Performance of preferentially expressed antigen in melanoma (PRAME) immunohistochemistry for metastatic melanoma in cytology specimens.

BACKGROUND: Preferentially expressed antigen in melanoma (PRAME) has been introduced as a new melanoma marker and potential target for immunotherapy. While PRAME immunohistochemistry (IHC) is well documented in surgical pathology, similar data in cytology are limited. Metastatic melanoma is frequently diagnosed via cytology samples in which IHC plays an important role. We aimed to accordingly evaluate the performance of PRAME IHC in diagnosing metastatic melanoma in cytology samples relative to other commonly used melanoma markers. MATERIALS AND METHODS: The study included 156 archival cytology cases, of which 93 were melanoma cases and 63 nonmelanoma cases (controls). All cases underwent PRAME IHC staining on cell blocks. Nuclear staining of PRAME was evaluated using a quantitative and qualitative scale. Other melanocytic IHC stain results (SOX10, S-100, Melan-A, and HMB45) were also documented. RESULTS: PRAME was detected in tumor cells in 86% of melanoma cases, which was significantly lower than SOX10 (100%) (p < .01), and similar to HMB45 (84%) and Melan-A (82%). S-100 had the lowest sensitivity of 71%. In comparison to other types of melanomas, spindle cell melanoma exhibited higher negativity for PRAME IHC (4/10 = 40%). PRAME was also expressed in some nonmelanocytic malignancies including carcinoma (5/22 = 23%), sarcoma (5/15 = 33%), and hematologic malignancies (1/9 = 11%). Overall, PRAME showed a sensitivity of 86%, specificity of 82%, positive predictive value of 70%, and negative predictive value of 92% for metastatic melanoma. CONCLUSIONS: PRAME is a useful marker for the diagnosis of melanoma in cytology material, but it is less sensitive than SOX10. PRAME is also expressed in other nonmelanocytic tumors which limits its specificity.

Metastatic prostate cancer diagnosed by fine-needle aspiration: Contemporary cytopathologic and biomarker assessment with clinical correlates.

INTRODUCTION: The diagnosis of metastatic prostatic cancer (MPC) by fine needle aspiration (FNA) can usually be rendered by typical cytomorphologic and immunohistochemical (IHC) features. However, MPC diagnosis may be complicated by transformation to atypical phenotypes such as small cell carcinoma, typically under pressure from androgen deprivation therapy (ADT). Predictive and prognostic biomarkers can also be assessed by IHC. This study illustrates how careful assessment of cytologic and biomarker features may provide therapeutic and prognostic information in MPC. DESIGN: We reviewed our anatomic pathology archives for MPC diagnosed by FNA from January 2014 to June 2021. Clinical histories, cytology slides, and cell blocks were reviewed. Extensive IHC biomarker workup was performed, including markers of prostate lineage, cell-cycle dysfunction, Ki-67, neuroendocrine markers, PDL1, and androgen receptor splice variant 7. Cases were reclassified into three categories: conventional type, intermediary type, and high-grade neuroendocrine carcinoma (HGNC). RESULTS: Eighteen patients were identified. Twelve had conventional MPC, including six of six ADT-naive patients. Six of twelve (50%) with prior ADT were reclassified as intermediary or HGNC. Four intermediary cases included two with squamous differentiation and two with pro-proliferative features. Two HGNC cases had typical small cell carcinoma cytomorphology. Expression of PDL1 was identified in two cases and ARv7 in three cases. Five of five intermediary and HGNC patients died of disease versus six of eleven with with conventional type. CONCLUSIONS: Aggressive cytomorphologic variants were commonly identified in patients with prior ADT. Identification of nonconventional cytomorphology and increased proliferation can provide important prognostic information. Recognition of these changes is important for an accurate diagnosis, and the identification of high-grade variants can affect therapeutic decision-making. Clinically actionable biomarkers such as PDL1 and ARv7 can be assessed by IHC.

Approach to Fine Needle Aspiration of Adrenal Gland Lesions.

