Angiocentric Lesions of the Head and Neck

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1 Angiocentric Lesions of the Head and Neck Cynthia M. Magro MD Director of Dermatopathology Professor in Pathology and Dermatology Weill Medical College of Cornell University New York

2 Introduction Benign lesions: Eosinophilic angiocentric fibrosis Wegener s granulomatosis Microscopic polyarteritis nodosa Allergic granulomatosis of Churg and Strauss Chronic cocaine abuse Neoplastic/angiommunoproliferative lesions: Lymphomatoid Granulomatosis NK and NK like T cell lymphomas

3 Eosinophilic Angiocentric Fibrosis A form of chronic fibrosing vasculitis along with erythema elevatum diutinuum and granuloma faciale First reported by Homes and Panje in 1983 as so called intranasal granuloma faciale ; may co-exist with GF No definite gender predilection (? F predominance, mean age 47 years No systemic stigmata of vasculitis

4 Eosinophilic Angiocentric Fibrosis Nasal stuffiness, recurrent epistaxis Nonspecific mucosal thickening, saddle nose deformity, fibrotic obstruction of the nasal cavity Other sites: larynx, upper trachea, subglottic area

5 10 yr hx recurrent epistaxis Developed nosedefomrity over 15 mos Holme SH et al. Br J Dermatol 2005

6 Eosinophilic Angiocentric Fibrosis Two components to the histopathology Vasculitis (nodular arrangement around ectatic vessels comprising plasma cells, eosinophils, neutrophils Fibrosis

8 Arthus type III with a Th2 skewing Initial trigger: drug or infection Predisposing factors Allergic diathesis Prior nasal trauma

10 Erythema Elevatum Diutinum Symmetrical Nodular lesions Joint surfaces HIV CTD Gammopathy PCV UC Professor E Wilson Jones Institute Of Dermatology

13 Erdheim Chester Disease Non X histiocytopathy occuring in middle aged adults Long bones (ankles knees), pituitary, HL, skin, liver, kidneys, orbit The Robert Bendheim Digital Atlas of Ophthalmology

15 Foamy histocytes CD68 positive CD1A S100 - CD68+

16 Cocaine Induced Midline Destructive Lesion Chronic intranasal use(mean 7.5 years) causes destruction of nasal and midfacial bones Amount massive (2.16 g per day) Epistaxis, chronic nasal discharge, SN deformity, oronasal regurgitation of food and nasal speech Hard palate, lateral nasal wall, nasal septum ANCA in some patients

17 DiCosola et al. Int J Oral Maxillary Facial surgery 2007

18 Endothelial cell necrosis Luminal/mural fibrin deposition Tissue necrosis

19 Pathogenesis Derived from the leaf of erythroxylon coca plant and is available as a hydrochloride salt of IV/IN adminstation Effects are to release catecholamines from adrenal glands Basis of the changes: vasoconstriction and toxic effect on endothelial cells Hence other manifestations include DIC Renal TMA (HUS like)

20 Intranasal prescription drug as a cause of palatal perforation Case provided by Parish P. Sedghizadeh 31-year-old Caucasian man presented to OSU dental clinic with difficulty speaking Dysphonia resulted from palatal perforation Perforation repaired surgically by ENT previously, but reopened Patient had a history of Lortab (opioid) abuse with intranasal route of administration

22 Small Vessel ANCA positive Wegener s granulomatosis Microscopic polyarteritis nodosa Allergic granulomatosis of Churg and Strauss Idiopathic GNl Vasculitis

23 Anti-neutrophilic cytoplasmic antibody Antibodies which are targeted against neutrophil and monocyte antigens Evidence that these antibodies are pathogenic: Correlation of titers with disease activity In vitro activation of neutrophils with ANCA Neonatal MPAN Remission with B cell depletion therapy Effective animal models with anti MPO ANCA

24 ANCA C-ANCA: cytoplasmic with central interlobular accentuation( active generalised WG) typically reflects PR3 specificity P-ANCA): the nuclear lobes are outlined, and there is some nuclear extension ( MPO: 60% MPAN) Atypical C-ANCA (atypical): fluorescence is flatter ; no interlobular fluorescence ( in RA, IBD) A/ P fluorescence. Multiple antigenic specificities including PR3, MPO, bactericidal permeability increasing protein, cathepsin G, elastase, lactoferrin, and lysozyme (IBD,RA)

