Skeletal Radiol DOI 10.1007/s00256-014-2032-1
CASE REPORT
Regression of an enchondroma: a case report and proposed etiology Anirban Sensarma & John E. Madewell & Jeanne M. Meis & Rajendra Kumar & Patrick P. Lin & Behrang Amini
Received: 6 August 2014 / Revised: 11 September 2014 / Accepted: 6 October 2014 # ISS 2014
Abstract Enchondromas are common benign bone lesions that are found in the medullary cavity of tubular bones, usually at the metaphysis. Regression is highly unusual, and loss of matrix mineralization in an existing enchondroma should prompt investigation for malignant transformation. We present the case of a 50-year-old woman with an enchondroma of the proximal humeral metadiaphysis, which underwent loss of matrix mineralization that corresponded to replacement with marrow fat on MRI. This transformation of the cartilage tumor matrix into normal bone marrow may occur in a process similar to that seen with endochondral ossification.
has punctate and flocculent calcifications in the shapes of arcs and rings. Loss of uniform matrix mineralization may be due to replacement of the existing chondroid matrix with myxoid or necrotic areas, and should raise concern for the development of chondrosarcoma [3, 4]. We present an unusual case of an enchondroma in the proximal humerus, which gradually decreased in size with partial replacement of the chondroid matrix by normal marrow fat without treatment. Although the exact cause of this regression is not known, we hypothesize a possible explanation of this interesting change.
Keywords Enchondroma . Regression . Radiography . MRI
Case Report
Introduction Enchondromas are common benign intramedullary cartilaginous lesions that account for 10–25 % of all benign bone tumors and have a peak incidence in the 2nd through 4th decades of life [1, 2]. The cartilaginous tumor matrix often A. Sensarma : J. E. Madewell : R. Kumar : B. Amini (*) Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Unit 1475, Houston, TX 77030, USA e-mail: [email protected] A. Sensarma e-mail: [email protected] J. M. Meis Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA P. P. Lin Department of Orthopedic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
A 50-year-old woman initially presented to an orthopedic surgeon at an outside facility with 2 months of atraumatic left arm pain. The pain was described as deep and was exacerbated with activity. The patient also had a history of thyroid carcinoma, which was treated with partial thyroidectomy and radioactive iodine 6 years prior to presentation. Radiographs obtained at an outside facility (not available for review) reportedly showed an enchondroma. Due to the presence of pain and history of thyroid carcinoma, a core needle biopsy of the lesion was obtained. Biopsy showed a grade 1 chondrosarcoma, and the patient was referred to our institution for management. Review of the submitted pathology (Fig. 1) at our institution revealed a chondroid lesion, representing either a grade 1 chondrosarcoma or cartilage neoplasm of indeterminate biological potential. On physical examination at our institution, there was tenderness to palpation of the proximal one third of the left humerus. There was no swelling or erythema, and the patient had full range of motion and strength in the left shoulder. Radiographs obtained at our institution (Fig. 2a) demonstrated an intramedullary cartilaginous lesion in the left
Skeletal Radiol
Fig. 1 Pathological specimens, with representative areas showing a scattered fragments of cartilage and marrow elements, b relatively hypocellular cartilage with minimal atypia, and c endochondral ossification (arrow) with very low cellularity of chondroid elements