Adrenal gland lesions are present in 1% to 5% of patients and are most commonly identified incidentally on abdominal imaging. Fine needle aspiration (FNA) cytology plays an important role in the initial workup of adrenal gland nodules, especially in patients with a known history of malignancy. The most common reason for adrenal gland FNA is to differentiate benign adrenal lesions, such as adrenal cortical adenoma, from metastatic malignancy. However, there is a significant cytomorphologic overlap between primary and metastatic adrenal neoplasms. This review focuses on the current state of adrenal gland FNA cytology, with an emphasis on distinguishing adrenocortical adenoma from carcinoma and adrenal cortical neoplasms from metastatic malignancies. The role of immunohistochemistry in specifically diagnosing adrenal neoplasms is discussed. Proposed diagnostic classification systems for adrenal gland FNA cytology are also described.

Pronounced squamous cell contamination in biliary tract cytology: A diagnostic pitfall.

Squamous cells are rarely found in biliary tract cytology specimens, and when present are typically scant in quantity. Over an 8-year time period, two cases at our institution reporting abundant squamous cells were identified. Both patients underwent endoscopic retrograde cholangiopancreatography with bile duct brushings and removal of a migrated biliary stent. The migrated stents were retrieved using rat toothed forceps and required removal of the endoscope through the esophagus with the stent exposed to esophageal and oral mucosa outside of the endoscope. Cytologic examination of the accompanying biliary stent material accordingly revealed abundant benign squamous cells. However, bile duct brushings showed benign ductal epithelial cells without squamous cells. Prior and subsequent cytology and bile duct surgical pathology specimens did not show squamous metaplasia. Migrated biliary stents that require endoscopic withdrawal increase the risk of contaminating samples with squamous cells. Recognition of this unique scenario is important, as the differential diagnosis includes squamous metaplasia and squamous neoplasia.

Salivary gland neoplasms with basaloid features in the era of the Milan system for reporting salivary gland cytology: Classification and interobserver agreement.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has been shown to have moderate to good reproducibility for categorization of salivary gland fine-needle aspiration (FNA) specimens. Less is known of its accuracy and interobserver reproducibility for categorization of the diagnostically difficult group of basaloid neoplasms. METHODS: Forty-five salivary gland specimens with a basaloid morphology (pleomorphic and monomorphic adenomas and adenoid cystic carcinomas) were independently assigned by seven cytopathologists to one of the MSRSGC categories. Interobserver agreement was assessed for average agreement, chance expected agreement and by Cohen's κ and diagnostic accuracy. Correlation of the salivary gland neoplasm of unknown malignant potential (SUMP) category with histologic diagnosis and benign or malignant designation along with interobserver reproducibility were calculated. RESULTS: Average observed agreement for assignment to the MSRSGC was 46% and Cohen's κ = 0.2%. The SUMP category did not correlate with tumor type or with the benign or malignant nature of the neoplasm. Diagnostic specificity and sensitivity were 92% and 100% for consensus diagnosis, but were 76% and 77% for individual diagnoses. CONCLUSION: The interobserver agreement in categorizing basaloid neoplasms by the MSRSGC is poorer than for salivary gland lesions overall. This reflects the difficulty in diagnosing basaloid neoplasms. Nonetheless, diagnostic accuracy appears similar to that of salivary gland neoplasms as a whole.

NR4A3 Immunostain Is a Highly Sensitive and Specific Marker for Acinic Cell Carcinoma in Cytologic and Surgical Specimens.

