Chondromyxoid Fibroma of the Pelvis: Institutional Case Series With a Focus on Distinctive Features

Abstract

Chondromyxoid fibroma (CMF) is a relatively uncommon benign bone tumor of cartilaginous differentiation. The primary pitfall in the histopathologic diagnosis of CMF is confusion with a high-grade chondrosarcoma, owing to the atypical stellate and spindled cells set within a chondromyxoid background. CMF is particularly challenging to diagnose within the pelvis, where clinical suspicion for chondrosarcoma is high and benign lesions may grow to a large size to occupy the pelvic bones. In our practice, we noted this difficulty in several consecutive cases, especially when older patients presented with CMF within the pelvis. This prompted an institutional retrospective case review of all CMF within the pelvis. In 10 cases, we found overall that CMF of pelvis occurred in an older age range (mean age = 48.6 years), was larger in size (mean size = 6.0 cm), and showed a higher rate of soft tissue extension (50%) as compared with prior reports of nonpelvic CMF. Typical histologic features of CMF were seen in all cases; however, a high frequency of dystrophic calcification (50%) and necrosis (30%) was observed. Of interest, these aggregate demographic, radiologic, and histologic findings are all consistent with a benign neoplasm that has grown undetected within the pelvis over a long period of time. Recognition of these differences between pelvic CMF and tumors involving other sites will aid in avoiding misdiagnosis of this uncommon entity.

Introduction

Chondromyxoid fibroma (CMF) is a relatively uncommon benign bone tumor of cartilaginous differentiation. It represents less than 1% of all primary bone neoplasms.¹ CMF was first described in 1948 by Jaffe and Lichtenstein, who differentiated the neoplasm from chondrosarcoma based on its benign clinical behavior.² The peak incidence is in the second decade of life³; however, a second peak has been noted from the fifth to seventh decades of life.¹ A slight male predominance has been reported.^4,5 CMF commonly involves the metaphysis of long bones such as the tibia and femur.¹

Histologically, CMF is typically a lobulated tumor with spindled and stellate cells in a myxoid to chondroid matrix, with zones of fibrous tissue. Tumors tend to have central hypocellularity, with condensation of the nuclei, hypercellularity, and multinucleated giant cells in the periphery. Frank hyaline cartilage formation is rare. Histologic overlap between some CMF lesions and chondroblastoma has been described.³ Moderate cellular pleomorphism, calcifications, reactive bone formation, and secondary aneurysmal bone cyst (ABC) changes may also be seen. Mitoses are rare and are usually sparse when present.^1,3,5 Atypical mitotic figures are not observed. Necrosis is not a common histologic feature.

The primary pitfall in the histopathologic diagnosis of CMF is confusion with a high-grade chondrosarcoma due to the atypical stellate and spindled cells set within a chondromyxoid background. CMF is particularly challenging to diagnose within the pelvis, where clinical suspicion for chondrosarcoma is high, and benign lesions may grow to a large size to occupy the pelvic bones. In our practice, we noted this difficulty in several consecutive cases, especially in older patients presenting with CMF within the pelvis. This prompted an institutional retrospective review of all cases of pelvic CMF. In 10 cases, we found overall that CMF of the pelvis occurred in an older age range, was larger in size, and had a higher frequency of soft tissue extension as compared with prior reports of nonpelvic CMF. Typical features of CMF were seen in all cases; however, a high frequency of calcification and necrosis was also observed.

Material and Methods

Ten cases of CMF were identified in our surgical pathology archives (dated 1994–2018). Institutional review board approval was obtained, which included a waiver of informed consent for this retrospective case series. The clinical, radiographic, and histological data of the 10 cases were compiled. Three pathologists (ADW, EFM, and AWJ) independently verified the diagnoses. Maximal tumor diameters were measured with either computed tomography (CT) or magnetic resonance image (MRI) by a Vitrea viewer (Vital Images, Inc, Minnetonka, MN).

Results

Patient Demographics

Of the 10 available cases of pelvic CMF, 5 patients (5/10, 50%) were males. Patient age ranged from 34 to 68 years (mean = 48.6 years; Table 1). The majority of tumors occurred in patients in their fifth and sixth decades of life (Figure 1). Four patients presented with pain (4/10), including buttock pain (n = 2), pelvic pain (n = 1), and lower extremity pain (n = 1). Of the tumors within the pelvic ring, 6 cases (6/10, 60%) were located in the ileum, 1 case in the acetabulum, 1 in the pubis, and 1 in the sacrum. A specific site of origin was not recorded for the remaining case.

Table 1.

Patient Demographics and Summary of Clinical Data.