proximal humeral metadiaphysis with punctate matrix mineralization. There was minimal endosteal scalloping and no cortical disruption. MRI (Fig. 2b–d) confirmed an intramedullary chondroid lesion extending from the physeal line into the proximal diaphysis for a length of 8.5 cm. The lesion had low signal on T1-weighted images (WI), high signal on T2-WI (Fig. 3a), and peripheral and septal enhancement on post-contrast images. There was mild endosteal scalloping anteriorly, but no cortical disruption or extraosseous soft tissue component was present. There was supraspinatus tendinosis. Based on reassuring findings on imaging, the decision was made to proceed with lidocaine injection of the left rotator cuff in the orthopedics office to asses for rotator cuff pathology as the etiology of the pain. On several follow-up visits over the course of a year, the pain had improved, but the patient continued to have occasional mild discomfort in the shoulder and upper arm. This was attributed to the rotator cuff and the patient was managed conservatively with 6-month and then yearly clinical and imaging follow-up for the next 7 years. MRI over this period (Fig. 3a–h) showed a slow decrease in
the size of the lesion and replacement of the distal portion of the lesion with marrow fat (Fig. 4). This was appreciated only in retrospect, as each follow-up study had been directly compared only to the most recent prior study and interpreted as stable. The MRIs, which were obtained with a large field of view for assessment of the bone lesion, revealed supraspinatus tendinosis, but no rotator cuff tear or muscle atrophy. The area of marrow signal abnormality now measured approximately 5 cm. The patient had not received any therapy during this period. After another year of follow-up, the patient developed worsening shoulder pain and decreased range of motion. Imaging at this time (Fig. 3h) revealed no concerning findings related to the lesion. Due to the presence of symptoms and patient concerns for the presence of a chondrosarcoma, the lesion was treated by curettage, argon beam ablation and bone grafting. The biopsy results (Fig. 5) demonstrated a nonaggressive cartilage tumor, but due to the patient's pain, a lowgrade chondrosarcoma was not entirely excluded. Two additional years of follow-up imaging revealed no recurrent disease. The patient is currently asymptomatic, 11 years after initial presentation.
Fig. 2 Baseline imaging in March 2003. a Frontal radiograph of the humerus reveals a lesion in the proximal metadiaphysis with internal ring and arc calcifications (black arrows) and minimal endosteal scalloping (white arrow). There was no cortical disruption, fracture or periosteal reaction. b Coronal T1-WI reveals the full extent of the lesion, which involved the proximal 8.5 cm of the metadiaphysis. Horizontal lines
indicate the levels for axial images in panels c and d. Axial postcontrast T1-WIs without fat suppression through proximal (c) and distal (d) portions of the lesion reveal an intramedullary lesion with peripheral enhancement and internal low-signal foci corresponding to chondroid matrix mineralization
Skeletal Radiol Fig. 3 Follow-up imaging over a period of 7 years. a–h Long-axis T2-weighted images with fat suppression from June 2003 (a) to January 2010 (h). Panels b–h are in the coronal plane. Panel a is in the sagittal plane because of the poor image quality of the coronal fluid-sensitive sequence obtained at that time
Regression of an enchondroma has been reported only once in the English language literature [5]. Baruchin et al. [5] described a case of a 16-year-old girl with a pathological fracture
through an enchondroma of the right hand small finger, which resolved with splinting after the patient declined surgery. Serial radiography showed healing of the fracture and reconstitution of the medullary cavity to normal appearance. The chondroid lesions in Ollier disease have been reported to
Fig. 4 Images obtained in June 2010, 7 years after baseline imaging and in the absence of therapy. a Frontal radiograph of the humerus reveals a lesion in the proximal metaphysis with internal ring and arc calcifications (arrow). b Coronal T1-WI reveals the full extent of the lesion, which now involves the proximal 5 cm of the metaphysis. Horizontal lines indicate
the levels for axial images in panels c and d. c Axial post-contrast T1-WI with fat suppression through the proximal portion of the lesion reveals an intramedullary lesion with peripheral enhancement corresponding to chondroid matrix mineralization. d Axial image more distally shows no evidence of the lesion seen initially (compare to Fig. 2d)
Discussion
Skeletal Radiol
