Durable clinical response to radiotherapy in an unresectable masticator space nodular fasciitis: a case report

Introduction

Background

Nodular fasciitis is a benign, self-limited, myofibroblastic proliferation often misdiagnosed as a malignant neoplasm due to its rapid and infiltrative growth pattern (1). It is also known historically as subcutaneous pseudosarcomatous fibromatosis. It commonly affects adults 20 to 40 years of age with equal sex distribution. Although it may occur in any location, most cases involve the extremities or trunk; only 13–20% occurs in the head and neck region, mostly seen in children and young adults (2). Etiology is still unknown; history of preceding trauma is thought to be a factor and is attributed to increased proliferation of fibroblasts and myxoid matrix, infiltration of inflammatory cells, and neoangiogenesis (2). Diagnosis remains a challenge, especially in resource-limited settings where unavailability of immunohistochemical stains and break-apart fluorescence in situ hybridization (FISH) hinders accurate and definitive diagnosis. Nodular fasciitis, being a diagnostic conundrum, therefore, may be underreported and literature regarding treatment options is limited.

Complete excision remains the standard treatment for nodular fasciitis; these lesions rarely recur and are associated with good outcomes (1,2). Intralesional triamcinolone injection as an alternative treatment for cosmetically sensitive regions has been reported safe and effective as well (3). For unresectable cases of nodular fasciitis and unable to receive other medical treatments, alternative treatments are limited with scarce literature.

Rationale and knowledge gap

After a systematic search, we only found two reports describing outcomes with radiotherapy (RT) for nodular fasciitis in the head and neck (2,4). Both cases required urgent treatment for dyspnea; one was unfit for surgery, and one was refractory to surgical and intralesional steroids. The responses varied, with one case responding to RT while the other did not. The role of RT for nodular fasciitis remains unclear.

Objective

We report a case of an unresectable nodular fasciitis in the head and neck and its clinical outcomes with RT. We present this article in accordance with the CARE reporting checklist (available at https://fomm.amegroups.com/article/view/10.21037/fomm-23-63/rc).

Case presentation

A 67-year-old male presented with ill-fitting dentures due to an enlarging left hard palate mass in January 2022. He was seen by a head and neck surgeon who then performed a biopsy revealing a pathologic diagnosis of a spindle cell neoplasm. Immunohistochemical (IHC) stains were positive for Desmin and smooth muscle actin (SMA) which are markers for myogenic differentiation and smooth muscle or myofibroblastic tumors, respectively, and negative for cytokeratin (CK), CD34, S100, and ß-catenin, which are markers for epithelial tumors, hematopoietic or endothelial cells, Schwann cells or melanocytes, and fibromatosis, respectively; these IHC stains are interpreted as suggestive of nodular fasciitis by the attending pathologist. Break-apart FISH for USP6 fusion which would strengthen the diagnosis is not available locally. Understanding and accepting the implications, the patient opted to forgo sending out the specimen for further testing abroad due to logistic and financial burden. Magnetic resonance imaging (MRI) of the paranasal sinuses and neck showed a left masticator space mass measuring 4.9 cm × 3.5 cm × 5.2 cm that bulges into nasal and nasopharyngeal passages. The naso-, oro-, and hypopharynx, oral tongue, floor of mouth, and the remainder of the oral cavity were normal. No neck lymphadenopathies were noted. The patient was advised surgery with predicted good outcomes as resection is still the standard of care but the patient did not consent to the procedure. He opted for medical management with steroids receiving methylprednisolone 4 mg every 12 hours orally but was discontinued after a week due to impaired blood glucose control. At 6 months from initial diagnosis, the patient complained of severe oral intake impairment due to the obstruction of the oral cavity by the rapidly enlarging mass. A computed tomography (CT) scan was requested showing significant growth of the mass now measuring 6 cm × 4.4 cm × 5.8 cm, partially extending to the left side of the oral cavity, left parapharyngeal space, nasopharynx, and nasal vault, involving the left mandibular ramus, maxilla, greater wing of sphenoid, and left medial and lateral pterygoids. This was then deemed unresectable by the surgeon. With the lack of available treatment options, he was referred for RT.

On initial radiation oncology consultation, seven months after initial diagnosis, a large hard palate mass was seen on physical examination and MRI (Figures 1,2), partially obstructing the oral passages with left cheek swelling (Figures 1A,2A). No trismus was noted. The patient was apprised of the paucity of empirical evidence on the effectiveness of RT for nodular fasciitis, given the rarity of the condition, and the risk for RT-induced secondary malignancy, which he understood and accepted.

