Skeletal Radiol DOI 10.1007/s00256-013-1772-7
CASE REPORT
Desmoplastic fibroma of the rib with cystic change: a case report and literature review Taketo Okubo & Tsuyoshi Saito & Tatsuya Takagi & Yoshiyuki Suehara & Kazuo Kaneko
Received: 7 August 2013 / Revised: 23 October 2013 / Accepted: 28 October 2013 # ISS 2013
Abstract Desmoplastic fibroma (DF) is a rare, locally aggressive, solitary tumor microscopically composed of welldifferentiated myofibroblasts with abundant dense collagen deposition. The most common sites are the long tubular bones and mandible. To our knowledge, only five cases of DF in the ribs have been reported. Here, we report a case of DF in this rare location with unusual radiological findings. A 40-yearold man presented with a 4-year history of swelling of the right chest wall. Radiographs revealed a mass at the right 9th rib, and computed tomography demonstrated a mass of 14× 12×8 cm at the right 9th rib with expanded cystic change and marked calcification that appeared to have arisen from the bone. Open biopsy suggested DF. Total excision was performed, and the chest wall was reconstructed. The surgical specimen was a yellowish tumor with multilocular cystic change containing a viscous liquid. The tumor was composed of a proliferation of less-atypical spindle-shaped cells in a collagenous background. The cystic change was observed in the extra-osseous lesion. No β-catenin cytoplasmic/ nuclear accumulation was detected, and no β-catenin or GNAS genetic mutations were detected. A final diagnosis of DF was made on the basis of the pathological and radiological findings. The patient was successfully treated with total excision of the tumor with no evidence of recurrence 6 months after surgery. Keywords Desmoplastic fibroma . Rib . β-catenin . Cystic change T. Okubo : T. Takagi : Y. Suehara : K. Kaneko Department of Orthopaedic Surgery, School of Medicine, Juntendo University, Tokyo, Japan T. Okubo : T. Saito (*) Department of Human Pathology, School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan e-mail: [email protected]
Introduction Desmoplastic fibroma (DF) is a rare, locally aggressive, solitary tumor [1]. The reported incidences of DF among all primary and benign bone tumors are 0.06–0.11 % and 0.3 %, respectively [2, 3]. Any bone can be affected, and the most common sites are the long tubular bones (56 %), mandible (26 %), and pelvis (14 %) [4, 5]. Although DF has been reported in rarer locations, DF arising from a rib is extremely rare. To our knowledge, only five cases of DF in the ribs have been reported in the literature [6–9]. The radiological characteristics of DF in magnetic resonance imaging (MRI) and computed tomography (CT) scans are described in detail in several reported cases [3, 10–13]. Typical radiological features include osteolytic lesion with destruction of the cortical bone and pseudotrabeculation [1]. Cystic change is a rare feature and has been reported in only three cases on the basis of MRI findings [10]. However, these findings may be seen in other bone tumors such as fibrous dysplasia (FD), hemangioma, eosinophilic granuloma, and low-grade osteosarcoma. The rarity and nonspecific radiographic findings of DF sometimes make radiological diagnosis difficult. Histologically, DF is composed of a proliferation of slender, spindle-shaped cells within an abundant collagenous matrix. Cellular pleomorphism and atypia are minimal or absent, and mitoses are rare. Thus, the important pathological characteristics for differential diagnosis include extra-abdominal desmoid tumor and low-grade fibrosarcoma of the bone [1]. Extra-abdominal desmoid tumors particularly exhibit histological and immunohistological features that overlap with those of DF, making it difficult to differentiate them in cases involving both soft tissue and bone [1]. Both tumors exhibit immunohistochemical expressions of some myogenic markers such as SMA and M-actin. The epidemiological, histological, and immunohistochemical findings of DF
Skeletal Radiol
suggest DF is the osseous counterpart of the more common desmoid-type fibromatosis of soft tissue [14]. Extraabdominal desmoid tumors are associated with the activation of the Wnt/β-catenin signaling pathway (i.e., the APC/βcatenin/Tcf pathway), and β-catenin mutation is frequently observed [15]. These findings demonstrate that β-catenin Fig. 1 a Radiography revealed loss of the definition of the posterolateral 9th rib with a soft tissue mass with subtle calcification. b–f CT scan showing the presence of a mass (14×12×8 cm) at the right 9th rib with expanded cystic change and marked calcification. The proximal portion of the right 9th rib showed a tumor located in the medulla of the rib was penetrating both the external and internal cortices, suggesting the tumor originated from inside of the rib (b). The 9th rib was destructed (c), and calcification was observed within the tumor (d). Transverse view (e) and coronal view (f) showing a tumor with multilocular cystic change and calcification (after contrast administration). g, h The irregularity of the fat plain around the mass (after contrast administration)
Fig. 2 a Surgical specimen showing a yellowish tumor with multilocular cystic change. b, c The tumor was composed of a proliferation of less atypical spindle-shaped cells in a collagenous background with prominent small vessels (b; ×40, c; ×200). d The tumor was proliferating intermingled with skeletal muscle fibers, and surface of the cystic space lacks lining epithelial cells (×40). e Engulfed trabeculae of the lamellar bone were seen (x40). f: Spindle cells were negative for βcatenin cytoplasmic/nuclear accumulation (x100)
Skeletal Radiol
Skeletal Radiol
plays an important role in extra-abdominal desmoid tumors. However, β-catenin mutations have not been detected in DF thus far; moreover, β-catenin nuclear/cytoplasmic accumulation has been reported in some cases, although it is generally through cytoplasmic staining [14]. Thus, there is no genetic evidence indicating DF is the intra-osseous counterpart of desmoid tumor. This report presents a case of DF arising from an unusual location with rare cyst formation.
