Sie können Operatoren mit Ihrer Suchanfrage kombinieren, um diese noch präziser einzugrenzen. Klicken Sie auf den Suchoperator, um eine Erklärung seiner Funktionsweise anzuzeigen.
Findet Dokumente, in denen beide Begriffe in beliebiger Reihenfolge innerhalb von maximal n Worten zueinander stehen. Empfehlung: Wählen Sie zwischen 15 und 30 als maximale Wortanzahl (z.B. NEAR(hybrid, antrieb, 20)).
Findet Dokumente, in denen der Begriff in Wortvarianten vorkommt, wobei diese VOR, HINTER oder VOR und HINTER dem Suchbegriff anschließen können (z.B., leichtbau*, *leichtbau, *leichtbau*).
To describe the morphological features and explore the molecular profiles of pleomorphic adenomas (PA) with abundant lymphoid stroma and HMGA2 rearrangements, and to compare them with classic lymphadenomas, in order to identify a potential molecular and morphological overlap.
Methods
Four cases of PA with abundant lymphoid stroma and HMGA2 rearrangements were identified from four different institutions in France and Japan. Their characterisation was performed through a detailed pathological, immunohistochemical, and molecular analysis.
Results
All tumours were well-circumscribed and encapsulated, predominantly composed of ductal and tubular structures with scattered myoepithelial cells embedded within a dense lymphoid stroma rich in non-atypical lymphocytes. Immunohistochemistry was positive for CK7, p63, p40, SOX10, S100, and HMGA2, and negative for PLAG1. The Ki67 proliferation index was low. Molecular analyses revealed no MDM2 amplification and excluded EBV infection. Clonality studies confirmed a polyclonal lymphoid infiltrate. Targeted DNA and RNA sequencing found no mutation; however, three cases harboured HMGA2::WIF1 fusions and one harboured HMGA2::RPSAP52 fusion. In the transcriptomic analysis, these tumours clustered together with classic lymphadenomas, separated from other salivary gland neoplasms.
Conclusions
The present study reports four cases of pleomorphic adenoma characterised by abundant lymphoid stroma and HMGA2 rearrangements, for which transcriptomic analysis found that the lymphoid stroma shared a profile similar to that observed in lymphadenomas. Given this distinctive morphological and molecular feature, we propose the designation “lymphadenoma-like” for this novel subtype of pleomorphic adenoma.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Introduction
Pleomorphic adenoma (PA) is the most common epithelial neoplasm of salivary glands, accounting for 80% of all salivary gland tumours [1]. While the majority of PAs develop in the parotid gland, some cases occur in the submandibular gland as well as in minor salivary glands of the oral cavity [1]. These tumours are characterised by a high morphological diversity, as highlighted by their name, “pleomorphic adenoma”; it exhibits the greatest variation observed in any single organ [2], presenting significant differences in cell types, architectural patterns, and stromal components. These elements can be nearly absent or compose approximately the entire tumour in some cases. This extensive morphological variability is particularly prominent in PAs of the major salivary glands.
PA is characterised by gene rearrangements[3‐5] that involve the PLAG1 gene on chromosome 8q12 in approximately 50% of cases [3], and the HMGA2 gene on chromosome 12q13-15, found in approximately 20% of cases [6]. Recent studies have highlighted genotype–phenotype relationships in PAs; for instance, canalicular-like PAs have been associated with HMGA2::WIF1 gene fusions [7], while oncocytic PAs frequently involve PLAG1 rearrangements and, with ZBTB47-AS1 as gene partner in some cases [8]. Additionally, carcinoma ex pleomorphic adenoma with distinctive nuclear features has been linked to MDM2 gene amplification [9].
Anzeige
Four cases with PA characterised by an abundant lymphoid stroma associated with biphasic epithelial and myoepithelial proliferation have been identified in our institution, two other French institutions as well as in a Japanese institution [10] In all of these cases, HMGA2 gene fusion and overexpression of HMGA2 have been found. Since these PAs share similarities with lymphadenomas, the aim of the present study was to describe the morphological features of these tumours, explore their molecular profiles, and to compare them with those of classic lymphadenomas, in order to identify a potential molecular and morphological overlap.
