Isolated Horner Syndrome as the Sole Presentation of Pediatric Parapharyngeal Rhabdomyosarcoma

Abstract

Isolated Horner syndrome (HS) in young children warrants thorough investigation for occult malignancy, despite its rarity as a presenting sign. This report details a unique case of a 30 month-old male presenting with sudden-onset, isolated left HS as the sole manifestation of rhabdomyosarcoma (RMS) in parapharyngeal space. Contrast-enhanced magnetic resonance imaging (MRI) revealed a 2.5 × 3.5 × 5 cm lesion within the left poststyloid parapharyngeal space, displacing the carotid artery anteriorly, and the internal jugular vein posteriorly. Gross total resection via a transcervical approach was performed; intraoperatively, the tumor involved the cervical sympathetic trunk, necessitating its sacrifice, resulting in persistent postoperative HS. Histopathological and immunohistochemical analysis (positive CK, PLAP, CD99) confirmed a diagnosis of embryonal RMS. The child received adjuvant chemoradiotherapy. One-year follow-up with positron emission tomography - computed tomography (PET-CT) showed no evidence of recurrence. This case underscores several critical points: (1) Isolated HS in young children necessitates urgent neuroimaging to exclude malignancy, even in the absence of palpable masses or neurological deficits; (2) The parapharyngeal space, though an exceptionally rare primary site for RMS (constituting a minor subset of head and neck cases), carries significant implications due to its proximity to the sympathetic chain, readily causing HS via mass effect; (3) MRI is pivotal for diagnosis and surgical planning in this anatomically complex region; (4) Multimodal therapy is essential for local control in embryonal RMS; (5) Sacrifice of the sympathetic trunk during resection likely leads to permanent HS, a factor for preoperative counseling. Vigilant long-term follow-up remains crucial.

Introduction

Rhabdomyosarcoma (RMS) represents the most common soft tissue sarcoma in the pediatric population, accounting for ~4% to 7% of childhood malignancies, with 35% to 40% arising in the head and neck region. ¹ While frequently involving sites such as the orbit, nasopharynx, and paranasal sinuses, primary RMS originating within the parapharyngeal space is exceptionally rare, constituting a minor subset of head and neck cases.^2,3 This deep anatomical location poses significant diagnostic and therapeutic challenges due to its proximity to critical neurovascular structures, including the cervical sympathetic chain.^2,3 Horner syndrome (HS)—characterized by the triad of ptosis, miosis, and anhidrosis—is an uncommon presenting feature of head and neck malignancies in children. When it occurs, it typically stems from disruption of the oculosympathetic pathway by mass effect, trauma, or iatrogenic injury.^4-6 Although neuroblastoma is the malignancy most frequently associated with pediatric HS, RMS—particularly in the parapharyngeal region—is a rare but recognized etiology.^4,7 The syndrome’s onset early in life may further lead to iris heterochromia due to impaired melanocyte migration, though this is more typical of congenital rather than acquired cases. ⁵

This report details the case of a 30 month-old male who presented with isolated, sudden-onset left HS as the sole manifestation of a primary embryonal RMS occupying the left poststyloid parapharyngeal space. This case underscores the diagnostic significance of HS as a potential indicator of occult malignancy in young children and highlights the parapharyngeal space as a critical, albeit rare, site for RMS with unique clinical implications.

Case Presentation

A 30-months-old male without personal or familial history was admitted to Otolaryngology clinic with sudden onset of partial left eyelid ptosis, without additional symptoms. On examination there was an isolated left HS (Figure 1), the rest of physical examination was within normal. A contrast-enhanced magnetic resonance imaging (MRI) scan was performed, revealing a left-sided lesion situated in the poststyloid parapharyngeal space, measuring 2.5 × 3.5 × 5 cm. The lesion displayed high signal intensity on T2-weighted images and caused anterior displacement of the carotid artery and posterior displacement of the internal jugular vein (Figure 2). The decision of surgical resection was made, the transcervical approach was done to access the parapharyngeal space, intraoperative, an un capsulated lesion which involve the sympathetic trunk, the tumor was resected totally with the involved sympathetic tissue. After the surgery, there was no observed improvement in the symptoms of HS. Hisological examination showed malignant small round cell tumor in keeping with high-grade sarcoma. The differential diagnosis includes RMS, among others (Figure 3), the immunohistochemical (IHC) stains were performed and showed positive CK, PLAP, and CD99, the morphology and IHC staining were consist with RMS. The child was referred to an oncologist to initial the chemoradiotherapy. After 1 year of follow-up with senescence PET-CT imaging, no signs of recurrence were observed (Figure 4).

Figure 1.

Left Horner syndrome, partial eyelid ptosis, and myosis.

Figure 2.

Axial (a) and coronal (b) MRI showing a left-sided lesion (asterisk) with high signal intensity. MRI, magnetic resonance imaging.

Figure 3.

Microscopic examination shows small, spindled, and round cells with hyperchromatic nuclei and prominent nucleoli along eosinophilic cytoplasm.

Figure 4.

PET-CT scan after 2 months of surgery showing no signs of recurrence.

