Turk J Med Sci2007; 37 (4): 243-249© TÜB‹TAKE-mail: [email protected]
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CASE REPORT
Sacral Chondroblastic Osteosarcoma Misdiagnosed asChondrosarcoma and Chordoma
Abstract: Chondroblastic osteosarcoma (COS), a subgroup of intramedullary osteosarcoma, is usually locatedin the knee region of the body. It is most common in adolescents and early adulthood. COS has similar clinicaland radiological features to those of conventional osteosarcomas.
A 17-year-old male suffered from walking problems and lower limb pain. CT and MRI revealed a mass withsoft tissue density and bone destruction at the level of L5-S1. It was described as “posttraumatic hematoma”.In cytopathologic examination, initial diagnosis was chordoma in fine-needle aspiration cytology (FNAC),chondrosarcoma in incisional biopsy, and finally COS in total resection specimen.
Because sacral location of COS is very rare, this report aimed to discuss radiological and pathological diagnosticpitfalls of COS in light of the literature.
Key Words: Chondroblastic osteosarcoma, chondrosarcoma, chordoma, sacrum
Kondrosarkom ve Kordoma ile Kar›flt›r›lan Sakral Kondroblastik Osteosarkom
Özet: Kondroblastik osteosarkoma(COS), intramedüller osteosarkom’un bir alt grubudur ve genelde dizbölgesinde yerleflir. Ergenlik ça¤›nda s›kt›r. COS’un klinik ve radyolojik bulgular› di¤er osteosarkomlara benzer.
Yürüme problemleri ve alt ekstremitede a¤r› yak›nmas› olan 17 yafl›nda bir hastan›n tomografi ve MRincelemelerinde L5-S1 düzeyinde yumuflak doku dansitesinde ve kemikte destrüksiyona yol açan kitle saptand›.Kitle ‘posttravmatik hematom’ olarak rapor edildi. ‹nce i¤ne aspirasyon biyopsisi(FNAC) kordoma, insizyonelbiyopsisi kondrosarkoma olarak rapor edildi ve sonuçta COS total olarak ç›kar›ld›.
Anahtar Sözcükler: Konroblastik Osteosarkom, Kondrosarkom, kordoma, Sakrum
Nusret AKPOLAT1
Hanefi YILDIRIM2
Kürflat POYRAZ2
1 Department of Pathology, Faculty of Medicine, F›rat University, Elaz›¤ - TURKEY
2 Department of Radiology, Faculty of Medicine, F›rat University, Elaz›¤ - TURKEY
Received: October 09, 2006Accepted: June 26, 2007
Correspondence
Nusret AKPOLATDepartment of Pathology,
Faculty of Medicine, F›rat University,
23119 Elaz›¤ - Turkey
Introduction
Chondroblastic osteosarcoma (COS) is a subgroup of intramedullary osteosarcoma,and primarily involves the femur and tibia. It is most common in adolescents and in earlyadulthood and constitutes 9-25% of osteosarcomas. COSs show similar clinical andradiological features to those of conventional osteosarcomas. Morphologically, they arecharacterized with chondroid and osteoid differentiation (1-3).
Chondrosarcoma (CS) is the third most frequent bone tumor (20-30%) followingmyelomas and osteosarcomas, respectively. They mostly occur in elderly patients with apeak incidence in the sixth decade. Shoulder, pelvis, proximal femur and costalinvolvement are frequently seen, but sacral involvement is very rare (2%) (4).
Chondroid chordomas (CC) are rare malignant tumors that are frequently located inthe sphenooccipital region and predominantly seen in early adulthood and males. Theyarise from embryological notochord remnants. They are considered a subgroup of classicchordomas because of their clinical and pathological differences from classic chordomas(5-8).
These three neoplasms show chondroid differentiation. Therefore, in small biopsyspecimens, differential diagnosis is difficult. Morphologically accurate diagnosis ismandatory because of different treatment and clinical features of these three malignantneoplasms. In this report, problems and solutions related to these three differententities are discussed.
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Case Report
A 17-year-old male patient with walking problemsand complaints of lower limb pain was admitted to theNeurosurgery Department of Firat University, FiratMedical Center. Computed tomography (CT) showed amass lesion with soft tissue density and bone destructionat the level of L5-S1, indicating a posttraumatichematoma. Magnetic resonance imaging (MRI) findingsincluded an enhancing inflammatory soft tissue mass thatcompressed on the nerve roots at the level of L5-S2 withbone destruction. The mass was extending into the spinalcanal and involved S1 and S2 vertebral bodies (Figure 1).
In CT-guided fine-needle aspiration cytology (FNAC)of this lesion, small multinucleolar, pleomorphic,transparent malignant tumoral cells with oval-roundnucleus or fusiform large nucleus in myxomatousbackground were observed (Figure 2).Immunohistochemical staining for S-100 (Lab VisionCorporation, CA, USA) and vimentin (Lab VisionCorporation, CA, USA) were positive. In FNAC, chordomawas diagnosed.
