Recurrent Vision Fluctuations and Orbital Signs Unmasking T-Cell Lymphoma: A Case Report

Abstract

Introduction

Orbital T-cell lymphoma is a rare and diagnostically challenging malignancy that can closely mimic inflammatory conditions such as Tolosa-Hunt syndrome (THS), particularly due to overlapping clinical and radiological features.

Case Presentation

We report the case of a 21-year-old male who initially fulfilled the ICHD-3 criteria for THS, demonstrating unilateral painful ophthalmoplegia and transient steroid responsiveness. However, recurrence of symptoms and subsequent histopathological evaluation confirmed the presence of extranodal orbital T-cell lymphoma. This case underscores the critical importance of maintaining a high index of suspicion for malignancy in steroid-responsive orbital syndromes, especially when atypical features or relapses occur. Early biopsy and multidisciplinary coordination enabled timely initiation of CHOEP chemotherapy, leading to slight clinical improvement. This report adds to the growing body of literature emphasizing the masquerade potential of lymphoid malignancies in orbital inflammation.

Conclusion

Orbital T-cell lymphoma can mimic benign inflammatory conditions such as orbital cellulitis. Prompt biopsy and multidisciplinary evaluation are crucial for accurate diagnosis and timely initiation of appropriate treatment.

Introduction

Extranodal orbital lymphomas are uncommon and represent a small fraction of orbital masses, with T-cell lymphomas accounting for less than 2% of cases [1]. Their clinical presentation often overlaps with non-malignant inflammatory conditions such as Tolosa-Hunt syndrome (THS) or idiopathic orbital inflammatory syndrome (IOIS), posing a significant diagnostic challenge [1]. THS, classically characterized by painful ophthalmoplegia with granulomatous inflammation of the cavernous sinus, is a diagnosis of exclusion. While transient steroid responsiveness is considered typical of THS, similar responses have been documented in orbital pseudotumors and lymphomas, leading to potential misdiagnosis and delayed treatment [2]. While orbital lymphomas masquerading as THS have been described, these were almost exclusively B-cell histologies [3]. To our knowledge, this is the first reported case of orbital peripheral T-cell lymphoma in a young adult initially misdiagnosed as THS. This case highlights that suspicion for malignancy must be maintained even in younger patients, as also emphasized by Alkatan et al. [4] in pediatric orbital lymphoma. Given the aggressive nature of T-cell lymphomas and their potential to masquerade as benign inflammatory disorders, early biopsy remains indispensable when atypical features such as relapse, systemic symptoms, or imaging inconsistencies arise [2]. We present a case of orbital T-cell lymphoma in a young male, initially mistaken for THS, underscoring the masquerade potential of lymphoid malignancy and the role of timely tissue diagnosis in optimizing outcomes.

Case Presentation

A 21-year-old male was brought to our hospital with left-sided periorbital swelling, redness, and pain. Symptoms began 1 week earlier with eyelid puffiness and progressed to eye pain, reduced eye movements, and fever at home along with blurring of vision. His parents denied recent trauma or nasal discharge, but reported that 7 months earlier he had been hospitalized at another facility for suspected severe left orbital cellulitis, which was treated with IV antibiotics (details of that treatment were not fully available) and steroids. Due to persistent symptoms over several months, he was referred to Al-Shifa Trust Eye Hospital, Rawalpindi.

On examination, the patient appeared in moderate distress but was alert. The left eyelids were markedly swollen and erythematous, with extension of edema beyond the orbital margins. There was moderate proptosis of the left eye. Conjunctival chemosis (swelling) was present, and the sclera appeared injected. Extraocular movements of the left eye were severely restricted, especially on upgaze and lateral gaze, and caused significant pain. The right eye was completely normal. The patient presented with a visual acuity (VA) of 6/9p in the left eye and grade 1 relative afferent pupillary defect, which showed a transient improvement to 6/9 following administration of an initial dose of 1 g intravenous corticosteroid in 500 mL normal saline. However, within a few hours, the vision declined to 6/18. Notably, 1 week prior to presentation, the patient had experienced a similar episode, with VA in the left eye deteriorating to 6/36, which subsequently improved to 6/9p following oral corticosteroid therapy (exact dosage unavailable). In view of the steroid responsiveness, a second intravenous corticosteroid dose was administered, resulting in an improvement of VA to 6/6p. The patient was advised to complete a total of five daily doses of corticosteroid therapy. Despite this initial improvement, 1 week after initiating treatment, a left orbital excision biopsy was planned; however, the result of the biopsy was unremarkable. Postoperatively, the patient’s left eye vision deteriorated dramatically to no light perception.