Case report A 40-year-old man presented with a 4-year history of swelling of the right chest wall without pain. Physical examination revealed a hard mass (14×10 cm) with neither tenderness nor hypoesthesia. Radiography revealed loss of the definition of the posterolateral 9th rib with a soft tissue mass with subtle calcification (Fig. 1a). CT demonstrated the presence of a mass (14×12×8 cm) at the right 9th rib with expanded cystic change and marked calcification (Fig. 1b–f). An intramedullary tumor located in the proximal portion of right 9th rib was penetrating both the external and internal cortices, suggesting the tumor originated from inside of the rib (Fig. 1b). Furthermore, the fat plane around the mass was not preserved in part (Fig. 1g and h). Open biopsy was performed, and pathological features included the proliferation of spindle-shaped cells against a background of dense collagen fibers. The pathological diagnosis was extraabdominal desmoid tumor vs. DF. Total excision and chest wall reconstruction were performed. The surgical specimen was a yellowish tumor with multilocular cystic change containing a viscous liquid (Fig. 2a). The tumor was composed of a proliferation of less atypical spindle-shaped cells in a collagenous background with focal myxoid change (Fig. 2b, c). Mitotic figures were rare. The tumor was proliferating in part intermingled with the surrounding skeletal muscles, though the periosteum was unclear on the surgical specimen. The
cystic change was observed in the extra-osseous lesion, and there were no cells lining the cystic space (Fig. 2d). Engulfed trabeculae of the lamellar bone and reactive bone formation were also noted, although no C- or J-shaped woven bone trabeculae reminiscent of FD were observed (Fig. 2e). No βcatenin cytoplasmic/nuclear accumulation was detected by immunohistochemistry (Fig. 2f). Furthermore, no β-catenin genetic mutations, which are reported to occur frequently in desmoid tumors [15–19], were detected by PCR following direct sequencing. In addition, to exclude the possibility of the stromal-rich form of FD [20], mutations of GNAS at Arg201 and Gln227, which are reported to be observed in more than 90 % of FD cases [21, 22], were also analyzed; however, no GNAS mutations were detected. The final diagnosis of DF was made on the basis of the pathological and radiological findings together with genetic information. There were no signs of recurrence 6 months after surgery.
Discussion DF was first described by Jaffe in 1958 and is a rare primary bone tumor that can affect any bone [23]. However, DF arising from a rib is extremely rare; to our knowledge, only five cases have been published in the English literature [6–9]. Table 1 summarizes all cases including the present case. The chief complaint was swelling in two cases. Tumor size ranges from 110 to 140 mm. Major radiographic findings include osteolytic change and cortical bone destruction. Cystic change was only demonstrated in the present case. Total excision and chest wall reconstruction were performed in two cases. Recurrence was observed in two cases treated with curettage. The therapeutic procedures in the other two cases are unknown. The major radiologic features of DF are osteolytic lesion with destruction of the cortical bone and invasion into the surrounding soft tissue without periosteal reaction [1]. CT and
Table 1 Summary of reported cases of desmoplastic fibroma in rib Author
Age Sex Clinical symptoms
Location Size(mm)
Butters et al. [6]
17
M
Pain and swelling
lt. 6th
–
Taconis et al. [7]
57
F
Swelling
rt. 5th
–
Barbashina et al. [8] Ayadi-Kaddour et al. [9]
19 45
M M
Ayadi-Kaddour et al. [9]
55
F
Present case
40
M
Swelling lt. 10th Pain, paresthesia rt. 2nd and hypoesthesia Swelling rt. 8th or 9th Swelling rt. 9th
lt. left; rt. right; NED No evidence of disease
110 70 100
Radiographic findings
Treatment
Follow-up/ outcome
Osteolytic, nondestructive Osteolytic, destruction, endosteal scalloping, soft tissue extension Osteolytic, destruction Expansive formation
Resection
–
Curettage
Recurrence after 9 years/9 years
Total excision Resection
– NED/4 years
Osteolytic, soft tissue extension 140 × 120 × 80 Cystic, destruction
Wide resection Recurrence after 2 years/2 years Total excision NED/6 months
Skeletal Radiol
MRI are effective tools for evaluating the degree of bone destruction and invasion into the surrounding soft tissue and useful for planning surgery. However, the radiological findings of DF may be seen in other bone lesions such as FD, hemangioma, eosinophilic granuloma, and low-grade osteosarcoma. Furthermore, the pathological differential diagnosis of DF includes benign and low-grade malignant bone tumors including FD, low-grade fibrosarcoma, low-grade intraosseous osteosarcoma, non-ossifying fibroma [24], and softtissue tumors invading bone sufficiently or deeply, producing defects [1]. Since the radiological and pathological findings of these tumors overlap, making a correct diagnosis while considering all features is essential. A particularly important differential diagnosis is