Journal of Pathology and Translational Medicine

Original Article

Special AT-rich sequence-binding protein 2 (SATB2) in the differential diagnosis of osteogenic and non-osteogenic bone and soft tissue tumors: Sharon Milton, Anne Jennifer Prabhu, V. T. K. Titus, Rikki John, Selvamani Backianathan, Vrisha Madhuri; J Pathol Transl Med. 2022;56(5):270-280. Published online September 13, 2022; DOI: https://doi.org/10.4132/jptm.2022.07.11

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Background
The diagnosis of osteosarcoma (OSA) depends on clinicopathological and radiological correlation. A biopsy is considered the gold standard for OSA diagnosis. However, since OSA is a great histological mimicker, diagnostic challenges exist. Immunohistochemistry (IHC) can serve as an adjunct for the histological diagnosis of OSA. Special AT-rich sequence-binding protein 2 (SATB2) was recently described as a reliable adjunct immunohistochemical marker for the diagnosis of OSA.
Methods
We investigated the IHC expression of SATB2 in 95 OSA and 100 non-osteogenic bone and soft tissue tumors using a monoclonal antibody (clone EPNCIR30A). The diagnostic utility of SATB2 and correlation with clinicopathological parameters were analyzed.
Results
SATB2 IHC was positive in 88 out of 95 cases (92.6%) of OSA and 50 out of 100 cases (50.0%) of primary non-osteogenic bone and soft tissue tumors. Of the 59 bone tumors, 37 cases (62.7%) were positive for SATB2, and of the 41 soft tissue tumors, 13 cases (31.7%) were positive for SATB2. The sensitivity of SATB2 as a diagnostic test was 92.6%, specificity 50%, positive predictive value 63.8%, and negative predictive value 87.7%.
Conclusions
Although SATB2 is a useful diagnostic marker for OSA, other clinical, histological and immunohistochemical features should be considered for the interpretation of SATB2.

Citations

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Favorable treatment response to high‐grade sarcoma in neurofibromatosis 1
Michelle H. Talukder, Mauli M. Patel, Tala Al‐Saghir, Ghadir K. Katato, Janet Poulik, William J. Powell, Alysia K. Kemp, Steven Miller, Danielle Bell, Jeffrey W. Taub
Pediatric Blood & Cancer.2023;[Epub] CrossRef

Case Studies

Rosette-forming epithelioid osteosarcoma in the rib: a rare case of location and morphology: Sun-Ju Oh; J Pathol Transl Med. 2021;55(6):406-409. Published online August 3, 2021; DOI: https://doi.org/10.4132/jptm.2021.06.22

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Abstract PDF: The rib is an unusual location for osteosarcoma and is reported in only 2% of all cases. The major histological variants of osteosarcoma are osteoblastic, chondroblastic, and fibroblastic, with a few rare variants including one epithelioid type. This report describes a 44-year-old male with an osteolytic mass in the right seventh rib. Histological examination revealed osteosarcoma with unique features of epithelioid appearance and rosette structures. To the best of our knowledge, this is the first reported case of a rosette-forming osteosarcoma of the rib that showed epithelioid morphology. Despite successful surgery, the patient’s prognosis was poor because this malignancy had an unusual location within the axial skeleton and was a rare histological variant.

Multifocal Osteosarcoma of the Skull: Multiple Primary or Metastatic? A Case Report: Hyuck Cho, Bong-jin Park, Yong-Koo Park; Korean J Pathol. 2014;48(2):146-150. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.146

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Abstract PDF

Osteosarcoma of the skull is a very rare condition. Moreover, it is extremely rare for osteosarcoma to present as multiple lesions confined to the skull. A 58-year-old woman was admitted with two masses in the parietal area of the skull, accompanied by mild headache and tenderness. Imaging revealed two masses with a heterogeneous consistency in the cranial bones. Excision craniectomy was performed and the pathology was consistent with osteoblastic osteosarcoma. Two nodules in the heart were found on routine follow-up imaging while the patient was undergoing chemotherapy. The nodules were biopsied and found to be metastatic osteosarcoma.