Clinical examination revealed a relative afferent pupillary defect in the left eye, along with restriction of extraocular movements in all gazes and optic disc edema. Unfortunately, the vision in the left eye did not recover and remained at no perception of light thereafter. Following this, the patient was advised to undergo a repeat recti and orbital biopsy approximately 1 month after the previous biopsy, at Aga Khan Hospital, Karachi. The results of that biopsy revealed T-cell orbital lymphoma. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000549456).

Investigations

Initial laboratory results revealed the following:

• 1.White blood cell count: 15.2 × 10³/µL (88% neutrophils).
• 2.Erythrocyte sedimentation rate: 55 mm/h (normal <20 mm/h).
• 3.C-reactive protein (CRP): 120 mg/L (normal <10 mg/L).
• 4.Blood glucose: normal.
• 5.HIV screening: negative.
• 6.P-ANCA, C-ANCA, and GBM antibodies: negative (to rule out vasculitis and autoimmune causes).
• 7.First biopsy report: Left orbital cyst biopsy suggested fibroadipose tissue showing congested blood vessel. No cyst lining, fibrosis, necrosis, granuloma, or any evidence of malignancy is seen. Morphological findings are not consistent with IgG4-related disease or Wegener’s granulomatosis.
• 8.Second biopsy report: Left lateral rectus muscle biopsy revealed fibrocollagenous tissue fragment with mild lymphoid infiltrate, while left orbital biopsy showed atypical lymphoid infiltrate with histochemical features favoring T-cell lymphoma.
• 9.Immunostain: These atypical lymphoid cells show positivity for CD3 immunohistochemical stains with a subset staining for CD4 immunostain. CD8 immunostain highlights relatively small number of small lymphocytes. CD5 immunostain shows loss of staining in these atypical CD3-positive mononuclear cells. CD30, CD20, CD34, CD56, MPO, and TdT immunohistochemical stains are negative. Histiocytes are highlighted on CD68 and CD163 immunohistochemical stain. Ki-67 shows high proliferative index of approximately 60% in the atypical T lymphoid infiltrate.

Given the history of a previous orbital cellulitis and the current clinical presentation, urgent imaging was performed to evaluate for orbital involvement. That includes the following.

Contrast-Enhanced MRI

A contrast-enhanced MRI of the brain and orbits (Fig. 1) was performed. There are diffuse, non-mass-like extraocular intra-orbital altered MR signals seen in left orbit, involving the extraconal and intraconal compartments of predominantly retrobulbar region along with mild pre-septal swelling. It is involving all extraocular muscles with their diffuse swelling involving muscle belly and tendons. Lacrimal gland is mildly swollen. Retrobulbar fat stranding is visible. Mild diffuse perineural enhancement is seen along left optic nerve.

Fig. 1.

Sagittal section of MRI brain and orbit with contrast.

CT Scan with Contrast

A CT scan with contrast (Fig. 2) showed left-sided exophthalmos, diffuse swelling, and enhancement of the intra-orbital muscles, as well as pre-septal swelling and enhancement of intra-orbital fat stranding.

Fig. 2.

Axial section of CT scan.

Ultrasound Abdomen

There was hepatomegaly with spleen in upper limits of normal size and heterogeneously hypoechoic pancreas with slight irregular margins (online suppl. material: Figure S1a, S1b and S1c).

Differential Diagnosis

The differential diagnosis for this case included the following:

• 1.Orbital T-cell lymphoma (final diagnosis): As confirmed by biopsy; accounts for <2% of all extranodal lymphomas yet can mimic THS clinically.
• 2.THS: The MRI findings along with the patient’s age and the absence of significant sinus or infectious findings usually support the diagnosis of THS. In this case, biopsy result ruled out THS.
• 3.Granulomatosis with polyangiitis: It typically presents with fever, fatigue, weight loss, sinus infections, coughing, and wheezing. However, negative ANCA antibodies and unremarkable ultrasound findings did not support this diagnosis.
• 4.Orbital pseudotumor: It is often present with painful ophthalmoplegia and proptosis, mimicking neoplastic or inflammatory conditions. However, recurrence of symptoms and histopathological findings made this diagnosis unlikely.
• 5.Orbital cellulitis: The presentation with pain, swelling, and limited eye movements initially suggested orbital cellulitis. However, the absence of fever progression, the lack of significant orbital tenderness, and normal imaging findings for sinusitis made this diagnosis less likely.
• 6.Cluster headaches: Although cluster headaches can present with severe orbital pain, they typically do not cause the proptosis, ocular motility limitations, or fever seen in this patient. The episodic nature of his symptoms and the patient’s age further argued against this diagnosis.
• 7.Sinusitis with orbital extension: The patient’s prior history of sinusitis led to initial concern for sinusitis-related orbital involvement. However, the MRI revealed no significant sinus pathology, and the patient’s symptoms did not fit typical sinusitis.

