Search Results (67)

Background/Objectives: Ciliated epithelial change in endometrial lesions is a recognized morphologic finding, but its immunophenotypic correlates and biological significance remain insufficiently defined. We investigated whether endometrial lesions with ciliated epithelial change show reproducible immunohistochemical alterations across benign, premalignant, and malignant diagnostic categories. Methods: We performed a retrospective immunohistochemical study of 315 formalin-fixed paraffin-embedded eutopic uterine endometrial specimens (no endometriotic/ectopic lesions included) collected between 2019 and 2024 and distributed equally across seven diagnostic categories (n = 45 each): normal endometrium, endometrial polyp, hyperplasia with cystic/disordered glands, hyperplasia with crowded glands, atypical hyperplasia/EIN, endometrioid carcinoma, and serous carcinoma. Marker expression was quantified by digital image analysis and compared between lesions with and without ciliated epithelial change, including lesions with ciliated epithelial change showing cytological atypia. Results: Ciliated epithelial change (CEC) was identified in 86/315 cases (27.3%), including 41 cases (13.0%) with atypical CEC. In benign categories, lesions with CEC showed lower E-cadherin expression and higher β-catenin expression, including more frequent nuclear β-catenin localization. In carcinomas, these patterns were not recapitulated and instead showed an opposite or attenuated profile, supporting a context-dependent rather than linear model. Vimentin was consistently reduced in lesions with CEC across diagnostic categories. p53 and CD44 showed heterogeneous findings and were less informative than the adhesion- and phenotype-related markers. Conclusions: Endometrial lesions with CEC show reproducible, context-dependent immunohistochemical alterations, most consistently involving E-cadherin, β-catenin, and vimentin. In particular, nuclear β-catenin reactivity in this setting should not be interpreted as evidence of canonical Wnt-pathway activation in the absence of CTNNB1 sequencing or validated downstream readouts, and the carcinoma findings cannot be assigned to a specific TCGA/ProMisE molecular subgroup using immunohistochemistry alone. The observations should therefore be regarded as exploratory and warrant validation in studies incorporating molecular classification, direct ciliogenesis markers (FOXJ1, acetylated α-tubulin, basal body markers), and outcome data. Full article

Phyllodes tumours (PTs) of the breast are rare fibroepithelial neoplasms with potentially aggressive behaviour, characterised by rapid growth, a significant risk of local recurrence, and occasional metastatic spread. Optimal management remains controversial, particularly regarding surgical margins, adjuvant radiotherapy, and the relevance of molecular markers in predicting tumour behaviour. A PRISMA 2020-guided qualitative systematic review was conducted of studies published between January 2000 and December 2024 in PubMed/MEDLINE, Scopus, and Web of Science. Eligible studies included malignant PTs of the breast and addressed at least one of the following domains: molecular pathology, surgical margins and local recurrence, adjuvant radiotherapy, or predictors of recurrence and metastasis. A clinical case of malignant PT treated at our institution is presented as an illustrative study. Thirty-four studies met the inclusion criteria. Evidence suggests that margin status, stromal proliferative activity, and selected molecular markers influence recurrence risk. Several retrospective studies suggest that adjuvant radiotherapy may improve local control in selected high-risk malignant PTs, although the evidence remains heterogeneous, retrospective, and potentially affected by treatment-selection bias, and no consistent survival benefit has been demonstrated. Molecular alterations, including MED12 mutations, TERT promoter mutations, TP53 alterations, and increased Ki-67 expression, have been associated with tumour progression and aggressive behaviour. A 44-year-old woman presented with a 2.4 cm left breast mass on radiological examination. Lumpectomy revealed a malignant PT with stromal hypercellularity, nuclear atypia, and a mitotic index of 20/10 HPF with close margins. Immunohistochemistry showed positivity for CD99, Bcl-2, and CD34 with a Ki-67 proliferation index of 20%. The patient underwent wide local re-excision followed by adjuvant radiotherapy (60 Gy), and at 24-month follow-up, the patient remained disease-free. Evidence synthesis highlights the importance of complete surgical excision, multidisciplinary management, and consideration of adjuvant radiotherapy in selected malignant PTs. Emerging molecular profiling may contribute to improved biological understanding and future risk stratification of malignant PTs, although its routine clinical utility remains to be validated in prospective studies. Full article