OBJECTIVES: Salivary gland acinic cell carcinoma (AciCC) has recognizable cytomorphologic features that can overlap with benign and malignant entities, creating a diagnostic challenge. AciCC harbors a t(4;9) translocation increasing nuclear receptor subfamily 4 group A member 3 (NR4A3) expression, detectable by immunohistochemistry (IHC) on surgical resection (SR). NR4A3 IHC cytology data are limited. Here, we examine NR4A3 IHC on smears, cell blocks (CBs), and SRs of AciCC and its mimickers. METHODS: Our cohort comprised AciCC (including high-grade transformation), secretory carcinoma, mucoepidermoid carcinoma (MEC), Warthin tumor, pleomorphic adenoma (PA), cellular PA, carcinoma ex-PA, oncocytic carcinoma, oncocytoma, and nodular oncocytosis. NR4A3 IHC (Santa Cruz Biotechnology and Origene antibodies) was positive if more than 5% tumor cells showed nuclear staining. RESULTS: Among CBs, 90% of AciCC cases and none of the mimickers expressed NR4A3. Among SRs, 100% of AciCC cases showed diffuse NR4A3, whereas one high-grade MEC expressed focal NR4A3. Concordance was 95% with two antibody clones. Sensitivity, specificity, positive predictive value, and negative predictive value were 90%, 100%, 100%, and 94.7% for CBs and 100%, 98.8%, 92.3%, and 100% for SRs, respectively. NR4A3 immunostaining was demonstrable on smears from an AciCC case. CONCLUSIONS: NR4A3 IHC can be a robust diagnostic tool to identify AciCC, especially for cytology specimens.

Cytologic features of small cell melanoma.

Small cell melanoma (SCM) is an aggressive variant of malignant melanoma (MM), which has been rarely described in the cytology literature. The aim of this study was to describe the clinical and cytologic features of a series of cases of metastatic SCM with discussion of the differential diagnosis of metastatic SCM diagnosed by fine-needle aspiration (FNA). A retrospective review of cases was performed, identifying two FNA cases and one core biopsy with touch preparation of metastatic SCM. Clinical presentation, cytomorphology features, ancillary tests, and final diagnoses were documented and analyzed. Patients ranged in age from 69 to 85 years-old. Cytomorphologic features included the presence of a monomorphic population of dispersed small round blue cells, with scant cytoplasm, high nuclear to cytoplasmic ratios, dense nuclear chromatin, and inconspicuous nucleoli. Acinar like arrangement (n = 2) and nuclear molding (n = 1) were also present. All cases showed diffuse positivity for the melanocytic markers SOX10 and Melan A by immunohistochemistry (IHC). Expression of neuroendocrine markers was variable. Diagnosing metastatic SCM at unusual anatomic sites by FNA cytology is a challenging task, especially in patients without known prior history of melanoma. Cytomorphology of SCM is unique, differing from conventional MM in many aspects, including the presence of acinar formations and a lack of typical melanoma features, such as large cells, intracytoplasmic melanin, and macronucleoli. IHC is critical for establishing the diagnosis of SCM.

Comparison of Diagnostic Rates and Concordance with Subsequent Surgical Resections between Conventional Smear and ThinPrep Preparations versus ThinPrep Only in Thyroid Fine Needle Aspiration (T-FNA) Specimens.

BACKGROUND: Thyroid fine needle aspiration (T-FNA) is a mainstay in management of thyroid nodules. However, the preparation of T-FNA specimens varies across institutions. Prior studies have compared diagnostic rates between different specimen preparations of T-FNA specimens and their associated advantages and disadvantages. However, few have compared the rates of all diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) between liquid-based preparations (LBPs) and a combination of LBP and conventional smear (CS) preparations. Our study compares TBSRTC diagnostic rates between these 2 cohorts and correlates cytologic diagnoses with subsequent thyroid resections to evaluate rates of neoplasia (RON) and malignancy (ROM). METHODS: 584 consecutive thyroid FNA specimens were collected and stratified by preparation type (ThinPrep [TP] vs. CS & TP). Diagnostic rates for each TBSRTC diagnostic category were calculated. The institution's electronic medical records database was searched for histologic diagnoses of previously sampled thyroid nodules to evaluate the RON and ROM. RESULTS: Of 584 thyroid FNA specimens, 73 (12.5%) and 511 (87.5%) were evaluated by TP only and CS & TP, respectively, reflecting the predominance of rapid on-site evaluation (ROSE) with CS for T-FNAs at our institution. Of the TP only and CS & TP cohorts, 29 (39.7%) and 98 (19.2%) had subsequent resections, respectively. The frequency of non-diagnostic cases was lower in the CS & TP cohort (12.7% vs. 26%). While the diagnostic rate of follicular lesion of undetermined significance was similar for both cohorts, SFN categorization was only utilized in the CS & TP cohort (1.5% vs. 0%). Although RON and ROM were similar between cohorts in many of the TBSRTC categories, there was a higher RON associated with non-diagnostic specimens in the TP only cohort when the denominator included all non-diagnostic cases. CONCLUSION: The combination of CS and LBP may potentially decrease the non-diagnostic rate of T-FNA specimens as well as the number of passes required for diagnosis, particularly with ROSE. Evaluation of morphologic features highlighted in conventional smears may facilitate diagnostic categorization in the "suspicious for follicular neoplasm" category.

