Abstract
Histiocytoses are caused by an accumulation of dendritic cells or macrophages. Five groups are distinguished: the Langerhans cell group, cutaneous and mucocutaneous non-Langerhans cell histiocytoses, malignant histiocytoses, Rosai-Dorfman disease, and hemophagocytic lymphohistiocytosis. The rare Langerhans cell histiocytoses include localized to generalized as well as self-limiting to life-threatening manifestations in children and adults. The bones and skin are most frequently affected. The more frequent, usually benign non-Langerhans cell histiocytoses are based on nodular to diffuse macrophage-dominated dermatitis. The xanthogranuloma family mainly affects children, and spontaneous remission usually occurs. Further histiocytoses are very rare. Malignant histiocytosis or hemophagocytic lymphohistiocytosis can be life threatening.
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The Langerhans Group (L-Group)
Allen CE, Merad M, McClain KL (2018) Langerhans-cell histiocytosis. N Engl J Med 379:856–868
Arico M (2016) Langerhans cell histiocytosis in children: from the bench to bedside for an updated therapy. Br J Haematol 173:663–670
Chasset F, Barete S, Charlotte F et al (2016) Cutaneous manifestations of Erdheim-Chester disease (ECD): clinical, pathological, and molecular features in a monocentric series of 40 patients. J Am Acad Dermatol 74:513–520
Courtillot C, Laugier Robiolle S, Cohen Aubart F et al (2016) Endocrine manifestations in a monocentric cohort of 64 patients with Erdheim-Chester disease. J Clin Endocrinol Metab 101:305–313
Diamond EL, Subbiah V, Lockhart AC et al (2018) Vemurafenib for BRAF V600-mutant Erdheim-Chester disease and Langerhans cell histiocytosis: analysis of data from the histology-independent, phase 2, open-label VE-BASKET study. JAMA Oncol 4:384–388
Egeler RM, Katewa S, Leenen PJ et al (2016) Langerhans cell histiocytosis is a neoplasm and consequently its recurrence is a relapse: in memory of Bob Arceci. Pediatr Blood Cancer 63:1704–1712
Emile JF, Abla O, Fraitag S et al (2016) Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood 127:2672–2681
Hervier B, Haroche J, Arnaud L et al (2014) Association of both Langerhans cell histiocytosis and Erdheim-Chester disease linked to the BRAFV600E mutation. Blood 124:1119–1126
Johnson WT, Patel P, Hernandez A et al (2016) Langerhans cell histiocytosis and Erdheim-Chester disease, both with cutaneous presentations, and papillary thyroid carcinoma all harboring the BRAF(V600E) mutation. J Cutan Pathol 43:270–275
Kobic A, Shah KK, Schmitt AR et al (2020) Erdheim-Chester disease: expanding the spectrum of cutaneous manifestations. Br J Dermatol 182(2):405–409
Krooks J, Minkov M, Weatherall AG (2018a) Langerhans cell histiocytosis in children: Diagnosis, differential diagnosis, treatment, sequelae, and standardized follow-up. J Am Acad Dermatol 78:1047–1056
Krooks J, Minkov M, Weatherall AG (2018b) Langerhans cell histiocytosis in children: History, classification, pathobiology, clinical manifestations, and prognosis. J Am Acad Dermatol 78:1035–1044
Luder CM, Nordmann TM, Ramelyte E et al (2018) Histiocytosis – cutaneous manifestations of hematopoietic neoplasm and non-neoplastic histiocytic proliferations. J Eur Acad Dermatol Venereol 32:926–934
Mazor RD, Manevich-Mazor M, Kesler A et al (2014) Clinical considerations and key issues in the management of patients with Erdheim-Chester disease: a seven case series. BMC Med 12:221–223
Oneal PA, Kwitkowski V, Luo L et al (2018) FDA approval summary: vemurafenib for the treatment of patients with Erdheim-Chester Disease with the BRAFV600 mutation. Oncologist 23:1520–1524
Rigaud C, Barkaoui MA, Thomas C et al (2016) Langerhans cell histiocytosis: therapeutic strategy and outcome in a 30-year nationwide cohort of 1478 patients under 18 years of age. Br J Haematol 174(6):887–898
Cutaneous Non-Langerhans Cell Histiocytoses (C Group)
Bork K, Hoede N (1988) Hereditary progressive mucinous histiocytosis in women. Report of three members in a family. Arch Dermatol 124:1225–1229
Breier F, Zelger B, Reiter H et al (2002) Papular xanthoma: a clinicopathological study of 10 cases. J Cutan Pathol 29:200–206
Eisendle K, Linder D, Ratzinger G et al (2008) Inflammation and lipid accumulation in xanthoma disseminatum: therapeutic considerations. J Am Acad Dermatol 58(2 Suppl):S47–S49
