ࡱ> qsp7 QbjbjUU "~7|7|MlHHHHHHH\\y;}}}:::::::$/< O>n;H}}}}};}HH3;}}}}HH:}}:}"}#4HH6 [}%\}56I;0y;56>}>6}\\HHHH Dermatopathology1. Premalignant & Malignant Epithelial TumorsActinic Keratosis: epith. dysplasia introduced by UVR; more common in fair skinned people; UVR damages keratinocyte DNA (poss. Langerhanss cells) Gross: rough, red w/ indistinct borders Micro: epith. dyplasia in lower1/3 of epidermis; solar elastosis in dermis Comment: can become SCC; may regress; treat early b/c of unknown progression Squamous Cell Carcinoma (SCC): most arise from AKs; carcinogens, chronic ulcers; scars, arsenic, HPV, and radiation can also be factors; individuals w/ DNA repair defects and/or imm.supp. (i.e. transplant) are at greater risk G: flesh colored to red; often scaly; CIS (Bowens) often presents as scaly erythematous plaque resembling psoriasis M: Nodular proliferation of dysplastic keratinocytes; fingers of tumor may infiltrate derm.; CIS replaces epid. w/ atyp. keratinocyte C: UV induced SCC of skin rarely (5%) metastasizes to regional nodes; other precursors (i.e.scars) = more aggressive; actinic SCC of mucous membrane = more likely to metastasize Basal Cell Carcinoma (BCC): most common cancer; rarely metastasizes but is hematogenous; occurs on sun exposed areas but is not as directly related as SCC G&M: Three presentations: 1. Noduloulcerative: translucent telangiectatic papule +/- ulcer; nodular prolif. of basaloid cells in a fibromucinous stroma, may have infiltrating tumor at the deep aspects of the tumor 2. Superficial: scaley red patch; mult. buds of basaloid tumor cells along derm/epiderm jxn 3. Sclerosing: scar-like plaque; infiltrating slender strands of basaloid tumor cells in fibrous stroma -all tend to show peripheral nuclear palisading C: Patients w/ basal cell nevus syndrome may have hundreds of tiny BCCs; some lesions may become quite destructive if ignored; other signs of this phenotype include frontal losing jaw, cysts, and bifid ribs; these pts. have PTC gene mutations. Merkel Cell Carcinoma: rare cutaneous neuroendocrine CA that may be lethal or mistaken for BCC Melanoma: may also occur on mucosal surfaces, leptomeninges, uveal tract of eye; sunlight is only 1 factor; genetics can play a role (i.e. dysplastic nevus syndrome) G: ABCDs: Asymmetry, Border irregularity, Color heterogenieity, Diameter > 6mm M: Growth phases: Radial (cant metastasize) 1. Pagetoid larger cells w/ buckshot scatter of atyp. cells at all levels of epid. 2. Lentiginous cells singly & in nests along derm/epider jxn; extend into appendages Vertical (tumorigenic-can metastasize) nodule of atypical cells growing into dermis C: 4 classic types: Superficial spreading (Pagetoid) Lentigo maligna Acral Lentiginous Nodular differs from other 3 b/c it has no radial phase; other have radial to vertical progression 2. Malignant Dermal TumorsDermatofibrosarcoma Protuberans (DFSP): one of many dermal and subcuticular sarcomas G: nodule or plaque (may be several cms) w/ nodules in it M: Storiform pattern; often infiltrates fat; clear surgical margins difficult, CD34 + C: rarely metastasize but are destructive (even larger than BCC) 3. Malignant Tumors of Cellular Immigrants to the SkinHistiocytosis X (Langerhans cells histiocytosis): several variants; book refers to Letterer-Siwe variant G: Letterer-Siwe disease often looks like seborrheic dermatitis with tiny hemangiomas M: Several patterns exist but at least some histiocytes are present (w/ foam cytoplasm); eosinos & Lycs are also present; the characteristic cell contains organelles called Birbeck Granules and marks w/ S-100 protein and CD1a Cutaneous T-Cell Lymphoma (CTCL): skin involvement w/ poss. leukemia G: several presentations including: red scaly patches; plaques and nodules; diffuse itchy red scaly skin M: due to clonal prolif. of malignant CD4 positive Lycs (Sezary-Lutzner cells clusters of these cells = Pautrier micro-abscesses) C: Mycosis fungiodes = CTCL w/ patches or plaques and or nodules(tumors) Erythroderma + Leukemia = Sezary Syndrome 4. Disorders of Pigmentation and MelanocytesVitiligo: patchy hypo/depigmentation due to malanocyte damage/loss (unknown mech.); albinism = absence of tyrosinose Freckle (ephilis): tan-brown macules on sun-exposed skin M: hyperpigmentation of rete; NO proliferation of melanocytes (unknown mech.) Melasma: patchy facial and neck hyperpigmentation (often mask-like) M: Epidermal type has hyperpigmented basal layer of keratinocytes; Dermal type has incontinent melanin in papillary dermis C: cause = Hms?; classically occurs