Background/Objectives: Trichoblastoma is a benign follicular adnexal tumor that typically arises on the head and neck. Large variants at atypical locations pose considerable diagnostic challenges because their clinical presentation can be indistinguishable from malignant soft tissue neoplasms. Herein, we describe a case of trichoblastoma presenting as a large subcutaneous thigh mass that was correctly diagnosed by fine-needle aspiration cytology. Case Presentation: A 49-year-old male presented with a 7 cm, slowly enlarging, subcutaneous mass in the left thigh of 20 years’ duration. Magnetic resonance imaging raised the possibility of a low-grade sarcoma. Fine-needle aspiration cytology yielded cohesive clusters of basaloid cells with peripheral palisading, delicate spindle-shaped follicular stromal cells intimately admixed with the epithelial component, and orangeophilic keratinous material in the background. The absence of nuclear atypia, mitotic figures, and mucinous stroma supported a preoperative cytological diagnosis of a benign follicular germinative tumor consistent with trichoblastoma, thereby guiding conservative surgical excision. Histopathological examination confirmed the diagnosis. Immunohistochemistry revealed focally positive BerEP4, CD34-positive stroma, negative androgen receptor, and positive bcl-2, consistent with trichoblastoma and distinguishing the tumor from basal cell carcinoma. The patient remained recurrence-free 12 months after surgery. Conclusions: Careful assessment of characteristic cytomorphological features, particularly a dual population of basaloid epithelial cells with peripheral palisading and specialized follicular stromal cells, is vital for the accurate preoperative cytological characterization of trichoblastoma, even at atypical anatomical sites. Full article

Background: Severe lung compromise from COVID-19, ARDS, and recently AH3N2 can progress to life-threatening hypoxia. Past experience led to standardized protocols that assumed similarity to SARS-CoV. Methods: COVID-19 pathophysiology and histopathological lung biopsy photomicrographs are analyzed. Results: Pneumolysis is defined as progressive alveolar–capillary destruction resulting from SARS-CoV-2 attack on pneumocytes. In the final stages preceding pneumolysis, molecular mechanisms in the lungs include apoptosis in alveolar epithelial type I and II cells, compromising alveolar regeneration, and necrosis, resulting in leakage of intracellular contents and amplifying inflammation. Pyroptosis, driven by inflammasome activity, further disrupts alveolar integrity in ARDS. Histopathological findings include Masson bodies, alveolar-coating cells with nuclear atypia, reactive pneumocytes and reparative fibrosis, intra-alveolar hemorrhage, moderate inflammatory infiltrates and abscesses, microthrombi, hyaline membrane remnants, and emphysema. The three theoretical pathophysiological stages of progressive hypoxemia (silent hypoxemia, gasping, and death zone) are shown. Conclusions: Silent hypoxemia rapidly progresses to critical hypoxemia. This progression results from progressive pneumolysis, inflammation, immune overexpression, autoimmunity, and HAPE-type edema, leading to acute pulmonary insufficiency. Long-lasting COVID-19 can result in fibrosis and, as a compensatory mechanism, polierythrocythemia. The proposed treatment (based on tolerance to hypoxia and the hemoglobin factor) includes prompt oxygen administration, control of inflammatory and immune responses, antibiotics, rehydration, erythropoietin and platelet aggregation inhibitors. Full article