Performance of Afirma genomic sequencing classifier vs gene expression classifier in Bethesda category III thyroid nodules: An institutional experience.

BACKGROUND: Afirma gene expression classifier (GEC) is an adjunct to thyroid fine needle aspiration shown to improve pre-operative risk assessment and reduce unnecessary surgery of indeterminate thyroid nodules. Genomic sequencing classifier (GSC) is a newer version aiming to improve specificity and positive predictive value (PPV) of Afirma testing. There are limited studies comparing GSC vs GEC. This study was undertaken to compare these classifiers in terms of diagnostic performance and effect on clinical management of indeterminate thyroid nodules. METHODS: The study cohort consisted of patients with thyroid nodules that had a recurrent cytologic diagnosis of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) and were tested by either GEC or GSC. Patient demographics, nodule size, and clinical follow-up were recorded. Benign call rate (BCR) of Afirma testing, rate of subsequent surgery (RSS), rate of histology-confirmed malignancy (RHM), as well as diagnostic sensitivity, specificity, PPV, negative predicative value (NPV), and accuracy were calculated and compared between GSC and GEC cohorts. RESULTS: Among 264 AUS/FLUS thyroid nodules, 127 and 137 were tested with GEC and GSC, respectively. Compared to GEC, GSC demonstrated increased BCR (77.3% vs 52%), decreased RSS (31.4% vs 51.2%), greater RHM (29% vs 9.8%) associated with a suspicious Afirma result, as well as improved specificity (82.8% vs 54.5%), PPV (29% vs 9.8%), and diagnostic accuracy (83.9% vs 56.7%), while maintaining high sensitivity and NPV. CONCLUSION: Afirma GSC substantially improved BCR, RSS, RHM, and diagnostic performance, enhancing appropriate triage and thereby helped avoid unnecessary surgery in AUS/FLUS thyroid nodules.

Cytologic findings in effusions from patients with SARS-CoV-2 infection.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with "flu-like" upper respiratory tract symptoms and pneumonia. Body cavity effusions develop in a subset of patients with advanced disease. Although SARS-CoV-2 is known to be present in certain body fluids (eg, blood) of COVID patients, it remains unclear if body cavity fluids are sites of infection. Our aim was to characterize the cytologic and clinical findings in COVID-19 patients with effusions. MATERIALS AND METHODS: A record search for all cases of body cavity effusion cytology in SARS-CoV-2 positive patients from March 1, 2020, to September 1, 2020, was performed. Clinical history, fluid chemical analysis, cytologic findings, and patient outcomes were recorded. All cytology slides were reviewed. In situ hybridization (ISH) targeting SARS-CoV-2 spike protein transcript (V-nCoV2019-S) was performed on cell block material in all cases. RESULTS: A total of 17 effusion cytology cases were identified among 15 COVID patients, including 13 pleural, 2 pericardial, and 2 peritoneal. Most (13 of 15) patients were hospitalized for COVID complications. Eight patients died during hospitalization, 7 from COVID complications. All fluids were transudative by protein criteria. Lymphocytic or histiocytic inflammation predominated in 12 of 17 cases. Five exhibited hemophagocytosis. No viral cytopathic changes or extra-medullary megakaryocytes were seen. Viral RNA was not detected in any case by ISH. CONCLUSIONS: Body cavity effusion is an ominous finding in patients with advanced COVID-19 disease. Such effusions tend to be transudative with lymphohistiocytic inflammation, and commonly exhibit hemophagocytosis, an otherwise rare finding in effusion cytologies. No direct infection of cellular elements by SARS-CoV-2 was identified by ISH.