Hilker O, Kovneristy A, Varga R et al (2012) Progressive nodular histiocytosis. J Dtsch Dermatol Ges 11:301–307
Höck M, Zelger B, Schweigmann G et al (2019) The various clinical spectra of juvenile xanthogranuloma: imaging for two case reports and review of the literature. BMC Pediatr 19:128
Miguel D, Lukacs J, Illing T, Elsner P (2016) Treatment of necrobiotic xanthogranuloma – a systematic review. J Eur Acad Dermatol Venereol 31:221–235
Patsatsi A, Kyriakou A, Sotiriadis D (2014) Benign cephalic histiocytosis: case report and review of the literature. Pediatr Dermatol 31:547–550
Selmi C, Greenspan A, Huntley A, Gershwin ME (2015) Multicentric reticulohistiocytosis: a critical review. Curr Rheumatol Rep 17:511–516
Seward JL, Malone JC, Callen JP (2004) Generalized eruptive histiocytosis. J Am Acad Dermatol 50:116–120
Wood AJ, Wagner MV, Abbott JJ, Gibson LE (2009) Necrobiotic xanthogranuloma: a review of 17 cases with emphasis on clinical and pathologic correlation. Arch Dermatol 145:279–284
Zelger BW, Cerio R (2001) Xanthogranuloma is the archetype of non-Langerhans cell histiocytoses. Br J Dermatol 145:369–371
Zelger BW, Sidoroff A, Orchard G, Cerio R (1996) Non-Langerhans cell histiocytoses. A new unifying concept. Am J Dermatopathol 18:490–504
Rosai-Dorfman Disease (R Group)
Abla O, Jacobsen E, Picarsic J et al (2018) Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease. Blood 131:2877–2890
Colmenero I, Molho-Pessach V, Torrelo A et al (2012) Emperipolesis: an additional common histopathologic finding in H syndrome and Rosai-Dorfman disease. Am J Dermatopathol 34:315–320
Goyal G, Ravindran A, Young JR, Mayo Clinic Histiocytosis Working Group et al (2019) Clinicopathological features, treatment approaches, and outcomes in Rosai-Dorfman disease. Haematologica 105(2):348–357
Molho-Pessach V, Ramot Y, Camille F et al (2014) H syndrome: the first 79 patients. J Am Acad Dermatol 70:80–88
Rossbach HC, Dalence C, Wynn T, Tebbi C (2006) Faisalabad histiocytosis mimics Rosai-Dorfman disease: brothers with lymphadenopathy, intrauterine fractures, short stature, and sensorineural deafness. Pediatr Blood Cancer 47:629–632
Senniappan S, Hughes M, Shah P et al (2013) Pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) syndrome is associated with severe chronic inflammation and cardiomyopathy, and represents a new monogenic autoinflammatory syndrome. J Pediatr Endocrinol Metab 26:877–882
Malignant Histiocytoses (M Group)
Pileri SA, Grogan TM, Harris NL et al (2002) Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology 41:1–29
Hemophagocytic Lymphohistiocytosis (H Group)
Chellapandian D, Hines MR, Zhang R et al (2019) A multicenter study of patients with multisystem Langerhans cell histiocytosis who develop secondary hemophagocytic lymphohistiocytosis. Cancer 125:963–971
Feldmann J, Callebaut I, Raposo G et al (2003) Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3). Cell 115:461–473
Henter JI, Horne A, Arico M et al (2007) HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 48:124–131
Imashuku S (2007) Systemic type Epstein-Barr virus-related lymphoproliferative diseases in children and young adults: challenges for pediatric hemato-oncologists and infectious disease specialists. Pediatr Hematol Oncol 24:563–568
Janka GE, Lehmberg K (2014) Hemophagocytic syndromes – an update. Blood Rev 28:135–142
Kogl T, Muller J, Jessen B et al (2013) Hemophagocytic lymphohistiocytosis in syntaxin-11-deficient mice: T-cell exhaustion limits fatal disease. Blood 121:604–613
La Rosée P, Horne A, Hines M et al (2019) Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood 133:2465–2477
Lehmberg K, McClain KL, Janka GE, Allen CE (2014) Determination of an appropriate cut-off value for ferritin in the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 61:2101–2103
Lehmberg K, Sprekels B, Nichols KE et al (2015) Malignancy-associated haemophagocytic lymphohistiocytosis in children and adolescents. Br J Haematol 170:539–549
Molleran Lee S, Villanueva J, Sumegi J et al (2004) Characterisation of diverse PRF1 mutations leading to decreased natural killer cell activity in north American families with haemophagocytic lymphohistiocytosis. J Med Genet 41:137–144
First Describer