25 Atypical CANCA CANCA with PR3 Specificity PANCA without MPO PANCA with MPO PANCA without myeloperoxidase Savage J et al. Antineutrophil cytoplasmic antibodies And associated diseases: A review of the clinical And laboratory features. Kidney International 2000:57:

26 1. Pauci immune: no IgG/IgAIC 2. ANCA produced by plasma Cells 3. Infection leads to localized production of TNF alpha Resulting in neutrophil apoptosis Which leads to displacement of Antigen (MPO/PR3) 4. ANCA binds to neutrophils Leads to neutrophil burst 5. Subsequent adherance to endothelial cells 6. Resulting in a release of variou Cytokines and enzymes

27 Wegener s Granulomatosis Multiorgan systemic vasculitic syndrome Skin, lung, kidney, upper airways, and orbit Oral involvement: strawberry gums Mid line facial necrosis Probably a role for CMI Nasal S aureus may be implicated(homology with PR3) Main clinical features: Palpable purpura, cutaneous ulcers, orbital swelling, sinusitis, renal dysfunction, dyspnea and hemoptysis Isolated WG: skin, orbit, lung or sinuses

28 Clinical Images Courtesy Dr. Carl Allen Ohio State University

29 Wegener s Granulomatosis Small vessel vasculitis which may be granulomatous or neutrophilic in subtype Neutrophilic and granulomatous inflammation with variable tissue necrosis Palisading granuloma of Churg Strauss In isolated organ Wegener s granulomatosis the commonest tissue expression of the disease process is one of extravascular inflammation comprising neutrophils and histiocytes

30 Courtesy Of Dr. Carl Allen

32 Dr. Carl Allen Oral Patholog OSU

33 During active and recurrent disease There are increased numbers of T cells Manifesting a Th1 Dominant cytokine profile Are T cells specific for PR3?

34 Allergic granulomatosis of Churg and Strauss Clinical Features A systemic small vessel vasculitic syndrome in the setting of an atopic diathesis (MPO positive in less than 50% of cases) (1) a history of asthma, (2) eosinophilia > 10%, (3) mononeuropathy or polyneuropathy, (4) nonfixed pulmonary infiltrates, (5) paranasal sinus abnormalities (6) biopsy showing extravascular eosinophils To render a diagnosis requires 4 of the 6 criteria listed above

35 AGCS Prodromal phase(years): asthma, allergic rhinitis sinonasal polyposis Second phase: PBE, eosinophilic tissue infiltrates The third phase: systemic vasculitis (i.e. polyneuropathy). Main affected organs: GI tract, heart, skin, paranasal sinuses, lungs, and peripheral nervous system Two broad categories:anca +(NGN, cutaneous vasculitis, Mononeuritis vs negative ANCA (tissue eosinophilia with cardiomyopathy

36 Allergic granulomatosis of Churg and Strauss : Pathology and pathophysiology Inciting Trigger: inhaled allergens, desensitization shots and infection Pathology: Vasculitis with dominant involvement of small arteries and venules (MPO ANCA cases LCV while ANCA- may show an eosinophilic vasculopathy ) Palisading Churg-Strauss granuloma Tissue eosinophilia

37 Ref: Bacciu A et al. Ear nose And thorat manifestations Of Churg Strauss. Acta Oto-Laryngologica 2006 Eosinophilic polyposis Necrotizing inflammation Eosinophilic vasculopathy Activated eosinophils releasing cytotoxic enzymes IgE immune complexes cause the tissue eosinophilia

38 ANCA PO+ ANCA MPO negative

39 Polyarteritis nodosa : Microscopic PAN Systemic necrotizing small vessel vasculitis, ; no extravascular inflammation Male preponderance Onset of illness fever, maliase, arthralgias, anorexia, weight loss (constitutional symptoms may antedate the vasculitis for years) Renal involvement major feature(necrotizing GN) Lung involvement 50% Upper respiratory tract 33% less than in AGCS and WG Mononeuritis multiplex PANCA with MPO specificity in the majority of cases; at times dual specificity with CANCA at lower titers

