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Table of Contents
BRIEF REPORT
Year : 2021  |  Volume : 39  |  Issue : 4  |  Page : 202-205

Calcified angioleiomyoma – Histopathologic and ultrasonographic analysis of the calcification process


1 Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan; Department of Dermatology, Akasaka Toranomon Clinic, Minato Tokyo, Japan
2 Department of Medical Education, Showa University, Shinagawa, Tokyo, Japan
3 Department of Pathology, Yokosuka Kyosai Hospital, Kanagawa, Yokosuka, Japan
4 Department of Dermatology, Akasaka Toranomon Clinic, Minato Tokyo, Japan

Date of Submission11-Apr-2021
Date of Decision04-Oct-2021
Date of Acceptance10-Oct-2021
Date of Web Publication29-Dec-2021

Correspondence Address:
Dr. Ming-Hsiu Hsieh
Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, 3-9, Fukura, Yokohama Shi Kanazawa Ku, Kanagawa Ken, 236-0004
Japan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ds.ds_43_21

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  Abstract 


Historically, angioleiomyoma is a subtype of leiomyoma that comprises about 4%–5% of all benign soft tissue tumors, and calcifications occur in 2%–3% of them. Because of the very low incidence of calcifications, their mechanism of formation is still unknown. In this article, we present the five cases of angioleiomyomas with calcification and discuss the ultrasonographic features in three of those cases. In general, from the aspect of ultrasonography, angioleiomyomas are recognized as hypoechogenic homogenous structures with peritumoral or intratumoral vascularity. However, our cases revealed heterogeneity or hyperechogenicity in inclusions, which has never been reported before. Histologically, calcifications were found not only under the dystrophic pathway which were considered in the past literature but also have the possibility under the metastatic pathway. According to our findings, we also classified the ultrasonographic patterns into three patterns according to the progression and distribution of calcifications. This is the first report to identify the location and possible pathways of calcifications and to classify the ultrasonographic features of calcified angioleiomyomas.

Keywords: Acoustic shadow, angioleiomyoma, calcification, punctate calcification, ultrasonographic features


How to cite this article:
Hsieh MH, Izumi M, Nakatani Y, Ohara K. Calcified angioleiomyoma – Histopathologic and ultrasonographic analysis of the calcification process. Dermatol Sin 2021;39:202-5

How to cite this URL:
Hsieh MH, Izumi M, Nakatani Y, Ohara K. Calcified angioleiomyoma – Histopathologic and ultrasonographic analysis of the calcification process. Dermatol Sin [serial online] 2021 [cited 2022 Jan 28];39:202-5. Available from: https://www.dermsinica.org/text.asp?2021/39/4/202/334163




  Introduction Top


Angioleiomyomas are small, round, encapsulated subcutaneous tumors that occur in vascular vessels. The frequency of angioleiomyomas has been reported to be 4%–5% of all benign soft-tissue tumors. In very limited cases, calcifications inside the tumor masses are observed, representing 2%–3% of all angioleiomyomas.[1],[2],[3],[4] The mechanism of calcification is still unknown, and reports on its ultrasonographic features are also limited. We have experienced 86 cases of angioleiomyomas over a 40-year period in the Toranomon Hospital and the Akasaka Toranomon Clinic in Tokyo. There were only nine cases (10.4%) with preoperative imaging examinations of ultrasonography, and 5 cases (5.8%) had calcification. Here, we introduce the five cases of angioleiomyomas with calcification and report the ultrasonographic features of three of those cases. We also speculate about the mechanism of calcification based on our experience and previous studies.


  Methods and Results Top


None of our cases presented with endocrine, electrolytic or renal problems, autoimmune diseases, or had a traumatic history. The ultrasonography of cases 1, 2, and 5 was performed at 13 MHz by the same technician in the ultrasonography department.

