Role of the Immunohistochemical ZEB1 Expression in Uterine Mesenchymal Neoplasms

The distinction of mesenchymal tumors of the uterus is a frequent diagnostic challenge in gynecologic pathology. Especially, distinguishing low-grade endometrial stromal sarcoma (ESS) from leiomyoma or distinguishing low-grade ESS from high-grade ESS can be difficult. Epithelial-mesenchymal transition (EMT) is a physiological and pathological process in which epithelial cells lose their morphological features, become elongated and acquire mesenchymal traits. The signaling pathway of Zinc finger E-box binding homeobox 1 (ZEB1) is one of the most significant pathways involved in the EMT process and it has a crucial role in cancer progression, metastasis, and therapy resistance. We studied a series of 69 uterine mesenchymal neoplasms including 18 endometrial stromal sarcomas (10 cases of low grade and 8 cases of high grade endometrial stromal sarcomas), 26 leiomyosarcomas (8 cases of grade 1 and 19 cases of grade 2-3 leiomyosarcomas), 15 leiomyomas, and 10 rhabdomyosarcomas, using an antibody ZEB1. We graded the leiomyosarcomas depending on the FNCLCC grading system. It was observed that leiomyosarcoma was more intensely stained with ZEB1 than leiomyoma (P < 0.001) and high-grade ESS was significantly more intensely stained with ZEB1 protein than low-grade ESS (P < 0.004). It also was observed that high-grade leiomyosarcoma was significantly more intensely stained with ZEB1 protein than low-grade leiomyosarcoma (P < 0.000). Our data suggest that Zeb1 can be used to differentiate high-grade sarcomas from their low-grade counterparts as well as benign and malignant smooth muscle tumors of the uterus.

Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study

Solitary fibrous tumors (SFT) are mesenchymal neoplasms with a favorable prognosis usually originating from the visceral pleura. Rarely, they may occur at various extrapleural sites and show malignant behavior coupled with dedifferentiation. NAB2-STAT6 fusion gene and STAT6 nuclear expression are biomarkers for diagnosis of SFT in addition to CD34, Bcl-2, and CD99. Furthermore, several reports have shown specific NAB2-STAT6 fusion variants and loss of STAT6 protein expression are associated with malignancy. We report a rare case of retroperitoneal SFT which rapidly progressed to death within 35 days after admission. Autopsy found a primary tumor containing both benign and malignant histologies, with multiple metastatic sites similar to the malignant, dedifferentiated tumor. STAT6 was detected in the primary differentiated tumor but not in the primary dedifferentiated tumor or lung/liver metastases. However, the NAB2-STAT6 fusion gene (NAB2ex6/STAT6ex16 variant) was detected in the primary tumor and lung/liver metastases. Intriguingly, fusion gene expression at the transcriptional level was downregulated in the dedifferentiated tumors compared to the differentiated tumor. We further performed target DNA sequencing and found gene mutations in TP53, FLT3, and AR in the dedifferentiated tumors, with TP53 mutations especially found among them. We demonstrate that downregulation of NAB2-STAT6 fusion gene at the transcriptional level is associated with malignant SFT for the first time. Moreover, the present study supports the idea that TP53 mutations promote malignancy in SFTs.

Evidence from a Series of 104 Equine Sarcoids Suggests That Most Sarcoids in New Zealand Are Caused by Bovine Papillomavirus Type 2, although Both BPV1 and BPV2 DNA Are Detectable in around 10% of Sarcoids