w/ pregnancy (Mask of Pregnancy) Lentigo = Melanocytic Nevi 5. Benign Epithelial TumorsSeborrheic Keratosis (SK): benign keratinocyte prolif. in mid-older people G: rough (warty); flesh colored to brown/black; on trunk; looks Stuck on M: proliferation of basaloid keratinocytes, may be squamoid; cystic foci of lamellated keratin (horn pseudocyst) C: tiny dark SKs on face of darker skinned people are called Dermatosis Papulosa Nigra; rapid occurrence of large #s of SKs may be assoc. w/ internal malignancy (Leser-Trelat sign) Acanthosis Nigricans: common in obese young-mid aged people; may signify hyperinsulinemia (->Type II DM); may actually be easier to see on extensor surfaces of joints, elbows, knees, toes, than on neck; skin is folded rather than thickened. Fibroepithelial Polyps (aka skin tag, acrochondron, squamous papilloma): may be assoc. w/ acanthosis nigricans and DM; some on the neck may have thick SK-like epith. while others may have a more fibrous core. Epitheloid Cysts: 90% of all cutaneous cysts; most from follicular infundibulum; epidermal inclusion cysts due to injury do occur; acne cysts are epidermoid cysts G: dome shaped nodule w/ poral opening fixed to epidermis; may be multiple M: wall and cyst keratin look like surface skin Trichilemmal (Pilar) Cysts: about 10% of cysts; mainly on scalp; multiple ones inherited as AD trait (women) G: dome shaped papule fixed to epidermis; NO pore; may be firmer M: lining like middle part of hair follicle; pink homogenous keratin Dermoid Cysts: rare but most common on face of infant; lined like epidermoid cyst but have tiny hair follicle elements (sebaceous) Steatocystoma: single or multiple oily centered w/ sebaceous glands in wall; on trunks of teenagers and older people Keratoancanthoma: self healing squamous cell carcinoma; classic type is a rapidly growing nodule w/ a keratin filled center Appendage tumors: flesh colored papules and nodules: table 27-2, p.1183 Nevocellular Nevi: melanocytic nevi are benign tumors of melanocytes; may go thru many forms in life cycle; Mole is the common term for melanocytic nevus; types of nevi have general areas of occurrence; most fair-skinned people get 40 or so moles in a lifetime (few after age 40); UVR seems to play a role G& M: Lentigo simplex = 1-2mm brown/black macule - hyperpig., ( #s of melanocytes at tips of rete ridges Junctional nevus = 2-3mm (distal extremities) clusters of melanocytes and hyperpig. at tips of rete Compound nevus = 3-5mm brown papule (trunk and prox. extremities) clusters of same and nests/sheets/strands of nml Intradermal nevus = 3-5mm flesh colored papule (face) junctional component disappears leaving the dermal component; older lesions may resemble neurofibromas or be fat infiltrated -cytological atypia is absent C: some variants on the theme of melanocytic nevus are on P. 1176 Dysplastic Nevi: poss. a percusor for melanoma esp. in patients w/ dysplastic nevus syndrome (rare AD trait in which people develop large #s of dysplastic nevi in late childhood); felt to be abbherant differentiation of common nevi; sporadic occurences mean nothing. G: predominately on trunk and prox. extremities; larger than common nevi and have some border and color irregularities M: may be junctinal or compound; lentiginous proliferation of melanocytes singly and in nests; lateral bridging of one rete to another; concentric and lamellar dermal fibrosis; patchy lymphocytic infiltrate at base of melanocytic proliferation; +/- cellular atypia 6. Benign Dermal NeoplasmsBenign Fibrous Histiocytoma (Dermatofibroma, DF) may not be a true neoplasm G: Firm dermal papule that indents when pressed on sides (dimple sign); reddish tan to brown/black; most commonly occur on womens legs; may be mult.; assymp. M: more or less circumscribed proliferation of spindled fibroblasts; may appear to trap normal collagen bundles; some foamy macros; CD 34 neg. Xanthomas: not neoplasms but collections of foamy macrophages often assoc. w/ hyperlipidemia; types include eruptive(fleshy), tuberous and tendinous(yellow nodules), plane(streaks), xanthelasma (eyelids may not be assoc. w/ hyperlipidemia) Cherry Angiomas: common tiny capillary hemangiomas in adults; no indication of internal disease Strawberry Hemangiomas: rapidly growing capillary hemangiomas in infants; may involute; particularily likely to have internal organ involvement if mult. lesions aare presentBenign Tumor of Cellular Imigrants to the SkinMastocytosis: Variants: 1. Mastocytoma: one or a few lesions; localized dermal nodule of mast cell