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Year : 2019  |  Volume : 3  |  Issue : 1  |  Page : 20-23

Osteosarcoma presenting with massive malignant pleural effusion

1 Division of Pathology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India
2 Division of Imageology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India
3 Division of Medical Oncology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India

Date of Web Publication3-May-2019

Correspondence Address:
Dr. Renu Sukumaran
Division of Pathology, Regional Cancer Centre, Thiruvananthapuram, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/oji.oji_7_19

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Osteosarcoma is an aggressive primary bone tumor arising from primitive bone-forming cells. The most frequent site of metastasis is the lung followed by bone. However, osteosarcoma presenting as malignant pleural effusion during the initial presentation is extremely rare. Involvement of more than one bone at the time of initial presentation is rare and it is confusing whether these multiple lesions represent multiple primaries or metastasis. We report the case of a 17-year-old male who presented with fever and breathlessness of 1-month duration. Examination revealed massive pleural effusion. Pleural fluid cytology showed malignant cells. On examination, a scalp swelling was also noted. Radiological evaluation revealed multiple bony lesions involving the skull, femur, humerus, and vertebrae. Biopsy of the lesion in the humerus confirmed the diagnosis of osteosarcoma.

Keywords: Malignant pleural effusion, metastasis, multifocal osteosarcoma

How to cite this article:
Sukumaran R, Nayak N, Mony RP, Kaur J, Nair SG. Osteosarcoma presenting with massive malignant pleural effusion. Oncol J India 2019;3:20-3

How to cite this URL:
Sukumaran R, Nayak N, Mony RP, Kaur J, Nair SG. Osteosarcoma presenting with massive malignant pleural effusion. Oncol J India [serial online] 2019 [cited 2022 May 27];3:20-3. Available from: https://www.ojionline.org/text.asp?2019/3/1/20/257618

  Introduction Top

Osteosarcoma is a high-grade, intraosseous, malignant neoplasm in which the neoplastic cells produce bone. The clinical course is characterized by aggressive local growth and rapid hematogenous systemic dissemination. Pulmonary metastasis followed by skeletal deposits is the frequent pattern of systemic dissemination.[1],[2] Rarely, multiple bones are involved in the initial presentation itself. The absence of visceral involvement at the time of diagnosis may be taken as evidence of multifocal rather than metastatic bone disease. The presence of lesions at multiple sites indicates poor prognosis and can cause challenges in treatment decisions.

Many cases of osteosarcoma may harbor micrometastasis in the lung in the initial presentation itself. In spite of dramatic response to treatment, around 25%–30% develop metastasis after treatment.[1],[2],[3] The lung is the most common site of metastasis. However, pleural metastasis is very rare in osteosarcoma particularly at the time of presentation. Herein, we report a case of osteosarcoma with malignant pleural effusion at the time of presentation with multiple bone involvement.