An institutional experience: A retrospective analysis of the effect of transitioning from follicular lesion of undetermined significance to atypia of undetermined significance with subclassified atypia on interobserver concordance, rates of neoplasia, and rates of malignancy.

INTRODUCTION: The rate of malignancy (ROM) in thyroid fine needle aspirations (FNA) classified under "atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS), including Hürthle cell type (HLUS)" category of The Bethesda system for reporting thyroid cytopathology (TBSRTC) in literature is highly variable. The 2018 TBSRTC was updated to note a preferred categorization of AUS cases into subcategories. This study evaluates the impact of AUS subclassification on rates of neoplasia (RON), rates of malignancy (ROM), and cytopathologist (CP) concordance. METHODS: 93 thyroid FNAs previously diagnosed as FLUS or HLUS from January 1, 2013 to December 31, 2014 with subsequent surgical resection were identified. Four CPs reclassified these cases using TBSRTC AUS subcategories of follicular cells with architectural and/or cytologic atypia, predominantly Hürthle cells, and atypical lymphocytes. RON and ROM were calculated for each diagnostic subcategory for each CP. RESULTS: The original RON and ROM for FLUS cases were 31.4% and 15.1% and were 77.8% and 22.2% for HLUS cases. 10.8% of cases showed diagnostic concordance amongst the four CPs. The most frequently utilized subcategory was architectural atypia. RON ranges for architectural atypia, cytologic atypia, architectural and cytologic atypia, and predominantly Hürthle cells were 28.1% to 35.7%, 0% to 33.3%, 35.3% to 66.7%, and 57.1% to 87.5%. The range of ROM was 13.9% to 16.7%, 0% to 33%, 0% to 42.9%, and 0% to 25%, respectively. CONCLUSION: RON for AUS predominantly Hürthle cells subcategory was higher than previously reported, which may indicate use for tailored patient management pathways. AUS subclassification can result in significant interobserver variability. Therefore, institutions may consider consensus/quality control sessions to optimize diagnostic concordance.

Cytomorphology and diagnostic pitfalls of sebaceous and nonsebaceous salivary gland lymphadenoma: A multi-institutional study.

BACKGROUND: Salivary gland lymphadenoma (LAD) is a rare benign neoplasm comprising sebaceous (SLAD) and nonsebaceous (NSLAD) types. Despite established histologic criteria, limited data on cytomorphology, tumor heterogeneity, and overlap with other entities make the diagnosis of LAD by fine needle aspiration (FNA) challenging. We describe a multi-institutional cohort of 14 LADs with cytology, clinical, radiologic, and histopathologic data. METHODS: Our cohort included nine SLAD and five NSLAD with corresponding histopathology. Mean patient age and M:F ratio were 60.4 years (range 45-86 years) and 1:2 for SLADs and 57.4 years (range 42-80 years) and 1:1.5 for NSLADs, respectively. One NSLAD patient had a germline predisposition for Cowden syndrome. Glass slides and whole slide images of air-dried Diff-Quik (DQ), alcohol-stained Papanicolaou smears (Pap) and cellblocks were reviewed for key cytomorphologic findings. RESULTS: FNAs from SLAD and NSLADs demonstrated vacuolated and basaloid epithelial clusters within a lymphoid background. Vacuolated cells from SLAD showed sebaceous cells with microvesicular cytoplasm indenting a central nucleus. Vacuolated cells from NSLAD were columnar with eccentric nuclei, corresponding to abluminal glandular cells. SLADs were classified using the Milan System for Reporting Salivary Gland Cytopathology as nondiagnostic (11.1%), nonneoplastic (44.4%), atypia of uncertain significance (AUS) (22.2%), and salivary gland neoplasm of uncertain malignant potential (SUMP) (22.2%). NSLADs were classified as AUS (40%), SUMP (40%) and Benign Neoplasm (20%). CONCLUSION: Although rare, knowing the cytologic features of salivary LAD is important to avoid diagnostic pitfalls. Vacuolated cells can be prominent in both SLAD and NSLAD aspirates. Diagnostic issues arise from insufficient sampling of all tumor components leading to marked variation in diagnostic classification of LAD.