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Osteosarcoma multicéntrico sincrónico. Un caso en niño de 10 años y revisión de la literatura
Jesús Pérez-García, Osvaldo Velasco-Donado, Karoll Robles-Pérez
Revista Española de Patología.2022; 55: S11. CrossRef
Reconstruction using a frozen autograft for a skull and humeral lesion of synchronous multicentric osteosarcoma after undergoing successful neoadjuvant chemotherapy: a case report and review of the literature
Yoshihiro Araki, Katsuhiro Hayashi, Norio Yamamoto, Akihiko Takeuchi, Shinji Miwa, Kentaro Igarashi, Takashi Higuchi, Kensaku Abe, Yuta Taniguchi, Hirotaka Yonezawa, Sei Morinaga, Yohei Asano, Takayuki Nojima, Hiroyuki Tsuchiya
BMC Surgery.2021;[Epub] CrossRef
What’s that big thing on your head? Diagnosis of a large frontoparietal lesion on an Eastern Zhou skull from Henan, China
Kate Pechenkina, Wenquan Fan, Xiaodong Luo
International Journal of Paleopathology.2019; 26: 84. CrossRef
Kalvaryumda multifokal osteosarkom: Nadir bir vaka sunumu ve literatür derlemesi
Neslihan KURTUL, Nursel YURTTUTAN, A. Yasir BAHAR, Gökmen AKTAŞ
Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi Dergisi.2019; 14(3): 151. CrossRef
Radiological review of skull lesions
Carrie K. Gomez, Scott R. Schiffman, Alok A. Bhatt
Insights into Imaging.2018; 9(5): 857. CrossRef
Multifocal Osteosarcoma
Somali Gavane, Anita P. Price, Heather Magnan, Sonia Mahajan, Neeta Pandit-Taskar
Clinical Nuclear Medicine.2017; 42(4): e202. CrossRef

Original Article

14-bp Insertion/Deletion Polymorphism of the HLA-G Gene in Osteosarcoma Patients.: Ahrim Moon, Su Kang Kim, Joo Ho Chung, Ki Yong Na, Liliana G Olvi, Eduardo Santini-Araujo, Youn Wha Kim, Yong Koo Park; Korean J Pathol. 2011;45(5):485-490.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.485

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Abstract PDF

BACKGROUND
The major histocompatibility complex class I, G (human leukocyte antigen-G [HLA-G]) gene plays a vital role in the suppression of immune responses. Recently, a number of studies have reported an association between HLA-G and diseases (pregnancy complications, organ transplantation, and tumors). Some of the studies have revealed that the 14-bp insertion/deletion polymorphism might be associated with various diseases. The aim of the present study was to explore a possible influence of the 14-bp insertion/deletion polymorphism on osteosarcoma.
METHODS
Genomic DNA was extracted from 75 formalin-fixed, paraffin-embedded tumor tissues derived from patients with conventional osteosarcoma (OSA) and 183 peripheral blood samples of healthy controls. Fifty-eight cases were South Korean patients with OSA and 17 cases were Argentine patients with OSA. The HLA-G 14-bp insertion/deletion polymorphism at exon 8 of the HLA-G locus was analyzed by polymerase chain reaction.
RESULTS
There was a significantly different distribution profile for the 14-bp genotypes between the Korean OSA and Korean control groups. Specifically, there were more heterozygote 210 bp/224 bp genotypes in the Korean OSA group when compared to the Korean control group (62.1% vs 40.4%, p=0.002).
CONCLUSIONS
The results suggest that HLA-G heterozygote patients may be more susceptible to OSA in the Korean population.

Citations

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14-bp Insertion/Deletion Polymorphism of the HLA-G gene in Breast Cancer among Women from North Western Iran
Mehdi Haghi, Mohammad Ali Hosseinpour Feizi, Majid Sadeghizadeh, Abbas Sahebghadam Lotfi
Asian Pacific Journal of Cancer Prevention.2015; 16(14): 6155. CrossRef

Case Report

Parotid Gland Carcinosarcoma with Osteosarcoma as a Sarcomatous Component: A Case Report with Fine Needle Aspiration Cytologic Findings.: Se Min Jang, Young Jin Jun, Hulin Han, Ki Seok Jang, Seung Sam Paik; Korean J Pathol. 2011;45(4):412-416.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.412

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Abstract PDF

Carcinosarcoma of the salivary glands is a rare malignant tumor showing both malignant epithelial and mesenchymal components. Herein, we present a carcinosarcoma of the parotid gland in a 67-year-old man consisting of osteosarcoma and adenocarcinoma components with fine needle aspiration cytological findings. The tumor was composed predominantly of osteosarcoma and small areas of adenocarcinomatous components and a hyalinized nodule reminiscent of pleomorphic adenoma. The tumor showed infiltrative growth features with perineural, lymphatic, and vascular invasion. Despite postoperative adjuvant radiation therapy, multiple metastatic lesions occurred in the both lungs 5 months after surgery. As salivary gland carcinosarcoma has been known to demonstrate highly aggressive behavior, an accurate pathological diagnosis is prerequisite for appropriate treatment.