extra-abdominal desmoid tumor invading the bone and low-grade fibrosarcoma of the bone [1]. Typical fibrosarcoma is more cellular with a herringbone pattern that exhibits more pleomorphism and mitotic activity [25]. However, determining malignancy using a small biopsy sample is very difficult. FD is a common tumor, especially in this site, and an important differential diagnosis that must be excluded, especially for a small biopsy sample [1]. Cystic change in FD is a well-recognized and well-recorded phenomenon. Furthermore, stromal-rich forms of FD with minimal woven bone production are well known to exist [20]. GNAS mutation in FD is another well-established phenomenon [21, 22], and is useful for differentiating FD from other bone tumors. However, because no GNAS mutations were detected in the present case, the possibility of the stromal-rich form of FD was excluded. Radiological findings that can confirm the tumor is originating from a bone are essential for differentiating DF from bony invasion of extra-abdominal desmoid tumors, because it is impossible to differentiate these lesions on the basis of conventional microscopic features alone. In addition, cystic changes in desmoid tumors have been reported in a few cases, particularly those arising from the pancreas [26–28]. In the present case, the CT scan shown in Fig. 1b led us to speculate that the tumor originated from the rib. Furthermore, in addition to radiological findings, immunohistochemical and genetic information of β-catenin are necessary, because the APC/β-catenin pathway is well known to be associated with desmoid-type fibromatosis as well as Gardner syndrome, hereditary desmoid-type fibromatosis, and sporadic desmoidtype fibromatosis [15, 16]. Although β-catenin expression occurred in seven out of 14 DF cases in the literature, most of them exhibited cytoplasmic staining and only two exhibited nuclear β-catenin staining [11, 14]. On the other hand, almost all desmoid tumors exhibit diffuse nuclear staining of βcatenin [15, 16]. However, the present case did not exhibit any β-catenin cytoplasmic/nuclear staining of β-catenin, thus favoring the diagnosis of DF. Furthermore, β-catenin (CTNNB1) mutations are reported very frequently in desmoid
tumors [17–19, 29, 30], although they are absent in DF [14]. On this basis, some authors argue that there is no genetic evidence indicating DF is the intra-osseous counterpart of desmoid tumors. However, the frequency of β-catenin mutation in desmoid tumors appears to differ with respect to ethnicity, being lower in Japanese patients [15, 16]. These findings collectively indicate that β-catenin plays a rather important role in the tumorigenesis of desmoid tumors but not in DF; furthermore, the detection of β-catenin mutations may be a specific diagnostic tool for the diagnosis of desmoid tumors [19, 29]. Neither β-catenin (CTNNB1) mutation nor β-catenin accumulation was detected in the present case, further corroborating the diagnosis of DF. The local recurrence rate in DF treated with curettage or intra-lesional resection is at least 40 % [3, 11, 30, 31]. Some authors regard this tumor’s aggressive behavior as “borderline” or “semimalignant” rather than benign [2, 3, 30]. The current consensus is that total excision is the best treatment for DF [3, 30, 31]. The present patient was successfully treated with total excision of the tumor with no evidence of recurrence 6 months after surgery. Acknowledgments We greatly appreciate the help of Drs. Taito Asahina and Ryohei Kuwatsuru of the Department of Radiology, Juntendo University, School of Medicine. This work was supported in part by a Grant-in-Aid for General Scientific Research from the Ministry of Education, Science, Sports, and Culture (#23590434 to Tsuyoshi Saito), Tokyo, Japan. Conflict of interest The authors confirm that they have no conflicts of interest related to this article.
References 1. Dorfman HD, Czerniak B. Bone tumors. St. Louis, Mo: Mosby, 1998. p.559-606. 2. Dahlin DC, Unni KK. In: Thomas, editor. Bone tumors. Springfield: Charles C. Thomas; 1984. p. 375–8. 3. Gebhardt MC, Campbell CJ, Schiller AL, Mankin HJ. Desmoplastic fibroma of bone: a report of 8 cases and review of the literature. J Bone Joint Surg Am. 1985;67:732–47. 4. Smith SE, Kransdorf MJ. Primary musculoskeletal tumors of fibrous origin. Semin Musculoskelet Radiol. 2000;4:73–88. 5. Perlick L, Zander D, Wallny T, Zhou H. Desmoplastic fibroma of the fibula. A difficult clinical, radiological and histological diagnosis. Zentralbl Chir. 2000;125:895–9. 6. Butters M, Hamann H, Mohr W. Desmoplastic fibroma of the rib. Thorac Cardiovasc Surg. 1985;33:317–8. 7. Takonis WK, Schutte HE, van der Heul RO. Desmoplastic fibroma of bone: a report of 18 cases. Skeletal Radiol. 1994;23:282–8. 8. Barbashina V, Karabakhtsian R, Aisner S, Bolanowski P, Patterson F, Hameed M. Desmoplastic fibroma of the rib. Arch Pathol Lab Med. 2002;126:721–2. 9. Ayadi-Kaddour A, Ben Slama S, Braham E, Abid L, Ismail O, Smati B, et al. Desmoplastic fibroma of the rib: two case reports. Ann Pathol. 2005;25:398–401.
