monocyte/macrophage disorders northeast regional medical center/kcom
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Monocyte/Macrophage Disorders
Northeast Regional Medical Center/KCOM
Granuloma Annulare
Localized
Generalized
Macular
Deep
Perforating
In HIV
In Lymphoma
Granuloma Annulare
Common, Idiopathic, all races
50% patients IgM and C3 in vessels
LCV changes sometimes seen
Suggests Ab mediated vasculitis
Common in HIV patients
EBV sometimes found
Occurs in resolved lesions Zoster
GA - Histology
Classic – 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.
GA- Histology
Interstitial – 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
Interstitial GA
Upper dermis
“Skip areas”
Mucin
Deep dermis, subQ
No “skip” areas
No mucin
NLD
Localized GA
Young adults
Acral
Annular, scalloped
White or pink flat topped papules spread peripherally
75% clear in 2 yrs
25% last 8 yrs
Diffuse GA
MC women past middle age
Diabetes reported in 20% cases
MC neck, upper trunk, shoulders
MC form of GA seen in HIV.
Clears spontaneously in 3-4 years.
Difficult to treat.
Subcutaneous GA
Aka Deep, Pseudorheumatoid Nodule
MC children, boys > girls 2:1
MC ages 5-12.
Acral distribution
History of trauma preceding lesion
Asymptomatic but often an extensive workup is done to rule out JRA.
Perforating GA
MC dorsum of hands
Papules with central keratotic core
Core represents transdermal elimination of degenerated or “necrobiotic” material in center of palisaded histiocytes.
GA in HIV disease
GA may occur at all phases of HIV disease.
Typically papular lesions
60% Diffuse, 40% Localized
Photodistributed and perforating lesions may occur
GA and Lymphoma
Rare
Atypical presentation:
Facial or Palmar
Painful
Any type of lymphoma can occur.
Lymphoma may occur before or after the GA.
GA- Treatment
Biopsy, IL, Cryo, topical Vit. E, Excision
GENERALIZED: Problematic
Oral steroids, high dose but high relapse rate – diabetes complicates
Dapsone, Nicotinomide, SSKI, Cyclosporine, Accutane.
Annular Elastolytic Giant Cell Granuloma of Meischer/Actinic
Granuloma of O’Brien
Annular Elastolytic Giant Cell Granuloma of Meischer/Actinic
Granuloma of O’Brien
Variants of GA.
AEGCG – solitary atrophic thin yellow plaque on the forehead, NLD-like.
AGOB – Photo- distribution, papules and plaques
Histo: Like GA, but with Giant Cells, Elastophagocytosis
Histo: Like GA, but with Giant Cells, Elastophagocytosis
Histo: Like GA, but with Giant
Cells, Elastophago-
cytosis
Photoexacerbated GA
Granuloma Mulitforme of Leiker
Similar histology to AEGCG & AGOB
Only Central Africa, Adults > 40 yrs old.
Upper Trunk and Arms
Begin as small papules, expand into round or oval plaques 15cm wide and as much as 4mm in height.
Must rule out tuberculoid leprosy.
Granuloma Mulitforme of Leiker
Sarcoidosis
Multisystem Disease
Lungs, lymph nodes, skin and eyes MC.
10x more frequent in blacks in US
Women under age 40
Irish, African, Afro-Caribbean.
Presence inversely proportional to the incidence of TB and/or Leprosy.
Sarcoidosis
Etiology unknown
HLA-A1 – Lofgren’s syndrome
HLA-B13 – Chronic & Persistent form
HLA-B8
HLA-DR3
Final common pathway is granuloma formation
NON-CASEATING GRANULOMAS COMPOSED OF EPITHELIOID CELLS AND OCCASIONAL LANGERHAN’S GIANT CELLS
“NAKED” GRANULOMAS
“NAKED” meanse a sparse rather than a dense infiltrate. Lymphocytes, macrophages & fibroblasts may occur
Asteroid Body inside a multinucleated giant cell
SCHAUMANN OR CONCHOIDAL BODIES ARE COMPOSED OF CALCIUM CARBONATE. THEY ARE EASILY MISSED (LEFT) IF NOT VIEWED UNDER POLARIZED LIGHT (RIGHT)
Sarcoidosis AKA….