Discussion

This unique presentation of embryonal RMS manifesting solely as isolated HS expands the diagnostic paradigm for pediatric oculosympathetic pathway disruption. Beyond confirming RMS’s rare parapharyngeal predilection, it compels deeper consideration of tumor biology, imaging nuances, and long-term implications distinct from classical RMS presentations or other Horner-associated malignancies. This case of a 30 month-old male presenting with isolated, sudden-onset left HS as the sole manifestation of embryonal RMS in the post-styloid parapharyngeal space underscores several critical clinical and diagnostic considerations. While RMS accounts for 4% to 7% of childhood malignancies, with 35% to 40% occurring in the head and neck region, primary involvement of the parapharyngeal space remains exceptionally rare, constituting only 14.3% of head and neck RMS cases in large series.^1,2 The deep anatomical location adjacent to the cervical sympathetic chain directly explains the HS presentation—characterized by ptosis, miosis, and anhidrosis—via mass effect disrupting the oculosympathetic pathway.^1,4 Although neuroblastoma is the malignancy most frequently associated with pediatric HS, RMS must be considered in the differential, particularly when lesions involve the parapharyngeal region.^1,5,8

The absence of other neurological deficits or systemic symptoms in this case highlights the diagnostic challenge. HS as an isolated finding is an uncommon but critical indicator of occult malignancy in young children, necessitating urgent neuroimaging.^1,5,8 MRI, as performed here, is indispensable for delineating parapharyngeal masses. Key features favoring RMS over mimics (eg, lymphoma or nasopharyngeal carcinoma) include heterogeneous T2 signal, heterogeneous enhancement, necrosis, and higher mean ADC values. ⁷ In this patient, MRI revealed anterior displacement of the carotid artery and posterior displacement of the internal jugular vein, reflecting the tumor’s proximity to critical neurovascular structures—a factor complicating surgical resection. ¹ Surgical management of parapharyngeal RMS is fraught with challenges due to anatomical constraints. The transcervical approach enabled gross total resection, but intraoperative involvement of the sympathetic trunk necessitated its sacrifice, explaining the persistence of HS postoperatively. ¹ Notably, no clear resection margins were achieved, aligning with literature indicating that only 42.9% of head and neck RMS cases undergo surgery, and microscopic residual disease is common. ² This underscores the imperative for multimodal therapy. Adjuvant chemoradiotherapy, guided by protocols like the Cooperative Weichteilsarkom Studie, is essential for local control and survival. The patient’s referral for chemoradiotherapy postresection reflects standard management, with regimens typically involving vincristine, actinomycin-D, and ifosfamide for intermediate-risk disease. ² The favorable outcome at 1 year follow-up (no recurrence on PET-CT) aligns with data showing 5 year overall survival rates up to 91.3% for head and neck RMS treated with multimodal therapy. ² Factors contributing to this include embryonal histology (85.7% of pediatric cases), age <10 years, localized disease (IRS stage 3), and absence of metastasis—all positive prognostic indicators observed here.^2,7 Nevertheless, long-term surveillance is crucial due to risks of recurrence (25% in some series) and secondary malignancies from alkylating agents and radiotherapy. ² An intriguing aspect is the potential for iris heterochromia, though not observed here. Congenital or very early-acquired HS can impair melanocyte migration, leading to lighter iris pigmentation ipsilateral to the lesion.^1,5 This phenomenon, documented in neuroblastoma-related cases, may theoretically occur if sympathetic disruption happens before age 2 years. ⁵ Our patient’s age (30 months) may have mitigated this risk, though long-term ophthalmologic monitoring remains prudent.

The poststyloid parapharyngeal space’s confinement between the carotid sheath and skull base creates a “compression corridor” for the sympathetic plexus. Tumor extension here may cause HS earlier than in other sites, even with smaller volumes (eg, 2.5-5 cm), due to confined neurovascular anatomy.^1,4,8 For unresectable sympathetic chain involvement, proton beam therapy could reduce long-term morbidity versus conventional radiotherapy. Its Bragg peak spares contralateral structures (eg, salivary glands, optic pathways), critical in young children to avoid xerostomia, growth asymmetry, or secondary malignancies—reported risks.^2,4 Despite the tumor’s size (3.5 cm), no nodal involvement (N0) was observed. This contrasts with alveolar RMS but aligns with embryonal subtypes, where nodal spread is rare (<10%). Tumor biology (not size) may drive metastatic behavior, emphasizing histology’s prognostic role.^1,2 While PET-CT showed no recurrence, its sensitivity for detecting microscopic residual disease in RMS is suboptimal. Future protocols could incorporate circulating tumor DNA or FDG-PET/MRI fusion for earlier relapse detection, especially in high-risk sites like the parapharyngeal space.^1,7 Unlike neuroblastoma (often cervical/mediastinal) or iatrogenic injury, parapharyngeal RMS causes HS via direct extracranial sympathetic compression.^5,6 This contrasts with middle ear RMS, where intracranial extension is typical. Anatomic origin dictates the oculosympathetic disruption level.^4,8

Conclusion

This case accentuates that isolated HS in young children, even without palpable masses or neurological deficits, warrants rigorous investigation for occult malignancy. The parapharyngeal space, though a rare site for RMS, carries unique implications due to its proximity to the sympathetic chain. MRI is pivotal for early detection and differentiation from other tumors. Multimodal therapy—incorporating surgery, chemotherapy, and radiotherapy—optimizes outcomes, particularly for embryonal subtypes. Persistent HS postresection may reflect unavoidable sacrifice of sympathetic fibers and should be anticipated during surgical counseling. Vigilant long-term follow-up is essential to monitor recurrence and late effects of treatment.