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Background: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) recommends an upper limit of 10% for atypia of undetermined significance (AUS). Recent data suggest that this category might be overused when the rate of cases with molecular positive results is low. As a quality metric, the AUS and positive call rates for this facility's cytology laboratory and each cytopathologist (CP) were calculated. Methods: A retrospective analysis of all thyroid cytology cases in a 4.5‐year period was performed. Cases were stratified by TBSRTC, and molecular testing results were collected for indeterminate categories. The AUS rate was calculated for each CP and the laboratory. The molecular positive call rate (PCR) was calculated with and without the addition of currently negative to the positive results obtained from the ThyroSeq report. Results: A total of 7535 cases were classified as nondiagnostic, 7.6%; benign, 69%; AUS, 17.5%; follicular neoplasm/suspicious for follicular neoplasm, 1.4%; suspicious for malignancy, 0.7%; and malignant, 3.8%. The AUS rate for each CP ranged from 9.9% to 36.8%. The overall PCR was 24% (range, 13%–35.6% per CP). When including cases with currently negative results, the PCR increased to 35.5% for the cytology laboratory (range, 13%–42.6% per CP). Comparison analysis indicates a combination of overcalling benign cases and, less frequently, undercalling of higher TBSRTC category cases. Conclusions: The AUS rate in the context of PCR is a useful metric to assess cytology laboratory and cytopathologists' performance. Continuous feedback on this metric could help improve the overall quality of reporting thyroid cytology. Assessing the atypia of undetermined significance rate in the context of positive call rate and time serves as a valuable metric for evaluating cytopathologists proficiency and overall laboratory performance and helps identify trends to provide valuable feedback. [ABSTRACT FROM AUTHOR]

Background: The atypia of undetermined significance (AUS) category is heterogeneous, leading to variations in its use. To prevent excessive usage, the AUS rate should be ≤10%. Although this recommendation aims to maintain diagnostic quality, it lacks supporting data. The AUS:Malignant (AUS:M) ratio has been proposed as a metric tool to evaluate AUS use. Furthermore, integrating ThyroSeq v3 (TSV3) positive call rate (PCR) and the molecular‐derived risk of malignancy (MDROM) have been put forward as performance improvement tools. The authors reviewed their AUS:M ratios, TSV3 PCR, MDROM, and ROM. Methods: Thyroid aspirates evaluated in the laboratory (from August 2022 to September 2023) by seven cytopathologists (CPs) were identified. AUS:M ratio, MDROM, ROM, and TSV3 PCR results for the laboratory and each CP were recorded and analyzed. Results: A total of 2248 aspirates were identified (462 AUS and 80 malignant). The AUS:M ratio for the laboratory was 5.8 (CPs range, 2.8 to 7.3). The TSV3 PCR for the laboratory was 23% (CPs range, 11% to 41%). The MDROM for the laboratory was 19% (CPs range, 9% to 31%), whereas the ROM was 36% (CPs range, 29% to 50%). Linear regression analysis of AUS:M ratio versus TSV3 PCR and MDROM demonstrated a moderate positive correlation but a weak negative correlation to the ROM. Deviations from established targets were attributed to multiple factors. Conclusion: The findings of this study underscore the importance of using a combination of metrics to evaluate diagnostic practices. By dissecting the practice patterns of each CP, the authors can measure different aspects of their performance and provide individualized feedback. Quality metric tools in thyroid cytology can offer valuable feedback to individual cytopathologists and laboratories, contributing to improving diagnostic practices. [ABSTRACT FROM AUTHOR]