Skeletal Radiol 10. Kim SY, Chung HW, Lee SY, Hong SH, Hwang JY, Kim MJ. Cystic changes in desmoplastic fibroma of bone: a new MRI finding. Clin Radiol. 2012;67:1170–4. 11. Nedopil A, Raab P, Rudert M. Desmoplastic fibroma: a case report with three years of clinical and radiographic observation and review of the literature. Open Orthop J. 2013;8:40–6. 12. Stefanidis K, Benakis S, Tsatalou E, Ouranos V, Chondros D. Computed tomography and magnetic resonance imaging of desmoplastic fibroma with simultaneous manifestation in two unusual locations: a case report. J Med Case Rep. 2011;24(5): 28. 13. Bertoni F, Calderoni P, Bacchini P, Campanacci M. Desmoplastic fibroma of bone. A report of six cases. J Bone Joint Surg Br. 1984;66: 265–8. 14. Hauben EI, Jundt G, Cleton-Jansen AM, Yavas A, Kroon HM, Van Marck E, et al. Desmoplastic fibroma of bone: an immunohistochemical study including beta-catenin expression and mutational analysis for beta-catenin. Hum Pathol. 2005;36: 1025–30. 15. Matono H, Oda Y, Nakamori M, Tamiya S, Yamamoto H, Yokoyama R, et al. Correlation between beta-catenin widespread nuclear expression and matrix metalloproteinase-7 overexpression in sporadic desmoid tumors. Hum Pathol. 2008;39:1802–8. 16. Saito T, Oda Y, Kawaguchi K, Tanaka K, Matsuda S, Tamiya S, et al. Possible association between higher beta-catenin mRNA expression and mutated beta-catenin in sporadic desmoid tumors: real-time semiquantitative assay by TaqMan polymerase chain reaction. Lab Invest. 2002;82:97–103. 17. Huss S, Nehles J, Binot E, Wardelmann E, Mittler J, Kleine MA, et al. 9. β-catenin (CTNNB1) mutations and clinicopathological features of mesenteric desmoid-type fibromatosis. Histopathology. 2013;62: 294–304. 18. Le Guellec S, Soubeyran I, Rochaix P, Filleron T, Neuville A, Hostein I, et al. CTNNB1 mutation analysis is a useful tool for the diagnosis of desmoid tumors: a study of 260 desmoid tumors and 191 potential morphologic mimics. Mod Pathol. 2012;25: 1551–8.
19. Bo N, Wang D, Wu B, Chen L, Ruixue M. Analysis of β-catenin expression and exon 3 mutations in pediatric sporadic aggressive fibromatosis. Pediatr Dev Pathol. 2012;15:173–8. 20. Shidham VB, Chavan A, Rao RN, Komorowski RA, Asma Z. Fatty metamorphosis and other patterns in fibrous dysplasia. BMC Musculoskelet Disord. 2003;4:20. 21. Shi RR, Li XF, Zhang R, Chen Y, Li TJ. GNAS mutational analysis in differentiating fibrous dysplasia and ossifying fibroma of the jaw. Mod Pathol. 2013;26:1023–31. 22. Toyosawa S, Yuki M, Kishino M, Ogawa Y, Ueda T, Murakami S, et al. Ossifying fibroma vs. fibrous dysplasia of the jaw: molecular and immunological characterization. Mod Pathol. 2007;20:389–96. 23. Jaffe HL. Tumors and tumorous conditions of the bones and joints. Philadelphia: Lea & Febiger; 1958. p. 298–303. 24. Hopkins KM, Huttula CS, Kahn MA, Albright JE. Desmoplastic fibroma of the mandible: review and report of two cases. J Oral Maxillofac Surg. 1996;54:1249–54. 25. Chopra R, Bhardwaj M, Premsagar IC. Fibrosarcoma of the meninges. Rare Tumors. 2010;2:e3. 26. Rao RN, Agarwal P, Rai P, Kumar B. Isolated desmoid tumor of pancreatic tail with cyst formation diagnosed by beta-catenin immunostaining: a rare case report with review of literature. J Pancreas. 2013;14:296–301. 27. Pho LN, Coffin CM, Burt RW. Abdominal desmoid in familial adenomatous polyposis presenting as a pancreatic cystic lesion. Fam Cancer. 2005;4:135–8. 28. Amiot A, Dokmak S, Sauvanet A, Vilgrain V, Bringuier PP, Scoazec JY, et al. Sporadic desmoid tumor. An exceptional cause of cystic pancreatic lesion. J Pancreas. 2008;9:339–45. 29. Colombo C, Bolshakov S, Hajibashi S, Lopez-Terrada L, Wang WL, Rao P, et al. 'Difficult to diagnose' desmoid tumours: a potential role for CTNNB1 mutational analysis. Histopathology. 2011;59:336–40. 30. Bohm P, Krober S, Greschniok A, Laniado M, Kaiserling E. Desmoplastic fibroma of bone: a report of two patients, review of the literature, and therapeutic implications. Cancer. 1996;78:1011–23. 31. Inwards CY, Unni KK, Beabout JW, Sim FH. Desmoplastic fibroma of bone. Cancer. 1991;68:1978–83.
