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Thyroid nodules are common, but only 5-15% are cancerous. Fine-needle aspiration cytology is the gold-standard examination for determining the nature of a thyroid nodule, with results reported according to the Bethesda International Classification as updated in 2023. However, 20-30% of nodules are cytologically indeterminate. The challenge here is to avoid unnecessary diagnostic surgery, since 70% of these nodules are benign, although thyroid cancer remains a possibility. Nodule size, growth rate and ultrasonographic or elastographic characteristics can guide management, but have not been shown to have robust diagnostic performance. Thyroid scintigraphy with iodine-123, MIBI and 18F-FDG PET/CT have shown some usefulness, but their efficacy and cost-benefit ratio remain debatable. Artificial intelligence should help clarify the diagnosis of thyroid nodules, but these approaches have yet to be validated in routine clinical practice. Molecular tests performed during aspiration of a thyroid nodule, marketed mainly in the United States, offer robust prospects, as they show good negative predictive values to rule out malignancy when the test is negative, but their high cost limits widespread use in Europe. In France, the development of molecular tests for research purposes is being encouraged. In conclusion, although progress has been made, management of indeterminate thyroid nodules remains complex and relies on a medical decision shared with the patient, pending validation of new diagnostic tools., Competing Interests: Disclosure of interest The authors declare that they have no competing interest., (Copyright © 2025 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Fine-needle aspiration (FNA) cytological analysis fails to confirm the benignity or malignancy of Bethesda III, IV and V thyroid nodules. Molecular tests performed on FNA samples have demonstrated interesting results in improving the diagnosis of these nodules. The aim of this study was to assess the performance of a large next-generation sequencing (NGS) panel in thyroid nodules with indeterminate cytology (Bethesda III, IV and V)., Methods: Retrospective, monocentric study including 121 patients with cytologically indeterminate thyroid nodules (Bethesda III, IV and V) who underwent a routine FNA procedure for molecular testing using the AmpliSeq general cancer NGS panel, with an available final histological diagnosis. The main objective was to estimate the negative predictive value (NPV) of malignancy of the AmpliSeq panel in Bethesda III and IV thyroid nodules. Performance assessment (sensitivity, specificity, positive predictive value (PPV) and NPV) was carried out in the grouped categories III and IV, in the overall cohort and in each Bethesda category. The final histological diagnosis was used as the designated gold standard., Results: Histologically, 86 nodules were benign and 35 nodules were malignant. Molecular analysis yielded a positive result in 40 nodules. Panel performances assessed in the grouped categories Bethesda III and IV demonstrated a 55.0% (95% CI: 31.5; 76.9) sensitivity, a 76.9% (95% CI: 66.0; 85.7) specificity, a 37.9% (95% CI: 25.7; 51.9) PPV and an 87.0% (95% CI: 80.2; 91.7) NPV, considering a 20% prevalence of malignancy., Conclusions: The performances of the AmpliSeq panel are promising; however, the NPV is not sufficient to avoid diagnostic surgery in cytologically indeterminate thyroid nodules., Significance Statement: Different ancillary molecular tests have been marketed in the USA and are integrated into the management of thyroid nodules with indeterminate cytology. Unfortunately, none of these molecular tests are currently available in France and clinicians lack effective tools for the management of these nodules. The aim of this work was to assess the performance of a large general-cancer targeted NGS panel in a series of thyroid nodules with indeterminate cytology (i.e. Bethesda III and IV categories and, to some extent, the Bethesda V category), managed in a French university medical center referral for thyroid tumors.

Objectives: Tumor molecular genotyping plays a key role in improving the management of advanced thyroid cancers. Molecular tests are classically performed on Formalin-Fixed Paraffin-Embedded (FFPE) carcinoma tissue. However alternative molecular testing strategies are needed when FFPE tumoral tissue is unavailable. The objective of our study was to retrospectively assess the performance of targeted DNA and RNA-based Next Generation Sequencing (NGS) on the fine needle aspirate from thyroid cancer cervical recurrences to determine if this strategy is efficient in clinical practice., Design/methods: A retrospective study of 33 patients who had had DNA and/or RNA-based NGS on ultrasound (US)-guided fine needle aspirates of cervical thyroid cancer recurrences in our Department from July 2019 to September 2022., Results: In total, 34 DNA and 32 RNA-based NGS analyses were performed. Out of the 34 DNA-based NGS performed, 27 (79%) were conclusive allowing the identification of an oncogenic driver for 18 patients (53%). The most common mutation (n = 13) was BRAF c.1799T>A. Out of the 32 RNA-based NGS performed, 26 were interpretable (81%) and no gene fusion was found. The identification of a BRAFV600E mutation was decisive for one patient in our series, who was prescribed dabrafenib and trametinib., Conclusions: NGS performed on fine needle aspirates of neck lymph node metastases enabled the identification of an oncogenic driver alteration in 53% of the cases in our series of advanced thyroid cancer patients and could significantly alter patient management.