Background: Risk stratification of indeterminate thyroid nodules (Bethesda III–IV) remains difficult and often triggers unnecessary procedures. Ultrasound-based ACR TI-RADS and the 2023 Bethesda System are widely used, but the incremental value of combining them and the role of size thresholds needs prospective validation. Objective: The objective of this study was to prospectively compare the diagnostic performance of ACR TI-RADS and the 2023 Bethesda System, alone and in combination, for predicting malignancy in thyroid nodules, with dedicated analyses of indeterminate lesions (Bethesda categories III–IV), including subtypes of Bethesda III (nuclear atypia vs. other atypia), and the impact of nodule size. Methods: Histopathology was available for 131 nodules. Diagnostic metrics (sensitivity, specificity, PPV, NPV), ROC curves (DeLong comparison), and Youden indices were calculated for individual and combined thresholds; a 16 mm size cut-off was explored. Results: Malignancy was confirmed in 105/131 nodules (80.2%). Bethesda outperformed TI-RADS (AUC 0.87 vs. 0.69; DeLong p = 0.041). Malignancy rates rose with higher categories (e.g., TI-RADS 5: 93.6%; Bethesda category V: 100%; Bethesda category VI: 100%) and were markedly elevated in the histologically confirmed subset for Bethesda category III (32/41; 78.0%) and IV (6/8; 75.0%). The combined requirement of TI-RADS ≥ 4 and Bethesda ≥ 4 maximized specificity (96.2%) and PPV (98.4%) with a high Youden J (0.552), supporting a rule-in strategy in category IV of Bethesda. Size alone was a weak discriminator (AUC 0.66); within Bethesda III–IV nodules, malignancy did not differ significantly by the 16 mm threshold (p = 1.00). ROC using continuous tumor size yielded AUC = 0.66; the ROC-derived optimal cut-off was 16 mm. Applying this split produced sensitivity 0.80 and specificity 0.50. Conclusions: Integrating ACR TI-RADS with Bethesda cytology significantly improves specificity and PPV for indeterminate thyroid nodules, supporting a morphology-driven approach over traditional size-based thresholds. Incorporation of combined sonographic–cytologic criteria into management algorithms may reduce unnecessary interventions and optimize patient care. Full article

Background: Differentiating atypical endometrial hyperplasia, also known as endometrial intraepithelial neoplasia (EAH/EIN) from endometrial hyperplasia without atypia is crucial due to the higher risk of progression to endometrioid adenocarcinoma, associated with atypical lesions. Immunohistochemical markers such as PAX2 and PTEN have emerged as potential adjuncts to improve diagnostic accuracy in morphologically challenging cases. Objective: To evaluate the diagnostic value of PAX2 and PTEN expression in distinguishing atypical from endometrial hyperplasia without atypia in the Bulgarian population. Materials and Methods: A total of 96 endometrial hyperplasia cases (48 typical, 48 atypical) were included. Histopathological evaluation was performed on hematoxylin and eosin–stained sections, with two experienced pathologists confirming diagnoses according to the WHO criteria. Immunohistochemical analysis of PTEN and PAX2 was conducted on formalin-fixed, paraffin-embedded tissue sections. Results: PTEN expression loss was observed in 6% (3/48) of hyperplasia without atypia cases, compared with 81.3% (38/48) of EAH/EIN cases. For PAX2, strong nuclear staining was retained in 60% (29/48) of endometrial hyperplasia without atypia cases, with no complete loss of expression. In contrast, 64.6% (31/48) of EAH/EIN cases showed complete loss of PAX2 expression, while only 35.4% (17/48) preserved nuclear immunoreactivity. Together, these results highlight clear and consistent differences in PTEN and PAX2 expression between hyperplasia without atypia and EAH/EIN and may aid pathologists in distinguishing these two entities in routine diagnostic practice. Conclusions: Expression loss of PAX2 and PTEN is significantly associated with EAH/EIN. Immunohistochemical evaluation of these markers provides valuable adjunctive information for the diagnosis of morphologically ambiguous cases and may enhance diagnostic reproducibility and accuracy. Incorporating PAX2 and PTEN into routine assessment may guide appropriate clinical management and risk stratification of patients with endometrial hyperplasia. Full article

