Recurrent intracranial myoepithelioma: clinical course and long-term follow-up. Illustrative case

Abstract

BACKGROUND

Intracranial myoepithelial carcinomas are exceedingly rare tumors associated with a poor prognosis. A review of the literature revealed only 6 published cases, none of which include follow-up longer than 2 years.

OBSERVATIONS

A 26-year-old female presented with headaches, fatigue, and vision changes. She was found to have a rare intracranial myoepithelioma in the parafalcine region. Over the next 7 years, she experienced multiple recurrences managed with surgery and radiation therapy. The patient eventually became pregnant, and a new lesion was identified in her first trimester. Following close observation and a cesarean section, the rapidly growing lesion wasresected, and consistent with prior myoepithelioma.

LESSONS

The authors present the seventh case of primary, intracranial malignant myoepithelioma and the only such case with follow-up longer than 2.5 years. With aggressive management, patients navigating intracranial myoepithelial carcinoma can experience robust survival with conserved quality of life.

https://thejns.org/doi/10.3171/CASE25136

Malignant myoepithelioma, or myoepithelial carcinoma, is an exceedingly rare lesion of myoepithelial cells. Myoepithelial tumors occur most commonly as benign myoepithelioma in the salivary glands, accounting for < 2% of all salivary gland tumors.¹,² Malignant transformation has been observed from pleomorphic adenoma, benign myoepithelioma, or de novo.³,⁴ Malignant myoepithelioma carcinomas confer a poor prognosis, with two-thirds of patients experiencing either recurrent disease or distant metastases.⁵,⁶ Further complicating these cases, myoepitheliomas are extremely heterogeneous histologically, with variable morphology and expressivity for myoepithelial markers on immunohistochemical analysis.⁵ Primary lesions of this pathology rarely arise intracranially, with a review of the literature yielding just 12 published cases, only 6 of which reported malignant processes (Table 1). The maximum follow-up period in these cases was 2.5 years, demonstrating a paucity of information regarding long-term outcomes in patients with these rare tumors.

TABLE 1.

All currently published cases of intracranial myoepithelial carcinoma and their key characteristics

Authors & Year	Age, yrs	Sex	Presenting Symptoms	Tumor Location	Positive IHC	Treatment	Follow-Up
Nieder et al., 200512	34	F	Bitemporal hemianopsia	Sella	NA	Resection, chemo, & radiation	20 mos
Edrogan et al., 200714	46	F	Intradural hemorrhage	Lt frontal dura	S100, keratin, SMA, calponin, GFAP	Resection	4 mos
Hong et al., 20131	48	F	Diplopia & blepharoptosis	Lt cavernous sinus	S100, SMA, GFAP, vimentin	Resection	2 mos
Choy & Pytel, 201613	10	M	Headaches, emesis, & diplopia	Rt cerebral hemisphere	S100, desmin, EMA, GFAP, cytokeratin CAM5.2, cytokeratin AE1/AE3, p63, calponin, GLUT1, CD34, vimentin	Resection	2.5 yrs
Gupta et al., 201610	2	F	Dysmetria & ataxia	Lt parieto-occipital	S100, SMA, cytokeratin, CAM5.2, EMA	Resection & chemo	9 mos
Ballari, 202211	28	M	Headache	Lt temporoparietal	S100, cytokeratin, GFAP, calponin, p63, SATB2	Radiation	2 mos
Present case	26	F	Headache, fatigue, & vision changes	Frontal parafalcine region	S100, calponin, GFAP	Resection (×3), radiation (×2)	7 yrs

Chemo = chemotherapy; IHC = immunohistochemistry.

Illustrative Case

A 26-year-old, right-handed woman with no significant medical history presented to an outside hospital with severe headaches, fatigue, and blurry vision. She was found to have a large cystic lesion in the right frontal lobe, which was subsequently resected (Fig. 1). Pathology was suggestive of a benign myoepithelioma. Given a lack of malignant histopathological features, she was observed over the following year. Subsequent MRI performed 1 year later revealed an enhancing nodular lesion along the falx occluding the superior sagittal sinus that was suspicious for recurrence. Care was transferred to our institution, where the recurrence was treated with stereotactic radiosurgery (SRS; Fig. 2). She subsequently developed chronic headaches, which were managed with Botox injections, and neuroimaging findings remained stable for 2 years until the appearance of two small recurrences in the frontal parafalcine region.

FIG. 1.

Axial and sagittal preoperative (A) and postoperative (B) T1-weighted MR images with contrast showing the patient’s initial presentation of a cystic right frontal lobe lesion.

FIG. 2.

Axial and sagittal pre-SRS (A) and post-SRS (B) T1-weighted MR images with contrast showing the patient’s initial recurrence of their myoepithelioma.

Both recurrences continued to grow, and the patient eventually became symptomatic with mild left pronator drift, decreased balance, and substantial weight loss. The larger, 4-cm symptomatic lesion was resected via an uncomplicated bifrontal craniotomy. Histopathological assessment remained consistent with the prior myoepithelioma, although an increased mitotic rate and focal necrosis were newly suggestive of malignancy, prompting additional SRS targeting a small area of residual. Given prior case reports demonstrating efficacy in other myoepithelial carcinomas, a course of pazopanib, a tyrosine kinase inhibitor, was initiated.⁷ She then underwent 3 years of observation without recurrence on imaging. During this time, the patient became pregnant, and a surveillance MRI study was obtained early in her first trimester without contrast. Imaging revealed a new 5 × 8–mm parasagittal lesion located along the anterior left frontal lobe, favoring a meningioma. Repeat imaging 4 months later revealed that the lesion had nearly doubled in size to 1.3 × 1.0 cm (Fig. 3). At that time, the extra-axial lesion appeared heterogeneous, with several apparent calcifications or mineralizations, further aligning with a likely meningioma. Mild regional mass effect was noted without vasogenic edema. Although consistent with a radiation-induced meningioma, primary glial neoplasm and metastases could not be ruled out. Growth of this presumed meningioma was attributed to pregnancy-related increases in estrogen and progesterone levels.⁸,⁹ With only mild headache symptoms, the patient underwent an uncomplicated cesarean section.