CASE REPORT
Desmoplastic fibroma of the rib with cystic change: a case report and literature review Taketo Okubo & Tsuyoshi Saito & Tatsuya Takagi & Yoshiyuki Suehara & Kazuo Kaneko
Received: 7 August 2013 / Revised: 23 October 2013 / Accepted: 28 October 2013 # ISS 2013
Abstract Desmoplastic fibroma (DF) is a rare, locally aggressive, solitary tumor microscopically composed of welldifferentiated myofibroblasts with abundant dense collagen deposition. The most common sites are the long tubular bones and mandible. To our knowledge, only five cases of DF in the ribs have been reported. Here, we report a case of DF in this rare location with unusual radiological findings. A 40-yearold man presented with a 4-year history of swelling of the right chest wall. Radiographs revealed a mass at the right 9th rib, and computed tomography demonstrated a mass of 14× 12×8 cm at the right 9th rib with expanded cystic change and marked calcification that appeared to have arisen from the bone. Open biopsy suggested DF. Total excision was performed, and the chest wall was reconstructed. The surgical specimen was a yellowish tumor with multilocular cystic change containing a viscous liquid. The tumor was composed of a proliferation of less-atypical spindle-shaped cells in a collagenous background. The cystic change was observed in the extra-osseous lesion. No β-catenin cytoplasmic/ nuclear accumulation was detected, and no β-catenin or GNAS genetic mutations were detected. A final diagnosis of DF was made on the basis of the pathological and radiological findings. The patient was successfully treated with total excision of the tumor with no evidence of recurrence 6 months after surgery. Keywords Desmoplastic fibroma . Rib . β-catenin . Cystic change T. Okubo : T. Takagi : Y. Suehara : K. Kaneko Department of Orthopaedic Surgery, School of Medicine, Juntendo University, Tokyo, Japan T. Okubo : T. Saito (*) Department of Human Pathology, School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan e-mail: [email protected]
Introduction Desmoplastic fibroma (DF) is a rare, locally aggressive, solitary tumor [1]. The reported incidences of DF among all primary and benign bone tumors are 0.06–0.11 % and 0.3 %, respectively [2, 3]. Any bone can be affected, and the most common sites are the long tubular bones (56 %), mandible (26 %), and pelvis (14 %) [4, 5]. Although DF has been reported in rarer locations, DF arising from a rib is extremely rare. To our knowledge, only five cases of DF in the ribs have been reported in the literature [6–9]. The radiological characteristics of DF in magnetic resonance imaging (MRI) and computed tomography (CT) scans are described in detail in several reported cases [3, 10–13]. Typical radiological features include osteolytic lesion with destruction of the cortical bone and pseudotrabeculation [1]. Cystic change is a rare feature and has been reported in only three cases on the basis of MRI findings [10]. However, these findings may be seen in other bone tumors such as fibrous dysplasia (FD), hemangioma, eosinophilic granuloma, and low-grade osteosarcoma. The rarity and nonspecific radiographic findings of DF sometimes make radiological diagnosis difficult. Histologically, DF is composed of a proliferation of slender, spindle-shaped cells within an abundant collagenous matrix. Cellular pleomorphism and atypia are minimal or absent, and mitoses are rare. Thus, the important pathological characteristics for differential diagnosis include extra-abdominal desmoid tumor and low-grade fibrosarcoma of the bone [1]. Extra-abdominal desmoid tumors particularly exhibit histological and immunohistological features that overlap with those of DF, making it difficult to differentiate them in cases involving both soft tissue and bone [1]. Both tumors exhibit immunohistochemical expressions of some myogenic markers such as SMA and M-actin. The epidemiological, histological, and immunohistochemical findings of DF
Skeletal Radiol
suggest DF is the osseous counterpart of the more common desmoid-type fibromatosis of soft tissue [14]. Extraabdominal desmoid tumors are associated with the activation of the Wnt/β-catenin signaling pathway (i.e., the APC/βcatenin/Tcf pathway), and β-catenin mutation is frequently observed [15]. These findings demonstrate that β-catenin Fig. 1 a Radiography revealed loss of the definition of the posterolateral 9th rib with a soft tissue mass with subtle calcification. b–f CT scan showing the presence of a mass (14×12×8 cm) at the right 9th rib with expanded cystic change and marked calcification. The proximal portion of the right 9th rib showed a tumor located in the medulla of the rib was penetrating both the external and internal cortices, suggesting the tumor originated from inside of the rib (b). The 9th rib was destructed (c), and calcification was observed within the tumor (d). Transverse view (e) and coronal view (f) showing a tumor with multilocular cystic change and calcification (after contrast administration). g, h The irregularity of the fat plain around the mass (after contrast administration)
Fig. 2 a Surgical specimen showing a yellowish tumor with multilocular cystic change. b, c The tumor was composed of a proliferation of less atypical spindle-shaped cells in a collagenous background with prominent small vessels (b; ×40, c; ×200). d The tumor was proliferating intermingled with skeletal muscle fibers, and surface of the cystic space lacks lining epithelial cells (×40). e Engulfed trabeculae of the lamellar bone were seen (x40). f: Spindle cells were negative for βcatenin cytoplasmic/nuclear accumulation (x100)
Skeletal Radiol
Skeletal Radiol
plays an important role in extra-abdominal desmoid tumors. However, β-catenin mutations have not been detected in DF thus far; moreover, β-catenin nuclear/cytoplasmic accumulation has been reported in some cases, although it is generally through cytoplasmic staining [14]. Thus, there is no genetic evidence indicating DF is the intra-osseous counterpart of desmoid tumor. This report presents a case of DF arising from an unusual location with rare cyst formation.
