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Year : 2014  |  Volume : 57  |  Issue : 1  |  Page : 109-112
Cytokeratin - positive rib osteosarcoma metastasizing to the small intestine

1 Department of Pathology, Osaka Medical College, Osaka, Japan
2 Department of Internal Medicine, Osaka Medical College, Osaka, Japan
3 Department of Radiology, Osaka Medical College, Osaka, Japan

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Date of Web Publication17-Apr-2014


Osteosarcoma (OS) is a malignant tumor in which osteoid or bone is produced directly by tumor cells. Some OS cells are positive for cytokeratin (CK) and epithelial membrane antigen by immunohistochemistry (IHC) and this may lead to a misdiagnosis of metastatic carcinoma, particularly when the tumor location is unusual. On the other hand, gastrointestinal metastasis of OS is rare. We present the case of a 67-year-old Japanese man with a small intestinal intussusception due to metastasis of a CK-positive rib OS. The tumor cells were positive for CK, osteopontin and osteonectin by IHC and a diagnosis of a CK-positive chest wall OS metastasizing to the small intestine was considered. Osteoid or bone formation was histologically absent and therefore chest wall OS had to be differentially diagnosed from metastatic carcinoma of unknown origin. A postmortem histological analysis confirmed a rib OS. Awareness of CK-positive OS is important for making a correct diagnosis and for disease management and an immunohistochemical analysis of the tumor for expression of osteopontin and osteonectin may be used to support the diagnosis. In addition, this case shows that rib OS can metastasize to the gastrointestinal tract, albeit rarely, which may induce an intestinal intussusception.

Keywords: Cytokeratin, intussusception, osteonectin, osteosarcoma, osteopontin, small intestinal

How to cite this article:
Kuwabara H, Fujita K, Yuki M, Goto I, Hanafusa T, Shibayama Y. Cytokeratin - positive rib osteosarcoma metastasizing to the small intestine. Indian J Pathol Microbiol 2014;57:109-12

How to cite this URL:
Kuwabara H, Fujita K, Yuki M, Goto I, Hanafusa T, Shibayama Y. Cytokeratin - positive rib osteosarcoma metastasizing to the small intestine. Indian J Pathol Microbiol [serial online] 2014 [cited 2022 Jan 27];57:109-12. Available from: https://www.ijpmonline.org/text.asp?2014/57/1/109/130915

   Introduction Top

Osteosarcoma (OS) is the most common primary bone tumor in children and adolescents with a second smaller peak of OS occurring in adults older than 40 years. [1] The majority originates in the long bones of the extremities such as the distal femur, proximal tibia and proximal humerus. However, rib involvement is only seen in 3% of all OS cases. [2] The most common metastatic sites of OS are the lungs followed by skeletal deposition and gastrointestinal metastases are extremely rare. [1],[3] Here, we describe a 67-year-old man with intussusception of the small intestine caused by a metastatic rib OS.

Cytokeratin (CK) and epithelial membrane antigen (EMA) immunoreactivity are rarely seen in OS, particularly in epithelioid OS. [4],[5],[6] This may lead to the misdiagnosis of metastatic carcinoma. Therefore, to distinguish between these diseases, analysis of the expression of osteonectin and osteopontin by immunohistochemistry (IHC) may be useful.

   Case Report Top

This was a case report of a 67-year-old man, who had no history of receiving radiation or of having a pre-existing bone lesion, consulted a local hospital, complaining of a left neck protuberant tumor. A chest X-ray showed a right chest mass and he was admitted to our hospital for further evaluation. A computed tomography (CT) examination of the chest revealed a 12-cm mass in the right chest wall involving the third and fourth ribs and the third rib was sclerotic [Figure 1]a. A Tc99m-methylene diphosphonate bone scan showed radionuclide activity in the right third and fourth ribs and first lumbar vertebrae [Figure 1]b. Serum alkaline phosphatase was 543 U/L (normal 100-330) and serum carcinoembryonic antigen, squamous cell carcinoma and CYFRA21-1 were normal. Percutaneous needle biopsy of the chest tumor was performed under CT guidance and histopathological findings showed a cellular tumor composed of polygonal cells with an eosinophilic cytoplasm, irregular nuclei and prominent nucleoli. Mitotic figures were numerous and epithelial-like proliferation was seen [Figure 2]a. Osteoid and osseous formation was absent. Tumor cells were positive for CK [Figure 2]b, EMA, CD99, vimentin, osteopontin [Figure 2]c and osteonectin and negative for thyroid transcription factor-1, CD45 and CD31 by IHC. They were negative for melanosomes. EMA and CD99 were positive in the Golgi areas [Table 1]. From these findings, a diagnosis of CK-positive chest wall OS was suspected, with differential diagnosis of metastatic carcinoma. Aspiration biopsy cytology of the left neck tumor showed the same findings as biopsied chest tumor specimens [Figure 3].

