Sunday, April 16, 2017

[考生加油]Dermatological Recall: Chapter 148. Non-Langerhans Cell Histiocytosis

Chapter 148. Non-Langerhans Cell Histiocytosis

如果要儘快掌握本章重點,不妨看一下筆者仿照Surgical Recall寫的Dermatological Recall。
  • 建議可以先遮住右邊,想一下答案大概是什麼。
  • (5)表示答案有五項。(訣)表示有筆者自編的口訣。

Non-Langerhans Cell Histiocytosis(NLCH)= class II histiocytosis: Introduction
BCH = benign cephalic histiocytosis; ECD = Erdheim–Chester disease; GEH = generalized eruptive histiocytosis; JXG = juvenile xanthogranuloma; MRH = multicentric reticulohistiocytosis; NXG = necrobiotic xanthogranuloma; PNH = progressive nodular histiocytosis; PX = papular xanthoma; SHML = sinus histiocytosis with massive lymphadenopathy; XD = xanthoma disseminatum.
  1. NLCH的定義為何?
Proliferation of histiocytes(非Langerhans cells)
  1. 良惡性、預後、病程長短如何?
A benign, self-healing course lasting a few years
(but can be invasive)
  1. NLCH的病理特徵為何?
A dense, diffuse, less epidermotropic(相較LCH) infiltrate of histiocytes +lymphocytes, plasma cells, eosinophils, and Touton giant cells.
  1. NLCH的免疫染色為?
CD68+(macrophage/dendritic cell markers)
CD1a & CD207
  1. NLCH如果S100(+),一定是哪一種?
  1. NLCH一般好發於何處?
Head, trunk, and skin folds(除了PNH spare skin folds)
  1. 哪些NLCH會影響mucosa?
  1. 除皮膚外,NLCH常會影響那些器官?
Ocular, joint and visceral impairment, , diabetes insipidus(DI>BCH)
  1. 雖然NLCH分類不易,目前大致上分哪兩類?
Infantile/Adult: isolated lesions/ cutaneous/ self-healing or stable [JXG/PX, PNH, GEH/BCH]
Mn: JPG (一種圖片格式)
Adult: coalescing plaque/ systemic/ progressive or aggressive [MRH, ECD, NXG, XD, SHML]
Mn: Mends這些疾病需要進一步修復
Image not available.
  1. 哪些NLCH只好發於小孩?
  1. 哪些NLCH只好發於成人?
Mn: Mends這些疾病需要進一步修復
  1. 哪些NLCH同時發生於小孩與成人?
GEH, PNH (Mn: Geriatrics老人醫學與Pediatrics小兒醫學)
  1. 哪些NLCH好發於男性或女性?
M: PX, XD  F: RH
  1. NLCH的可能原因為何?
Virus-induced local immune
Solitary: local trauma
Diffuse: internal malignancies & autoimmune dzs
  1. NLCH病理下最重要的細胞為?
Histocyte: 各分類請見下表
  1. 哪些histiocytosis會有epidermotrophic的行為?
  1. 何謂vacuolated histiocytes?
Epitheloid histiocytes: an abundant light, poorly limited cytoplasm (BCH/GEH)
  1. 何謂scalloped histiocytes?
Xanthomatized histiocytes with microvilli
  1. 何謂oncocytic histiocytes?
Histiocytes with an abundance of eosinophilic, homogeneous cytoplasm + fine granules(ground-glass)
  1. 哪些NLCH有lipid-laden foam cells?
JXG/ PX, PNH/spindle cell XG, & NXG (Xantho!)
  1. NLCH的lipid profile大多如何?
  1. 哪些NLCH是isolated lesions?
  1. 哪些NLCH會變plaque?
  1. 哪些NLCH會自己好,大多不用治療?
  1. 哪些NLCH數量不多可以直接切除?
  1. 哪種NLCH不會自己好但預後好不用治療?
  1. 哪些NLCH的治療不多,且大多不成功?
Mn: Mends這些疾病需要進一步修復
Juvenile Xanthogranuloma (JXG)& Papular xanthoma(PX)
  1. 哪種JXG患者易有多顆病灶?
  1. JXG的行為如何?
benign, self-healing
  1. JXG的臨床特徵為何?
Asymptomatic yellowish/orange/red/brown papulonodular lesions at skin and other organs(eye)
Histiocytes with lipidation( no metabolic disorder)
  1. JXG有哪些臨床form?(7)


2-5 mm小
Hemispheric papule

upper part of the body
10–20 mm大
translucent round nodule with telangiectases


small + large

en plaque

Coalesce into a plaque

blueberry muffin baby

Bluish papules and nodules
head, trunk, & proximal extremities
Multiple lichenoid