Background: Dilated cardiomyopathy (DCM) is a myocardial disorder characterized by structural and functional abnormalities, in particular left or biventricular chamber dilatation and systolic dysfunction, occurring without evidence of coronary artery disease, hypertension, valvular disease, or congenital heart defects. It is a significant cause of sudden cardiac death, particularly in young individuals, often remaining undiagnosed until autopsy. Methods: A systematic review of the literature was conducted following PRISMA guidelines to revisit the main postmortem findings (gross, microscopic, and genetic) useful to perform the postmortem diagnosis of DCM. Scientific databases (PubMed and Scopus) were searched for articles published up to February 2025 describing postmortem findings in individuals diagnosed with DCM. Inclusion criteria were focused on studies reporting macroscopic cardiac findings, and microscopic and genetic variants identified postmortem or in related familial studies. Data were extracted and categorized to identify consistent diagnostic markers and to assess the frequency and relevance of genetic findings in autopsy-confirmed DCM cases. From 2081 initial records, 30 studies met inclusion criteria. Two reviewers independently performed study selection and data extraction, and methodological limitations of the included studies were considered qualitatively to inform the synthesis. Results: Common macroscopic features included increased heart weight (often > 350 g), dilated left or biventricular chambers, and thinning of the ventricular walls. Histologically, the most consistent findings were diffuse interstitial fibrosis, myocyte hypertrophy, and nuclear atypia. Particular attention was given to morphological features essential to distinguish between genetic and nongenetic forms of DCM and, thus, useful to perform a differential diagnosis with disease having a DCM-like pattern. Notably, truncating variants in genes such as TTN, FLNC, DSP, PKP2, and MYH7 were frequently reported, particularly in young decedents with no significant history of cardiac disease. However, only about half of reviewed studies included any form of genetic analysis, reflecting a significant gap in current practice for forensic pathologists. Conclusions: DCM may cause sudden death without prior symptoms, making genetic testing essential to uncover the diagnosis, especially in cases with a negative phenotype. Therefore, molecular autopsy combined with careful macroscopic and microscopic analysis can strengthen the forensic assessment. Full article

Background: Endometrial hyperplasia (EH) represents a precursor lesion in the development of endometrial carcinoma, particularly the endometrioid subtype. Among the molecular pathways involved, microsatellite instability (MSI) resulting from DNA mismatch repair (MMR) deficiency has gained increasing attention as an early event in endometrial carcinogenesis. Objective: This study aimed to evaluate the expression of key MMR proteins (MLH1, PMS2, MSH2, and MSH6) in endometrial hyperplasia without atypia and endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (EAH/EIN) to determine the prevalence and potential implications of MMR deficiency at the precancerous stage. Methods: Fifty-six cases of EH were analyzed, including 28 endometrial hyperplasia without atypia and 28 EAH/EIN. Immunohistochemical (IHC) analysis was performed to assess the nuclear expression of MMR proteins. Loss of expression was defined as complete absence of epithelial nuclear staining with retained stromal positivity. Results: MMR protein expression was retained in all cases of endometrial hyperplasia without atypia, while total loss of one or more MMR proteins was observed in 3 of 28 (10.7%) EAH/EIN. The most frequent pattern involved concurrent MLH1/PMS2 loss, consistent with sporadic MLH1 promoter hypermethylation. One case exhibited isolated MSH6 loss, suggesting a potential Lynch syndrome, and another showed combined MSH6/PMS2 loss. Conclusions: MMR deficiency appears confined to atypical EH, supporting its role as an early molecular alteration in the neoplastic sequence leading to endometrioid carcinoma. Identification of abnormal MMR expression in EH may facilitate risk stratification, guide reflex testing for MLH1 methylation, and prompt genetic counseling for hereditary cancer predisposition. Full article