The salivary glands cytology is one of the most challenging area in cytopathology because of the wide diversity of benign and malignant tumors also because of their heterogeneity. However, fine needle aspiration cytology, with magnetic resonance imaging, represents a first-line examination to guide a possible surgical procedure and its extent. An accurate diagnosis of a specific tumor is sometimes difficult to assess in cytology. Also, as for gynecological, thyroid or urinary cytologies, a panel of experts met to develop a cytological classification of salivary gland lesions associated with a risk of malignancy and management proposals. The Milan System for Reporting Salivary Gland Cytopathology was published in 2018. The French Society of Clinical Cytology (SFCC) offers here an official summarized French version oh this terminology and recommends its use., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objective: Many systems for risk stratification of thyroid nodule with ultrasound (US) have been proposed and the EU-TIRADS issued by the ETA in 2017 was the last to have been published. The present study was undertaken to evaluate whether the malignancy risk of each category corresponded to the given range of the guidelines and assess the diagnostic value of EU-TIRADS in a multi-institutional trial with histology as gold standard., Design: Three institutions in Switzerland, France and United Kingdom shared this retrospective study. Enrolment period was 2013-2017. Included were patients who had undergone surgery with a detailed preoperative thyroid US., Methods: Cancer risk was calculated for each EU-TIRADS score. Predictivity tests were estimated. Nonparametric statistical analysis was used., Results: The final series included 1058 nodules of which 257 (24.3%) carcinomas. Nodules were classified as EU-TIRADS 2, 3, 4 and 5 in 6.7, 46.4, 26.2 and 20.7%, respectively. Cancer prevalence was 1.4, 3.5, 17 and 87.7% in classes 2-5, respectively (P < 0.0001). EU-TIRADS 5 had a significantly higher cancer rate than the other summed categories (7.7%; P < 0.0001) with OR 84.7. When EU-TIRADS 4 and 5 were combined, 93% sensitivity and 97% NPV were found and findings of the three institutions were quite similar. Using the recommended criteria for FNA negative predictive value was 90.9%., Conclusions: The cancer rate was within or close to the given range described in the EU-TIRADS guidelines. The diagnostic value was satisfactory. The results were similar in the three institutions participating in the study., (© 2019 John Wiley & Sons Ltd.)

Context: The rate of thyroid cancer is increasing in France, as well as concerns about overdiagnosis and treatment., Objectives: To examine the care pathway of patients who undergo thyroid surgery in France and detect potential pitfalls., Design: A large observational study based on medical reimbursements, 2009-2011., Setting: Data from the Sniiram (National Health Insurance Information System)., Patients: Patients with thyroid surgery in 2010, classified into 4 groups: thyroid cancer, benign nodule, goitre or multiple nodules, other (hyperthyroidism, head-neck cancer)., Main Outcome Measures: Medical investigations during, prior and after thyroidectomy., Results: A total of 35 367 patients underwent surgery (mean age 51 years, 80% women): 17% had a reported diagnosis of thyroid cancer, 20% benign nodule, 38% goitre or multiple nodules and 25% another diagnosis. The ratio of thyroidectomies with cancer over thyroidectomies with benign nodule was 0.8 and varied across regions. In the year preceding surgery, 82% of patients had an investigation by thyroid ultrasonography, 21% thyroid scintigraphy, 34% fine-needle aspiration cytology, 40% serum calcitonin assay and 54% serum calcium assay. In the following year, all patients with total thyroidectomy and 44% of patients with partial thyroidectomy and a diagnosis of benign nodule were taking thyroid hormone therapy. 100 patients had been reoperated for a compressive haematoma and 63 died during the first month, half of whom had been operated for cancer. Mean rates of recurrent laryngeal nerve injury and hypocalcaemia (requiring blood tests plus treatments within 4-12 months) were estimated at 1.5% and 3.4%, respectively, and were higher in the cancer group (2.3% and 5.7%)., Conclusions: This almost nationwide study demonstrates the suboptimal management of patients prior to thyroidectomy in France. It suggests overdiagnosis and potential harms to patients, and calls for a review of the relevance of thyroidectomy, particularly with regard to microcancers., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: To evaluate prospectively the diagnostic accuracy of the thyroid imaging reporting and data system (TI-RADS) and its interobserver agreement and to estimate the reduction of indications of fine-needle aspiration biopsies (FNABs)., Design: A prospective comparative study was designed., Methods: In 2 years, 4550 nodules in 3543 patients were prospectively scored using a flowchart and a six-point scale and then submitted to US-FNAB. Results were read according to the Bethesda system. Histopathological results were available for 263 cases after surgery. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value, and accuracy were calculated for the gray-scale score, elastography, and a combination of both methods. Interobserver agreement was calculated using the kappa statistic. The reduction in the number of FNABs was estimated., Results: When compared with cytopathological results, sensitivity, specificity, NPV, and accuracy were 95.7, 61, 99.7, and 62% for the TI-RADS gray-scale score; 74.2, 91.1, 98, and 90% for elastography; and 98.5, 44.7, 99.8, and 48.3% for a combination of both methods respectively. When compared with histopathological results, the sensitivity of the gray-scale score, elastography, and a combination of both methods were 93.2, 41.9, and 96.7% respectively. Interobserver agreement for the six-point scale and the recommendation for biopsy were substantial (κ value=0.72 and 0.76 respectively). The reduction in the number of FNABs was estimated to be 33.8%., Conclusion: The TI-RADS score has high sensitivity and NPV for the diagnosis of thyroid carcinoma. A hard nodule should always be considered as suspicious for malignancy but elastography cannot be used alone. Combination of elastography with gray-scale can be used to improve sensitivity or specificity. Interobserver agreement and decrease in unnecessary biopsies are significant.