Fig. 5 Final curettage specimen showing a a hypocellular cartilage component with endochondral ossification. Note host bone (white arrow). b Higher magnification of the most cellular areas seen in the curettage specimen with associated endochondral ossification (black arrow)
regress or disappear in adulthood [6, 7]; however, this is stated without reference to proven cases or demonstration of tumor regression. We have presented a case of regression of an enchondroma in an adult, which was documented on radiography and MRI. On radiography, this manifested as loss of matrix mineralization of the lesion, which would be interpreted as a sign of malignant transformation [3, 4]. However, as shown on MRI, this corresponded to replacement of the distal lesion matrix by normal marrow fat. While there is no known explanation for regression of a low-grade chondroid lesion, we propose a process similar to endochondral ossification as a possible etiology. Endochondral ossification in the diaphysis begins with differentiation of chondrocytes into hypertrophic chondrocytes, which mineralize the extracellular matrix and then undergo apoptosis [8, 9]. This extracellular cartilage matrix favors vascular invasion and the recruitment of chondroclasts and osteoclast progenitors [8–10]. The chondroclasts and osteoclast progenitors degrade the cartilage matrix [8, 9], while the maturing osteoblast precursors produce osteoid or non-mineralized bone matrix [11]. The mature osteoblasts promote mineralization of the osteoid matrix by accumulation of calcium hydroxyapatite [11], while osteoclasts resorb the mineralized matrix and help form the bone marrow cavity [9]. This process of resorption of the cartilage matrix of the lesion followed by production and subsequent resorption of the osteoid matrix may be used to explain the resorption of the cartilage lesion and subsequent replacement by bone marrow fat.
Conclusion While typically associated with malignant transformation, loss of matrix mineralization in an enchondroma can also represent
maturation of the cartilaginous lesion into bone marrow and may occur through a process analogous to endochondral ossification. Acknowledgments This work was supported in part by the Cancer Center Support Grant (NCI Grant P30 CA016672). Conflicts of Interest The authors have no conflicts of interest.
References 1. Lucas DR, Bridge JA. Chondromas: enchondroma, periosteal chondroma, and enchondromatosis. In: Fletcher CDM, Unni KK, Mertens F, editors. Pathology and genetics of tumours of soft tissue and bone. Lyon: IARC Press; 2002. p. 237–40. 2. Brien EW, Mirra JM, Kerr R. Benign and malignant cartilage tumors of bone and joint: their anatomic and theoretical basis with an emphasis on radiology, pathology and clinical biology. I. The intramedullary cartilage tumors. Skelet Radiol. 1997;26(6):325–53. 3. Unni KK. Cartilaginous lesions of bone. J Orthop Sci. 2001;6(5): 457–72. 4. Murphey MD, Flemming DJ, Boyea SR, Bojescul JA, Sweet DE, Temple HT. Enchondroma versus chondrosarcoma in the appendicular skeleton: differentiating features. Radiographics. 1998;18(5): 1213–37. 5. Baruchin A, Rosenberg L, Itzchaki M. Spontaneous restitution ad integrum of a fractured enchondroma in a finger. Int J Tissue React. 1981;3(1):17–20. 6. Miyawaki T, Kinoshita Y, Iizuka T. A case of Ollier's disease of the hand. Ann Plast Surg. 1997;38(1):77–80. 7. Anshu BY, Nalinimohan C, Gangane N. Cytodiagnosis of Ollier's disease: a case report. Diagn Cytopathol. 2009;37(7):513–5. 8. Ortega N, Behonick DJ, Werb Z. Matrix remodeling during endochondral ossification. Trends Cell Biol. 2004;14(2):86–93. 9. Karsenty G, Wagner EF. Reaching a genetic and molecular understanding of skeletal development. Dev Cell. 2002;2(4):389–406. 10. Ortega N, Wang K, Ferrara N, Werb Z, Vu TH. Complementary interplay between matrix metalloproteinase-9, vascular endothelial growth factor and osteoclast function drives endochondral bone formation. Dis Model Mech. 2010;3(3–4):224–35. 11. Dirckx N, Van Hul M, Maes C. Osteoblast recruitment to sites of bone formation in skeletal development, homeostasis, and regeneration. Birth Defects Res Part C Embryo Today: Reviews. 2013;99(3):170–91.
