Lethal midline granuloma is a rare, aggressive Non-Hodgkin lymphoma of the head and neck. Most cases are of natural killer (NK)/T-cell origin and typically feature the extensive destruction of the nasal structures and nasopharynx with possible dissemination to the skin, soft tissues, gastrointestinal tract, and testes.
Lethal midline granuloma, also known as polymorphic reticulosis or malignant midline reticulosis [1], is an aggressive Non-Hodgkin lymphoma of the head and neck that arises in the sinonasal structures and nasopharynx. This progressive disease manifests as a necrotizing, destructive midfacial lesion with the erosion of the nasal bone, cartilage, and soft tissue, as well as perforation of the nasal septum [2] [3]. The vast majority of cases originate from NK/T cell lineage while some emerge from B-cell or peripheral T-cell lineage [4] [5]. Advanced disease is characterized by involvement of extranodal sites such as the skin, soft tissues, gastrointestinal tract, and testes [6] [7].
This lymphoma has a predilection for males and develops approximately in the fourth decade [3]. Symptomology includes constitutional symptoms such as weight loss, fatigue, fever, and night sweats. Patients typically present with nasal pain, obstruction, nasal stuffiness, epistaxis, and possibly purulent rhinorrhea. Facial swelling and pain are also common. Moreover, affected individuals experience dysphagia, odynophagia, hoarseness, trismus, and velopharyngeal dysfunction. Other features include impaired vision and hearing, diplopia, orbital swelling, conjunctivitis, otalgia, and refractory sinusitis. Patients with lung involvement exhibit cough, dyspnea, and difficulty with breathing while those with gastrointestinal (GI) metastasis report early satiety, a feeling of fullness, and possibly evidence of perforation and bleeding.
Physical exam
Upon observation, key findings include facial swelling and erythema. Close inspection may reveal ulceration of the skin, palate, tonsil, and other structures. Additionally, there are likely nasal, orbital, and neck masses. A neurologic exam is necessary for proptosis and cranial neuropathies. Finally, disseminated disease features may include abdominal mass, hepatosplenomegaly, and testicular mass.
A patient presenting with the above clinical picture should raise suspicion for lethal midline granuloma or other similar diseases. The assessment consists of the patient and family history, a thorough physical exam, and the appropriate studies.
Laboratory tests
Patients should be evaluated with a complete blood count (CBC) and a complete metabolic panel (CMP) that includes renal and liver function tests and measurement of calcium and uric acid. The results may be notable for anemia, lymphocytopenia, and elevated lactic dehydrogenase (LDH). Very importantly, Epstein-Barr virus (EBV) titers must be obtained.
Imaging
To clarify the severity and staging of the disease, comprehensive imaging must be performed. Patients should be evaluated with computed tomography (CT) scan of the neck, chest, abdomen, and pelvis. Specifically, CT of the neck and magnetic resonance imaging (MRI) of the head provide crucial information regarding intracranial extension as well as skull base invasion [8]. Other useful modalities include flexible nasopharyngoscopy and direct laryngoscopy.
Immunohistochemistry
Biopsy of the primary lesion is a pertinent component of the workup. Numerous samples should be obtained since extensive necrosis is often present. The biopsy may be repeated if the tissue specimens are inadequate. Additionally, disseminated cases may warrant bone marrow biopsy.
Immunohistochemical analysis of the involved tissue reveals an immunophenotypic profile characteristic for positive markers such as CD2, cytoplasmic CD56, and cytoplasmic CD3 epsilon, but negative for surface CD3/Leu4 [9] [10]. Moreover, nearly all cases demonstrate an association with Epstein-Barr virus [9] [11]. Furthermore, the histological findings include angiocentric patterns with angiodestruction [12] with lymphoid infiltrate [6].