Endoscopic endonasal approach for resection of sellar leiomyosarcoma metastasis: illustrative case

Abstract

BACKGROUND

Leiomyosarcoma (LMS) is a rare neoplasm that arises from tissues of embryonic mesodermal origin. Primary tissues of origin can include smooth muscle cells of the abdominopelvic viscera, blood vessels, or arrector pili muscles. LMS is known to metastasize to the lungs, with few reported cases of spread to the central nervous system.

OBSERVATIONS

A 66-year-old male with cutaneous LMS of the left forearm with metastases to the lungs and kidney that had been treated with chemoradiation presented with worsening headaches. Magnetic resonance imaging revealed a sellar lesion. An endocrine workup was unremarkable. Imaging over 6 months revealed rapid interval growth. Positron emission tomography demonstrated moderate uptake. Given the rapid growth, the patient was offered an endoscopic endonasal approach for resection. Pathology confirmed LMS.

LESSONS

To the authors’ knowledge, this is the first documented case of LMS metastasis to the sella. Pituitary carcinoma or metastases to the sellar region should be in the differential among patients with sellar region tumors with a rapid growth rate, bony erosion, or findings of lesions in the upper cervical lymph nodes or soft tissue. Tumors that show significant interval growth should raise suspicion for nonadenomatous lesions, and surgical intervention should be considered even in the absence of endocrinological dysfunction or cranial neuropathies.

https://thejns.org/doi/10.3171/CASE2435

Leiomyosarcomas (LMSs) are exceedingly rare neoplasms that arise from tissues of embryonic mesodermal origin, more specifically from smooth muscle cells of the abdominopelvic viscera or blood vessels.^1–3 Generally, a patient’s prognosis worsens as the lesion depth increases; treatment can include Mohs surgery and adjuvant radiation. Follow-up requires annual chest radiographs to monitor for pulmonary metastatic disease.⁴ Cutaneous LMS is characterized histologically by dermal proliferation of elongated spindle-shaped cells with cigar-shaped nuclei and eosinophilic cytoplasm organized in interweaving fascicles.² Of note, several other malignant neoplasms display spindle-shaped cell morphology, making immunohistochemical evaluation instrumental in achieving a definitive diagnosis of LMS.⁵ Superficial LMS accounts for 5%–10% of all soft tissue sarcomas and is stratified into deep subcutaneous and superficial cutaneous variants according to the primary site of origin.^{5, 6} The subcutaneous LMS subtype accounts for the overwhelming majority of all superficial LMSs, while the cutaneous subtype corresponds to 2%–3% of all superficial LMSs.⁶

Primary intracranial LMS typically presents in immunocompromised individuals and is exceptionally rare in immunocompetent patients.^{7, 8} Definitive treatment algorithms in these patients have not yet been established, but prior reports suggest an aggressive multifaceted approach, combining maximal resection with adjuvant chemoradiation, given a lack of targeted therapeutics.⁹ Although there are currently no definitive treatment algorithms for LMS, several novel therapeutic advances are in development and being investigated in phase 2 and 3 trials, including agents targeting DNA repair pathways, receptor tyrosine kinase and intracellular signaling pathways, immunotherapies, and novel combinations of chemotherapies.¹⁰ A greater understanding of tumor biology will facilitate future advances in the treatment of LMS, with the potential to improve current standards of care in this population.

Metastatic LMS most frequently invades the lungs but can disseminate to any region of the body. The prevalence of metastasis in LMS has been reported to be as high as 60% and 5% in patients with subcutaneous LMS and cutaneous LMS, respectively.^11–13 Intracranial metastasis of LMS occurs in less than 1% of cases and presents a unique challenge, as little is known about the ideal clinical management strategies in this population. Intracranial lesions discovered in the context of systemic LMS require judicious evaluation to select the appropriate course of action. In the context of sellar involvement, efforts must be made to distinguish between the various benign neoplasms that typically arise in this region and metastatic disease. In this report, we detail our experience managing a patient with LMS metastasizing to the sella and discuss key factors to consider in the preoperative period to aid in distinguishing between adenomatous and aggressive sellar lesions. To our knowledge, this is the first reported case of LMS sellar metastasis in the English-language literature.

