Histiocytoses: A Review of the Most Recent Classification System

A look at the proposed new classification system, grouping the histiocytoses into five categories, with tabular summaries for differential diagnosis.

By Jolie Krooks, BS, Milen Minkov, MD, PhD, and Klemens Rappersberger, MD
 

Histiocytes are immune cells found in various tissues throughout the body whose functions are diverse and include housekeeping via phagocytosis, activating the immune system via antigen presentation to T cells, and promoting peripheral tolerance via proliferation of regulatory T cells.1,2 Histiocytes of the skin include the CD14+ dendritic cells and macrophages of the dermis and CD14- Langerhans cells of the epidermis and mucosa.3,4 Langerhans cells share unique properties with both macrophages and dendritic cells. Like dendritic cells, macrophages and Langerhans cells may be long-standing byproducts of fetal hematopoiesis in the yolk sac and liver or may be renewed by bone marrow myeloid precursor cells during severe inflammatory conditions. However, in contrast to dendritic cells, macrophages and Langerhans cells self-renew during stable conditions.5-7 Nevertheless, Langerhans cells more closely resemble dendritic cells than macrophages in their ability to migrate to lymph nodes in order to present antigens to and stimulate T lymphocytes.8

The pathologic propagation of histiocytic cells encompasses over 100 different subtypes of rare disorders collectively referred to as the histiocytoses.9 Of the histiocytoses, Langerhans cell histiocytoses (LCH) is the most common, affecting an estimated four to five per million children per year (age 0-15).10,11 LCH affects children in >90 percent of cases.12

The first classification of the histiocytoses, established by the Working Group of the Histiocyte Society in 1987, classified the histiocytoses as Langerhans cell-related, non-Langerhans cell-related, or malignant.13 The original classification was updated in 1997 by a joint effort of the Histiocyte Society and the WHO Committee on Histiocytic/Reticulum Cell Proliferations to “disorders of varied biological behavior” and malignant, which included further subdivision to dendritic cell-related, macrophage-related, and monocyte-related. “Disorders of varied biological behavior” represented non-malignant disorders of diverse clinical severities.14

Since then, there have been breakthroughs regarding the specific molecular mechanisms involved in the pathogenesis of many of the histiocytoses, especially those pertaining to LCH and Erdheim-Chester disease. The identification of specific mutations in the MAPK pathway, shared by both LCH and Erdheim-Chester disease, has shaped the way researchers regard these disorders in relation to each other, and there has been a shift in considering these disorders as neoplastic, rather than as simply inflammatory, conditions.15-20 Considering these new insights, Emile et al recently presented a new classification of the histiocytoses.9 Specifically, in this new classification, the histiocytic disorders are grouped into five categories based on clinical, genetic, and (immuno)-histologic features: Langerhans (L); cutaneous and mucocutaneous (C); malignant (M); Rosai-Dorfman disease (R); and hemophagocytic lymphohistiocytosis (H).9

Indicative of the relevance of the histiocytoses to dermatology is the fact that there is a distinct category for histiocytoses with predominantly cutaneous and mucocutaneous manifestations. Additionally, many of the systemic clinical forms (including the malignant entities) can also present with cutaneous manifestations. Other histiocytoses classification systems have also emphasized the dominating role of the skin.21 Accordingly, correct diagnosis may depend on the expertise of the dermatologist and dermatopathologist.

This review includes a discussion of the proposed classification system from Emile et al and the pathogenesis of the different histiocytic disorders, and provides tabular summaries of the clinical presentation, the cutaneous manifestations, and the characteristic immunohistochemical findings (Tables 1-6).

Histiocytoses groups

L group. The Langerhans (L) group consists of Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), Mixed LCH/ECD, and Indeterminate cell histiocytosis (ICH), grouped together due to similarities in both clinical presentation and disease pathogenesis. Specifically, activating mutations in the MAPK pathway are central to disease pathogenesis in this group; the MAPK pathway is essential for cell growth, differentiation, and apoptosis.15-17 Still, it is important to note that mutations in the MAPK pathway, i.e. BRAFV600E, MAP2K1, KRAS, are not specific to LCH, ECD, and ICH, as these mutations have been implicated in non-histiocytic tumors and in other histiocytoses, including histiocytic sarcoma, interdigitating dendritic cell sarcoma, dendritic cell sarcoma, follicular dendritic cell sarcoma, and Rosai-Dorfman disease.22

Emile et al consider ECD as a specific manifestation of extracutaneous/disseminated juvenile xanthogranuloma (JXG) with activating mutations in the MAPK pathway.9 Indeed, the co-existence of ECD and LCH lesions in the same patient is attributed to MAPK pathway activating mutations, particularly BRAF-V600E, in bone marrow progenitors, monocytes, and myeloid dendritic cells. Furthermore, the diseases are not distinguishable by a specific distribution of mutant cell involvement.23 Of the 19 percent of patients with ECD that have mixed LCH/ECD, 89 percent have BRAF mutations.18 Observations of BRAF-V600E mutations in 58 percent of ECD patients20 and 56 percent of LCH patients19 have been confirmed by other studies.24-29 Of note to dermatologists, BRAF-V600E mutation is significantly more prevalent in patients with cutaneous involvement (EDC: 76 percent;30 LCH: 77 percent31). In addition to BRAF-V600E, mutations in other genes activating the MAPK pathway, as well as additional mutations in BRAF, have also less frequently been observed.20,32-37

Due to the rarity of ICH, studies assessing BRAF-V600E mutation status have been limited to isolated case reports and case series.22,38,39 Nevertheless, considering ICH’s histologic and clinical overlap with LCH, a shared primary component of disease pathogenesis would be expected. Specifically, like the pathologic cells observed in LCH, those of ICH also express CD1a and S100, but are negative for CD207 (langerin), an antibody to Birbeck granules. Indeterminate cells are considered dermal dendritic precursors of Langerhans cells that have not been acted upon by TGF-Β, a cytokine that promotes migration from the dermis to the epidermis and the acquisition of Birbeck granules.40

Despite the overlap between ICH and LCH, recent report of a NCOA2-ETV3 gene fusion identified in three cases of ICH, but absent in 11 cases of LCH, may indicate that they are distinct clinical entities.41 However, more research is needed to possibly identify this mutation in isolated LCH cases, and further follow-up is needed to identify whether its presence in the three ICH cases will be associated with another malignancy (one patient had a history of breast cancer; follow-up for all cases was only four to five months). When identified in six children with acute lymphoblastic leukemia, NCOA2-ETV3 gene fusion was also associated with a significant number of NOTCH1 mutations.42 NOTCH1 pathway mutations have been implicated in upregulation of the MAPK pathway43 and have been identified in LCH patients with a history of T-cell acute lymphoblastic leukemia.44

C group. By Emile et al’s categorization, the cutaneous and mucocutaneous (C) group consists of non-LCHs primarily localized to the skin and/or mucosa, (though systemic involvement may also be observed), and is divided into the xanthogranuloma (XG) family and non-XG family. The XG family includes: juvenile xanthogranuloma (JXG); adult xanthogranuloma (AXG); solitary reticulohistiocytoma (SRH); benign cephalic histiocytosis (BCH); generalized eruptive histiocytosis (GEH); progressive nodular histiocytosis (PNH); and xanthoma disseminatum (XD). The non-XG family includes: cutaneous Rosai-Dorfman disease (RDD); necrobiotic xanthogranuloma (NXG); and multicentric reticulohistiocytosis (MRH).9 As noted, Emile et al adapted their classification system from Weitzman and Jaffe, who also distinguished cutaneous non-LCHs as either JXG or non-JXG.21 While disorders of the JXG family share the same immunophenotype, they vary in clinical presentation and histologic appearance (Table 2).