  Case Report Top

A 17-year-old male presented with fever and breathlessness of 1-month duration. Examination of respiratory system showed reduced chest movements on the left side. Trachea was shifted to the right, and there was stony dullness on percussion. On auscultation, breath sounds were markedly reduced on the left side. Chest X-ray revealed features of massive left-sided pleural effusion. Pleural fluid aspiration cytology showed atypical cells arranged singly and in small clusters. Individual cells were having moderate amount of cytoplasm, enlarged irregular nuclei with irregularly clumped chromatin, and small nucleoli [Figure 1]a,[Figure 1]b,[Figure 1]c. Occasional mitoses were noted. Cell block preparation also showed malignant cells [Figure 1]d. The cells were negative for cytokeratin, Placental alkaline phosphatase (PLAP), and desmin. Serum germ-cell tumor markers were normal. Frontal radiograph of the chest showed complete white out of the left hemithorax with contralateral trachea-mediastinal shift and splaying of the left ribs [Figure 2]a. Contrast-enhanced computed tomography (CECT) scan of the thorax showed gross left-sided pleural effusion with thickened, enhancing parietal and visceral pleura with multiple scattered calcified pleural plaques and significant mass effect [Figure 2]b and [Figure 2]c. Few calcified pleural plaques with calcified parenchymal nodules were noted in the right lung [Figure 2]d. During detailed clinical workup, the patient gave history of a scalp swelling in the frontal area, not associated with pain, which was detected incidentally few days before the episode of breathlessness. There was a bony hard nontender swelling of 3 cm × 2.5 cm in the left frontal region. CECT scan of the brain showed an expansile focally destructive bony lesion in the left frontal calvarium extending across the midline sagittal suture with involvement of both the outer and the inner tables and a spiculated periosteal reaction. Further radiological evaluation revealed contour deformity involving the left humeral head with marked irregular periosteal reaction and irregular cortical break [Figure 3]a and [Figure 3]b. Irregular sclerosis with cortical break was seen involving the left femur. Multiple sclerotic foci were seen in the right humerus, left femur, and thoracic vertebrae [Figure 4]a,[Figure 4]b,[Figure 4]c along with small parenchymal nodular lesion in the right lung lower lobe [Figure 4]d. Biopsy from the left humerus was taken. Microscopy showed a neoplasm composed of atypical cells with ovoid/irregular hyperchromatic nuclei surrounded by lace-like pattern of osteoid. A diagnosis of osteosarcoma was made [Figure 5].
Figure 1: (a) Pleural fluid cytology showing atypical cells arranged in small clusters (Pap, ×100). (b and c) Higher power showing atypical cells with anisonucleosis, irregular chromatin, and small nucleoli (Pap, ×400). (d) Cell block preparation showing atypical cells (H and E, ×400)

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Figure 2: (a) Frontal radiograph of the chest demonstrates complete white out of the left hemithorax with contralateral trachea-mediastinal shift and splaying of the left ribs. (b and c) Coronal and axial contrast-enhanced computed tomography images demonstrate gross left-sided pleural effusion with near total collapse consolidation of the left lung and inversion of the left hemidiaphragm. Scattered calcified plaques are seen along both parietal and visceral pleura. (d) Few calcified plaques along parietal pleura in the right lung (blue arrow)

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Figure 3: (a) Frontal radiograph of the left shoulder reveals a sclerotic metaphyseal lesion with extension into epiphysis, wide zone of transition, and periosteal reaction. (b) Axial contrast-enhanced computed tomography images with bone window demonstrating an expansile sclerotic lesion causing contour deformity and cortical destruction of the metaphyseal region of the left humerus

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Figure 4: (a) Synchronous sclerotic foci in the right humerus. (b) Left femur and (c) thoracic vertebrae. (d) Small parenchymal nodular lesion in the right lung lower lobe (blue arrow)

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Figure 5: Biopsy lesion humerus showing malignant cells of similar morphology with production of osteoid (H and E, ×400)

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  Discussion Top

Osteosarcoma is the most common primary bone tumor in children and young adults. Aggressive local growth and early metastatic dissemination are the characteristic biological behaviors of osteosarcoma. Hematogenous spread is common, and the most common metastatic site is the lung.[1] Around 10% of patients will have distant metastasis at the time of initial presentation.[2] A significant percentage of patients will have micrometastasis in the lung at the time of diagnosis. Although the lung is the most common site of hematogenous metastasis of osteosarcoma, pleural metastasis is uncommon.

Pleural metastasis

Pleural metastasis in osteosarcoma is unusual. Most of the reported cases occurred after the initial treatment. Most commonly reported CT appearance is the presence of single or multiple pleura-based nodules with concomitant lung parenchymal metastasis.[3],[4] Isolated pleural metastasis without lung metastasis is rare. Still rarer is the presence of diffuse involvement of pleura with pleural thickening.[4]

Pleural metastasis in osteosarcoma can occur by two mechanisms: direct contact of pleura with the lung metastasis and hematogenous spread of osteosarcoma.

