Pathology International最新文献

Glioneuronal and neuronal tumors (GNTs) are slow-growing, lower-grade neuroepithelial tumors characterized by mature neuronal differentiation and, less consistently, glial differentiation. Their identification has traditionally relied on histological proof of neuronal differentiation, reflecting the well-differentiated nature of GNTs. However, after discovering genetic alterations in GNTs, particularly those in the MAP-kinase pathway, it became evident that histological diagnoses do not always correlate with genetic alterations and vice versa. Therefore, molecular-based classification is now warranted since several inhibitors targeting the MAP-kinase pathway are available. The World Health Organization classification published in 2021 applied DNA methylation profiling to segregate low-grade neuroepithelial tumors. As GNTs are essentially indolent, radical resection and unnecessary chemoradiotherapy may be more harmful than beneficial for patients. Preserving tumor tissue for potential future treatments is more important for patients with GNTs.

We report a case of adult T-cell leukemia/lymphoma (ATLL) with angioimmunoblastic T-cell lymphoma (AITL/nTFHL-AI)-like feature. An 88-year-old Japanese woman with seropositive for the Human T-lymphotropic virus type 1 (HTLV-1) was incidentally diagnosed with generalized lymphadenopathy. Biopsy of the cervical lymph node demonstrated the proliferation of small- or medium-sized and large atypical lymphocytes associated with eosinophils, high endothelial venules, and clear cells. Immunohistochemical analysis revealed atypical lymphocytes were CD3- and CD4-positive. Atypical T cells bore the T-follicular helper phenotype (PD1, ICOS, and BCL6) and were positive for CD25 and chemokine receptor 4. Epstein-Barr virus encoded RNA-positive cells were scattered in the background via in situ hybridization. The histological findings were similar to those of AITL/nTFHL-AI; however, the immunohistochemical results did not exclude the possibility of ATLL. Southern blot analysis detected integration of HTLV-1 proviral DNA. The RHOA Gly 17 Val (G17V) mutation was detected by the peptide nucleic acid-locked nucleic acid clamp method. Finally, the patient was diagnosed with ATLL with AITL-like feature and exhibited a similar morphology, immunophenotype, and mutational signature to AITL/nTFHL-AI. ATLL mimics other types of T-cell lymphomas. Thus, in HTLV-1 endemic areas, routine screening for HTLV-1 serology is necessary to avoid misdiagnosis of other lymphoid malignancies.

Most elements of filamentous fungi seen in human tissue by pathologists are hyphae, and encountering other elements may interfere with diagnosis. Sporangia and chlamydospores are such elements that have been described in only a few case reports. We present an autopsy case with the extremely rare coexistence of Mucorales sporangia and chlamydospores in the lung. These fungal elements must be recognized and identified accurately because they can easily be mistaken for other fungi, microorganisms, or degenerated tissue structures.

Pregnancy-associated breast cancer has been increasing. In this study, we analyzed patients with breast cancer that occurred during pregnancy (PrBC) and compared their genetic profiles with those of patients with breast cancer that did not occur during pregnancy, within 1 year after childbirth nor during lactation (non-PrBC). We performed gene expression analyses of patients with PrBC and non-PrBC using microarrays and qRT-PCR. Microarray analysis showed that 355 genes were upregulated in the luminal-type PrBC group compared to those in the non-PrBC group. The C-X-C motif chemokine ligand 13 (CXCL13) gene was the most upregulated in the PrBC group compared to that in the non-PrBC group, especially in the luminal A-type (p = 0.016). This result was corroborated by the qRT-PCR analysis of microdissected cancer cells (p < 0.001). A negative correlation was observed between CXCL13 and estrogen receptor 1 (ESR1) mRNA expression levels in luminal A-type breast carcinoma (p < 0.001). Our results provide clues for a better understanding of breast cancer pathogenesis during pregnancy.