M group. The malignant histiocytoses (M) group is comprised of histiocytic sarcoma (HS); indeterminate cell sarcoma (ICS); Langerhans cell sarcoma (LCS); and follicular dendritic cell sarcoma (FDCS). Patients must present with rapidly progressing tumors for diagnosis. Tumor cells must also express at least two of the following macrophage/dendritic cell markers: CD68, CD163, CD4, and lysozyme. Malignant histiocytoses may be primary or secondary to another hematologic neoplasm.9

R group. Rosai-Dorfman disease (RDD), also referred to as sinus histiocytosis with massive lymphadenopathy, has an unknown etiology. Emile et al categorize classical RDD separately from RDD isolated to the skin into the R group and C group, respectively.9 RDD may be classical (nodal), extranodal, familial, neoplasia-associated, and immune disease-associated.9

Classical (nodal) RDD is a self-limited, benign disease that typically presents with bilateral painless cervical lymphadenopathy accompanied by systemic signs. Involvement of other lymph nodes is also commonly observed.45 Extranodal involvement has been observed in about 40 percent of cases, and the skin is the most frequent extranodal site (11 percent).46 Nevertheless, isolated cutaneous involvement (C group) is rare (three percent).46 Of note, in addition to distinct clinical presentations, epidemiologic factors regarding disease prevalence differs between classical RDD and RDD with isolated cutaneous involvement (Tables 3 and 5). Familial cases of RDD present in patients with the inherited conditions H syndrome and autoimmune lymphoproliferative syndrome.9 A discussion of these conditions is beyond the scope of this paper.

H group. Haemophagocytic lymphohistiocytosis (HLH), a disorder marked by excessive immune activation with resulting tissue damage,47 comprises the H group, and may be either inherited (primary) or acquired (secondary). HLH may be observed at any age, though generally patients presenting with primary disease are significantly younger than those presenting with secondary disease.48

Primary disease is either familial or attributed to an inherited immunodeficiency. Familial haemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive disorder occurring almost exclusively in infants49 that results from mutations in genes encoding proteins involved in granule-mediated cellular cytotoxicity,50-57 a means by which natural killer and T cells destroy infected or neoplastic cells. In addition to HLH inherited as an independent condition in the familial form, HLH may also develop secondary to an inherited immunodeficiency, such as Chédiak–Higashi syndrome,58,59 X-linked lymphoproliferative syndrome,60,61 Griscelli syndrome,62,63 and Hermansky-Pudlak syndrome.64,65 Secondary HLH develops in patients with acquired conditions that elicit excessive inflammation, such as those with autoimmune disease and/or other rheumatologic conditions,66-70 malignancy,71-75 organ or hematopoietic stem cell transplant,76-79 metabolic disorders,80-84 and infection.70,73,85-88 When secondary HLH occurs in patients with an underlying rheumatologic condition, the disease is referred to as “macrophage activation syndrome (MAS).”

Conclusion

Dermatologists are often essential in the diagnosis and management of histiocytic disorders due to the prevalence of cutaneous involvement, and should therefore be familiar with their unique clinical presentations, cutaneous manifestations, and immunohistochemical findings. Familiarity with Emile et al’s classification system will aid dermatologists in forming a differential diagnosis and in managing histiocytoses patients.

The authors are grateful to Prof Ronald Jaffe for his critical comments and suggestions concerning the pathology descriptions.

The authors did not receive funding and there are no conflicts of interest to report.

Jolie Krooks, BS is a pre-med student at Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL.

Milen Minkov, MD, PhD is at Medical University of Vienna, Rudolfstiftung Hospital, and Sigmund Freud Private University in Vienna, Austria.

Klemens Rappersberger, MD is at Rudolfstiftung Hospital and Sigmund Freud Private University in Vienna, Austria.

1. Filipovich A, McClain K, Grom A. Histiocytic disorders: recent insights into pathophysiology and practical guidelines. Biol Blood Marrow Transplant. 2010;16(1 Suppl):S82-89.

2. Senechal B, et al. Expansion of regulatory T cells in patients with Langerhans cell histiocytosis. PLoS Med. 2007;4(8):e253.

3. Ochoa MT, Loncaric A, Krutzik SR, Becker TC, Modlin RL. “Dermal dendritic cells” comprise two distinct populations: CD1+ dendritic cells and CD209+ macrophages. J Invest Dermatol. 2008;128(9):2225-2231.

4. Caux C, Lebecque S, Liu J-Y, al. e. Developmental Pathways of human myeloid dendritic cells. In: Lotze M, Thomson A, eds. Dendritic cells: biology and clinical application. San Diego: Academic Press; 1999:63-92.

5. Merad M, Manz MG, Karsunky H, et al. Langerhans cells renew in the skin throughout life under steady-state conditions. Nat Immunol. 2002;3(12):1135-1141.

6. Chorro L, Sarde A, Li M, et al. Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network. J Exp Med. 2009;206(13):3089-3100.

7. Soucie EL, Weng Z, Geirsdóttir L, et al. Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells. Science. 2016;351(6274):aad5510.

8. Tomura M, Hata A, Matsuoka S, et al. Tracking and quantification of dendritic cell migration and antigen trafficking between the skin and lymph nodes. Sci Rep. 2014;4:6030.

9. Emile JF, Abla O, Fraitag S, et al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood. 2016;127(22):2672-2681.

10. Guyot-Goubin A, Donadieu J, Barkaoui M, Bellec S, Thomas C, Clavel J. Descriptive epidemiology of childhood Langerhans cell histiocytosis in France, 2000-2004. Pediatr Blood Cancer. 2008;51(1):71-75.

11. Salotti JA, Nanduri V, Pearce MS, Parker L, Lynn R, Windebank KP. Incidence and clinical features of Langerhans cell histiocytosis in the UK and Ireland. Arch Dis Child. 2009;94(5):376-380.

12. Greenberger JS, et al. Results of treatment of 127 patients with systemic histiocytosis. Medicine (Baltimore). 1981;60(5):311-338.

13. Histiocytosis syndromes in children. Writing Group of the Histiocyte Society. Lancet. 1987;1(8526):208-209.

14. Favara BE, Feller AC, Pauli M, et al. Contemporary classification of histiocytic disorders. The WHO Committee On Histiocytic/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocyte Society. Med Pediatr Oncol. 1997;29(3):157-166.

15. Jeng M. Langerhans Cell Histiocytosis Enters the Genomics Age. Oncology (Williston Park). 2016;30(2):140-141.

16. Wan PT, Garnett MJ, Roe SM, et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell. 2004;116(6):855-867.

17. Machnicki MM, Stoklosa T. BRAF-a new player in hematological neoplasms. Blood Cells Mol Dis. 2014;53(1-2):77-83.

18. Hervier B, Haroche J, Arnaud L, et al. Association of both Langerhans cell histiocytosis and Erdheim-Chester disease linked to the BRAFV600E mutation. Blood. 2014;124(7):1119-1126.

19. Badalian-Very G, et al. Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood. 2010;116(11):1919-1923.

20. Emile JF, et al. Recurrent RAS and PIK3CA mutations in Erdheim-Chester disease. Blood. 2014;124(19):3016-3019.

21. Weitzman S, Jaffe R. Uncommon histiocytic disorders: the non-Langerhans cell histiocytoses. Pediatr Blood Cancer. 2005;45(3):256-264.

22. Facchetti F, et al. Histiocytic and dendritic cell neoplasms: what have we learnt by studying 67 cases. Virchows Arch. 2017.

23. Milne P, Bigley V, Bacon CM, et al. Hematopoietic origin of Langerhans cell histiocytosis and Erdheim-Chester disease in adults. Blood. 2017;130(2):167-175.

24. Satoh T, Smith A, Sarde A, et al. B-RAF mutant alleles associated with Langerhans cell histiocytosis, a granulomatous pediatric disease. PLoS One. 2012;7(4):e33891.