Materials and Methods
Cases Identification
The four cases of PA exhibiting morphological and molecular features similar to those of lymphadenomas were retrospectively retrieved from the archives of the authors' institutions.10 All cases from France were identified through the national expert pathology network for rare head and neck tumours (REFOR), which greatly facilitated their recognition. To test the hypothesis that these morphologically similar tumours share a common molecular pathogenesis, a control group composed of seven cases with classic lymphadenomas was included. The control cases underwent parallel molecular analyses to explore potential similarities or distinctions in their pathogenesis. The study was approved by an institutional review board.
Immunohistochemistry
The immunohistochemical analysis was conducted using an automated immunostainer (Ventana BenchMark ULTRA, Roche, Tucson, AZ, USA). Initially, 4-μm-thick sections of formalin-fixed paraffin-embedded (FFPE) tissues were deparaffinised in xylene and rehydrated in ethanol. A solution from Ventana Medical Systems was used to block endogenous peroxidase activity, followed by antigen retrieval using ULTRA Cell Conditioning Solution (ULTRA CC1; Ventana Medical Systems). The process involved primary antibody incubation and applying the avidin–biotin–peroxidase complex technique. Reactions were visualised using diamino-3,3′-benzidine tetrahydrochloride substrate solution (SIGMAFAST; Sigma-Aldrich, Tucson, AZ, USA). The tissues were counterstained with haematoxylin. The primary antibodies and their final dilutions were as follows: CK7 (OV-TL, 1:1000; Biogenex), Epithelial Membranous Antigen EMA (E29, Ventana, prediluted), p40 (BC28, Ventana, prediluted), p63 (4A4, Ventana, prediluted), S100 (PL, Ventana, prediluted), SOX10 (SP267, Ventana, prediluted), PLAG1 (clone EP398, 1:600; Epitomics), CKAE1/AE3-Ki67 (AE1/AE3 and Ki67 30.9, Ventana, prediluted), MDM2 (IF2, Invitrogen, prediluted), HMGA2 (HMGA2-P1, 1:200, Biocheck), and Ki67 (clone MIB1, Dako, prediluted). Each case was reviewed by two pathologists, experts in head and neck pathology (ZA and NB).
Fluorescence in situ Hybridisation (FISH) for MDM2 Amplification
FISH analysis was performed on FFPE tissue sections to assess MDM2 gene amplification. Dual-colour FISH assays used commercially available probes targeting the MDM2 locus at 12q15 and the centromeric region of chromosome 12 (CEP12; e.g., Vysis, Abbott Molecular). Sections of 4-μm thickness were deparaffinised, rehydrated, and subjected to pre-treatment protocols, comprising heat-induced epitope retrieval and enzymatic digestion, following the manufacturer's instructions. Hybridisation was conducted overnight at 37 °C in a humidified chamber. Post-hybridisation washes were performed to remove unbound probes, and nuclei were counterstained with DAPI. Fluorescence signals were analysed using a fluorescence microscope with appropriate filters. At least 50 non-overlapping tumour cell nuclei were evaluated per case. The MDM2/CEP12 signal ratio was calculated and a ratio ≥ 2.0 was considered indicative of gene amplification. Cases exhibiting complex signal patterns or polysomy were interpreted with caution, and additional analyses were performed to confirm amplification status, when accurate.
Anzeige
In situ Hybridisation with Digoxigenin-labelled Epstein-Barr virus-encoded RNA probe
After deparaffinisation and rehydration of FFPE tissue sections, a digoxigenin-labelled Epstein-Barr virus-encoded RNA (EBER) probe was applied. The slides were covered with coverslips and incubated in a humidified chamber at 37 °C for 2 h to facilitate hybridisation. Post-hybridisation, sections were washed in stringent buffer (e.g., 2 × SSC) to remove unbound probe. Detection was carried out using an anti-digoxigenin antibody conjugated to alkaline phosphatase, followed by staining using a chromogenic substrate such as nitro-blue tetrazolium/5-bromo-4-chloro-3'-indolyphosphate (NBT/BCIP). Slides were counterstained with nuclear fast red, dehydrated, cleared, and mounted. Positive controls included EBV-positive tissues known to express EBERs, ensuring assay sensitivity, while negative controls were processed identically without the EBER probe to assess nonspecific staining. EBER expression was identified by distinct nuclear staining in EBV-infected cells, with the presence of nuclear signals in positive controls and their absence in negative controls, confirming the assay's specificity and reliability.