Besnier-Boeck-Schaumann Disease
Boeck’s sarcoid
Besnier’s lupus pernio
Schaumann’s benign lymphogranulomatosis
Sarcoid Skin Involvement
Anywhere from 9% to 37% of cases.
2 types: specific and non-specific
Specific: granulomas on biopsy
Non-Specific: reactive, Erythema Nodosum
Skin findings may occur before, during or after systemic findings.
Sarcoid – like syphillis, mimics many other dz’sPapules, nodules, plaques.
Subcutaneous nodules.
Scar sarcoid, erythroderma.
Ulcerations, verrucous.
Ichthyosiform, hypomelanotic
Papular Sarcoid
MC form
AKA Miliary Sarcoid
Face, eyelids, neck, shoulders
May involute to macules
Ddx: syringomas
Papular Sarcoid
Papular Sarcoid
Papular Sarcoid
Papular Sarcoid
Annular SarcoidosisCentral clearing Hypo-pigment-ationAtrophyScarringFavor head & neckAssoc. with chronic sarcoidosis
Annular Sarcoidosis
Hypopigmented Sarcoid
May be the earliest sign of sarcoidosis in blacks.
MC extremities
Visually macular, but often have a palpable dermal or subQ component in center of lesion
Hypopigmented Sarcoid
Lupus Pernio
Violaceous
Nose, cheeks, lips
Forehead, ears
43% associated with punched out bone lesions.
37% Ocular lesions
Nasal perforation
Punched-Out Lytic lesions, Bone Cysts
Ulcerative Sarcoidosis
Lupus Pernio
Lupus Pernio
Lupus Pernio
Lupus Pernio
Darier-Roussy Sarcoid5% or fewer of patients with sarcoidosis have subcutaneous nodules.
Darier-Roussy (SubQ)
Scar Sarcoid
Scar Sarcoid
Erythrodermic Sarcoid
Extremely Rare
Begins as erythematous patches that become confluent.
Ichthyosiform Sarcoid
Legs
Arms
No palpable component
Ichthyosiform Sarcoid
Alopecia
Occurs in 2 settings;
1) Existing plaques extend onto scalp.
--leads to permanent scarring.
2) Macular lesions appear on scalp resembling Alopecia Areata
--may be permanent or reversible
Morpheaform Sarcoid
Rare
Dermal Fibrosis
Simulates Morphea
Antimalarials may help.
Morpheaform Sarcoid
Morpheaform Sarcoid
Mucosal Sarcoid
Pinhead sized papules
Grouped or fused together to form a plaque.
Erythema Nodosum in Sarcoid
MC nonspecific cutaneous finding in sarcoidosis
Young females
Anterior shins
Good prognosis
Lofgren’s Syndrome = fever, arthralgias, hilar adenopathy, fatigue, EN
Systemic Sarcoidosis
MC – Lungs
Ocular 20-30%
Bones & Liver 20%, elevated Alk Phos.
Renal, Hypercalcemia
Heart, CNS, Spleen
Elevated ACE levels to follow disease activity only.
Heerfort’s Syndrome
Parotid gland enlargement
Lacrimal gland enlargement
Uveitis
Fever
Sarcoidosis
Mikulicz’s Syndrome
Sarcoidosis with enlargement of the;
Lacrimal glands
Submaxillary and Parotid glands.
Problematic: numerous conditions involving enlarged partoid glands have since been named after Dr. Mikulicz.
CXR- Hilar Adenopathy
Sarcoidosis in Fingers
Sarcoidosis in Fingers
CNS
Candle-wax drippings – granulomatous uveitis
Sarcoid - Treatment
Systemic Corticosteroids
Antimalarials
Methotrexate
Thalidomide
Non-X HistocytosesJuvenile Xanthogranuloma
Benign Cephalic Histiocytosis
Solitary/Multicentric Reticulohistiocytosis
Generalized Eruptive Histiocytoma
Necrobiotic Xanthogranuloma
Xanthoma Disseminatum
Papular Xanthoma
Indeterminate Cell Histiocytosis
Progressive Nodular Histiocytoma
Hereditary Progressive Mucinous Histiocytosis
Rosai-Dorfman Disease
Sea-Blue Histiocytosis
Juvenile Xanthogranuloma (JXG)
MC Non-Langerhans’ histiocytosis
1st year of life, usu. white males
80% are solitary, well demarcated, firm, rubbery red to pink with yellow tinge
Regress in 3-6 years with atrophy.