Lichenoid papules

  1. PX有何特徵?
Rapidly become xanthomatous, 2-12 mm, a generalized distribution, 不融合成plaques.(xanthomatous, 局限在皮膚)
  1. JXG的常見皮外表現為?
Eye involvement: spontaneous hyphema(前房積血), glaucoma, and blindness. 是這個良性病的主要併發症
  1. Juvenile chronic myelogenous leukemia (JMML)和哪種JXG有關?
Nodular JXG with systemic involvement
Papular JXG with NF1
  1. Papular JXG常會有哪種色素性疾病?
Café-au-lait macules(an excellent marker of NF1)
  1. JXG該做哪些lab檢查?
不需要,除非懷疑Juvenile CML
  1. JXG的病理特徵為何?
A polymophous, xanthomatous histiocytic infiltrate in upper dermis(Foam cells, foreign-body giant cells, and Touton giant cells), Fat stains(+), inflammatory cells(Nφ/Eφ/L)
EM: lipid vacuoles, cholesterol clefts, no Birbeck granules(網球拍)
  1. JXG的免疫染色特徵為?
Positive: CD68/Ki-M1P, factor XIIIa
Negative: CD1a, & S100
  1. PX的病理特徵為何?
Monomorphous, xanthomatous cells and Touton giant cells, little inflammatory cells & no extracellular lipid
  1. PX的免疫染色和JXG最大不同為?
No factor XIIIa
  1. JXG要和哪些疾病D/D?
各種xanthoma, 各種histiocytosis, 各種granulomatous disease(GA/sarcoidosis), mastocytoma, Spitz n, molluscum, DF(很像棕色的JXG)
  1. JXG的治療與預後如何?
不用治療,3–6 年自己好
  1. 眼睛的JXG可如何治療?
Systemic steroids, low-dose radiotherapy, chlorambucil
Generalized Eruptive Histiocytosis (GEH)&Benign Cephalic histiocytosis(BCH)
  1. GEH的臨床特徵為?
Numerous asymptomatic pink/dark red, 3-10 mm firm, round/oval papules(很多一公分以下偏紅的papules)
  1. 成人與小孩的GEH有何不同?
Adults: mucous membranes(+/-)
Children: mucous membranes(-)
  1. BCH和GEH的差異為何?
A limited GEH: orange–red/red–brown(較偏橘褐) , 2-8mm(較小), upper face , or head & neck.
  1. GEH/BCH的行為如何?
benign, self-healing
  1. GEH/BCH有什麼全身性併發症?
沒有(只有BCH曾有少數diabetes insipidus)
  1. GEH的病理特徵為何?
A dense, monomorphous, vacuolated(nonxanthomatous, epitheloid) histiocytes in papillary/mid-dermis, arranged in nests around vessels.(Foamy cell, giant cell 極少)
  1. GEH的病理特徵為何?
Positive: CD68
Negative: CD1a, & S100
  1. GEH/BCH要和哪些疾病D/D?
各種xanthoma, 各種histiocytosis, 各種granulomatous disease(GA/sarcoidosis), mastocytoma(類似JXG的D/D,但GEH的病灶很多)
  1. GEH/BCH的治療與預後如何?
Progressive nodular histiocytosis(PNH)
  1. PNH的行為如何?
benign, but progressive
  1. PNH的臨床特徵為何?(有兩型)
Superficial papules: numeous yellow-orange 2–10 mm papules on body surface, oral, laryngeal, & conjunctival mucosae, sparing flexural areas
Deep nodules: 1-5 cm dermal nodules+ overlying telangiectasia on the trunk.
  1. PNH的局限型稱為?
Spindle cell XG
  1. PNH的病理特徵為何?
XG with storiform, spindle-shaped histiocytes
  1. PNH的免疫染色為何?
Positive: CD68
Negative: CD1a, & S100
  1. PNH要和哪些疾病D/D?
各種xanthoma, 各種histiocytosis, 各種granulomatous disease(GA/sarcoidosis), mastocytoma(類似JXG的D/D,但PNH的病灶很多)
  1. PNH的預後與治療如何?
Xanthoma disseminatum(XD)& Erdheim–Chester disease(ECD)
  1. XD和ECD的行為如何?
XD: benign, self-healing or persistent
ECD: progressive
  1. XD的臨床特徵為何?
Numeous (red–brown→yellowish) papules merge quickly, forming soft plaques symmetrically involve skin(face, eyelids, trunk, proximal limbs, folds) & mocosa (mouth, pharynx, larynx, conjunctiva, and cornea)
  1. ECD的臨床特徵為?
Chronic mild bone pain localized in the lower limbs.
  1. ECD和XD的差異為何?
A progressive form, visceral manifestations, elderly.
  1. XD有哪些visceral manifestations?
BM: osteolytic lesions, multiple myeloma, Waldenström macroglobulinemia, and monoclonal gammopathy,
Lungs, liver, kidney, heart, and CNS
  1. XD引起的DI有何特徵?
Vasopressin-sensitive transitory DI, polyuria and polydipsia are mild.
  1. 哪些疾病會出現Diabetes insipidus(DI) ?
  1. XD影響CNS時如何檢查?
