultrastructurally, tumor cells contained elliptical or irregular nuclei with distinct nucleoli. There were large amounts of dilated rough endoplasmic reticulum (rER) and thin myofilaments associated with local dense bodies in the cytoplasm (Figure 5). What is the diagnosis?

Figure 2.

Figure 3.

Figure 4.

Figure 5.

DIAGNOSIS

Low‐grade myofibroblastic sarcoma (LGM).

DISCUSSION

LGM is a recently defined malignant mesenchymal/soft‐tissue tumor that shows myofibroblastic differentiation (7). The diagnosis of myofibroblastic tumor is difficult due to their rarity and the uncertainties in identifying the myofibroblast (2). The attributes of a myofibroblast place it midway between a smooth muscle cell and a fibroblast with defining ultrastructural markers of both cell types, i.e., the myofilaments and fibronectin fibrils 1, 3. Myofibroblasts are not a constituent of normal untraumatized tissues but rather predominate under conditions of trauma (wound‐healing) or abnormality (inflammatory and reactive conditions) (2). Myofibroblastic lesions fall into two categories: benign tumors or tumor‐like lesions of myofibroblasts, and malignant myofibroblastic sarcomas including LGM 2, 3.

LGM is a rarely encountered pathology and less than 100 cases have been described (2). It occurs most commonly in the head and neck region, including the oral cavity, pharynx and parapharyngeal regions, proximal extremities and trunk, with occasional cases in the abdomen or pelvis (2). Notably, few intracranial LGMs have ever been documented in the literature, with only one report early in 1988 (5). The microscopic examination and ultrastructural findings described in the case were quite similar to ours, but LGM was not a diagnostic entity at that time.

The relationship of the previous cerebral trauma and surgery (as well as the sliver clips) to the LGM in this case is speculative, but intriguing since myofibroblastic lesions are associated with reactive and reparative conditions. The question of the cells of origin of this tumor is also interesting. Myofibroblasts have long been thought to derive from local resident mesenchymal cells, particularly fibroblasts, and perhaps less commonly smooth muscle cells, pericytes and/or endothelial cells. However, more recently, recruitment from bone‐marrow‐derived circulating fibrocytes and epithelial‐to‐mesenchymal transformation have also been proposed as mechanisms explaining the cellular origin of myofibroblasts (2). In this case, the affected vessels bearing the silver clips and bone‐marrow‐derived cells migrating to the inflammatory field could be the potential origin of tumor transformation.

It is tempting to speculate that the silver clips in the case had a causative role in the tumorigenesis. However, silver as a carcinogen is not well documented in the literature. The silver clip developed by Cushing in early 20th century has greatly facilitated intraoperative blood control in the early evolution of neurological surgery (8). Nowadays, it's still occasionally used for controlling bleeding from large vessels that otherwise can not be safely coagulated. Subcutaneous implantation of silver foil has been reported to induce formation of fibrosarcomas (6), whereas intramuscular injection of silver powders failed to prove the carcinogenesis (4). The carcinogenic activity may stem from the interaction with the sulfur or amino radicals of proteins, or alternatively the local toxic effects of silver (6). Although silver clips have not been documented in other myofibroblastic tumors, this case illustrates that such associations should be sought for.

ABSTRACT

A 47 year‐old man, who previously underwent epilepsy surgery in which silver clips had been used for hemostasis, presented with left extremity weakness. Investigation revealed a mass lesion of right frontal lobe near the place of previous surgery and where the silver clips resided. Intra‐operative findings revealed a huge cerebral tumor with poor blood supply and circumscribed by adjacent gliosis, with the silver clips located within the tumor parenchyma. Histologically, the tumor was composed of spindle‐shaped cells with fusiform and tapered nuclei. The cells were positive for a‐SMA, but negative for vimentin, pancytokeratin, EMA and CD34. Ultrastructurally, tumor cells had abundant dilated rER and thin myofilaments with local dense bodies, confirming the histological diagnosis of Low‐grade Myofibroblastic Sarcoma (LGM). LGM is a rare tumor with cerebral involvement being exceptionally unusual. Only one similar case has ever been described in the English‐language literature. That our case was related to previously placed silver clips in epilepsy surgery further adds to the novelty.