Pathology & Oncology Research最新文献

Clear cell renal cell carcinoma (ccRCC) is the most common renal malignancy. However, the combined clinical and biological scores commonly used to predict the clinical outcome are imperfect and need improvement. The main goal of our study was to assess the effect of mtDNA genetics on the prognosis of ccRCC patients and to explore morphologic correlation. Mitochondrial DNA copy number (mtDNAcn) variation between tumor and paired matched healthy kidney tissue was assessed by real-time quantitative PCR and expressed as a ratio in 105 patients. According to this median ratio, the cohort was divided into two groups: "LOW" (n = 53) and "HIGH" (n = 52). Cancer-Specific Survival (CSS) and Disease-Free Survival were assessed in each group. The tumor samples were classified into two subtypes (Clear or Eosinophilic cells) according to the cytoplasmic morphology. CSS was significantly reduced in the "HIGH" than in the "LOW" group with respective 5-year survival rates: 78.7% (CI 95: 64.8-95.5) and 95.5% (CI 95 87.1-100.0) (Hazard Ratio: 7.4 (CI 95: 1.9-29.9, p = 0.027*) in multivariate analysis, including pathological classification, tumor size, International Society of Urological Pathology grade, lymphovascular invasion, dedifferentiated pattern, necrosis and adjuvant therapy. Next-generation sequencing of mtDNA was performed on 14 tumors and matched healthy kidney tissue. No hotspot mutation or redundant large deletion was found. None of the variants or large deletions identified had an impact on prognosis. MtDNAcn variation in tumor relative to normal kidney appears as an independent prognostic factor in ccRCC, which was also associated with eosinophilic morphology. MtDNA content could be considered an additional prognostic factor, in combination with other predictive parameters. Furthermore, these results underline the importance of the role of mitochondria in ccRCC and the need for further functional studies to understand the pathophysiological mechanisms better and consider therapies targeting mitochondrial metabolism.

Background: Fundic gland tumors are a rare subtype of gastric tumors with fundic gland differentiation. This group of tumors has a low incidence rate and shows indistinctive cellular atypia, obvious structural atypia, special tissue morphology, and clinical prognosis, thus leading to diagnostic challenges.

Aim: We aimed to investigate the clinical and endoscopic characteristics and pathological features of gastric adenocarcinoma of the fundic gland (GA-FG) to provide a better understanding of this disease.

Methods: We collected data from patients diagnosed as having GA-FG at Guangdong Provincial People's Hospital between January 2019 and April 2024. The analysis focused on their clinical data, endoscopic characteristics, pathological morphological characteristics, immunohistochemistry results, treatment, and prognosis.

Results: Among the four patients were two men and two women (age range, 52-65 years). The tumors were mainly located in the gastric fundus and gastric body, and the lesions commonly had a superficial bulge. Three patients had an initial diagnosis of oxyntic gland adenoma, which was diagnosed as GA-FG after complete resection. These tumors were negative for MUC5AC, but showed diffuse strong positivity for MUC6 and pepsinogen I, and synaptophysin expression.

Conclusion: GA-FG is a rare gastric tumor with unique morphological features. As it is difficult to diagnose with a biopsy, immunohistochemistry plays an important role in the differential diagnosis. Oxyntic gland adenoma can be regarded as the intramucosal stage of GA-FG. Although all patients were negative for MUC5AC expression, MUC6 and pepsinogen I can help the diagnosis of GA-FG.

This case study delves into the link, between exposure to Bisphenol A (BPA) and kidney issues filling a gap in human focused research found in studies. The individual, a 72-year man with a history of BPA exposure in a plastics manufacturing facility experienced a gradual decline in kidney function over 18 months. Medical tests showed kidney disease with a buildup of lipofuscin in renal tubular cells upon examination. This discovery suggests a connection between BPA exposure and kidney damage underscoring the need for investigation. The lack of human based evidence highlights the importance of research to understand the toxic effects of BPA on the kidneys. In addition, to its implications this case emphasizes the importance of improving safety protocols and raising awareness among healthcare professionals in relevant work environments to reduce potential health risks associated with BPA exposure.