CASE REPORT
Regression of an enchondroma: a case report and proposed etiology Anirban Sensarma & John E. Madewell & Jeanne M. Meis & Rajendra Kumar & Patrick P. Lin & Behrang Amini
Received: 6 August 2014 / Revised: 11 September 2014 / Accepted: 6 October 2014 # ISS 2014
Abstract Enchondromas are common benign bone lesions that are found in the medullary cavity of tubular bones, usually at the metaphysis. Regression is highly unusual, and loss of matrix mineralization in an existing enchondroma should prompt investigation for malignant transformation. We present the case of a 50-year-old woman with an enchondroma of the proximal humeral metadiaphysis, which underwent loss of matrix mineralization that corresponded to replacement with marrow fat on MRI. This transformation of the cartilage tumor matrix into normal bone marrow may occur in a process similar to that seen with endochondral ossification.
has punctate and flocculent calcifications in the shapes of arcs and rings. Loss of uniform matrix mineralization may be due to replacement of the existing chondroid matrix with myxoid or necrotic areas, and should raise concern for the development of chondrosarcoma [3, 4]. We present an unusual case of an enchondroma in the proximal humerus, which gradually decreased in size with partial replacement of the chondroid matrix by normal marrow fat without treatment. Although the exact cause of this regression is not known, we hypothesize a possible explanation of this interesting change.
Keywords Enchondroma . Regression . Radiography . MRI
Case Report
Introduction Enchondromas are common benign intramedullary cartilaginous lesions that account for 10–25 % of all benign bone tumors and have a peak incidence in the 2nd through 4th decades of life [1, 2]. The cartilaginous tumor matrix often A. Sensarma : J. E. Madewell : R. Kumar : B. Amini (*) Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Unit 1475, Houston, TX 77030, USA e-mail: [email protected] A. Sensarma e-mail: [email protected] J. M. Meis Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA P. P. Lin Department of Orthopedic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
A 50-year-old woman initially presented to an orthopedic surgeon at an outside facility with 2 months of atraumatic left arm pain. The pain was described as deep and was exacerbated with activity. The patient also had a history of thyroid carcinoma, which was treated with partial thyroidectomy and radioactive iodine 6 years prior to presentation. Radiographs obtained at an outside facility (not available for review) reportedly showed an enchondroma. Due to the presence of pain and history of thyroid carcinoma, a core needle biopsy of the lesion was obtained. Biopsy showed a grade 1 chondrosarcoma, and the patient was referred to our institution for management. Review of the submitted pathology (Fig. 1) at our institution revealed a chondroid lesion, representing either a grade 1 chondrosarcoma or cartilage neoplasm of indeterminate biological potential. On physical examination at our institution, there was tenderness to palpation of the proximal one third of the left humerus. There was no swelling or erythema, and the patient had full range of motion and strength in the left shoulder. Radiographs obtained at our institution (Fig. 2a) demonstrated an intramedullary cartilaginous lesion in the left
Skeletal Radiol
Fig. 1 Pathological specimens, with representative areas showing a scattered fragments of cartilage and marrow elements, b relatively hypocellular cartilage with minimal atypia, and c endochondral ossification (arrow) with very low cellularity of chondroid elements