25. Cao XX, Sun J, Li J, et al. Evaluation of clinicopathologic characteristics and the BRAF V600E mutation in Erdheim-Chester disease among Chinese adults. Ann Hematol. 2016;95(5):745-750.

26. Berres ML, Lim KP, Peters T, et al. BRAF-V600E expression in precursor versus differentiated dendritic cells defines clinically distinct LCH risk groups. J Exp Med. 2014;211(4):669-683.

27. Sahm F, Capper D, Preusser M, et al. BRAFV600E mutant protein is expressed in cells of variable maturation in Langerhans cell histiocytosis. Blood. 2012;120(12):e28-34.

28. Haroche J, Charlotte F, Arnaud L, et al. High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses. Blood. 2012;120(13):2700-2703.

29. Emile JF, Charlotte F, Amoura Z, Haroche J. BRAF mutations in Erdheim-Chester disease. J Clin Oncol. 2013;31(3):398.

30. Chasset F, Barete S, Charlotte F, et al. Cutaneous manifestations of Erdheim-Chester disease (ECD): Clinical, pathological, and molecular features in a monocentric series of 40 patients. J Am Acad Dermatol. 2016;74(3):513-520.

31. Héritier S, Emile JF, Barkaoui MA, et al. BRAF Mutation Correlates With High-Risk Langerhans Cell Histiocytosis and Increased Resistance to First-Line Therapy. J Clin Oncol. 2016;34(25):3023-3030.

32. Diamond EL, Durham BH, Haroche J, et al. Diverse and Targetable Kinase Alterations Drive Histiocytic Neoplasms. Cancer Discov. 2016;6(2):154-165.

33. Berres ML, Merad M, Allen CE. Progress in understanding the pathogenesis of Langerhans cell histiocytosis: back to Histiocytosis X? Br J Haematol. 2015;169(1):3-13.

34. Nelson DS, van Halteren A, Quispel WT, et al. MAP2K1 and MAP3K1 mutations in Langerhans cell histiocytosis. Genes Chromosomes Cancer. 2015;54(6):361-368.

35. Brown NA, Furtado LV, Betz BL, et al. High prevalence of somatic MAP2K1 mutations in BRAF V600E-negative Langerhans cell histiocytosis. Blood. 2014;124(10):1655-1658.

36. Chakraborty R, Hampton OA, Shen X, et al. Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis. Blood. 2014;124(19):3007-3015.

37. Bentel JM, Thomas MA, Rodgers JJ, et al. Erdheim-Chester disease associated with a novel, complex BRAF p.Thr599_Val600delinsArgGlu mutation. BMJ Case Rep. 2017;2017.

38. Fedoriw Y, Kim YS, Vergilio JA, Chen ZW, Weiss LM, O’Malley DP. BRAF V600E mutation-specific immunohistochemistry is a rare finding in dendritic cell- and histiocyte-derived tumors. Leuk Lymphoma. 2015;56(4):1132-1133.

39. O’Malley DP, Agrawal R, Grimm KE, et al. Evidence of BRAF V600E in indeterminate cell tumor and interdigitating dendritic cell sarcoma. Ann Diagn Pathol. 2015;19(3):113-116.

40. Toebak MJ, et al. Dendritic cells: biology of the skin. Contact Dermatitis. 2009;60(1):2-20.

41. Brown RA, Kwong BY, McCalmont TH, et al. ETV3-NCOA2 in indeterminate cell histiocytosis: clonal translocation supports sui generis. Blood. 2015;126(20):2344-2345.

42. Strehl S, Nebral K, König M, et al. ETV6-NCOA2: a novel fusion gene in acute leukemia associated with coexpression of T-lymphoid and myeloid markers and frequent NOTCH1 mutations. Clin Cancer Res. 2008;14(4):977-983.

43. Liu ZJ, Xiao M, Balint K, et al. Inhibition of endothelial cell proliferation by Notch1 signaling is mediated by repressing MAPK and PI3K/Akt pathways and requires MAML1. FASEB J. 2006;20(7):1009-1011.

44. Rodig SJ, Payne EG, Degar BA, et al. Aggressive Langerhans cell histiocytosis following T-ALL: clonally related neoplasms with persistent expression of constitutively active NOTCH1. Am J Hematol. 2008;83(2):116-121.

45. La Barge DV, Salzman KL, Harnsberger HR, et al. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): imaging manifestations in the head and neck. AJR Am J Roentgenol. 2008;191(6):W299-306.

46. Foucar E, Rosai J, Dorfman R. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): review of the entity. Semin Diagn Pathol. 1990;7(1):19-73.

47. Henter JI, et al. Hypercytokinemia in familial hemophagocytic lymphohistiocytosis. Blood. 1991;78(11):2918-2922.

48. Pei R, Wang Z, Wang Y, et al. A multicenter retrospective etiological analysis of 601 patients with hemophagocytic lymphohistiocytosis in China. Zhonghua Nei Ke Za Zhi. 2015;54(12):1018-1022.

49. Ishii E, et al. Nationwide survey of hemophagocytic lymphohistiocytosis in Japan. Int J Hematol. 2007;86(1):58-65.

50. Ohadi M, Lalloz MR, Sham P, et al. Localization of a gene for familial hemophagocytic lymphohistiocytosis at chromosome 9q21.3-22 by homozygosity mapping. Am J Hum Genet. 1999;64(1):165-171.

51. Dufourcq-Lagelouse R, Jabado N, Le Deist F, et al. Linkage of familial hemophagocytic lymphohistiocytosis to 10q21-22 and evidence for heterogeneity. Am J Hum Genet. 1999;64(1):172-179.

52. Stepp SE, Dufourcq-Lagelouse R, Le Deist F, et al. Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science. 1999;286(5446):1957-1959.

53. Trizzino A, zur Stadt U, Ueda I, et al. Genotype-phenotype study of familial haemophagocytic lymphohistiocytosis due to perforin mutations. J Med Genet. 2008;45(1):15-21.

54. Lee SM, Sumegi J, Villanueva J, et al. Patients of African ancestry with hemophagocytic lymphohistiocytosis share a common haplotype of PRF1 with a 50delT mutation. J Pediatr. 2006;149(1):134-137.

55. Yoon HS, Kim HJ, Yoo KH, et al. UNC13D is the predominant causative gene with recurrent splicing mutations in Korean patients with familial hemophagocytic lymphohistiocytosis. Haematologica. 2010;95(4):622-626.

56. Santoro A, Cannella S, Bossi G, et al. Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis. J Med Genet. 2006;43(12):953-960.

57. zur Stadt U, Rohr J, Seifert W, et al. Familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) is caused by mutations in Munc18-2 and impaired binding to syntaxin 11. Am J Hum Genet. 2009;85(4):482-492.

58. Nielsen C, et al. Infantile hemophagocytic lymphohistiocytosis in a case of chediak-higashi syndrome caused by a mutation in the LYST/CHS1 gene presenting with delayed umbilical cord detachment and diarrhea. J Pediatr Hematol Oncol. 2015;37(2):e73-79.

59. Elevli M, et al. Chediak-higashi syndrome: a case report of a girl without silvery hair and oculocutaneous albinism presenting with hemophagocytic lymphohistiocytosis. Turk J Haematol. 2014;31(4):426-427.

60. Bird JA, McClain KL, Rosenblatt HM, Abramson SL, Hanson IC. Hemophagocytic lymphohistiocytosis in a patient with x-linked lymphoproliferative disease. Allergy Asthma Proc. 2009;30(4):458-462.

61. Sankararaman S, Riel-Romero RM, Jeroudi M, Gonzalez-Toledo E. Epstein-Barr virus induced hemophagocytic lymphohistiocytosis in X-linked lymphoproliferative disease. J Neurosci Rural Pract. 2014;5(2):171-174.

62. Love PB, Patterson SS, Prose NS, Atwater AR. Griscelli syndrome associated with hemophagocytic lymphohistiocytosis. J Drugs Dermatol. 2012;11(9):1126.