Background: Basaloid salivary gland neoplasm of uncertain malignant potential (B‐SUMP) is an indeterminate diagnostic subcategory, with pleomorphic adenoma (PA) representing the most common benign neoplasm. Pleomorphic adenoma gene 1 (PLAG1) staining is frequently seen in PAs and could aid in distinguishing them from other basaloid neoplasms. The authors evaluated the utility of PLAG1 immunocytochemistry (ICC) in differentiating PAs from other basaloid neoplasms in smears and liquid‐based cytology (LBC) specimens. Methods: In total, 45 B‐SUMP cytology aspirates and corresponding surgical excision specimens were identified. PLAG1 immunostaining was performed in all aspirates and surgical excision specimens and was scored as positive (strong/diffuse), equivocal (focal/weak), or negative. Results: PLAG1 ICC was performed directly on 38 smears and seven LBC specimens. PLAG1 was positive in 29 of 45 cases (64%), whereas six of 45 (13%) were equivocal, and 10 of 45 (22%) were negative. PLAG1‐positive aspirates included 26 (90%) PAs, two (7%) basal cell adenomas (BCAs), and one (3%) carcinoma ex‐PA. PLAG1‐equivocal aspirates included four (67%) PAs and two (33%) BCAs, whereas negative aspirates included five (50%) BCAs, four (40%) adenoid cystic carcinomas, and one (10%) metastatic adenosquamous carcinoma. The sensitivity, specificity, positive, and negative predictive values were 87%, 86%, 93%, and 75%, respectively. Diagnostic accuracy was 87%. Conclusions: PLAG1 ICC is useful when positive (strong/diffuse) and can be reliably performed on smears and LBC specimens. PLAG1 was positive in most PAs and in a small subset of BCAs. Therefore, in the absence of atypical cytologic features, PLAG1‐positive tumors could be diagnosed as benign, with a note favoring PA versus BCA. In contrast, PLAG1‐negative/equivocal tumors should remain in the B‐SUMP category. PLAG1 immunocytochemistry is useful for the diagnosis of pleomorphic adenoma when strong/diffusely positive and can be reliably performed directly on alcohol‐fixed conventional smears and liquid‐based cytology specimens. It may help enhance diagnostic accuracy in challenging cases and reduce indeterminate diagnoses. [ABSTRACT FROM AUTHOR]

The proposed diagnostic category of "low‐risk oncocytic renal neoplasm" consists of both oncocytomas and a subset of chromophobe renal cell carcinomas but has a 5‐year survival of at least 95%–100%. [ABSTRACT FROM AUTHOR]

Background: ThyroSeq molecular testing assesses the probability of malignancy (POM) in thyroid fine‐needle aspiration cytology (FNAC) with indeterminate cytology. The aim was to investigate whether Bethesda category IV (BIV) subcategories are associated with specific molecular alterations, molecular‐derived risk of malignancy (MDROM), and risk of malignancy (ROM). Methods: FNAC slides, associated ThyroSeq, version 3, Genomic Classifier results, and surgical follow‐up were retrieved for BIV nodules. Nodules were subcategorized as follicular neoplasm (FN) with or without cytologic atypia or oncocytic follicular neoplasm (OFN). The MDROM, ROM, and frequency of molecular alterations in FN and OFN were analyzed. p <.05 was considered significant. Results: A total of 92 FNAC were identified and subcategorized into 46 FN (15 with and 31 without cytologic atypia) and 46 OFN. The benign call rate and the positive call rate were 49% and 51%, respectively. The MDROM in BIV was 34.3%, trending lower in OFN than in FN. RAS mutations were significantly more frequent in FN when compared to OFN (p =.02). Chromosomal copy number alterations were more often present in OFN than in FN (p <.01). On histologic follow‐up, ROM in OFN was trending lower than in FN (p =.1). The most common diagnosis in OFN was oncocytic adenoma, whereas follicular variant papillary thyroid carcinoma was most common in FN. Conclusions: The MDROM and ROM were trending lower in OFN compared with FN, and the molecular alterations differed between OFN and FN subcategories. The molecular‐derived risk of malignancy and risk of malignancy were trending lower in oncocytic follicular neoplasm (OFN) compared with follicular neoplasm (FN). RAS mutation was more frequent in FN, whereas copy number alteration was more prevalent in OFN. [ABSTRACT FROM AUTHOR]