We retrospectively reviewed the case of a single patient who had undergone an endoscopic endonasal approach (EEA) with ultrasound guidance for the resection of a rapidly growing sellar mass. The surgical technique and information related to ultrasound guidance are described, followed by the case report. The case review and reports followed the CARE guidelines.

Illustrative Case

A 66-year-old male had a 12-year history of metastatic cutaneous LMS of the forearm with renal metastasis and pulmonary nodules. The patient had a prior treatment history of partial lung lobe resection, cryoablation, and gemcitabine and docetaxel systemic therapy. His pertinent medical history included a 9-year history of hypothyroidism following a thyroid lobe resection, currently treated with 175 μg levothyroxine. The patient’s initial lesion had appeared 12 years earlier in the form of a 6.0 × 2.5 × 2.5–cm mass on his left forearm. Histopathological analysis revealed a malignant spindle-celled neoplasm with a high mitotic count (24/10 HPF) and Ki-67 > 20%, positive for smooth muscle actin and caldesmon.

The new onset of headaches prompted brain magnetic resonance imaging (MRI), which demonstrated a sellar lesion initially suspicious for an adenoma (Fig. 1A and B). As there were no vision or endocrinological abnormalities, the patient was managed conservatively with interval imaging and hormone reassessment. Six-month follow-up pituitary MRI showed significant growth from approximately 13 × 12 × 11 mm (anterior-posterior [AP], cranial-caudal [CC], latero-lateral [LL]; Fig. 1A and B) to 19 × 20 × 20 mm (AP, CC, LL; Fig. 2) with suprasellar extension, invasion of the left cavernous sinus, and complete encapsulation of the left cavernous carotid (Fig. 2A–C). At this point, the tumor eroded the left posterior clinoid and a portion of the dorsum sellae (Fig. 2E). Positron emission tomography (PET) showed faint ¹⁸F-fluorodeoxyglucose (FDG) uptake in the sella compared to areas of known malignancy in the right femur and left parotid (Fig. 1D, F, and H). These findings failed to exclude metastatic disease or nonfunctional cystic macroadenoma given the lesion’s heterogeneous enhancement pattern (Fig. 2B–D). The patient was neurologically intact on examination. Given this rapid interval growth and lack of definitive diagnosis, together with the unaffected endocrinological function, resection was recommended.

FIG. 1.

Initial axial contrast (A) and coronal noncontrast (B) T1-weighted MRI of an LMS metastasis. White arrows show a mass within the sella abutting the left ICA with mass effect on the pituitary and stalk deviation to the right (B). Preoperative FDG-PET/CT images (C–H) obtained at the 6-month follow-up. Yellow arrows show areas of malignancy including an osseous lesion in the right femur (standardized uptake value [SUV] 4.2, G) and left parotid nodules (SUV 4.1, H). The pituitary mass demonstrated faint FDG uptake (blue arrows, D and F). Panels C and E highlight normal cerebral uptake of FDG; image brightness/contrast settings are constant between panels C and D and E–H.

FIG. 2.

Coronal T2-weighted (A) and contrast T1-weighted (B) MRI, as well as axial (C) and sagittal (D) contrast T1-weighted MRI and CT angiography (E) of a Knosp grade 4 sellar neoplasm at the 6-month follow-up. The mass was heterogeneously enhancing and hypervascular on T1-weighted imaging with complete encapsulation of the left cavernous ICA and showed bony invasion of the posterior sphenoid sinus wall as well as the left posterior clinoid (E). White arrows indicate the tumor.