The aim of this study was to evaluate the T-cell receptor (TCR) Vbeta repertoire in the two main histological subtypes of nodal non-anaplastic peripheral T-cell lymphoma: Not Otherwise Specified (NOS) and angioimmunoblastic lymphoma (AIL). Frozen lymph node tissues of eight NOS and six AIL were analyzed. A reverse transcriptase polymerase chain reaction (RT-PCR) was carried out to assess the expression of the 24 Vbeta gene families. Our study showed a broad TCR Vbeta repertoire in AIL and NOS, with a slight increase in the number of Vbeta families in AIL (16 vs 10 on agarose gels). Nevertheless, there was a clear difference in four cases. A predominant Vbeta family was observed in two NOS, whereas no predominant Vbeta family was observed in the AIL. Two AIL showed the whole Vbeta repertoire, whereas it was never observed in NOS. This pattern may help to categorize these histopathological entities and further suggests a differential T-cell response. These results show that numerous reactive T-cells are present both in AIL and NOS. Possibly, they play a role in the growth of these lymphomas.

The clinicopathologic case of a 69-year-old-female patient with a big caruncular melanoma is reported. Tumor was excised surgically and underwent external conventional radiation therapy with no recurrence two years later. Histopathology endorsed the clinical diagnosis and thickness of the tumor measured 5.5 mm. The bad prognosis of the caruncular location was reinforced by the tumor thickness. A better knowledge of conjunctival melanomas characteristics might allow an earlier diagnosis and a better prognosis as irradiation following surgical treatment appears efficient on unifocal limited melanomas.

We report the case of a 70-year-old patient who presented with Mooren's ulcer in her right eye following extracapsular cataract extraction combined with trabeculectomy. She was successfully treated by a sclerocorneal graft combined with a large conjunctival resection. Clinical and histological features, and therapeutic outcomes are discussed and compared to previously published data.

Rearrangement of the bcl-2 gene at the MBR (major breakpoint region) locus with the immunoglobulin heavy-chain joining region has been reported in a high proportion of follicular lymphomas. This rearrangement has also been reported in very few normal B cells of the blood, tonsils, follicular lymphoid hyperplasia (FLH) of the lymph nodes. HIV infection is often associated at the onset of the disease with FLH, but the presence of rearranged bcl-2 B cells in these lymph nodes has not been described. In using a standard PCR assay with Southern blot or a semi-nested PCR on 48 cases of FLH, we demonstrated that there were a few bcl-2 rearranged B cells in HIV FLH, at almost the same level as that in non-HIV-related FLH. The usual absence of bcl-2 rearrangement in the HIV-associated B-cell lymphomas suggests that the bcl-2 oncogene in the rearranged B cells of FLH is not cooperating with other oncogenes during HIV lymphomagenesis.