Case report A 40-year-old man presented with a 4-year history of swelling of the right chest wall without pain. Physical examination revealed a hard mass (14×10 cm) with neither tenderness nor hypoesthesia. Radiography revealed loss of the definition of the posterolateral 9th rib with a soft tissue mass with subtle calcification (Fig. 1a). CT demonstrated the presence of a mass (14×12×8 cm) at the right 9th rib with expanded cystic change and marked calcification (Fig. 1b–f). An intramedullary tumor located in the proximal portion of right 9th rib was penetrating both the external and internal cortices, suggesting the tumor originated from inside of the rib (Fig. 1b). Furthermore, the fat plane around the mass was not preserved in part (Fig. 1g and h). Open biopsy was performed, and pathological features included the proliferation of spindle-shaped cells against a background of dense collagen fibers. The pathological diagnosis was extraabdominal desmoid tumor vs. DF. Total excision and chest wall reconstruction were performed. The surgical specimen was a yellowish tumor with multilocular cystic change containing a viscous liquid (Fig. 2a). The tumor was composed of a proliferation of less atypical spindle-shaped cells in a collagenous background with focal myxoid change (Fig. 2b, c). Mitotic figures were rare. The tumor was proliferating in part intermingled with the surrounding skeletal muscles, though the periosteum was unclear on the surgical specimen. The
cystic change was observed in the extra-osseous lesion, and there were no cells lining the cystic space (Fig. 2d). Engulfed trabeculae of the lamellar bone and reactive bone formation were also noted, although no C- or J-shaped woven bone trabeculae reminiscent of FD were observed (Fig. 2e). No βcatenin cytoplasmic/nuclear accumulation was detected by immunohistochemistry (Fig. 2f). Furthermore, no β-catenin genetic mutations, which are reported to occur frequently in desmoid tumors [15–19], were detected by PCR following direct sequencing. In addition, to exclude the possibility of the stromal-rich form of FD [20], mutations of GNAS at Arg201 and Gln227, which are reported to be observed in more than 90 % of FD cases [21, 22], were also analyzed; however, no GNAS mutations were detected. The final diagnosis of DF was made on the basis of the pathological and radiological findings together with genetic information. There were no signs of recurrence 6 months after surgery.
Discussion DF was first described by Jaffe in 1958 and is a rare primary bone tumor that can affect any bone [23]. However, DF arising from a rib is extremely rare; to our knowledge, only five cases have been published in the English literature [6–9]. Table 1 summarizes all cases including the present case. The chief complaint was swelling in two cases. Tumor size ranges from 110 to 140 mm. Major radiographic findings include osteolytic change and cortical bone destruction. Cystic change was only demonstrated in the present case. Total excision and chest wall reconstruction were performed in two cases. Recurrence was observed in two cases treated with curettage. The therapeutic procedures in the other two cases are unknown. The major radiologic features of DF are osteolytic lesion with destruction of the cortical bone and invasion into the surrounding soft tissue without periosteal reaction [1]. CT and
Table 1 Summary of reported cases of desmoplastic fibroma in rib Author
Age Sex Clinical symptoms
Location Size(mm)
Butters et al. [6]
17
M
Pain and swelling
lt. 6th
–
Taconis et al. [7]
57
F
Swelling
rt. 5th
–
Barbashina et al. [8] Ayadi-Kaddour et al. [9]
19 45
M M
Ayadi-Kaddour et al. [9]
55
F
Present case
40
M
Swelling lt. 10th Pain, paresthesia rt. 2nd and hypoesthesia Swelling rt. 8th or 9th Swelling rt. 9th
lt. left; rt. right; NED No evidence of disease
110 70 100
Radiographic findings
Treatment
Follow-up/ outcome
Osteolytic, nondestructive Osteolytic, destruction, endosteal scalloping, soft tissue extension Osteolytic, destruction Expansive formation
Resection
–
Curettage
Recurrence after 9 years/9 years
Total excision Resection
– NED/4 years
Osteolytic, soft tissue extension 140 × 120 × 80 Cystic, destruction
Wide resection Recurrence after 2 years/2 years Total excision NED/6 months
Skeletal Radiol
MRI are effective tools for evaluating the degree of bone destruction and invasion into the surrounding soft tissue and useful for planning surgery. However, the radiological findings of DF may be seen in other bone lesions such as FD, hemangioma, eosinophilic granuloma, and low-grade osteosarcoma. Furthermore, the pathological differential diagnosis of DF includes benign and low-grade malignant bone tumors including FD, low-grade fibrosarcoma, low-grade intraosseous osteosarcoma, non-ossifying fibroma [24], and softtissue tumors invading bone sufficiently or deeply, producing defects [1]. Since the radiological and pathological findings of these tumors overlap, making a correct diagnosis while considering all features is essential. A particularly important differential diagnosis is