Pathology International最新文献

Recent studies suggest that lung adenocarcinoma cells are closely associated with the tumorigenesis of large-cell neuroendocrine carcinoma via cellular transformation. However, morphological evidence, along with genetic abnormalities before, during, and after transformation, is quite limited. We present here a case of combined large-cell neuroendocrine carcinoma and adenocarcinoma exhibiting acinar and solid patterns. Adenocarcinoma cells with abundant mucin, exhibiting positivity for both napsin-A and neuroendocrine markers, were partially found in the acinar adenocarcinoma component and extensively observed in the solid adenocarcinoma component. Next-generation sequencing using extracted genomic DNA from the three components revealed homozygous TP53 (missense) and STK11 (nonsense) mutations in all three components, suggesting monoclonal origin. Furthermore, MYC gene amplification, recently presumed to be a pivotal driver in neuroendocrine transformation, was observed in both the solid adenocarcinoma and large-cell neuroendocrine carcinoma components. These genetic findings corresponded to pre- and post-transformation morphology, providing compelling evidence that some kinds of adenocarcinomas may serve as a precursor of large-cell neuroendocrine carcinoma.

We previously reported that strong immunoreactivity (IR) of estrogen-responsive finger protein (Efp), also known as tripartite motif-containing 25 (TRIM25), predicts poor prognosis in patients with estrogen receptor-positive and -negative invasive breast cancers. In the present study, we investigated the clinicopathological role of Efp and ZCCHC3, the latter of which is an Efp interactor, in a triple-negative breast cancer (TNBC) cohort which was composed of 118 Japanese female breast cancer patients underwent surgical treatment. Efp and ZCCHC3 IRs were analyzed using specific antibodies for these proteins. We demonstrated that positive Efp IR was significantly associated with shorter distant disease-free survival (p = 0.0108) and that positive ZCCHC3 IR was also significantly associated with shorter distant disease-free survival (p = 0.0153). Notably, ZCCHC3 IR was positively associated with Efp IR (p = 0.003). When IRs of the two proteins were combined, double positivity was associated with shorter distant disease-free survival (p = 0.0007) and was an independent factor for poor prognosis. These results suggest that IR positivity of Efp and ZCCHC3 has clinical significance as a poor prognostic factor in patients with TNBC. Thus, we propose that the combined use of both IRs can be used as a prognostic marker for TNBC.

Tenosynovitis with psammomatous calcification (TPC) is an extremely rare condition. It was first described as a characteristic subtype of idiopathic calcifying tenosynovitis, with only 40 cases reported to date. Here, we present a case of TPC affecting a female patient in her late teens, with no relevant medical history. She presented with discomfort and pain in the right first toe. A 10-mm mushroom-like calcified mass was observed in the metatarsophalangeal joint on radiographs. The surgical specimen revealed chronic synovitis with calcification. Numerous psammomatous bodies are observed in the synovium, often with granulomatous reactions. After removal of the mass, no recurrence has been observed for 5 years. Although the etiology of TPC has been suggested to be related to repetitive trauma to the tendon or peritendinous soft tissue, the composition and mechanism of calcification remain unclear because of its rarity. In this report, we also discuss the calcification mechanism in TPC, supported by scanning electron microscopy and energy-dispersive x-ray spectroscopy findings.

Prostate cancer (PCa) is the second most common cancer in men globally. Its growth is driven by oxidative stress associated with inflammation, aging, and environmental factors, including diet and lifestyle. These factors contribute to multiple stages of PCa progression, including progression to castration-resistant prostate cancer (CRPC). Therefore, oxidative stress represents an intriguing target for PCa chemoprevention and treatment. In vivo experimental models are crucial for understanding the mechanisms of PCa development, validating chemopreventive and therapeutic approaches, and translating preclinical results into clinical applications. We established a transgenic rat for adenocarcinoma of the prostate (TRAP) model, a transgenic rat that efficiently develops androgen-dependent adenocarcinoma, pathologically and biologically mimicking human PCa progression, to clarify the mechanisms of tumor progression, including the involvement of oxidative stress, and established a system for screening the chemopreventive effects of agents against PCa. Additionally, we derived a CRPC model from the TRAP model and developed a distant metastasis model, providing a comprehensive multistage rat model of prostate carcinogenesis. This review presents findings on the molecular mechanisms of PCa and the chemopreventive effects of natural compounds with antioxidant properties, such as polyphenols. We additionally described the potential for repositioning existing drugs with antiandrogenic activity for PCa chemoprevention.

NTRK-rearranged spindle cell neoplasm is a group of tumors characterized by NTRK1/2/3 gene fusion. Recently, tumors with other kinase fusion genes were reported to exhibit similar morphologies. Herein, we discuss an adult-onset soft tissue tumor with similar histologic patterns as kinase gene fusion-related tumors but with BRAF and NRAS mutations. A female in her 40s had a 40 mm tumor with an unclear border in the soft tissue of her foot joint. Short spindle-shaped tumor cell proliferation with abundant capillaries and collagen fiber bundles were observed. The tumor infiltrated the subcutaneous adipose tissue, exhibiting a lipofibromatosis-like pattern. Immunohistochemically, the tumor cells coexpressed CD34, S-100, and BRAF V600E. Whole-exome sequencing revealed BRAF p.V600E and NRAS p.Q61K mutations. Since BRAF activation occurs in BRAF fusion gene tumors and BRAF mutations, they could share a similar mechanism in tumorigenesis. This case suggests the further expansion of kinase-related spindle cell tumors.