The guidelines for the workup of thyroid nodules have been established in adult populations and secondarily applied to paediatric populations. In particular, The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is commonly applied to both adult and paediatric thyroid nodules. However, as paediatric nodules have distinct molecular drivers and behavioural trajectories, there is renewed interest in diagnostic and management strategies that are paediatric specific. Here, we review key differences between paediatric and adult thyroid cancer and recent literature evaluating the use of TBSRTC in paediatric populations.

BACKGROUND: Limited data exist on assessing the risk of active tuberculosis (TB) in immunocompromised individuals during screening for latent tuberculosis infection (LTBI).
OBJECTIVE: To assess the risk of progression to active TB for indeterminate interferon-γ release assays (IGRA) results in immunocompromised individuals during screening for LTBI.
METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched without start date or language restrictions on 18 April 2023.
METHODS: Cohort study or randomized controlled trials that investigated the risk of progression to active TB for indeterminate IGRA during LTBI screening.
METHODS: Immunocompromised individuals. TEST: IGRA (T-SPOT.TB and QuantiFERON).
UNASSIGNED: None.
UNASSIGNED: A modified version of the Newcastle-Ottawa Scale.
UNASSIGNED: Fixed effects meta-analysis was used to obtain two pooled risk ratios (RRs). RR-ip represented disease progression rate in untreated individuals with indeterminate IGRA versus positive IGRA. RR-in represented disease progression rate in untreated individuals with indeterminate IGRA versus negative IGRA.
RESULTS: Among the 5102 identified studies, 28 (14 792 immunocompromised individuals) were included. The pooled RR-ip and RR-in for cumulative incidence were 0.51 (95% CI, 0.32-0.82; I2 = 0%) and 2.94 (95% CI, 1.78-4.85; I2 = 0%), respectively. In addition, 11 studies reporting person-year data were included to verify the reliability of cumulative incidence results. The pooled RR-ip and RR-in for person-year incidence were 0.40 (95% CI, 0.19-0.82; I2 = 13%) and 2.67 (95% CI, 1.24-5.79; I2 = 23%), respectively.
CONCLUSIONS: Indeterminate IGRA results in immunocompromised individuals may represent an intermediate risk of progression to active TB, with half the risk for positive results and three times for negative results. Proper follow-up and management of patients with indeterminate results are crucial for mitigating progression risk and improving patient outcomes.

We aimed to evaluate the indeterminate rate of interferon gamma release assays (IGRAs) in the detection of latent tuberculosis infection (LTBI).
On 15 November 2022, we searched the PubMed® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, the Netherlands), and Cochrane Library databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two investigators independently extracted the study data and assessed their quality using a modified quality assessment of diagnostic accuracy studies (i.e., QUADAS-2) tool. A random-effects model was used to calculate pooled results.
We included 403 studies involving 486,886 individuals and found that the pooled indeterminate rate was 3.9% (95% CI 3.5%-4.2%). The pooled indeterminate rate for QuantiFERON®-TB (QFT) was similar to that for T-SPOT®.TB (T-SPOT) [odds ratio (OR) = 0.88, 95% CI 0.59-1.32]; however, the indeterminate rate for a new generation of QFT (QFT-plus) was lower than that of T-SPOT (OR = 0.24, 95% CI 0.16-0.35). The indeterminate rate in the immunocompromised population was significantly higher than that in healthy controls (OR = 3.51, 95% CI 2.11-5.82), and it increased with the reduction of CD4+ cell count in HIV-positive patients. Children\'s pooled indeterminate rates (OR = 2.56, 95% CI 1.79-3.57) were significantly higher than those of adults, and the rates increased as the children\'s age decreased.
On average, 1 in 26 tests yields indeterminate IGRA results in LTBI screening. The use of advanced versions of the QuantiFERON-TB assay (QFT-plus), may potentially reduce the occurrence of an indeterminate result. Our study emphasizes the high risk of immunosuppression and young age in relation to indeterminate IGRA, which should receive more attention in the management of LTBI.
PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020211363, CRD42020211363.

