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deep soft tissue of the vulvovaginal and pelviperineal region

Deep (aggressive) angiomyxoma

Histopathology

Deep angiomyxoma is uniformly paucicellular and composed of bland-looking, small oval, spindle, and stellate cells interspersed  haphazardly in abundant myxoedematous stroma containing delicate collagen fibrils. Tumour lacks a capsule, and soft tissue infiltration (entrapment of muscle, nerve, and adipose tissue) {25925211; 9023551; 18637148} is common. The stroma characteristically contains a prominent vascular component, ranging from capillary-like to medium/large-sized blood vessels, some of which have thick, muscular walls. Isolated or small bundles of smooth muscle cells, sometimes with a perivascular arrangement, can be seen. Mitotic activity and cytonuclear atypia are virtually absent. These following unusual features can be seen: i)  alternating myxoid to fibro-sclerotic areas; ii) hypercellular areas, frequently with perivascular cuffing; perivascular hyalinization with occasional obliteration of the vascular lumens;  iii) fascicular arrangement of the spindle cells with a neurofibroma-like areas. Recurrrent tumors often show fibro-sclerotic stroma with a well represented vascular component, often with perivascular hyalinization (new reference: 35204448). The neoplastic cells are constantly stained with desmin (Figure 2B) and variably with SMA, ER/PR and/or CD34 {11002763; 21804399; 25925211; 22288973; 15626915; 15735978}. HMGA2 nuclear immunoreactivity is present in most cases {20551826; 20834238}(new reference: 35204448).

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PubMed references:

3997139: Bégin LR, Clement PB, Kirk ME, et al. Aggressive angiomyxoma of pelvic soft parts: a clinicopathologic study of nine cases. Hum Pathol. 1985 Jun;16(6):621-8.

6684403: Steeper TA, Rosai J. Aggressive angiomyxoma of the female pelvis and perineum. Report of nine cases of a distinctive type of gynecologic soft-tissue neoplasm. Am J Surg Pathol. 1983 Jul;7(5):463-75.

8646730: Fetsch JF, Laskin WB, Lefkowitz M, et al. Aggressive angiomyxoma: a clinicopathologic study of 29 female patients. Cancer. 1996 Jul;78(1):79-90.

9023551: Granter SR, Nucci MR, Fletcher CD. Aggressive angiomyxoma: reappraisal of its relationship to angiomyofibroblastoma in a series of 16 cases. Histopathology. 1997 Jan;30(1):3-10.

11002763: McCluggage WG, Patterson A, Maxwell P. Aggressive angiomyxoma of pelvic parts exhibits oestrogen and progesterone receptor positivity. J Clin Pathol. 2000 Aug;53(8):603-5.

11550285: Nucci MR, Weremowicz S, Neskey DM, et al. Chromosomal translocation t(8;12) induces aberrant HMGIC expression in aggressive angiomyxoma of the vulva. Genes Chromosomes Cancer. 2001 Oct;32(2):172-6.

15626915: McCluggage WG. A review and update of morphologically bland vulvovaginal mesenchymal lesions. Int J Gynecol Pathol. 2005 Jan;24(1):26-38.

15735978: van Roggen JF, van Unnik JA, Briaire-de Bruijn IH, et al. Aggressive angiomyxoma: a clinicopathological and immunohistochemical study of 11 cases with long-term follow-up. Virchows Arch. 2005 Feb;446(2):157-63.

16246403: McCluggage WG, Jamieson T, Dobbs SP, et al. Aggressive angiomyxoma of the vulva: Dramatic response to gonadotropin-releasing hormone agonist therapy. Gynecol Oncol. 2006 Mar;100(3):623-5.

16568309: Micci F, Panagopoulos I, Bjerkehagen B, et al. Deregulation of HMGA2 in an aggressive angiomyxoma with t(11;12)(q23;q15). Virchows Arch. 2006 Jun;448(6):838-42.

17654722: Medeiros F, Erickson-Johnson MR, Keeney GL, et al. Frequency and characterization of HMGA2 and HMGA1 rearrangements in mesenchymal tumors of the lower genital tract. Genes Chromosomes Cancer. 2007 Nov;46(11):981-90.

18295664: Rawlinson NJ, West WW, Nelson M, et al. Aggressive angiomyxoma with t(12;21) and HMGA2 rearrangement: report of a case and review of the literature. Cancer Genet Cytogenet. 2008 Mar;181(2):119-24.

18637148: McCluggage WG. Recent developments in vulvovaginal pathology. Histopathology. 2009 Jan;54(2):156-73.

20551826: McCluggage WG, Connolly L, McBride HA. HMGA2 is a sensitive but not specific immunohistochemical marker of vulvovaginal aggressive angiomyxoma. Am J Surg Pathol. 2010 Jul;34(7):1037-42.

20834238: Dreux N, Marty M, Chibon F, et al. Value and limitation of immunohistochemical expression of HMGA2 in mesenchymal tumors: about a series of 1052 cases. Mod Pathol. 2010 Dec;23(12):1657-66.

21804399: Bigby SM, Symmans PJ, Miller MV, et al. Aggressive angiomyxoma [corrected] of the female genital tract and pelvis--clinicopathologic features with immunohistochemical analysis. Int J Gynecol Pathol. 2011 Sep;30(5):505-13.

22288973: Sutton BJ, Laudadio J. Aggressive angiomyxoma. Arch Pathol Lab Med. 2012 Feb;136(2):217-21.

25925211: Schoolmeester JK, Fritchie KJ. Genital soft tissue tumors. J Cutan Pathol. 2015 Jul;42(7):441-51.

31142482: Lee MY, da Silva B, Ramirez DC, et al. Novel HMGA2-YAP1 fusion gene in aggressive angiomyxoma. BMJ Case Rep. 2019 May;12(5):

35985684: Panagopoulos I, Gorunova L, Andersen K, et al. Fusion of High Mobility Group AT-hook 2 Gene (HMGA2) With the Chromosome 12 Open Reading Frame 42 Gene (C12orf42) in an Aggressive Angiomyxoma With del(12)(q14q23) as the Sole Cytogenetic Anomaly. Cancer Genomics Proteomics. 202219(5):576-583.

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