Virchows Archiv最新文献

Intraductal carcinoma (IDC) is a rare tumor of the salivary glands. Here, we report a unique case of apocrine IDC of the parotid gland of a 60-year-old male, exhibiting a striking sebaceous-like differentiation. Microscopically, the tumor displayed a papillary growth pattern with apocrine cells (AR-positive; S100/SOX10-negative) and distinct areas harboring clear, vacuolated cells resembling sebaceous cells (CK7/S100/SOX10-positive; AR negative). Molecular genetic analysis revealed mutations in AKT1 and BRAF genes. An AKT1 gene mutation has earlier been described in sclerosing polycystic adenoma (SPA), suggesting a possible link between IDC and SPA, while BRAF V600E mutations were reported in an oncocytic subtype of IDC, but not in the apocrine one. Since IDC is an indolent disease, its recognition is a key to prevent unwarranted overtreatment. Further evidence is needed to determine whether apocrine IDC with sebaceous-like differentiation represents a novel morphological variant of the apocrine subtype of IDC or a novel salivary gland entity.

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a recently defined thyroid nodule category characterized by follicular architecture with papillary nuclear features but lacking classical papillary carcinoma features like papillae or psammoma bodies. The diagnosis of NIFTP is based on histological examination and excludes cases with high-risk mutations like BRAFV600E. NIFTP carries a low risk of recurrence and distant metastasis, prompting a more conservative surgical approach compared to classical papillary thyroid carcinoma. The management of NIFTP typically involves lobectomy with postoperative monitoring of thyroglobulin levels and performing neck ultrasounds. While the identification of NIFTP represents a significant advancement in thyroid cancer diagnosis, challenges remain in refining preoperative diagnostic tools and establishing optimal long-term follow-up strategies. The objective of this review is to provide a comprehensive overview of NIFTP, including its histopathological characteristics, molecular profile, clinical presentation, diagnostic criteria, management strategies, and future research directions.

We hereby report the case of an epithelioid neoplasm arising from pterygopalatine fossa in a 13-year-old child harboring PANX3::GLI1 fusion and MDM2 amplification. Identified chimeric gene can explain observed signs of osteogenic differentiation. We discuss the challenges in differential diagnosis from osteogenic tumors and soft tissue neoplasms with epithelioid morphology. Our case is the first report of a tumor with such genetic abnormalities and it is about to replenish the spectrum of rare GLI1-rearranged tumors.

Somatic variant testing through next-generation sequencing (NGS) is well integrated into Swiss molecular pathology laboratories and has become a standard diagnostic method for numerous indications in cancer patient care. Currently, there is a wide variation in reporting practices within our country, and as patients move between different hospitals, it is increasingly necessary to standardize NGS reports to ease their reinterpretation. Additionally, as many different stakeholders-oncologists, hematologists, geneticists, pathologists, and patients-have access to the NGS report, it needs to contain comprehensive and detailed information in order to answer the questions of experts and avoid misinterpretation by non-experts. In 2017, the Swiss Institute of Bioinformatics conducted a survey to assess the differences in NGS reporting practices across ten pathology institutes in Switzerland. The survey examined 68 reporting items and identified 48 discrepancies. Based on these findings, the Swiss Society of Molecular Pathology initiated a Delphi method to reach a consensus on a set of recommendations for NGS reporting. Reports should include clinical information about the patient and the diagnosis, technical details about the sample and the test performed, and a list of all clinically relevant variants and variants of uncertain significance. In the absence of a consensus on an actionability scheme, the five-class pathogenicity scheme proposed by the ACMG/AMP guideline must be included in the reports. The Swiss Society of Molecular Pathology recognizes the importance of including clinical actionability in the report and calls on the European community of molecular pathologists and oncologists to reach a consensus on this issue.

Aggressive large B-cell lymphomas (LBCL) are a heterogeneous group of lymphomas with variable biological characteristics, for which the identification of MYC rearrangements (MYCr) is a defining and prognostic feature. Both the International Consensus Classification and the 5th edition of the World Health Organization Classification of Hematolymphoid Tumors recommend performing cytogenetic studies in all aggressive LBCL to detect MYCr. Since MYCr incidence is low, cost-effective screening tools are necessary. We asked whether the immunohistochemical combined profile of CD10, LMO2, and MYC could be a useful tool to screen for MYCr. For this purpose, we used two strategies: first, a scoring system assigning 0 points each for CD10 - , LMO2 + , and MYC - and 1 point for CD10 + , LMO2 - , and MYC + , adding the results, and second, an algorithm that selected tumors with CD10 + /LMO2 - profile and/or MYC overexpression. All analyses were performed in a training series including 482 cases from a single center and a validation series of 124 patients from two centers. The resulting system classified cases in scores from 0 to 3. Scores 0 and 1 had low MYCr (0/92 and 7/224, 3%, respectively), being higher for scores 2 (40/98, 41%) and 3 (61/68, 90%) (P < 0.001) in the training cohort. The incidence of MYCr in the validation series was as follows: score 0, 0/29 cases; score 1, 3/64 (5%); score 2, 10/23 (43.5%); score 3, 8/8 (P < 0.001). Sensitivity and negative predictive values were respectively 93.5% and 97.8% for the training and 85.7% and 96.8% for the validation cohorts. The algorithm rescued 2 and 1 MYCr cases included in score 1 from both series. In conclusion, we suggest that both approaches combining the interpretation of CD10/LMO2/MYC by immunohistochemistry are useful to screen for MYCr.