Many subtypes of bone and soft tissue tumours harbour specific chromosome translocations leading to chimeric fusion genes. The identification of these specific fusion genes is the basis of molecular diagnoses in such tumours. Break-apart FISH is a robust method that is commonly used to identify these translocations and provide diagnostic support to histological interpretations. The signal patterns of the break-apart probes are usually easily interpreted. However, some cases show abnormal signal patterns leading to equivocal and challenging interpretation. The incidence of these abnormal patterns is largely unknown. Using a retrospective cohort we explored the incidence of abnormal signal patterns across common bone and soft tissue tumour types to raise awareness of this occurrence and to aid in the interpretation. In total, 1,087 bone and soft tissue tumours tested by break-apart probes were examined. The abnormal signal patterns were classified as deletion, additional copy and amplification, which were found at highest frequency in low-grade fibromyxoid sarcoma (32%, 6/19), and at moderate frequencies in those from alveolar rhabdomyosarcoma (10%, 9/94), nodular fasciitis (9%, 18/209), synovial sarcoma (8%, 17/207) and Ewing sarcoma/round cell sarcoma with EWSR1-non-ETS fusions (6%, 29/497). The lowest frequency was found in clear cell sarcoma (1%, 1/61). Despite the equivocal results from the abnormal signal patterns, the specific fusion genes were confirmed by orthogonal molecular techniques such as FISH with fusion probes, RT-PCR or next-generation sequencing.

Background: Benign fibro-osseous lesions are characterized by the replacement of normal bone with cellular fibrous connective tissue with new bone formation. The published cytogenetic information on these tumors is limited to only few cases. Here, we report the cytogenetic and molecular genetic findings of a fibro-osseous tumor.

Methods: A fibro-osseous lesion was investigated for genetic abnormalities using banding cytogenetics, fluorescence in situ hybridization (FISH), RNA sequencing, and direct cycle Sanger sequencing.

Results: The karyotype was 46,XX,t(4;11;14;12)(q35;p15;q22;q13)[7]/46,XX [3], with no rearrangement of HMGA2. RNA sequencing revealed two FRMD6::PTH chimeric transcripts, originating from the fusion point 14q22;11p15 of the t(4;11;14;12). In these transcripts, exon 1 of FRMD6 fused to either exon 1 or exon 2 of PTH. Direct cycle sequencing confirmed the presence of these FRMD6::PTH chimeric transcripts.

Conclusion: This study reports, for the first time, the presence of the FRMD6::PTH chimera in fibro-osseous tumor. In this chimera the expression of the entire coding region of PTH is regulated by the ubiquitously expressed FRMD6 gene promoter. Dysregulation of PTH expression may have significant implications for processes regulated by PTH protein.

Objective: This study aimed to assess the likelihood of detecting cancer in final pathology and evaluate the accuracy of intraoperative frozen-section assessment in cases of endometrioid intraepithelial neoplasia (EIN).

Material and methods: We included patients diagnosed with EIN at Hacettepe University Hospital who subsequently underwent hysterectomy at the same center between January 2011 and March 2023. EIN diagnoses made at other institutions were re-evaluated and confirmed by co-author gynecopathologists.

Results: A total of 354 patients diagnosed with EIN underwent hysterectomy. The majority of patients (68.5%) had a final diagnosis of EIN. Endometrial cancer (EC) was identified in 11.3% (n = 40) of patients in the final pathology. Advanced age (≥50 years) (OR = 2.52; 95% CI: [1.27-4.96]; p = 0.006) and menopausal status (OR = 2.62; 95% CI: [1.34-5.11]; p = 0.004) were significantly associated with an increased risk of EC. Among 263 patients who underwent intraoperative frozen-section assessment, EC was detected in 12.9% (n = 34). The sensitivity and specificity of frozen-section assessment for EC detection were 41.1% and 100%, respectively. The frozen-section assessment failed to identify only one of the seven patients who required staging surgery.

Conclusion: Our study demonstrates that a preoperative EIN diagnosis carries an 11.3% risk of concurrent EC. Additionally, the likelihood of EC is significantly higher in older and postmenopausal patients. The majority of patients requiring staging surgery were identified by frozen-section assessment. Our findings indicate that frozen-section assessment provides the necessary information for adequate surgical treatment in EIN cases.

Low-grade oncocytic tumor (LOT) of the kidney is a recently recognized renal neoplasm with distinctive morphologic, immunophenotypic, and molecular features that distinguish it from other eosinophilic tumors such as oncocytoma and chromophobe renal cell carcinoma (chRCC). This study presents a comprehensive analysis of 20 LOTs from 19 patients, integrating clinicopathological, immunohistochemical, and genetic data. LOTs typically appeared as small, unilateral, well-circumscribed tumors with a tan-brown cut surface, composed of uniform eosinophilic cells with round nuclei and occasional perinuclear halos. Key histological hallmarks included an extensive capillary network and central edematous areas without necrosis or significant atypia. Immunohistochemically, all tumors showed strong diffuse CK7 positivity and CD117 negativity, with universal expression of GATA3, GPNMB, and L1CAM. Whole-exome and panel-based sequencing revealed recurrent mutations in the mTOR signaling pathway, including MTOR, TSC1, and ATM genes. mTORC1 activation was confirmed immunohistochemically in one case. No evidence of aggressive behavior or metastasis was observed during the follow-up period (median: 4.5 years). Comparative analysis demonstrated that LOT patients were diagnosed at an older age than those with chRCC and had smaller tumors overall. This study reinforces the notion that LOT is a distinct renal tumor entity with consistent morphology, immunoprofile, and mTOR-pathway-related genetic alterations. Despite overlapping features with other eosinophilic renal neoplasms, the specific immunohistochemical profile and indolent clinical course support LOT's classification as a unique diagnostic category.