Objective We report the results of a retrospective five-year study within a veteran population aimed at correlating abnormal thyroid fine-needle aspiration (FNA) diagnosis with associated molecular testing to the histology of the surgical resection. Methods A retrospective analysis of abnormal thyroid FNAs with associated molecular testing and surgical outcome was conducted from January 1, 2015 to December 31, 2020. Aspirates were classified using the Bethesda system for reporting thyroid cytopathology, including atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), suspicious for malignancy (SM), and malignant. Pertinent data, including patient demographics, imaging, and ancillary testing were reviewed. A thyroid cancer mutation panel assessing the most common mutations and rearrangements associated with neoplasia was utilized. The results of molecular testing were directly compared and correlated with final cytological and histological diagnosis. Results A total of 1850 thyroid aspirates were performed, 200 of which were given an abnormal cytologic diagnosis. Thirty-six samples were submitted for molecular testing and subsequent surgical follow-up. Four were called malignant on cytology. 32 were placed in an indeterminate category (89%). Within indeterminate cases: 53% exhibited positive molecular mutations (n=17), 34% no mutation detected (n=11), and 13% insufficient quantity for testing (n=4). Upon surgical resection in the mutation-positive group: 18% had no malignancy (n=3), and the remaining 82% were positive for malignancy (n=14). Mutations in the histologically malignant group included: 57% BRAF (n=8), 21% NRAS (n=3), 7% HRAS (n=1), 7% KRAS (n=1), and 7% PAX8/PPAR gamma (n=1). In indeterminate cases with no mutation detected, 10 cases were found to be benign, and one case of malignancy was diagnosed. The probability of indeterminate diagnosis in combination with no mutation yielded a 91% chance of benign entity and 9% chance of malignancy. We demonstrated 93% sensitivity and 91% negative predictive value (NPV) for the risk of malignancy in indeterminate cytology specimens with ancillary molecular testing. There was 77% specificity and 82% positive predictive value (PPV) for our data set. Conclusions In indeterminate samples, the detection of a mutation was highly predictive of malignancy and a strong indicating factor for surgery with a high sensitivity and NPV. Molecular testing refined or established the diagnosis in 89% of the cases. Our results indicate that molecular testing of thyroid nodules enhances the accuracy of FNA cytology and the subsequent surgical outcome.

BACKGROUND: Indeterminate pulmonary nodules (IPNs) are frequently encountered on staging computed tomography (CT) in colorectal cancer (CRC) patients and they create diagnostic dilemmas. This systematic review and pooled analysis aims to estimate the incidence and risk of malignancy of IPNs and provide an overview of the existing literature on IPNs in CRC patients.
METHODS: EMBASE, Pubmed and the Cochrane database were searched for papers published between January 2005 and April 2020. Studies describing the incidence of IPNs and the risk of malignancy in CRC patients and where the full text was available in the English language were considered for inclusion. Exclusion criteria included studies that used chest X-ray instead of CT, liver metastasis cohorts, studies with less than 60 CRC patients and reviews.
RESULTS: A total of 18 studies met the inclusion criteria, involving 8637 patients. Pooled analysis revealed IPNs on staging chest CT in 1327 (15%) of the CRC patients. IPNs appeared to be metastatic disease during follow up in 16% of these patients. Regional lymph node metastases, liver metastases, location of the primary tumour in the rectum, larger IPN size and multiple IPNs are the five most frequently reported parameters predicting the risk of malignancy of IPNs.
CONCLUSIONS: A risk stratification model for CRC patients with IPNs is warranted to enable an adequate selection of high risk patients for IPN follow up and to diminish the use of unnecessary repetitive chest CT-scans in the many low risk patients.

The recent introduction of noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) in the World Health Organization classification of thyroid tumors has significantly modified the risk of malignancy of cytological diagnoses. In fact, while this tumor was previously classified as a carcinoma (the encapsulated, noninvasive form follicular variant of papillary thyroid carcinoma), it is now considered a neoplasm with low malignant potential. Given that the cytological features of NIFTP are not specific and overlap with other pathologic entities, there is no specific cytological diagnostic category for NIFTP. To obtain more robust information about the cytological findings associated with NIFTP, published articles were systematically reviewed, and a meta-analysis of the data was conducted.
The review was conducted according to PRISMA guidelines. A comprehensive literature search of the PubMed/MEDLINE and Scopus databases was conducted using a combination of terms \"noninvasive,\" \"encapsulated,\" \"follicular variant,\" \"NIFTP,\" and \"thyroid cancer.\" The search was updated to June 2018, and references of the retrieved articles were also screened. Only original articles reporting the classification of histologically proven NIFTPs with cytological findings according to The Bethesda System for Reporting Thyroid Cytopathology were eligible for inclusion.
The literature search revealed 117 articles, of which 15 were included in the study. All studies were retrospective. A total of 915 NIFTP cases were retrieved. The incidence of cases cytologically classified according to the Bethesda system was as follows: non-diagnostic 3%, benign 10%, atypia of undetermined significance or follicular lesion of undetermined significance 30%, follicular neoplasm or suspicious for a follicular neoplasm 21%, suspicious for malignancy 24%, and malignant 8%. Mild heterogeneity between the studies was found. Publication bias was absent.
This meta-analysis shows that the cytological diagnoses associated with NIFTP by fine-needle aspiration cytology includes a wide spectrum of findings. The majority of cases are cytologically indeterminate, and the remainder may be read as non-diagnostic, benign, or malignant. In order to develop an accurate presurgical diagnosis of these cases, further cytological and/or molecular characteristics need to be identified.