Case 1

A 72-year-old Japanese woman visited us with a 10-year history of a dome-shaped, firm, and freely movable subcutaneous nodule, about 11 mm in diameter, on her internal left plantar arch with paroxysmal pain. Ultrasonography revealed a 5.5 mm × 9.9 mm well-circumscribed oval-shaped mass with an anechogenic base and central hyperechogenicity accompanied with an acoustic shadow. Power Doppler analysis revealed both internal and peri-tumoral vascularity [Figure 1]a. Histology demonstrated an encapsulated tumor surrounded by numerous hypertrophic or dilated vessels and adventitia-like structures. The large central calcification produced linear clefts histologically from a processing artifact and showed an acoustic shadow in ultrasonography [Figure 1]b. At higher magnification, various round or slit-like vessel lumens and multiple calcifications were observed [Figure 1]c. Some smooth muscle bundles and pleomorphic smooth muscle cells were also noted. A calcified angioleiomyoma was diagnosed.
Figure 1: Histologic and ultrasound analysis, Cases 1-5. (a-c) Case 1; (d-f) Case 2; (g-i) Case 3; (j and k) Case 4; (l-o) Case 5. (a) Central hyperechogenicity with posterior acoustic shadow. (b) A central calcification corresponding to the central hyperechogencity and the posterior acoustic shadow on ultrasonography (long arrow). (c) Round or slit-like vessel lumens and calcifications (arrows). (d) Hyperechogenic structure producing a posterior acoustic shadow. (h and i) Dystrophic calcification in smooth muscle bundles. (k) Large thrombosed calcification. (l) Heterogenicity with scattered punctate calcifications. (n and o) Tiny calcifications around disformed vascular walls and inside the vascular lumens. (o: von Kossa stain).

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Case 2

A 71-year-old Japanese woman presented with a slowly growing, scaling nodule of 20 years duration on her right heel. It was a firm and freely movable tumor 10 mm × 12 mm in diameter, with tenderness and a keratotic mass in the center. Ultrasonography revealed a well-encapsulated dome-shaped nodule with a heterogeneous structure in the base and a hyperechogenic structure in the upper part of the nodule, producing a posterior acoustic shadow [Figure 1]d. Histology revealed a well-encapsulated subcutaneous tumor with a large amorphous central calcification [Figure 1]e. At higher magnification, vessels with encircling bands of smooth muscles and satellite lumens surrounding the calcification area were observed. Calcium deposits were also observed in the extracellular matrix and the smooth muscle cells [Figure 1]f, leading to the diagnosis of calcified angioleiomyoma.

Case 3

A 70-year-old Japanese woman noticed a thumb-sized firm nodule on her right lower leg several years earlier. Histology demonstrated a well-encapsulated amorphous nodule with multiple large calcifications scattered in the central part of the tumor [Figure 1]g. At higher magnification, calcification was observed between smooth muscle bundles and as deposits in the bundles [Figure 1]h and [Figure 1]i. The diagnosis was a calcified angioleiomyoma.

Case 4

A 63-year-old Japanese woman presented with a 3-year history of a slowly growing nodule on her right calf. Physical examination revealed a 12 mm × 25 mm, light pink, firm, and freely movable subcutaneous nodule with tenderness. Histology demonstrated a well-encapsulated amorphous nodule with scattered calcifications [Figure 1]j. At higher magnification, calcification thrombi were recognized inside the vessel lumens with epithelioid cells and encircling bands of smooth muscles [Figure 1]k. It was diagnosed with a calcified angioleiomyoma.

Case 5

A 75-year-old Japanese woman developed an 8 mm × 11 mm dome-shaped subcutaneous nodule with radiating pain and tenderness on her left heel for 20 years. Ultrasonography revealed an encapsulated amorphous nodule with vascularity and heterogenous inclusion and multiple hyperechogenic dots scattered inside the tumor [Figure 1]l, which was suggestive of multiple tiny calcifications. The histology was consistent with angioleiomyoma, although calcified material was not easily visible at low power magnification with hematoxylin and eosin (HE) staining [Figure 1]m. Under higher magnification and von Kossa staining, multiple tiny calcifications were recognized surrounding the highly disformed vascular wall and inside the vascular lumens [Figure 1]n and [Figure 1]o, leading to the diagnosis of calcified angioleiomyoma.


