Multinucleate Cell Angiohistiocytoma

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Background

Multinucleate cell angiohistiocytoma is a benign fibrohistiocytic and vascular proliferation that was first reported by Smith and Wilson Jones in 1985.[1] Multinucleate cell angiohistiocytoma occurs predominantly on the extremities of middle-aged and elderly women.

Pathophysiology

The pathogenesis of multinucleate cell angiohistiocytoma is unknown. Some authors consider it a connective-tissue disorder, while others categorize it as a vascular tumor. Wilson Jones concluded that multinucleate cell angiohistiocytoma is a chronic inflammatory disorder of unknown cause manifested by vascular hyperplasia and connective-tissue cells that have lost their function after prolonged stimulation. Cesinaro et al argue for a role played by estrogen in the development of this lesion.[2]

Etiology

Multinucleate cell angiohistiocytoma is an acquired disorder of unknown cause. Puig et al propose the existence of an interaction between mast cells and factor XIIIa–positive fibrohistiocytic cells, which might contribute to vascular proliferation by the release of various proangiogenic cytokines.[3] Shapiro postulates that the condition may be related to trauma because it tends to occur on the dorsal aspects of the hands and around the knees.[4]

Epidemiology

Frequency

Multinucleate cell angiohistiocytoma is a rare disorder.[5] Fewer than 100 cases have been reported as of 2015.[6, 7, 8, 9, 10, 11]

Race

The frequency of multinucleate cell angiohistiocytoma in various races has not been reported.

Sex

The female-to-male ratio of persons affected with multinucleate cell angiohistiocytoma is approximately 5:1.

Age

Reported cases of multinucleate cell angiohistiocytoma have occurred in patients aged 24-74 years. Most cases of multinucleate cell angiohistiocytoma occur in middle-aged and elderly women.

Prognosis

Multinucleate cell angiohistiocytoma is a benign condition. Spontaneous resolution is uncommon.[12] No morbidity or mortality is associated with multinucleate cell angiohistiocytoma.

History

Multinucleate cell angiohistiocytoma presents as insidiously developing asymptomatic papules that usually develop on acral surfaces and tend to persist indefinitely.

Physical Examination

Multiple, grouped, well-circumscribed papules are red to violaceous to brownish in color.[13]

Multinucleate cell angiohistiocytoma lesions are smooth and firm, and they may be either dome shaped or flat topped.

A few cases of multinucleate cell angiohistiocytoma have been in an annular distribution, mimicking granuloma annulare.

Lesions of multinucleate cell angiohistiocytoma occur most commonly on the extremities. Acral areas such as the dorsal aspects of the hands, fingers, wrists, and legs are the most frequent sites. Unusual locations of multinucleate cell angiohistiocytoma include the forehead, the upper lip, the chest, oral cavity, and the orbit.[14, 15, 16]

Lesions usually are unilateral, but a few bilateral cases and one generalized case have been reported.

Multinucleate cell angiohistiocytoma lesions are usually asymptomatic to pruritic.

Procedures

Lesions of multinucleate cell angiohistiocytoma often mimic other conditions. A biopsy is the best way to exclude more serious disorders (eg, sarcoidosis, Kaposi sarcoma).[17]

Histologic Findings

Multinucleate cell angiohistiocytoma has a distinctive histologic appearance characterized by a vascular proliferation and bizarre multinucleated cells. In the upper and mid dermis, a proliferation of small blood vessels occurs, some of which have dilated lumina. The vessels have the histologic appearances of capillaries and small vessels. The endothelial cells lining the vessels are plump but lack atypia. A sparse perivascular lymphocytic infiltrate may be present. In addition, an increased number of mast cells has been reported.

The vascular proliferation is embedded in a fibrous stroma rich in fibrohistiocytic cells. The collagen bundles are slightly thickened and arranged haphazardly or parallel to the epidermis. Bizarre multinucleated cells are amongst the interstitial cells. These cells have 3-10 hyperchromatic nuclei that are closely aggregated or arranged in a ringlike fashion. The cytoplasm of these cells is often angulated or scalloped in outline (see the images below).



View Image

Biopsy specimen of multinucleate cell angiohistiocytoma. A vascular proliferation is embedded in a stroma rich in fibroblasts and histiocytes, some of....



