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Mesenchymal chondrosarcoma of the orbit: two cases and a brief review of the literature

Introduction

Since mesenchymal chondrosarcoma (MChS) was first described over half a century ago, in 1959 by Lichtenstein and Bernstein [1], about 500 cases have been reported. The hallmark of this rare, highly malignant neoplasm is a bimorphic histological pattern composed of small undifferentiated round cells with islands of cartilage. The cellular areas frequently demonstrate perivascular arrangement resembling a haemangiopericytoma-like pattern.

The incidence of MChS varies from 1% to 13% of all bone chondrosarcomas. Clinical symptoms are nonspecific and include swelling, pain, palpable slowly enlarging bone or soft tissue mass. It occurs most often in young adults, particularly in the second to fourth decade of life.

Cases of the skeletal location represent the majority accounting for 65-70%. Extraskeletal lesions comprise approximately 30-35%. Single cases (7%) of osseous MChS were classified as multicentric [2]. The extraskeletal MChS has a female predilection while the skeletal MChS affects men and women equally. In contrast to conventional chondrosarcomas, MChS of bone are found in the axial skeleton predominantly and the most frequently affected site is a craniofacial region (up to 30%) [2]. Majority of cases involves normal, unimpaired bone. The MChS arising as a secondary lesion to the prior fibrous dysplasia has also been reported [3].

Extraskeletal MChS typically occurs in the lower extremities, usually as an intramuscular, thigh lesion [4]. Cases with the unique location in the brain and meninges, heart, kidney, thyroid gland and pancreas have also been reported [5, 6]. Approximately 30 cases of the orbital involvement were reported including two cases of congenital MChS [7-10].

We describe two cases of MChS of the orbit. Case 1 was classified as a primary extraskeletal MChS of the orbit. Case 2 was diagnosed as a skeletal MChS of the ethmomaxillary complex with secondary orbit involvement. Case 2 has been presented as a Quiz case.

Case report

Clinical presentation



Case 1: A 31-year-old female, without past medical history, complained of difficulties with nasal respiration and headaches during the right eye movement. Computed tomography showed a tumor of the right ethmomaxillary complex measuring 39 mm × × 31 mm × 30 mm. Histopathology of the biopsy specimen revealed a small cell malignancy. Two months after initial diagnosis the patient was admitted to the Head and Neck Cancer Department of Maria Skłodowska-Curie Memorial Cancer Center for further evaluation and treatment. Physical examination revealed mild proptosis, restriction of the right eye mobility and anosmia. The chest X-ray and abdominal ultrasonography were normal with no evidence of metastatic disease.

Case 2: The case has been presented as a Quiz case. A 29-year-old female was admitted to the hospital with pain of her left eye and progressive proptosis for about 6 months. Ultrasound and computed tomography (CT) were performed and showed a tumor mass of the left orbit. Debulking of the tumor and subsequent pencil beam radiotherapy was performed. The patient developed tumor recurrence 3 years after the procedure with severe proptosis, movement restriction and blindness in the left eye. Magnetic resonance revealed tumor of the orbit encasing the left optic nerve and pushing forward the patient’s eye. Chest X-rays showed no metastatic disease.



Radiological imaging



Case 1: The magnetic resonance imaging demonstrated a well-delineated tumor of the right ethmoid bone 4.7 cm × 3.6 cm × 2 cm in size. The malignancy penetrated to the anterior part of cranium with focal meningeal involvement and extension to the medial side of the orbit. After intravenous contrast administration, the moderate heterogeneous enhancement of non-calcified component was noted (Fig. 1 A).

Case 2: The tumor was located in the upper part of the orbit with no evident involvement of the remaining orbital wall. In the magnetic resonance, a polycyclic, multinodular, well-delineated tumor invading the upper, medial and posterior part of the left orbit, 4.5 cm in diameter was found. The malignancy was attached to the eyeball and the optical nerve. The frontal bone and orbital roof defects were identified. The tumor demonstrated increased homogenous enhancement after intravenous contrast administration with focal areas of calcifications seen in T1 and T2-weighted images (Fig. 1 B).



Treatment



Case 1: The tumor has been partially excised without surgical margins. Enucleation was recommended; however, the patient did not agree to the surgical treatment. The biopsy specimen was taken at that point. The patient had four courses of neoadjuvant chemotherapy (DDP 40 mg combined with VP16 140 mg). She has had no distant metastases for 10 months.

Case 2: The patient underwent a radical surgery with enucleation of the left eye. Proton beam therapy and a reconstructive surgery were considered. For 3.5 years after the initial diagnosis no distant metastases have been noted.



Microscopic findings



The postoperative material of each case was fixed in formalin and embedded in paraffin. Five µm thick sections were cut from the paraffin blocks and stained with hematoxylin and eosin (HE). For immunohistochemistry, a DAKO autostainer automated staining system (DAKO Corporation, Carpinteria, CA, USA) was used with antibodies CD99, CD34, CD20, CD3 and LCA.

Both cases grossly appeared as a firm tan, multinodular tumor with hemorrhagic and necrotic foci as well as areas of calcification. The tumors were not well-delineated and the definite encapsulation was not present.

Microscopically, the tumors had a bimorphic pattern and were composed of cellular, undifferentiated, small mesenchymal cells and well-differentiated cartilage foci. The mesenchymal cells, small, round to spindle-shaped with hyperchromatic nuclei and scanty cytoplasm, occurred in sheets and surrounded vascular spaces in a haemangiopericytoma-like manner. Multiple calcifications within the central zone of cartilage were present.