63. Demircioğlu F, Aydın H, Erkoçoğlu M, Önay H, Dağıstan E. Griscelli Syndrome Presented with Status Epilepticus and Hemophagocytic Lymphohistiocytosis. Turk J Haematol. 2017;34(1):120-121.

64. Enders A, Zieger B, Schwarz K, et al. Lethal hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type II. Blood. 2006;108(1):81-87.

65. Jessen B, Bode SF, Ammann S, et al. The risk of hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type 2. Blood. 2013;121(15):2943-2951.

66. Fukaya S, Yasuda S, Hashimoto T, et al. Clinical features of haemophagocytic syndrome in patients with systemic autoimmune diseases: analysis of 30 cases. Rheumatology (Oxford). 2008;47(11):1686-1691.

67. Gupta D, Mohanty S, Thakral D, Bagga A, Wig N, Mitra DK. Unusual Association of Hemophagocytic Lymphohistiocytosis in Systemic Lupus Erythematosus: Cases Reported at Tertiary Care Center. Am J Case Rep. 2016;17:739-744.

68. So MW, et al. Successful rituximab treatment of refractory hemophagocytic lymphohistiocytosis and autoimmune hemolytic anemia associated with systemic lupus erythematosus. Mod Rheumatol. 2014;24(5):855-857.

69. Lehmberg K, et al. Differentiating macrophage activation syndrome in systemic juvenile idiopathic arthritis from other forms of hemophagocytic lymphohistiocytosis. J Pediatr. 2013;162(6):1245-1251.

70. Fitzgerald MP, et al. A case of EBV driven haemophagocytic lymphohistiocytosis complicating a teenage Crohn’s disease patient on azathioprine, successfully treated with rituximab. J Crohns Colitis. 2013;7(4):314-317.

71. Alaoua A, Gilbert G, Ghannouchi N, Houchlef M, Letaief A, Bahri F. Primary bilateral adrenal lymphoma revealed by hemophagocytic syndrome. Ann Endocrinol (Paris). 2011;72(3):247-250.

72. Li F, et al. Identification of clinical features of lymphoma-associated hemophagocytic syndrome (LAHS): an analysis of 69 patients with hemophagocytic syndrome from a single-center in central region of China. Med Oncol. 2014;31(4):902.

73. Buyse S, Teixeira L, Galicier L, et al. Critical care management of patients with hemophagocytic lymphohistiocytosis. Intensive Care Med. 2010;36(10):1695-1702.

74. Moritake H, Kamimura S, Nunoi H, et al. Clinical characteristics and genetic analysis of childhood acute lymphoblastic leukemia with hemophagocytic lymphohistiocytosis: a Japanese retrospective study by the Kyushu-Yamaguchi Children’s Cancer Study Group. Int J Hematol. 2014;100(1):70-78.

75. El-Masry M, Eisenbud L, Tran MH. Secondary hemophagocytic lymphohistiocytosis in the setting of metastatic renal cell carcinoma: a case report. J Med Case Rep. 2017;11(1):56.

76. Karras A, Thervet E, Legendre C, France GCdtdId. Hemophagocytic syndrome in renal transplant recipients: report of 17 cases and review of literature. Transplantation. 2004;77(2):238-243.

77. Taniai N, Akimaru K, Kawano Y, et al. Hemophagocytic syndrome after living-donor liver transplantation for fulminant liver failure: a case report. Hepatogastroenterology. 2005;52(63):923-926.

78. Diaz-Guzman E, Dong B, Hobbs SB, Kesler MV, Hayes D. Hemophagocytic lymphohistiocytosis after lung transplant: report of 2 cases and a literature review. Exp Clin Transplant. 2011;9(3):217-222.

79. Boelens JJ, Lazo G, Gaiser JF, Wulffraat NM. Epstein-Barr virus-associated haemophagocytic lympho-histiocytosis after stem cell transplantation. Bone Marrow Transplant. 2006;38(10):709-710.

80. Duval M, Fenneteau O, Doireau V, et al. Intermittent hemophagocytic lymphohistiocytosis is a regular feature of lysinuric protein intolerance. J Pediatr. 1999;134(2):236-239.

81. Kundak AA, Zenciroğlu A, Yaralı N, et al. An unusual presentation of galactosemia: hemophagocytic lymphohistiocytosis. Turk J Haematol. 2012;29(4):401-404.

82. Wu S, Gonzalez-Gomez I, Coates T, Yano S. Cobalamin C disease presenting with hemophagocytic lymphohistiocytosis. Pediatr Hematol Oncol. 2005;22(8):717-721.

83. Gholamreza B, Ghasem MA. Hemophagocytic lymphohistiocytosis syndrome associated with Gaucher disease type 2. Turk J Haematol. 2014;31(3):307-308.

84. Taurisano R, Maiorana A, De Benedetti F, Dionisi-Vici C, Boldrini R, Deodato F. Wolman disease associated with hemophagocytic lymphohistiocytosis: attempts for an explanation. Eur J Pediatr. 2014;173(10):1391-1394.

85. Bayhan G, Çenesiz F, Tanır G, Taylan Özkan A, Çınar G. First Case of Ascaris lumbricoides Infestation Complicated with Hemophagocytic Lymphohistiocytosis. Turkiye Parazitol Derg. 2015;39(2):164-166.

86. Gagnaire MH, Galambrun C, Stéphan JL. Hemophagocytic syndrome: A misleading complication of visceral leishmaniasis in children--a series of 12 cases. Pediatrics. 2000;106(4):E58.

87. Komatsuda A, Chubachi A, Miura AB. Virus-associated hemophagocytic syndrome due to measles accompanied by acute respiratory failure. Intern Med. 1995;34(3):203-206.

88. Santos JA, Neves JF, Venâncio P, Gouveia C, Varandas L. Hemophagocytic lymphohistiocytosis secondary to Falciparum malaria in a 5 year-old boy. Ann Hematol. 2015;94(1):161-163.

89. Degar B, Rollins B. Langerhans cell histiocytosis: malignancy or inflammatory disorder doing a great job of imitating one? Dis Model Mech. 2009;2:436-439.

90. El Demellawy D, et al. Langerhans cell histiocytosis: a comprehensive review. Pathology. 2015;47(4):294-301.

91. Girschikofsky M, Arico M, Castillo D, et al. Management of adult patients with Langerhans cell histiocytosis: recommendations from an expert panel on behalf of Euro-Histio-Net. Orphanet J Rare Dis. 2013;8:72.

92. Haupt R, Minkov M, Astigarraga I, et al. Langerhans cell histiocytosis (LCH): guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years. Pediatr Blood Cancer. 2013;60(2):175-184.

93. Haroche J, Amoura Z, Dion E, et al. Cardiovascular involvement, an overlooked feature of Erdheim-Chester disease: report of 6 new cases and a literature review. Medicine (Baltimore). 2004;83(6):371-392.

94. Campochiaro C, et al. Erdheim-Chester disease. Eur J Intern Med. 2015;26(4):223-229.

95. Bisceglia M, Cammisa M, Suster S, Colby TV. Erdheim-Chester disease: clinical and pathologic spectrum of four cases from the Arkadi M. Rywlin slide seminars. Adv Anat Pathol. 2003;10(3):160-171.

96. Zerbini MC, Sotto MN, de Campos FP, et al. Indeterminate cell histiocytosis successfully treated with phototherapy. Autops Case Rep. 2016;6(2):33-38.

97. Wang CH, Chen GS. Indeterminate cell histiocytosis: a case report. Kaohsiung J Med Sci. 2004;20(1):24-30.

98. Martín JM, et al. Histiocytosis with mixed cell populations. J Cutan Pathol. 2016;43(5):456-460.

99. Rodríguez-Jurado R, Vidaurri-de la Cruz H, Durán-Mckinster C, Ruíz-Maldonado R. Indeterminate cell histiocytosis. Clinical and pathologic study in a pediatric patient. Arch Pathol Lab Med. 2003;127(6):748-751.