No.	Age (Years)	Sex	Location	Diameter (cm)	Treatment	Follow-up (Months)
1	44	Male	Ilium	8.4	Curettage and allograft	12
2	40	Male	Pelvis	NA	Curettage	NA
3	68	Female	Ilium	4.6	NR	NA
4	57	Male	Ilium	7.9	Resection	6
5	36	Female	Ilium	2.1	Curettage	NA
6	44	Female	Sacrum	6.4	Embolization, resection, posterior fusion, and fibular autograft	24
7	56	Female	Ilium	6.5	Curettage and allograft	24
8	34	Female	Pubis	NA	Resection	NA
9	58	Male	Ilium	NA	Curettage and allograft	48
10	49	Male	Acetabulum	6.0	NR	NA

Abbreviations: NR, data not recorded; NA, not available.

Figure 1.

Patients’ age distribution. Patients in their fifth and sixth decades represent the majority of chondromyxoid fibroma in pelvis cases.

Radiographic Appearance

Radiologic images were available for review in 8 cases and are shown in Figure 2. The mean maximum dimension of the tumors was 6.0 cm (range = 2.1–8.4 cm). On X-ray, CMF was typically seen as an osteolytic lesion with a well-demarcated border (Figure 2A and B). Prominent intratumoral calcification was seen in one case (Figure 2B). On CT scan, tumors frequently appeared as osteolytic lesions, also with well-demarcated borders, and with soft tissue involvement in 4 cases (Figure 2C–E; 4/8 cases with available imaging, 50%). MRI imaging was available in 4 cases, and in each case showed hypointense to intermediate signal intensity on T1-weighted image (Figure 2F), and diffuse hyperintensity on T2-weighted images. On a T2 fat saturation image, heterogeneous intermediate to hyperintensity lesion was seen (Figure 2G). Suspected ABC change was seen in one case and was associated with adjacent bone edema (Figure 2H). Several MRI features previously reported to favor CMF over chondrosarcoma were examined in our cases, including (1) a low-signal intensity rim on all sequences and (2) a lack of or minimal bone or soft tissue edema.⁶ A low-intensity rim on all sequences was only seen in 2 of 4 cases (50%). In addition, more than minimal bone or soft tissue edema was present in 3 of 4 cases (75%).

Figure 2.

Representative radiologic images of pelvic chondromyxoid fibroma. Tumors are highlighted with red arrows. (A and B) Appearance by X-ray. (A) Well-demarcated radiolucent lesion in the right pubis. (B) Well-demarcated and primarily radiolucent lesion with prominent, internal, speckled calcification in the left iliac wing. (C-E) Appearance by computed tomography scan. Here and in 3 cases, osteolytic lesion with focal to prominent cortical disruption are seen with soft tissue extension, involving the right ilium (C and D) or left ilium (E). (F) Magnetic resonance (MR) T1-weighed image. Hypointensity area was seen in the right acetabulum. (G and H) MR T2-weighed images. (G) T2 fat saturation image. Heterogeneous intermediate to hyperintensity lesion was seen in the left ilium. (H) Suspected aneurysmal bone cyst change was seen ventral to the right sacrum. Pathological fracture and edematous change were both seen in the right sacrum (arrow head).

Histological Appearance

All samples exhibited typical histologic features of CMF, including a lobular architecture with central stellate cells in a chondromyxoid, basophilic matrix with adjacent fibrous septa, and peripheral hypercellularity (Figure 3A and B). Multinucleated giant cells were frequently seen (Figure 3C). Five cases (50%) showed dystrophic calcifications, which ranged from focal and punctate (3/5, 60%) to prominent and diffuse (2/5, 40%; Figure 3D and Table 2). Reactive bone formation was seen in 2 cases (20%). Mitotic figures were inconspicuous in 7 cases (70%). In 3 cases (30%), there were 1 to 2 mitoses per 10 high-power fields. Three cases (30%) showed focal necrosis. One tumor (10%) exhibited chondroblastoma-like foci (Figure 4A and B), which was accompanied by foci of frank hyaline cartilage. Here, sheets of oval-to-polyhedral cells with cleaved or lobulated nuclei were prominent in the chondroblastoma-like areas. This same tumor showed prominent secondary ABC change (Figure 4C and D). On higher magnification, the ABC wall showed typical reactive woven bone formation, multinucleated giant cells, and hemosiderin deposition (Figure 4D).

Figure 3.

Representative histologic images of pelvic chondromyxoid fibroma by routine hematoxylin-eosin. (A) Representative image of chondromyxoid fibroma demonstrating a lobular architecture with central stellate cells in a myxoid matrix and adjacent areas of hypercellularity. (B) Myxoid areas show stellate and spindled cells. Prominent thin-walled vessels may be seen. Multinucleated giant cells (C) are common. Diffuse calcifications (D) may be present. “A” was obtained at 5× magnification, “B” was obtained at 64×, “C” was obtained at 40×, and “D” was obtained at 10×.

