Pathology & Oncology Research最新文献

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.

The accurate distinction between primary and secondary mucinous ovarian cancers is a crucial tool for effective surgical and systematic treatment. Mucinous ovarian metastases of appendiceal origin are a special group of tumors because they appear even in half of female patients with primary appendiceal mucinous carcinomas and demonstrate pathological similarity to primary ovarian mucinous neoplasms. The current literature review focuses on the differences based on pre-operative symptoms, radiological findings, the spectrum of microscopic features, and the significance of the immunophenotype of each tumor. Treatment options, including surgical management and adjuvant chemotherapy protocols, are also briefly overviewed. In conclusion, the source of the ovarian tumor mass might be suggested by preoperative symptoms, values of antigens, and imaging findings. However, the confirmation of the tumor origin is only made after the postoperative pathological examination. Investigating the most accurate immunohistochemical markers and new molecular features may improve diagnostic efficiency in future research.

Background: MRI-based image-guided adaptive brachytherapy (IGABT) is a new approach for individual dose escalation and control of organ at risk (OAR) doses and toxicities in the treatment of locally advanced cervical cancer.

Methods: Various radiotherapy-related parameters and the feasibility of the treatment based on acute toxicity were analyzed in a total of 50 cases in two cohorts who received a brachytherapy (BT) boost after definitive chemoradiotherapy with either an MRI-based IGABT technique (24 patients) or CT-only image guidance (26 patients). For target volume, OAR delineation, and dose prescription, the EMBRACE II protocol was followed.

Results: The features of the target volumes and dose coverage did not differ between the two groups regarding teletherapy. At BT, however, while the High-Risk Clinical Target Volumes (CTVHR) did not differ the D90 dose coverage was significantly higher in the MRI-based IGABT group than in the non-MRI-based group (7.37 ± 0.55 Gy vs. 6.87 ± 0.84 Gy, p = 0.015). The CTVHR D98 doses showed a strong trend in favor of the MRI-based technique (6.16 ± 0.59 Gy, vs. 5.72 ± 0.95 Gy, p = 0.051). Cumulative doses to the CTVHR by means of both D90 and D98 were significantly higher in the MRI-based treatment group than the other group (86.64 ± 4.76 Gy vs. 81.56 ± 8.29 Gy, p = 0.011 and 77.23 ± 4.39 Gy vs. 73.40 ± 7.80 Gy, p = 0.037, respectively). Regarding OAR exposure, doses to the bladder, rectum, and sigmoid did not differ between the two cohorts.

Conclusion: Our first clinical results support the implementation of IGABT as a key component of image-guided adaptive radiotherapy (IGART) aiming at tumor dose-escalation and OAR protection.

Purpose: Positron emission tomography (PET) hybrid imaging targeting HER2 requires antibodies labelled with longer half-life isotopes. With a suitable radiation profile, ⁵²Mn coupled with DOTAGA as a bifunctional chelator is a potential candidate. In this study, we investigated the tumor HER2 specificity and the temporal biodistribution of the [⁵²Mn]Mn-DOTAGA(anhydride)-trastuzumab in preclinical models.

Methods: PET/MRI and PET/CT were performed on SCID mice bearing orthotopic and ectopic HER2-positive and ectopic HER2-negative tumors at 4, 24, 48, 72, and 120 h post-injection with [⁵²Mn]Mn-DOTAGA(anhydride)-trastuzumab. Melanoma xenografts were included for comparison of specificity.

Results: In vivo biodistribution demonstrated strong contrast in HER2-positive tumors, particularly in orthotopic tumors, where uptake was significantly higher than in the blood pool and other organs from 24 h onwards and consistently higher than in ectopic HER2-positive tumors at all time points. Significantly higher tumor-to-blood and tumor-to-muscle ratios were observed in HER2-positive ectopic tumors compared to HER2-negative tumors but only at 4 and 24 h; the differences were likely due to non-specific binding of the tracer. The ratios for orthotopic HER2-positive tumors were significantly higher than those for ectopic HER2-negative tumors and melanoma at all time points. However, the differences between HER2-positive and HER2-negative tumors decreased at later time points.

Conclusion: These results suggest that [⁵²Mn]Mn-DOTAGA(anhydride)-trastuzumab demonstrates efficient tumor-to-background contrast, emphasize the higher tumor uptake observed in orthotopic tumors, and highlight the influence of tumor environment characteristics on uptake.

Kaposi's sarcoma (KS) is a vascular intermediate malignant tumor classified into four clinical types: classic, AIDS-related, iatrogenic, and endemic. Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of KS. Six KSHV genotypes (A, B, C, D, E, and F) classified by K1 or two genotypes (P and M) by K15 have been reported. However, whether the KSHV genotype affects clinical presentation remains elusive. Herein, we investigated the association between viral genotypes and clinical presentations in patients with KS in Okinawa, an endemic area in Japan. Classic KS caused by KSHV genotype C was identified as the most common clinical type of KS in Okinawa. Conversely, 80% of the patients with AIDS-related KS were associated with genotype A. According to K15 genotyping, the population of genotype M was higher than that of genotype P. Although genotype M accounted for most cases of both classic and iatrogenic KS in Okinawa, genotype P constituted the majority of AIDS-related KS. Regarding the association between the K1 and K15 genotypes, single genotype A was associated with genotype P, whereas single genotype C was associated with genotype M. These K1 and K15 associations in Okinawa differed from those in Europe and Africa. In terms of the association between viral genotype and clinical types, A/P tended to be associated with AIDS-related KS and genotype C/M tended to be associated with classic KS. The findings of the current study suggest that the KSHV genotype in Okinawa differs from that in other countries, which is related to the KSHV geographic distribution and population migration. Our data also suggest that the viral genotype in Okinawa is associated with clinical presentations.

Introduction: Several novel morphological variants of inflammatory bowel disease (IBD)- associated dysplasias have been described in recent years. The objective of our study was to reevaluate some of our IBD-associated neoplasia cases and retrospectively identify the so-called non-conventional dysplasias (NCDs).

Methods: We established a database of IBD patients registered between 2011 and 2015 at the Department of Pathology, University of Szeged. Patients with neoplastic samples were extracted into a separate database. Clinical and pathological characteristics were documented for each case. Histological slides were retrospectively reviewed, and cases were reclassified.

Results: During the study period, 57 patients had neoplastic samples, and 47 patients were identified with conventional dysplasias (82.5%). A significant association was found between conventional dysplasias and dysplasia localization (P = 0.004), size (P = 0.012), endoscopic appearance (P = 0.006), grade (P = 0.011), macroscopic appearance of colorectal carcinoma (P = 0.009), and pT stage (P = 0.01). NCD was identified in 20 cases (35.1%). The most frequently observed subtype was serrated not otherwise specified (NOS) dysplasia (n = 6; 30%). Significant associations were detected between the development of NCD and several clinical-pathological features, including the occurrence (P < 0.001), localization (P = 0.001), size (P = 0.002), macroscopic appearance (P = 0.01), grade (P = 0.005), histological subtype (P = 0.003), pT (P = 0.003) and pM stage (P = 0.047) of colorectal carcinoma, as well as microsatellite status (P < 0.001).

Discussion: The identification of IBD-associated NCDs might play a crucial role in future clinical practice. Some authors suggest closer patient follow-up upon identification of these lesions and recommend random biopsy sampling in IBD patients to detect potentially occult lesions. Further studies involving larger national and international patient cohorts are warranted to gain a more comprehensive understanding of the clinical behavior of NCDs.