Presentation on theme: "Monocyte/Macrophage Disorders"— Presentation transcript:
1 Monocyte/Macrophage Disorders Northeast Regional Medical Center/KCOM
2 Granuloma Annulare Localized Generalized Macular Deep Perforating In HIVIn Lymphoma
3 Granuloma Annulare Common, Idiopathic, all races 50% patients IgM and C3 in vesselsLCV changes sometimes seenSuggests Ab mediated vasculitisCommon in HIV patientsEBV sometimes foundOccurs in resolved lesions Zoster
4 GA - HistologyClassic – histiocytes palisading around “necrobiotic” collagen. Granulomas located in the upper dermis with perivascular lymphocytic infiltrateNecrobiosis – “altered” collagen, paler grayer hue, fragmented, haphazardly arranged, more compact.Mucin prominent in older lesions.
5 GA- HistologyInterstitial – diffuse dermal infiltrate between collagen bundles consisting of histiocytes, monocytes, neutrophils.“Skip” areas of normal dermis seen.Interstitial mucin often seen.May be adjacent to classic granulomas
6 Interstitial GA NLD Upper dermis “Skip areas” Mucin Deep dermis, subQ No “skip” areasNo mucin
23 Subcutaneous GA Aka Deep, Pseudorheumatoid Nodule MC children, boys > girls 2:1MC ages 5-12.Acral distributionHistory of trauma preceding lesionAsymptomatic but often an extensive workup is done to rule out JRA.
36 Granuloma Mulitforme of Leiker Similar histology to AEGCG & AGOBOnly Central Africa, Adults > 40 yrs old.Upper Trunk and ArmsBegin as small papules, expand into round or oval plaques 15cm wide and as much as 4mm in height.Must rule out tuberculoid leprosy.
38 Sarcoidosis Multisystem Disease Lungs, lymph nodes, skin and eyes MC. 10x more frequent in blacks in USWomen under age 40Irish, African, Afro-Caribbean.Presence inversely proportional to the incidence of TB and/or Leprosy.
39 Sarcoidosis Etiology unknown HLA-A1 – Lofgren’s syndrome HLA-B13 – Chronic & Persistent formHLA-B8HLA-DR3Final common pathway is granuloma formation
40 NON-CASEATING GRANULOMAS COMPOSED OF EPITHELIOID CELLS AND OCCASIONAL LANGERHAN’S GIANT CELLS
41 “NAKED” GRANULOMAS“NAKED” meanse a sparse rather than a dense infiltrate. Lymphocytes, macrophages & fibroblasts may occur
43 Asteroid Body inside a multinucleated giant cell
44 SCHAUMANN OR CONCHOIDAL BODIES ARE COMPOSED OF CALCIUM CARBONATE SCHAUMANN OR CONCHOIDAL BODIES ARE COMPOSED OF CALCIUM CARBONATE. THEY ARE EASILY MISSED (LEFT) IF NOT VIEWED UNDER POLARIZED LIGHT (RIGHT)
46 Sarcoid Skin Involvement Anywhere from 9% to 37% of cases.2 types: specific and non-specificSpecific: granulomas on biopsyNon-Specific: reactive, Erythema NodosumSkin findings may occur before, during or after systemic findings.
47 Sarcoid – like syphillis, mimics many other dz’s Papules, nodules, plaques.Subcutaneous nodules.Scar sarcoid, erythroderma.Ulcerations, verrucous.Ichthyosiform, hypomelanotic
48 Papular Sarcoid MC form AKA Miliary Sarcoid Face, eyelids, neck, shouldersMay involute to maculesDdx: syringomas
79 Mikulicz’s Syndrome Sarcoidosis with enlargement of the; Lacrimal glandsSubmaxillary and Parotid glands.Problematic: numerous conditions involving enlarged partoid glands have since been named after Dr. Mikulicz.
87 Juvenile Xanthogranuloma (JXG) MC Non-Langerhans’ histiocytosis1st year of life, usu. white males80% are solitary, well demarcated, firm, rubbery red to pink with yellow tingeRegress in 3-6 years with atrophy.Ocular involvement rare, MC irisAssoc. with NF-1 and JCML
89 JXG Histopathology Non-encapsulated Infiltrate in the upper and mid reticular dermisMononuclear cells with abundant amphophilic cytoplasm that is poorly lipidized or vacuolated.