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Carcinosarcoma of the parotid gland with abdominal metastasis: a case report and review of literature
Chang Gok Woo, Seung-Myoung Son
World Journal of Surgical Oncology.2018;[Epub] CrossRef

Original Articles

The Global Histone Modification Patterns of Osteosarcoma.: Sung Im Do, Sung Jig Lim, Youn Wha Kim, Liliana G Olvi, Eduardo Santini-Araujo, Yong Koo Park; Korean J Pathol. 2011;45(2):146-150.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.2.146

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Abstract PDF: BACKGROUND
Epigenetic alteration may affect a patient's prognosis by altering the development and progression of the tumor. Some recent reports have identified a correlation between histone modification and patient outcome. However, no studies have been conducted on global histone modification in osteosarcomas.
METHODS
We investigated histone modification in 54 cases of osteosarcoma by performing immunohistochemical staining. The immunohistochemical expression of four histone modification markers, acetylated H4 lysine 12 (H4K12Ac), acetylated H3 lysine 18, trimethylated H3 lysine 27, and dimethylated H3 lysine 4 were evaluated.
RESULTS
High H4K12Ac expression was correlated with patient age (p=0.011). However, the other histone modification markers showed no correlation with any of the clinicopathological data such as survival, tumor grade, tumor site, metastasis, age, or gender.
CONCLUSIONS
Our study showed that all four histone modification markers are expressed in osteosarcoma (median expression rate, 40 to 60%). However, we did not find a correlation with the clinicopathological factors except for age. Further study to evaluate the reason for the association between H4K12Ac and patient age is needed.

Expression of Carbonic Anhydrase IX Correlates with Histologic Grade and Metastasis in Osteosarcoma.: Hye Rim Park, Jinwon Seo, Patrizia Bacchini, Franco Bertoni, Yong Koo Park; Korean J Pathol. 2010;44(4):384-389.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.384

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Abstract PDF: BACKGROUND
Carbonic anhydrase IX (CA9) is reportedly overexpressed in several types of carcinomas, but little is known about the expression pattern of CA9 in osteosarcoma. We aimed to assess the prevalence of CA9 expression and its prognostic implications in osteosarcoma patients.
METHODS
We compared immunohistochemical expression of CA9 between conventional, high-grade and low-grade, central osteosarcomas. Specimens were obtained before chemotherapy and stained with anti-human CA9 antibody. We also evaluated the histologic grade, presence of metastasis, and patient prognosis.
RESULTS
Among 38 samples of conventional high-grade osteosarcoma, 22 (57.9%) tumors displayed CA9 overexpression. Twenty-five cases of low-grade central osteosarcomas were all negative (p < 0.0001). CA9 expression was significantly associated with the presence of metastasis (p = 0.0010). The overall survival rate was significantly reduced with increased CA9 expression (p = 0.0012), higher histologic grade (p < 0.0001), and younger age (p = 0.0140). However, the overall survival rate was not significantly correlated with gender, tumor size, or American Joint Committee on Cancer stage.
CONCLUSIONS
CA9 expression is a frequent and tumor-specific event in osteosarcoma. CA9 expression is associated with higher grade tumors, metastasis and poor prognosis for the osteosarcoma patients.

Lyn Expression in Osteoblastic Osteosarcoma Tissues and Its Correlation with Clinicopathologic Factors.: Min Sun Jin, Shin Kwang Khang, Min Suk Kim, Hee Seung Choi, Jung Eun Lee, Kil Ho Kim, Dae Geun Jeon, Jae Soo Koh; Korean J Pathol. 2010;44(2):125-131.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.125

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Abstract PDF

BACKGROUND
The Src family kinases (SFKs) are involved in multiple aspects of tumorigenesis, such as, proliferation, migration, and angiogenesis, and are involved in the generation and progression of many types of tumors. Furthermore, dasatinib, a general SFKs inhibitor was recently approved for use in chronic myeloid leukemia. This study was performed to evaluate the expression of Lyn, a member of the SFKs, in osteosarcoma tissues.
METHODS
One hundred and sixteen patients with osteoblastic osteosarcoma were selected for Lyn expression analysis. The correlation between Lyn expression in tumor sections and patients' clinicopathologic characteristics and the prognostic significance of Lyn expression were evaluated.
RESULTS
Lyn was found to be expressed in 52 of the 116 patients (44.8%), and Lyn positive tumor was found to be significantly associated with a lytic tumor pattern on plain radiographs (p = 0.04). Furthermore, those positive for Lyn showed longer metastasis free survival (5-year metastasis free survival, 65.2% for Lyn positive and 46.8% for Lyn negative; p = 0.06), though this was only marginally significant.
CONCLUSIONS
Lyn was found to be overexpressed in osteosarcoma tissues, and this overexpression was found to be correlated with osteolysis.