infiltration; urticate, blister if rubbed (Darier sign); involutes eventually Urticaria pigmentosa: lesions like mastocytomas but usually slightly smaller/more numerous; tachycardia & diarrhea may occur to due release of hist. if rubbed vigorously Diffuse intracutaneous mastocytosis: diffuse skin infiltration w/ mast cells; diffuse edema causes skin to look like leather; concern exists for mast cell leukemia and organ involvement. Telangiectasia macularis eruptiva perstons: minimal ( in mast cells about dermal vessels; often no Derier sign; tan macules that may have telangiectasias on trunk; middle aged adults; most cells stain melachromatically (w/ Giesma and Toluidine blue) 7. Inflammatory Cutaneous DisordersIchthyosis: not really inflammatory; most are congenital/inherited -X-linked is due to def. of steroid sulfatase and prevents normal skin shedding; Acquired ichthyosis may be paraneoplastic Urticaria (Hives): allergic(Type I IgE mediated hypersensitivity) and non-allergic forms exist G: lesion is an edematous plaque that is called a wheal; usually w/ intense pruritus; usually gone w/in 24hrs; swelling of lip or eyelid = angioedema M: edema of the upper reticular dermis w/ minimal inflamm. infiltrate (if chronic may see eosinophils) C: all wheels are not urticaria; vasculitis, bullous impetigo, etc. also present w. wheals Dermatitis: 3 clinical presentations: 1. Acute = erythema, blisters, pruritus 2. Subacute = erythema, oozing, crustying, early scale formation, pruritus 3. Chronic = erythema, scaling, pruritus - other dermatitis are on table 27-3 (p. 1195) - allergic contact dermatitis is Type IV (cell mediated immunity); blisters are due to extreme spongiosis (intercellular edema) in epid. Erythema Multiforme (EM): EM minor assoc. w/ herpes simplex; EM major: Stevens Johnson Syn (SJS) wide spread severe disease w/ mucus membrane involvment and assoc. w/ allergic rxn to drugs or mycoplasma infxns (7-10 days) Toxic Epidermal Necrolysis explosive severe skin and mm damage w/ same causes (overnight) G: all three variants characterized by wheals, target lesions (true wheals w/ necrotic blistered center) and blisters; mm damage-major M: minimal cellular (Lyc) infiltrate; vacuolar alteration along the BM zone; Dead keratinocytes in the epid. sometimes to the point of full thickness epith. necrosis; similar histopathology occurs in GVHD and fixed drug eruption Psoriasis: common scaling dermatosis; may be assoc. w/ arthritis; Variants include: classic plaque (mica-like silvery); guttate (eruptive process w/ small scaly papules assoc w/ strep pyogenes); erythrodermic (red scaly skin); pustular (pustules in red plaques); pinpoint bleeding when scale is removed is Auspitz sign; nail dystrophies = 30% of patients M: regular acanthosis w/o spongiosis; parakeratotic scale; collections of PMNs in the epidermal living layer (spongiform pustule) and stratum corneum (Munros microabscesses) are pathognomonic. C: the Koebner phenomenonon = development of psoriasis at a site of non-specific trauma; psoriasis tend to be AD inheritance Lichen Planus: pruritic self-limited but potentially protracted disorder of skin and mm G: Violaceous papules (irregular, purple); fine grey-white lines on papules are called Wichham stria; mm has lacey white lesions M: dense band-like lymphocytic infiltrate obscures dermal-epid. jn (DEJ); irregular (saw-tooth) rete ridges; dead keratocysts (Civatte bodies) at DEJ; orthokeratotic hyperkeratosis C: may be assoc. w/ Hep C; malignant degeneration (SCC) may develop in chronic mm lesions; Koebner pheno. (lines) may occur Lupus Erythematosus: autoimmune connective tissue d/o; Localized (cutaneous) and multiorgan (SLE) forms exist G: sharply demarcated hyperkeratotic lesions (DLE); can be widely spread mainly on malar eminences (sun-exposed) w/ SLE M: superficial and deep periappendageal and pervascular lymphocytic infiltrate; vacuolar alteration along DEJ w/ BMZ thickening; necrotic keratinocytes in epidermis; varying amounts of mucin; granular DEJ band of Ig and complement on direct IMF C: positive lupus band on direct IMF; if band positive on non-sun exposed areas = more severe; ANA not pos. in skin-only cases Bullous Diseases: many skin diseases have a blistering component, some characteristic depending on site of blister cleavage plane; may be induced by autoimmune, friction, UVR, etc. Pemphigous group of Disorders: group of blistering d/o that may affect skin or mm; blisters are intraepidermal w/ acantholysis; due to antibodies to substances that hold cells together; several variants