FIG. 3.

Axial and coronal preoperative (A) and postoperative (B) T1-weighted MR images with contrast of the patient’s recurrent left frontal parasagittal lesion.

One month postpartum, the patient’s headaches progressed, and repeat MRI revealed further growth of the presumed meningioma to 4.5 × 4.5 × 4.5 cm with peripheral enhancement, nodularity, and necrosis (Fig. 4). A new dural-based lesion overlying the right frontal opercular area measuring 6.3 mm was also seen. Given her medical history, the rapid mass growth, central necrosis, and newly identified lesion, there was increased concern for metastases of her prior myoepithelioma. She underwent an uncomplicated left frontal craniotomy. Gross-total resection was achieved, and pathology revealed that the lesion was largely consistent with her prior specimens aside from a Ki-67 proliferation index increase to > 10% from only patchy elevations in the realm of 5%. Unlike her prior tumors, small foci of brain infiltration were noted. As before, there were primarily epithelioid cells within myxoid stroma, and immunohistochemical analysis revealed positivity for calponin, S100, and GFAP. There was slight positivity noted for cytokeratin 7 and progesterone receptors, although epithelial membrane antigen (EMA), p40, and p60 were all negative.

FIG. 4.

Axial and sagittal T1-weighted MR images with contrast of the patient’s dominant lesion and new right opercular lesion 1 month postpartum before (A) and after (B) resection.

Given the multifocal recurrence, a nuclear PET study was obtained and did not reveal evidence of any extracranial disease or other metastatic foci. The patient tolerated the procedure well. After a multidisciplinary discussion, the patient elected to undergo concurrent fractionated radiotherapy beginning 3 weeks after surgery, along with temozolomide. She will receive 60 Gy in 30 fractions to the operative bed, as well as the newly identified subcentimeter contralateral lesion.

Informed Consent

The necessary informed consent was obtained in this study.

Discussion

Observations

Summary of Locations

Including the case we have described, prior cases of intracranial myoepitheliomas have presented with an age range from 2 to 48 years (mean age 27.7 years) at the time of diagnosis.¹⁰,¹¹ Cases reported have been of varying location, sizes, and symptomatology (Table 1). Often, myoepitheliomas occur in the sellar region where they are suspected to arise from the remnants of Rathke’s pouch. These lesions are typically benign, however, and the only malignant sellar case reported by Nieder et al. resulted in the patient’s death shortly after diagnosis.¹²,¹³ Among the malignant cases of myoepithelioma, it seems that these lesions have some predilection for the parafalcine region as described here and by Edrogan et al. and Choy and Pytel.¹³,¹⁴

Histology and Pathological Review

Immunohistochemical analyses in prior case reports revealed similarly variable positivity for myoepithelial markers including smooth muscle actin (SMA), calponin, p63 and S100. The immunohistochemical findings in our patient share the inconsistent positivity for myoepithelial markers reported in prior cases, with positive staining for only GFAP, S100, and GFAP while EMA, p40, and p60 were all negative (Table 1). Of those reported, S100 appears to be the most reliable, with positive staining in every reported carcinomatous case to date.

Chemotherapy and Radiation Therapy Treatments

The ideal treatment paradigm for intracranial myoepithelial carcinoma has yet to be established; however, maximally safe resection with adjuvant chemoradiation has been best described. However, there are reports of lesion resistance to adjuvant therapies. Nieder et al. presented the case of a patient who, following incomplete resection, did not respond to either radiation therapy or chemotherapy with ifosfamide.¹² Certainly, in the case we have presented, it is difficult to discern if the delay in resection due to pregnancy portends a risk of progression-free or overall survival.

Despite the rarity of these lesions, this is not the first mention of intracranial myoepithelial carcinoma appearing consistent with meningioma radiographically.¹³ Choy and Pytel reported 2 myoepithelial lesions, one of which was malignant, that appeared extra-axial and were initially suspected to be meningiomas. The similarities between intracranial myoepithelioma and meningioma extend beyond radiographic features, with shared EMA and GLUT1 positivity on immunohistochemical analysis. Of note, our patient’s most recent recurrence also exhibited calcifications thought to favor meningioma.¹⁵

Despite commonly arising in young people, no published cases exist describing longitudinal outcomes beyond 2.5 years. Despite the short duration of published follow-up, half of all described patients had already died of their disease by the time of reporting.¹,¹¹,¹²

Lessons

This case highlights malignant intracranial myoepithelioma as a lesion that can present similarly to a meningioma radiographically. Contrary to prior case reports, our patient’s clinical course demonstrates the potential for robust survival with conserved quality of life among patients with this rare malignancy.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: all authors. Acquisition of data: Wierzbicki, Mahtabfar, Judy. Analysis and interpretation of data: all authors. Drafting the article: all authors. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Wierzbicki. Administrative/technical/material support: Wierzbicki, Shelley. Study supervision: Judy.

Correspondence

Matthew Wierzbicki: Thomas Jefferson University, Philadelphia, PA. matthew.wierzbicki@students.jefferson.edu.