Background: Fine‐needle aspiration cytology (FNAC) is generally the initial sampling method for salivary gland neoplasms. The cytomorphologic features of acinic cell carcinoma (AciCC) of salivary gland can overlap with other neoplastic and nonneoplastic entities. AciCCs harbor a recurrent t(4;9) rearrangement with upregulation of nuclear receptor subfamily 4 group A member 3 (NR4A3). NR4A3 protein overexpression has been shown to be highly sensitive and specific for the diagnosis of AciCC in histologic specimens and cell block preparations. However, data on NR4A3 immunocytochemistry (ICC) on conventional smears or liquid‐based cytology are limited. Methods: The authors identified 18 FNAC of histologically proven AciCC cases between 2013 and 2019. FNAC samples of diagnostic mimickers were likewise retrieved and included in the study cohort for comparison. The NOR1/NR4A3 mouse monoclonal antibody was applied directly to FNAC slides using a standard ICC technique. Results: The cohort included ethanol‐fixed Papanicolaou‐stained cytologic smears and liquid‐based preparations from 18 AciCC, one secretory carcinoma, four mucoepidermoid carcinomas, four salivary duct carcinomas, five pleomorphic adenomas (PA), five Warthin tumors, five oncocytomas, one oncocytic hyperplasia, and five nonneoplastic salivary gland cases. Strong nuclear staining for NR4A3 was present in all AciCC, weak nuclear staining was present in one PA, and all other non‐AciCC were negative (sensitivity, 100%; specificity, 97%). Conclusions: NR4A3 ICC can be used directly on FNAC conventional smears and liquid‐based cytology to reliably distinguish AciCC from its mimickers. This marker may be useful in cases where a cell block preparation is unavailable or inadequate. NR4A3 immunocytochemistry can be used directly on fine‐needle aspiration cytology conventional smears and liquid‐based cytology to reliably distinguish acinic cell carcinoma from its mimickers. This may be useful in cases where a cell block preparation is unavailable or inadequate. [ABSTRACT FROM AUTHOR]

Background: ThyroSeq assesses the probability of malignancy (POM) in thyroid fine‐needle aspiration cytology specimens diagnosed as atypia of undetermined significance (AUS). The authors investigated whether defined AUS subcategories are associated with specific molecular alterations, the molecular‐derived risk of malignancy (MDROM), and the risk of malignancy (ROM). Methods: Fine‐needle aspiration cytology reports of AUS and corresponding results from the ThyroSeq version 3 genomic classifier results were retrieved and subcategorized as follicular cells with either cytologic atypia (FC‐C), architectural atypia (FC‐A), both cytologic and architectural atypia (FC‐CA), or a predominance of Hurthle cells (PHC). The MDROM, ROM, and frequency of molecular alterations by subcategory were computed and analyzed, and p <.05 was considered significant. Results: The final analysis included 541 cases subdivided into 233 with FC‐A, 104 with FC‐C, 116 with FC‐CA, and 88 with PHC. The benign call rate and positive call rate for the AUS category were 72% and 28%, respectively, which varied between AUS subcategories. The MDROM by subcategory was 15.9% FC‐A, 20.5% FC‐C, 33.8% FC‐CA, and 14.4% PHC. Histologic follow‐up was available for 155 (28%) AUS cases with a follow‐up period ≥12 months. The 95% confidence intervals of the MDROMs overlapped with the ROMs. The highest MDROM and ROM were in the FC‐CA subcategory. RAS mutations were present in all subcategories. BRAF V600E mutations and papillary thyroid carcinoma were most frequent in the FC‐CA subcategory. Noninvasive follicular thyroid neoplasm with papillary‐like nuclear features was significantly more frequent in the FC‐C subcategory. Conclusions: The current results demonstrated that AUS subcategories are associated with specific genetic alterations, the MDROM, and the ROM. Molecular results and an awareness of various cancer probabilities within AUS subcategories can allow for a more tailored management. Fine‐needle aspiration cytology subcategories of atypia of undetermined significance have been associated with different probabilities of malignancy and risks of malignancy and are characterized by different molecular alterations. Molecular results and an awareness of various cancer probabilities within atypia of undetermined significance subcategories can allow more tailored management. [ABSTRACT FROM AUTHOR]

The adrenal glands produce a variety of hormones that play a key role in the regulation of blood pressure, electrolyte homeostasis, metabolism, immune system suppression, and the body’s physiologic response to stress. Adrenal neoplasms can be asymptomatic or can overproduce certain hormones that lead to different clinical manifestations. Oncocytic adrenal neoplasms are infrequent tumors that arise from cells in the adrenal cortex and display a characteristic increase in the number of cytoplasmic mitochondria. Since the rate-limiting step in steroidogenesis includes the transport of cholesterol across the mitochondrial membranes, in part carried out by the 18-kDa translocator protein (TSPO), we assessed the expression of TSPO in a case of adrenal oncocytic neoplasm using residual adrenal gland of the patient as internal control. We observed a significant loss of TSPO immunofluorescence expression in the adrenal oncocytic tumor cells when compared to adjacent normal adrenal tissue. We further confirmed this finding by employing Western blot analysis to semiquantify TSPO expression in tumor and normal adrenal cells. Our findings could suggest a potential role of TSPO in the tumorigenesis of this case of adrenocortical oncocytic neoplasm. [ABSTRACT FROM AUTHOR]