100. Calatayud M, Güell JL, Gris O, Puig J, Arrondo E, Huguet P. Ocular involvement in a case of systemic indeterminate cell histiocytosis: a case report. Cornea. 2001;20(7):769-771.

101. Zelger B, Burgdorf WH. The cutaneous “histiocytoses”. Adv Dermatol. 2001;17:77-114.

102. Manente L, et al. Indeterminate cell histiocytosis: a rare histiocytic disorder. Am J Dermatopathol. 1997;19(3):276-283.

103. Fernandez-Flores A, Manjon JA, Manzarbeitia F. Double immunostaining with CD1A and CD68 in the phenotypic characterization of indeterminate cell histiocytosis. Cesk Patol. 2008;44(2):37-39.

104. Tóth B, Katona M, Hársing J, Szepesi A, Kárpáti S. Indeterminate cell histiocytosis in a pediatric patient: successful treatment with thalidomide. Pathol Oncol Res. 2012;18(2):535-538.

105. Estrada-Veras JI, O’Brien KJ, Boyd LC, et al. The clinical spectrum of Erdheim-Chester disease: an observational cohort study. Blood Adv. 2017;1(6):357-366.

106. Chantorn R, Wisuthsarewong W, Aanpreung P, Sanpakit K, Manonukul J. Severe congenital systemic juvenile xanthogranuloma in monozygotic twins. Pediatr Dermatol. 2008;25(4):470-473.

107. Sivapirabu G, Sugo E, Wargon O. Juvenile xanthogranuloma: challenges in complicated cases. Australas J Dermatol. 2011;52(4):284-287.

108. Hernandez-Martin A, et al. Juvenile xanthogranuloma. J Am Acad Dermatol. 1997;36(3 Pt 1):355-367; 368-359.

109. Vanotti S, et al. Localized eruptive juvenile xanthogranuloma. Ann Dermatol Venereol. 2014;141(3):206-210.

110. Dehner LP. Juvenile xanthogranulomas in the first two decades of life: a clinicopathologic study of 174 cases with cutaneous and extracutaneous manifestations. Am J Surg Pathol. 2003;27(5):579-593.

111. Chang MW, Frieden IJ, Good W. The risk intraocular juvenile xanthogranuloma: survey of current practices and assessment of risk. J Am Acad Dermatol. 1996;34(3):445-449.

112. Cohen BA, Hood A. Xanthogranuloma: report on clinical and histologic findings in 64 patients. Pediatr Dermatol. 1989;6(4):262-266.

113. Chu AC. The confusing state of the histiocytoses. Br J Dermatol. 2000;143(3):475-476.

114. Zelger BW, Cerio R. Xanthogranuloma is the archetype of non-Langerhans cell histiocytoses. Br J Dermatol. 2001;145(2):369-371.

115. Zelger BW, Sidoroff A, Orchard G, Cerio R. Non-Langerhans cell histiocytoses. A new unifying concept. Am J Dermatopathol. 1996;18(5):490-504.

116. Chang, S-E., Cho S, Choi J-C. Clinicopathologic comparison of adult type and juvenile type xanthogranulomas in Korea. J Dermatol. 2001;28:413-418.

117. Shoo BA, Shinkai K, McCalmont TH, Fox LP. Xanthogranulomas associated with hematologic malignancy in adulthood. J Am Acad Dermatol. 2008;59(3):488-493.

118. Larson MJ, Bandel C, Eichhorn PJ, Cruz PD. Concurrent development of eruptive xanthogranulomas and hematologic malignancy: two case reports. J Am Acad Dermatol. 2004;50(6):976-978.

119. Pino Gil M, Miquel FJ, Velasco M, Vilata JJ, Aliaga A. Multiple xanthogranulomas in an adult, associated with essential thrombocytosis. Br J Dermatol. 1995;132(6):1018-1021.

120. Inoue H, Seichi A, Yamamuro K, Kojima M, Kimura A, Hoshino Y. Dumbbell-type juvenile xanthogranuloma in the cervical spine of an adult. Eur Spine J. 2011;20 Suppl 2:S343-347.

121. Miettinen M, Fetsch JF. Reticulohistiocytoma (solitary epithelioid histiocytoma): a clinicopathologic and immunohistochemical study of 44 cases. Am J Surg Pathol. 2006;30(4):521-528.

122. Caputo R, Grimalt R. Solitary reticulohistiocytosis (reticulohistiocytoma) of the skin in children: report of two cases. Arch Dermatol. 1992;128(5):698-699.

123. Shibuya R, et al. A plaque-type solitary reticulohistiocytoma in a two-year-old boy. Case Rep Dermatol. 2015;7(1):7-9.

124. Jih DM, et al. Benign cephalic histiocytosis: a case report and review. J Am Acad Dermatol. 2002;47(6):908-913.

125. Patsatsi A, Kyriakou A, Sotiriadis D. Benign cephalic histiocytosis: case report and review of the literature. Pediatr Dermatol. 2014;31(5):547-550.

126. Baler JS, DiGregorio FM, Hashimoto K. Facial papules in a child. Benign cephalic histiocytosis. Arch Dermatol. 1995;131(5):610-611, 613-614.

127. Gianotti F, Caputo R, Ermacora E, Gianni E. Benign cephalic histiocytosis. Arch Dermatol. 1986;122(9):1038-1043.

128. Sidwell RU, Francis N, Slater DN, Mayou SC. Is disseminated juvenile xanthogranulomatosis benign cephalic histiocytosis? Pediatr Dermatol. 2005;22(1):40-43.

129. Watabe H, et al. Case 2: Benign cephalic histiocytosis. Clin Exp Dermatol. 2002;27(4):341-342.

130. Koca R, Bektaş S, Altinyazar HC, Sezer T. Benign cephalic histiocytosis: a case report. Ann Dermatol. 2011;23(4):508-511.

131. Caputo R, et al. Generalized eruptive histiocytoma in children. J Am Acad Dermatol. 1987;17(3):449-454.

132. Gupta R. Cutaneous histiocytoses X. In: Freedberg, IM., Eisen E, Wolf K, eds. Dermatology in General Medicine. Vol 3. 5 ed. New York: McGraw Hill; 1999:1892-1902.

133. Chu A. Histiocytosis. In: Burns T, Breathnach S, Cox N, Griffiths C, eds. Rook’s Textbook of Dermatology. Vol 8. Oxford: Blackwell Publishing; 2010:55.51-55.33.

134. Winkelmann RK, Muller SA. Generalized eruptive histiocytoma. Arch Dermatol. 1963;88:586-596.

135. Cardoso F, Serafini NB, Reis BD, Nuñez MD, Nery JA, Lupi O. Generalized eruptive histiocytoma: a rare disease in an elderly patient. An Bras Dermatol. 2013;88(1):105-108.

136. Lan Ma H, Metze D, Luger TA, Steinhoff M. Successful treatment of generalized eruptive histiocytoma with PUVA. J Dtsch Dermatol Ges. 2007;5(2):131-134.

137. Fernández-Jorge B, Goday-Buján J, Del Pozo Losada J, Alvarez-Rodríguez R, Fonseca E. A case of generalized eruptive histiocytosis. Acta Derm Venereol. 2007;87(6):533-536.

138. Seward JL, Malone JC, Callen JP. Generalized eruptive histiocytosis. J Am Acad Dermatol. 2004;50(1):116-120.

139. Taunton OD, Yeshurun D, Jarratt M. Progressive nodular histiocytoma. Arch Dermatol. 1978;114(10):1505-1508.

140. Burgdorf WH, Kusch SL, Nix TE, Pitha J. Progressive nodular histiocytoma. Arch Dermatol. 1981;117(10):644-649.

141. Watanabe T, et al. Progressive nodular histiocytosis - A five-year follow up. Eur J Dermatol. 2008;18(2):200-202.

142. Kunimoto K, Uede K, Furukawa F. Progressive nodular histiocytosis. J Dermatol. 2010;37(12):1071-1073.

143. Gonzalez Ruíz A, Bernal Ruíz AI, Aragoneses Fraile H, Peral Martinez I, García Muñoz M. Progressive nodular histiocytosis accompanied by systemic disorders. Br J Dermatol. 2000;143(3):628-631.