An EEA to the sella was used to access the tumor.¹⁴ Intraoperative neuronavigation, anatomical landmarks, and ultrasound guidance (BK Medical) were used to remove the bone overlying the left internal carotid artery (ICA). The sellar dura was opened, and the lesion was immediately visualized; it had tawny coloring and a firm, rubbery consistency (Fig. 3B–D, Video 1). A pseudocapsular plane was developed around the tumor, allowing its dissection off the pituitary gland; this was continued through the left cavernous sinus and the medial aspect of the left ICA (Fig. 3E, Video 1). Given the firm nature of the tumor, careful debulking was performed using a pituitary rongeur and suction for countertraction, with frequent identification of the carotid artery using the acoustic micro-Doppler and endonasal ultrasound prior to debulking. Using a semisharp disc dissector, the tumor was carefully dissected from the adventitial layer of the carotid artery. A favorable plane was identified, and given the tumor’s firm consistency, mobilization of the tumor medially toward the empty surgical cavity led to removal of the tumor located lateral to the carotid artery and within the cavernous sinus. There was extension of the tumor through the arachnoid and diaphragm sella, into the suprasellar region. This tumor was carefully dissected away from surrounding glandular and neurovascular structures and removed. After resection, minimal cerebrospinal fluid weeping was noted from the diaphragm where the superior aspect of the tumor had invaded the suprasellar space. A small DuraGen plug (Integra) was placed through the defect, and additional DuraGen was placed to fill the sellar cavity. Given the low-flow leak, with no further seepage on Valsalva maneuver, a middle turbinate flap graft was placed and bolstered over the sellar defect.

FIG. 3.

Chronological time points during the resection. Dura overlying the tumor (A), and an empty resection cavity with the cavernous segment of the left ICA (E). Durotomy and relevant surgical anatomy (B–D). DL = dural leaflet; leICA = left ICA; leON = left optic nerve; OCR = opticocarotid recess; Plan. Sph. = planum sphenoidale; rICA = right ICA; rON = right optic nerve.

VIDEO 1. Clip showing EEA with real-time ultrasound guidance for the resection of sellar LMS metastasis. C4 = C4 segment; CN = cranial nerve; EMG = electromyography; f/u = follow-up; Hx = history; POD = postoperative day; SRS = stereotactic radiosurgery; SSEP = somatosensory evoked potential. Click here to view.

Pathology confirmed high-grade spindle cell malignancy consistent with metastatic LMS. Immunohistochemistry revealed AE1/3- and PAX8-negative cells, which were diffusely positive for calponin with focally positive smooth muscle actin (Fig. 4). Immediate postoperative head computed tomography (CT) imaging showed no acute complications (Fig. 5A–C). MRI at 1 month postoperatively showed gross-total resection of the lesion with preservation of the pituitary gland (Fig. 5D–G). The patient had no hormonal or electrolyte abnormalities in the postoperative setting. The patient was discharged home on postoperative day 2 after an uneventful course. A repeat endocrinological panel 1-week postoperatively revealed stable hormonal function. Two months postoperatively, the patient received linear accelerator–based stereotactic radiation to the sella and to the identified presumed left parotid metastatic lesions, both 30 Gy in 5 fractions. While the patient’s endocrine function is expected to decrease a few months after radiation therapy, as of his latest follow-up with endocrinology 2 weeks postradiation, his pituitary function was normal. The patient will have serial follow-up endocrinology and brain imaging appointments to monitor for pituitary function and recurrence, respectively.

FIG. 4.

Low-power view of the tumor (A, hematoxylin and eosin [H&E] stain) showing a high-grade spindle-cell malignancy with cells arranged in fascicles. In areas, a vaguely storiform pattern is visible. At higher power (B, H&E stain), the nuclear pleomorphism of the neoplasm is readily apparent. Note the trapped remnants of pituitary acini (center). Immunohistochemistry for pan-cytokeratin AE1/3 (CandD) highlights the trapped anterior pituitary cells but not the neoplasm. Immunohistochemistry for calponin (EandF), a smooth muscle marker, is diffusely positive with the tumor cells. Additional smooth muscle markers reveal desmin (Gand H) as largely negative, whereas weak positivity is seen for smooth muscle actin (IandJ).

FIG. 5.

CT imaging (A–C) showing postoperative changes and resection of the sellar LMS metastasis. No postoperative hemorrhages were apparent. Postoperative pituitary MRI at 1 month: coronal (D) and sagittal (E) contrast T1-weighted MRI and axial (F) and coronal (G) T2-weighted MRI. White and orange arrows indicate the right-deviated pituitary stalk and remaining gland, respectively.

