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

  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]

  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]

  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]

  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]

  9 Codes Corresponding ICD-10 Codes C84.5 Other and unspecified T-cell lymphomas Corresponding ICD-10-CM Codes (U.S. only) C86.0 Extranodal NK/T-cell lymphoma, nasal type (effective October 01, 2015) Signs and Symptoms Drenching night sweats Fatigue Fever [seer.cancer.gov]

• Asymptomatic

  The first three patients had no clinical symptoms at last follow-up, although complete endoscopy records are not available for patients 1 and 3, and persistent (but asymptomatic) disease at those times cannot be excluded. [doi.org]

  Typically, the viral infection, which afflicts >90% of the world population, occurs years before evidence of ENKTCL-NT, is carried in cells in a latent, asymptomatic form, and for unclear reasons becomes active in causing the disease. [en.wikipedia.org]

• Malaise

  […] 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]

• Rhinorrhea

  Rhinologic symptoms in Wegener's granulomatosis include progressive nasal obstruction, bloody rhinorrhea with crusting, and vague pain and tenderness of the nasal dorsum. [ncbi.nlm.nih.gov]

  Patients typically present with nasal pain, obstruction, nasal stuffiness, epistaxis, and possibly purulent rhinorrhea. Facial swelling and pain are also common. [symptoma.com]

  Organs Urinary tract:focal 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 [learningradiology.com]

• Nasal Ulcer

  The major symptoms are nasal stuffiness with or without nasal discharge. Oral or nasal ulcer with conjunctivitis may also occur. [ncbi.nlm.nih.gov]

  The major symptom is nasal stuffiness with or without nasal discharge. 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]

• Anosmia

  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]

  Patient's previous medical records disclosed h/o of nasal obstruction on and off and anosmia and histopathological diagnosis of previous biopsy was given as round cell tumor by a private lab and as tissue insufficient for reporting by TATA memorial hospital [jomfp.in]

• Rhinitis

  Abstract Six cases were described in which an initial clinical diagnosis of "rhinitis gangrenosa progressiva" or lethal midline granuloma was made. [ncbi.nlm.nih.gov]

  In contrast, no case of Wegener's granulomatosis or nonspecific rhinitis produced a true hybridization signal. [lup.lub.lu.se]

• 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]

• Vomiting

  No further management; 36 mo; NED CD3–/CD56+/TIA, granzyme, and/or perforin+/CD2+/CD5–/CD4–/CD8–/CD20–/CD30–/CD34–/CD68–/MPO–/EBER ISH–/polyclonal TCR Koh et al 3 1 NK-cell lymphoproliferative lesion, NKCE or LyGa Korea 14 1:0 Abdominal discomfort, vomiting [doi.org]

  Only 2 courses of SMILE were administered with adequate tolerance and some side effects, which were easily managed, such as queasiness, vomiting, weight loss and alopecia. [revistas.unal.edu.co]

• Vascular Disease

  Includes: autoimmune disease NOS collagen (vascular) disease NOS systemic autoimmune disease systemic collagen (vascular) disease Excludes1 autoimmune disease, single organ or single cell-type -code to relevant condition category M31 Other necrotizing [icd10coded.com]

• Erythema

  Case Report A 74 year-old healthy male presented with eight month-old complaints of erythema and swelling involving the nose and upper lip. [ijdvl.com]

  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. [symptoma.com]

  Ocular examination revealed bilateral peri-orbital edema with erythema, conjunctival chemosis with right upper eyelid completely replaced by crusts, exposing the cornea (Figure 1A) resulting in absent vision on the right side. [oatext.com]

  Clinical photo showing swelling and erythema on the dorsum of the nose All routine hematological and biochemical investigations were normal. HIV, HBsAg and VDRL were negative. [ncbi.nlm.nih.gov]

• Skin Disease

  SKIN DISEASE TREATMENT HUMAN HEPARIN PROTAMINES DERMATOLOGY Keyword (es) DERMATOLOGIA Classification Pascal 002 Biological and medical sciences / 002B Medical sciences / 002B08 Dermatology Discipline Dermatology Origin Inist-CNRS Database PASCAL INIST [pascal-francis.inist.fr]

• Epistaxis

  The patients complain of rhinorrhea, epistaxis, nasal stuffiness, obstruction and pain. [ncbi.nlm.nih.gov]

  Patients typically present with nasal pain, obstruction, nasal stuffiness, epistaxis, and possibly purulent rhinorrhea. Facial swelling and pain are also common. [symptoma.com]

• 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]

• Facial Pain

  Epistaxis and facial swelling may be in the clinical spectrum. With disease progression, facial pain and destructive sinonasal lesions may ensue. [ajnr.org]

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].

• 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]

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]

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 [8]. [ejo.eg.net]

LETHAL MIDLINE GRANULOMA TREATMENT APPROACH DR. [slideshare.net]

Cutaneous involvement is poorly described and the prognosis not well documented. [ncbi.nlm.nih.gov]

[…] and NK/T cell lymphoma prognosis. [doi.org]

Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology. [icd10coded.com]

A literature review was carried out, and recent concepts of the etiology and pathogenesis of this disease are presented. [ncbi.nlm.nih.gov]

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]

[…] 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]

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]

Epidemiology and pathogenesis of nasal NK/T-cell lymphoma: a mini-review. ScientificWorldJournal. 2011 Feb 14. 11:422-8. [Medline]. Swerdlow E, Campo E, Harris NE, et al. IARC, Lyon. [emedicine.medscape.com]

(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]

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]

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]

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]

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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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.
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