Peripheral T-cell lymphomas (PTCLs) are a group of non-Hodgkin lymphomas originating from mature T-lymphocytes. Despite encompassing several well-defined entities, about 25% of the PTCLs do not fulfill the requirements of any of the subcategories. These diseases are classified as PTCL, not otherwise specified (PTCL, NOS), and often associated with poor prognosis. Hereby we present a case of a female patient, diagnosed with PTCL, NOS from her skin biopsy specimen. Besides histology and immunohistochemistry, flow cytometry was used for phenotyping and staging (peripheral blood, bone marrow). Pathologic T-cells were found in all the investigated tissues, with a very unusual CD45 negative and surface CD3 dim immunophenotype. For proper differential diagnosis, we determined several markers with immunohistochemistry (CD3, CD4, CD7, CD8, CD30, PD1, Ki-67) and flow cytometry: (CD2, cytoplasmic CD3, surface CD3, CD4, CD5, CD7, CD8, CD9, CD10, CD19, CD20, CD26, CD34, CD38, CD45, CD48, CD56, CD99, CD123, surface TRBC1, cytosplasmic TRBC1, surface TRBC2, cytoplasmic TRBC2, MPO, TdT, Igκ, Igλ). Here we discuss the difficulties of the differential diagnostic process and highlight some potential pitfalls of flow cytometric analysis of the pathologic T-cells with such a rare immunophenotype. Despite several determined markers, the disease characteristics did not meet the criteria of any PTCL subtype, therefore the diagnosis remained PTCL, NOS. Due to the aggressive course of the disease, we lost the patient within 1 year after the diagnosis.

Introduction: We report the first case of an asymptomatic woman with osteoclast-like giant cell-rich cervical squamous cell carcinoma (OGC-rich cervical SCC), where the detection of cancer was made possible only by routine cytological screening. The presence of OGCs in cervical SCCs is an extremely rare phenomenon, with only 8 cases reported to date.

Case description: Two consecutive liquid-based cytology revealed high-grade squamous intraepithelial lesion (HSIL). Molecular testing detected HPV 18. Colposcopic findings strongly supported the clinical diagnosis of HSIL/suspicious for invasion. Histopathological examination of biopsy samples revealed typical keratinizing-type cervical SCC morphology. The patient subsequently underwent LEEP (loop electrosurgical excision procedure). Microscopic examination of resection specimen confirmed the previous diagnosis. Moreover, groups of large multinucleated cells were observed at the periphery of some invasive nests. Most of them presented the morphology of osteoclasts, whereas some giant cells were similar to Langhans cells. All the giant cells were positive for vimentin and CD68, negative for pancytokeratin. Owing to positive margins following the LEEP procedure, the patient underwent hysterectomy via the Wertheim technique. No adjuvant treatment was applied, and after the 9-month follow-up, the patient was alive with no recurrence.

Conclusion: Detailed literature review revealed that our case is the first case of keratinizing-subtype cervical OGC-rich SCC. Moreover, it is the youngest (33 yo.) patient with a significantly smaller diameter than previously reported cases. Unfortunately, owing to the small number of reported cases, the analysis did not allow us to draw conclusions about the potential prognostic or predictive value of OGC-rich morphology.

Introduction: Hairy cell leukemia (HCL) is an indolent B-cell lymphoproliferative disease. Interferon-alpha (IFN-alpha) was the first successfully used drug in HCL; its favourable effect has been known since the early 1980s. However, currently the first-line treatment of the disease consists of purine nucleoside analogs.

Objectives: The aim of our study was to assess the efficacy of pegylated IFN-alpha in HCL patients treated with this drug at a single university center.

Methods: We report the treatment characteristics and outcome of seven classical HCL patients treated with pegylated IFN-alpha at the Department of Internal Medicine and Oncology, Semmelweis University.

Results: As a result of pegylated interferon-alpha treatment, 3 of 7 patients (3/7) achieved an unconfirmed complete remission, 3 of 7 patients (3/7) achieved partial remission. One patient had stable disease while receiving pegylated IFN-alpha. Only mild adverse effects and no infectious complications were observed during our treatment.

Conclusion: Our clinical data support that pegylated IFN-alpha in monotherapy is effective and safe even in elderly and frail HCL patients. It may also be a preferred therapeutic option in patients with profound immunosuppression and in patients with severe active infections.