BAP1-deficient meningioma presenting with trabecular architecture and cytokeratin expression: a report of two cases and review of the literature

AimsBRCA (BReast CAncer gene)-associated protein 1 (BAP1), encoded by the BAP1 gene, a tumour suppressor that is lost in several cancers. Importantly, such mutations have been shown to be susceptible to poly (ADP-ribose) polymerase (PARP) inhibition in preclinical studies, offering hope for targeted therapy. While rare, BAP1 loss has been observed in a subset of rhabdoid and papillary meningioma and is associated with earlier recurrence. We seek to add to the literature on this rare disease and advocate for more routine BAP1 testing.MethodsWe present a report of two cases of BAP1-deficient meningioma and review the available literature on this rare entity.ResultsBoth cases present with a distinct trabecular architecture without rhabdoid or papillary features. Interestingly, both also presented with radiographic and histopathological findings unusual for meningioma. While immunohistochemistry and genetic sequencing confirmed BAP1 loss, DNA methylation analysis was required to confirm the final diagnosis.ConclusionsWe suggest that BAP1-deficient meningioma should be considered in the differential diagnosis of extra-axial central nervous system (CNS) tumours with atypical imaging or histopathological features and that BAP1 loss may constitute a clinically important meningioma subtype with opportunities for targeted therapy.

Non-Secretory Multiple Myeloma with Patchy Marrow Involvement and Aberrant Cytokeratin Expression

Non-secretory multiple myeloma is a rare form of the disease that presents a diagnostic challenge. A 69-year-old woman presented to the emergency department with a pathological fracture of the right clavicle, along with a history of asthenia and middle back pain in the preceding three months. Workup revealed multiple focal lytic bone lesions in the clavicles, ribs, skull and thoracic- lumbar-sacral spine, without evidence of anemia, hypercalcemia or renal failure, with no abnormal immunofixation in the serum or urine and with normal serum free light chain ratios. The Iliac crest bone marrow aspiration and biopsy revealed a scarcely involved marrow, However, biopsy of one of the focal bone lesions revealed a hypercellular bone marrow with phenotypically abnormal plasmocytes, along with an intriguing, albeit aberrant, cytokeratin expression. Non-secretory multiple myeloma is in itself a rare diagnosis. However, the combination of a patchy marrow involvement and aberrant cytokeratin expression makes this a noteworthy presentation.

The Expression of Selected Wnt Pathway Members (FZD6, AXIN2 and β-Catenin) in Canine Oral Squamous Cell Carcinoma and Acanthomatous Ameloblastoma

The Wnt signaling pathway is well known to be involved in many types of human cancer; however, in veterinary medicine, the investigation of individual Wnt members’ expression, and their role in or association with oral tumor pathogenesis, is still underevaluated. We aim to determine the expression pattern of Frizzled-6 (FZD6) as one of the Wnt receptors in two of the most common canine oral neoplastic lesions—canine oral squamous cell carcinoma (COSCC) and canine acanthomatous ameloblastoma (CAA). While COSCC is a malignant tumor with aggressive biological behavior and a tendency to metastasize, CAA is a benign tumor with high local invasiveness. In CAA, the expression of FZD6 was mostly located in the center of the epithelial tumorous tissue, and cells exhibiting features of squamous metaplasia were strongly positive. In well-differentiated COSCC, FZD6 was expressed in the tumorous epithelium as well as the tumorous stroma. There was a negative correlation between cytokeratin expression and FZD6 expression in COSCC, where the central parts of the epithelial tumorous tissue were often FZD6-negative. The non-differentiated COSCC with low expression of cytokeratin exhibited a diffuse FZD6 signal. The invasive front with areas of tumor budding exhibited high FZD6 expression with a loss of cytokeratin expression. Moreover, the expression of β-catenin and AXIN2 was increased in comparison to gingiva. In conclusion, our study revealed significant differences in the expression patterns and the levels of FZD6 between COSCC and CAA, indicating the differential engagement of the Wnt pathway in these tumors.

Effects of In Vitro Interactions of Oviduct Epithelial Cells with Frozen–Thawed Stallion Spermatozoa on Their Motility, Viability and Capacitation Status

Cryopreservation by negatively affecting sperm quality decreases the efficiency of assisted reproduction techniques (ARTs). Thus, we first evaluated sperm motility at different conditions for the manipulation of equine cryopreserved spermatozoa. Higher motility was observed when spermatozoa were incubated for 30 min at 30 × 106/mL compared to lower concentrations (p < 0.05) and when a short centrifugation at 200× g was performed (p < 0.05). Moreover, because sperm suitable for oocyte fertilization is released from oviduct epithelial cells (OECs), in response to the capacitation process, we established an in vitro OEC culture model to select a sperm population with potential fertilizing capacity in this species. We demonstrated E-cadherin and cytokeratin expression in cultures of OECs obtained. When sperm–OEC cocultures were performed, the attached spermatozoa were motile and presented an intact acrosome, suggesting a selection by the oviductal model. When co-cultures were incubated in capacitating conditions a greater number of alive (p < 0.05), capacitated (p < 0.05), with progressive motility (p < 0.05) and with the intact acrosome sperm population was observed (p < 0.05) suggesting that the sperm population released from OECs in vitro presents potential fertilizing capacity. Improvements in handling and selection of cryopreserved sperm would improve efficiencies in ARTs allowing the use of a population of higher-quality sperm.

A pelvic cavity malignant solitary fibrous tumor with dedifferentiation and multifocal cytokeratin expression

Background: Solitary fibrous tumor is an uncommon mesenchymal neoplasm that originates from fibroblasts and occurs predominantly in the visceral pleura. Pelvic cavity small sized malignant solitary fibrous tumor is very rare; it is easily misjudged by surgeons as a benign lesion and resected by laparoscopic surgery. When accompanied by dedifferentiation, malignant solitary fibrous tumor is difficult to diagnose by pathologists. Here, we describe a challenging case.Case presentation: A 47-year-old man was accidentally found to have a pelvic mass for three months, with pain and distension for seven days. The mass was adhered and compressed to the ureter and bladder. The right side of the pelvic cavity had a palpable and substantial mass, with no obvious associated pain. With an assumed diagnosis of a benign tumor, the patient underwent laparoscopic surgery to resect the tumor. Histologically, spindle cell areas and dedifferentiated areas were observed. Immunohistochemical analysis of dedifferentiated regions revealed cytokeratin showed multifocal expression. Vimentin and CD34 were abnormal negative. This case was diagnosed as a MSFT with dedifferentiation. The patient was well after the operation, but, unfortunately, he had a recurrence one year later.Conclusion: Pelvic cavity malignant solitary fibrous tumor is a rare tumor that is in frequently dedifferentiated and exhibiting cytokeratin expression. The diagnosis of this type of tumor can be confusing, and it should be distinguished from Synovial Sarcoma, Liposarcoma, and other malignant tumors. The expression of cytokeratin and the absence of vimentin and CD34 are pitfalls to diagnosis. In this case, there was still a high degree of malignancy despite the small size of the tumor. Clinical-image-pathological multidisciplinary analysis has a great effect on diagnosis and therapy of diseases. This case is a cautionary tale for surgeons and pathologists.