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Background: Activating point mutations of the RAS gene (NRAS, HRAS, and KRAS) can be seen in benign and malignant thyroid tumors; among these, NRAS mutations are more commonly seen. This study was conducted to evaluate the thyroid risk of malignancy (ROM) associated with RAS mutations in thyroid fine‐needle aspiration (FNA) at the authors' institution. Methods: The authors searched their electronic database system between January 2015 and May 2021 for thyroid FNA cases with any type of RAS mutation. Molecular alterations were identified with the ThyroSeq Genomic Classifier, ThyGeNEXT (thyroid oncogene panel)/ThyraMIR (miRNA classifier), or ThyroSure gene panel. Results: A total of 127 cases (age, 51 ± 14 years; 100 females and 27 males) were identified, and 72 had histologic follow‐up. The overall ROM associated with RAS mutations (with or without any other molecular alterations) was 29%, whereas the ROM was lower (18%) with RAS mutations only. Isolated NRAS, HRAS, and KRAS mutation–associated ROMs were 15%, 27%, and 14%, respectively. Among these RAS‐mutated cases, the cases with a Bethesda category IV cytologic diagnosis had a higher ROM than the cases with a category III diagnosis (38% vs 17%). Twenty‐one histologically confirmed malignant cases were mostly classified on cytology as category IV lesions (14 of 34; 41%), and the remainder were either category III (6 of 35; 17%) or V lesions (1 of 1; 100%). Conclusions: This study demonstrated that the overall RAS mutation–associated ROM in thyroid FNA was intermediate (29%), and isolated HRAS mutations appeared to have a higher ROM (27%) than NRAS and KRAS mutations (15% and 14%, respectively). A RAS mutation can be seen in benign or malignant thyroid diseases. The risk of malignancy is higher when an RAS mutation is associated with other molecular alterations, especially in Bethesda category IV cases. [ABSTRACT FROM AUTHOR]

Objectives: Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy, and early diagnosis, often aided by fine-needle aspiration (FNA), is key to improving patient prognosis. While the current literature describes some of the cytologic features (CFs) of this entity, a comprehensive examination of the CFs has not yet been performed.Methods: We retrospectively searched our electronic database for ATC cases with available slides between January 2008 and December 2019. Cases were examined for 22 CFs and compared with a control group of differentiated thyroid carcinoma.Results: A total of 18 ATC cases meeting our inclusion criteria were identified. Most cases showed moderate to high cellularity (83%) and epithelioid cytomorphology (83%). Architecture included either predominantly groups/clusters of tumor cells (56%) or single tumor cells (44%). The other CFs were as follows: nuclear enlargement (100%), nuclear crowding (89%), nuclear membrane irregularities (100%), multinucleated tumor cells (33%), and background acute inflammatory cells (50%). Of the CFs examined, statistically significant differences between ATC and the control groups were found in the following: nuclear pleomorphism, coarse/clumped chromatin, macronucleoli, apoptosis, and necrosis.Conclusions: Identification of key CFs in FNA coupled with the clinical history aids in the diagnosis of ATC and helps distinguish it from other mimickers. [ABSTRACT FROM AUTHOR]

Objectives: This study reviewed the institutional experience of performing calcitonin immunostain on an additional ThinPrep slide in fine-needle aspiration (FNA) diagnosis of medullary thyroid carcinoma (MTC).Methods: Thyroid FNA cases with MTC suspected or included in the differential diagnosis during cytologic evaluation and calcitonin immunostain performed were retrieved and reviewed.Results: Calcitonin immunostain was performed in 132 cases with 41 positive, 81 negative, and 10 indeterminate results. All calcitonin-positive cases had a cytologic diagnosis of MTC while all calcitonin-negative cases were cytologically classified as non-MTCs except for two cases suspicious for MTC. In 10 cases with an indeterminate calcitonin result, diagnoses of non-MTC and suspicious for MTC were rendered in 6 and 4 cases, respectively. Histopathologic follow-up was available in 85 (64%) cases. All cytologically diagnosed MTC cases were confirmed on histopathology. In 3 MTC cases with an indeterminate calcitonin result, 1 case was misclassified cytologically as follicular neoplasm. The calculated sensitivity, specificity, positive predictive value, and negative predictive value of calcitonin immunostain were all 100% for diagnosing MTC.Conclusions: Our study demonstrates the feasibility of performing calcitonin immunostain on an additional ThinPrep slide. Calcitonin immunocytochemistry is a valuable adjunct test for FNA diagnosis and differential diagnosis of MTC. [ABSTRACT FROM AUTHOR]

