SATB2 and MDM2 Immunoexpression and Diagnostic Role in Primary Osteosarcomas of the Jaw

Primary osteosarcomas of the jaw (OSJ) are rare, accounting for 6% of all osteosarcomas. This study aims to determine the value of SATB2 and MDM2 immunohistochemistry (IHC) in differentiating OSJ from other jawbone mimickers, such as benign fibro-osseous lesions (BFOLs) of the jaw or Ewing sarcoma of the jaw. Certain subsets of osteosarcoma harbor a supernumerary ring and/or giant marker chromosomes with amplification of the 12q13–15 region, including the murine double-minute type 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) genes. Special AT-rich sequence-binding protein 2 (SATB2) is an immunophenotypic marker for osteoblastic differentiation. Cases of OSJ, BFOLs (ossifying fibroma and fibrous dysplasia) of the jaw, and Ewing sarcoma of the jaw were retrieved from the Departments of Oral Pathology and Oral Medicine, Faculty of Dentistry, Obafemi Awolowo University and Lagos State University College of Medicine, Nigeria. All OSJ retrieved showed histologic features of high-grade osteosarcoma. IHC for SATB2 (clone EP281) and MDM2 (clone IF2), as well as fluorescence in situ hybridization (FISH) for MDM2 amplification, were performed on all cases. SATB2 was expressed in a strong intensity and diffuse staining pattern in all cases (11 OSJ, including a small-cell variant, 7 ossifying fibromas, and 5 fibrous dysplasias) except in Ewing sarcoma, where it was negative in neoplastic cells. MDM2 was expressed in a weak to moderate intensity and scattered focal to limited diffuse staining pattern in 27% (3/11) of cases of OSJ and negative in all BFOLs and the Ewing sarcoma. MDM2 amplification was negative by FISH in interpretable cases. In conclusion, the three cases of high-grade OSJs that expressed MDM2 may have undergone transformation from a low-grade osteosarcoma (LGOS). SATB2 is not a dependable diagnostic marker to differentiate OSJ from BFOLs of the jaw; however, it could serve as a valuable diagnostic marker in differentiating the small-cell variant of OSJ from Ewing sarcoma of the jaw, while MDM2 may be a useful diagnostic marker in differentiating OSJ from BFOLs of the jaw, especially in the case of an LGOS or high-grade transformed osteosarcoma.

Pediatric Patient With Neurological And Leukemic Peripheral Blood Involvement By Small Cell Variant Of ALK- Positive Anaplastic Large Cell Lymphoma (ALCL): Case Study

Casestudy Anaplastic large cell lymphoma (ALCL), is a T-cell lymphoma typically consisting of large lymphoid cells including characteristic horseshoe- shaped hallmark cells. The rare small cell morphological variant of ALCL may pose a challenge in diagnosis, especially when the initial presentation is unusual. Results Our patient, a 7-year-old girl presented with a headache. A complete blood count showed leukocytosis and anemia. The smear was reported to have segmented neutrophils, reactive lymphocytes, and monocytes. A spinal tap was performed and flow analysis identified a minute aberrant T cell population (0.3% of total), positive for CD3, CD4, bright CD7; negative CD5, CD8 in the CSF sample. The peripheral blood sample was reviewed again; some small- medium atypical lymphocytes, with irregular nuclear contours and cytoplasmic azurophilic granules were noted. Flow immunophenotyping displayed an aberrant T cell population positive for CD45, CD2, CD3, bright CD7, CD4, CD13; negative CD30, TdT CD5, CD8, CD117, CD34; consistent with T cell lymphoma/leukemia. A cell block prepared from peripheral blood sample showed blood with numerous atypical cells with irregular nuclei positive for ALK, CD30, CD3, CD4, CD7; negative CD5 and CD8. A diagnosis of leukemic ALK(+) ALCL was rendered, though classic hallmark cells were difficult to see. A marrow biopsy showed interstitial and sinusoidal pattern of mainly small to medium-sized cells with irregular nuclei. Molecular study revealed ALK gene alteration showing characteristic NPM1-ALK fusion. The patient underwent a bone bone marrow transplantation but recently relapsed with a submandibular lymph hode biopsy showing the presence of many larger ALCL cells. Conclusion Correct clinical diagnosis of the small-cell variant of ALCL is often challenging as the scarce “hallmark cells” are scattered and difficult to recognize. While leukemic peripheral blood involvement is rare in ALCL, an association has been reported with small-cell variants, which may be a potential explanation for the poor prognosis and aggressive nature of small-cell variant ALCL. A meticulous examination of peripheral blood smears, comprehensive immunophenotypic studies, and early bone marrow and lymph node/tissue biopsy are needed to facilitate diagnosis.