A 34-year-old Japanese man presented with an indolent nodule on the right flank. Computed tomography of the chest and abdomen demonstrated a large nodule measuring 55 mm × 50 mm in the abdominal oblique muscle layer of the right flank, and several small nodules were seen in the muscle layer throughout the body and subcutaneous tissue of the lower abdomen. 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography revealed nodular lesions in the bilateral parotid glands, bilateral cervical lymph nodes and lower lobe of the right lung. Intermittently, ground-glass shadows developed in the bilateral lungs. Histologically, sheet-like nodules in the abdominal oblique muscle layer and parotid gland were composed of large polygonal cells with convoluted nuclei and ample eosinophilic cytoplasm. Several lymphocytes and considerable eosinophils were intermingled. Lung biopsy demonstrated an inflammatory infiltrate of lymphocytes and considerable eosinophils in the alveoli. Immunohistochemically, polygonal cells were positive for S100 protein and CD1a, but negative for langerin and BRAFV600E . Some cells were positive for CD68. Electron microscopy demonstrated histiocytic cells with phagosomes and interdigitating processes. However, no Birbeck granules were observed. Eosinophilia was seen in the peripheral blood. Multifocal nodules and ground-glass shadows gradually diminished following systemic administration of oral prednisolone. We describe a case of indeterminate dendritic cell neoplasm with multifocal involvement of the muscle, subcutis, lymph node and parotid gland accompanied by chronic eosinophilic pneumonia that was successfully treated by systemic steroid therapy. Neither muscular nor parotid indeterminate dendritic cell neoplasms accompanied by eosinophilic pneumonia have been previously reported.

We describe the extent of and variables associated with irreproducible HIV-1 PCR positive results within South Africa\'s Early Infant Diagnosis (EID) program from 2010 to 2015 and propose criteria for differentiating indeterminate from clearly positive results using the COBAS® AmpliPrep/COBAS® TaqMan HIV-1 Qualitative Test version 2.0 (CAP/CTM Qual v2.0). Fourteen percent of specimens with an instrument-positive result that were repeat-tested yielded a negative result for which cycle threshold (Ct) proved to be the only predictive variable. A Ct <33.0 was found to be the most accurate threshold value for differentiating clearly positive from irreproducible cases, correctly predicting 96.8% of results. Among 70 patients with an irreproducible positive result linked to a follow up HIV-1 PCR test, 67 (95.7%) were negative and 3 (4.3%) were instrument-positive. Criteria differentiating clearly positive from indeterminate results need to be retained within EID services and infants with indeterminate results closely monitored and final HIV status determined.

Italian consensus for the classification and reporting of thyroid cytology was published in 2014 and it has been used in almost all Italian institutions. To date, there are not solid data on the reliability of Italian consensus for the classification and reporting of thyroid cytology in classifying low and high risk indeterminate nodules (Tir 3A and Tir 3B, respectively). Here, we reviewed and meta-analyzed the results of published articles to obtain evidence-based information on this topic.
A comprehensive literature exploration of online databases was conducted by searching all published papers citing Italian consensus for the classification and reporting of thyroid cytology. The search was updated until June 2017, and references of the retrieved articles were also screened. Only original articles reporting histologic follow-up of nodules cytologically classified as Tir 3A and Tir 3B were eligible for inclusion.
The literature search revealed 62 articles and six of these were eligible for the study. All papers were retrospective and published very recently. Overall, 423 indeterminate lesions, of which 180 Tir 3A and 243 Tir 3B, were found. Of these, 29 cancers were recorded in Tir 3A and 127 in Tir 3B. The pooled rate of malignancy was 17% (95% CI = 12 to 22%) in Tir 3A and 52% (95% CI = 46 to 58%) in Tir 3B. No significant publication bias was evident.
Italian consensus for the classification and reporting of thyroid cytology 2014 shows high reliability in discriminating indeterminate lesions at low risk of malignancy from those at high risk.