  Discussion Top


Angioleiomyomas were histologically classified into capillary/solid, cavernous, and venous types by Morimoto N. in Japan in 1973.[5] They described the capillary/solid type as smooth muscle bundles surrounding and intervening numbers compacted in slit-like vascular channels, the cavernous type as dilated vascular with smaller amounts of thickened smooth muscular walls, and the venous type as vascular in a venous type with thickened muscular walls and smooth muscle bundles.[5] In clinical practice, angioleiomyomas were described as elastic, hard, movable tumors sometimes presenting with gray-white color or paroxysmal pain or tenderness. The most common type of angioleiomyoma is the solid type (about 60%–70%), which has characteristic features of small size, female predominance, extremities location, paroxysmal pain, and tenderness.[5] The treatment of all types of angioleiomyomas is surgical resection, and recurrence is exceptional.[5] The main features of our cases are summarized in [Table 1]. The clinical characteristics of our patients are female predominance, old age (an average of 70.2 years old), tumor location on the lower leg or foot and a long history of duration which suggests repetitive irritation. According to the past literature and our five cases, most calcified angioleiomyomas are the solid type in histology with a longer history of duration, and symptoms and prognosis are the same as noncalcified angioleiomyomas of the solid type. The ultrasonographic features of calcified angioleiomyomas show a well-defined hypoechogenic homogeneous structure with peritumoral or intratumoral vascularity in common with noncalcified tumors.[6] Hyperechogenicity with posterior acoustic shadows is noted, because of large amounts of calcified material inside the tumor, like our cases 1 and 2. Sometimes, the ultrasonography presents scattered hyperechogenic dots inside the tumor caused by punctate calcifications [Figure 1]l, [Figure 1]o and [Figure 2].
Table 1: Case summary

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Figure 2: Three patterns of ultrasonography of angioleiomyomas. Pattern 1: Anechogenicity with vascularity. (Case without calcification in Akasaka Toranomon Clinic). Pattern 2: Heterogenicity with scattered punctate calcifications (circles: tiny calcifications, von Kossa stain). Pattern 3: Large calcification with an acoustic shadow.

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Histologically, calcifications are classified into dystrophic and metastatic ones.[7] Although calcifications of angioleiomyomas are rare, most studies categorized them as dystrophic calcifications because of their solid nature histologically and their acral predominance. Kumar et al.[7] indicated that repeated minor trauma, vascular contractures, degenerative changes, and ischemic necrosis might produce the accumulation of necrotic cellular debris and elastin degradation, which could result in the tendency for calcification.[4],[8],[9],[10] All of our cases presented with amorphous calcifications along the smooth muscle bundles, and tiny calcifications existed between bundles. Foci of calcifications were observed mainly in areas where smooth muscle cells were markedly degenerated or lost and were replaced by hyalinizing fibrous tissue and myxoid stroma. In Case 4, calcifying changes of the thrombus were also recognized in vessel lumens that denoted the necrosis of vessels. Those observations suggest the hypothesis that the slow vascular flow and mechanical irritation to the tumor might play a role in the formation of the dystrophic calcifications.

About metastatic calcification, Kacerovska et al. and Marco et al. proposed the concept that tumoral calcinosis, the phenomena of a periarticular calcium deposit tendency, may be related to the calcification process of angioleiomyomas.[4],[11] Kacerovska et al. thought that the increase in blood flow of tendons caused changes of the microcirculation, inducing angiogenesis, and giving the potential origin of angioleiomyomas.[4] Although our cases were not located around large joints and did not present hyperkalcemia or hyperphosphatemia, we observed calcium deposits around highly deformed vessels without surrounding tissue degeneration [Figure 1]n which were never noticed before. We presume that the highly distorted vessels, which may be caused by repetitive irritation and angiogenesis,[11] change the microcirculation making a condition similar to hypercalcaemia that leads to metastatic calcification around the vessels.