Mori et al. reported two cases of metastatic osteosarcoma with lung and pleural involvement. They suggested that the pleural lesions were kissing metastasis from the adjoining lung lesions. Even though the lung and pleural lesions appeared physically distinct, their adjacent areas come in contact with each other during inspiration, facilitating spread of the tumor.[5] Saha et al. reported the case of a 14-year-old male, who presented with pleural effusion, 4 years after mid-thigh amputation for osteosarcoma tibia. They also suggested kissing metastasis as a possible mechanism of spread.[6]

Multifocal osteosarcoma

Literature search shows differing views regarding the pathogenesis of multifocal osteosarcoma. It is not clear whether the bone lesions represent a multifocal origin of the tumor or simply bone-to-bone metastases. It can be synchronous when more than one lesion is present during initial diagnosis or metachronous if new lesions appear after initial treatment. Most authors agree that multifocal osteosarcoma represents multiple primary tumors in cases where the lungs are free of tumor.

The presence of micrometastasis in the lung at the time of initial presentation in many patients supports the theory of metastasis in multifocal/multicentric osteosarcoma.

Hatori et al. described a case of multicentric osteosarcoma with prominent lymphatic spread of sarcoma cells in the lungs. They also supported the possibility of bone-to-bone metastasis in multicentric osteosarcoma because of the presence of one larger and more extensive lesion in majority of patients with multicentric lesions and the presence of bone metastases in 41% of all osteosarcoma cases at autopsy. An anatomical route was postulated in the vertebral venous plexus system connecting the extremities and spine without passage through the lungs. This will explain the absence of pulmonary metastasis.[7]

The management and prognosis of metastatic osteosarcoma depend upon the number, sites, and size of metastasis. Involvement of proximal extremity or axial skeleton, large size of the lesion, detectable metastases at the time of diagnosis, and poor response to preoperative chemotherapy are the predictors of poor outcome.

Our case represents an unusual presentation of osteosarcoma, as the patient presented with respiratory symptoms alone. Even though multiple bone lesions were noted during detailed evaluation, bone pain was curiously absent. Osteosarcoma presenting as pleural effusion due to pleural metastases is extremely rare.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Tabone MD, Kalifa C, Rodary C, Raquin M, Valteau-Couanet D, Lemerle J. Osteosarcoma recurrences in pediatric patients previously treated with intensive chemotherapy. J Clin Oncol 1994;12:2614-20.  Back to cited text no. 1
Jeffree GM, Price CH, Sissons HA. The metastatic patterns of osteosarcoma. Br J Cancer 1975;32:87-107.  Back to cited text no. 2
Krishnamurthy K, Alghamdi S, Kochiyil J, Bruney GF, Poppiti RJ. Osteosarcoma presenting with malignant pleural effusion in a 55 year old. Respir Med Case Rep 2018;25:314-7.  Back to cited text no. 3
Marchiori E, Meena Barreto M, Zanetti G. Pleural metastasis of osteosarcoma. Ann Thorac Surg 2018;105:e87-8.  Back to cited text no. 4
Mori T, Yoshioka M, Iwatani K, Kobayashi H, Yoshimoto K, Nomori H. Kissing pleural metastases from metastatic osteosarcoma of the lung. Ann Thorac Cardiovasc Surg 2006;12:129-32.  Back to cited text no. 5
Saha D, Saha K, Banerjee A, Jash D. Osteosarcoma relapse as pleural metastasis. South Asian J Cancer 2013;2:56.  Back to cited text no. 6
[PUBMED]  [Full text]  
Hatori M, Ohtani H, Yamada N, Uzuki M, Kokubun S. Synchronous multifocal osteosarcoma with lymphatic spread in the lung: An autopsy case report. Jpn J Clin Oncol 2001;31:562-6.  Back to cited text no. 7


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

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