IGH::CCND1 translocation has been implicated as a preliminary finding in mantle cell lymphoma (MCL) and plasma cell myeloma, with cyclin D1 over-expression by immunohistochemistry stain, without gene rearrangement, reported in other hematologic neoplasms. CCND1 rearrangement has been reported infrequently as a secondary event in high-grade B-cell lymphomas. We present the case of an elderly man who was found to have a splenic marginal zone lymphoma with a heterozygous TP53 deletion. Years later at the time of relapse, the patient acquired a CCND1 rearrangement, in addition to a persistent TP53 deletion. Sequencing of the two lymphomas demonstrated clonal relatedness of the two processes. To our knowledge, this is the first report of a splenic marginal zone lymphoma with a TP53 deletion at diagnosis, evolving into a large B-cell lymphoma with a CCND1 rearrangement.

Pseudomyogenic hemangioendothelioma (PHE) is a rare, usually multifocal neoplasm typically affecting individuals in the second-to-fourth decade of life, with a male predominance. It often arises in the distal extremities and characteristically involves multiple tissue planes. Presentation of this neoplasm as a primary penile lesion is exceedingly rare, with only five cases previously documented in the literature. We report the clinicopathologic features of five additional PHEs presenting as primary penile tumors and review previously published cases. Tumors affected young to middle-aged adult patients and had a relatively bland clinical appearance, mimicking indolent lesions such as epidermal inclusion cysts. Microscopically, they were ill-defined nodules composed of plump spindle cells and round neoplastic cells with abundant, densely eosinophilic cytoplasm and eccentric nuclei resembling rhabdomyoblasts. Neoplastic cells demonstrated infiltrative growth, including foci of perineural invasion. Immunohistochemistry demonstrated invariable co-expression of keratins, endothelial markers (CD31 and/or ERG), and FOSB. In conclusion, penile PHE is rare but should be considered in the differential diagnosis of penile lesions with spindle cell and/or rhabdomyoblast-like morphology affecting young to middle-aged adult patients.

Primary central nervous system (CNS) diffuse large B-cell lymphoma with MYC and BCL2 rearrangements is a very rare lymphoma subtype. Deep brain stimulation is an effective minimally invasive therapeutic option for the treatment of refractory movement disorders, as well as some psychiatric disorders and chronic pain syndromes. Herein, we report a case of CNS lymphoma, which developed around an electrode of a deep brain stimulation (DBS) device. A 70-year-old woman with drug-resistant essential tremor was treated with bilateral thalamic DBS with significant symptomatic improvement over the following year. She presented to the emergency department with recurrent tremor, blurred vision, and confusion. Imaging showed a 4 cm heterogeneously enhancing centered around the DBS electrode. Pathologic evaluation and systemic workup confirmed a diagnosis of primary CNS diffuse large B-cell lymphoma. MYC and BCL2 rearrangements were identified. To our knowledge, this is the first reported case of a CNS lymphoma associated with a DBS electrode.

In hepatocellular carcinoma (HCC), CD147 expression contributes to tumor malignancy; however, its relationship with the tumor-immune microenvironment (TIME) remains unclear. This study aimed to elucidate the clinicopathological characteristics associated with CD147 expression in HCC and investigate its association with the TIME, specifically its association with tumor-infiltrating lymphocytes (TILs) and oncostatin M (OSM). Using 397 HCC specimens from patients undergoing curative-intent resection, we assessed CD147 expression in tumor cells and quantified OSM-positive cells and various TILs (CD8⁺, CD4⁺, FOXP3⁺, and CD20⁺ cells) in the TIME. Using tissue microarrays, these assessments were performed through immunohistochemical analysis. We investigated the associations between CD147 expression status, the density of OSM-positive cells, and the densities of various TILs. High CD147 expression, found in 332 specimens (83.6%), was associated with advanced clinical stage (P = 0.029), fibrosis (P = 0.036), and higher densities of FOXP3⁺ cells (P = 0.0039), CD4⁺ cells (P = 0.0012), and OSM-positive cells (P = 0.0017). In CD147-high tumors, OSM-positive cell density was associated with all assessed TIL subsets (CD8⁺, CD4⁺, FOXP3⁺, and CD20⁺ cells; all Ps < 0.001), whereas in CD147-low tumors, OSM-positive cell density was associated only with FOXP3⁺ cells (P = 0.0004). In HCC, CD147 expression is associated with an immunosuppressive TIME, characterized by increased FOXP3⁺ regulatory T cells and a correlation with OSM-positive cells. These results elucidate the potential mechanisms through which CD147 facilitates tumor-immune evasion, suggesting the CD147 - OSM axis as a promising target for therapeutic intervention in HCC.