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

Chapter 148. Non-Langerhans Cell Histiocytosis

鄭煜彬

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Non-Langerhans Cell Histiocytosis(NLCH)= class II histiocytosis: Introduction
開始之前，請先複習一下縮寫 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.
NLCH的定義為何?	Proliferation of histiocytes(非Langerhans cells)
良惡性、預後、病程長短如何?	A benign, self-healing course lasting a few years (but can be invasive)
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.
NLCH的免疫染色為?	CD68+(macrophage/dendritic cell markers) CD1a– & CD207–
NLCH如果S100(+)，一定是哪一種?	SHML
NLCH一般好發於何處?	Head, trunk, and skin folds(除了PNH spare skin folds)
哪些NLCH會影響mucosa?	PNH, DX, MRH, SHML
除皮膚外，NLCH常會影響那些器官?	Ocular, joint and visceral impairment, , diabetes insipidus(DI>BCH)
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
哪些NLCH只好發於小孩?	JXG, PX, BCH
哪些NLCH只好發於成人?	XD, ECD, MRH, NXG, SHML Mn: Mends這些疾病需要進一步修復
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)
哪些NLCH好發於男性或女性?	M: PX, XD  F: RH
NLCH的可能原因為何?	Unknown，但可能有三項： Virus-induced local immune Solitary: local trauma Diffuse: internal malignancies & autoimmune dzs
NLCH病理下最重要的細胞為?	Histocyte: 各分類請見下表
哪些histiocytosis會有epidermotrophic的行為?	LCH。NLCH大多不會。
何謂vacuolated histiocytes?	Epitheloid histiocytes: an abundant light, poorly limited cytoplasm (BCH/GEH)
何謂scalloped histiocytes?	Xanthomatized histiocytes with microvilli
何謂oncocytic histiocytes?	Histiocytes with an abundance of eosinophilic, homogeneous cytoplasm + fine granules(ground-glass)
哪些NLCH有lipid-laden foam cells?	JXG/ PX, PNH/spindle cell XG, & NXG (Xantho!)
NLCH的lipid profile大多如何?	Normal
哪些NLCH是isolated lesions?	JXG, PX, GEH, BCH, PNH
哪些NLCH會變plaque?	XD, ECD, MRH, NXG (沒有SHML)
哪些NLCH會自己好，大多不用治療?	JXG, PX, GEH, BCH
哪些NLCH數量不多可以直接切除?	JXG, SRH, NXG
哪種NLCH不會自己好但預後好不用治療?	PNH
哪些NLCH的治療不多，且大多不成功?	XD, ECD, MRH, NXG, or SHML Mn: Mends這些疾病需要進一步修復
Juvenile Xanthogranuloma (JXG)& Papular xanthoma(PX)
哪種JXG患者易有多顆病灶?	男性
JXG的行為如何?	benign, self-healing
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)
JXG有哪些臨床form?(7)	數量 大小 病灶 位置 Papular 多 2-5 mm小 Hemispheric papule upper part of the body Nodular 少 10–20 mm大 translucent round nodule with telangiectases Giant 少 >2cm大 Mixed 多 small + large Nodules en plaque 少 Coalesce into a plaque blueberry muffin baby 多 Bluish papules and nodules head, trunk, & proximal extremities Multiple lichenoid 超多 Lichenoid papules
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)
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
Juvenile chronic myelogenous leukemia (JMML)和哪種JXG有關?	Nodular JXG with systemic involvement Papular JXG with NF1
Papular JXG常會有哪種色素性疾病?	Café-au-lait macules(an excellent marker of NF1)
JXG該做哪些lab檢查?	不需要，除非懷疑Juvenile CML
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)
JXG的免疫染色特徵為?	Positive: CD68/Ki-M1P, factor XIIIa Negative: CD1a, & S100
PX的病理特徵為何?	Monomorphous, xanthomatous cells and Touton giant cells, little inflammatory cells & no extracellular lipid
PX的免疫染色和JXG最大不同為?	No factor XIIIa
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)
JXG的治療與預後如何?	不用治療，3–6 年自己好
眼睛的JXG可如何治療?	Systemic steroids, low-dose radiotherapy, chlorambucil
Generalized Eruptive Histiocytosis (GEH)&Benign Cephalic histiocytosis(BCH)
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)
成人與小孩的GEH有何不同?	Adults: mucous membranes(+/-) Children: mucous membranes(-)
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.
GEH/BCH的行為如何?	benign, self-healing
GEH/BCH有什麼全身性併發症?	沒有(只有BCH曾有少數diabetes insipidus)
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)
GEH的病理特徵為何?	Positive: CD68 Negative: CD1a, & S100
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)
GEH/BCH的治療與預後如何?	不用治療，幾年自己好
Progressive nodular histiocytosis(PNH)
PNH的行為如何?	benign, but progressive
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.
PNH的局限型稱為?	Spindle cell XG
PNH的病理特徵為何?	XG with storiform, spindle-shaped histiocytes