144. Robinson HM, Harmon LE, Firminger HI. Multiple Lipoidal Histiocytomas with regression. Arch Dermatol. 1963;88:660-667.

145. Torres L, Sánchez JL, Rivera A, González A. Progressive nodular histiocytosis. J Am Acad Dermatol. 1993;29(2 Pt 1):278-280.

146. Hilker O, Kovneristy A, Varga R, et al. Progressive nodular histiocytosis. J Dtsch Dermatol Ges. 2013;11(4):301-307.

147. Rodríguez HA, Saúl A, Galloso de Bello L, Tay J, Peyro E. Nodular cutaneous reactive histiocytosis caused by an unidentified microorganism: report of a case. Int J Dermatol. 1974;13(5):248-260.

148. Glavin FL, Chhatwall H, Karimi K. Progressive nodular histiocytosis: a case report with literature review, and discussion of differential diagnosis and classification. J Cutan Pathol. 2009;36(12):1286-1292.

149. Caputo R, Brezzi A, Vaccari G, Cavicchini S, Gianotti R. Progressive histiocytosis: description of a case of slow-course non-Langerhans cell histiocytosis. Dermatology. 2002;205(3):293-297;discussion 296-297.

150. Caputo R, Marzano AV, Passoni E, Berti E. Unusual variants of non-Langerhans cell histiocytoses. J Am Acad Dermatol. 2007;57(6):1031-1045.

151. Zelger BW, Staudacher C, Orchard G, Wilson-Jones E, Burgdorf WH. Solitary and generalized variants of spindle cell xanthogranuloma (progressive nodular histiocytosis). Histopathology. 1995;27(1):11-19.

152. Calverly DC, Wismer J, Rosenthal D, deSa D, Barr RD. Xanthoma disseminatum in an infant with skeletal and marrow involvement. J Pediatr Hematol Oncol. 1995;17(1):61-65.

153. Varotti C, Bettoli V, Berti E, Cavicchini S, Caputo R. Xanthoma disseminatum: a case with extensive mucous membrane involvement. J Am Acad Dermatol. 1991;25(2 Pt 2):433-436.

154. Knobler RM, Neumann RA, Gebhart W, Radaskiewicz T, Ferenci P, Widhalm K. Xanthoma disseminatum with progressive involvement of the central nervous and hepatobiliary systems. J Am Acad Dermatol. 1990;23(2 Pt 2):341-346.

155. Hammond RR, Mackenzie IR. Xanthoma disseminatum with massive intracranial involvement. Clin Neuropathol. 1995;14(6):314-321.

156. Davies CW, et al. Xanthoma disseminatum with respiratory tract involvement and fatal outcome. Thorax. 2000;55(2):170-172.

157. Caputo R, Veraldi S, Grimalt R, et al. The various clinical patterns of xanthoma disseminatum. Considerations on seven cases and review of the literature. Dermatology. 1995;190(1):19-24.

158. Caputo R, Monti M, Berti E, Gasparini G. Normolipemic eruptive cutaneous xanthomatosis. Arch Dermatol. 1986;122(11):1294-1297.

159. Yağci B, Varan A, Altinok G, Söylemezoğlu F, Cila A, Büyükpamukçu M. Xanthoma disseminatum in a child with cranial bone involvement. J Pediatr Hematol Oncol. 2008;30(4):310-312.

160. Paolini TS, Helm TN. Photo quiz. Xanthoma disseminatum. Cutis. 2000;65(6):351, 377-358, 384.

161. Altman J, Winkelmann RK. Diffuse normolipemic plane xanthoma. Generalized xanthelasma. Arch Dermatol. 1962;85:633-640.

162. Beurey J, Lamaze B, Weber M, Delrous JL, Kremer B, Chaulieu Y. Xanthoma disseminatum (Montgomery’s syndrome) (author’s transl). Ann Dermatol Venereol. 1979;106(4):353-359.

163. Altman J, Winkelman RK. Xanthoma disseminatum. Archives of Dermatology. 1962;86(5):582-596.

164. Kilinç Y, Ozşahinoglu C, Varinli S, Acar A, Kaya M. An unusual case of Xanthoma disseminatum. Int J Pediatr Otorhinolaryngol. 1992;23(1):73-79.

165. Turner A, Davidson J, White A. Xanthomatosis: some aspects of its blood chemistry and pathology, case 4. Edinburgh Medical Journal. 1925;32:153.

166. Weiss N, Keller C. Xanthoma disseminatum: a rare normolipemic xanthomatosis. Clin Investig. 1993;71(3):233-238.

167. Moloney JR. Xanthoma disseminatum: its otolaryngological manifestations. J Laryngol Otol. 1979;93(2):201-210.

168. Mishkel MA, Cockshott WP, Nazir DJ, Rosenthal D, Spaulding WP, Wynn-Williams A. Xanthoma disseminatum. Clinical, metabolic, pathologic, and radiologic aspects. Arch Dermatol. 1977;113(8):1094-1100.

169. Ringel E, Moschella S. Primary histiocytic dermatoses. Arch Dermatol. 1985;121(12):1531-1541.

170. Tran TH, Pope E, Weitzman S. Cutaneous Histiocytoses. In: Rook’s Textbook of Dermatology. 9 ed.2016:1-35.

171. Dalia S, Sagatys E, Sokol L, Kubal T. Rosai-Dorfman disease: tumor biology, clinical features, pathology, and treatment. Cancer Control. 2014;21(4):322-327.

172. Cook-Norris RH,et al. Purely cutaneous Rosai-Dorfman disease. Int J Dermatol. 2009;48(4):439-440.

173. Riyaz N, Khader A, Sarita S. Rosai-Dorfman syndrome. Indian J Dermatol Venereol Leprol. 2005;71(5):342-344.

174. Wang KH, Chen WY, Liu HN, Huang CC, Lee WR, Hu CH. Cutaneous Rosai-Dorfman disease: clinicopathological profiles, spectrum and evolution of 21 lesions in six patients. Br J Dermatol. 2006;154(2):277-286.

175. Chappell JA, Burkemper NM, Frater JL, Hurley MY. Cutaneous rosai-dorfman disease and morphea: coincidence or association? Am J Dermatopathol. 2009;31(5):487-489.

176. Bens G, Kerdraon R, De Kyvon JJ, Estève E. Indolent firm reddish papules. Cutaneous Rosai-Dorfman disease. Hautarzt. 2011;62(5):384-387.

177. Uniyal SK, Beena KR, Ramesh V, Mukherjee A. Cutaneous Rosai-Dorfman disease preceding inguinal lymphadenopathy. Int J Dermatol. 2002;41(7):404-406.

178. Rodríguez-Blanco I, Suárez-Peñaranda JM, Toribio J. Atypical presentation and dermoscopic evaluation of cutaneous Rosai-Dorfman Disease. Acta Derm Venereol. 2009;89(4):430-431.

179. Avilés-Izquierdo JA, Parra Blanco V, Alfageme Roldán F. Dermoscopic features of cutaneous Rosai-Dorfman disease. Actas Dermosifiliogr. 2012;103(5):446-448.

180. Burgdorf, W., Zelger B. The histiocytoses. In: Elder D, ed. Lever’s Histopathology of the Skin. 10 ed. Philadelphia: Lippincott Williams and Wilkins; 2009:678-679.