Figure 1 Clinical response of nodular fasciitis to IMRT. (A) Initial radiation oncology consultation; (B) 2-month post-RT follow-up; (C) 3-month post-RT follow-up; (D) 4-month post-RT follow-up; (E) 10-month post-RT. IMRT, intensity-modulated radiation therapy; RT, radiotherapy.

Figure 2 Representative T2-weighted MRI axial images. (A) Pre-RT; (B) 2-month post-RT; (C) 4-month post-RT; (D) 10-month post-RT. MRI, magnetic resonance imaging; RT, radiotherapy.

The patient was immobilized using a 5-point head, neck, and shoulders thermoplastic mask and then underwent CT simulation scan with 2.5 mm slice thickness. The gross tumor volume (GTV) was contoured as the gross lesion seen on CT simulation with MRI registration. The clinical target volume (CTV) includes the GTV only. The CTV was expanded to a 5-mm margin for the planning target volume (PTV) to account for the daily set-up errors and positioning uncertainties (Figure 3). Intensity-modulated radiation therapy (IMRT) technique which utilizes varying intensities across subdivisions of beams to optimize dose distribution was used to deliver the prescribed dose of 50 Gy in 200 cGy daily fractions given over 6 weeks while maximally sparing the organs-at-risk (OARs). The RT plan prioritized normal tissue constraints, as shown in the dose volume histogram (DVH), with OARs in yellow and PTV in red (Figure 3).

Figure 3 IMRT plan showing 95% isodose color wash and DVH. PTV, planning target volume; IMRT, intensity-modulated radiation therapy; DVH, dose volume histogram.

The patient tolerated the treatment well with grade 1 mucositis being the only acute toxicity. He was prescribed celecoxib 200 mg once daily as needed which afforded relief. At 2-week post-RT, partial regression of the hard palate mass was noted. At 2-month post-RT, significant further regression was noted, with relief of oral passage obstruction and oral intake impairment (Figure 1B). Follow-up MRI at this time showed slight regression of the size of the mass with post-RT changes (Figure 2B). At 3- and 4-month post-RT, there is near total resolution of the oral cavity component of the mass (Figure 1C,1D) with no radiation mucositis or dermatitis. Repeat MRI done at 4-month post-RT showed significant regression of the left masticator space component of the mass now measuring 4.7 cm × 4.9 cm × 4.5 cm (AP × T × CC) (Figure 2C). Total resolution of the oral cavity component was noted as well. The patient was then again advised surgery for a more definitive treatment. However, the patient still did not consent to the procedure. He instead opted for observation and close monitoring with frequent follow-up visits and repeat imaging. Repeat MRI done 10-month post-RT showed further interval regression of the mass now measuring 4.1 cm × 2.4 cm × 2.8 cm (AP × T × CC) and now appears more diffusely hypointense (Figure 2D). The oral cavity component is no longer seen (Figure 1E). No long-term toxicities such as trismus, chronic mucositis, dermatitis, xerostomia, dysgeusia, nor xerophthalmia were noted at 10-month post-RT. All procedures performed in this study were in accordance with the ethical standards of the University of Santo Tomas Hospital-Research Ethics Committee (USTH-REC) Protocol Reference No. 2023-08-065-TR-AP and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Nodular fasciitis was first described by Konwaler et al. (5) in 1955 as subcutaneous pseudosarcomatous fibromatosis; Mehregan coined the term nodular fasciitis in 1966. It is characterized by its rapid growth, infiltrative pattern, and high mitotic rate hence the historical term pseudosarcoma (1). Pathologic features as listed by Maloney et al. (1) include plump myofibroblastic spindle cells with slightly basophilic cytoplasm and inconspicuous nucleoli, loosely organized into irregular fascicles, lack of hyperchromasia, pleomorphism, atypical mitoses, foci with myxoid, discohesive, feathery appearance, “tissue culture” pattern, irregular or infiltrative border, interspersed extravasated erythrocytes, leukocytes, giant cells, and association with fascia. These lesions stain positive for SMA and negative for S100 and CK, with Desmin usually negative but may occasionally be positive (6). More than 90% demonstrates USP6 rearrangement, with t(17;22)(p13;q13) resulting in USP6-MYH9 fusion gene being the most common (7). FISH break-apart can detect USP6 locus rearrangement regardless of fusion partner and has a high sensitivity of 86–92% and 100% specificity (1,7). There are three subtypes based on relation to fascia: subcutaneous, intramuscular, and fascial; whether these subtypes affect treatment response and prognosis is unknown. The standard treatment for nodular fasciitis is complete excision (1,2,4). Local recurrence after surgical removal is rare and should prompt reevaluation. Intralesional steroid injection is also an alternative treatment. Intralesional triamcinolone was documented to be safe and effective in one case of periorbital nodular fasciitis with complete regression of the tumor (3). For our case, however, due to the bulky mass being unresectable, systemic dose of steroids rather than local was preferred with the aim of size reduction but was eventually discontinued due to poor glucose control and poor response.