In microscopic examination of the biopsy specimen,lobulated chondroid areas and neoplastic cells were seenin myxoid background. In cartilaginous areas, there were
Figure 1. MRI shows soft tissue lesion inflicting vertebral destructionin the presacral region (L5-S2).
Figure 2. FNAC: Neoplastic cells show nuclear membrane irregularity, coarse chromatin, pleomorphismand hyperchromasia (MGG, x1000).
neoplastic chondrocytes, some with large nucleus andcoarse chromatin and some with one or more nucleolusand irregular-edged fine chromatin within lacunae whichwere surrounded by hyaline matrix. Cytoplasms of theneoplastic chondrocytes were narrow with clear
perinuclear halo (Figure 3). Malignant cells were presentwith evident pleomorphism and hyperchromatic nucleusand without a characteristic pattern within large myxoidareas around chondroid areas (Figure 4). Based on thesefindings, the diagnosis was CS (grade I-II).
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Figure 3. Malignant chondroid cells and coagulation necrosis (H&E, x400).
Figure 4. Malignant mesenchymal cells with hyperchromatic and pleomorphic nuclei in myxoidbackground (H&E, x200).
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The tumor was totally resected. The specimenconsisted of two pieces (8x6x3 cm and 7x5x2 cm) thatcontained bone and soft tissue components. Inmicroscopic examination, there were lobulated malignantchondroid areas and oval-spindle shaped malignant cellsin myxoid background. Osteoid formation was locatedbetween spindle malignant cells. Enchondral ossificationwas shown in chondroid areas. The tumor was diagnosedas grade III COS.
In immunohistochemical stain, neoplastic cells werepositive for cytokeratin (Lab Vision Corporation, CA,USA), epithelial membrane antigen (EMA) (Lab VisionCorporation, CA, USA) and S-100 (Lab VisionCorporation, CA, USA). For this reason, initial biopsyspecimens were reassessed. Serial cutting was done ofthe small biopsy material and the material on the slidewas larger than of the first slides. There were smallosteoid focuses (Figure 5) and large enchondralossification areas. It was concluded that the first biopsyhad been misdiagnosed as CS.
The patient received radiotherapy. No local recurrenceor metastasis was detected in the postoperative 25thmonth.
Discussion
CSs are the third most frequent bone tumors with apredilection for male gender. Peak incidence is in the sixthdecade. The shoulder, pelvis, proximal femur, and costaeare the most frequent sites of involvement. Sacralinvolvement (2%) is highly rare (4).
Conventional CSs may be hyalinized, myxoid or mixed.Hyaline CSs are characterized with hypercellular hyalinecartilage with atypical chondrocytes within lacunae.Conversely, in myxoid CSs, atypical chondrocytes are notseen in the lacunae and constitute large neoplastic cellgroups in myxoid matrix. Neoplastic cells areimmunohistochemically positive for vimentin and S-100and negative for epithelial markers such as keratin andEMA in CSs. Generally, typical CS diagnosis can be basedon these findings, but myxoid variant can be confusedwith chordoma (4,6).
Chordomas have three subtypes: classical,dedifferentiated, and chondroid. Unlike conventionalchordoma, CC involves the sphenooccipital region, and itis more frequent in early adulthood with a betterprognosis (5,6). Conventional chordomas include largeepithelioid cell cords within vesicular myxoid stroma and
Figure 5. Osteoid production (H&E, x400).
solid nests. Chondroid variant differs from typicalchordoma with its hyalinized stroma and might beconfused with CS. Differential diagnosis of CS and CC isdifficult (7,8). In myxoid CS, neoplastic chondrocytes arerelatively small and narrow. They do not show nestformation. Conversely, chordoma cells are larger andhave dense eosinophilic cytoplasms. They form groups,and desmosomes can be seen between cells.Immunohistochemical staining is very important indifferential diagnosis of these two tumors. Chordomasare immunohistochemically positive for vimentin, S-100,EMA and cytokeratin (9,10).
Clinical behavior, recurrence, and metastaticcharacteristics of CS and CC are very different.Therefore, differential diagnosis based on pathologicalevaluation is necessary. Theoretically, it is possible todifferentiate CC from classic CS with morphology, but inpractice, it is difficult. Thus, false diagnosis is possible. Ina study with 200 skull base CS, 34% of the cases werediagnosed as chordoma initially; however, furthermorphologic and immunohistochemical assessmentsshowed that these were actually CS (6).
COS and conventional osteosarcoma have similarclinical, radiological, and prognostic features. COSsconstitute 9-25% of conventional osteosarcomas (2).COS can be confused with CS in small biopsy specimens,and differential diagnosis can be difficult. Differentialdiagnosis is necessary because of clinical and treatmentdifferences between these two neoplasms. Clinicalcharacteristics such as age and location and radiologicalfindings help in differentiation of these two neoplasms.Osteoid formation within the tumor is the mostimportant morphologic diagnostic feature. It is notalways possible to obtain osteoid formation in smallbiopsy specimens. As a consequence, cases with COSmight be misdiagnosed as CS. False diagnosis rate hasbeen reported to be as high as 44% (3).