MRI: foci of abnormally high signal intensity
  1. ECD如何檢查?
XR: symmetric sclerosis at long bones of the lower limbs, diaphyseal & metaphyseal regions.
  1. XD的病理特徵為何?
Early: a mixture of histiocytes, foam cells(lipid-laden), and inflammatory cells(像JXG,不過是scalloped cells)
Late: foam cells with microvilli(scalloped) &Touton giant cells + Siderosis
  1. ECD的病理特徵為何?
Lipid-laden histiocytes +Touton giant cells and eosinophils, surrounded by fibrosis.
  1. XD要和哪些疾病D/D?
  1. XD有哪些併發症?
Conjunctival inflammation & respiratory obstruction (dyspnea & dysphagia).
CNS: Seizures, DI, and growth retardation(GH不足)
  1. XD的預後與治療如何?
Diabetes insipidus: vasopressin RT/CT/cryothorapy/steroid可試,但無法治癒。
(1) a self-healing form, (2) a persistent form(common)兩者預後好
(3) a progressive form (ECD)預後不好,易pulmonary fibrosis
Solitary cutaneous reticulohistiocytosis=reticulohistiocytoma cutis, diffuse cutaneous reticulohistiocytosis(RH), and multicentric reticulohistiocytosis(MRH)
  1. MRH的行為如何?
  1. MRH的臨床特徵為?
Few millimeters to 2 cm, scattered and isolated, round, translucent, yellow-rose or yellow-brown papulonodular lesions on skin(hands, juxta-articular regions, head) and mucosae(oral, nasal, pharyngeal). Sometimes grouping into plaques. (Pruritus: 33%)
Nail changes: brittleness, longitudinal ridging, and atrophy
arthropathy and other visceral symptoms.
  1. MRH可能由哪些NLCH變來?
GEH or adult JXG可能變MRH
  1. MRH會很像哪些疾病?(4)
Xanthomatous lesions: 30%, like xanthoma
Facial nodules: like leonine face
Periarticular nodules: like rheumatoid nodules
Erythematous, photodistributed macules/papules: like DM
  1. 哪些疾病會出現Leonine face? (6)
Pachydermoperiostosis(一種hypertrophic osteoarthropathy), Leoprosy, Diffuse Cutaneous Leishmaniasis, Mycosis fungoides, Monocytic or myelomonocytic leukemia, MRH
Mn: 1P 2L 3M
  1. 何謂coral beads?
Periungual papules along nail folds(40% of cases)
  1. Solitary cutaneous reticulohistiocytosis的臨床特徵為?
A single firm, rapidly growing nodule varying in color from yellow-brown to dark red on the head, preceded by trauma. No systemic involvement.
  1. Diffuse cutaneous reticulohistiocytosis
firm, smooth, asymptomatic (pinkish yellow→red–brown) 3–10 mm papulonodular lesions scattered diffusely over the skin. No systemic involvement.
  1. MRH影響其他器官的症狀為何?
Osteoarticular: severe chronic diffuse symmetrical polyarthritis with arthralgias at hands (80%), knees (70%), wrists (65%)
Muscle: myositis, myotonia, and myoatrophy
Cardiopulmonary: pericarditis, cardiac insufficiency, pleuritis, pulmonary infiltration
Eyes: exophthalmos, conjunctival infiltration
GI: gastric ulcer
Thyroid: thyroid nodules
Fever, weight loss, and weakness
  1. MRH如何破壞軟硬骨?
Activated histiocytes放urokinase
  1. Familial histiocytic dermatoarthritis是什麼?
A form of MRH, familial occurrence, dermatitis, arthritis and typical ocular involvement (glaucoma, uveitis, and cataracts).
  1. MRH和哪些malignancy有關?
Bronchial, breast, gastric, and cervical ca. (Lymphomas myelodysplastic syndromes, & melanoma較少)
(只有15-27%有關,還不算是paraneoplastic dz.)
  1. MRH還和哪些疾病有關
Autoimmune diseases, systemic vasculitis, tuberous sclerosis, and tuberculosis.
  1. MRH有哪些lab上的特徵?
↑ESR, anemia, hypercholesterolemia
  1. MRH的病理特徵為何?
Early: histiocytes and lymphocytes(似其他histiocytoses)
Late: large, mononucleated or multinucleated oncocytic histiocytes (fine granules, ground-glass appearance)
  1. Fine granules in histiocytes內含什麼?
Glycolipids and/or glycoproteins: PAS(+)after diastase
Neutral fat: Sudan black(+), scarlet red(+)