Clonality Study
Clonality study was performed according to the EuroClonality/BIOMED-2 protocol [11]. Immunoglobulin heavy chain (IG) H and IGK assays were used for BCR study using the following primers: FR1, FR2, FR3, DH–JH, Ig kappa, and Ig lambda. TCR Clonality was assessed using the BIOMED-2 primer sets for TCR gamma (TCRG) Table 1.
Table 1
Clinical and pathological features
Age (years)
Sex
Tumour size (cm)
Site
Diagnosis
Molecular alterations
41
M
3.4
R parotid
Pleomorphic adenoma
HMGA2::WIF1
25
F
2
R parotid
Pleomorphic adenoma
HMGA2::WIF1
54
F
2.1
L parotid
Pleomorphic adenoma
HMGA2::RPSAP52
70
F
1.3
L parotid
Pleomorphic adenoma
HMGA2::WIF1
69
F
1.1
Parotid
Lymphadenoma
None
50
M
1.2
Parotid
Lymphadenoma
None
72
M
1.5
Parotid
Lymphadenoma
None
71
M
3.9
Parotid
Lymphadenoma
None
75
M
2.5
Parotid
Lymphadenoma
None
61
M
5.0
Parotid
Lymphadenoma
None
77
M
4.5
Parotid
Lymphadenoma
None
F, Female; L, Left; M, Male; R, Right
DNA variant Analysis and Microsatellite Instability Evaluation from DNA Sequencing
The Sophia Genetics “Solid Tumor Solution” pancancer panel was used, which covers alterations of major oncogenes and tumour suppressor genes that are dysregulated in solid tumours (Sophia Genetics). Variants were interpreted using the SophiaDDM version 4 interface with OncoPortal (Sophia Genetics). Only pathogenic (pathogenicity class 5 according to the American College of Medical Genetics) variants were included in the analysis. The detection of microsatellite instability relied on the observation of instability in the length of a subset of 117 homopolymers, presenting a length of at least 12 nucleotides within the target regions of the SC_CLSO_v5 panel. (supplementary Table 1). The selection of the most relevant loci was based on the statistical criteria using an in-house algorithm [12].
Whole-exome Capture RNA-SEQUENCING on FFPE
Exome-based RNA capture sequencing was performed on FFPE samples; the data were further analysed to detect fusion genes and small nucleotide variations, and to compare expression profiles presenting more than 8000 other samples using clustering methods. The molecular basis of the technique, technical protocol, and bioinformatic algorithms used have been previously described [13]. This analysis was performed on a control cohort composed of 31 cases of colon adenocarcinoma, 25 cases of angiomatoid fibrous histiocytoma, 21 cases of pleomorphic adenoma, 13 cases of inflammatory myofibroblastic tumour, 13 cases of adenoid cystic carcinoma, 11 cases of marginal zone lymphoma, 11 cases of oncocytoma, 8 cases of acinic cell carcinoma, 7 cases of lymphadenoma, 4 cases of carcinoma ex pleomorphic adenoma, and 2 cases of pleomorphic adenoma with rich lymphoid stroma.
Statistical analysis
Distributions of expression values within each group were assessed for normality using the Kolmogorov–Smirnov test. Pairwise comparisons of expression profiles were conducted using Fisher’s exact test for variance comparison, followed by t-tests with Bonferroni correction for multiple testing. Differentially expressed genes were identified using the Python package PyDESeq2. Unsupervised clustering analyses were performed on all genes without selection. A clustering tree was created using the Ward method, represented as a dendrogram using the scikit-learn package in Python, and distance evaluation was carried out using Pearson’s and Spearman’s correlation methods.
Results
Clinical Findings
The mean age of the four included patients with PA (three females and one male) was 48 years (range: 25–70 years). The mean tumour size was 2.2 cm (range: 1.3–3.4). All tumours arose from the parotid gland, two were located in the right parotid and two in the left. Complete surgical resection was performed in all cases. No recurrence was observed during the follow-up period.