View Image

Bizarre multinucleated cells are present in the stroma surrounding the vascular proliferation.

Immunohistochemical studies may be useful in confirming the diagnosis of multinucleate cell angiohistiocytoma and in differentiating it from other vascular and fibrous proliferations. The lesional vessels label with factor VIII–related antigen (factor VIII-RA), EN-4, BMA-120, PAL-E, and Ulex europaeus agglutinin I (UEA-I). These findings indicate a capillary and venular nature of the vessels. Polymerase chain reaction analysis reveals no evidence of human herpesvirus-8 (HHV-8) infection, as may be found in Kaposi sarcoma.

The multinucleated cells stain with vimentin, but they do not label with the macrophage markers lysozyme, MAC 387, and alpha-1-antitrypsin. The multinucleated cells are also negative for S-100 protein, factor XIII, and human leukocyte antigen DR (HLA-DR). The mononuclear interstitial cells label with vimentin, factor XIIIa, and CD68.

Medical Care

Multinucleate cell angiohistiocytoma has not been shown to respond to any medical therapy.

Surgical Care

Surgical excision of multinucleate cell angiohistiocytoma may be recommended for cosmetic reasons.

Laser therapy has resulted in clinical resolution of the lesions with not scarring. Kopera et al reported successful treatment with an argon laser.[18]  Richer and Lui reported successful treatment with a 585-nm pulsed dye laser.[19]

Treatment using intense pulsed light has also been reported.[20]

Perez et al reported a case with a good response to cryosurgery.[21]

Long-Term Monitoring

Further follow-up care is not needed because multinucleate cell angiohistiocytoma is not known to be associated with any systemic diseases and because it has a biologically benign course.

Medication Summary

No medical therapy is available for multinucleate cell angiohistiocytoma.

Author

Diane M Scott, MD, Dermatologist, Arch Health Partners

Disclosure: Nothing to disclose.

Coauthor(s)

Daniel Davis, MD, Associate Professor, Departments of Dermatology, Otolaryngology, and Pathology, University of Arkansas for Medical Science

Disclosure: Nothing to disclose.

Specialty Editors

David F Butler, MD, Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

Disclosure: Nothing to disclose.

Paul Krusinski, MD, Director of Dermatology, Fletcher Allen Health Care; Professor, Department of Internal Medicine, University of Vermont College of Medicine

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.

Additional Contributors

Abdul-Ghani Kibbi, MD, Professor and Chair, Department of Dermatology, American University of Beirut Medical Center, Lebanon

Disclosure: Nothing to disclose.

Acknowledgements

Frances Ramos-Ceballos Staff Physician, Department of Dermatology, University of Arkansas for Medical Sciences

Frances Ramos-Ceballos is a member of the following medical societies: American Academy of Dermatology, Phi Beta Kappa, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