Aims The study of haemangiomas in end-stage renal disease ( ESRD). Methods and results Twenty ESRD nephrectomies from 16 patients (aged 9 months-68 years) were due to hypertension (four), focal segmental glomerulosclerosis (four), lupus nephritis (three), diabetes (one), Ig A nephropathy (one), hereditary nephritis (one), congenital nephrotic syndrome (one) and unknown cause (one). Haemangiomas appeared as a single mass (15), two masses (one), three masses (one), four masses (two) and eight masses (one) per kidney. Tumours measured 0.2-3.5 cm. Four patients had bilateral haemangiomas. All tumours were in the medulla and often abutted renal sinus fat. All except one of the tumours were anastomosing haemangiomas, showing isolated or interconnected sinusoidal capillary-sized vascular channels lined by a single layer of benign cuboidal CD34+, CD31+, D2-40− endothelial cells, separated by loose stroma with spindle cells. One tumour was a cellular capillary haemangioma. Intravascular growth was seen in nine specimens. All haemangiomas had extramedullary haematopoiesis. Acquired cystic kidney disease ( ACKD) was seen in 11 kidneys (nine patients), renal cell carcinoma ( RCC) in five, ACKD-associated RCC precursors in three, Wilms' tumour in one and papillary adenomas in five. Conclusions Anastomosing haemangioma appears as a distinctive clinicopathological entity developing in kidneys with ESRD, with or without ACKD. [ABSTRACT FROM AUTHOR]

We report a case of cutaneous malignant melanoma associated with extensive pseudoepitheliomatous hyperplasia. Pseudoepitheliomatous hyperplasia may mimic squamous cell carcinoma and may complicate the diagnosis of cutaneous melanoma. This diagnostic pitfall is important to both recognize and be cognizant of, so as to avoid diagnostic errors. The observation of the pseudoepitheliomatous hyperplasia, in this case with an extensive proliferation of eccrine ducts, provides further evidence that cutaneous pseudoepitheliomatous hyperplasia arises within the eccrine apparatus. [ABSTRACT FROM AUTHOR]

Reports on a postoperative pressure-induced alopecia. Role of apoptosis in non-scarring alopecia; Observation of distinguishing features; Characteristic common to forms of alopecia.

Systemic lymph node metastasis is a rare event in malignant mesothelioma. It is even more exceptional when systemic lymph node metastasis is the initial clinical presentation. Review of literature discloses only four cases in which metastatic lymphadenopathy was the only symptom of malignant mesothelioma. We, herewith, report three cases where the initial diagnosis of malignant mesothelioma was made by biopsy of enlarged lymph nodes, which were the only clinical presentation. Immunohistochemistry played a pivotal role in elucidating the mesothelial origin of their unusual systemic lymph node metastasis. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma needs to be separated from small cell carcinoma metastatic from visceral sites to skin. Pulmonary small cell carcinoma is the most common primary site of small cell carcinoma. We evaluated the immunophenotypic characteristics of 21 Merkel cell carcinomas and 33 small cell carcinomas of lung using thyroid transcription factor-1 and cytokeratin 20. Thyroid transcription factor-1 was 100% specific for the diagnosis of small cell carcinoma of lung associated with a diagnostic sensitivity of 85%. Cytokeratin 20 was present in 95% of Merkel cell carcinomas; however, 33% of small cell carcinoma of lung were also positive. Both antibodies typically demonstrate diffuse and intense staining of their respective tumor cells. We conclude that thyroid transcription factor-1 is a sensitive and specific marker for small cell carcinomas of lung and that a combination of thyroid transcription factor-1 and cytokeratin 20 is indicated to assist in the differentiation of metastatic small cell carcinoma of lung from merkel cell carcinoma. [ABSTRACT FROM AUTHOR]

The article presents a study which evaluated the use of p63 for distinction of glandular versus squamous lesions in cervicovaginal specimens. p63 is said to be a useful immunocytochemical marker for differentiating primary grandular pathology from high-grade intraephithelial lesions (HSIL) in cervicovaginal specimens. The researchers concluded that p63 may be a diagnostic pitfall in atrophic cervicovaginal specimens.