Citations

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Eight Aging-Related Genes Prognostic Signature for Cervical Cancer
Meilin Yin, Yanhua Weng, Ferenc Olasz
International Journal of Genomics.2023; 2023: 1. CrossRef
LYN expression predicts the response to dasatinib in a subpopulation of lung adenocarcinoma patients
Yu Jin Kim, Sungyoul Hong, Minjung Sung, Min Jeong Park, Kyungsoo Jung, Ka-Won Noh, Doo-Yi Oh, Mi-Sook Lee, Ensel Oh, Young Kee Shin, Yoon-La Choi
Oncotarget.2016; 7(50): 82876. CrossRef

Case Report

Metastatic Osteosarcoma to the Prostate: A Case Report.: Hyoung Yeon Seo, Jae Hyuk Lee, Chang Soo Park, Jin Gyoon Park, Sung Taek Jung; Korean J Pathol. 2009;43(5):475-477.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.475

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Abstract PDF: The most common site for the metastasis of osteosarcoma is the lung, and other sites of metastases include the bone, lymph node, pleura and liver. Although unusual extrapulmonary metastases have been reported with the improvement of the therapeutic results for the primary lesions, they are exceptionally rare. We report here on a case of prostatic metastasis of an osteosarcoma of the proximal tibia, and this developed seven years after successful resection, and four years after resection of a pulmonary metastasis. Radical prostatectomy was performed, and histological examination demonstrated metastatic osteosarcoma. To the best of our knowledge, this is the first case of prostatic metastasis of osteosarcoma in the medical literature.

Original Article

Immunohistochemical Sdtudy of Cytokeratin and Epithelial Membrane Antigen Expression in Osteosarcoma.: Jong Yup Bae, Mee Yon Cho, Soon Hee Jung; Korean J Pathol. 1996;30(10):920-927.

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Abstract PDF: Immunohistochemical analysis of 24 paraffin-embedded osteosarcomas was studied to evaluate the expression of simple cytokeratin, basal cytokeratin and epithelial membrane antigen(EMA) according to the histologic subtypes and anatomical locations. Mean age of the patients was 18 years. Anatomical locations of the tumors were femur(8), tibia(10), humerus(4), lumbar spine(1), and zygomatic arch(1). Histologic subtypes included osteoblastic(14), fibroblastic(4), chondroblastic(4), epithelioid(1), and mixed osteoblastic and fibroblastic(1). All were positive in the immunohistochemical stain for vimentin. The expression of cytokeratin and/or EMA was found in 10 cases(41.7%) regardless of anatomical locations and histologic subtypes. Positive immunoreaction for EMA was demonstrated in osteoblastic(5), chondroblastic(2), epithelioid(1), and mixed osteoblastic and fibroblastic(1) types. Osteoblastic (2), chondroblastic(2), and epithelioid(1) types among them also showed immunoreactivity with anti-simple cytokeratin monoclonal antibody, NCL-5D3. The expression of basal cytokeratin (NCL-LL002) was found in two osteoblastic, one chondroblastic, one epithelioid, and one mixed osteoblastic and fibroblastic types. These findings indicate that cytokeratin and EMA immunoreactivity can not be regarded as an absolute specific marker of the epithelial origin of tumor and may also occur in osteosarcoma.

Case Reports

Sarcomatoid Carcinoma with Heterologous Osteosarcomatous Component of the Prostate: A case report.: Eun Sun Jung, Young Jin Choi, Seok Jin Kang, Byung Gee Kim, Sun Moo Kim, Sang In Shim; Korean J Pathol. 1996;30(12):1144-1149.

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Abstract PDF: Sarcomatoid carcinoma of prostate has been rarely reported and occasionally difficult to distinguish from a true sarcoma or carcinosarcoma. A case of sarcomatoid carcinoma of the prostate, which has been occured in 61-year-old male patient is presented. The tumor consists of carcinomatous areas with epithelioid cells, sarcomatoid areas with spindle cells and foci of heterologous osteosarcoma component. The phenotypic nature of the tumor was confirmed immunohistochemically by positive reaction for cytokeratin, epithelial membrane antigen, vimentin and prostate specific acid phosphatase in both sarcomatous and carcinomatous components.