Within 1 week of histological confirmation, the patient commenced systemic chemotherapy on a modified CHOEP protocol (cyclophosphamide 1,200 mg/m² IV on day 1, doxorubicin 50 mg/m² IV on day 1, vincristine 2 mg IV on day 1, etoposide 100 mg/m² IV on days 1–3, dexamethasone 12 mg IV on day 0 as pre-phase). Gastroprotection (esomeprazole 40 mg PO daily) and antidiarrheal support (dioctahedral smectite 1 sachet PO as needed) were added. After the first cycle, the patient’s symptoms showed slight improvement. The patient tolerated these interventions without complications.

Discussion

This case highlights the diagnostic complexity surrounding painful ophthalmoplegia in patients. While initially presumed to be THS, the eventual diagnosis of orbital T-cell lymphoma underscores the critical importance of maintaining a broad differential, particularly when typical features such as steroid responsiveness and imaging findings overlap with other serious pathologies. Peddi et al. [5] reported a B-cell lymphoma initially diagnosed as THS, while Baig et al. [6] described a Burkitt lymphoma in an HIV-positive patient that mimicked THS. These reports, however, involved B-cell histologies. Our case is unique due to the T-cell phenotype, young age, and steroid-responsive course, adding to the spectrum of malignancies presenting as painful ophthalmoplegia. THS, classically described as a painful ophthalmoplegia due to granulomatous inflammation in the cavernous sinus, remains a diagnosis of exclusion. Its rarity and symptom overlap with conditions such as orbital cellulitis or IOIS often lead to initial misclassification [7, 8]. However, this case illustrates how THS can be mimicked by malignancy, and that steroid responsiveness should not be viewed as confirmatory. The presence of recurrent symptoms, dramatic relapse upon steroid tapering, and constitutional signs are all red flags that should prompt consideration of alternative diagnoses [9].

Imaging continues to play a pivotal role in the evaluation of orbital and cranial nerve involvement. Although MRI can help detect inflammation in the cavernous sinus and exclude some differential diagnoses, such as abscesses or overt tumors, it may not always reliably differentiate between THS and neoplastic causes, especially lymphomas with pseudotumor-like presentations [9]. This case also reiterates the point that recurrent orbital “cellulitis”, particularly when unresponsive to antibiotics warrants a careful reevaluation. Classical pyogenic cellulitis typically resolves within 48–72 h with appropriate antibiotics; persistence should prompt investigations for resistant organisms, abscess formation, or noninfectious mimics such as lymphoma [10]. In our case, initial features such as pansinusitis and neutrophilia suggested infection, yet the dramatic steroid response, negative cultures, and relapse pattern raised suspicion of a sterile inflammatory or neoplastic process. While IOIS is a known mimic and is often steroid-responsive, marked sinus opacification and relapse are atypical [11].

IgG4-related ophthalmic disease may also resemble IOIS [12], but was excluded via serology and histology. Although the initial steroid response led to temporary symptom control, the eventual histopathological diagnosis of T-cell lymphoma necessitated the initiation of systemic chemotherapy. This shift from a presumed inflammatory to a malignant etiology exemplifies the pitfall of assuming THS in the absence of confirmatory biopsy, especially when symptoms persist or recur despite therapy. Prior reports have documented both orbital pseudotumors and lymphomas masquerading as THS, reinforcing the need for vigilance [8, 11]. Steroid responsiveness alone must not delay biopsy when atypical features arise. Routine early tissue sampling could expedite targeted therapy, which, in the case of T-cell lymphoma is time-sensitive and crucial for preserving vision and life [11].

This case underscores the necessity of interdisciplinary collaboration. Input from ophthalmology, neurology, and ENT was essential in refining the diagnosis and ensuring prompt treatment. Early recognition of a noninfectious, neoplastic process, followed by timely histological diagnosis and multimodal therapy, ultimately guided a favorable outcome. Such coordinated, vigilant care remains the cornerstone in managing diagnostically elusive orbital pathologies [13]. In conclusion, steroid-responsive painful ophthalmoplegia warrants an exhaustive evaluation. In our patient, biopsy revealed orbital T-cell lymphoma, leading to escalation from corticosteroids to curative-intent chemotherapy. Multidisciplinary coordination and readiness to revise preliminary diagnoses are essential for favorable outcomes.

Statement of Ethics

This retrospective review of patient data did not require ethical approval in accordance with local/national guidelines. Written informed consent for publication of the case details and accompanying images was obtained from the patient.

Conflict of Interest Statement

All authors have no conflicts of interest.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

Rabia Asim and Johar Abbas wrote the manuscript and performed a literature review. Johar Abbas, Saadullah Ahmad, and Faizan Tahir supervised the writing and submission of this case report. The patient received direct clinical care from Saadullah Ahmad and Faizan Tahir. Johar Abbas reviewed the manuscript before submission.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

The data that support the findings of this study are not publicly available due to privacy reasons but are available from the corresponding author upon reasonable request.