Unusual association of orbital tumour and rhino-orbital-cerebral mucormycosis

Abstract

In developing tropical countries, rhino-orbital-cerebral mucormycosis has been a cause of severe morbidity and mortality during the COVID-19 pandemic. Classically, it develops as an aggressive angioinvasive destruction of nasal, orbital and cerebral involvement. Blindness is a major disabling complication. The association of mucor in cancer is linked with immunosuppression caused by radiation and/or chemotherapy. In this case report, we tried to explore the diverse possibilities of neck swelling, nasal discharge, ocular swelling and dimness of vision in a teenage boy. Rhabdomyosarcoma is a rare tumour of the soft tissue, connective tissue or bone. This type of unusual association or coexistence of rhabdomyosarcoma with mucormycetes is rarely seen in literature.

Background

Rhino-orbital-cerebral mucormycosis (ROCM) has been an epidemic during the COVID-19 pandemic. It is associated with significant morbidity and mortality in developing countries.¹ It manifests classically with progressive nasal, orbital and cerebral involvement with blindness being an important disabling morbidity. Hyperglycaemia, excessive usage of steroid and COVID-19 illness have been linked to the development of ROCM.² There has been evidence of mucor infection in patients suffering from cancer. This is mainly due to immunosuppression caused by means of chemotherapy and/or radiotherapy.³ Rhabdomyosarcoma is a rare malignancy of soft tissue, connective tissue or bone.⁴ The association of rhabdomyosarcoma in mucor is not well documented. We illustrate a case of orbital tumour associated with ROCM. The interesting part of this case is that orbital manifestations were misleading. It was because we thought of isolated ROCM in this case amidst the settings of the COVID-19 pandemic.

Case presentation

A teenage boy presented with fever and subsequent painful swelling of the right side of the neck for 28 days. It was followed by swelling of the right eye with diminution of vision for 25 days. There was history of passage of blackish-red nasal discharge, nasal blockage and swelling of the nose. The right-sided ocular swelling was acute in onset and gradually progressive with associated protrusion of the eyeball. There was restriction of movements in all directions in the right eye. It was associated with acute-onset gradually progressive painless diminution of vision in the right eye along with ocular redness and watering. There was no history of cough, headache, vomiting, convulsion, altered mentation, paraesthesia, weakness of face or limbs, difficulty in swallowing or hearing, change in voice. There was no history of COVID-19 illness, diabetes mellitus, steroid usage, thyroid disease, tuberculosis, trauma or any similar illness in the past. His general examination revealed the presence of multiple firm to hard, tender immobile swellings in the right cervical area of 2.5×2 cm² size and postauricular area of 2×2 cm² size (figure 1).

Figure 1.

(A) The right eye revealed proptosis with restriction of movement in all directions, periorbital oedema more marked in the lower lid (white arrow). (B) At follow-up demonstrating reduced lid oedema. (C) The right cervical/postauricular area revealed multiple firm tender mobile swellings suggestive of lymphadenopathy (white arrow). (D) Regression of swelling after anticancer therapy.

Nervous system examination showed normal higher mental function. There were features suggestive of optic nerve involvement of the right eye. The visual acuity was finger counting positive at two metres, colour vision was affected, with presence of relative afferent pupillary defect in the right eye. There was proptosis of the right eye with restriction of movement in all directions along with periorbital oedema (more in the lower lid of the right eye) (figure 1). The rest of the neurological and other systemic examinations were unremarkable.

Investigations

His haematological and biochemical parameters were within normal limits. The markers of inflammation revealed C reactive protein 19.9 mg/L, lactate dehydrogenase 774.1 IU/L, D-dimer 1.65 ug/mL, ferritin 91.2 ug/mL, with normal procalcitonin, renal, liver, thyroid functions and electrolytes.

MRI study revealed well-defined heterogeneously enhancing soft tissue lesion (measuring approximately 56 × 43 × 63 mm³) involving the nasal cavity on the right side. It was causing total luminal obstruction with osseous destruction and involvement extending into the ipsilateral sphenoid, frontal and ethmoid sinuses with erosion of the lateral wall of the right sphenoid sinus (figure 2). There was right-sided orbital infiltration into the extraconal fat of the medial half of the right orbit upto the orbital apex. It abutted the right optic nerve with axial proptosis and intracranial extension in the form of dural enhancement along the right temporal and bilateral basifrontal lobes without parenchymal involvement. Multiple discrete and conglomerated enlarged necrotic lymphnodes displaying signal intensity alterations are noted involving the right retro/parapharyngeal space, bilateral level II, III, IV, right intraparotid region and right 1B. The largest lymphnode measured approximately 29x23 mm in left retro/parapharyngeal space.

Figure 2.

MRI (2A) T2-weighted axial section (2B) revealed well-defined heterogeneously enhancing soft tissue lesion (white arrow) involving the nasal cavity on the right side causing its total luminal obstruction with osseous destruction and involvement extending into the ipsilateral sphenoid, frontal and ethmoid sinuses with erosion of the lateral wall of the right sphenoid sinus.

