bubble_chart Overview

Malignant granuloma often originates in the nose and gradually extends to the midline of the face. It is a rare granuloma characterized clinically by progressive necrotic ulcers. The cause of this disease remains unclear, and pathological examinations typically reveal chronic nonspecific granulomatous tissue and necrosis, with infiltration of various inflammatory cells. Due to the diverse pathological manifestations, the nomenclature and classification vary widely, including terms such as necrotizing granuloma, lethal midline granuloma, idiopathic granuloma of the midface, and midline malignant reticulosis. Currently, the term "malignant granuloma" is commonly used in clinical practice.

bubble_chart Etiology

Unknown. Based on clinical and pathological features, the disease is speculated to be a tumor. There are various theories, including allergic reactions, autoimmune responses, and infections.

(1) Tumor-like Theory Many scholars believe this disease is a malignant tumor of the lymphoid tissue system. The pathological tissue resembles a fleshy tumor of reticulum cells or lymphoma, exhibiting tumor-like proliferation of atypical cells and mitotic figures, but without necrotic blood vessels or multinucleated giant cells. Since the lesions are initially confined to the nasal and respiratory regions, and in advanced stages, similar lesions appear in various parts of the body—such as internal organs, lymph nodes, and bone marrow—resembling malignant tumor metastasis. Most patients are sensitive to radiation, supporting the tumor theory, but definitive clinical and pathological evidence is still lacking.

(2) Allergic or Autoimmune Theory Recent studies suggest that this disease may be an early vascular lesion caused by an allergic reaction—specifically, hypersensitivity of blood vessels to bacterial toxins, resembling Arthus necrosis. Immunoglobulin deposits are found in capillary walls, and immune complexes are detected in the serum of patients during active disease phases. Immunosuppressive therapy can alleviate symptoms. Immunofluorescence tests reveal C3 and IgG on the glomerular basement membrane. Electron microscopy shows coarse granular deposits resembling immune complexes within the basement membrane, and circulating immune complexes are elevated. Therefore, some propose that malignant granuloma of the nose, periarteritis nodosa, and Wegener's granulomatosis belong to the same category of diseases, differing only in clinical manifestations—all being autoimmune disorders. The significant therapeutic effect of corticosteroids clinically also supports this theory.

(3) Infection Theory The pathology of this disease often shows chronic inflammatory changes, yet no specific pathogenic bacteria, viruses, or fungi have been definitively identified. Recent studies have discovered Coxsackie virus particles in cell cultures of malignant granuloma tissue and in patient sera, suggesting a possible association between this disease and viral infection.

bubble_chart Pathological Changes

Based on the characteristics of the lesions and pathological changes, they can be categorized into two types:

(1) **Tumor-like Type** The lesions often originate in the nasal region, though some may first appear in the palate or pharynx before spreading to the nose. The primary sites are the facial midline and upper respiratory tract, characterized by progressive granulomatous ulceration and necrosis. The destruction is extensive, potentially affecting bones and cartilage, even leading to facial disfigurement. Patients in the advanced stage often succumb to massive hemorrhage or exhaustion. The pathological changes vary significantly and primarily manifest in the following four patterns: ① Non-specific inflammatory granulomatous tissue containing inflammatory cells of various morphologies. ② Non-specific inflammatory granulomatous tissue with numerous giant cells. ③ Non-specific inflammatory granulomatous tissue with abundant histiocytes. ④ Non-specific inflammatory granulomatous tissue exhibiting marked necrosis. These four patterns often coexist in a mixed form, typically dominated by lymphocytes, along with a mix of plasma cells and varying numbers of histiocytes. These cells tend to cluster around blood vessels, showing a propensity for perivascular infiltration. Although these cells display moderate atypia, they cannot be diagnosed as malignant tumors. While the pathological changes in Wegener's granulomatosis also involve non-specific granulomas, its distinguishing features include multinucleated giant cells and necrotizing vasculitis. These serve as diagnostic criteria for differentiating malignant granuloma from Wegener's granulomatosis.