Background/Objectives: Fumarate hydratase-deficient leiomyomas (dFH-LMs) are a rare subtype of uterine smooth muscle tumors (USMTs) with implications for hereditary leiomatosis and renal cell carcinoma (HLRCC). Although several morphologic clues have been proposed, their diagnostic reproducibility is poorly defined. We aimed to determine the diagnostic significance of histopathologic features associated with fumarase deficiency and the reproducibility of key morphologic criteria for defining dFH-LMs. Methods: A retrospective analysis was performed on 45 USMTs that were initially classified as atypical leiomyomas (ALMs). The cohort comprised patients aged 21 to 75 years who had surgery at one tertiary medical care center from 2016 to 2025. Hematoxylin–eosin (H&E) slides were independently examined by three pathologists for features associated with FH deficiency, including eosinophilic globules, staghorn-like vessels, diffuse nuclear atypia, “bizarre” nuclei, and prominent nucleoli with halos. Molecular status was determined by immunohistochemistry (IHC) for fumarate hydratase (FH) and S-(2-succino)-cysteine (2SC). Interobserver agreement was quantified using Fleiss’s κ and Cohen’s κ. Results: Loss of FH expression was detected in 26/45 tumors (57.7%). Eosinophilic globules occurred in 88.5% of dFH-LMs, but only in 15.8% of ALMs (p < 0.001). By majority consensus (≥2 of 3 reviewers), the eosinophilic globules predicted FH deficiency with a sensitivity of 88.0% and a specificity of 85.0%; interobserver reproducibility was substantial (κ = 0.63). Staghorn-like vessels occurred in 73.1% of dFH-LMs vs. 26.3% of ALMs (p = 0.02) and diffuse nuclear atypia (84.6%) was also more frequent in dFH-LMs (p = 0.01). Patients with dFH-LMs were significantly younger than those with ALMs (Median, 34 vs. 41 years). Conclusions: Eosinophilic globules, staghorn-like vessels and diffuse nuclear atypia have been shown to have high diagnostic value and could be considered morphologic indicators of dFH-LMs. The substantial interobserver reproducibility of eosinophilic globules makes this feature particularly promising for routine clinical practice. Full article

Uterine angiomyolipoma (AML) is an exceptionally rare mesenchymal tumor of the perivascular epithelioid cell tumor (PEComa) family. Most cases are benign and exhibit a triphasic histologic pattern. Although extragenital PEComas typically show strong, diffuse HMB-45 reactivity, uterine AMLs/PEComas often exhibit weak or negative staining, thereby introducing diagnostic uncertainty. We describe a rare case of uterine AML with diffuse nuclear atypia in a postmenopausal woman, which mimicked a degenerative leiomyoma or leiomyosarcoma. A 49-year-old postmenopausal woman presented with the rapid enlargement of a uterine mass that had been followed for four years as a presumed leiomyoma. Imaging revealed a well-circumscribed uterine mass with heterogeneous enhancement, cystic degeneration, and restricted diffusion on MRI. A total hysterectomy was performed. Grossly, the tumor measured 8 cm. Microscopically, it consisted of pleomorphic epithelioid cells (70%), mature adipose tissue (20%), and thick-walled vessels. Immunohistochemistry revealed diffuse smooth muscle actin (SMA) positivity, while Human Melanoma Black (HMB)-45 and Melan-A were negative. Only one mitosis per 50 HPF was identified, with no atypical mitoses or necrosis, and the Ki-67 index was low (<5%). The patient has remained disease-free for 56 months post-surgery. This case represents the first documented HMB-45-negative uterine angiomyolipoma with diffuse nuclear atypia, characterized by a low mitotic index, low Ki-67 proliferation rate, and a benign 56-month follow-up. It broadens the morphologic spectrum of uterine AML, demonstrating that diffuse nuclear atypia can occur in HMB-45-negative tumors with benign behavior, and that atypia alone should not be interpreted as evidence of malignancy. Recognition of this rare variant is essential to avoid misdiagnosing it as leiomyosarcoma. Full article