At 5 days later, the patient complained of abdominal pain, nausea and vomiting. The abdomen showed distension and bowel sounds were absent. A fecal occult blood test was positive. An abdominal CT scan showed an intussusception of the terminal ileum due to a tumor and some polyps in the small intestine [Figure 4]a. Endoscopic emergency surgery was performed and jejunum 10-90 cm distal from the ligament of Treiz, which had multiple ulcerated polyps with maximum 0.5-3.5 cm, was resected [Figure 4]b. In addition, the ileum, which had a mass of 6 cm diameter located 2 cm distal from the terminal ileum, was also resected [Figure 4]c. The overlying mucosa was ulcerated and necrotic with bleeding. This, the largest metastatic lesion, was considered to be the cause of the intussusception. Histological findings of the resected small intestines showed that the lesions were mainly located in the submucosa and had invaded blood vessels. The histopathological appearance of these specimens was identical to the chest and left neck tumors [Figure 4]d and e and the right chest wall tumor metastasizing to the small bowel and left neck subcutaneous tissue was diagnosed. Following surgery, the abdominal symptoms subsided but the chest wall tumor quickly enlarged and the pelvic mass gradually enlarged. Chest and abdominal pain also gradually increased and he received radiation to the right chest and abdomen. The patient's pain decreased, but his general condition had deteriorated and he died 4 months after the initial symptoms had appeared.
Figure 1: Imaging studies. (a) A chest computed tomography with contrast demonstrates a 12-cm right chest mass, which connects with the third sclerotic rib. The underlying lung is collapsed. (b) Tc99mmethylene
diphosphonate bone scan. Increased activity in the right third and fourth ribs and first lumbar vertebrae is shown

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Figure 2: Microscopical features of the chest wall tumor. (a) Epithelioid tumor cells with indented nuclei, prominent nucleoli and abundant eosinophilic cytoplasm (H and E, ×400). (b) Cytokeratin-positive tumor cells (×200). (c) Osteopontin-positive tumor cells (×200)

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Figure 3: Cytopathological features of the neck tumor. A polygonal cell with indented nuclei, fine chromatin and prominent nucleoli and a mitotic cell (Papanicolaou stain, ×800)

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Figure 4: Small intestinal tumor. (a) An abdominal computed tomography scan with contrast showed an intussusception of the terminal ileum (red arrows: terminal ileum tumor; a yellow arrow: a tumor as a polyp). (b) Polypoid lesions in the jejunum. (c) A 6-cm tumor, 2 cm distal from the terminal ileum. (d) Tumor cells in the submucosa (H and E, ×1). (e) Epithelioid tumor cells in the submucosa (H and E, ×400)

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Table 1: Antibodies used in immunohistochemistry

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An autopsy of the chest and neck was performed 15 h after death. He was 54 kg and 170 cm. Thoracotomy disclosed a tumor, 15 × 11 cm in size, involving the third and fourth ribs. It was adherent to the right lung pleura and causing significant compression of the right lung. Tumor nodules consisted of polygonal cells with an epithelioid structure. These tumor cells showed severe pleomorphism and frequent mitoses, similar to what was found in the small intestinal tumors. Multinucleated cells were also seen and osteoid and osseous formation was evident. IHC studies yielded the same results as determined for the biopsied material. The tumor cells were seen to fill and expand the Haversian systems of the third rib and infiltrating into the cortex and surrounding connective tissue [Figure 5]a and b. From these, the case was diagnosed as being an osteoblastic conventional OS of the right third rib. The right intercostal muscle, both lungs [Figure 6], both pleura, right fourth rib, diaphragm, left neck subcutaneous tissue, thyroid and both hilar lymph nodes were invaded by tumor cells. Fluorescence in situ hybridization analysis using the LSI EWSR1 (22q12) dual color, break apart rearrangement probe (Vysis, Abbott Park, IL, USA), revealed no rearrangement of the EWSR1 gene region on chromosome 22q12.
Figure 5: (a) Tumor cells in the right third rib. Tumor cells in the intramedullary and cortex, bone membrane and surrounding connective tissue (H and E, ×1). (b) High power view of tumor cells (H and E, ×200)

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Figure 6: Microscopic features of the left lung tumor. Polygonal tumor cells with lace-like osteoid formation (left side) (H and E, ×200)

