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 , 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  . The vast majority of cases originate from NK/T cell lineage while some emerge from B-cell or peripheral T-cell lineage  . Advanced disease is characterized by involvement of extranodal sites such as the skin, soft tissues, gastrointestinal tract, and testes  .
This lymphoma has a predilection for males and develops approximately in the fourth decade . 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.
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.
Entire Body System
Nasal complaints and fever were frequent manifestation, and physical findings showed necrotic, granulomatous lesions in the nasal cavity in all cases. The survival ranged from 4 to 24 months, giving a mean value of 13 months. [ncbi.nlm.nih.gov]
Hypertension Fever 【 Note: HBsAg is present in of patients with PAN. Surgery Minimal Nursing Breastfeeding Nurses Forward Advantage & Limitations of Minimal acess surgery. 【 Provides Wide field of Vision ! [pinterest.com.mx]
Haug Browse recently published Learning/CME Learning/CME View all learning/CME CME Case 3-2019: A 70-Year-Old Woman with Fever, Headache, and Progressive Encephalopathy Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura Randomized [nejm.org]
[…] often presents with nasal obstruction and/or destruction of adjacent structures May extend into sinuses but does not primarily involve them Marrow and nodes involved only if disseminated Other sites Skin, soft tissue, GI tract, testis May have fever, malaise [surgpathcriteria.stanford.edu]
Other symptoms include fever, malaise, weight loss, a skin lesion like systemic lupus erythematosus (40% of patients), and central nervous system symptoms, including ataxia, mental confusion, and seizures. [headnecksurgery.wordpress.com]
Thirty-five to forty-five percent of patients present with a history of malaise, fever, night sweats, and/or weight loss. [en.wikipedia.org]
- Nasal Ulcer
Oral or nasal ulcer with conjunctivitis may also occur. Perforation of the nasal septum with mutilation of the surrounding tissues eventually occurs.[ 6 ] This entity is associated with Epstein Barr virus. [ncbi.nlm.nih.gov]
Oral or nasal ulcer with conjunctivitis may also occur, and perforation of the nasal septum with mutilation of the surrounding tissues eventually occurs . [ejo.eg.net]
There was no history of epistaxis, anosmia, post nasal drip, oral bleed or cough. Right sided cervical and submandibular lymphadenopathy was observed. [ncbi.nlm.nih.gov]
- Nasal Pain
Patients typically present with nasal pain, obstruction, nasal stuffiness, epistaxis, and possibly purulent rhinorrhea. Facial swelling and pain are also common. [symptoma.com]
- Saddle Nose
Saddle-nose deformity and cauliflower ear are frequent complications. Laryngeal involvement is rare. Presenting symptoms include hoarseness, dyspnea, and rarely hemoptysis. [headnecksurgery.wordpress.com]
Jaw & Teeth
Face, Head & Neck
- Facial Pain
With disease progression, facial pain and destructive sinonasal lesions may ensue. [ajnr.org]
- Facial Edema
Coronal (left) and axial (right) CT scans of the sinus reveal severe pansinusitis with abnormal nasopharyngeal thickening, right facial edema and right temporal bone opacification. [emedicine.medscape.com]
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.
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.
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 . Other useful modalities include flexible nasopharyngoscopy and direct laryngoscopy.
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  . Moreover, nearly all cases demonstrate an association with Epstein-Barr virus  . Furthermore, the histological findings include angiocentric patterns with angiodestruction  with lymphoid infiltrate .
The patterns of failure suggest a role for more aggressive local-regional treatment, as well as more effective chemotherapy. [ncbi.nlm.nih.gov]
Differential diagnosis Wegener's granulomatosis non-Hodgkin lymphoma of the nose and the paranasal sinuses (sinonasal NHL) Treatment and prognosis So far no defined treatment protocols. [med-college.de]
The results of the combined treatment are not encouraging and have yielded 5-year survival rates ranging from 20 to 80%; unfortunately, disease progression occurs rapidly despite the treatment . [ejo.eg.net]
We hereby review current knowledge about the epidemiology, clinical manifestations, radiographic characteristics, and pathologic features of LMG with those of M. irregularis infection and their associations. [ncbi.nlm.nih.gov]
(This Japanese retrospective analysis of cutaneous lymphomas describes epidemiology of various cutaneous lymphomas with emphasis on dermatologic manifestations.) Greer, JP. “Therapy of peripheral T/NK neoplasms”. Hematology. 2006. pp. 331-7. [dermatologyadvisor.com]
[…] destructive lesion s Pain in the chest, abdomen, or bone s (for no known reason) Ulcerated nodular skin lesion s Weight loss (for no known reason) Diagnostic Exams Flow cytometry Immunohistochemistry Immunophenotyping Progression and Transformation None Epidemiology [seer.cancer.gov]
Etiology Pathophysiology The direct role of EBV in the pathogenesis of ENKL has been widely debated. This was further complicated by the presence of EBV in non-malignant cells as well as the association of EBV with other non-ENKL nasal tumors. [dermatologyadvisor.com]
However, EBV nodal NKTCL is manifested primarily by its involvement in lymph nodes; it also has clinical, pathological, pathophysiological, and genetic features that differ significantly from those of ENKTCL-NT. [en.wikipedia.org]
T-cell lymphoma Angioimmunoblastic T-cell lymphoma Anaplastic large-cell lymphoma T-cell proliferations of uncertain malignant potential include the following: Lymphomatoid papulosis Hodgkin lymphoma Histiocytic and dendritic-cell neoplasms Mastocytosis Pathophysiology [emedicine.medscape.com]
The pathophysiological mechanisms involved in this disease and specific diagnostic criteria were also described (10, 11). [ajnr.org]
Hemophagocytic lymphohistiocytosis: advances in pathophysiology, diagnosis, and treatment. J Pediatr. 2013 ;163(5): 1253 – 1259. doi: 10.1016/j.jpeds.2013.06.053 ]. Letendre and co-workers [ 4 Parikh SA, Kapoor P, Letendre L, et al. [doi.org]
The threat of it can also be used to prevent your children from becoming fixated with bogies. [everything2.com]
Li, Jie Chen, Qu Lin, Xiao-Kun Ma, Min Dong, Li Wei, Zhan-Hong Chen and Xiang-Yuan Wu, Efficacy and Tolerance of Pegaspargase-Based Chemotherapy in Patients with Nasal-Type Extranodal NK/T-Cell Lymphoma: a Pilot Study, Asian Pacific Journal of Cancer Prevention [doi.org]
There is no known preventive for granuloma inguinale, although it is rare where sanitary living conditions prevail. The drainage from lesions may be infectious and handwashing and basic cleanliness are required. [medical-dictionary.thefreedictionary.com]
Phase 2 Brentuximab vedotin 35 Association of L-asparaginase-Methotrexate-Dexamethasone for Nasal and Nasal-type Natural Killer (NK)-T-cell Lymphoma Completed NCT00283985 Phase 2 Kidrolase;Methotrexate;Dexamethasone;Erwinase 36 Cyclophosphamide for Prevention [malacards.org]
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- Chan JK, Yip TT, Tsang WY, et al. Detection of Epstein-Barr viral RNA in malignant lymphomas of the upper aerodigestive tract. Am J Surg Pathol. 1994;18(9):938-46.
- Metgud RS, Doshi JJ, Gaurkhede S, Dongre R, Karle R. Extranodal NK/T-cell lymphoma, nasal type (angiocentric T-cell lymphoma): A review about the terminology. J Oral Maxillofac Pathol. 2011;15(1):96-100.