9

CASE REPORTCutaneous Metaplastic Synovial Cyst: Case Report and Literature

Review from the Dermatological Point of ViewMasahiro Fukuyama,1,2 Yohei Sato,1 Jun Hayakawa1 and Manabu Ohyama1,3*

1Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan2Division of Dermatology, Tachikawa Hospital, Tokyo, Japan

3Department of Dermatology, Keio University School of Medicine, Tokyo, Japan

(Received for publication on February 27, 2016)(Revised for publication on May 14, 2016)(Accepted for publication on June 9, 2016)

(Published online in advance on June 17, 2016)

Cutaneous metaplastic synovial cysts (CMSCs) are rare tumors typically comprising a solitary, well-circumscribed cystic mass that is not connected to the joint. Synovial cysts have been reported predomi-nantly by orthopedists or pathologists; however, the presence of CMSC is not generally well recognized by dermatologists. Herein, we report a CMSC in a 68-year-old woman receiving systemic corticosteroid therapy for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA). We attempt to delin-eate the clinical characteristics of this unusual neoplasm by reviewing the literature, focusing especially on dermatological descriptions. Histologic examination of the surgical specimen in the current case revealed that the cystic wall was lined with layers of flattened synovial cell-like cells and connective tis-sues, mimicking the synovial membrane. Positive immunoreactivity of the lining cells against vimentin was detected, but no immunoreactivity against cytokeratin, carcinoembryonic antigen (CEA), CD68, or S-100 was detected. The pathogenesis of CMSC remains unclear, but it has been tightly linked to direct traumatic stimuli or relative tissue fragility, which potentially accounts for CMSC development in our case. Most CMSCs reported by dermatologists are located on the extremities, whereas those de-scribed by other specialists tend to be distributed more globally. Preoperative diagnoses are often either epidermal cyst or suture/foreign body granuloma. Incomplete surgical excision of usual synovial cysts may lead to local recurrence, which has been reported in oral and maxillofacial surgery, but not in der-matologic surgery. This fact could be explained by the technical difficulties of surgical excision related to anatomical location. Dermatologists need to be aware of CMSC, and CMSC should be included in the differential diagnosis of subcutaneous cysts. (doi: 10.2302/kjm.2016-0002-CR; Keio J Med 66 (1) : 9–13, March 2017)

Keywords: cutaneous metaplastic synovial cyst, dermatology, eosinophilic granulomatosis with polyangiitis, corticosteroid, vimentin

Introduction

Cutaneous metaplastic synovial cyst (CMSC) is a rare subcutaneous tumor that typically presents as a solitary, well-circumscribed and tender cystic mass.1 Histologi-cally, the cystic cavity is surrounded by synovial cell-like cells that resemble the cells observed in hyperplastic

synovium.2 Villous-like structures often protrude into the lumen of the cyst.2 CMSC usually appears at the site of previous surgery or trauma and is not related to joint or synovial structures.3 CMSC is not considered to be a true cyst because it lacks a definite epithelial lining.1 Synovial cysts have been predominantly discussed in the field of orthopedic medicine or pathology. To date, as few as 30

Reprint requests to: Manabu Ohyama, MD, PhD, Department of Dermatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-0004, Japan, E-mail: manabuohy@ ks.kyorin-u.ac.jpCopyright © 2016 by The Keio Journal of Medicine

Fukuyama M, et al: Cutaneous Metaplastic Synovial Cyst10

CMSC cases, including our case, have been reported in the literature. Nineteen of these cases were described by dermatologists. Here, we report a case of solitary CMSC on the left lower thigh of a 68-year-old Japanese woman. We attempt to delineate its clinical characteristics by re-viewing the literature from the dermatological point of view.