  1. MRH要和哪些疾病D/D?
其他histiocytosis: PNH, XD(多顆/大顆)
Rheumatoid dz: Rheumatoid arthritis, Fibroblastic rheumatism
Deposition: Lipoid proteinosis, self-healing cutaneous mucinosis
其他: Dermatomyositis, Lepromatous leprosy, Sarcoidosis
  1. MRH有哪些併發症?
主要和visceral involvement有關:
Upper airway: dysphonia and/or dysphagia.
Cardiopulmonary manifestations: may be fatal.
Bones: mutilating inflammatory polyarthritis
All the visceral organs: weight loss and pyrexia
  1. Purely cutaneous forms RH的治療與預後如何?
自消,但diffuse, purely cutaneous form可能變成MRH
  1. MRH的治療與預後如何?
MTX, etanercept, systemic steroid(dexamethasone, prednisolone+azathioprine), Leflunomide
預後和osteoarticular manifestations, visceral involvement, underlying neoplasms有關
Mucocutaneous: 會自消或持續存在
Osteoarticular: stable or progressive destruction
Necrobiotic Xanthogranuloma(NXG)
  1. NXG的行為如何?
  1. NXG的臨床特徵為何?
Indurated red–orange to violaceous or yellow papulonodules/plaques with central atrophy with telangiectasias or ulceration
Face/periorbital(85%)> trunk> extremities
Monoclonal gammopathy相關疾病:Hepatosplenomegaly(20%), Myeloma, arthropathy(IC在關節), HTN, neuropathy(IC在神經), neoplastic syndrome, primary biliary cirrhosis, and Graves disease.
  1. NXG的Lab為何?
Paraproteinemia (immunoglobulin G κ or λ light chains, 90%), Cryoglobulinemia (40%), neutropenia/leucopenia/anemia(myeloma相關)
  1. NXG的病理特徵為何?
N: clearly defined necrosis are sharply delineated from the surrounding granuloma.
X: lipid-laden foam cells: lipid droplet & cholesterol crystals
G: a mixture of lymphocytes, epithelioid cells, foam cells, Touton giant cells, and atypical, very large, bizarrely angulated, multinucleated giant cells.
  1. NXG要和哪些疾病作D/D?
各種Hyperlipemic xanthoma, 各種NLCH(XD/JXG, & MRH), 各種necrobiosis (GA, Necrobiosis lipoidica)
  1. NXG有哪些併發症?
Periorbital involvement: 各種眼睛問題、blindness。
Others: N/V, epistaxis, back pain, and Raynaud phenomenon
  1. NXG的治療預後如何?
Intermitent systemic steroid, low dosages chlorambucil/ melphalan(但無法防止MM). RT & plasmapheresis.
A chronic, often progressive course, 預後和extracutaneous involvement and visceral tumors(MM)有關,可以很好(MGUS: monoclonal gammopathy of uncertain significance)或很差(MM)。
Sinus Histiocytosis with Massive Lymphadenopathy (Rosai–Dorfman Disease羅賽-豆腐門)
  1. SHML的主要臨床表現為何?
Nodal disease: massive bilateral painless cervical LAP + Fever
  1. 台灣的SHML主要影響何處?
  1. Cutaneous SHML的臨床表現為何?
Yellowish macules/patches, reddish-brown eroded or ulcerated papules/plaques/nodules
Periocular involvement: lobulated induration of eyelids
  1. 其他常見的extranodal noncutaneous sites包括何處?
Eye, upper respiratory tract(nasal cavity/paranasal sinuses), 網狀上皮系統(liver, spleen, testes, skeleton), 神經系統, salivary glands
  1. SHML的lab為何?
↑ESR, leukocytosis with neutrophilia, and polyclonal hypergammaglobulinemia.
較少出現:moderate anemia (60%), lymphopenia, ↑ EBV titer
  1. SHML的病理特徵為何?
藍:Lymphocytes, plasma cells, and polymorphonuclear leukocytes, typically eosinophils
白:Foamy, multinucleated histiocytes with large vesicular nuclei and abundant pale cytoplasm
Emperipolesis: phagocytosis of leukocytes/lymphocytes
  1. SHML要和哪些疾病作D/D?
嚴重的cervical lymph nodes
Infections: Abscesses, tuberculosis, AIDS
Hodgkin disease, leukemia, sarcoidosis,
  1. SHML有哪些併發症?
影響Eye, upper respiratory tract, 網狀上皮、神經系統
  1. SHML治療與預後如何?
數月至數年後自消,不需治療。Extranodal lesions先出現LAP
Space-occupying影響器官功能時:systemic steroids or chemotherapeutic regimens

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