Abbot AFD (1936) Letterer-Siwe’s disease. Splenohepatomegaly associated with widespread hyperplasia of non-lipoid-storing macrophages; discussion of the so-called reticuloendothelioses. Am J Dis Child 51:499–522
Adamson HG (1905) Society intelligence: the Dermatological Society in London. Br J Dermatol 17:222
Altman J, Winkelmann RK (1962) Diffuse normolipemic plane xanthoma. Generalized xanthelasma. Arch Dermatol 85:633–640
Ausset E (1899) Un cas de diabete insipide chez un enfant de 4 ans; eruption xanthelasmique generalisee concomitante. Bull Mem Soc Med Hospitaux de Paris 3s(XV):150–155
Champard E (1897) De xanthelasma generalize. Fr Med 26:10–12
Chester W (1930) Über Lipoidgranulomatose. Virchows Arch A Pathol Anat Physiol 279:561–602
Christian H (1920) Defects in membraneous bones, exophthalmus and diabetes insipidus; an unusual syndrome of dyspituitarism. Med Clin North Am 3:849–871
Destombes P (1965) Adenites avec surcharge lipidique, de l’enfant ou de l’adulte jeune, observees aux Antilles et au Mali. (Quatre observations). Bull Soc Pathol Exot Filiales 58:1169–1175
Farquhar JW, Claireaux AE (1952) Familial haemophagocytic reticulosis. Arch Dis Child 27:519–525
Gagel O (1941) Eine Granulationsgeschwulst im Gebiet des Hypothalamus. Z Neurol 172:710–722
Gianotti F, Caputo R, Ermacora E (1971) Singulière histocytose infantile a cellules avec particules vermiformes intracytosplasmiques. Bull Soc Fr Dermatol Syphiliogr 78:232–233
Goltz RW, Laymon CW (1954) Multicentric reticulohistiocytosis of the skin and synovia; reticulohistiocytoma or ganglioneuroma. Arch Derm Syphilol 69:717–731
Hand AJ (1893) Polyuria and tuberculosis. Arch Pediatr (New York) 10:673–675
Hashimoto K, Pritzker MS (1973) Electron microscopic study of reticulohistiocytoma. An unsusual case of congenital, self-healing reticulohistiocytosis. Arch Dermatol 107:263–270
Kossard S, Winkelmann RK (1980) Necrobiotic xanthogranuloma with paraproteinemia. J Am Acad Dermatol 3:257–270
Letterer E (1924) Aleukämische Retikulose. Ein Beitrag zu den proliferativen Erkrankungen des retikuloendothelialen Apparates. Frankf Z Pathol 30:377–394
Lichtenstein L (1953) Histiocytosis X; integration of eosinophilic granuloma, Letterer-Siwe disease and Hand-Schüller-Christian disease as related manifestations of a single nosologic entity. Arch Pathol 56:84–102
MacDonagh JER (1912) A contribution to our knowledge of the naevoxanthoendotheliomata. Br J Dermatol 24:86–99
Montgomery HOA (1938) Xanthomatous correlation of clinical, histopathological and chemical studies of cutaneous xanthoma. Arch Derm Syphilol 37:373–402
Nezelof C, Basset F, Rousseau MF (1973) Histiocytosis X histogenetic arguments for a Langerhans cell origin. Biomedicine 18:365–371
Robinson HM Jr, Harmon LE, Firminger HI (1963) Multiple lipoidal histiocytomas with regression. Arch Dermatol 88:660–667
Rosai J, Dorfman RF (1969) Sinus histiocytosis with massive lymphadenopathy. A newly recognized benign clinicopathological entity. Arch Pathol 87:63–70
Schüller A (1915) Über einen eigenartigen Schädeldefekt im Kindesalter (“Landkartenschädel”). Fortschr Geb Röntgenstr 23:12–18
Shafer WG (1971) Verruciform xanthoma. Oral Surg Oral Med Oral Pathol 31:784–789
Siwe SA (1933) Die Retikuloendotheliose, ein neues Krankheitsbild unter den Hepatosplenomegalien. Z Kinderheilkd 55:212–247
Target JH (1897) Giant-cell tumors of the integument. Trans Pathol Soc Lond 48:230–235
Winkelmann RK, Muller SA (1963) Generalized eruptive histiocytoma. A benign papular histiocytic reticulosis. Arch Dermatol 88:586–596
Winkelmann RK, Kossard S, Fraga S (1980) Eruptive histiocytoma of childhood. Arch Dermatol 116:565–570
Wood GS, Hu CH, Beckstead JH et al (1985) The indeterminate cell proliferative disorder: report of a case manifesting as an unusual cutaneous histiocytosis. J Dermatol Surg Oncol 11:1111–1119
Zak FG (1950) Reticulohistiocytoma (“ganglioneuroma”) of the skin. Br J Dermatol Syph 62:351–355
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Ratzinger, G., Zelger, B. (2020). Histiocytoses. In: Plewig, G., French, L., Ruzicka, T., Kaufmann, R., Hertl, M. (eds) Braun-Falco´s Dermatology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-58713-3_112-1
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DOI: https://doi.org/10.1007/978-3-662-58713-3_112-1
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