Referring to the ultrasonography and histological calcified condition of our five cases, we classified the features of ultrasonography according to the condition and distribution of calcifications into three patterns [Figure 2]:

1. Anechogenicity with vascularity

2. Heterogenicity with scattered punctate calcifications

3. Large calcifications with acoustic shadows.


  Conclusion Top


Our study is the first to propose the hypothesis of the metastatic calcification of angioleiomyomas and to report the classification according to the ultrasonographic features of angioleiomyomas with respect to the conditions of calcification. Although the treatment and prognosis are the same as the noncalcified angioleiomyomas, we believe that this report improves our understanding of the calcification process of angioleiomyomas and the preoperative differential diagnosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

Prof. Kuniaki Ohara, an editorial board member at Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.



 
  References Top

1.
Sakai E, Asai E, Yamamoto T. Acral calcified angioleiomyoma. Eur J Dermatol 2010;20:121-2.  Back to cited text no. 1
    
2.
Murata H, Matsui T, Horie N, Sakabe T, Konishi E, Kubo T. Angioleiomyoma with calcification of the heel: Report of two cases. Foot Ankle Int 2007;28:1021-5.  Back to cited text no. 2
    
3.
Maheshwari AV, Temple HT, Murocacho CA. Calcified angiomyomas of the foot: A case report. Foot Ankle Int 2008;29:449-55.  Back to cited text no. 3
    
4.
Kacerovska D, Michal M, Kreuzberg B, Mukensnabl P, Kazakov DV. Acral calcified vascular leiomyoma of the skin: A rare clinicopathological variant of cutaneous vascular leiomyomas: Report of 3 cases. J Am Acad Dermatol 2008;59:1000-4.  Back to cited text no. 4
    
5.
Hachisuga T, Hashimoto H, Enjoji M. Angioleiomyoma. A clinicopathologic reappraisal of 562 cases. Cancer 1984;54:126-30.  Back to cited text no. 5
    
6.
Kang BS, Shim HS, Kim JH, Kim YM, Bang M, Lim S, et al. Angioleiomyoma of the extremities: Findings on ultrasonography and magnetic resonance imaging. J Ultrasound Med 2019;38:1201-8.  Back to cited text no. 6
    
7.
Kumar V, Abbas AK, Aster JC, editors. Pathologic Calcification. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Philadelphia, PA:Elsevier Saunders; 2015. p. 65-6.  Back to cited text no. 7
    
8.
Ronchetti I, Boraldi F, Annovi G, Cianciulli P, Quaglino D. Fibroblast involvement in soft connective tissue calcification. Front Genet 2013;4:22.  Back to cited text no. 8
    
9.
Díaz-Flores L, Gutiérrez R, Alvarez-Argüelles H, González-Gómez M, García Mdel P, Díaz-Flores L Jr. Ultrastructure and histogenesis of the acral calcified angioleiomyoma. Ultrastruct Pathol 2016;40:24-32.  Back to cited text no. 9
    
10.
Watson KE, Parhami F, Shin V, Demer LL. Fibronectin and collagen I matrixes promote calcification of vascular cells in vitro, whereas collagen IV matrix is inhibitory. Arterioscler Thromb Vasc Biol 1998;18:1964-71.  Back to cited text no. 10
    
11.
Marco VS, Bosch SB, Almeida LV. Acral angioleiomyoma with tumoral calcinosis: A complication of the insertional Achilles tendinopathy. J Cutan Pathol 2017;44:661-4.  Back to cited text no. 11
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1]



 

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