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   Discussion Top

The CK-positive rib OS with a small intestinal metastasis was presented. A premortem diagnosis of OS was not confirmed because of the absence of osteoid or bone formation in the biopsied specimens. In addition, the following two complications made a diagnosis of OS challenging. First, OS changes of the rib were not obvious in the X-ray. OS of the rib is difficult to diagnose because of the rarity of the lesion, the periosteal reaction such as 'sunburst', destruction and making calcification of the rib difficult to visualize and assess in the chest X-ray compared with OS of the extremities. [2],[7] Abdulrahman et al. in their study have reported that OS should be suspected if the CT scan reveals a dense calcification within a mass that is centered in a rib, as seen in our case. [8] Second, tumor cells showed an epithelial structure and they were positive for epithelial antigens, CK and EMA by IHC. Histological differential diagnosis included metastatic carcinoma and these antigens are expressed in some sarcomas. For example, CK expression is documented in epithelioid sarcoma, synovial sarcoma, angiosarcoma, leiomyosarcoma, mesothelioma and extrarenal rhabdoid tumor, while EMA is seen in epithelioid sarcoma, synovial sarcoma, perineurinoma, meningioma and anaplastic large cell lymphoma. [9] 4.5% of OS are positive for CK, in which epithelioid features and pleomorphisms are prominent. [5] On the other hand, rosette-forming epithelioid OS, which is a highly aggressive tumor, is positive for EMA and negative for CK. [4] This shows that CK and EMA positivity does not exclude OS and expression of osteopontin, osteonectin and osteocalcin by IHC may be useful for differentiating carcinoma from OS.

OS has a tendency to metastasize through the hematogenous route and appear primarily in the lung. [1] Of the 25 patients with chest wall OS who initially had only local disease, 13 (52%) developed distant metastases to the lung alone (eight cases), lung and bone (four cases) and lung and colon (one case). [2] Gastrointestinal metastasis of OS is rare and Panizo-Santos et al. have reported on a patient with a small intestinal tumor that presented as a polyp that had metastasized from the right tibia. [3] This tumor was seen in the submucosa and invaded the blood vessels, suggesting a hematogenous metastasis. Our case showed the same metastatic pattern, which induced multiple polyps. The biggest small intestinal tumor was the cause of the intussusception. In contrast to intussusception in children, 54.5% of adult intussusceptions were due to a tumor, of which 27.3% were malignant. [10]

Awareness of CK-positive OS is important to make a correct diagnosis and for disease management and the use of IHC to assess the expression of osteopontin and osteonectin may be useful for distinguishing OS from metastatic carcinoma. In addition, this case shows that a rib OS, which rarely metastasizes to the gastrointestinal tract, can induce a small intestinal intussusception.

   References Top

1.Rosenberg AE, Cleton-Jansen AM, de Pinieux G, Deyrup AT, Hauben E, Squire J. Conventional osteosarcoma. In: Fletcher CDM, Bridge JA, Hogendoom PCW, Mertens F, editors. World Health Organization Classification of Tumors. Pathology and Genetics of Tumors of Soft Tissue and Bone. Lyon: IARC Press; 2012. p. 282-8.  Back to cited text no. 1
2.Burt M, Fulton M, Wessner-Dunlap S, Karpeh M, Huvos AG, Bains MS, et al. Primary bony and cartilaginous sarcomas of chest wall: Results of therapy. Ann Thorac Surg 1992;54:226-32.  Back to cited text no. 2
3.Panizo-Santos A, Sola I, Lozano M, de Alava E, Pardo J. Metastatic osteosarcoma presenting as a small-bowel polyp. A case report and review of the literature. Arch Pathol Lab Med 2000;124:1682-4.  Back to cited text no. 3
4.Okada K, Hasegawa T, Yokoyama R. Rosette-forming epithelioid osteosarcoma: A histologic subtype with highly aggressive clinical behavior. Hum Pathol 2001;32:726-33.  Back to cited text no. 4
5.Okada K, Hasegawa T, Yokoyama R, Beppu Y, Itoi E. Osteosarcoma with cytokeratin expression: A clinicopathological study of six cases with an emphasis on differential diagnosis from metastatic cancer. J Clin Pathol 2003;56:742-6.  Back to cited text no. 5
6.Layfield LJ, Emerson L, Crim JR, Randall L. Squamous differentiation and cytokeratin expression in an osteosarcoma: A case report and review of the literature. Clin Med Pathol 2008;1:55-9.  Back to cited text no. 6
7.Lim W, Ahmad Sarji S, Yik Y, Ramanujam T. Osteosarcoma of the rib. Biomed Imaging Interv J 2008;4:e7.  Back to cited text no. 7
8.Abdulrahman RE, White CS, Templeton PA, Romney B, Moore EH, Aisner SC. Primary osteosarcoma of the ribs: CT findings. Skeletal Radiol 1995;24:127-9.  Back to cited text no. 8
9.Folpe AL, Gown AM. Immunohistochemistry for analysis of soft tissue tumors. In: Enzinger & Weiss's Soft Tissue Tumors. China: Mosby; 2008. p. 129-74.  Back to cited text no. 9
10.Wang N, Cui XY, Liu Y, Long J, Xu YH, Guo RX, et al. Adult intussusception: A retrospective review of 41 cases. World J Gastroenterol 2009;15:3303-8.  Back to cited text no. 10

Correspondence Address:
Hiroko Kuwabara
Department of Pathology, Osaka Medical College, 2-7 Takatsuki, Osaka 569-8686
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.130915

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

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