Pathological and Immunohistochemical Findings
All four tumours in the present series were well-circumscribed and surrounded by a fibrous capsule (Fig. 1A). The neoplastic proliferation exhibited a combination of duct-like slit structures and sheets of spindle cells, highlighting the characteristic biphasic architecture (Fig. 1B). The duct structures were lined by a single layer of cuboidal to cylindrical epithelial cells, contributing to the biphasic appearance (Fig. 1C). In all cases, the stroma was markedly inflammatory, predominantly composed of non-atypical lymphocytes (Fig. 1D), and showed a variable background of fibro-myxoid and hyalinised areas (Fig. 1E). Notably, two cases displayed foci of cartilaginous differentiation (Fig. 1F). Cytologically, two cases had small cuboidal to cylindrical epithelial cells with eosinophilic cytoplasm and vesicular chromatin as well as prominent nucleoli (Fig. 1G). In contrast, one case had distinctive “gear-like” nuclear atypia within the epithelial component (Fig. 1H). The associated spindle cells did not exhibit significant cytologic atypia, and no mitotic activity or tumour necrosis was observed in any of the cases.
Fig. 1
Histological features of pleomorphic adenoma characterised by abundant lymphoid stroma. At low-power magnification, a well-circumscribed nodule surrounded by a fibrous capsule was observed (A, HES, × 4). The tumour cells exhibited a combination of duct-like slit structures and sheets of spindle cells (B, HES, × 10). The ductal structures were lined by a single layer of cuboidal to columnar epithelial cells (C, HES, × 40), with a markedly inflamed stroma composed predominantly of non-atypical lymphocytes (D, HES, × 20) and variable zones of hyalinisation (E, HES, × 20). Foci of cartilaginous stroma were present (F, HES, × 20), as well as small cuboidal to columnar epithelial cells with eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli (G, HES, × 40). The epithelial component also contained cells displaying “gear-like” nuclear atypia with fragmented chromatin (H, HES, × 40)
The immunohistochemical analysis revealed a diffuse expression of CK7 in both epithelial and myoepithelial cells dispersed within the lymphoid-rich stroma (Fig. 2A). P40, P63 (Fig. 2B), PS100, and SOX10 (Fig. 2C) were also expressed by the myoepithelial cells and a scattered positivity was found throughout the lymphoid stroma. EMA was selectively expressed in the ductal epithelial cells, further supporting an epithelial differentiation (Fig. 2D). PLAG1 remained negative in all cases. A strong nuclear expression of HMGA2 was found in both epithelial and myoepithelial cells within the inflammatory background (Fig. 2E). A combined staining composed of AE1/AE3 and Ki67 demonstrated AE1/AE3 positivity in both cell populations, while Ki67 staining was restricted to lymphocytic elements, confirming a low proliferative index of the tumour cells (Fig. 2F). Additionally, MDM2 nuclear expression was observed in the epithelial component in one case (Fig. 2G).
Fig. 2
immunohistochemical profile of pleomorphic adenoma characterised by abundant lymphoid stroma. Immunohistochemical profile illustrated positivity CK7 (A, × 20), scattered myoepithelial component positivity throughout the lymphoid stroma with P63 (B, × 20) and SOX10 (C, × 20). EMA expressed in the ductal epithelial cells (D, × 20). HMGA2 presenting a strong nuclear positivity in both epithelial and myoepithelial cells within the inflammatory background (E, × 20), combined staining of AE1/AE3 (brown) and Ki67 (red) demonstrated AE1/AE3 positivity in both cell populations, while Ki67 rarely labelling the epithelial elements (F, × 20). The MDM2 nuclear expression in the epithelial component of case 2 (G, × 20) was observed focally. The in-situ hybridisation with the EBER probe was negative for EBV virus (H, × 20)
In all cases, the FISH analysis found no evidence of MDM2 gene amplification. The MDM2/CEP12 signal ratios were consistently below the amplification threshold of 2, and no case exhibited an increased copy number of the MDM2 gene. These findings displayed the absence of both amplification and copy number gain of MDM2.
In situ hybridisation with the EBER probe
The in situ hybridisation with the EBER probe was negative for EBV virus in all cases, while the technique worked properly as confirmed by a positive external control on the same slide (Fig. 2H).
DNA and RNA Sequencing
All four cases underwent targeted panel DNA and RNA sequencing. No mutation was identified. Three of them harboured an HMGA2::WIF1 fusion (Fig. 3A). The fourth one harboured an HMGA2::RPSAP52 fusion (Fig. 3B).
Fig. 3
Schematic representations of HMGA2 fusions. In the first, second, and fourth cases, the fusion involved exon 3 of the HMGA2 gene and exon 4 of the WIF1 gene (A), while the third case harboured a fusion between exon 3 of HMGA2 and exon 1 of the RPSAP52 gene (B)
Clonality study performed in one case revealed no evidence of a monoclonal B-cell population, supporting the polyclonal nature of the lymphoid infiltrate.