Background and Clinical Significance: Warty (condylomatous) squamous cell carcinoma (SCC) of the uterine cervix is a rare papillary variant of SCC, usually associated with good prognosis. Case Presentation: We report the clinical case of a postmenopausal woman with vaginal bleeding, anemia, and an enlarged, exophytic tumor mass protruding from the cervix. MRI showed a solid–necrotic cervical–uterine mass with invasion of bladder, rectum, both parametria, and the left ureter, with regional lymphadenopathy and FIGO IVA stage was established. Biopsies from the cervical tumor revealed invasive, well-differentiated SCC with conspicuous koilocytic atypia in superficial and deep nests, consistent with warty (condylomatous) SCC. Immunohistochemistry showed p16 overexpression, an intermediate nuclear proliferation rate, and a non-mutational pattern for p53 immunostaining. Radiotherapy was recommended but the patient’s condition deteriorated rapidly and she died three months after initial diagnosis. Due to the rarity of this type of tumor, we conducted a search on PubMed, Scopus, and Web of Science from inception to 31 July 2025 and we identified ten reports available for evaluation. A total of 32 cases were identified, usually with FIGO stage I or II, mostly with low-risk HPV infection and with good prognosis. Conclusions: The advanced stage and limited tolerance for therapy in this case emphasize the importance of HPV vaccination and HPV-based screening to prevent late, non-curable presentations. Accurate distinction from condyloma acuminatum and verrucous or papillary SCC is clinically relevant because management and outcomes differ. Since some of the cases reported in the literature had a worse clinical course, with shorter disease-free survival and overall survival, including our case, further research is mandatory in the future to unravel those features which might predict a poor outcome. Full article

Uterine leiomyomas are a heterogenous group of benign mesenchymal tumours. While diagnosis is usually achieved through clinical assessment and pelvic ultrasound (PU), atypical subtypes are not as easily recognisable and can be mistaken for malignant tumours such as leiomyosarcoma or ovarian carcinoma. We describe the case of a 41-year-old patient who presented with increasing bulk symptoms, urinary frequency and growth of a hydropic leiomyoma (HLM) of the left lateral and posterior uterine wall that had been known for 10 years, confirmed with previous biopsy. The tumour filled the entire pelvic cavity in PU and was increasingly difficult to delineate; therefore an abdominal hysterectomy without oophorectomy was performed. Gross tissue examination showed an irregularly enlarged, asymmetric uterus with an intrauterine subserosal mass and an extrauterine papillary tumour arising from the right and posterior uterine wall. The tumour measured 20 × 17 × 10 cm in size. Numerous smooth muscle nodules were observed within the uterus and extending into the extrauterine component in a continuous transition, exhibiting a benign, bland appearance. The nodules were separated by abundant edematous connective tissue with increased vascularization. Histopathological analysis revealed low mitotic activity with no evidence of nuclear atypia, pleomorphism, or necrosis. Immunohistochemical staining confirmed the diagnosis of a benign smooth muscle tumour. Our findings confirm a rare, benign smooth muscle neoplasm with both intrauterine and extrauterine involvement, and add to the existing literature regarding presentation, diagnostic and therapeutic challenges associated with HLM. Full article

Gynecologic perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms characterized by the co-expression of melanocytic markers (HMB-45 and Melan-A) and smooth muscle markers (SMA, desmin, and caldesmon). The uterus is the most common organ affected, with approximately 110 cases reported worldwide, while occurrences in the cervix, vagina, ovary, and other gynecologic locations are exceptionally rare. These tumors typically present with nonspecific symptoms such as abnormal uterine bleeding and pelvic pain, often mimicking other uterine neoplasms. Histopathologically, PEComas exhibit epithelioid and spindle cell morphology with variable nuclear atypia, mitotic activity, and characteristic immunohistochemical profiles. Although most PEComas behave benignly, a subset demonstrates malignant potential, associated with larger tumor sizes, an increased mitotic index, necrosis, and vascular invasion; however, standardized diagnostic criteria remain scarce. Molecular alterations frequently involve the mTOR signaling pathway through tuberous sclerosis complex (TSC) 1 and TSC2 gene mutations, offering potential targets for therapy. Surgical resection with clear margins remains the cornerstone of treatment. For advanced or metastatic cases, mTOR inhibitors have shown promising efficacy, whereas the role of radiotherapy remains uncertain. This review aims to synthesize current knowledge regarding the epidemiology, clinical presentation, histologic features, malignant potential, and treatment of uterine PEComas, emphasizing the importance of accurate histopathological classification and molecular profiling to guide individualized therapeutic strategies. Full article