exist Vulgaris (80%): due to antibody to Desmoglein 3 (adhesin); mm lesions often proceed skin lesions; flaccid blisters on trunk, face, and prox. extremities; suprabasal blister; may become lethal Foliaceous: endemic in S. America, but also sporadic cases; crusty (intact blisters rare); mm almost never involved Vegetans: hyperplastic lesions in intertriginous areas (axilla & groin); oozing and crusting w/o obvious blistering Erythematous: localized foliaceous; mainly on face; may be assoc. w/ SLE M: all have pos. direct IMF net wire pattern in epidermis on indirect; acantholytic keratinocytes float in blisters Bullous Pemphigoid (BP): Sub-epidermal blisters; tense blisters; patients older; mm involvement rare; due to antibodies to BMZ M: sub-epidermal blisters often contain eosinophils; fine BMZ band of complement and sometimes Ig Dermatitis Herpetiformis (DH): a blistering disease assoc. w/ gluten sensitivity but only rarely w/ enteropathy (GSE) G: grouped vesicles or erosions on an erythematous base on extensor surfaces; very pruritic M: micro abscesses of PMNs destroy dermal papillae; direct IMF shows granular deposits of IgA in dermal papillae C: HLA-B8 and HLA-DRw3 are often assoc. 8. Non-inflammatory Blistering DiseasesFriction Blisters: common; subcorneal split; high heat and moisture are predisposing factors Mechanobullous Disorders (Epidermolysis bullosa): diseases w/ genetic defects in elements nec. to hold skin together; several variants; blister w/ minimal frictional trauma Porphyria: due to genetic or acquired deficits in genes for enzymes,etc.; Porphyria Cutanea Tarda is the most common = blistering and scarring w/ milial cyst formation in sun-exposed areas (esp. hands), hypertrichosis of temples ((hair), often assoc. w/ hemochromatosis 9. Disorders of Epidermal AppendagesAcne Vulgaris: inflammatory d/o of sebaceous follicles; effects 80% of teenagers; initial lesions are non-inflamm. (comedomes); but papules, pustules, nodules, cysts, and scarring may ensue 10. Panniculitis: inflamm. of fat lobules or fibrous connective tissue septae in sub cutis (often on legs)Erythema Nodosum: really a septitis of unknown etiology commonly on skin; may be assoc. w/ strep., birth control pills, sarcoid, TB, etc.; lesions somewhat painful but almost never drain thru skin surface Erythema Induratum: more of an inflammation of fat lobules, commonly on post. legs; assoc. w. TB or unknown; may ulcerate 11. Infection and InfestationWarts: benign keratinocyte neoplasms cause by HPV (esp. types 16, 18, 31, 33, 35 assoc. w/ rare AR d/o called Epidermodysplasia Verruciformis); several variants Common: verrucous papules on most surfaces; may grow rapidly and bleed w/ minor trauma; show filiform epidermal projections w/ parakeratosis, dilated papillary capillaries and areas of large keratohyaline granules; few koilocytes possible Moist: occur on mms and in intertriginous areas; less verrucous; show a proliferation of keratinocytes w/ kocloyctosis Flat: slightly raised; maybe hyperpigmented; legs and face are common; may be spread by scratching; show min. keratinocyte proliferation w/ obvious koilocytosis Plantar: often show massive keratohaline-like granules Molluscum Contagiousum: caused by Pox virus (DNA); spread by physical contact and fomites G: 2-4mm papules w/ central dell (opening to a hair follicle); may be much larger if immunosuppressed M: can see cytoplasmic inclusion (molluscum bodies) in material expressed from lesion (35 microns); also present on biopsy C: topical steroids may actually encourage spreading in patients w/ atopic dermatitis Impetigo: Bullous from caused by Staph. aureus; group A Strep may also be present (erythema at edges of crusted lesion seen); cutaneous strains of strep have been known to be nephritogenic also; Bullous form has acantholytic dermal cells, staph., and PMNs in a sub-corneal blisterSuperficial Fungal Infections: 3 genera: Dermatophytes = Trichophyton, Epidermophyton, and Microsporum -Onchomycosis = infxn of nails; but includes all genera not just these 3 -Tinea versicolor is caused by Malassezia furfur (hyper and hypo-pigmented patches on trunk) -Fungal wall stains w/ PAS are usefuls (as is KOH) Arthopod Bites, Stings, and Infestations (see book) Pediculosis: louse infestation due to Head-capitis, Body-Vagabonds disease, or Pubic-crabs; lice are blood feeders and bites may become infected Scabies (Sarcoptes scabiei var hominis): burrows in skin at stratum corneum; spreads by repeated physical contact; 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