Lethal Midline Granuloma - Clinical Features, Diagnosis, and Treatment

Introduction:

Lethal midline granuloma is an exceptionally rare condition, first identified by MC Bride in 1897. It manifests as necrotic granulomas, leading to the destruction of nasal and paranasal sinus tissues, including bone, cartilage, and soft tissues. Patients experience a swift and aggressive progression of the disease, resulting in rapid destruction of the nose and midline facial structures, hence the name ‘lethal midline granuloma.’ This condition, also known as NK/T-cell lymphoma, can affect individuals across a wide age range, with a higher incidence in males. It is predominantly observed in Asian and Mexican populations.

What Is Lethal Midline Granuloma?

Lethal midline granuloma is a serious condition that affects the midfacial area, causing damage to the tissues lining the upper part of the throat and digestive system. People with this condition often experience symptoms like a runny nose, nosebleeds, congestion, and pain. The disease can make the nose tissue thicker and cause severe damage to the midfacial area, including the nasal septum and bones. While it usually starts in the upper throat and digestive tract, it can spread to other body parts. Some patients may also develop general symptoms like fever and fatigue. This condition is also known as polymorphic reticulosis or Stewart's granuloma. It is mostly linked to a type of lymphoma called NK (natural killer)/T cell lymphoma (NKTL).

What Are the Clinical Features of Lethal Midline Granuloma?

The disease usually has three stages: the early stage, the active stage, and the final stage. In the final stage, the disease causes thickening of the mucous membranes, severe damage to the nose structure, upper lip, and palate, and can even spread to other parts of the body, leading to death. Common symptoms include a stuffy or runny nose, mouth or nose sores, and sometimes eye irritation. Doctors can identify it by looking for extensive ulcers and abnormal lymphatic tissue under a microscope.

The other common symptoms indicative of lethal midline granuloma include:

• Persistent swelling in the neck area.

• Pain and swelling on the dorsum of the nose.

• Radiating pain to the face and head.

• Nasal stuffiness, mucopurulent discharge, and fever.

• Inflamed, erythematous, and tender areas on the nose and nasolabial fold.

• Presence of crust-covered masses within the nasal cavity.

• Absence of epistaxis, anosmia, postnasal drip, oral bleed, or cough.

• Observation of cervical and submandibular lymphadenopathy.

• Diffuse edema may be observed over the left cheek and periorbital region.

• There is a saddle deformity in the nose, accompanied by foul-smelling crusts and a small anterior septal perforation.

• Endoscopic examination may reveal pink granulations near the middle meatus along with bony sequestrates.

• The oral examination may show a midline ulcer over the hard palate, with intact underlying bone.

• An ocular examination may indicate periorbital edema with erythema over the upper eyelid, conjunctival chemosis, and normal ocular movements and vision.

How Is Lethal Midline Granuloma Diagnosed?

The diagnosis process of lethal midline granuloma involves several steps. First, doctors assess the patient's symptoms and medical history through a clinical evaluation. Then, imaging tests such as CT (computed tomography) scans and MRI (magnetic resonance imaging) scans help them visualize the extent of the disease and its impact on nearby structures. Finally, a biopsy of affected tissue is essential for confirming the diagnosis. During this histopathological examination, doctors look under a microscope for specific signs, like abnormal inflammation and atypical cells. They may also use special staining techniques to identify markers associated with lymphoid malignancies.

What Are the Diagnostic Findings Commonly Observed in Patients With Lethal Midline Granuloma?

1. Hematological Investigations:

• Leukocytosis with relative lymphocytosis.

• Raised erythrocyte sedimentation rate.

2. Urine and Sputum Analysis:

• Normal findings in urine microscopy and sputum analysis.

3. Biochemical Tests:

• Negative results for c-antineutrophil cytoplasmic antibodies (ANCA), p-ANCA, and human immunodeficiency virus enzyme-linked immunosorbent assay (HIV ELISA).

4. Computed Tomographic Scans:

• Soft tissue thickening was observed in the left nasal cavity and maxillary sinus.

• Bony erosion and anteroinferior septal perforation were noted.

• There is no evidence of orbital invasion.

5. High-Resolution Computed Tomography of Chest:

• Nonhomogeneous opacities were detected in the right upper zone and perihilar region.

6. Nasal Biopsy Findings:

• Presence of granulation tissue.

• Fragments of necrotic bone were observed.

• Absence of identified granuloma.

• Negative fungal culture and acid-fast bacilli staining.

What Is the Treatment for Lethal Midline Granuloma?

Treatment for lethal midline Granuloma can vary depending on how severe the disease is and the patient's overall health.

It often includes different approaches:

• Chemotherapy: This involves using powerful medications like Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (known as CHOP) to treat LMG, especially when it is linked with lymphoma.

• Radiation Therapy: High-energy rays are directed at the affected area to shrink the granulomatous lesions, ease symptoms, and prevent them from returning. Another method, intensity-modulated radiation therapy (IMRT), might be used for better precision.

• Surgical Treatment: In some cases, surgery may be an option if the disease is limited to a specific area and can be removed completely. However, because LMG tends to spread, more than surgery is needed.

• Immunomodulatory Therapy: Certain medications, like interferon-alpha and Rituximab, can help regulate the immune system and have shown promise in treating LMG, especially if it is related to EBV (Epstein-Barr virus) infection or immune system problems.

• Supportive Care: Besides treating the disease directly, managing symptoms and improving the patient's quality of life is important. This can include pain management and ensuring they get proper nutrition.

What Are the Differential Diagnoses for Lethal Midline Granuloma?

• Other possible causes to consider are trauma, infections like tuberculosis, syphilis, leprosy, rhinoscleroma, and actinomycosis (caused by bacteria), as well as fungal infections such as aspergillosis and mucormycosis.

• Toxic substances like cocaine or chromium salts, inflammatory conditions like sarcoidosis, Wegener’s granulomatosis, and systemic lupus erythematosus, and neoplastic conditions like basal cell carcinoma, neuroblastoma, rhabdomyosarcoma, and lymphoma should be considered as potential causes.

Conclusion:

This disease is extremely aggressive and can get worse very quickly. If not treated, it can be deadly, with almost everyone affected dying from complications like severe infection, blood vessel rupture, or brain abscess. Research has shown that a combination of chemotherapy and targeted radiation therapy can help some patients live longer without the disease getting worse. Because this illness can be hard to recognize, doctors need to be very cautious and act fast to diagnose and treat it early, giving patients the best chance of surviving longer.