PNH的免疫染色為何?	Positive: CD68 Negative: CD1a, & S100
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)
PNH的預後與治療如何?	不會自己好，但病人健康無虞。
Xanthoma disseminatum(XD)& Erdheim–Chester disease(ECD)
XD和ECD的行為如何?	XD: benign, self-healing or persistent ECD: progressive
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)
ECD的臨床特徵為?	Chronic mild bone pain localized in the lower limbs.
ECD和XD的差異為何?	A progressive form, visceral manifestations, elderly.
XD有哪些visceral manifestations?	BM: osteolytic lesions, multiple myeloma, Waldenström macroglobulinemia, and monoclonal gammopathy, Lungs, liver, kidney, heart, and CNS
XD引起的DI有何特徵?	Vasopressin-sensitive transitory DI, polyuria and polydipsia are mild.
哪些疾病會出現Diabetes insipidus(DI) ?	LCH, XD, BCH.
XD影響CNS時如何檢查?	MRI: foci of abnormally high signal intensity
ECD如何檢查?	XR: symmetric sclerosis at long bones of the lower limbs, diaphyseal & metaphyseal regions.
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
ECD的病理特徵為何?	Lipid-laden histiocytes +Touton giant cells and eosinophils, surrounded by fibrosis.
XD要和哪些疾病D/D?	各種histiocytosis
XD有哪些併發症?	Conjunctival inflammation & respiratory obstruction (dyspnea & dysphagia). CNS: Seizures, DI, and growth retardation(GH不足)
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)
MRH的行為如何?	progressive
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.
MRH可能由哪些NLCH變來?	GEH or adult JXG可能變MRH
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
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
何謂coral beads?	Periungual papules along nail folds(40% of cases)
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.
Diffuse cutaneous reticulohistiocytosis	firm, smooth, asymptomatic (pinkish yellow→red–brown) 3–10 mm papulonodular lesions scattered diffusely over the skin. No systemic involvement.
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
MRH如何破壞軟硬骨?	Activated histiocytes放urokinase
Familial histiocytic dermatoarthritis是什麼?	A form of MRH, familial occurrence, dermatitis, arthritis and typical ocular involvement (glaucoma, uveitis, and cataracts).
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.)
MRH還和哪些疾病有關	Autoimmune diseases, systemic vasculitis, tuberous sclerosis, and tuberculosis.
MRH有哪些lab上的特徵?	↑ESR, anemia, hypercholesterolemia
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)
Fine granules in histiocytes內含什麼?	Glycolipids and/or glycoproteins: PAS(+)after diastase Neutral fat: Sudan black(+), scarlet red(+)
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
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
Purely cutaneous forms RH的治療與預後如何?	自消，但diffuse, purely cutaneous form可能變成MRH
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)
NXG的行為如何?	progressive
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.
NXG的Lab為何?	Paraproteinemia (immunoglobulin G κ or λ light chains, 90%), Cryoglobulinemia (40%), neutropenia/leucopenia/anemia(myeloma相關)
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.
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)
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
NXG的治療與預後如何?	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)
SHML的主要臨床表現為何?	Nodal disease: massive bilateral painless cervical LAP + Fever
台灣的SHML主要影響何處?	Skin(只佔全世界SHML10%)
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
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
SHML的lab為何?	↑ESR, leukocytosis with neutrophilia, and polyclonal hypergammaglobulinemia. 較少出現：moderate anemia (60%), lymphopenia, ↑ EBV titer
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
SHML要和哪些疾病作D/D?	嚴重的cervical lymph nodes Infections: Abscesses, tuberculosis, AIDS Hodgkin disease, leukemia, sarcoidosis,
SHML有哪些併發症?	影響Eye, upper respiratory tract, 網狀上皮、神經系統 HIV/CMV惡化
SHML的治療與預後如何?	數月至數年後自消，不需治療。Extranodal lesions先出現LAP 免疫功能異常→預後不好 Space-occupying影響器官功能時：systemic steroids or chemotherapeutic regimens