Anzeige
Global Clustering Analysis from Whole RNA Sequencing
Clustering analyses based on gene expression profiling were conducted on the control cohort. The analyses demonstrated that the two investigated cases of PA with abundant lymphoid stroma clustered with all cases of classic lymphadenoma in the control cohort, resulting in a distinct and separate group from other tumour types, including marginal zone lymphomas (Fig. 4A). A dendrogram of a hierarchical clustering was performed and displayed also that the three cases of PA with abundant lymphoid stroma clustered with all cases of classic lymphadenoma in the control cohort, resulting in a distinct and separate group from other tumour types, including marginal zone lymphomas (Fig. 4B).
Fig. 4
Transcriptome based clustering analysis. (A) After nonlinear dimensionality reduction (Uniform Manifold Approximation and Projection [UMAP]), the cases of pleomorphic adenoma with rich lymphoid stroma and lymphadenoma formed a distinct group, demonstrating transcriptomic proximity and a shared gene expression profile. (B) In the dendrogram analysis, the cases of pleomorphic adenoma with rich lymphoid stroma and lymphadenoma formed a distinct group, demonstrating transcriptomic proximity and a shared gene expression profile and had significant differences (p < 0.001)
Seven cases of lymphadenoma were identified, comprising one female and six male patients, their mean age was 71 years (range: 50–77 years). All tumours were located in the parotid gland, and the mean tumour size was 2.8 (range: 1.1–5.0). Histologically, each tumour exhibited classic features of lymphadenoma, characterised by abundant lymphoid stroma interspersed with epithelial ducts and nests, without evidence of chondromyxoid stroma or matrix formation(supplementary Fig. 1). The immunohistochemical analysis was positive for CK7 and p63, whereas it was negative for SOX10 and S100. The Ki67 proliferation index was lower than 10% in all cases. Targeted RNA sequencing did not reveal any HMGA2, PLAG1, or MAML2 gene fusions.
Discussion
In the present study, the transcriptomic analysis of four cases of PA characterised by abundant lymphoid stroma and HMGA2 rearrangements revealed that the lymphoid stroma shared a transcriptomic profile similar to that observed in lymphadenomas. These four cases were identified during expert consultation, underscoring the diagnostic challenge in distinguishing PA from other entities such as lymphadenomas, lymphoepithelial carcinomas, carcinoma ex-pleomorphic adenoma, or even marginal zone lymphomas.
Abundant lymphoid stroma within salivary gland tumours, referred to as tumour-associated lymphoid proliferation (TALP), represents a distinctive histological feature. The underlying cause of this pronounced lymphoid reaction remains uncertain. In some cases, the morphology may closely resemble that of a lymph node, which is one of the many challenges in interpreting salivary gland lesions. [14‐16] This feature can lead to diagnostic pitfalls, particularly misclassification with other lymphoid-rich entities. Among these, marginal zone lymphoma represents the most challenging differential diagnosis; herein, this diagnostic was excluded based on the absence of B-cell clonality. Non-sebaceous lymphadenoma is also among the most common benign salivary gland tumors with prominent lymphoid stroma. However, this diagnosis was excluded in our cases based on the strong HMGA2 immunohistochemical positivity observed in the epithelial component. [17] Lymphoepithelial carcinoma was likewise considered but ruled out due to the negative EBER in situ hybridisation and the positive immunostaining for SOX10, S100, and HMGA2 [18, 19]. In addition, one case exhibited nuclear atypia with a “gear-like” appearance, a feature previously associated with carcinoma ex-pleomorphic adenoma and MDM2 amplification. However, FISH analysis did not demonstrate MDM2 amplification, and the tumour presented a low proliferative index, therefore arguing against malignant transformation [9, 20].
Anzeige
In the presence of a lymphoepithelial proliferation associated with a myxoid and/or chondroid stroma, the diagnosis should point toward a PA, even though two cases in the current series showed no histological features suggestive of such a lesion. In this context, and especially in the absence of a myxoid and/or chondroid stroma,.Accurate diagnosis predominantly relies on immunohistochemistry. Markers such as SOX10, S100, and HMGA2 are valuable to confirm PA and distinguish it from mimicking entities. Taken together, the present findings highlight both the morphological and molecular heterogeneity of PAs and emphasise the potential need for an integrated diagnostic approach combining morphological and immunohistochemicalanalyses to ensure correct classification and optimal management.