Table 2.

Comparison of CMF Histological Characteristics Between Current Study and Previously Reported Mayo Clinic Data³.

Histologic Characteristics	Current Study	Prior Report of 84 Cases in Flat Bones3,a	Prior Report of 278 Cases3
Calcification	50%	36.9%	35.3%
Reactive bone formation	20%	11.9%	15.1%
Mitoses/10 HPF identified	30%	9.5%	11.2%
Necrosis	30%	10.7%	11.9%
Secondary ABC component	10%	10.7%	8.6%
Chondroblastoma-like foci	10%	7.1%	8.3%
Hyaline cartilage	10%	15.5%	18.7%

Abbreviation: CMF, chondromyxoid fibroma; HPF, high-power field; ABC, aneurysmal bone change.

^aCases in flat bones included pelvis, ribs, vertebra, and sacrum.

Figure 4.

Representative histologic images of pelvic chondromyxoid fibroma by routine hematoxylin-eosin. In a single case, chondroblastoma-like foci as well as aneurysmal bone cyst (ABC) changes were seen. (A) More typical chondromyxoid fibroma appearance in this case, including lobular growth pattern with central hypocellularity, spindled and stellate cells in a chondromyxoid matrix. (B) In the same tumor, a chondroblastoma-like foci. (C) In the same tumor, cystic blood-filled spaces with ABC change. (D) High magnification of the ABC wall, with woven bone formation, multinucleated giant cells, and hemosiderin deposition. “A” was obtained at 10×, “B” was obtained at 20×, “C” was obtained at 5×, and “D” was obtained at 40×.

Treatment

Treatment information was available for 8 of the 10 patients (Table 1). Of these patients, 5 (62.5%) had curettage with or without allograft. Three patients (37.5%) underwent resection. The patient with the sacral lesion underwent preoperative embolization followed by resection and posterior spinal fusion from L3 to the ilium. The follow-up period ranged from 6 months to 4 years (mean follow-up = 22.8 months). None of the tumors recurred.

Discussion

We examined the clinical, radiologic, and histologic features of 10 cases of CMF from the Johns Hopkins University institutional archives. Several distinguishing features were identified in pelvic CMF as compared with CMF involving other sites, as reported in the literature. Distinguishing features of pelvic CMF in our series included older age, larger size, higher incidence of soft tissue extension by imaging, and higher incidence calcification and necrosis by histology as compared with prior reports of nonpelvic CMF.^3,7

In terms of demographics, CMF commonly occurs in the second and third decades of life.^1,3 The average patient age in this series was 48.6 years. This average age is similar to that of chondrosarcoma,^8,9 further complicating accurate diagnosis in cases which exhibit histologic overlap. No gender predominance was seen in our series.

In terms of imaging characteristics, CMF is typically an expansile lobulated or oval osteolytic lesion.⁶ CT imaging is useful, especially in small lesions that cannot be detected by X-ray. In our series, purely osteolytic lesions were seen in most cases (9/10, 90%), while prominent calcification was seen in one case. Soft tissue extension was detected in 4/8 cases with available radiography (50%), which is higher than most reports.^3,6 For example, the Mayo Clinic reported soft tissue extension in 25% of CMF involving flat bones, which was not increased over other sites of involvement.³ As in our series, CMF has a characteristic MRI appearance. On MRI T1-weighted images, lesions typically show low to intermediate intensity, and may have internal hyperintense foci.¹⁰ Lesions are hyperintense on T2-weighted images^6,10 with T2 short tau inversion recovery or T2 fat saturation images showing an intermediate to hyperintense signal (Figure 2G).⁶ In prior reports, a low-signal intensity rim on all MRI sequences, and lack of or minimal bone or soft tissue edema, helped distinguish a diagnosis of CMF over chondrosarcoma.⁶ In the current study, these MR findings were not reliably identified in those 4 cases with available imaging. For example, 50% of tumors did not show clear low-intensity rims on all MRI sequences, and 75% of tumors demonstrated surrounding edema that was estimated to be more than minimal.

Several distinguishing histologic features of CMF were observed in our case series (Table 2). Microscopic calcification was observed in 50% of the cases, which ranged from focal to diffuse. The reported rate of calcifications ranges from 13% to 25% radiologically^3,4,6,11 and by histology most often less than 35%.³ Necrosis is an uncommon feature of CMF, and usually raises concern for malignancy. The rate of necrosis was 30% in this series. In contrast, the Mayo Clinic reported necrosis in 11.9% of all CMF, and 10.7% of CMF within flat bones.³ It is important to recognize that necrosis can occur in benign lesions, and its presence alone should not lead to a malignant diagnosis. Secondary ABC in CMF is an uncommon, but recognized, phenomenon, previously reported to involve approximately 8% of CMF in general.³ Our series suggested that ABC changes are slightly more common in pelvic CMF (10% of cases), which is in agreement with the Mayo Clinic report (ABC areas in 8.6% of all CMF and 10.7% in CMF of flat bones).³ Finally, a single lesion showed mixed features of CMF and chondroblastoma. This is a well-described histologic variant that has a benign clinical course and occurs in a reported 8.3% of CMF.³

