NKX3-1 (NK3 homeobox 1)

MCS is a rare, high-grade sarcoma with limited treatment options. Targeted therapies against HEY1::NCOA2-associated pathways are promising and are currently under investigation.

These findings suggest that the two components are part of the same neoplastic process and, given the presence of urothelial carcinoma in situ, possibly represent the first reported example of urothelial carcinoma with divergent prostatic differentiation. Awareness of divergent differentiation in urothelial carcinomas has important diagnostic, prognostic and therapeutic implications and can be resolved with the use of ancillary molecular studies.

Accurate distinction of poorly differentiated prostate carcinoma from urothelial carcinoma requires correlation with prior diagnoses and a focused immunohistochemical panel, as misclassification carries significant therapeutic implications. Pathologists should maintain awareness of this uncommon mimic.

Following debulking, the patient's symptoms resolved, and a watchful-waiting strategy was adopted for the tracheal tumor, while curative-intent therapy for prostate cancer continued. This case highlights that 18F-PSMA PET/CT may reveal rare, intensely PSMA-avid non-prostatic neoplasms and underscores the importance of recognizing atypical uptake patterns to avoid misinterpretation during prostate cancer staging.

This case highlights the pitfall of "diagnostic anchoring" to a previous malignancy and emphasizes that new pulmonary lesions, even decades after an initial cancer diagnosis, necessitate histological confirmation to differentiate between recurrence and a second primary malignancy. Video-assisted thoracoscopic surgery (VATS) remains a safe and effective diagnostic approach in such clinically ambiguous scenarios.

However, these features may not correlate with prognosis. This study represents the first systematic radiologic evaluation of NFATC2-rearranged bone sarcomas, highlighting distinctive characteristics that may aid pathologists in their initial diagnostic assessments.

A 53-year-old man with metastatic, castration-sensitive prostate cancer (cT3bN1M1b, PSA 9.39 ng/mL, Gleason 4 + 5) underwent androgen deprivation therapy using bicalutamide and leuprorelin. After 73 cycles, chemotherapy was discontinued, and the patient has remained in remission during follow-up. This case highlights the potential efficacy of carboplatin and paclitaxel in treating poorly differentiated CRPC, suggesting the need for further investigation into platinum-based regimens for aggressive prostate cancer variants.

Subsequent radium-223 therapy further reduced bone metastases and normalized ALP levels, leading to substantial functional recovery. Furthermore, the favorable response to EP highlights the potential role of platinum-based chemotherapy in managing low-PSA, high-grade PC. Additional cases are needed to refine the clinical characterization of AVPC and establish evidence-based treatment guidelines.

Immunostain for androgen receptor was strongly and diffusely positive in the primary tumor and in the nodal metastasis, which together with focal staining for NKX3.1 were suggestive of primary prostatic origin and invited consideration of androgen deprivation therapy. This report highlights a rare prostatic Ewing-family sarcoma harboring an EWSR1::FEV fusion and immunophenotypic features that mimic a neuroendocrine carcinoma.

Given the frequency of NKX3.1 expression in benign bronchial elements, pathologists should interpret NKX3.1 staining in transbronchial FNAs with caution to avoid misdiagnosing metastatic prostatic adenocarcinoma.

Notably, NKX3.1-positive malignant cells were also identified in a follow-up voided urine sample. This case underscores the potential utility of urine cytology, particularly when supplemented by immunocytochemistry, in the diagnosis of prostate cancer.

We propose that the initial IHC panel should include TRPS1, CK7 and CK20. In TRPS1-negative cases, additional immunostains should be performed: CDX2 and SATB2 for colonic; p63, GATA3 and uroplakin II/III for urothelial; and PSA and NKX3.1 for prostatic secondary EMPD.