(2) **Allergic Type (Autoimmune Type)** Wegener's granulomatosis mostly falls under this category, typically divided into localized and systemic forms. It is primarily caused by hypersensitivity-induced vascular inflammation. In addition to multiple granulomas, it presents as refractory, progressive ulcerative necrosis, which may be confined to the upper respiratory tract or involve the lungs and other organs. When the lungs are affected, it manifests as multiple nodules, often with cavitation. Kidney involvement leads to focal renal necrosis or glomerulonephritis. It can also cause systemic vascular damage, with fibrous exudates and granulomatous tissue present in the blood vessels. In Wegener's granulomatosis, ulcerative necrosis commonly occurs internally, affecting organs such as the nose, palate, throat, trachea, kidneys, spleen, adrenal glands, and lungs. Patients often die from systemic exhaustion or uremia.

bubble_chart Clinical Manifestations

Stewart classified the clinical manifestations of malignant granuloma into the late stage [third stage]:

1. **Prodromal Stage**: The symptoms resemble those of a common cold or sinusitis, including intermittent nasal obstruction accompanied by watery or bloody discharge. It may also present as nasal dryness with crust accumulation. Local examination reveals general inflammatory signs, and granulomatous ulcers may appear on the nasal septum. This stage can last 4 to 6 weeks.

2. **Active Stage**: Nasal congestion or complete obstruction occurs, with purulent and often foul-smelling discharge. The general condition is still manageable, but symptoms such as night sweats, poor appetite, and low-grade fever (or occasionally high fever) are common. Conventional antibiotic treatment is ineffective. Local examination shows swelling, erosion, and ulceration of the nasal mucosa, presenting as granulomatous lesions with grayish-white necrotic surfaces. The condition typically starts in the inferior turbinate or nasal septum, and severe cases may lead to external nasal swelling. Progression of the disease can result in perforation of the nasal septum or palate. This stage may persist for weeks to months.

3. **Terminal Stage**: The patient becomes debilitated and cachectic, with severe facial disfigurement. Extensive destruction of the nasal mucosa, cartilage, bone, and surrounding tissues (such as the face, orbit, forehead, or even the skull base) occurs. Eyelid and conjunctival swelling, proptosis, and visual impairment develop. Ultimately, death results from exhaustion, hemorrhage, or complications such as meningitis.

bubble_chart Diagnosis

The diagnosis of this disease is not difficult based on clinical manifestations, histopathology, and laboratory tests. Key diagnostic points include: ① Any progressive granulomatous ulcerative necrosis occurring in the nasal region or midface should first raise suspicion of this disease. ② Pathological examination: Chronic nonspecific granulomatous sexually transmitted disease changes, along with the presence of atypical reticular cells or mitotic figures, confirm the diagnosis. ③ Severe local lesions but relatively good systemic condition. ④ Generally, no enlargement of local lymph nodes. ⑤ Laboratory findings: Decreased white blood cell count and increased erythrocyte sedimentation rate. ⑥ Advanced-stage patients often exhibit persistent remittent fever, progressive emaciation, and systemic failure. Early diagnosis and treatment yield a better prognosis. Clinically, it should be differentiated from nasal subcutaneous nodules, atrophic rhinitis, and malignant tumors, with repeated biopsies being the only reliable method for distinction.

bubble_chart Treatment Measures

Currently, a comprehensive treatment approach is primarily adopted.

1. Supportive Therapy Patients experience significant systemic depletion, making it essential to enhance nutrition, administer blood transfusions or intravenous fluids, and correct systemic exhaustion to facilitate further treatment.

2. Corticosteroid and Antibiotic Therapy For patients in the active phase with nasal and facial ulceration, systemic exhaustion, persistent high fever, and poor appetite, high-dose corticosteroid shock therapy is recommended. Once symptoms in the nasal and facial regions and systemic conditions improve, the dose should be reduced to a maintenance level until clinical recovery is achieved. Concurrently, antibiotics should be administered to control infections. During this phase, Lomustine (CCNU) is routinely used. Its mechanism resembles alkylating agents, inhibiting nucleic acid and protein synthesis in the body, with rapid efficacy—particularly notable for its antipyretic effects. Adults are prescribed 120mg orally every 3–5 weeks, totaling 5–6 doses, with a cumulative dose of 600–840mg.

3. Anticancer Drug Therapy Clinical reports exist of successful treatment using anticancer drugs. Examples include combining 6-mercaptopurine with corticosteroids, methotrexate administered via external carotid artery pulsed perfusion followed by oral administration, and subsequent switching to 5-fluorouracil. Bleomycin combined with radiotherapy has also shown excellent efficacy.

4. Radiotherapy Malignant granulomas are sensitive to radiation, making radiotherapy a primary treatment method. Cobalt-60 teletherapy and fractionated irradiation are commonly employed, with a total dose of 60Gy (6000rad). Recurrent cases may receive additional irradiation. Alternatively, deep X-ray fractionated irradiation can be used, with doses ranging from (129–387)×10⁻⁴C per session, administered every other day or daily, and a total dose varying between (2580–15480)×10⁻⁴C.

5. Local Management For nasal and facial ulcerations, crusts, or abscesses, daily cleaning is necessary. In cases of abscess formation, incision and drainage should be performed.