extra-abdominal desmoid tumor invading the bone and low-grade fibrosarcoma of the bone [1]. Typical fibrosarcoma is more cellular with a herringbone pattern that exhibits more pleomorphism and mitotic activity [25]. However, determining malignancy using a small biopsy sample is very difficult. FD is a common tumor, especially in this site, and an important differential diagnosis that must be excluded, especially for a small biopsy sample [1]. Cystic change in FD is a well-recognized and well-recorded phenomenon. Furthermore, stromal-rich forms of FD with minimal woven bone production are well known to exist [20]. GNAS mutation in FD is another well-established phenomenon [21, 22], and is useful for differentiating FD from other bone tumors. However, because no GNAS mutations were detected in the present case, the possibility of the stromal-rich form of FD was excluded. Radiological findings that can confirm the tumor is originating from a bone are essential for differentiating DF from bony invasion of extra-abdominal desmoid tumors, because it is impossible to differentiate these lesions on the basis of conventional microscopic features alone. In addition, cystic changes in desmoid tumors have been reported in a few cases, particularly those arising from the pancreas [26–28]. In the present case, the CT scan shown in Fig. 1b led us to speculate that the tumor originated from the rib. Furthermore, in addition to radiological findings, immunohistochemical and genetic information of β-catenin are necessary, because the APC/β-catenin pathway is well known to be associated with desmoid-type fibromatosis as well as Gardner syndrome, hereditary desmoid-type fibromatosis, and sporadic desmoidtype fibromatosis [15, 16]. Although β-catenin expression occurred in seven out of 14 DF cases in the literature, most of them exhibited cytoplasmic staining and only two exhibited nuclear β-catenin staining [11, 14]. On the other hand, almost all desmoid tumors exhibit diffuse nuclear staining of βcatenin [15, 16]. However, the present case did not exhibit any β-catenin cytoplasmic/nuclear staining of β-catenin, thus favoring the diagnosis of DF. Furthermore, β-catenin (CTNNB1) mutations are reported very frequently in desmoid
tumors [17–19, 29, 30], although they are absent in DF [14]. On this basis, some authors argue that there is no genetic evidence indicating DF is the intra-osseous counterpart of desmoid tumors. However, the frequency of β-catenin mutation in desmoid tumors appears to differ with respect to ethnicity, being lower in Japanese patients [15, 16]. These findings collectively indicate that β-catenin plays a rather important role in the tumorigenesis of desmoid tumors but not in DF; furthermore, the detection of β-catenin mutations may be a specific diagnostic tool for the diagnosis of desmoid tumors [19, 29]. Neither β-catenin (CTNNB1) mutation nor β-catenin accumulation was detected in the present case, further corroborating the diagnosis of DF. The local recurrence rate in DF treated with curettage or intra-lesional resection is at least 40 % [3, 11, 30, 31]. Some authors regard this tumor’s aggressive behavior as “borderline” or “semimalignant” rather than benign [2, 3, 30]. The current consensus is that total excision is the best treatment for DF [3, 30, 31]. The present patient was successfully treated with total excision of the tumor with no evidence of recurrence 6 months after surgery. Acknowledgments We greatly appreciate the help of Drs. Taito Asahina and Ryohei Kuwatsuru of the Department of Radiology, Juntendo University, School of Medicine. This work was supported in part by a Grant-in-Aid for General Scientific Research from the Ministry of Education, Science, Sports, and Culture (#23590434 to Tsuyoshi Saito), Tokyo, Japan. Conflict of interest The authors confirm that they have no conflicts of interest related to this article.
References 1. Dorfman HD, Czerniak B. Bone tumors. St. Louis, Mo: Mosby, 1998. p.559-606. 2. Dahlin DC, Unni KK. In: Thomas, editor. Bone tumors. Springfield: Charles C. Thomas; 1984. p. 375–8. 3. Gebhardt MC, Campbell CJ, Schiller AL, Mankin HJ. Desmoplastic fibroma of bone: a report of 8 cases and review of the literature. J Bone Joint Surg Am. 1985;67:732–47. 4. Smith SE, Kransdorf MJ. Primary musculoskeletal tumors of fibrous origin. Semin Musculoskelet Radiol. 2000;4:73–88. 5. Perlick L, Zander D, Wallny T, Zhou H. Desmoplastic fibroma of the fibula. A difficult clinical, radiological and histological diagnosis. Zentralbl Chir. 2000;125:895–9. 6. Butters M, Hamann H, Mohr W. Desmoplastic fibroma of the rib. Thorac Cardiovasc Surg. 1985;33:317–8. 7. Takonis WK, Schutte HE, van der Heul RO. Desmoplastic fibroma of bone: a report of 18 cases. Skeletal Radiol. 1994;23:282–8. 8. Barbashina V, Karabakhtsian R, Aisner S, Bolanowski P, Patterson F, Hameed M. Desmoplastic fibroma of the rib. Arch Pathol Lab Med. 2002;126:721–2. 9. Ayadi-Kaddour A, Ben Slama S, Braham E, Abid L, Ismail O, Smati B, et al. Desmoplastic fibroma of the rib: two case reports. Ann Pathol. 2005;25:398–401.