Objectives: Sinonasal inverted papilloma (SNIP) is a rare benign tumor that has potential for malignant transformation, usually into squamous cell carcinoma (SCC). The pre-operative differentiation between SNIP and SNIP-SCC is essential in determining the therapeutic strategy, but it is a challenge, as biopsies may fail to recognize the malignant part of the tumor. Further, a SNIP can also be locally aggressive and thus mimic a malignant tumor. This retrospective study compares the pre-operative differences in computed tomography (CT) and histologic findings between patients with a benign SNIP and those with a SNIP-SCC. Methods: Eight patients with SNIP-SCC were selected from the hospital registries of the Department of Otorhinolaryngology, Helsinki University Hospital (Helsinki, Finland). For each case a comparable SNIP case without malignancy was selected. Five histopathologic samples of both the SNIP and SNIP-SCC tumors were retrieved. CT images and the histopathologic samples were re-evaluated by two observers. Results: The nasal cavity and ethmoid and maxillary sinuses were the most common sites for both tumor types. The SNIP tumors were mostly unilateral, and the SNIP-SCC tumors were both unilateral and bilateral. Only SNIP-SCC tumors demonstrated bone defects and orbital or intracranial invasion. Dysplastic findings such as dyskeratosis, nuclear atypia, and maturation disturbances were seen only in the SNIP-SCC tumors. Conclusions: Bony destruction and invasion of adjacent structures in pre-operative CT images seem to be pathognomonic signs of SNIP-SCC based on this series. To differentiate between SNIP and SNIP-SCC tumors all available pre-operative investigations are warranted. Full article

Background/Objectives: The 2023 revision of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) simplified the subcategorization of category III into two groups: “AUS-nuclear” and “AUS-other”. The aim of this study was to investigate the risk of malignancy (ROM) of individual BSRTC categories with a particular emphasis on the “AUS-nuclear” and “AUS-other” subcategories and to check whether the low-risk follicular-cell-derived thyroid neoplasm (LRTN) interpretation or EU-TIRADS class of the nodule modify ROM. Methods: The analysis covered the FNA results of 18,225 nodules in 12,470 patients. The rate of malignancy (the upper limit of ROM) was established on the basis of the assessment of 1660 nodules treated surgically in 978 patients. Results: In the broadest variant, with all LRTNs regarded as malignant, the ROM for subsequent categories was as follows: I: 0.4–3.5%, II: 0.1–1.3%, III: 3.8–17.7%, IV: 23.3–27.8%, V: 79.6–90.1%, and VI: 86.3–100.0%. In AUS-nuclear nodules, the ROM was 10.5–28.9%, while in AUS-other nodules, it was 2.2–12.2%. The exclusion of NIFTP or all LRTNs from cancers mainly affected the ROM of AUS-nuclear nodules: 9.4–25.9% or 8.6–23.7%, respectively. EU-TIRADS 5 class increases the ROM in AUS-nuclear nodules to 78.3%, OR: 15.7 and in AUS-other to 40.7%, OR: 6.6. Conclusions: The 2023 BSRTC is a welcome step towards simplification of the way nodules are classified within category III. The AUS-nuclear subcategory is associated with a two-times-higher incidence of malignancy than the AUS-other regardless of LRTN interpretation and EU-TIRADS class of the nodule. The EU-TIRADS 5 class of the nodule is helpful in the identification of category III nodules with a high risk of malignancy. Full article