The liver's unique cellular structure makes it a frequent site for metastatic cancer. In colorectal liver metastasis (CRLM), surgical resection is essential for long-term survival. Histopathological growth patterns (HGPs) in CRLM, including desmoplastic and nondesmoplastic patterns, provide critical prognostic information. Tumor budding (TB) and poorly differentiated clusters (PDCs), indicators of aggressive cancer behavior, are evaluated using standardized histological scoring systems and are linked to epithelial-mesenchymal transition. This study explored the correlation between HGPs, TB, and PDCs in CRLM. Archived data from Thammasat University Hospital, including resected CRLM specimens, were analyzed. This study evaluated 51 CRLM resection specimens treated with preoperative systemic therapy, finding most to be nondesmoplastic with low TB and grade 1 PDC. Desmoplastic growth was significantly more prevalent in cases receiving preoperative chemotherapy than those that did not. Higher 3-year mortality was noted in nondesmoplastic groups and those with higher TB and tumor regression grade (TRG) scores. Significant correlations were observed between HGPs, TB, and PDCs, despite challenges in assessing these parameters due to issues with noncancer cells, extracellular mucin, bile ductular proliferation, and retraction artifacts. This study underscores the prognostic significance of HGPs, TB, PDCs, and TRG scores in CRLM, highlighting the need for precise histopathological evaluation for more accurate prognostic implications.

The identification of CD30 expression by immunohistochemistry is essential for the treatment of lymphomas using an antibody-drug conjugate targeting CD30. However, no standardized protocol for CD30 staining has been available. In this study, we compared three common automated immunostaining platforms {Bond III (B III), Dako Omnis (DO) and Ventana BenchMark ULTRA (VBMU)}. A primary antibody for CD30, the Ber-H2 clone, was diluted 50- to 400-fold for B III and DO, and ready-to-use antibody was used for VBMU. An enhancement step using a linker was introduced in all protocols. First, several candidate dilutions were selected for each platform by staining six cases. These candidate conditions were then confirmed with 60 cases of various types of peripheral T-cell lymphomas (PTCLs). The concordance rates of CD30 expression among platforms differed depending on cutoff values and antibody dilutions, except for anaplastic large cell lymphoma. The concordance rates among three platforms in the evaluation of "positive" or "negative" were 100% and 97% when the cutoff values were 1% and 10% respectively, if using 400-diluted antibody in B III and 100-diluted antibody in DO. This study demonstrated the feasibility of equalizing CD30 staining of PTCLs among different platforms by adjusting protocols.

The dual-stratified pathway of endometrial carcinomas (ECs) has long been dominant. However, in 2013, The Cancer Genome Atlas (TCGA) defined four EC subgroups with distinctive prognoses. Inspired by TCGA, in 2018, the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) provided four pragmatic molecular classifiers to apply surrogate immunohistochemical markers to TCGA subgroup categorization. These trends prompted the revision of 2020 WHO Classification of Female Genital Tumors, 5th edition (2020 WHO classification), in which four molecular subtypes are recognized: POLE-ultramutated; mismatch repair-deficient; p53-mutant; and no specific molecular profile. In the 2020 WHO classification, the diagnostic algorithm is characterized by prioritizing POLEmut over other molecular abnormalities. Following the 2020 WHO classification, Federation of International Gynecology and Obstetrics (FIGO) proposed a new staging system in 2023. The updated system focuses on diagnostic parameters, such as histological type and grade, lymphovascular space invasion, and molecular alterations. These new histomolecular diagnostic concepts of ECs are being accordingly introduced into the routine pathology practice. For the first time, the 2020 WHO classification includes mesonephric-like adenocarcinoma (MLA) as a novel histological entity, mimicking the conventional mesonephric adenocarcinoma, but is considered of Müllerian ductal origin.

Although there are clear morphologic criteria for the diagnosis of papillary thyroid carcinoma (PTC), when the morphology is untypical or overlaps, accurate diagnostic indicators are necessary. Since few studies investigated the role of down-regulated genes in PTC, this article aims to further explore the molecular markers associated with PTC. We conducted bioinformatics analysis of gene microarrays of PTC and normal adjacent tissues. Besides, quantitative real-time quantitative polymerase chain reaction array and immunohistochemical staining were used to investigate the expression of the major down-regulated genes. The results indicated that several important down-regulated genes, including TLE1, BCL2, FHL1, GHR, KIT, and PPARGC1A were involved in the process of PTC. Compared to normal adjacent tissues, the mRNA expression of the major genes was down-regulated in PTC (p＜0.05). Immunohistochemically, FHL1 shows negative or low expression in PTC tissues (p＜0.05). BCL2 did not show a significant difference between PTC and normal thyroid tissues (p > 0.05). TLE1, KIT, PPARGC1A and GHR showed negative expression in both tumor and normal tissues. These results suggested that FHL1 could serve as a novel tumor marker for precise diagnosis of PTC.