Ocular involvement rare, MC iris
Assoc. with NF-1 and JCML
JXG Histopathology
Non-encapsulatedInfiltrate in the upper and mid reticular dermisMononuclear cells with abundant amphophilic cytoplasm that is poorly lipidized or vacuolated.
MULTINUCLEATED “FOAM” CELLS aka TOUTON GIANT CELLS ALONG WITH EOS, NEUTS, LYMPHS.
STAINS:
+ CD1
+ FACTOR
XIIIa
- S100
Benign Cephalic Histiocytosis
Rare
Males 2:1, Onset 6-12 months of age
Begins on head, cheeks, spreads to neck and upper trunk
Multiple reddish yellow papules 2-3mm, may coalesce into a reticulate pattern.
Involute over 2 to 8 years with atrophy
BENIGN CEPHALIC HISTIOCYTOSIS
DIFFUSE DERMAL INFILTRATION OF NON-LIPIDIZED HISTIOCYTIC CELLS, S-100 NEGATIVE
Reticulohistiocytosis
Solitary form – aka Reticulohistiocytic Granuloma or Reticulohistiocytoma
Solitary form has no systemic involvement
Multicentric form – aka Multicentric Reticulohistiocytosis
Underlying malignancy in 30%
Reticulohistiocytic Granuloma
Reticulohistiocytic Granuloma: Multinucleate Giant Cells, Histiocytes, Lymphocytes with some stroma fibrosis
Multicentric Reticulohistiocytosis
Multisystem disease, 5th decade, F>M.
90% Face & hands, red-brown papules and nodules
Paronychia: “coral bead” appearance
Joints symmetrically involved with mutilating arthritis, telescoping shortening of digits, doigts en lorgnette, opera-glass fingers, RF is negative
1/3 have high cholesterol, xanthelasma
“Coral Bead” Paronychia
Classic Ground Glass Touton Giant Cells, PAS +
90% Face & Hands
Tx: Multicentric Reticulohisticytosis
Treatment is problematic because mutilating arthritis requires immunosuppressive therapy.
Immunosuppressive therapy can worsen underlying malignancies
Prednisone, Antimalarials, MTX, Cytoxan, PUVA, Nitrogen mustard.
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?
Generalized Eruptive Histiocytoma
GENERALIZED ERUPTIVE HISTIOCYTOMA:
DERMAL INFILTRATE OF NON-LIPIDIZED MONONUCLEAR HISTIOCYTES, S-100 IS NEGATIVE
GENERALIZED ERUPTIVE HISTIOCYTOMA:
DERMAL INFILTRATE OF NON-LIPIDIZED MONONUCLEAR HISTIOCYTES, S-100 IS NEGATIVE
Necrobiotic Xanthogranuloma (NXG)Multisystem disease of older adults
Characteristic periorbital yellow plaques that resemble xanthelasmas except that they are deep, firm, indurated and may extend into the orbit
Trunk & proximal extremity lesions are orange-red plaques with an active red border and an atrophic border with superficial telangiectiasias.
NXG: Periorbital yellow plaques that resemble xanthelasmas except that they are deep, firm, indurated, may involve the orbit
NXG: Trunk & proximal extremity lesions are orange-red plaques w/ active red border & an
atrophic border with superficial telangiectasias
NXG: conjunctivitis, keratitis, scleritis, uveitis, iritis, ectropion or proptosis
NXG: Process extends into the fat, obliterating fat lobules. Extensive zones of degenerated collagen or “necrobiosis” surrounded by palisaded macrophages.