Diagnosis and categorization of malignant effusions: A 6-year review from a single academic institution.

BACKGROUND: Cytologic detection of malignant cells in pleural, peritoneal, or pericardial effusion most likely indicates advanced stage of malignant disease. There are a few studies updating the categorization of malignant effusions. METHODS: The electronic pathology database was searched to identify consecutive cases of malignant effusion during a 6-year period. Patient age and gender, origins of known malignancy, and cytologic diagnoses were recorded and summarized. RESULTS: A total of 1059 specimens included 561 (53%) pleural, 441 (41.6%) peritoneal, and 57 (5.4%) pericardial fluids. Most of the pleural (516, 92.0%), peritoneal (418, 94.8%), and pericardial (53, 93.0%) specimens were derived from patients with a single known malignancy. More common origins involving pleural fluid were lung (152, 27.1%) followed by breast (103, 18.4%) and gastrointestinal tract (76, 13.5%). The most common etiology for women and men was breast (102, 30.8%) and lung (67, 36.2%), respectively. More common origins involving peritoneal fluid were gastrointestinal (158, 35.8%) and gynecologic (156, 35.4%) tracts, and breast (46, 10.4%). The most common etiology for women and men was Mullerian (156, 55.5%) and gastrointestinal tract (94, 68.6%), respectively. Most common origins involving the pericardial fluid were breast (20, 37.7%) and lung (17, 29.8%). Breast and lung were the most common etiology for women (20, 57.1%) and men (8, 44.4%), respectively. CONCLUSIONS: Breast and lung remain to be the most common origin of both malignant pleural and pericardial effusion for women and men, respectively. The most common origin involving peritoneal effusion is Mullerian for women and gastrointestinal tract for men.

Thyroid paraganglioma: A diagnostic pitfall in thyroid FNA.

BACKGROUND: Thyroid paragangliomas are extremely rare and often are misdiagnosed by preoperative fine-needle aspiration (FNA) because their cytologic features overlap with those of other thyroid neoplasms. The objective of this study was to review the cytomorphology in a series of thyroid paragangliomas and correlate the findings with histopathology. METHODS: Five thyroid paraganglioma cases that underwent FNA were reviewed. Their clinical presentation, radiology features, cytomorphology, ancillary tests, and histopathology were analyzed. RESULTS: All patients were women with an average age of 49 years (age range, 35-61 years) and presented with an asymptomatic, solitary thyroid nodule. Radiologically, these nodules (size range, 1.8-3.0 cm) were well circumscribed, hypoechoic, and hypervascular. FNA smears showed clusters of loosely cohesive, medium-to-large epithelioid cells with clear-to-eosinophilic and occasionally foamy cytoplasm that had indistinct cytoplasmic borders. The nuclei were round to oval with focal nuclear membrane irregularities, inconspicuous nucleoli, focal marked anisonucleosis, and occasional intranuclear pseudoinclusions. Naked nuclei, variable numbers of plasmacytoid cells, multinucleated giant cells, and sustentacular cells were present in the background along with blood vessels and lymphocytes. Cytology diagnoses were incorrect and included follicular neoplasm (n = 4) and follicular lesion of undetermined significance (n = 1). Final histopathology with immunohistochemistry revealed conventional paraganglioma (n = 3) or sclerosing paraganglioma with invasive features (n = 2). CONCLUSIONS: All thyroid paragangliomas were misdiagnosed on FNA as follicular neoplasms, in part because of the rarity of these tumors in this location and cytomorphology mimicking follicles. The absence of colloid, the presence of naked nuclei, focal marked anisonucleosis, and the presence of sustentacular cells are important cytology clues.

Fine needle aspiration of salivary gland carcinomas with high-grade transformation: A multi-institutional study of 22 cases and review of the literature.

