Expanding the spectrum of tyrosine kinase fusions in calcified chondroid mesenchymal neoplasms: Identification of a novel PDGFRA::USP8 gene fusion.

Calcified chondroid mesenchymal neoplasms represent a distinct, and recently recognized, spectrum of tumors. To date most cases have been reported to be characterized by FN1 gene fusions involving multiple potential tyrosine kinase partners. Following incidental identification of a tumor morphologically corresponding to calcified chondroid mesenchymal neoplasm, but with a PDGFRA::USP8 gene fusion, we undertook a retrospective review to identify and characterize additional such cases. A total of four tumors were identified. Each was multilobulated and composed of polygonal-epithelioid-stellate cells with a background of chondroid matrix containing distinctive patterns of calcification. Targeted RNA sequencing revealed an identical PDGFRA (exon 22)::USP8 (exon 5) gene fusion in each case. Subsequent immunohistochemical staining confirmed the presence of PDGFRα overexpression. In summary, we report a series of four tumors within the morphologic spectrum of calcified chondroid mesenchymal neoplasms. In contrast to prior reports, these tumors harbored a novel PDGFRA::USP8 gene fusion, rather than FN1 rearrangement. Our findings expand the molecular diversity of these neoplasms, and suggest they are united through activation of protein kinases.

VIM::KMT2A-rearranged sarcomas: A report of two new cases confirming an entity with distinct histologic features.

The recently described KMT2A-rearranged sarcomas are rare emerging entities where the KMT2A gene fuses with YAP1 and, less commonly, VIM, resulting in two distinct morphologies. Unlike the sclerosing epithelioid fibrosarcoma-like features that characterize tumors with KMT2A::YAP1 fusions, VIM::KMT2A-rearranged sarcomas are more uniformly cellular and lack the extensively sclerotic background seen in the former. Most tumors behave aggressively with metastases on presentation. Here, we describe the clinicopathologic and molecular findings in two additional cases of VIM::KMT2A rearranged sarcomas that arose in the deep soft tissues of adult males. Both tumors were composed of hypercellular fascicles of uniform spindle cells with pale eosinophilic cytoplasm and ovoid nuclei. The stroma had scant delicate collagen with occasional thin-walled ectatic blood vessels and perivascular hyalinization. Immunohistochemical studies showed an unspecific staining pattern with diffuse positivity for CD99 and BCL2 and variable staining for S100 protein. RNA-sequencing detected the presence of VIM::KMT2A gene fusion involving VIM exon 4 and KMT2A exon 2 in both cases. Sarcomas with VIM::KMT2A gene fusions seem to have sufficient morphologic features to warrant distinction from KMT2A-rearranged sarcomas with YAP1 partner. Without the benefit of molecular testing, these tumors pose a diagnostic challenge due to their lack of specific immunohistochemical profile and great morphologic overlap with other monomorphic spindle cell neoplasms.

Spindle Cell Tumors of the Sinonasal Tract: A Diagnostic Update with Focus on Ancillary Workup.

Spindle cell neoplasms arising in the head and neck may be challenging to recognize due to their relative rarity. While underlying molecular alterations are increasingly elucidated, testing for these features may not be readily available. In most cases, combinations of key morphologic features and diagnostic immunohistochemical markers can be used to replace molecular diagnostics. Conversely, some molecular alterations and expression of their surrogate biomarkers are not specific for any one entity, and it is important to recognize these to avoid diagnostic pitfalls. In this review, we discuss both old and new spindle cell tumors of the sinonasal tract, with an emphasis on histologic features and clinically relevant immunohistochemical markers serving as surrogate markers for underlying genomic alterations.

Biphasic synovial sarcoma with myoepithelial features: a distinctive variant with a predilection for the foot.