proximal humeral metadiaphysis with punctate matrix mineralization. There was minimal endosteal scalloping and no cortical disruption. MRI (Fig. 2b–d) confirmed an intramedullary chondroid lesion extending from the physeal line into the proximal diaphysis for a length of 8.5 cm. The lesion had low signal on T1-weighted images (WI), high signal on T2-WI (Fig. 3a), and peripheral and septal enhancement on post-contrast images. There was mild endosteal scalloping anteriorly, but no cortical disruption or extraosseous soft tissue component was present. There was supraspinatus tendinosis. Based on reassuring findings on imaging, the decision was made to proceed with lidocaine injection of the left rotator cuff in the orthopedics office to asses for rotator cuff pathology as the etiology of the pain. On several follow-up visits over the course of a year, the pain had improved, but the patient continued to have occasional mild discomfort in the shoulder and upper arm. This was attributed to the rotator cuff and the patient was managed conservatively with 6-month and then yearly clinical and imaging follow-up for the next 7 years. MRI over this period (Fig. 3a–h) showed a slow decrease in
the size of the lesion and replacement of the distal portion of the lesion with marrow fat (Fig. 4). This was appreciated only in retrospect, as each follow-up study had been directly compared only to the most recent prior study and interpreted as stable. The MRIs, which were obtained with a large field of view for assessment of the bone lesion, revealed supraspinatus tendinosis, but no rotator cuff tear or muscle atrophy. The area of marrow signal abnormality now measured approximately 5 cm. The patient had not received any therapy during this period. After another year of follow-up, the patient developed worsening shoulder pain and decreased range of motion. Imaging at this time (Fig. 3h) revealed no concerning findings related to the lesion. Due to the presence of symptoms and patient concerns for the presence of a chondrosarcoma, the lesion was treated by curettage, argon beam ablation and bone grafting. The biopsy results (Fig. 5) demonstrated a nonaggressive cartilage tumor, but due to the patient's pain, a lowgrade chondrosarcoma was not entirely excluded. Two additional years of follow-up imaging revealed no recurrent disease. The patient is currently asymptomatic, 11 years after initial presentation.
Fig. 2 Baseline imaging in March 2003. a Frontal radiograph of the humerus reveals a lesion in the proximal metadiaphysis with internal ring and arc calcifications (black arrows) and minimal endosteal scalloping (white arrow). There was no cortical disruption, fracture or periosteal reaction. b Coronal T1-WI reveals the full extent of the lesion, which involved the proximal 8.5 cm of the metadiaphysis. Horizontal lines
indicate the levels for axial images in panels c and d. Axial postcontrast T1-WIs without fat suppression through proximal (c) and distal (d) portions of the lesion reveal an intramedullary lesion with peripheral enhancement and internal low-signal foci corresponding to chondroid matrix mineralization
Skeletal Radiol Fig. 3 Follow-up imaging over a period of 7 years. a–h Long-axis T2-weighted images with fat suppression from June 2003 (a) to January 2010 (h). Panels b–h are in the coronal plane. Panel a is in the sagittal plane because of the poor image quality of the coronal fluid-sensitive sequence obtained at that time
Regression of an enchondroma has been reported only once in the English language literature [5]. Baruchin et al. [5] described a case of a 16-year-old girl with a pathological fracture
through an enchondroma of the right hand small finger, which resolved with splinting after the patient declined surgery. Serial radiography showed healing of the fracture and reconstitution of the medullary cavity to normal appearance. The chondroid lesions in Ollier disease have been reported to
Fig. 4 Images obtained in June 2010, 7 years after baseline imaging and in the absence of therapy. a Frontal radiograph of the humerus reveals a lesion in the proximal metaphysis with internal ring and arc calcifications (arrow). b Coronal T1-WI reveals the full extent of the lesion, which now involves the proximal 5 cm of the metaphysis. Horizontal lines indicate
the levels for axial images in panels c and d. c Axial post-contrast T1-WI with fat suppression through the proximal portion of the lesion reveals an intramedullary lesion with peripheral enhancement corresponding to chondroid matrix mineralization. d Axial image more distally shows no evidence of the lesion seen initially (compare to Fig. 2d)
Discussion
Skeletal Radiol