NXG: Foam Cells with abundant infiltrate of lymphocytes, plasma cells
NXG: Cholesterol Clefts
NXG and Malignancy
80% IgG monoclonal paraproteinemia (Kappa)
Bone marrow may show plasmacytosis, anemia, leukopenia, myeloma, myelodysplastic syndromes.
Cause unknown, course progressive
Treat aimed at paraproteinemia: Melaphan, Chlorambucil, Corticosteroids, Plasmapheresis, Alpha Interferon-2b
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
XD - Periorbital
XD - Axillary
XD - Pathology
Xanthoma Cells
Eosinophilic Histiocytes
Numerous Touton giant cells
Inflammatory cell infiltrate usually present.
Papular Xanthoma
Small yellowish papules
Localized or generalized
No tendency to merge into plaques
Aggregates of foam cells in the dermis without a cellular or histiocytic phase
Absence of inflammatory cells.
Indeterminate Cell Histiocytosis
Dermal precursors of Langerhan’s cells
S-100 positive
CD1 positive
NO BIRBECK GRANULES!
Chronic without spontaneous involution
No systemic involvement
Progressive Nodular Histiocytosis
Superficial papules & deeper nodules
Diffuse, symmetrical, non-flexural.
Larger lesions may ulcerate, become painful
Face lesions may coalesce into leonine facies
General health is good
Progressive Nodular Histiocytosis
Histo: DF-like, few Toutons, lacks the PAS+ ground glass giant cells of MRH.
Stains positive for Vimentin, CD68, Factor XIIIa
Stains negative for S-100 and CD34
Hereditary Progressive Mucinous Histiocytosis in
WomenAD 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
Hereditary Progressive Mucinous Histiocytosis in
Women
May histologically differentiate from other non-X histiocytoses as follows:
Familial pattern
Abundant mucin + Alcian blue staining
Lack of lipidized and multinucleated cells
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
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…..
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
RDD - Emperipolesis – Histiocytes engulf plasma cells and lymphocytes
RDD - Emperipolesis
RDD - Treatment
Radiation
Chemotherapy
Systemic corticosteroids
Thalidomide
Sea-Blue Histiocytosis
Familial or Acquired
Characteristic and diagnostic cell is a histiocyte containing cytoplasmic granules that stain as follows:
Blue-green with Geimsa
Blue with May-Gruenwald
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
Sea-Blue Histiocytosis – Bone Marrow
X-type Histiocytoses
Hashimoto-Pritzker aka Congenital Self-Healing
Reticulohistiocytois
Histiocytosis X Aka Letterer-SiweAka Hand-Schuller ChristianAka Eosinophilic Granuloma
Hashimoto-Pritzker
Onset: birth or very soon thereafter
Solitary or multinodular
Red, brown, pink or dusky
Lesions > 1 cm characteristically ulcerate as they resolve
Asymptomatic, resolves in 8 to 24 weeks
Hashimoto-Pritzker
Hashimoto-Pritzker Before and After
Hashimoto-Pritzker
Hashimoto-Pritzker
EM: 10-25% of cells have Langerhans’ cell granules, but this does not distinguish
Hashimoto-Pritzker from Histiocytosis X.
H&E: large mononuclear cells & multinucleated giant cells with ground glass or foamy cytoplasm
S-100 stain CD1a stain
HASHIMOTO-PRITZKER
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.
Histiocytosis X
Proliferation of Langerhans’ cellsMC-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
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.
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 system
B) Visceral involvement with or without bone lesions, diabetes insipidus, LAD or rash but WITH signs of organ dysfunction.
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.
Histicytosis X - scalp
Often mistaken for SD, but focal hemorrhage is present
Often mistaken for SD, but focal hemorrhage is present
Histiocytosis X - TX
Skin only: topical steroids, nitrogen mustard, PUVA, Interferon Alpha.extensive disease but without organ dysfunction: oral corticosteroids Extensive disease with orgain dysfunction: Vinblastine, Cyclosporine, Radiation. Refractory: 2-chlorodeoxyadenosine
SLICK RICK SAYS: “DON’T FORGET TO TURN IN YOUR TEST QUESTIONS”
THE END