Skeletal Radiol 10. Kim SY, Chung HW, Lee SY, Hong SH, Hwang JY, Kim MJ. Cystic changes in desmoplastic fibroma of bone: a new MRI finding. Clin Radiol. 2012;67:1170–4. 11. Nedopil A, Raab P, Rudert M. Desmoplastic fibroma: a case report with three years of clinical and radiographic observation and review of the literature. Open Orthop J. 2013;8:40–6. 12. Stefanidis K, Benakis S, Tsatalou E, Ouranos V, Chondros D. Computed tomography and magnetic resonance imaging of desmoplastic fibroma with simultaneous manifestation in two unusual locations: a case report. J Med Case Rep. 2011;24(5): 28. 13. Bertoni F, Calderoni P, Bacchini P, Campanacci M. Desmoplastic fibroma of bone. A report of six cases. J Bone Joint Surg Br. 1984;66: 265–8. 14. Hauben EI, Jundt G, Cleton-Jansen AM, Yavas A, Kroon HM, Van Marck E, et al. Desmoplastic fibroma of bone: an immunohistochemical study including beta-catenin expression and mutational analysis for beta-catenin. Hum Pathol. 2005;36: 1025–30. 15. Matono H, Oda Y, Nakamori M, Tamiya S, Yamamoto H, Yokoyama R, et al. Correlation between beta-catenin widespread nuclear expression and matrix metalloproteinase-7 overexpression in sporadic desmoid tumors. Hum Pathol. 2008;39:1802–8. 16. Saito T, Oda Y, Kawaguchi K, Tanaka K, Matsuda S, Tamiya S, et al. Possible association between higher beta-catenin mRNA expression and mutated beta-catenin in sporadic desmoid tumors: real-time semiquantitative assay by TaqMan polymerase chain reaction. Lab Invest. 2002;82:97–103. 17. Huss S, Nehles J, Binot E, Wardelmann E, Mittler J, Kleine MA, et al. 9. β-catenin (CTNNB1) mutations and clinicopathological features of mesenteric desmoid-type fibromatosis. Histopathology. 2013;62: 294–304. 18. Le Guellec S, Soubeyran I, Rochaix P, Filleron T, Neuville A, Hostein I, et al. CTNNB1 mutation analysis is a useful tool for the diagnosis of desmoid tumors: a study of 260 desmoid tumors and 191 potential morphologic mimics. Mod Pathol. 2012;25: 1551–8.
19. Bo N, Wang D, Wu B, Chen L, Ruixue M. Analysis of β-catenin expression and exon 3 mutations in pediatric sporadic aggressive fibromatosis. Pediatr Dev Pathol. 2012;15:173–8. 20. Shidham VB, Chavan A, Rao RN, Komorowski RA, Asma Z. Fatty metamorphosis and other patterns in fibrous dysplasia. BMC Musculoskelet Disord. 2003;4:20. 21. Shi RR, Li XF, Zhang R, Chen Y, Li TJ. GNAS mutational analysis in differentiating fibrous dysplasia and ossifying fibroma of the jaw. Mod Pathol. 2013;26:1023–31. 22. Toyosawa S, Yuki M, Kishino M, Ogawa Y, Ueda T, Murakami S, et al. Ossifying fibroma vs. fibrous dysplasia of the jaw: molecular and immunological characterization. Mod Pathol. 2007;20:389–96. 23. Jaffe HL. Tumors and tumorous conditions of the bones and joints. Philadelphia: Lea & Febiger; 1958. p. 298–303. 24. Hopkins KM, Huttula CS, Kahn MA, Albright JE. Desmoplastic fibroma of the mandible: review and report of two cases. J Oral Maxillofac Surg. 1996;54:1249–54. 25. Chopra R, Bhardwaj M, Premsagar IC. Fibrosarcoma of the meninges. Rare Tumors. 2010;2:e3. 26. Rao RN, Agarwal P, Rai P, Kumar B. Isolated desmoid tumor of pancreatic tail with cyst formation diagnosed by beta-catenin immunostaining: a rare case report with review of literature. J Pancreas. 2013;14:296–301. 27. Pho LN, Coffin CM, Burt RW. Abdominal desmoid in familial adenomatous polyposis presenting as a pancreatic cystic lesion. Fam Cancer. 2005;4:135–8. 28. Amiot A, Dokmak S, Sauvanet A, Vilgrain V, Bringuier PP, Scoazec JY, et al. Sporadic desmoid tumor. An exceptional cause of cystic pancreatic lesion. J Pancreas. 2008;9:339–45. 29. Colombo C, Bolshakov S, Hajibashi S, Lopez-Terrada L, Wang WL, Rao P, et al. 'Difficult to diagnose' desmoid tumours: a potential role for CTNNB1 mutational analysis. Histopathology. 2011;59:336–40. 30. Bohm P, Krober S, Greschniok A, Laniado M, Kaiserling E. Desmoplastic fibroma of bone: a report of two patients, review of the literature, and therapeutic implications. Cancer. 1996;78:1011–23. 31. Inwards CY, Unni KK, Beabout JW, Sim FH. Desmoplastic fibroma of bone. Cancer. 1991;68:1978–83.