Small Cell Osteosarcoma Similar to Ewing's Sarcoma in Histologic Findings and MIC2 Expression: A case report.: Yoon Mee Kim, Suk Woo Yang, Mee Yon Cho, Soon Won Hong, Byung Ho Choi; Korean J Pathol. 1999;33(3):204-209.

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Abstract PDF: Small cell osteosarcoma is a rare form of osteosarcoma and the histological differential diagnosis from other small round cell tumors (SRCTs) is difficult. The immunohistochemical stain for MIC2 has been considered an useful diagnostic marker for Ewing's sarcoma and primitive neuroectodermal tumors but recently, other SRCTs such as malignant lymphoma and embryonal rhabdomyosarcoma also showed positive reaction. Therefore, the usefulness of MIC2 must still be proven. We experienced a case of small cell osteosarcoma of the mandible in a 25-year-old man. Histologically, the tumor consisted of small round cells that resembled those of Ewing's sarcoma. Immunohistochemically, the tumor cells expressed diffuse strong positive reaction for MIC2 gene products. However, the scanty foci of lacy osteoid material between the tumor cells seemed to be diagnostic of osteosarcoma. The histologic and immunohistochemical findings of this case suggest close relationship between small cell osteosarcoma and Ewing's sarcoma.

Spontaneous Pneumothorax as a Complication of Pulmonary Metastasis of Osteosarcoma A case report.: Min Kyung Kim, Bong Kyung Shin, Wha Eun Oh, Ae Ree Kim, Nam Hee Won, Jong Sang Choi; Korean J Pathol. 1999;33(4):281-284.

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Abstract PDF: Spontaneous pneumothorax is a known, but relatively rare complication of pulmonary metastases of sarcoma. A 19-year-old man was presented with chest pain and dyspnea for three days and was diagnosed as left pneumothorax. After bleb resection, microscopic examination revealed metastatic osteosarcoma forming subpleural fistula and dystrophic calcification. Four years ago, he had had limb salvage operation and chemotherapy for osteosarcoma of left femur. After two and a half years he had a bleb resection for right pneumothorax without any evidence of metastasis. Six months later, he was found to have a 4x3cm sized lung mass in the right lower lobe. After lobectomy, he was diagnosed as pulmonary metastasis of osteosarcoma. Pneumothorax is the common complication of metastatic osteosarcoma to the lung and it may be presented before the pulmonary metastasis is clinically evident. It is important to recognize a pneumothorax of the patients with osteosarcoma as a possible sign of metastases.

Primary Osteosarcoma of the Breast: A case report.: Dong Chool Kim, Yun Kyung Lee, Ho Jong Jeon, Sung Chul Lim; Korean J Pathol. 2000;34(9):677-679.

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Abstract PDF: We report a case of primary osteosarcoma of the breast which is rare and exhibits poor prognosis. A 52 years-old-woman was admitted with rapidly growing right mammary mass. A huge lobulated dense mass with speckled calcifications, suggesting malignancy, was observed on mammography. She underwent a radical mastectomy. Grossly, the mass measured 16 14 6 cm and showed grayish white hard lobulated tissue with focal hemorrhage and necrosis. Light microscopically, the tumor was confirmed as an osteosarcoma devoid of any epithelial components. In postoperative whole body bone scan, there was no evidence of the other malignancy. To the best of our knowledge, the present case is the first report of primary osteosarcoma of the breast in Korea.

Intestinal Metastasis of Osteosarcoma Presenting with Intussusception: A Case Report.: Seong Ho Yoo, Min A Kim, Kyu Joo Park, Joon Koo Han, Sang Hoon Lee, Chong Jai Kim, Eui Keun Ham; Korean J Pathol. 2002;36(4):271-273.

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Abstract PDF: Metastatic osteosarcoma most commonly affects the lungs and other bones. Intestinal intussusception caused by metastatic osteosarcoma is very rare. We report a case of metastatic osteosarcoma of the intestine in a 39-year-old female. She underwent surgical resection of the left femur due to osteosarcoma and received additional chemotherapy 3 years ago. Pulmonary metastasis was found two years later and the patient complained of abdominal pain, nausea and vomiting after 8 months following excision of the lung nodules. Abdominal computed tomography revealed intussusception with a suspected polypoid mass in the distal portion of the jejunum. The histologic findings of the resected bowel were those of osteosarcoma. This is the first case of documented intestinal metastasis of osteosarcoma in Korea. It is suggested that the tumor metastasis to the small intestine should be considered in patients with previous osteosarcoma, when the patient presents with acute abdominal symptoms and intussusception.

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