Immunohistochemically, the positive membranous staining with CD99 was present. The reactions for CD34, CD3, CD20 and LCA antibodies were negative.

Discussion

Mesenchymal chondrosarcoma (MChS), both skeletal and extraskeletal are high-grade aggressive tumors with a tendency for local recurrence and distant metastasis. Based on the published reports, approximately one third of all MChS are located extraskeletally, mostly in the lower extremities, meninges and the orbit [2]. The orbital location is rare and up-to-date only about 30 cases have been reported [7-9]. According to the review of the literature, most of the orbital tumors affect young patients, predominantly females (70-75%) [2]. Moreover, two congenital cases of MChS were described [9, 10]. The most frequent clinical symptoms are related to slowly enlarging soft- tissue mass and include progressive proptosis, gradually decreasing visual acuity, diplopia, ptosis and severe headache. As the tumor enlarges and becomes more advanced, the papillary edema is a typical finding in fundoscopy [7-9].

The imaging studies play an important role in the diagnostic evaluation of patients with the orbital MChS. On classical radiographs and computed tomography scans, a nonspecific soft- tissue mass is seen, often with mineralization areas of the cartilaginous matrix [11, 12]. Magnetic resonance imaging is more accurate in visualizing the infiltration of surrounding tissues by the tumor as well as determining areas of necrosis [13]. In addition, the prominent, diffuse and heterogeneous enhancement after intravenous administration of contrast is appreciated. The high-flow vessels which may accompany the haemangiopericytoma-like areas may be identified [11].

The microscopic hallmark of MChS is a bimorphic pattern consisting of an admixture of highly cellular areas of undifferentiated mesenchymal cells with islands of well-differentiated cartilage [2, 14]. The immunohistochemical studies indicate the positive vimentin reaction for mesenchymal cells and S-100 for chondroid cells [15, 16]. Differential diagnosis of MChS may be difficult as the only available material is frequently a biopsy specimen. It should include a group of small round cell tumors: lymphoma, alveolar rhabdomyosarcoma, synovial sarcoma, Ewing sarcoma family of tumors, neuroblastoma and also an extraocular retinoblastoma, osteochondroma, meningioma and solitary fibrous tumor previously classified as haemangiopericytoma. Additional diagnostic tools include immunohistochemical, cytogenetic and molecular studies [17-19].

In a study of Naumann et al. [20], the cytogenetic analysis (Spectral Karyotype Analysis and Fluorescence in Situ Hybridization) of 3 MChS samples revealed the same chromosomal Robertsonian translocation der(13;21)(q10;q10). The authors emphasize that in 5 cases of previously analyzed MChS, the rearrangement has not been identified. Moreover, the molecular impact of the der(13;21)(q10;q10) still remains unclear. The remaining cytogenetic changes which were found in that study included loss of chromosome 8 and 20 material and gain of chromosome 12 material. Gatter et al. [21] describes the trisomy 8 as the sole cytogenetic abnormality in MChS. In other cytogenetic studies, a wide spectrum of genetic changes have been found. Szymańska et al. [22] reported multiple aberrations, i.e. t(4;9)(q23;q22), t(1;20)(q21;q13), add(10)(q?26), trisomy of chromosome 16 and ?del(19)(p13). Richkind et al. describe an apparently balanced t(4;19)(q35;q13.1) as the only MChS cytogenetic change [23]. Mandahl et al. revealed the complex hypertetraploid karyotype. An interesting finding of Sainati et al. was identification of t(11;22)(q24;q12) translocation. The authors suggest a genetic relationship between MChS, Ewing sarcoma and primitive peripheral neuroectodermal tumor (PNET). In accordance with the above hypothesis, an existence of the distinct tumor subgroup defined as “t(11;22)-small, round cell tumors” has been postulated [24].

The complexity and heterogeneity of MChS chromosomal aberrations, as well as its rarity, make it difficult to interpret the results obtained. The multicentric studies seem to be the only reliable way to clarify the cytogenetic and molecular changes of MChS. Recent molecular studies of MChS revealed a novel fusion of genes HEY1 and NCOA2 [25].

The “gold standard” of MChS treatment is a radical surgical excision of the tumor if clinically and anatomically feasible. Because MChS is a rare malignancy there are no recommendations for radiotherapy with or without concomitant chemotherapy [4, 14]. The combined treatment should be advised in unresectable MChS cases and when the surgical margins are inadequate after surgery. There is a high frequency of local recurrences and distant metastases, most commonly to the lungs, regional lymph nodes and bones. The estimated survival rate is about 55% after 5 years and 27% after 10 years.

In conclusion, we present two cases of orbital MChS. The clinical presentation, imaging results and histopathological examination were typical of this rare entity. The presence of small, undifferentiated cells may be misinterpreted as Ewing sarcoma family of tumors, small cell osteosarcoma, lymphoma or rhabdomyosarcoma. Islands of cartilage and haemangiopericytoma-like pattern frequently facilitate the diagnosis of MChS.

References

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Address for correspondence

Anna Szumera-Ciećkiewicz MD

ul. Roentgena 5

02-781 Warsaw, Poland

e-mail: annacieckiewicz@coi.waw.pl