“indeterminate significance”

A CT scan of the chest demonstrated punctate lung nodules of indeterminate significance.

Cytological diagnosis from FNA samples typically follows the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), categorizing nodules into clearly benign (Bethesda II) and malignant (Bethesda VI), as well as categories with indeterminate significance, notably Bethesda III (atypia of undetermined significance [AUS]) and Bethesda IV (follicular neoplasm [FN]) [ 4 , 5 ].

Clonal hematopoiesis of indeterminate significance Clonal hematopoiesis of indeterminate potential (CHIP) is a hematologic disorder characterized by age-related acquisition of mutations in hematopoietic stem cells [ 65 ], leading to a clonal myeloid cell population that is associated with increased systemic inflammation [ 66 ].

2 ). A CT scan of the abdomen and pelvis 2 months prior to hospital admission found the right upper quadrant lesion most likely attributable to scar tissue, of clinically indeterminate significance.

9 Our patient’s case is unusual in that, based on gene sequencing, laboratory, and clinical findings, she is a compound heterozygote for a previously unreported nonsense mutation and a missense mutation of indeterminate significance ( Figure 1 ).

americanum ticks is currently of indeterminate significance to human health.

Although of indeterminate significance, WNV has been detected in ticks (Hyalomma marginatum marginatum nymph) [ 16 ].

Even though there is growing evidence that clonal hematopoiesis of indeterminate significance may indeed be more prevalent in AID-patients compared to the general population, this need not necessarily be true compared to cancer patients. 125 , 126 The increased preexisting genomic hits and germline mutations in this patient group may further confound the extrapolation. 127 Conversely, the integration of genetic sequences into the host genome—even when restricted to T cells and despite advances in vector safety—carries the potential risk of insertional mutagenesis, which may drive malignant transformation.

There were also sub-centimeter enhancing foci in the liver, of indeterminate significance.

The laboratory reported that the variant was of “indeterminate significance” and yet that it may increase cancer risk.

Magnetic resonance imaging (MRI) of the brain with contrast similarly showed no acute intracranial findings but did reveal a new punctate enhancement in the left medial orbital gyrus of indeterminate significance and inflammatory changes within the paranasal sinuses.

Routine parafibromin stain in maxillary and mandible masses amid HJT is currently incompletely implemented in daily practice, having yet an indeterminate significance.

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Cytogenetics and molecular screening revealed abnormal karyotype in two patients (of 16 available [12.5%]; one patient with del(Y) and one patient with dup(2)) and a mutation in DNMT3A (p.L373V, variant allele frequency [VAF]: 10.3%) in one patient (of 12 available [8.3%]) consistent with the presence of clonal haematopoiesis of indeterminate significance (CHIP) or clonal cytopenia of undeterminate significance.

The cytology included were: Atypical squamous cells of indeterminate significance (ASC-US); atypical squamous cell of undeterminated significance which can not be excluded from high-grade intraepithelial lesions (ASC-H); low-grade squamous intraepithelial lesion (LSIL); high-grade squamous intraepithelial lesion (HSIL); squamous carcinoma; atypical glandular cells of undetermined significance (AGC-NOS); atypical glandular cells favor neoplasic (AGC-H); and atypical cells with undertemined origin (ACs) ( Table 1 ).

Clonal heterogeneity of indeterminate significance [ 30 , 31 ] has been described and although it doesn’t warrant immediate changes to patient care, it is being monitored carefully in a variety of settings.

The above-mentioned categories are defined as follows: TIR1 - inadequate or cystic-hemorrhagic sample-IN; TIR2 - non-neoplastic lesion (BL); TIR3 - follicular/indeterminate neoplasm including atypical cells of indeterminate significance (FN/AUS); TIR4 - suspicious for malignancy (SM); and TIR5 - positive for malignancy (PM).

It is important to have baseline comprehensive tumor based genetic testing to avoid erroneous diagnoses from clonal hematopoiesis of indeterminate significance.

Hence, the number of mutations considered of unknown or indeterminate significance was high.

Other studies, however, draw attention to specific drawbacks, such as the difficulty in identifying variants of indeterminate significance, with changes in variant interpretation up to 43 % [66] .

In terms of laterality, 3.2% of patients demonstrated bilateral nodule of indeterminate significance, while 3.9% demonstrated a unilateral pulmonary nodule.

The analysis revealed 4 mutated genes, comprising 1 pathogenic mutation and 3 mutations of indeterminate significance.

The patient was identified to have a heterozygous variant of indeterminate significance for neurogenic differentiation factor 1 ( NEUROD1 ) ( NM_002500.4 ), c.514C > T, p.(Leu172Phe).

This showed a 2 mm round right apical lung nodule of indeterminate significance.

The role of MEG also extends to the identification of a probable contributory lesion in MRIs with multiple lesions, or in lesions of indeterminate significance ( 54 ).