Synovial sarcoma (SS) is a tumor known for its classic monophasic spindle cell or biphasic morphology. However, it exhibits a wide range of histologic variations, leading to diagnostic challenges. Here, we present four cases of molecularly confirmed, biphasic SS originating in the feet and displaying myoepithelial differentiation. The patients were two men and two women with an age range from 19 to 71 years (mean, 45 years). Each tumor showed foci with conventional spindle cell morphology. The epithelial components included areas with nests and cords of epithelioid cells set within a hyalinized and sclerotic stroma. The cytoplasm was clear to pale and eosinophilic. The nuclei were ovoid-round with fine chromatin and small to inconspicuous nucleoli. Mitotic figures were present (2-13 per 10 high-power fields; mean, 6.5). Immunohistochemical studies showed variable staining of the myoepithelial-like regions for low molecular weight keratins, EMA, p63, and S100 protein. Molecular studies confirmed the presence of SS18::SSX1/2 fusion in all four tumors. These cases highlight an unusual variant of synovial sarcoma with an apparent predilection for the distal lower extremity and suggest that differentiation of biphasic synovial sarcoma may be impacted by the anatomic site. Awareness of this variant is important to avoid misclassification and potential treatment and prognostic implications.

Clinicopathologic and genomic characterizations of brain metastases using a comprehensive genomic panel.

Central nervous system (CNS) metastasis is the most common brain tumor type in adults. Compared to their primary tumors, these metastases undergo a variety of genetic changes to be able to survive and thrive in the complex tissue microenvironment of the brain. In clinical settings, the majority of traditional chemotherapies have shown limited efficacy against CNS metastases. However, the discovery of potential driver mutations, and the development of drugs specifically targeting affected signaling pathways, could change the treatment landscape of CNS metastasis. Genetic studies of brain tumors have so far focused mainly on common cancers in western populations. In this study, we performed Next Generation Sequencing (NGS) on 50 pairs of primary tumors, including but not limited to colorectal, breast, renal and thyroid tumors, along with their brain metastatic tumor tissue counterparts, from three different local tertiary centers in Saudi Arabia. We identified potentially clinically relevant mutations in brain metastases that were not detected in corresponding primary tumors, including mutations in the PI3K, CDK, and MAPK pathways. These data highlight the differences between primary cancers and brain metastases and the importance of acquiring and analyzing brain metastatic samples for further clinical management.

Pelvic Radiation-Induced Sarcoma With Rhabdomyoblastic Differentiation Following Treatment of Cervical Cancer.

Radiation-induced sarcomas (RIS) are a rare long-term complication of radiation therapy, with a reported incidence of 2.5-5.5%. They usually develop several years following exposure to radiotherapy. The most common reported subtypes are undifferentiated pleomorphic sarcoma, angiosarcoma, and leiomyosarcoma. Breast cancer is the most common primary malignancy preceding RIS, followed by uterine cervical carcinoma. Only a few cases of RIS with rhabdomyoblastic differentiation have been reported in the literature, usually following the treatment of retinoblastoma. Herein, we report a rare case of RIS with rhabdomyoblastic differentiation in the pelvic region developing 12 years after cervical cancer radiation therapy.

Attitudes and beliefs on organ donation among students in a university in Central Saudi Arabia.

OBJECTIVES: Thousands of people with end-stage organ disease and organ failures die waiting for donations. Although, Saudi Arabia has an active center for organ transplantation, the number of donors is still low. The study focus was the attitudes, beliefs, and knowledge of university students toward organ donation, because the youth are agents of change in their communities and could help to promote organ donation.   METHODS: This study had a cross-sectional design and included randomly selected 195 students (97 males and 98 females) between the ages of 19-25 in Qassim University between January and March 2013. A 23-question self-administrated questionnaire in both Arabic and English was completed. The questionnaire was pre-tested on 10 students for validity and reliability. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, USA) version 13.  RESULTS: The primary source of students' knowledge on organ donation was television (61.5%). Most students (85.1%) believed that there is low public awareness regarding the subject. However, 37.4% of the students agreed to donate in the future and 68.2% would donate for a relative. One-third of students knew about organ donation cards, but none have signed them. The main reason for refusal was fear of side effects (51.8%). Half of the students (48.7%) think there are misconceptions of the Islamic perspective, as a result there are fewer donors. Medical students showed significantly higher knowledge about organ donation cards and the effectiveness of transplantation as a treatment compared to non-medical students.   CONCLUSIONS: College students have little knowledge on the benefits of organ donations. Further, religious misconceptions and accessibility of donor cards are barriers to donations. Public health promotion campaigns could address religious beliefs while a systematic intervention should be put in place to make donor registration more available. A nationwide study with a larger sample size addressing the same objectives needs to be conducted.