Background: This study investigated p16 by immunohistochemistry (IHC) on cellblocks (CBs) and human papillomavirus (HPV) by polymerase chain reaction (PCR) in fine‐needle aspiration (FNA) of head and neck squamous cell carcinoma (HNSCC). Methods: Receiver operating characteristic (ROC) curve analysis was used to assess test performance in CBs compared with p16 IHC in 42 surgical specimens from patients with HNSCC and in correlation with HPV by PCR in cytology specimens. The study assessed HPV by PCR in FNA specimens as a substitute for p16 IHC in surgical specimens. Results: Of 42 cases, 38 CBs showed malignant cells as cohesive clusters of viable cells with or without single tumor cells, whereas 4 specimens were composed exclusively of single tumor cells and degenerated cells. All p16‐negative surgical specimens showed an absence of p16 staining in the corresponding CBs (n = 16). In the p16‐positive surgical cases (n = 26), corresponding CBs with tumor clusters (n = 23) showed heterogeneous p16 expression ranging from 40% to 100%; however, scoring single cells was challenging and unreliable because of cellular degradation. ROC curve inspection showed the optimal threshold to be at least 40% p16 staining in tumor clusters with 100% sensitivity and specificity. In cases with inadequate CBs, HPV by PCR on needle rinse showed 88% sensitivity and 100% specificity for p16 expression in surgical specimens. Conclusions: A cutoff of at least 40% p16 expression in tumor clusters may be appropriate for p16 positivity in cytology CB specimens. A positive HPV finding by PCR on needle rinse can be used as a substitute for p16 expression in surgical specimens. Cytology fine‐needle aspiration specimens with tumor clusters in cellblock sections are reliable in determining p16 status by immunohistochemistry in head and neck squamous cell carcinoma. A cutoff of at least 40% in tumor clusters correlates with positive human papillomavirus in cytology specimens and p16 immunohistochemistry in surgical specimens. [ABSTRACT FROM AUTHOR]

Background: Hürthle cell features are frequently observed on the fine‐needle aspiration (FNA) cytology of thyroid nodules and often pose a diagnostic challenge because of a significant overlap between cytomorphologic features seen in benign and malignant lesions. Molecular alterations (MAs) associated with these lesions are not well described. The objective of the current study was to evaluate the molecular profile of Hürthle cell lesions classified as Hürthle cell neoplasm (HCN) on cytologic evaluation. Methods: The authors retrospectively reviewed their electronic database for cytologic diagnoses of HCN from January 1, 2017 to March 31, 2020. Results: In total, 279 cases from 275 patients who had a diagnosis of HCN were included in the study. Molecular testing results were available in 85 cases (51 with MAs and 34 without MAs) and, of those, 42 had histologic follow‐up available. Eight of 10 malignant cases had MAs, whereas the remaining 2 cases were negative for MAs. The most frequently encountered predominant genetic alterations or classifier findings were chromosome copy number alterations (n = 15), followed by NRAS (n = 8), KRAS (n = 7), suspicious (n = 6), EIF1AX (n = 4), TSHR (n = 3), gene overexpression (n = 3), positive microRNA classifier (n = 2), and 1 each of BRAF K601E, TERT, and HRAS mutations. One hundred thirty‐seven cases had histologic follow‐up available; of those, 28 were classified as malignant, and 109 were classified as benign (neoplastic and nonneoplastic). The overall risk of malignancy associated with HCN was 20%, and the risk of HCN with MAs was 25%. Conclusions: The cytologic diagnosis of HCN includes various MAs without any obvious trend, and most malignant cases (80%) have some type of MA. Cases with a cytologic diagnosis of Hürthle cell neoplasm exhibit various molecular alterations, but no consistent association is observed in histologically benign or malignant cases. Because molecular data pertinent to Hürthle cell neoplasms are evolving, identifying additional molecular findings along with the fine‐needle aspiration results may direct future larger cohort studies to discover any association. [ABSTRACT FROM AUTHOR]