References

  1. Smith NP, Wilson Jones E. Multinucleate cell angiohistiocytoma: a new entity. Br J Dermatol. 1985. 113(suppl 29):15.
  2. Cesinaro AM, Roncati L, Maiorana A. Estrogen receptor alpha overexpression in multinucleate cell angiohistiocytoma: new insights into the pathogenesis of a reactive process. Am J Dermatopathol. 2010 Oct. 32(7):655-9. [View Abstract]
  3. Puig L, Fernandez-Figueras MT, Bielsa I, Lloveras B, Alomar A. Multinucleate cell angiohistiocytoma: a fibrohistiocytic proliferation with increased mast cell numbers and vascular hyperplasia. J Cutan Pathol. 2002 Apr. 29(4):232-7. [View Abstract]
  4. Shapiro PE, Nova MP, Rosmarin LA, Halperin AJ. Multinucleate cell angiohistiocytoma: a distinct entity diagnosable by clinical and histologic features. J Am Acad Dermatol. 1994 Mar. 30(3):417-22. [View Abstract]
  5. Roy SF, Dong D, Myung P, McNiff JM. Multinucleate cell angiohistiocytoma: A clinicopathologic study of 62 cases and proposed diagnostic criteria. J Cutan Pathol. 2019 Aug. 46 (8):563-569. [View Abstract]
  6. Aloi F, Solaroli C, Tomasini C, Pippione M. Multinucleate cell angiohistiocytoma: a report of two cases. J Eur Acad Dermatol Venereol. 1998 Jul. 11(1):51-4. [View Abstract]
  7. Blanco Barrios S, Rodriguez Diaz E, Alvarez Cuesta C, Galache Osuna C, Requena Caballero C, Martinez Merino A, et al. Multinucleate cell angiohistiocytoma: a new case report. J Eur Acad Dermatol Venereol. 2005 Mar. 19(2):208-11. [View Abstract]
  8. Cribier B, Gambini C, Rainero M, Grosshans E. Multinucleate cell angiohistiocytoma. A review and report of four cases. Acta Derm Venereol. 1995 Sep. 75(5):337-9. [View Abstract]
  9. Jaconelli L, Kanitakis J, Ktiouet S, Faure M, Claudy A. Multinucleate cell angiohistiocytoma: report of three new cases and literature review. Dermatol Online J. 2009 Feb 15. 15(2):4. [View Abstract]
  10. Väkevä L, Saksela O, Kariniemi AL. Multinucleate cell angiohistiocytoma: a report of four cases in Finland. Acta Derm Venereol. 2003. 83(3):222-3. [View Abstract]
  11. Doane JA, Purdy K, Pasternak S. Generalized Multinucleate Cell Angiohistiocytoma. J Cutan Med Surg. 2015 May-Jun. 19 (3):323-5. [View Abstract]
  12. Moradi Tuchayi S, Garibyan L, Lee KC. Successful treatment of multinucleate cell angiohistiocytoma with fractionated ablative CO2 laser. JAAD Case Rep. 2019 Apr. 5 (4):297-299. [View Abstract]
  13. Frew JW. Multinucleate cell angiohistiocytoma: clinicopathological correlation of 142 cases with insights into etiology and pathogenesis. Am J Dermatopathol. 2015 Mar. 37 (3):222-8. [View Abstract]
  14. Jones AC, Mullins D, Jimenez F. Multinucleate cell angiohistiocytoma of the upper lip. Oral Surg Oral Med Oral Pathol. 1994 Dec. 78(6):743-7. [View Abstract]
  15. Rawal YB, Anderson KM, Rawal SY. Multinucleate cell angiohistiocytoma: an uncommon mucosal tumour. Clin Exp Dermatol. 2009 Apr. 34(3):333-6. [View Abstract]
  16. Shields JA, Eagle RC Jr, Shields CL, Sohmer KK. Multinucleate cell angiohistiocytoma of the orbit. Am J Ophthalmol. 1995 Sep. 120(3):402-3. [View Abstract]
  17. Jones WE, Cerio R, Smith NP. Multinucleate cell angiohistiocytoma: an acquired vascular anomaly to be distinguished from Kaposi's sarcoma. Br J Dermatol. 1990 May. 122(5):651-63. [View Abstract]
  18. Kopera D, Smolle J, Kerl H. Multinucleate cell angiohistiocytoma: treatment with argon laser. Br J Dermatol. 1995 Aug. 133(2):308-10. [View Abstract]
  19. Richer V, Lui H. Facial multinucleate cell angiohistiocytoma: long-term remission with 585 nm pulsed dye laser. Clin Exp Dermatol. 2016 Apr. 41 (3):312-3. [View Abstract]
  20. Fernandez-Jorge B, del Pozo J, Garcia-Silva J, Barja JM, Yebra-Pimentel MT, Fonseca E. Multinucleate cell angiohistiocytoma: treatment using intense pulsed light. Dermatol Surg. 2009 Jul. 35(7):1141-3. [View Abstract]
  21. Perez LP, Zulaica A, Rodriguez L, et al. Multinucleate cell angiohistiocytoma. Report of five cases. J Cutan Pathol. 2006 May. 33(5):349-52. [View Abstract]

Biopsy specimen of multinucleate cell angiohistiocytoma. A vascular proliferation is embedded in a stroma rich in fibroblasts and histiocytes, some of which are multinucleated.

Bizarre multinucleated cells are present in the stroma surrounding the vascular proliferation.

Biopsy specimen of multinucleate cell angiohistiocytoma. A vascular proliferation is embedded in a stroma rich in fibroblasts and histiocytes, some of which are multinucleated.

Bizarre multinucleated cells are present in the stroma surrounding the vascular proliferation.