Case Report

A 68-year-old Japanese woman presented with a 1-year history of a solitary mass on the anterior surface of the left lower leg. She had a 7-year medical history of EGPA that was well controlled by systemic corticosteroid therapy. On physical examination, a solitary, well-circumscribed, 35-mm-diameter tense cystic mass was noted (Fig. 1A). The mass was slightly painful and was almost freely mov-able over the underlying tissue and was not connected to the overlying skin. The results of all regular laboratory examinations were within normal limits. Ultrasonogra-phy detected a well-defined hypoechoic structure in the subcutaneous tissue (Fig. 1B). Based on these clinical findings, we made a tentative diagnosis of lymphangio-ma. The lesion, which was connected to the dermis and surrounded by subcutaneous fat tissue, was surgically removed. Histologic analysis revealed a cystic structure without distinct epithelial lining in the subcutaneous tis-sue (Fig. 1C). The cystic wall was lined with layers of flattened synovial cell-like cells and connective tissue, mimicking the synovial membrane (Fig. 1D). The lin-ing cells partially protruded into the cystic cavity. In the surrounding tissue, various structures, hyalinized con-nective tissue, fibroblastic cells, and inflammatory cells, were observed. Immunohistochemical analysis revealed that the lining cells were positive for vimentin (Fig. 1E), but negative for cytokeratin 14 (Fig. 1F), CEA, CD68, and S-100 (data not shown). The diagnosis of CMSC was made based on these findings.

Discussion

In 1953, Selye first reported experimental induction of cysts with a hyperplastic synovial-like structure at the site of artificial trauma in rats.4 Since then, cystic tumors with similar histopathological characteristics have been reported as synovial cysts, mostly in the field of ortho-pedics.5 These synovial cysts are likely triggered by ex-ternal insults. Synovial cysts develop mainly in bones or joints after orthopedic surgery, whereas CMSCs occur in the skin. Gonzalez et al. reported the first case as synovial metaplasia of the skin in 1987.1 To the best of our knowl-edge, only 30 CMSC cases (including our case) have been reported in the literature (Table 1). Approximately 60% of these cases were described by dermatologists. Analy-sis of the cases described in these reports indicated that CMSC can develop at any age, with the mean age at di-

agnosis being 41.5 years (range 7– 82 years). No sex dif-ferences were noted. The cystic masses ranged from 4 to 40 mm in diameter and were sometimes painful (N = 12). The most common locations were the limbs (N = 14), es-pecially in the palmoplantar region (N = 9). Most CMSCs reported by dermatologists were located on the extremi-ties, whereas those described by other specialists tended to be distributed more globally. Associated conditions in-cluded Ehlers-Danlos syndrome,3,10 rheumatoid arthritis (RA),11,13 and basal cell carcinoma (BCC).8 Characteristi-cally, 17 cases of CMSC (59%) developed at the scar site of operations or trauma, and the time of evolution after operation or trauma was from a few weeks to years (range 3 weeks to 2 years); however, our patient did not have such a history. Preoperative diagnoses by dermatologists were usually either epidermal cyst or suture/foreign body granuloma. CMSC was sometimes diagnosed as a mu-cous cyst by oral and maxillofacial surgeons.

Normal synovial tissue is usually crimped into folds and has two main layers. The outer layer, or subintima, contains blood and lymphatic vessels. The inner layer, or intima, consists of a sheet of flat synovial cells. The lining cells of CMSC resemble hyperplastic synovial membrane with partial hyalinization. The cyst wall has villous-like structures pointing toward the cystic cavity. Synovial cell-like cells in CMSC morphologically resemble true synovial cells and fibroblasts. These cells are difficult to be distinguished by those, such as dermatologists, who are unfamiliar with synovial tissue. Positive immunore-activity of lining cells against vimentin, but not against cytokeratin, CEA, or S-100,3 together with the absence of expression of synovium marker CD68, supports the diagnosis.

The pathogenesis of CMSC has also been linked to relative tissue fragility secondary to Ehlers-Danlos syn-drome3,10 and RA.11,13 Experimentally, normal synovium was formed by local mechanical disruption of the con-nective tissues in vivo.20 Synovial cell-like cells can be differentiated from mesenchymal stem cells during the wound healing process. A history of trauma was not not-ed in our case; however, long-term systemic corticoste-roid administration may have increased tissue fragility and led to CMSC formation.

Local recurrence of common synovial cysts has been noted. In addition, the synovial tissues may evolve ec-topically after the disruption of connective tissue during surgery. Interestingly, local recurrence has been reported in oral and maxillofacial surgery, but not in dermatologic surgery. This could be explained by the technical dif-ficulty of surgical excision relating to anatomical loca-tion. Close follow-up may be necessary in patients with underling diseases that predispose to the development of CMSC.