Background: Neurotrophic tyrosine kinase receptor (NTRK) rearrangement has been reported in a subset of papillary thyroid carcinoma (PTC) cases. Little is known about the cytomorphologic features of NTRK‐rearranged PTC. Methods: We report an institutional series of 13 fine‐needle aspiration (FNA) specimens of NTRK‐rearranged PTC with a predominantly indeterminate cytology diagnosis. NTRK3 or NTRK1 rearrangements were detected on FNA or surgical specimens by next‐generation sequencing. Results: The 13 patients had a median age of 18 years; 10 patients were female and 3 patients were male. In 10 (77%) cases, cytology was indeterminate, and histopathologic follow‐up was predominantly the follicular variant of PTC (n = 8 [62%]), mostly infiltrative subtype. Of 12 FNA specimens available for review, a predominant loosely cohesive group pattern was the most commonly encountered architectural pattern (n = 5 [41%]), followed by single cell (n = 3 [25%]), thick cord (n = 2 [17%]), and microfollicular pattern (n = 2 [17%]). Background lymphocytic thyroiditis was observed in 9 cases. At the cellular level, the cytoplasm was moderate and granular, occasionally vacuolated. Classic PTC nuclear features (eg, nuclear enlargement, elongation, grooves, and nuclear membrane irregularity) were present but were often focal and subtle. Chromatin was often granular. Intranuclear pseudoinclusions were absent or rare. Conclusion: Our study demonstrates that most cases of NTRK rearrangement lack classic PTC cytomorphologic characteristics. Loosely cohesive groups and single cells with granular, sometimes vacuolated cytoplasm and subtle nuclear features are often seen on FNA specimens. Recognizing these characteristics may be helpful to preoperatively prompt molecular testing, including NTRK rearrangement analysis. Fine‐needle aspirates of NTRK‐rearranged papillary thyroid carcinoma (PTC) show loosely cohesive groups and single cells in addition to microfollicles and thick cords. At the cellular level, classic nuclear features of PTC are subtle, whereas moderate to abundant granular and vacuolated cytoplasm and often granular chromatin are distinctive characteristics. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine whether Ki-67 index evaluated on cytologic material could reliably grade pancreatic neuroendocrine tumors (PanNETs).Methods: Cases with adequate cell block and available surgical specimens were included. Ki-67 index was calculated using "eyeballing," "hot spot," and "complete" counting methods.Results: The overall concordance rates between cytology and surgical specimens were 71%, 73%, and 59%, respectively, by using eyeballing, hot spot, and complete counting approaches. All grade 1 tumors were correctly graded on cytology, but in grade 2 tumors concordance rates were only 36%, 41%, and 9%, respectively. All grade 2 tumors were undergraded when cell blocks contained fewer than 1,000 cells, while concordance rate increased to 57%, 64%, and 14%, respectively, in cases with 1,000 cells or more.Conclusions: Grade 2 PanNETs can be significantly undergraded when Ki-67 index is evaluated on cell block material. In cases with 1,000 or more cells, the hot spot counting method has better correlation with surgical specimens. [ABSTRACT FROM AUTHOR]

* In this short review, we discuss primary diffuse large B-cell lymphoma of the testis, an entity that is most commonly seen in older patients. The most common clinical presentation is a unilateral testicular mass. Microscopically, the tumor shows diffuse infiltration of lymphocytes between intact seminiferous tubules. Spermatogenic arrest, interstitial fibrosis, and tubular hyalinization are commonly seen. The tumor is positive for B-cell markers by immunohistochemistry. Treatment has traditionally been with orchiectomy and combination chemotherapy; however, only a minority of patients enjoy a prolonged disease-free survival. Differential diagnosis includes seminoma and viral and granulomatous orchitis. doi:10.5858/arpa.2010-0158-RS, Primary testicular lymphoma is a collection of neoplasms that comprises only 1% to 9% of testicular neoplasms. However, it is the most common malignant testicular tumor in men older than [...]

* In this short review, we discuss clear cell adenocarcinoma of the urinary bladder, a rare tumor that primarily affects women. The histogenesis of this neoplasm is uncertain; in some tumors the clinicopathologic and histologic features are suggestive of a mullerian origin. Clear cell adenocarcinoma consists of cells with abundant clear cytoplasm, arranged in solid, glandular, or tubulocystic patterns. These tumors are positive for pancytokeratin, cytokeratin 7, and CA 125 immunohistochemical stains. Patients typically present with gross hematuria, dysuria, and discharge. The natural history is poorly understood and patient outcomes remain unclear. Currently, surgery is the treatment of choice. Nephrogenic adenoma is the most important differential diagnostic consideration, followed by metastatic clear cell carcinoma., Clear cell adenocarcinoma (CCA) usually arises from the female genital tract. However, CCA is sometimes found in the lower urinary tract in women, most commonly involving the urethra, (1) where [...]

* Amnion nodosum is commonly regarded as a placental hallmark of severe and prolonged oligohydramnios. It consists of nodules of amorphous granular material present on the surface of the amnion. We reviewed all 45 cases of amnion nodosum from our placental database from 1994 through 2003 (study group). The control group consisted of 45 cases from the same database matched for gestational age but without amnion nodosum. Oligohydramnios, multiple pregnancy, perinatal mortality, macerated stillbirths, and chronic twin-twin transfusion were the most common clinical features encountered in the study group. Luminal vascular abnormalities of chorionic villi, fibrosis of chorionic villi, and placental edema were the placental features that were more frequently present in the study group. (Arch Pathol Lab Med. 2007;131:1829-1833), Amnion nodosum (AN) is a placental lesion consisting of numerous small nodules on the amnion of the chorionic disc, placental membranes, or the umbilical cord. Prior to 1950 when Landing [...]

The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous- sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 × 10-4), increased frequency of nonsynonymous SSNVs in Pan- Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 × 10-17); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers ATrich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers. [ABSTRACT FROM AUTHOR]