Clinical and radiological findings must be used fordifferential diagnosis of COS and CS (Table 1). The mostimportant clinical findings are patient’s age and locationof the lesion. As in our case, the radiological differentialdiagnosis of an atypically located lesion might beimpossible. Unni (2) emphasized that in an adolescentpatient or a patient in his/her early adulthood, if thetumor morphologically constitutes a neoplastic cartilageand osteoid formation does not accompany, unlessproven to the contrary, it must be considered and treated
as COS. CS is predominantly seen in the elderly (4th-6thdecade) and is highly rare in adolescents and earlyadulthood. Prognosis in CS is better and metastatictendency is lower (4).
Our case was initially reported as chordoma based onthe cytology. Further evaluation of biopsy specimenindicated CS, while the final evaluation of the specimenshowed COS. Therefore, the following points should beconsidered throughout the diagnostic process:
1. For accurate diagnosis of bone tumors, clinicalfindings such as the age of the patient and locationof the lesion as well as the radiologic findingsshould be taken into consideration. Misdiagnosis isunavoidable if diagnosis is based on morphologicalfindings alone (1). In our patient, we attempted todiagnose in view of the morphological findingsalone, not along with clinical and radiologicalfindings. Pathologists sometimes experience thiskind of important problem, which may be called“morphology fanaticism” or “morphologycaptivity”. Morphology captivity originates fromthe idea that only morphological findings aresufficient for the answers to problems withoutany contribution by other diagnostic findings.Although morphology is important in diagnosis incertain cases, it is necessary to base the diagnosison other findings as well, which is also true fordiagnoses of bone tumors.
2. The patient’s age is a significant parameter foraccurate diagnosis. Our patient was 17 years old.According to Unni (4), tumors with chondroiddifferentiation and without any osteoid formationin teenage patients must be diagnosed asosteosarcoma, unless proven to the contrary.
3. Another finding that cytologically supportschordoma is the location of the tumor becausechordoma is the most frequent neoplasm thatoriginates from the sacrum. In addition, thepresence of neoplastic cells with vacuolizedcytoplasms, which are like physaliphorous tumorcells, is supportive of a chordoma. Althoughphysaliphorous cells are specific for chordoma,this finding is not diagnostic because these cellsmay also be seen in myxomatous tumors (myxoidCS) (10). However, for myxoid CS and chordoma,cytological diagnosis cannot be established
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accurately without immunohistochemicalassessment.
4. If clinical, radiological and morphologic findingsare discordant, the lesion should be described andother possible diagnoses should be kept in mind toachieve an accurate diagnosis.
5. When diagnosis is made based on small biopsyspecimens, whole tissue in all blocks should be cut
with serial sections and no result should bedeclared without assessment of the entire tissue.In our case, the blocks cut with serial sections andtheir further reassessment showed diagnosticosteoid areas in two-fold compared to theprevious evaluations of tissue sections, whichsupported osteosarcoma.
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Table 1. Basic features of CC, CS and COS and comparison with our case.
CC CS COS OUR CASE
Age Early adulthood Adult - elderly Adolescent - teenage 17
Location Sphenooccipital Pelvis and shoulder (48%) Femur and tibia (67%) SacralSacral 2% Sacral <1%
M/F 2.3/1 1.2/1 1.5/1 M
Clinical findings Pain, compression Swallowing, pain, Swallowing, pain, Pain, walking symptoms pathologic fracture pathologic fracture disorder
Radiology Irregular bone Cortical erosion Metaphyseal Hematoma?destruction or thickening radiolucent mass Soft tissue infection?
Bone expansion Spurs, extension toCalcification soft tissue, Codman
triangle, calcification
Macroscopy Lobulated, myxoid mass Lobulated chondroid Cortical penetration Curetted biopsy Cartilage appearance Myxoid changes ± Periost reaction material
Extension to soft tissuePseudocapsulated
Microscopy Cartilage lobules Cell with small and Lobulated Lobulated malignantFibrous septa narrow cytoplasm chondrosarcomatous chondroid areas,Hard groups, No cohesive groups, tumor Oval-spindle shapedcordon or nest forming cells surrounded Osteoid formation malignant cell in epithelial cells, by matrix, Necrosis, giant cell ± myxoid backgroundDesmosome-like mineralization ±, Enchondralintercellular connections, ossification ± ossificationPhysaliphorous cells Osteoid formation
IHC CK, EMA, Vim, S100 and S100, Vim (+), S100, Vim (+), S100, CK,5-nucleotidase (+) CK, EMA (-) Rarely CK, EMA (+) EMA (+)
Treatment Surgery + Surgery + Chemotherapy + Surgery +Radiotherapy Radiotherapy Surgery Radiotherapy
Distant metastasis 22% 0% Frequent Absent
Recurrence 70% 1.5-53% 4% Absent
10-year survey 35-45% 88-98% 75% -
COS: Chondroblastic osteosarcoma. CS: Chondrosarcoma. CC: Chondroid chordoma. IHC: Immunohistochemistry. M: Male. F: Female. CK: Cytoker-atin. Vim: Vimentin. EMA: Epithelial membrane antigen.
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