There is scarce literature on the radiotherapeutic management of unresectable head and neck nodular fasciitis. Çelik et al. (2) reported use of RT for a case of an 82-year-old female with laryngeal nodular fasciitis presenting with progressive dyspnea unfit for laryngectomy and unresponsive to triamcinolone injection. However, RT was discontinued due to the patient’s worsening status. Another report by Stadlhofer et al. (4) used RT for a case of a 41-year-old female with laryngeal nodular fasciitis presenting with progressive dyspnea and stridor who refused laryngectomy; she instead underwent multiple tumor debulking and triamcinolone injection, but regrowth of laryngeal mass was apparent leading to progressive dyspnea which eventually required tracheostomy. RT was instituted to reduce regrowth tendency, with the subglottic mass receiving 36 Gy in 18 fractions using conformal photon technique. A significant tumor volume reduction was noted allowing sufficient airflow post-RT and definitive tracheostomy closure was done 12 months post-RT. Similar results were seen in our case where RT caused significant volume reduction of the nodular fasciitis affording relief of oral cavity obstruction and addressing the patient’s primary concern on oral intake. This may suggest that RT can be offered as an alternative treatment for unresectable head and neck nodular fasciitis whose mass effect compromises oral or airway function requiring urgent treatment if definitive surgical modality is not an option. Of note is the higher dose received by the patient in our case compared to lower doses used in similar hyperproliferative benign diseases; since the possibility of a low-grade sarcoma, although highly unlikely, is not completely ruled out, we decided to give a standard neoadjuvant dose of 50 Gy in the event that the patient reconsiders surgery after response. The mechanism of RT effects on nodular fasciitis remains to be elucidated. For benign diseases in general, radiation inhibits cell proliferation and suppresses cell differentiation by a combination of different cellular effects that vary between cell lines, with mitotic delay, reduced division probability, and mitosis-related cell death being the commonly described mechanisms (8). This may have implications in hyperproliferative processes such as fibroblast proliferation seen in keloids, wherein tissue stroma effects of radiation impede fibroblast migration and accelerates apoptosis by transforming the lesion into a hypocellular, hypovascular, and hypoxic tissue. Two prospective studies on keloids favored RT over intralesional steroids and cryotherapy (9,10), with RT groups showing lower recurrence. It should be emphasized, however, that while both diseases involve fibroblast proliferation, it is difficult to derive definitive extrapolations between diseases because of inherent pathophysiologic differences, and that mechanisms of radiation effect may not necessarily be similar. Additionally, site-specific toxicities of radiation therapy (e.g., for head and neck: xerostomia, mucositis, dysphagia, myofibrosis, osteoradionecrosis, and secondary neoplasms) must be considered and adequately explained to the patient. The risk of radiation-induced cancer, although varying considerably based on site of treatment, age, field size and dose, should also be discussed with the patient; this is important particularly for the pediatric age group who are at higher risk compared to elderly patients (11). It is important that approach to such patients remains as a multidisciplinary decision, and that the benefits and risks of all possible modalities including RT are thoroughly explained to the patient.

Given the inherent limitations of a case report, in the background of scarce literature of reported cases, we acknowledge the limits of generalizability of the findings. In addition, diagnostic challenges associated with nodular fasciitis, particularly in resource-limited settings, highlight the need for better access for advanced tools which were unavailable locally; this may add an element of uncertainty to the case. Furthermore, the lack of a standardized RT protocol for nodular fasciitis necessitates caution in adopting the regimen used and emphasizes the need for a thorough multidisciplinary approach in such cases. Nonetheless, this study includes a comprehensive documentation of a rare case with complexities limiting the treatment option to primary RT alone, contributing to the limited existing literature on radiotherapeutic management for this condition.

Conclusions

We report a case of a masticator space nodular fasciitis with durable radiologic and symptomatic response to RT without late toxicity. Cases of nodular fasciitis treated with RT are underreported, and to our knowledge, this is the first case to be treated with primary RT in the reported literature. As presented in this article, primary RT can lead to favorable and durable clinical outcomes. It is imperative nevertheless to emphasize the importance of a comprehensive and multidisciplinary approach in managing these cases.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://fomm.amegroups.com/article/view/10.21037/fomm-23-63/rc

Peer Review File: Available at https://fomm.amegroups.com/article/view/10.21037/fomm-23-63/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://fomm.amegroups.com/article/view/10.21037/fomm-23-63/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the University of Santo Tomas Hospital-Research Ethics Committee (USTH-REC) Protocol Reference No. 2023-08-065-TR-AP and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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