T/NK cell non-Hodgkin’s lymphoma of the sinonasal tract

Sheahan, Patrick; Donnelly, M. J.; O’Reilly, Seamus; Murphy, Maurice

doi:10.1258/0022215011909710

Cited by 20 publications

(12 citation statements)

References 10 publications

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“…1,2 The hallmark pathologic finding of destructive midline granulomatous (DMG) disease is caseating granulomas characteristically involving the nose, sinuses, palate, and upper airways, especially the subglottis. Although WG usually includes renal involvement and circulating antineutrophil antibodies (ANCAs), local nasopharyngeal WG without associated antibodies occurs.…”

Section: Introductionmentioning

confidence: 99%

Hypomorphic Rag mutations can cause destructive midline granulomatous disease

Ravin

Cowen

Zarember

et al. 2010

Blood

114

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IntroductionProgressive granulomatous tissue destruction of the midface and the upper airways is most commonly caused by Wegener granulomatosis (WG) or malignancies such as natural killer (NK)/T-cell lymphomas and, to a lesser extent, cocaine abuse or infections. 1,2 The hallmark pathologic finding of destructive midline granulomatous (DMG) disease is caseating granulomas characteristically involving the nose, sinuses, palate, and upper airways, especially the subglottis. Although WG usually includes renal involvement and circulating antineutrophil antibodies (ANCAs), local nasopharyngeal WG without associated antibodies occurs. 3 Standard therapy for these diseases involves immunoablative chemotherapy to halt disease progression, in contrast to immunosupportive measures required to treat primary immune deficiencies. We describe in this report the first patient with clinical manifestations of a WG-like destructive midline granulomatosis with underlying novel compound heterozygote mutations in Rag1.The recombination activation genes, Rag1 and Rag2, perform a critical role in the somatic rearrangement and assembly of the modular genes for variable (V), diversity (D), and joining (J) gene segments of immunoglobulins and of antigen receptor genes. [4][5][6] After binding to conserved recombination signal sequences (RSSs) that flank individual V, D, or J gene segments, the Rag1/2 complex introduces a nick in the DNA, followed by formation of a coding end hairpin. Nonhomologous end joining DNA repair then takes place to generate the diverse VDJ contiguous regions that are essential for defense against many different pathogens. In addition to initiating the double-strand DNA breaks, the Rag complex stabilizes recombination intermediates to promote repair and editing of the modified genes. 6,7 Rag proteins are indispensable for lymphocyte development and differentiation, and defects in Rag manifests as T-and B-deficient severe combined immunodeficiency (T-B-SCID) or Omenn syndrome (OS) in infancy. These syndromes are characterized by early-onset profound deficiency in T and B cells for SCID and by early-onset erythroderma, hepatosplenomegaly, eosinophilia, and hyper immunoglobulin E (IgE) in OS.In stark contrast, our patient presented for evaluation of a DMG process at 14 years of age with normal numbers of CD3 ϩ T and CD19 ϩ /CD20 ϩ B cells and with normal total IgG levels. Evaluation in subsequent years showed dysregulated hyperinflammatory responses with appearance of new granulomatous lesions after environmental or viral triggers. This report further extends the clinical spectrum of Rag mutations, and our data support the view that, in addition to susceptibility to infections and autoimmunity, hyperinflammation is an important component of Rag deficiency and may be the primary clinical manifestation leading to diagnosis when lymphocyte counts are normal. Hypomorphic Rag mutations should be considered in "idiopathic" destructive granulomatous disease. MethodsThe subjects were enrolled on protocol 05-I-213 approved by...

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Section: Introductionmentioning

confidence: 99%

Hypomorphic Rag mutations can cause destructive midline granulomatous disease

Ravin

Cowen

Zarember

et al. 2010

Blood

114

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“…The difficulty in the diagnostic process leads to a presentation of an advanced stage of the lymphoma, which then predicts poor prognosis for the patient. As the nature of the disease is one of progressive tissue necrosis, multiple large biopsy specimens are required before sufficient tissue with scattered malignant cells is discovered [45][46][47][48][49][50]. Careful immunohistochemical assessment is thus vital in order to differentiate these lymphomas from other malignancies as well as benign inflammatory processes.…”

Section: Discussionmentioning

confidence: 99%

Lymphomas of the head and neck in dermatological practice

Sokołowska‐Wojdyło¹,

Sikorska²,

Florek³

et al. 2012

pdia

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“…10 This entity encompasses less than 0.5% of cases of extranodal lymphomas in the Western world and affects men slightly more than women (3:1), generally peaking in the sixth decade. 1,3 It typically presents with midline destruction, septal perforation, and surrounding tissue necrosis.…”

Section: Discussionmentioning

confidence: 99%

“…While the etiology of NK/T-cell lymphoma remains unclear, an association with Epstein-Barr virus is suspected to have a role in the tumorigenesis of this lymphoma. 1,2,7,10 The differential diagnoses of NK/T-cell lymphoma includes cocaine abuse, trauma, infection (bacterial, fungal, parasitic), inflammatory disease (sarcoidosis, Wegener's granulomatosis, systemic lupus erythematosus, polyarteritis nodosa), and neoplastic processes (squamous or basal cell carcinoma, esthesioneuroblastoma, adenoid cystic carcinoma, or additional sinonasal lymphoma). 12,13 Initial diagnostic studies may aid in the delineation of this disease process through the elimination of other diagnoses.…”

Section: Discussionmentioning

confidence: 99%