Equine sarcoids are common mesenchymal neoplasms of horses that are caused by cross-species infection by deltapapillomaviruses. While bovine papillomavirus (BPV) 1 and 2 are the most common causes, there are differences between countries regarding which of these BPV types cause the majority of sarcoids. Additionally, no causative PV can be detected in a subset of sarcoids, suggesting that other PV types could be rarer causes of these neoplasms. In the present study, consensus PCR primers and PCR primers specific for the five deltapapillomavirus types currently known to cause mesenchymal neoplasia (BPV1, BPV2, BPV13, BPV14, and Ovis aries PV2 DNA) were used to investigate the presence of PV DNA in 104 sarcoids from three defined regions in New Zealand and from two distinct time periods separated by 15 years. PV DNA was detected in 94 (90.4%) sarcoids. Of the sarcoids containing PV DNA, 83 (88.3%) contained only BPV2 DNA, 9 (9.6%) BPV1 and BPV2 DNA, and 2 (2.1%) only BPV1 DNA. No other PV types were detected. The predominance of BPV2 is consistent with studies of sarcoids from North America but dissimilar to studies of sarcoids from Europe and Australia. Detection rates of BPV1 and BPV2 were similar in sarcoids from different regions of New Zealand and in sarcoids from different time periods. These results suggest that most equine sarcoids in New Zealand are caused by BPV2 and thus if vaccines are developed to prevent sarcoids, vaccines that provide good protection against BPV2 will be required in this country.

Intraosseous solitary myofibroma of the orbit in an adolescent woman

A 16-year-old woman presented with a painless, progressive, hard swelling in the left inferolateral orbital wall for the past 1 year. There was no diminution of vision or limitation of ocular motility. Imaging revealed an intraosseous, well-defined, expansile, soft tissue lesion in the inferolateral wall of the left orbit. A left anterior orbitotomy with complete surgical excision was performed. Histopathological evaluation of the specimen revealed fascicular pattern of spindle cells with a rich network of slit-like, branching blood vessels. Tumour cells exhibited smooth muscle actin and vimentin positivity but were negative for CD-34 and STAT-6. In absence of any systemic manifestation, a diagnosis of intraosseous solitary orbital myofibroma was made. The case highlights the importance of integrating clinical, radiological and histopathological features in overcoming the diagnostic challenge of differentiating myofibroma from other mesenchymal neoplasms. It also brings forth the importance of complete resection and curettage to prevent recurrence.

Histopathologic spectrum of glomangioma: A clinico-pathologic review

Introduction/Objective Glomus tumors are mesenchymal neoplasms with glomus body type modified smooth muscle cell differentiation. Most glomus tumors have a benign clinical course. However, rarely, they display malignant histologic features. Methods/Case Report We undertook a retrospective study using a natural language search in CoPath to find surgical pathology cases from 1993-2020 containing “glomus” in the pathology diagnosis. All relevant cases were included, and clinicopathologic data were reviewed in detail. Results (if a Case Study enter NA) A total of 66 tumors were identified, of which 42 were in female (63.6%) and 24 in male (36.4%) patients. The age at surgery ranged from 22 to 79 years with a median of 47.5. Females were significantly younger than males at presentation (p=0.025) by 8.8±3.8 years. Forty cases (60.6%) were located on the digits, 24 in nonvisceral soft tissue of extremities, trunk, and lip (36.4%), and one each in stomach and breast parenchyma. Sixty-three (95.5%) were benign (of which one recurred locally), 2 (3%) were malignant, and 1 (1.5%) was atypical. Four (6%) were multicentric. One case showed mixed histology (oncocytic and classic features) and one was classified as glomangiomatosis. The malignant cases each presented with a single tumor in lower extremity soft tissue in female patients (aged 33 and 49 years). The tumors measured 0.5 and 1.8 cm respectively and showed marked cytologic atypia in both and increased mitotic activity in the first. They were both completely excised. Conclusion The majority of glomus tumors are benign, however 3% are malignant. The most common location is the digits, followed by soft tissue. This tumor is more commonly seen in female patients. Unusual histologic variants such as glomangiomatosis and oncocytic component at times may create some difficulty to reach the diagnosis, especially on small biopsies. Unusual locations such as stomach can lead to a wrong diagnosis such as carcinoid, especially in a small biopsy material.