90 MULTINUCLEATED “FOAM” CELLS aka TOUTON GIANT CELLS ALONG WITH EOS, NEUTS, LYMPHS. STAINS:+ CD1+ FACTORXIIIa- S100
91 Benign Cephalic Histiocytosis RareMales 2:1, Onset 6-12 months of ageBegins on head, cheeks, spreads to neck and upper trunkMultiple reddish yellow papules 2-3mm, may coalesce into a reticulate pattern.Involute over 2 to 8 years with atrophy
93 Reticulohistiocytosis Solitary form – aka Reticulohistiocytic Granuloma or ReticulohistiocytomaSolitary form has no systemic involvementMulticentric form – aka Multicentric ReticulohistiocytosisUnderlying malignancy in 30%
95 Reticulohistiocytic Granuloma: Multinucleate Giant Cells, Histiocytes, Lymphocytes with some stroma fibrosis
96 Multicentric Reticulohistiocytosis Multisystem disease, 5th decade, F>M.90% Face & hands, red-brown papules and nodulesParonychia: “coral bead” appearanceJoints symmetrically involved with mutilating arthritis, telescoping shortening of digits, doigts en lorgnette, opera-glass fingers, RF is negative1/3 have high cholesterol, xanthelasma
100 Tx: Multicentric Reticulohisticytosis Treatment is problematic because mutilating arthritis requires immunosuppressive therapy.Immunosuppressive therapy can worsen underlying malignanciesPrednisone, Antimalarials, MTX, Cytoxan, PUVA, Nitrogen mustard.
101 Generalized Eruptive Histiocytoma Widespread symmetric papules, trunk and proximal extremities, come in cropsProgressive development of new lesions over several years with eventual spontaneous involution to hyper-pigmented maculesFlesh, brown or violaceous papulesControversy: is this just xanthoma disseminatum? MRH? Indeterminate cell histiocytosis?
103 GENERALIZED ERUPTIVE HISTIOCYTOMA: DERMAL INFILTRATE OF NON-LIPIDIZED MONONUCLEAR HISTIOCYTES, S-100 IS NEGATIVE
104 GENERALIZED ERUPTIVE HISTIOCYTOMA: DERMAL INFILTRATE OF NON-LIPIDIZED MONONUCLEAR HISTIOCYTES, S-100 IS NEGATIVE
105 Necrobiotic Xanthogranuloma (NXG) Multisystem disease of older adultsCharacteristic periorbital yellow plaques that resemble xanthelasmas except that they are deep, firm, indurated and may extend into the orbitTrunk & proximal extremity lesions are orange-red plaques with an active red border and an atrophic border with superficial telangiectiasias.
106 NXG: Periorbital yellow plaques that resemble xanthelasmas except that they are deep, firm, indurated, may involve the orbit
107 NXG: Trunk & proximal extremity lesions are orange-red plaques w/ active red border & an atrophic border with superficial telangiectasias
108 NXG: conjunctivitis, keratitis, scleritis, uveitis, iritis, ectropion or proptosis
109 NXG: Process extends into the fat, obliterating fat lobules NXG: Process extends into the fat, obliterating fat lobules. Extensive zones of degenerated collagen or “necrobiosis” surrounded by palisaded macrophages.
110 NXG: Foam Cells with abundant infiltrate of lymphocytes, plasma cells
112 NXG and Malignancy 80% IgG monoclonal paraproteinemia (Kappa) Bone marrow may show plasmacytosis, anemia, leukopenia, myeloma, myelodysplastic syndromes.Cause unknown, course progressiveTreat aimed at paraproteinemia: Melaphan, Chlorambucil, Corticosteroids, Plasmapheresis, Alpha Interferon-2b
113 Xanthoma Disseminatum Serum lipids are normal, MC young malesMucocutaneous, discreet, disseminatedIntertriginous distributionDiabetes Insipidus 40% due to xanthomatous infiltration of the pituitary gland.Chronic and Benign, may persist, may involute spontaneously after some years
117 Papular Xanthoma Small yellowish papules Localized or generalized No tendency to merge into plaquesAggregates of foam cells in the dermis without a cellular or histiocytic phaseAbsence of inflammatory cells.