11Keio J Med 2017; 66 (1): 9–13

Fig. 1 (A) A solitary, well-circumscribed, 35-mm-diameter cystic mass was noted on the left lower leg. (B) Ultrasonography revealed a hypoechoic structure in the subcutaneous tissue. (C) A cystic structure without epithelial lining was noted (hematoxylin–eosin [HE], original magnification ×40). (D) The cystic wall consisted of flattened cells resembling synovial cells (arrowheads) and connective tissues (HE, ×400). (E) Positive immunoreactivity against vimentin (black arrowhead) was detected in the lining cells (arrowheads) (×400). (F) Negative immunoreactivity against cytokeratin14 was observed (×400).

Fukuyama M, et al: Cutaneous Metaplastic Synovial Cyst12

Acknowledgments

We would like to thank Ms. Yoshimi Yamazaki for tech-nical assistance with the immunohistochemical study.

Conflict of Interest

The authors have no conflicts of interest to report.

References

1. Gonzalez JG, Ghiselli RW, Santa Cruz DJ: Synovial metaplasia of the skin. Am J Surg Pathol 1987; 11: 343–350. [Medline] [Cross-Ref]

2. Kim BC, Choi WJ, Park EJ, Kwon IH, Cho HJ, Kim KH, Kim KJ: Cutaneous metaplastic synovial cyst of the first metatarsal head area. Ann Dermatol 2011; 23(Suppl 2): S165–S168. [Medline] [CrossRef]

3. Guala A, Viglio S, Ottinetti A, Angeli G, Canova G, Colombo E, Dardano F, Danesino C, Valli M: Cutaneous metaplastic synovial cyst in Ehlers-Danlos syndrome: report of a second case. Am J Dermatopathol 2008; 30: 59–61. [Medline] [CrossRef]

4. Selye H: On the mechanism through which hydrocortisone affects the resistance of tissues to injury; an experimental study with the granuloma pouch technique. J Am Med Assoc 1953; 152: 1207–1213. [Medline] [CrossRef]

Table 1 Summary of previously reported cases of CMSC

Author Age/sex Site Pre-existing lesion

Associated condition

Time of evolu-tion Size (mm) Clinical diagnosis

Gonzalez1

82 F Chest Surgical scar ― 10 months 4 Periprosthetic infection in scar27 F Abdomen Surgical scar ― 9 months 6 Suture granuloma77 M Abdomen Surgical scar ― 3 years 7 Suture granuloma

Stern6* 7 F Scalp Surgical scar ― N/A N/A Suture granulomaGomez7 28 M Arm Biopsy wound ― N/A N/A N/A

Bhawan8*

40 M Finger ― ― N/A N/A Leiomyoma vs. eccrine poroma40 F Palm Puncture wound ― N/A N/A Foreign body granuloma20 M Abdomen Surgical scar ― N/A N/A Suture granuloma67 M Face ― BCC N/A N/A BCC

Beham9 15 F Knee Trauma ― 3 months 8 N/A45 F Hand Trauma ― Several months N/A N/A

Nieto10* 15 F Elbow ― EDS N/A 17 × 12 Molluscoid pseudotumorSingh11* 72 M Buttock ― RA N/A N/A Epidermal inclusion cyst

Lin5* 61 F Buttock Surgical scar Atherosclerosis 3 weeks 10 Inflammatory epidermal cystYang12* 80 F Buttock ― ― N/A N/A Traumatic panniculitis

Choonha-karn13*

55 F Toe ― RA N/A N/A N/A46 M Thumb ― RA N/A N/A N/A

Goiriz14*

64 F Wrist Trauma ― 6 months 7 N/A63 F Finger ― Arthrosis 3 months 4 N/A51 M Foot ― ― 1 year 10 N/A36 F Abdomen Surgical scar ― 1 year 5 N/A60 M Abdomen Surgical scar ― 1 year 10 N/A

Ramdial15 23 M Chest Surgical scar Gynecomastia 2 years 6 × 4 × 4 GynecomastiaChakravarthy16 34 M Neck Surgical scar Several months N/A Epidermoid cyst

