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Lethal Midline Granuloma

Lethal Midline Reticulosis

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.


Presentation

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.

Fever
  • 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]
  • 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.[symptoma.com]
  • 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]
  • Abstract - Figures Preview Abstract For almost 50 years, ebolaviruses and related filoviruses have been repeatedly reemerging across the vast equatorial belt of the African continent to cause epidemics of highly fatal hemorrhagic fever.[doi.org]
Malaise
  • 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]
  • […] 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]
  • 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, and perforation of the nasal septum with mutilation of the surrounding tissues eventually occurs [6] .[ejo.eg.net]
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]
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]
Dysphagia
  • 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.[symptoma.com]
  • Dysphonia, dyspnea, and dysphagia are the usual symptoms. Pathognomonic of laryngeal sarcoid is a diffusely enlarged, pale pink, turbanlike epiglottis. Lesions in the orbit include orbital masses, lacrimal swelling, and uveitis.[headnecksurgery.wordpress.com]
Odynophagia
  • 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.[symptoma.com]
  • CASE REPORT: A 23-year-old man presented at our institution 5 months ago with odynophagia, evening fever, dry cough, and weight loss.[arquivosdeorl.org.br]
Abdominal Mass
  • 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.[symptoma.com]
Early Satiety
  • 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.[symptoma.com]
Otalgia
  • Other features include impaired vision and hearing, diplopia, orbital swelling, conjunctivitis, otalgia, and refractory sinusitis.[symptoma.com]
Epistaxis
  • Patients typically present with nasal pain, obstruction, nasal stuffiness, epistaxis, and possibly purulent rhinorrhea. Facial swelling and pain are also common.[symptoma.com]
  • There was no history of trauma, nasal obstruction, or epistaxis. The patient did not take medical advice and opted for other options; during this period the patient developed maggots in the wound.[ejo.eg.net]
  • Over time, the cough had become associated with runny brown, foul-smelling discharge, worsening of the patient's general condition and epistaxis.[arquivosdeorl.org.br]
  • […] glomerulonephritis (50%) Joints:migratory polyarthropathy (56%) Skin:inflammatory skin lesions (44%) Eyes and ears:proptosis and otitis media (29%) Heart and pericardium: myocardial infarction (28%) CNS: neuritis (22%) Symptoms Rhinorrhea Sinusitis Epistaxis[learningradiology.com]
  • Nasal obstruction, edema, epistaxis, crusting, and nasal mass were described. Topical, intralesional, and systemic steroids are the mainstays of treatment.[headnecksurgery.wordpress.com]
Facial Pain
  • With disease progression, facial pain and destructive sinonasal lesions may ensue.[ajnr.org]
Cranial Neuropathy
  • A neurologic exam is necessary for proptosis and cranial neuropathies. Finally, disseminated disease features may include abdominal mass, hepatosplenomegaly, and testicular mass.[symptoma.com]

Workup

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].

Lymphocytopenia
  • The results may be notable for anemia, lymphocytopenia, and elevated lactic dehydrogenase (LDH). Very importantly, Epstein-Barr virus (EBV) titers must be obtained.[symptoma.com]
Granulomatous Tissue
  • But if they've found an expanding eruption of granulomatous tissue gnawing a cavity behind your nose and eyeballs, then you'd better start reading the fine print on your life insurance policy.[hypochondriacheaven.com]

Treatment

  • The patterns of failure suggest a role for more aggressive local-regional treatment, as well as more effective chemotherapy.[ncbi.nlm.nih.gov]
  • The treatment for malignant lymphoma (polymorphic reticulosis) is primarily radiation, especially when confined to one site.[ncbi.nlm.nih.gov]
  • However, there are definite indications for radiation treatment for benign diseases that do not respond to conventional methods of treatment.[books.google.com]
  • In polymorphic reticulosis, thhe best results of treatment are obtained in localized lesions of the upper airway treated early with irradiation; a poorer outcome is associated with multifocal involvement, which necessitates systemic therapy.[ncbi.nlm.nih.gov]
  • LETHAL MIDLINE GRANULOMA TREATMENT APPROACH DR.[slideshare.net]