118 Indeterminate Cell Histiocytosis Dermal precursors of Langerhan’s cellsS-100 positiveCD1 positiveNO BIRBECK GRANULES!Chronic without spontaneous involutionNo systemic involvement
119 Progressive Nodular Histiocytosis Superficial papules & deeper nodulesDiffuse, symmetrical, non-flexural.Larger lesions may ulcerate, become painfulFace lesions may coalesce into leonine faciesGeneral health is good
120 Progressive Nodular Histiocytosis Histo: DF-like, few Toutons, lacks the PAS+ ground glass giant cells of MRH.Stains positive for Vimentin, CD68, Factor XIIIaStains negative for S-100 and CD34
121 Hereditary Progressive Mucinous Histiocytosis in Women AD or X-linkedFew to numerous flesh to red-brown papules up to 5mm in diameterFace, arms, forearms, hands, legsOnset 2nd decadeSlow progression, no tendency to spontaneous involution, no systemic involvement
122 Hereditary Progressive Mucinous Histiocytosis in Women May histologically differentiate from other non-X histiocytoses as follows:Familial patternAbundant mucin + Alcian blue stainingLack of lipidized and multinucleated cells
123 Rosai-Dorfman Disease Aka Sinus Histiocytosis with Massive LymphadenopathyOnset 1st or 2nd decade of lifeFever, massive cervical LAD, polyclonal hyperglobulinemia, leukocytosis, anemia, elevated SED rate.Males and blacks MC.Skin involvement in 43% of casesMost patients with skin lesions are > age 40
124 Rosai-Dorfman Disease Isolated or disseminated yellow-brown papules or nodules, or macular erythema. Large annular lesions resembling GA may occur.HHV-6 identified in numerous reports.May clear spontaneouslySkin biopsy non-specific unless emperipolesis is present but lymph node pathology is characteristic…..
125 Rosai-Dorfman Disease – LN Biopsy Expansion of the sinuses by large foamy histiocytes admixed with plasma cellsCD4, Factor XIIIa and S-100 positiveNo Birbeck granules
129 Sea-Blue Histiocytosis Familial or AcquiredCharacteristic and diagnostic cell is a histiocyte containing cytoplasmic granules that stain as follows:Blue-green with GeimsaBlue with May-Gruenwald
130 Sea-Blue Histiocytosis Lesions include papules, eyelid swelling and patchy gray pigmentation of the face and upper trunk.Infiltrates marrow, spleen, liver, lymph nodes, lungs and skin in some cases.Similar findings seen in patients with Myelogenous leukemia and Neimann-Pick Disease, and following prolonged use of IV fat supplementation
133 Hashimoto-Pritzker Onset: birth or very soon thereafter Solitary or multinodularRed, brown, pink or duskyLesions > 1 cm characteristically ulcerate as they resolveAsymptomatic, resolves in 8 to 24 weeks
141 H-P MANAGEMENT Must rule out Histiocytosis-X as both present similarly Rule out systemic involvement with physical exam, CBC, LFT, Bone survey.If any of the above are abnormal, consider liver-spleen scan and bone marrow biopsy.
142 Histiocytosis X Proliferation of Langerhans’ cells MC-Bone, Skin, Lymph, Lungs, Liver and Spleen, Endocrine glands, CNS.Children age 1-4 years oldLymphs are clonal, but not as atypical appearing as lymphoma cells – debate as to whether this is neoplastic v. reactive
143 Histiocytosis X RESTRICTED TYPES: A) Biopsy proven skin rash without other involvementB) Monostotic lesions, with or without diabetes insipidus, LAD or rashC) Polyostotic lesions with or without diabetes insipidus, LAD or rash.
144 Histiocytosis X EXTENSIVE TYPE: A) Visceral involvement with or without bone lesions, diabetes insipidus, LAD or rash but WITHOUTsigns of organ dysfunction of lung, liver or hematopoetic systemB) Visceral involvement with or without bone lesions, diabetes insipidus, LAD or rash but WITH signs of organ dysfunction.
145 Histiocytosis X Distribution MC is Letterer-Siwe: Tiny red, red-brown or yellow papules that are widespread but favor the intertriginous areas, behind ears and scalp.Lesions may erode or weep.In children, LS distribution is assoc. with multisystem disease, but in adults 25% have disease limited to skin only.