Guala3 7 M Knee ― EDS N/A 20 N/A

Inchingolo17 26 F Face Injection of hyaluronic acid ― N/A 5 Injection-site reaction

Kim2* 51 F Foot ― ― N/A 6.2 × 13.1 N/AShim18* 18 M Face Acne scar ― 6 months 30 Epidermal cyst

Kermani19 29 M Face Surgical scar ― 8 years 20 × 40 CMSCOur case* 68 F Lower leg ― EGPA 1 year 35 Lymphangioma

* Described by dermatologists. EDS, Ehlers-Danlos syndrome; N/A: not available

13Keio J Med 2017; 66 (1): 9–13

5. Lin YC, Tsai TF: Cutaneous metaplastic synovial cyst: unusual presentation with “a bag of worms”. Dermatol Surg 2003; 29: 198–200. [Medline]

6. Stern DR, Sexton FM: Metaplastic synovial cyst after partial ex-cision of nevus sebaceus. Am J Dermatopathol 1988; 10: 531–535. [Medline] [CrossRef]

7. Gómez Dorronsoro ML, Martinez-Peñuela JM, Ruiz de la Her-mosa J: Metaplastic synovial cyst. Am J Surg Pathol 1988; 12: 649–650. [Medline]

8. Bhawan J, Dayal Y, González-Serva A, Eisen R: Cutaneous meta-plastic synovial cyst. J Cutan Pathol 1990; 17: 22–26. [Medline] [CrossRef]

9. Beham A, Fletcher CD, Feichtinger J, Zelger B, Schmid C, Humer U: Synovial metaplasia of the skin. Virchows Arch A Pathol Anat Histopathol 1993; 423: 315–318. [Medline] [CrossRef]

10. Nieto S, Buezo GF, Jones-Caballero M, Fraga J: Cutaneous meta-plastic synovial cyst in an Ehlers-Danlos patient. Am J Dermato-pathol 1997; 19: 407–410. [Medline] [CrossRef]

11. Singh SR, Ma AS, Dixon A: Multiple cutaneous metaplastic sy-novial cysts. J Am Acad Dermatol 1999; 41: 330–332. [Medline] [CrossRef]

12. Yang HC, Tsai YJ, Hu SL, Wu YY: Cutaneous metaplastic syno-vial cyst – a case report and review of literature. Dermatol Sinica 2003; 21: 275–279.

13. Choonhakarn C, Tang S: Cutaneous metaplastic synovial cyst. J Dermatol 2003; 30: 480–484. [Medline] [CrossRef]

14. Goiriz R, Ríos-Buceta L, Alonso-Pérez A, Jones-Caballero M, Fraga J, García-Diez A: Cutaneous metaplastic synovial cyst. J Am Acad Dermatol 2005; 53: 180–181. [Medline] [CrossRef]

15. Ramdial PK, Singh Y, Singh B: Metaplastic synovial cyst in male breast. Ann Diagn Pathol 2005; 9: 219–222. [Medline] [Cross-Ref]

16. Chakravarthy KM, Lavery KM, Barrett AW: Recurrent cutane-ous metaplastic synovial cyst. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007; 103: e42–e44. [Medline] [CrossRef]

17. Inchingolo F, Tatullo M, Abenavoli FM, Marrelli M, Inchingolo AD, Servili A, Inchingolo AM, Dipalma G: A hypothetical corre-lation between hyaluronic acid gel and development of cutaneous metaplastic synovial cyst. Head Face Med 2010; 6: 13–15. [Med-line] [CrossRef]

18. Shim WH, Jwa SW, Song M, Kim HS, Ko HC, Kim BS, Kim MB: Cutaneous metaplastic synovial cyst of the cheek generated by repetitive minor trauma. Ann Dermatol 2011; 23(Suppl 2): S235–S238. [Medline] [CrossRef]

19. Kermani H, Dehghani N, Dehghani S, Behnia H, Pourdanesh F, Mohajerani H: Cutaneous metaplastic synovial cyst: a case report and literature review. Iran Red Crescent Med J 2015; 17: e22467. [Medline] [CrossRef]

20. Drachman DB, Sokoloff L: The role of movement in embryonic joint development. Dev Biol 1966; 14: 401–420. [CrossRef]