Fig. 5 Final curettage specimen showing a a hypocellular cartilage component with endochondral ossification. Note host bone (white arrow). b Higher magnification of the most cellular areas seen in the curettage specimen with associated endochondral ossification (black arrow)
regress or disappear in adulthood [6, 7]; however, this is stated without reference to proven cases or demonstration of tumor regression. We have presented a case of regression of an enchondroma in an adult, which was documented on radiography and MRI. On radiography, this manifested as loss of matrix mineralization of the lesion, which would be interpreted as a sign of malignant transformation [3, 4]. However, as shown on MRI, this corresponded to replacement of the distal lesion matrix by normal marrow fat. While there is no known explanation for regression of a low-grade chondroid lesion, we propose a process similar to endochondral ossification as a possible etiology. Endochondral ossification in the diaphysis begins with differentiation of chondrocytes into hypertrophic chondrocytes, which mineralize the extracellular matrix and then undergo apoptosis [8, 9]. This extracellular cartilage matrix favors vascular invasion and the recruitment of chondroclasts and osteoclast progenitors [8–10]. The chondroclasts and osteoclast progenitors degrade the cartilage matrix [8, 9], while the maturing osteoblast precursors produce osteoid or non-mineralized bone matrix [11]. The mature osteoblasts promote mineralization of the osteoid matrix by accumulation of calcium hydroxyapatite [11], while osteoclasts resorb the mineralized matrix and help form the bone marrow cavity [9]. This process of resorption of the cartilage matrix of the lesion followed by production and subsequent resorption of the osteoid matrix may be used to explain the resorption of the cartilage lesion and subsequent replacement by bone marrow fat.
Conclusion While typically associated with malignant transformation, loss of matrix mineralization in an enchondroma can also represent
maturation of the cartilaginous lesion into bone marrow and may occur through a process analogous to endochondral ossification. Acknowledgments This work was supported in part by the Cancer Center Support Grant (NCI Grant P30 CA016672). Conflicts of Interest The authors have no conflicts of interest.
References 1. Lucas DR, Bridge JA. Chondromas: enchondroma, periosteal chondroma, and enchondromatosis. In: Fletcher CDM, Unni KK, Mertens F, editors. Pathology and genetics of tumours of soft tissue and bone. Lyon: IARC Press; 2002. p. 237–40. 2. Brien EW, Mirra JM, Kerr R. Benign and malignant cartilage tumors of bone and joint: their anatomic and theoretical basis with an emphasis on radiology, pathology and clinical biology. I. The intramedullary cartilage tumors. Skelet Radiol. 1997;26(6):325–53. 3. Unni KK. Cartilaginous lesions of bone. J Orthop Sci. 2001;6(5): 457–72. 4. Murphey MD, Flemming DJ, Boyea SR, Bojescul JA, Sweet DE, Temple HT. Enchondroma versus chondrosarcoma in the appendicular skeleton: differentiating features. Radiographics. 1998;18(5): 1213–37. 5. Baruchin A, Rosenberg L, Itzchaki M. Spontaneous restitution ad integrum of a fractured enchondroma in a finger. Int J Tissue React. 1981;3(1):17–20. 6. Miyawaki T, Kinoshita Y, Iizuka T. A case of Ollier's disease of the hand. Ann Plast Surg. 1997;38(1):77–80. 7. Anshu BY, Nalinimohan C, Gangane N. Cytodiagnosis of Ollier's disease: a case report. Diagn Cytopathol. 2009;37(7):513–5. 8. Ortega N, Behonick DJ, Werb Z. Matrix remodeling during endochondral ossification. Trends Cell Biol. 2004;14(2):86–93. 9. Karsenty G, Wagner EF. Reaching a genetic and molecular understanding of skeletal development. Dev Cell. 2002;2(4):389–406. 10. Ortega N, Wang K, Ferrara N, Werb Z, Vu TH. Complementary interplay between matrix metalloproteinase-9, vascular endothelial growth factor and osteoclast function drives endochondral bone formation. Dis Model Mech. 2010;3(3–4):224–35. 11. Dirckx N, Van Hul M, Maes C. Osteoblast recruitment to sites of bone formation in skeletal development, homeostasis, and regeneration. Birth Defects Res Part C Embryo Today: Reviews. 2013;99(3):170–91.