181. Jat KR, Panigrahi I, Srinivasan R, et al. Cutaneous Rosai-Dorfman disease: presenting as massive bilateral eyelid swelling. Pediatr Dermatol. 2009;26(5):633-635.

182. Chu P, LeBoit PE. Histologic features of cutaneous sinus histiocytosis (Rosai-Dorfman disease): study of cases both with and without systemic involvement. J Cutan Pathol. 1992;19(3):201-206.

183. Kong YY, Kong JC, Shi DR, et al. Cutaneous rosai-dorfman disease: a clinical and histopathologic study of 25 cases in China. Am J Surg Pathol. 2007;31(3):341-350.

184. Tsang WY, Chan JK, Ho WK, Yu HC, Chow LT. Extranodal Rosai-Dorfman disease: an uncommon cause of persistent nodule in the ear. J Laryngol Otol. 1992;106(3):249-251.

185. Kang JM, Yang WI, Kim SM, Lee MG. Sinus histiocytosis (Rosai-Dorfman disease) clinically limited to the skin. Acta Derm Venereol. 1999;79(5):363-365.

186. Scheel MM, Rady PL, Tyring SK, Pandya AG. Sinus histiocytosis with massive lymphadenopathy: presentation as giant granuloma annulare and detection of human herpesvirus 6. J Am Acad Dermatol. 1997;37(4):643-646.

187. Lu CI, Kuo TT, Wong WR, Hong HS. Clinical and histopathologic spectrum of cutaneous Rosai-Dorfman disease in Taiwan. J Am Acad Dermatol. 2004;51(6):931-939.

188. Brenn T, et al. Cutaneous rosai-dorfman disease is a distinct clinical entity. Am J Dermatopathol. 2002;24(5):385-391.

189. Spicknall KE, Mehregan DA. Necrobiotic xanthogranuloma. Int J Dermatol. 2009;48(1):1-10.

190. Mehregan DA, Winkelmann RK. Necrobiotic xanthogranuloma. Arch Dermatol. 1992;128(1):94-100.

191. Kossard S, Winkelmann RK. Necrobiotic xanthogranuloma with paraproteinemia. J Am Acad Dermatol. 1980;3(3):257-270.

192. Burgdorf W, Bernhard Z. The Histiocytoses. In: Elder D, ed. Lever’s Histopathology of the Skin. 9 ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:697-698.

193. Ugurlu S, Bartley GB, Gibson LE. Necrobiotic xanthogranuloma: long-term outcome of ocular and systemic involvement. Am J Ophthalmol. 2000;129(5):651-657.

194. Chave TA, Hutchinson PE. Necrobiotic xanthogranuloma with two monoclonal paraproteins and no periorbital involvement at presentation. Clin Exp Dermatol. 2001;26(6):493-496.

195. Johnston KA, Grimwood RE, Meffert JJ, Deering KC. Necrobiotic xanthogranuloma with paraproteinemia: an evolving presentation. Cutis. 1997;59(6):333-336.

196. Flann S, et al. Necrobiotic xanthogranuloma with paraproteinaemia. Clin Exp Dermatol. 2006;31(2):248-251.

197. Sabet LM, et al. An unusual cause of refractive chronic bilateral leg ulceration. J Cutan Med Surg. 2004;8(6):432-437.

198. Chang SE, Lee WS, Lee MW, et al. A case of necrobiotic xanthogranuloma without paraproteinemia presenting as a solitary tumor on the thigh. Int J Dermatol. 2003;42(6):470-472.

199. Criado PR, Vasconcellos C, Pegas JR, et al. Necrobiotic xanthogranuloma with lambda paraproteinemia: case report of successful treatment with melphalan and prednisone. J Dermatolog Treat. 2002;13(2):87-89.

200. Finan MC, Winkelmann RK. Necrobiotic xanthogranuloma with paraproteinemia. A review of 22 cases. Medicine (Baltimore). 1986;65(6):376-388.

201. Wood AJ, Wagner MV, Abbott JJ, Gibson LE. Necrobiotic xanthogranuloma: a review of 17 cases with emphasis on clinical and pathologic correlation. Arch Dermatol. 2009;145(3):279-284.

202. Rapini RP. Multicentric reticulohistiocytosis. Clin Dermatol. 1993;11(1):107-111.

203. Goto H, Inaba M, Kobayashi K, et al. Successful treatment of multicentric reticulohistiocytosis with alendronate: evidence for a direct effect of bisphosphonate on histiocytes. Arthritis Rheum. 2003;48(12):3538-3541.

204. Tani M, Hori K, Nakanishi T, Iwasaki T, Ogawa Y, Jimbo T. Multicentric reticulohistiocytosis. Electron microscopic and ultracytochemical studies. Arch Dermatol. 1981;117(8):495-499.

205. Perrin C, Lacour JP, Michiels JF, Flory P, Ziegler G, Ortonne JP. Multicentric reticulohistiocytosis. Immunohistological and ultrastructural study: a pathology of dendritic cell lineage. Am J Dermatopathol. 1992;14(5):418-425.

206. Barrow MV, Holubar K. Multicentric reticulohistiocytosis. A review of 33 patients. Medicine (Baltimore). 1969;48(4):287-305.

207. Bogle MA, Tschen JA, Sairam S, McNearney T, Orsak G, Knox JM. Multicentric reticulohistiocytosis with pulmonary involvement. J Am Acad Dermatol. 2003;49(6):1125-1127.

208. West KL, Sporn T, Puri PK. Multicentric reticulohistiocytosis: a unique case with pulmonary fibrosis. Arch Dermatol. 2012;148(2):228-232.

209. Yoshimura K, Sato J, Imokawa S, Kageyama H, Tokura Y, Suda T. Organizing pneumonia associated with multicentric reticulohistiocytosis. Respirol Case Rep. 2015;3(4):125-127.

210. Yang HJ, Ding YQ, Deng YJ. Multicentric reticulohistiocytosis with lungs and liver involved. Clin Exp Dermatol. 2009;34(2):183-185.

211. Benucci M, Sulla A, Manfredi M. Cardiac engagement in multicentric reticulohistiocytosis: report of a case with fatal outcome and literature review. Intern Emerg Med. 2008;3(2):165-168.

212. Lambert CM, Nuki G. Multicentric reticulohistiocytosis with arthritis and cardiac infiltration: regression following treatment for underlying malignancy. Ann Rheum Dis. 1992;51(6):815-817.

213. Yee KC, et al. Cardiac and systemic complications in multicentric reticulohistiocytosis. Clin Exp Dermatol. 1993;18(6):555-558.

214. Catterall MD, White JE. Multicentric reticulohistiocytosis and malignant disease. Br J Dermatol. 1978;98(2):221-224.

215. Tariq S, et al. Multicentric reticulohistiocytosis (MRH): case report with review of literature between 1991 and 2014 with in depth analysis of various treatment regimens and outcomes. Springerplus. 2016;5:180.

216. Fett N, Liu RH. Multicentric reticulohistiocytosis with dermatomyositis-like features: a more common disease presentation than previously thought. Dermatology. 2011;222(2):102-108.

217. Ben Abdelghani K, Mahmoud I, Chatelus E, Sordet C, Gottenberg JE, Sibilia J. Multicentric reticulohistiocytosis: an autoimmune systemic disease? Case report of an association with erosive rheumatoid arthritis and systemic Sjogren syndrome. Joint Bone Spine. 2010;77(3):274-276.

218. Takahashi M, Mizutani H, Nakamura Y, Shimizu M. A case of multicentric reticulohistiocytosis, systemic sclerosis and Sjögren syndrome. J Dermatol. 1997;24(8):530-534.

219. Carey RN, Blotzer JW, Wolfe ID, Glusman SM, Arnett FC. Multicentric reticulohistiocytosis and Sjögren’s syndrome. J Rheumatol. 1985;12(6):1193-1195.