Although two previous studies reported an association between TALP and PA, they did not investigate the potential presence of gene fusions in such tumours. [10, 21] The present study is the first to demonstrate TALP in a subset of PAs harbouring an HMGA2 fusion, presenting four cases underscoring the recurrent nature of this alteration within this context. Notably, the HMGA2::WIF1 gene fusion was once again identified in a new subtype of PA, further reinforcing that this rearrangement is not restricted to any particular PA subtype. [22]
While limited by the small number of cases, the independent identification of four cases with this PA subtype across four separate institutions supports both its reproducibility and potential clinical relevance. This consistent recognition in diverse settings strongly suggests that lymphoid stroma-rich, HMGA2-rearranged PAs represent a genuine morphological entity. Based on these distinctive features, we propose the designation “lymphadenoma-like pleomorphic adenoma” for this emerging subtype characterized by the absence of chondromyxoid stroma.
Conclusion
The present study reports four cases of pleomorphic adenoma characterised by abundant lymphoid stroma and HMGA2 rearrangements. Transcriptomic analysis found that the lymphoid stroma in these tumours shares similarities with the profile observed in lymphadenomas. Given these distinctive morphological and molecular features, we propose the designation “lymphadenoma-like pleomorphic adenoma” for this subtype. Further studies with larger cohorts are warranted to better define its clinical and pathological features and to clarify its diagnostic and prognostic implications.
Anzeige
Acknowledgements
The authors thank each institution’s Centre de Ressources Biologiques for their support, specifically Charlene Champin, and the Direction de la Recherche en Santé-HCL for language editing and critical suggestions.
Declarations
Conflict of interest
The authors declare no competing interests.
Ethics approval
The study was approved by the research ethics committee of the Hospices Civils de Lyon (no. 20_5087).
Consent to Participate
No identifying information is included in the case report, and the study meets the waiver criteria set by the institutional review board.
Anzeige
Consent for Publication
For this type of study consent to participate is not required.
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
WHO Classification of Tumours Editorial Board. (2022) Head and Neck tumours [Internet]. Lyon: International Agency for Research on Cancer.Available from:https://tumourclassification.iarc.who.int/chapters
2.
Rito M, Fonseca I (2018) Salivary gland neoplasms: does morphological diversity reflect tumor heterogeneity. Pathobiology 85:85–95CrossRefPubMed
3.
Stenman G (2005) Fusion oncogenes and tumor type specificity–insights from salivary gland tumors. Semin Cancer Biol 15:224–235CrossRefPubMed
4.
Weinreb I (2013) Translocation-associated salivary gland tumors: a review and update. Adv Anat Pathol 20:367–377CrossRefPubMed
5.
Skálová A, Stenman G, Simpson RHW, Hellquist H, Slouka D, Svoboda T et al (2018) The role of molecular testing in the differential diagnosis of salivary gland carcinomas. Am J Surg Pathol 42:e11–e27CrossRefPubMed
6.
Andreasen S, von Holstein SL, Homøe P, Heegaard S (2018) Recurrent rearrangements of the PLAG1 and HMGA2 genes in lacrimal gland pleomorphic adenoma and carcinoma ex pleomorphic adenoma. Acta Ophthalmol 96:e768–e771CrossRefPubMed
7.
Agaimy A, Ihrler S, Baněčková M, Costés Martineau V, Mantsopoulos K, Hartmann A et al (2022) Hmga2-WIF1 rearrangements characterize a distinctive subset of salivary pleomorphic adenomas with prominent trabecular (canalicular adenoma-like) morphology. Am J Surg Pathol 46:190–199CrossRefPubMed
8.
Alsugair Z, Perrot J, Descotes F, Lopez J, Champagnac A, Pissaloux D et al (2024) Characterization of a molecularly distinct subset of oncocytic pleomorphic adenomas/myoepitheliomas harboring recurrent ZBTB47-AS1::PLAG1 gene fusion. Am J Surg Pathol. https://doi.org/10.1097/PAS.0000000000002206CrossRefPubMedPubMedCentral
9.
Alsugair Z, Fieux M, Descotes F, Lopez J, Cordonnier C, Russel J et al (2024) Peculiar nuclear atypia associated with MDM2 gene amplification in carcinoma ex-pleomorphic adenoma harbouring an alteration of HMGA2. Histopathology 85:338–346CrossRefPubMed
10.