Prognosis

  • Cutaneous involvement is poorly described and the prognosis not well documented.[ncbi.nlm.nih.gov]
  • The prognosis for patients with LMG-NTL is significantly worse than for patients with other types of head and neck non-Hodgkin lymphomas (NHL).[ncbi.nlm.nih.gov]
  • Stress is made on the use of repeated biopsy until the specific histological diagnosis can be made so that specific treatment as breifly outlined, can be carried out to insure the best prognosis.[ncbi.nlm.nih.gov]

Etiology

  • A literature review was carried out, and recent concepts of the etiology and pathogenesis of this disease are presented.[ncbi.nlm.nih.gov]
  • Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology.[icd10coded.com]
  • The different etiological aspects of this syndrome are discussed.[ncbi.nlm.nih.gov]
  • Its etiology and pathogenesis are uncertain, probably varied, and the distinction between inflammatory and malignant processes is difficult despite extensive clinical and histopathologic evaluation.[ncbi.nlm.nih.gov]
  • Although there is strong association between autoantibodies against cytoplasmic constituents of neurophils and monocytes in patients with active Wegener's granulomatosis, the exact pathogenic mechanism in Wegener's granulomatosis and the etiology is still[ncbi.nlm.nih.gov]

Epidemiology

  • 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]
  • Song, Epidemiology and Pathology of T- and NK-Cell Lymphomas, T-Cell and NK-Cell Lymphomas, 10.1007/978-3-319-99716-2_1, (1-29), (2018).[doi.org]
  • […] 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]
Sex distribution
Age distribution

Pathophysiology

  • 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]
  • 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 pathophysiological mechanisms involved in this disease and specific diagnostic criteria were also described (10, 11).[ajnr.org]

Prevention

  • 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]
  • BCL-X L prevents tBID from activating BAX and prevents BAX from oligomerizing resulting in the inhibition of MOMP.[doi.org]

References

Article

  1. Mehta V, Balachandran C, Bhat S, Geetha V, Fernandes D. Nasal NK/T cell lymphoma presenting as a lethal midline granuloma. Indian J Dermatol Venereol Leprol. 2008;74(2):145-7.
  2. Patel V, Mahajan S, Kharkar V, Khopkar U. Nasal extranodal NK/T-cell lymphoma presenting as a perforating palatal ulcer: A diagnostic challenge. Indian J Dermatol Venereol Leprol. 2006;72(3):218-21.
  3. Mallya V, Singh A, Pahwa M. Lethal midline granuloma. Indian Dermatol Online J. 2013;4(1):37-39.
  4. Batra P, Shah N, Mathur S. Midline lethal granuloma: A clinical enigma. Indian J Dent Res. 2003;2003;14(3):174-83.
  5. Mendenhall WM, Olivier KR, Lynch JW, Mendenhall NP. Lethal midline granuloma-nasal natural killer/T cell lymphoma. Am J Clin Oncol. 2006;29(2):202–6.
  6. Chan JKC, Sin VC, Wong KF, et al. Nonnasal lymphoma expressing the natural killer cell marker CD56: A clinicopathologic study of 49 cases of an uncommon aggressive neoplasm. Blood. 1997; 15;89(12):4501-13.
  7. Kwong YL, Chan ACL, Liang R, et al. CD56+ NK lymphomas: Clinicopathological features and prognosis. Br J Haematol. 1997;97(4):821-9.
  8. Ooi GC, Chim CS, Liang R, Tsang KW, Kwong YL. Nasal T-cell/natural killer cell lymphoma: CT and MR imaging features of a new clinicopathologic entity. AJR Am J Roentgenol. 2000; 174(4):1141-5.
  9. Jaffe ES, Chan JKC, Su IH, et al. Report of the workshop on nasal and related extranodal angiocentric T/natural killer cell lymphoma: Definitions, differential diagnosis, and epidemiology. Am J Surg Pathol. Am J Surg Pathol. 1996;20(1):103-11.
  10. Kwong YL, Chan ACL, Liang RHS. Natural killer cell lymphoma/leukemia: Pathology and treatment. Hematol Oncol. 1997;15(2):71-9.
  11. 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.
  12. 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.

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Last updated: 2019-07-11 20:37