40 Nonangiocentric Mid line facial destruction Relapsing polychondritis Trigeminal Trophic ulcer Ozena

41 Relapsing Polychondritis Causes considerable nasal destruction attributable to antibodies to type II collagen and chondrocytes resulting in cartilage damage; trachea, heart valves and various joints May be a paraneoplastic disorder associated with tumors of the bladder, breast, bronchus, colon, lung, pancreas, rectum and vocal cords although the most common underlying neoplasia is one of lymphoreticular and myeloid dyscrasia Mouth + genital ulcers, inflamed cartilage: MAGIC syndrome(rp BD overlap)

42 Antibody-Mediated Chondrocyte Necrosis End Stage BOS showing Zones of Cartilage Disappearance Resembling Relapsing Polychondritis

43 Trigeminal Trophic Syndrome Crescent shaped ulcer involving the ala and nostrils extending onto the cheek and upper lip with sparing of the nasal tip Temporal association between an iatrogenic insult to the trigeminal ganglia done to control trigeminal pain In most cases there is surgical removal of the Gasserian ganglion Median time of 1 year between surgery and ulcer development Self mutilation may be an additional factor

44 Rashid RM and Khachemoune A Trigeminal Trophic Syndrome Journal of the European Academy of Dermatology And Venereology 2007

45 Ozena Atrophic rhinitis Widened nasal cavities Severe intranasal crusting Fetid intranasal green secretions Nasal obstruction Severe and progressive wasting of the nasal bones Etiology: widened nasal cavities leads to excessive evaporation of moisture

46 Lymphomatoid Granulomatosis Angiocentric and angiodestructive lesion involving the lungs and extranodal sites including oral cavity and upper respiratory tract, CNS and skin First described in 1972 as a form of angiodestructive polymorphic inflammatory response indeterminate in regards to biological behavior Lipford and Jaffe coined the term angiocentric immunoproliferative lesions(grade I-III) Immune dysregulation: Wiskott Aldrich syndrome and following transplantation

47 Lymphomatoid Granulomatosis The earlier phases of LYG is a reactive CD4 dominant angiocentric infiltrate responding to a variable number of EBV infected transformed large B cells(grade I and II) Tissue injury occurs early in the disease due to striking nature of the reactive but dysregulated angiocentric inflammation With disease progression the infected EBV positive B cells evolve to a large cell B cell lymphoma defining an extranodal angiocentric B cell lymphoma(grade III) T and or B cell clonality can be seen

50 CD4 CD8

51 Transition Into Large cell B cell lymphomna EBER

52 Courtesy Of Dr. Carl Allen, OSU Oral Pathology

53 Courtesy of Dr. Carl Allen OSU Oral Pathology

54 EBER CD20

55 Natural Killer(NK) Cell and NK-like T cell Lymphomas Aggressive lymphoma nasal (lethal midline granuloma), nasal type(oftentimes primary in the skin and aggressive (rarely involves the skin) (survival 10 to 30%) CD2/CD56+(other NK markers like CD16 and CD57-),CD4-,CD8-, no surface CD3 or TCR define, BF1- NK lymphomas, often EBER related CD2, CD56 +, surface/ cytoplasmic CD3+, CD4-CD8- /CD4-CD8+with TCR rearrangement define NK like T cell lymphomas(not EBER related)

58 EBER CD56

60 CD3 cytoplasmic membrane staining CD3 intracytoplasmic staining

61 Conclusion A broad spectrum of angiocentric inflammatory, toxic nonimmunogenic and neoplastic events can eventuate into a relatively homogeneous clinical presentation despite a varied histopathology An appreciation of the morphologic nuances and its pathophysiologic basis is critical to the establishment of the correct diagnosis, a pivotal determinant in patient management and outcome

SHO Teaching. Dr. Amir Bhanji Consultant Nephrologist, Q.A hospital, Portsmouth

SHO Teaching. Dr. Amir Bhanji Consultant Nephrologist, Q.A hospital, Portsmouth SHO Teaching Vasculitis Renal medicine Dr. Amir Bhanji Consultant Nephrologist, Q.A hospital, Portsmouth OUTLINE What is vasculitis Causes Classification Brief look into ANCA Associated Vasculitis (AAV)