Tsuchiya M, Kikuchi Y, Nagao T, Watabe S, Shimizu Y, Oshima Y et al (2024) Pleomorphic Adenoma With Disrupted Biphasic Ductal Structures Attributed to Lymphoid Infiltration: A Case Report. Cureus. https://doi.org/10.7759/cureus.72799CrossRefPubMedPubMedCentral
11.
van Dongen JJM, Langerak AW, Brüggemann M, Evans PAS, Hummel M, Lavender FL et al (2003) Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 concerted action BMH4-CT98-3936. Leukemia 17:2257–2317CrossRefPubMed
Macagno N, Pissaloux D, de la Fouchardière A, Karanian M, Lantuejoul S, Galateau Salle F et al (2022) Wholistic approach: transcriptomic analysis and beyond using archival material for molecular diagnosis. Genes Chromosomes Cancer 61:382–393CrossRefPubMed
14.
Kurian EM, Miller R, Mclean-Holden AL, Oliai BR, Bishop JA (2020) Low molecular weight cytokeratin immunostaining for extrafollicular reticulum cells is an effective means of separating salivary gland tumor-associated lymphoid proliferation from true lymph node involvement. Head Neck Pathol 14:593–597CrossRefPubMed
15.
Auclair PL (1994) Tumor-associated lymphoid proliferation in the parotid gland. Oral Surg Oral Med Oral Pathol 77:19–26CrossRefPubMed
16.
DiGiuseppe JA, Corio RL, Westra WH (1996) Lymphoid infiltrates of the salivary glands. Curr Opin Oncol 8:232–238CrossRefPubMed
17.
Seethala RR, Thompson LDR, Gnepp DR, Barnes EL, Skalova A, Montone K et al (2012) Lymphadenoma of the salivary gland: clinicopathological and immunohistochemical analysis of 33 tumors. Mod Pathol 25:26–35CrossRefPubMed
18.
Whaley RD, Carlos R, Bishop JA, Rooper L, Thompson LDR (2020) Lymphoepithelial carcinoma of salivary gland EBV-association in endemic versus non-endemic patients: a report of 16 cases. Head Neck Pathol 14:1001–1012CrossRefPubMedPubMedCentral
Bishop JA, Nakaguro M, Palsgrove D, Gagan J, Koduru P, Rooper L et al (2025) 12q amplification characterizes a distinctive salivary gland tumor with bizarre myoepithelial atypia. Head Neck Pathol 19:31CrossRefPubMed
21.
Krishnan V, Victor AR, Bose S, Bakkar R (2023) Lymphoid cell rich fine-needle aspirations of the salivary gland: what is the risk of malignancy? Cytojournal 20:11CrossRefPubMedPubMedCentral
22.
Alsugair Z, Lépine C, Descotes F, Lanic M-D, Pissaloux D, Tirode F et al (2024) Beneath HMGA2 alterations in pleomorphic adenomas: Pathological, immunohistochemical, and molecular insights. Hum Pathol 152:105633CrossRefPubMed
Im Jahr 2025 wurde die S2k-Leitlinie Früher Schwangerschaftsverlust im 1. Trimenon veröffentlicht. In dieser Leitlinie werden sowohl für gestörte Frühgraviditäten als auch Schwangerschaften unklarer Lokalisation mit daraus resultierendem Abort …
Lymphome im Kindesalter sind selten – und oft schwer einzuordnen. Die aktuellen Klassifikationen sowie die erstmals erschienene WHO-Klassifikation unterstützen bei der Einteilung. In dieser Übersicht werden die aktuellen Klassifikationen, Biologie und Diagnostik pädiatrischer Lymphome mit Fokus auf seltene indolente Entitäten sowie reaktive, Lymphom-imitierende Läsionen vorgestellt.
Schwerpunkt: Kinderpathologie: Von früher Plazenta bis Neoplasien
Advanced and widespread molecular techniques have deepened our understanding of mesenchymal lesions, revealing considerable overlap among morphologically defined entities now known to be related to protein kinases (PKs). This paradigm shift is …
Benigne Tumoren und Läsionen im Kopfbereich bei Kindern sind selten und können eine diagnostische Herausforderung sein. Im Rahmen dieses Artikels werden ausgewählte seltene kindliche, benigne Läsionen im Kopfbereich vorgestellt mit dem Ziel, die …