Patient Informed Consent

The necessary patient informed consent was obtained in this study.

Discussion

Observations

Metastatic disease is relatively rare in the sellar and suprasellar regions. Primary breast and lung cancers are the first and second most common causes of sellar metastases, respectively.¹⁵ Of note, metastasis to the sella comprises 1% of all tumors that require transsphenoidal surgery; however, autopsy rates for metastatic lesions in a series of 60 patients with breast cancer were as high as 26.6%.^16–18 In addition, intracranial metastasis from LMS is a rare phenomenon, with only 11 cases of nonuterine LMS-derived brain metastases described. To our knowledge, the case presented herein is the first reported case of metastatic LMS to the sella. A gross-total resection was obtained; however, it is important to note that given the use of adjuvant radiation, a subtotal resection would have been sufficient had there been any concerns at surgery. Empiric radiation was considered; however, given the risks to endocrinological function, with a high probability of adenoma, surgery was pursued for diagnosis and treatment.

There has been 1 case of primary intracranial sellar LMS described in the literature.¹⁹ The patient was found to have unilaterally worsening vision in the right eye, with imaging revealing enlargement of the pituitary fossa and erosion of the dorsum sellae, as was shown in our case. The tumor was found to extend into the suprasellar space and sphenoid sinus. Preoperative endocrine assays demonstrated normal levels of pituitary hormones. The patient was treated with craniotomy, in which subtotal resection was achieved, and a course of adjuvant postoperative photon beam radiation therapy (50 Gy). The patient showed no evidence of recurrence at more than 2.5 years of follow-up and no evidence or history of extracranial disease.

Given the rarity of malignant sellar lesions and the resulting literature bias on imaging intervals for surveilling these tumors,^20–24 features that can heighten suspicion for aggressive sellar lesions are discussed herein. Sellar metastases can present with distinct imaging patterns that can assist providers in identification.²⁵ Bone erosion, as opposed to primary enlargement of the sellar space as seen on CT, is suggestive of malignant processes,²⁶ as demonstrated in our case. This has been hypothesized to be the result of direct enzymatic degradation and overactivation of osteoclasts leading to osteolysis.²⁷ FDG-PET imaging can be a useful adjunct and can highlight hypermetabolic metastatic lesions; however, it is important to note that not all metastases are avid on FDG-PET and that benign adenomas can appear hypermetabolic. Furthermore, uptake can be difficult to assess given constitutive brain signal adjacent to these lesions. In our case, PET was equivocal, with the sellar lesion showing faint uptake when compared to areas of known malignancy (Fig. 1C–H). Therefore, the avidity of PET should be evaluated in the context of clinical history, as well as other radiological and laboratory findings.²⁵ Characteristic signs of metastatic disease on MRI include hypointensity relative to adjacent bone marrow on T1-weighted images, particularly in cases of osteolytic lesions, as well as homogeneous enhancement on contrast sequences; however, these findings have variable specificity.²⁶ Of note, initial tumor size and invasiveness at presentation are not always correlated with aggressive potential. In our case, initial imaging revealed no cavernous sinus invasion (Fig. 1A and B).

A clinical history of known primary tumor is key in narrowing the differential diagnosis of sellar metastasis. These lesions can often present with anterior and/or posterior gland dysfunction, including diabetes insipidus (DI), panhypopituarism, hyperprolactinemia (stalk effect), or selective anterior gland dysfunction.^{15, 25} When present, DI can be a manifestation of metastatic disease due to a greater likelihood of posterior pituitary metastasis; this is in contrast to anterior pituitary symptoms, which would be more likely encountered in adenomatous lesions.²⁸ The presence of neurological symptoms, including optic nerve involvement, as well as third, fourth, and sixth nerve palsies are also suggestive of more aggressive lesions, whereby adjacent neurological structures cannot acutely adapt to the pressure applied by a rapidly growing mass.¹⁵

In some cases, symptoms of sellar metastasis can be nonspecific. This was true in our case, where the neurological examination was unremarkable, and the patient reported a history of recurrent headaches. In this case, a high index of suspicion and early brain MRI, prior to the onset of neurological deficits, was critical in evaluating interval growth and increased the likelihood of a favorable surgical outcome. Therefore, in patients with a known history of primary disease, providers should maintain a low threshold for brain imaging and a short 3- to 6-month imaging interval, despite the absence of neurological deficits and the sole presence of nonspecific symptoms.

