Nasal lymphoma is a unique type of extranodal lymphoma that occurs in the nasal region, classified into T-cell, B-cell, and NK-cell lymphomas. Historically referred to as "malignant granuloma," it is clinically divided into two types: midline lethal granuloma (also known as Stewart granuloma) and Wegener’s granulomatosis. The former is confined to the midline of the face and upper respiratory tract, while the latter involves the lungs, kidneys, and other organs. It has been identified as a specific type of lymphoma, categorized as nasal cavity and paranasal sinus lymphoma.
This condition is more common in males, with a male-to-female ratio of approximately 2:1. The average age of onset is 40–60 years, but it can also appear in young adults and children. B-cell lymphoma is more frequently seen in the paranasal sinuses, particularly among Western populations, while extranodal NK/T-cell lymphoma (nasal type) tends to localize in the nasal cavity and is more prevalent in Asian populations compared to Western populations.
Etiology
The cause of nasal lymphoma remains unclear. It was previously thought to be associated with infections or autoimmune factors. The autoimmune hypothesis suggests that the disease results from an immune system imbalance triggered by nasal infections. Meanwhile, the tumor-like theory posits that the disease is a malignancy of lymphoid tissue, classified as either reticulocytic sarcoma or lymphoma. Research has shown that more than 95% of cases are related to Epstein-Barr virus (EBV) infection. In situ hybridization using probes targeting EBV-encoded small RNAs (EBER1/EBER2) reveals positivity in nasal NK/T-cell lymphoma tissue samples, alongside positive antibody tests for EBV. This suggests that viral infection may play a role in the disease’s pathogenesis.
Pathology
The disease often originates in the nasal region, primarily affecting the midline of the face and the upper respiratory tract, but it can initially present in the oral palate or pharynx before involving the nasal area. The pathological changes are characterized by progressive granulomatous ulcerative necrosis, with a high degree of tissue destruction that may invade bone and cartilage, resulting in facial disfigurement. Histopathologically, nasal lymphomas exhibit diffuse lymphoid infiltration and a vasocentric, vessel-destructive growth pattern, leading to tissue ischemia, necrosis, and mucosal ulceration. Necrosis is frequently observed in diagnostic biopsies and may delay the diagnosis. Multiple biopsies often improve diagnostic accuracy. A definitive diagnosis relies on histopathological and immunophenotypic analysis. In situ hybridization for EBV-encoded RNA can be used to confirm EBV infection.
Clinical Manifestations
The clinical course of nasal lymphoma is divided into three stages:
Prodromal Stage
This stage presents symptoms resembling a common cold or sinusitis, including intermittent nasal obstruction and watery or bloody nasal discharge. Dryness and crusting inside the nose may also occur. Local examination may reveal granulomatous ulcers on the inferior turbinate or nasal septum. This stage typically lasts 4–6 weeks.
Active Stage
Symptoms worsen, with severe nasal obstruction, purulent nasal discharge, and a foul odor. General health remains relatively intact, but patients may experience poor appetite, low-grade fever, or occasionally high fever unresponsive to antibiotic therapy. Local examination reveals swelling, erosion, ulceration, or granulomatous proliferation of the mucosa on the inferior turbinate or nasal septum, with grayish necrosis on the surface. Severe cases may develop external nasal deformities, septal perforation, or palatal perforation. Pharyngeal involvement manifests as granulomatous erosion or ulceration of the pharyngeal mucosa. This stage lasts from several weeks to several months.
Terminal Stage
Systemic weakness and cachexia are present, accompanied by facial disfigurement. The mucosa, cartilage, and bone of midline structures and adjacent tissues may be extensively and severely destroyed. Persistent remittent high fever, hepatosplenomegaly, liver failure, and disseminated intravascular coagulation (DIC) are common. Ultimately, patients succumb to massive hemorrhage or systemic organ failure.
Diagnosis
Diagnosis is generally not difficult when based on clinical presentation, pathology, and laboratory tests. Diagnostic criteria include:
- Progressive granulomatous ulcer originating in the nasal region or midface should raise suspicion of this condition.
- Significant local destruction is present, while the overall general condition remains relatively stable.
- Cervical or submandibular lymph nodes are generally not enlarged.
- Laboratory findings often show a decreased white blood cell count, an elevated erythrocyte sedimentation rate, increased immunoglobulin levels, and elevated serum complement levels. Bacterial, fungal, and viral cultures usually yield no specific results.
- Pathology findings indicate chronic nonspecific granulomatous changes. The diagnosis can be confirmed if atypical reticular cells or mitotic figures are observed. Immunohistochemical staining reveals lymphocytes positive for CD56 (+) and CD2 (+), along with positive Epstein-Barr virus (EBV) antibody tests, which indicate nasal NK/T-cell lymphoma.
Treatment
Nasal lymphoma, being a rare malignant tumor, lacks a specific standardized treatment protocol. Treatment plans are often selected according to the oncology guidelines for malignant lymphoma. Additionally, systemic supportive therapies have shown some effectiveness.