Using Southern blotting for the diagnosis of clonality in peripheral T-cell lymphomas (PTCLs), analysis of the T-cell receptor (TCR) gamma gene rearrangement was shown to be more informative than that of the TCR beta gene rearrangement. In order to amplify every VJ gamma rearrangement, a polymerase chain reaction (PCR) procedure using newly designed GC-clamp primers has been developed. All primers can be mixed in a single multiplex PCR. PCR products are analysed by denaturing gradient gel electrophoresis (DGGE), providing tumour-specific imprints inasmuch as the procedure characterizes N sequence polymorphism at the VJ junctions. In a series of 30 PTCL cases, the PCR procedure demonstrated 27 cases to be clonally rearranged and failed in three cases. PCR was more accurate than Southern blotting, showing 47 rearranged gamma alleles, four of which were undetectable on the Southern blot. When lymphomas were studied at different sites and at relapse, the DGGE pattern remained unchanged. In PTCL, the proposed PCR is helpful for the diagnosis and staging of the disease and should improve the follow-up monitoring. The undetectability of clonal rearrangements in a few cases is discussed in the light of concepts of lymphomagenesis and T-cell differentiation.

The authors report the case of a 35 year-old polynesian male admitted to hospital with a diagnosis of myeloma. Bone marrow study showed an intense plasmocytosis, mature, Marshalko type. A new physical examination disclosed polyadenopathies and the lymph node biopsy showed lymph node modifications typical of plasma cell type Castleman's disease. At the same time, the polytypic profile of the bone marrow plasmacytosis and of the hypergammaglobulinemia was demonstrated, thus confirming the reactive state of the plasmacytosis, due to Castleman's disease. Such massive, reactive plasmacytosis belong to one of the various pathological features of multicentric Castleman's disease. Thus, this disease should belong to the etiologic diagnosis of intense bone marrow plasmacytosis and be distinguished from multiple myeloma, sometimes associated to Castleman's disease, especially in case of POEMS syndrome.

The digestive tract is the most frequent site of extranodal malignant lymphomas. Lymphomatous polyposis is one of them, and its prognosis is poor. It corresponds to a digestive localization of mantle cell lymphoma. In most cases it is discovered following digestive symptoms. However, in some cases this digestive malignant lymphoma may be asymptomatic. Thus complete endoscopic exploration of the digestive tract including biopsies is necessary for every patient presented with lymph node mantle cell lymphoma.

The recombination events of the gamma and beta T-cell receptor (TCR) loci were analysed in a series of 39 peripheral T-cell lymphomas (PTCLs) in association with the expression of TCR chains. In TCR alpha beta PTCLs, 22/23 cases showed a gamma-gene rearrangement while only 18/23 showed a concomitant beta-gene rearrangement. The germline configuration of the beta locus was found in angiommunoblastic lymphadenopathy and lymphoepithelioid lymphomas. Three gamma delta PTCLs rearranged both gamma and beta genes. TCR silent PTCLs showed three different patterns of gamma- and beta-gene rearrangements. Three cases were in germline configuration for both loci; five cases had a rearranged gamma and a germline beta locus; and five cases had the two loci rearranged. Regarding the variable genes in the gamma-rearranged alleles, members of the V gamma I subgroup were the most frequently presented (39/50), followed by V gamma II, V gamma III, and V gamma IV (9/50, 1/50, and 1/50, respectively). Joining segment usage was as follows: J1 or J2 (32/50), JP1 or JP2 (17/50), and JP (1/50). Taken together, these data demonstrate that the gamma locus is more frequently rearranged whatever the TCR expression. The gamma-locus analysis provides a better diagnostic yield than the beta locus in the study of PTCL clonality.

Thrombotic microangiopathy has recently been documented in association with human immunodeficiency virus infection. The authors present the clinical laboratory, histologic and electron microscopic kidney study features of one case of thrombotic microangiopathy revealing human immunodeficiency virus infection. They also review 28 previously reported cases of thrombotic microangiopathy associated with human immunodeficiency virus infection and discuss different pathogenic hypothesis which could be involved in genesis of human immunodeficiency virus-associated thrombotic microangiopathy.

The authors describe the case of a 32 year-old woman with a congenital neurofibromatosis referred for excision of a painful subcutaneous nodule of the left popliteal space. The histological study showed a tumor displaying a biphasic pattern made of fascicles of benign spindle cells admixed with mucinous epithelium. Immunohistochemistry (cytokeratin X, ECA X) and electron microscopy helped to prove the true epithelial nature of the glandular components. Glandular schwannoma has rarely been described, especially in a benign histological pattern; this one has never been reported in association with Von Recklinghausen's disease. The histogenesis of the glandular schwannoma remains uncertain.