A significant tumor growth rate and tumor invasiveness are crucial radiographic signs of tumor aggressiveness and can radically influence the treatment course. However, the definition of what constitutes significant growth is unclear, with growth rates influenced by patient- and tumor-specific characteristics.²⁹ A study on the growth rate of 59 untreated nonfunctioning pituitary adenomas (NFPAs) demonstrated an average volumetric growth of 0.33 ± 0.68 cm³/year (34.4% ± 75.5%/year) over a mean period of 46.8 months, with 27% of tumors showing growth.³⁰ Of note, this study showed rates of stable NFPAs similar to those in 4 other cohort studies, whose rates ranged from 60% to 87.5%, all with an average follow-up duration of 46.8 months or more.^31–34

The rarity of aggressive sellar tumors and the associated lack of reported data on their volumetric and linear growth rates make it especially challenging to differentiate them from slow-growing NFPAs based on growth alone. However, according to Response Evaluation Criteria in Solid Tumors guidelines, pituitary carcinomas and metastases should be suspected in patients with a history of systemic disease and with sellar lesions that show a 20% or greater increase in maximum tumor diameter in less than 12 months.^{35, 36} Lastly, based on data from Hwang et al., NFPA becomes less likely with tumors that show volumetric growth rates greater than 1.00 cm³/year.³⁰

Limitations

The rarity of LMS and low incidence of spread to the central nervous system limit the strength of any statements made about treatment decisions and clinical outcomes in this report. The paucity of literature on the growth rate of aggressive sellar lesions allows limited conclusions to be made on differentiating these lesions from more benign ones, and any must be made based on the currently available evidence on nonaggressive sellar tumors. Future studies directed at elucidating these differences will allow more robust conclusions to be made on earlier identification of these rare albeit consequential lesions.

Lessons

Most pathology identified in the sellar region is relatively benign and often slow growing. However, rapid growth can be demonstrated in aggressive or metastatic sellar lesions. In the presence of equivocal findings on imaging and tests, as well as in cases of known malignancy, providers should maintain short-interval imaging follow-ups of 3–6 months after initial imaging diagnosis to surveil for tumor growth. Pituitary adenomas are the favored diagnosis in cases of pituitary incidentalomas, even with a cancer history. However, known metastatic disease and rapid interval growth on surveillance imaging can prompt surgical consideration—even without hormonal dyscrasias or vision changes.

Disclosures

Dr. Prevedello reported consulting for Stryker, Integra, and BK Medical; and royalties from Mizuho, KLS-Martin, and ACE Medical.

Author Contributions

Conception and design: Weber, Carlstrom, Finger, VanKoevering, Wu. Acquisition of data: Weber, Carlstrom. Analysis and interpretation of data: Carlstrom, Finger, VanKoevering, Wu. Drafting the article: Weber, Vignolles-Jeong. Critically revising the article: Weber, Vignolles-Jeong, Finger, VanKoevering, Prevedello, Wu. Reviewed submitted version of manuscript: Weber, Vignolles-Jeong, Finger, Dhaliwal, Kobalka, VanKoevering, Prevedello, Wu. Approved the final version of the manuscript on behalf of all authors: Weber. Administrative/technical/material support: Finger, Dhaliwal, Prevedello. Study supervision: Carlstrom, Prevedello, Wu. Figure composition: Kobalka.

Supplemental Information

Videos

  Video 1. https://vimeo.com/980649842.

Previous Presentations

This report was presented as a poster presentation at the 33rd Annual Meeting of the National American Skull Base Association, Atlanta, GA, February 16–18, 2024.

Correspondence

Matthieu D. Weber: The Ohio State University College of Medicine, Columbus, OH. matthieu.weber@osumc.edu.