220. Valentín-Nogueras SM, Seijo-Montes R, Montalván-Miró E, Sánchez JL. Langerhans cell sarcoma: a case report. J Cutan Pathol. 2013;40(7):670-675.

221. Ma X, Li W, Du J, Cai L, Zhang J. A case of an adult Langerhans cell sarcoma. Int J Dermatol. 2016;55(1):92-96.

222. Xu Z, et al. Langerhans cell sarcoma with an aberrant cytoplasmic CD3 expression. Diagn Pathol. 2012;7:128.

223. Howard JE, et al. Langerhans cell sarcoma: a systematic review. Cancer Treat Rev. 2015;41(4):320-331.

224. Chan J, et al. Follicular dendritic cell sarcoma. In: Swerdlow S, Campo E, Harris N, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Vol 2. 4 ed. Lyon, France: IARC Press; 2008:363-364.

225. Duan GJ, Wu F, Zhu J, et al. Extranodal follicular dendritic cell sarcoma of the pharyngeal region: a potential diagnostic pitfall, with literature review. Am J Clin Pathol. 2010;133(1):49-58.

226. Perez-Ordoñez B, Rosai J. Follicular dendritic cell tumor: review of the entity. Semin Diagn Pathol. 1998;15(2):144-154.

227. Chan J. Proliferative lesions of follicular dendritic cells: an overview, including a detailed account of follicular dendritic cell sarcoma, a neoplasm with many faces and uncommon etiologic associations. Adv Anat Pathol. 1997;4(6):387-411.

228. Perez-Ordonez B, Erlandson RA, Rosai J. Follicular dendritic cell tumor: report of 13 additional cases of a distinctive entity. Am J Surg Pathol. 1996;20(8):944-955.

229. Chang K, Weiss L. Other histiocytic and dendritic cell neoplasms. In: Jaffe E, Harris N, Vardiman J, Campo E, Arber D, eds. Hematopathology. 1 ed. Philadelphia, PA: Saunders/Elsevier; 2011:829-833.

230. Wang XI, Zhang S, Thomas JO, Adegboyega PA. Cytomorphology, ultrastructural, and cytogenetic findings in follicular dendritic cell sarcoma: a case report. Acta Cytol. 2010;54(5 Suppl):759-763.

231. Soriano AO, Thompson MA, Admirand JH, et al. Follicular dendritic cell sarcoma: a report of 14 cases and a review of the literature. Am J Hematol. 2007;82(8):725-728.

232. Grogg KL, Macon WR, Kurtin PJ, Nascimento AG. A survey of clusterin and fascin expression in sarcomas and spindle cell neoplasms: strong clusterin immunostaining is highly specific for follicular dendritic cell tumor. Mod Pathol. 2005;18(2):260-266.

233. Yu H, et al. Podoplanin (D2-40) is a novel marker for follicular dendritic cell tumors. Am J Clin Pathol. 2007;128(5):776-782.

234. Zhang H, et al. γ-Synuclein is a promising new marker for staining reactive follicular dendritic cells, follicular dendritic cell sarcoma, Kaposi sarcoma, and benign and malignant vascular tumors. Am J Surg Pathol. 2011;35(12):1857-1865.

235. Grogg KL, Lae ME, Kurtin PJ, Macon WR. Clusterin expression distinguishes follicular dendritic cell tumors from other dendritic cell neoplasms: report of a novel follicular dendritic cell marker and clinicopathologic data on 12 additional follicular dendritic cell tumors and 6 additional interdigitating dendritic cell tumors. Am J Surg Pathol. 2004;28(8):988-998.

236. Lee IJ, Kim SC, Kim HS, et al. Paraneoplastic pemphigus associated with follicular dendritic cell sarcoma arising from Castleman’s tumor. J Am Acad Dermatol. 1999;40(2 Pt 2):294-297.

237. Marzano AV, Vezzoli P, Mariotti F, Boneschi V, Caputo R, Berti E. Paraneoplastic pemphigus associated with follicular dendritic cell sarcoma and Castleman disease. Br J Dermatol. 2005;153(1):214-215.

238. Westphal FL, Lima LC, Santana LC, Netto JC, Amaral VC, Silva MoS. Castleman’s disease associated with follicular dendritic cell sarcoma and myasthenia gravis. J Bras Pneumol. 2010;36(6):819-823.

239. Wang J, Wu X, Deng H, et al. Response to rituximab in an anti-muscle-specific receptor tyrosine kinase- and anti-acetylcholine recepto-double-positive myasthenia gravis patient concomitant with follicular dendritic cell sarcoma. Neurosciences (Riyadh). 2016;21(1):77-78.

240. Bai LY, Kwang WK, Chiang IP, Chen PM. Follicular dendritic cell tumor of the liver associated with Epstein-Barr virus. Jpn J Clin Oncol. 2006;36(4):249-253.

241. Hornick JL, Jaffe ES, Fletcher CD. Extranodal histiocytic sarcoma: clinicopathologic analysis of 14 cases of a rare epithelioid malignancy. Am J Surg Pathol. 2004;28(9):1133-1144.

242. Vos JA, Abbondanzo SL, Barekman CL, Andriko JW, Miettinen M, Aguilera NS. Histiocytic sarcoma: a study of five cases including the histiocyte marker CD163. Mod Pathol. 2005;18(5):693-704.

243. Machado ES, et al. Histiocytic sarcoma. Rev Bras Hematol Hemoter. 2011;33(2):155-157.

244. Pileri SA, et al. Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology. 2002;41(1):1-29.

245. Deng A, Lee W, Pfau R, et al. Primary cutaneous Langerhans cell sarcoma without Birbeck granules: indeterminate cell sarcoma? J Cutan Pathol. 2008;35(9):849-854.

246. Ferran M, Toll A, Gilaberte M, Barranco C, Lloreta J, Pujol RM. Acquired mucosal indeterminate cell histiocytoma. Pediatr Dermatol. 2007;24(3):253-256.

247. Rosenberg AS, Morgan MB. Cutaneous indeterminate cell histiocytosis: a new spindle cell variant resembling dendritic cell sarcoma. J Cutan Pathol. 2001;28(10):531-537.

248. Sidoroff A, Zelger B, Steiner H, Smith N. Indeterminate cell histiocytosis--a clinicopathological entity with features of both X- and non-X histiocytosis. Br J Dermatol. 1996;134(3):525-532.

249. Vener C, Soligo D, Berti E, et al. Indeterminate cell histiocytosis in association with later occurrence of acute myeloblastic leukaemia. Br J Dermatol. 2007;156(6):1357-1361.

250. Frater JL, Kling CW, Obadiah JM, et al. Histiocytic sarcoma with secondary involvement of the skin and expression of CD1a: evidence of indeterminate cell differentiation? J Cutan Pathol. 2006;33(6):437-442.

251. Vaiselbuh SR, et al. Updates on histiocytic disorders. Pediatr Blood Cancer. 2014;61(7):1329-1335.

252. Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy. A newly recognized benign clinicopathological entity. Arch Pathol. 1969;87(1):63-70.

253. Destombes P, Destombes M, Martin L. Pseudotumoral lymph node lipidic histiocytosis. Further case in a young Martinique woman. Bull Soc Pathol Exot Filiales. 1972;65(3):481-488.

254. Zhang X, Hyjek E, Vardiman J. A subset of Rosai-Dorfman disease exhibits features of IgG4-related disease. Am J Clin Pathol. 2013;139(5):622-632.

255. Henter JI, Horne A, Aricó M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124-131.

256. Henter JI, Elinder G, Söder O, Ost A. Incidence in Sweden and clinical features of familial hemophagocytic lymphohistiocytosis. Acta Paediatr Scand. 1991;80(4):428-435.

 

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Practical Dermatology is the monthly publication that provides coverage of medical care, cosmetic advancements, and practice management for clinicians in the field. With straight-forward, how-to advice from experts in various fields, we strive to enhance quality of care and improve the daily operation of dermatology practices.