His chest X-ray, ECG and ultrasound abdomen were normal. He was found positive for fungal element in nasal scrapping and started liposomal amphotericin B therapy. Endonasal debridement was performed. The tissues were positive for fungal elements showing broad aseptate fungal hyphae in 20% Pottasium Hydroxide mount (KOH) mount (figure 3). The biopsy from the nasal debridement was also sent for histopathological examination. It showed infiltration of respiratory epithelium and necrosed fibrocollagenous tissue by small blue monomorphic round to oval cells. These cells were arranged in sheets and cord with hyperchromatic nuclei striped chromatin having high nucleo-cytoplasmic ratio and scanty cytoplasm. Immunohistochemistry of the lesion revealed desmin-positive and myogenin-positive status in the tumour cell with focal expression of cluster demarcation and negative status for leucocyte common antigen (figure 4). In view of malignancy, a detailed contrast-enhanced CT scan of thorax and abdomen was performed, which was negative for neoplastic tissue.

Figure 3.

Broad aseptate fungal hyphae (black arrow) of mucormycetes in 20% KOH mount of the tissue.

Figure 4.

Infiltration of respiratory epithelium and necrosed fibrocollagenous tissue by small blue monomorphic round to oval cells arranged in sheets and cord with hyperchromatic nuclei striped chromatin having high nucleocytoplasmic ratio and scanty cytoplasm (black arrow).

Differential diagnosis

The differentials included were nasopharyngeal carcinoma, esthesioneuroblastoma, Natural Killer (NK) cell tumour, other invasive fungal/bacterial infections.

Treatment

He responded well to standard liposomal amphotericin B therapy (10 mg/kg/day for 4 weeks) followed by posaconazole treatment (300 mg twice daily on day 1, then 30 mg per day for 2 months). He was referred to the oncology and radiation oncology department where he was given four cycles of chemotherapy and radiotherapy (45 greys in 25 fractions to local disease as photon therapy, followed by 46 greys in 23 fractions to neck nodes as electron boost over 2½ months). The patient was hospitalised for a month.

Outcome and follow-up

There was significant improvement due to therapy at 3 months with reduction in nasal, ocular and lymph node swelling but the vision of the right eye could not be saved.

Discussion

A teenage boy presented with acute-onset painful neck swelling, rapidly progressive right ocular swelling with progressive vision loss in the background of fever. He did not have COVID-19 illness, diabetes mellitus and had not received steroid therapy in the past. He was thoroughly evaluated and diagnosed as rhabdomyosarcoma (embryonal type) with mucormycetes co-infection. The clinical picture of rhino-orbital features in the background of the COVID-19 era (second wave) and ROCM epidemic led to suspecting fungal invasive disease in this patient. This was also confirmed by KOH staining of the fungal hyphae in cultures.

The element of cervical lymphadenopathy was the key pointer towards tumour due to its consistency and immobility. Imaging studies guided about the extent of the lesion and the nature of the lesion. Tissue biopsy in collaboration with immunohistochemistry stain yielded the diagnosis in this patient. Hyperglycaemia, which is usually seen to be associated with ROCM, was not seen in this patient at any point of time. Inflammatory markers like C reactive protein was elevated in this patient with normal procalcitonin levels, further supporting the diagnosis of inflammatory fungal infection. Standard antifungal therapy and adequate nasal tissue debridement with euglycaemia are the cornerstones in the management of ROCM.⁵ Liposomal amphotericin B was given for standard duration and dosing followed by oral posaconazole for 2 months. Rhabdomyosarcoma is managed as per staging with the help of chemoradiation.⁶ Regular cycles of chemotherapy with radiotherapy regressed the progression of the tumour in our case. The absence of metastasis to thoraco-abdominal organs is shown to have a favourable prognosis.⁷

In this patient, we tried to explore the different possibilities that can present with rhino-orbital presentation. He had evidence of mucor clinically in the form of fever, orbital swelling and blackish red nasal discharge. The diagnosis was confirmed with detection of broad aseptate fungal hyphae in 20% KOH mount from nasal debrided tissues along with clinical improvement with amphotericin B therapy. In view of prominent cervical lymphadenopathy, the nasal debrided tissue was sent for histopathological evaluation. Immunohistochemistry revealed embryonal-type rhabdomyosarcoma. This is an extremely rare case showing unusual association of rhabdomyosarcoma with mucor. This type of association or coexistence of rhabdomyosarcoma with mucormycetes is rarely seen in literature.

Previously, fungal infections were associated with immunocompromised states like diabetes mellitus, AIDS, chemotherapy, radiotherapy and haematological malignancies.⁸ Aspergillosis was found to be the most common mould infection followed by mucormycetes and fusariosis in a 5-year study of hospitalised patients with cancer.⁹ ROCM is not well described with orbital rhabdomyosarcoma and it is rather an important differential not to be missed out. Treatment of both the diseases is completely different and encouraging, and at the same time detrimental if undiagnosed. Hence, there can be suspicion of coexistence or possible association of tumour with mucormycetes infection, to be determined in future.

Learning points.

• Rhino-orbital-cerebral mucormycosis (ROCM) is an important invasive fungal infection in the COVID-19 era affecting nasal, orbital and cerebral structures.

• ROCM should be promptly treated for better clinical outcome.

• Tumours of the nasopharynx and orbits can mimic the presentation of ROCM.

• There can be coexistence or possible association of tumour with mucormycetes infection.

Ethics statements

Patient consent for publication

Consent obtained from parent(s)/guardian(s).