In our series, all diagnoses were made by incisional biopsy rather than needle core biopsy. This difference is important to note, as small cores of tissue may not contain enough detail to confidently diagnose CMF and rule out chondrosarcoma. Typical features of CMF, including chondroid, fibrous, and myxoid elements, are not always present on needle biopsy. Given the variability between tumors, the spatial variability within CMFs, and some of the distinctive features of pelvic CMF, as we will discuss, require a larger biopsy sample.

Genetically, recurrent rearrangements of various segments on chromosome 6 are reported in CMF.¹² Recently, glutamate receptor gene 1 was reported to be upregulated through gene fusion and promoter swapping in CMF.¹³ As an aside, the molecular features of cross-over CMF/chondroblastoma lesions have, to our knowledge, not yet been examined.

In this series, treatment consisted of resection of the lesion or curettage with or without allograft. Reported recurrence rates were approximately 25% following curettage^5,14; however, no recurrences were observed in this case series at time of most recent follow-up. For large sacral lesions, as seen in one patient in this series, posterior spinal fusion with instrumentation and autograft, in addition to resecting the lesion, may be necessary.^15,16 Radiation therapy is not recommended due to the risk of recurrence and possibility of secondary sarcoma.^1,5

For a practicing pathologist, the most important distinction to be made is between pelvic chondromyxoid fibroma and pelvic chondrosarcoma. A summary of clinical, radiologic, and pathologic features of both is provided in Table 3. Patient demographics are not helpful, and both pelvic CMF and chondrosarcoma have a similar mean patient age. Although pelvic chondrosarcomas are generally larger than pelvic CMF, there is substantial overlap in tumor size. Distinguishing CMF from chondrosarcoma by imaging is likewise not clear cut. In our experience, radiographic calcification is more common in chondrosarcoma, but is not a distinguishing feature. As well, features such as extrapelvic extension or the presence of bone and soft tissue edema do not reliably distinguish between these diagnostic entities. The diagnosis rests on histologic examination, where awareness of the key histologic appearance of CMF allows for diagnosis (Table 3). In our experience, an open biopsy rather than a core needle biopsy may be required for diagnostic certainty in some cases. Presently, no antigens distinguish CMF from chondrosarcoma by immunohistochemistry. IDH1 mutational analysis may at some point be a clinically useful tool, present in 59% of chondrosarcoma cases but absent in CMF.¹⁷

Table 3.

Comparison of Clinical, Radiographic, and Pathologic Characteristics Between Current Study on Pelvic CMF and Previous Reports of Pelvic Chondrosarcoma.

		Pelvic CMF in Current Study	Pelvic Chondrosarcoma Based on Prior Reports5,7,18
Clinical	Age (years)	48.6 (mean)	47 (mean)
	Sex	Equally distributed	Male predominance
	Size	6 cm (mean)	10 cm (mean)
Radiographic	Shape	Lobulated and smooth with sclerotic margin	Irregular margin and endosteal scalloping
	Calcification	Infrequent, 10%	Frequent, 75%
	MRI	T1WI hypointensity	Ring-and-arc enhancement early and exponential enhancement
		T2WI intermediate to hyperintensity
Pathologic		Spindled to stellate cells in a chondromyxoid matrix	Varies depending on grade of tumor
		Lobular growth with peripheral hypercellularity featuring multinucleated giant cells	Atypical chondrocytes in a chondroid to chondromyxoid matrix
		Less frequent hyaline cartilage	More frequent hyaline cartilage
			Lobular growth with peripheral ossification of cartilage

Abbreviations: CMF, chondromyxoid fibroma; MRI, magnetic resonance image; T1WI, T1-weighted image; T2WI, T2-weighted image.

In summary, CMF is a relatively uncommon benign skeletal tumor of cartilaginous differentiation. The primary pitfall in the histopathologic diagnosis of CMF is the confusion with a high-grade chondrosarcoma. In our case series study, CMF of the pelvis occurs in an older age range, is a larger size, includes frequent soft tissue extension, and shows on histologic analysis a high frequency of dystrophic calcification and necrosis as compared with prior reports of nonpelvic CMF.^3,7 Interestingly, these aggregate demographic, radiologic, and histologic findings are all consistent with a benign neoplasm that has grown undetected within the pelvis over a long period of time. Awareness of these distinguishing features of CMF of the pelvis will help avoid diagnostic confusion with chondrosarcoma.