BACKGROUND: High-grade transformation (HGT) is a rare process whereby conventional low- to intermediate-grade salivary gland carcinomas (SGC) transform into high-grade, poorly or undifferentiated malignancies with focal or complete loss of their conventional histomorphologic features. Because tumors with HGT are associated with a worse prognosis than their conventional counterparts, preoperative recognition of HGT may be of benefit for optimal patient management. Using a multi-institutional approach, we describe the largest fine needle aspiration (FNA) cohort of salivary gland carcinomas with HGT. METHODS: The archives of 9 large academic medical centers were searched, and 22 cases of SGC with HGT were identified by surgical excision accompanied by preoperative FNA. Clinical and cytomorphologic features were retrospectively reviewed. RESULTS: The male-to-female ratio was 14:8, and the mean patient age was 60.2 years. The average tumor size was 3.6 cm, and 19 cases were from the parotid gland. Acinic cell carcinoma with HGT was the most common tumor subtype, comprising 12 cases with HGT, followed by adenoid cystic carcinoma, secretory carcinoma, and other subtypes. Eighteen cases were classified as malignant; however, a specific diagnosis of HGT was not made. Sixteen cases contained a high-grade cytologic component, and 7 cases had a mixture of both conventional and high-grade components retrospectively. CONCLUSIONS: SGC with HGT should be considered in the differential diagnosis of a salivary gland aspirate exhibiting high-grade cytomorphologic features. The presence of distinct tumor populations, conventional and high-grade, should prompt consideration of HGT, especially when the conventional component is acinic cell carcinoma or adenoid cystic carcinoma.

Increasing prevalence of HPV in oropharyngeal carcinoma suggests adaptation of p16 screening in Southeast Asia.

BACKGROUND: Human papillomavirus (HPV) is etiologically linked to increasing oropharyngeal squamous cell carcinoma (OPSCC) rates in the Western world. However, the role of HPV in Southeast Asia, a high incidence region, hasn't been assessed. METHODS: 96 formalin-fixed, paraffin-embedded (FFPE) tissue blocks and corresponding patient data were obtained from Srinagarind Hospital, Thailand from 2012-2017. DNA from areas of 70 %+ cellularity were genotyped using polymerase chain reaction (PCR) and stained for p16, a surrogate marker for HPV. Inverse probability weights based on data from the hospital-based cancer registry were used in statistical analyses. Adjusted linear regression was used to assess changes in OPSCC HPV prevalence and conduct projections. Kaplan-Meier and Cox proportional hazard models were used to determine HPV-specific survival differences. RESULTS: 14 patients exhibited monoinfection with HPV16, two with HPV18 and one was HPV16/18 coinfected. PCR results were in agreement with p16 staining. On average, HPV + patients were more likely to have tonsil cancer (p-value:0.002). HPV prevalence increased by 2% annually (pvalue: 0.01), from 16 % in 2012 to 26 % in 2017. At the current rate, OPSCC HPV positivity will exceed 50 % by 2030. HPV positivity was shown to be protective in Kaplan-Meier (log-rank p = 0.02) and sex, age and stage adjusted Cox models (HR:0.34 [95 %CI:0.22, 0.52]). CONCLUSION: Given the increased prevalence and similarities in presentation of HPV + OPSCC to those observed in Western countries, the data suggest the adaptation of p16 staining and subsequent restaging of OPSCC tumors as suggested by the American Joint Committee on Cancer in Southeast Asia.

Low-grade squamous intraepithelial lesion on Papanicolaou test: follow-up rates and stratification of risk for high-grade squamous intraepithelial lesion.

INTRODUCTION: Low-grade squamous intraepithelial lesion (LSIL) Papanicolaou test is associated with moderate risk of high-grade squamous intraepithelial lesion (HSIL) at colposcopic biopsy. High-risk human papillomavirus (hrHPV) cotesting risk stratifies patients with LSIL Papanicolaou test, with higher rates of HSIL for those hrHPV+. hrHPV genotyping is not considered in current LSIL management algorithms. MATERIALS AND METHODS: We performed a 2-year retrospective review of LSIL Papanicolaou tests in patients 25 to 65 years old to assess rates of follow-up and HSIL at biopsy. Patient age, hrHPV cotest and genotype results, prior screening results, and follow-up testing for 3 years were recorded. RESULTS: A total of 71.5% (376 of 526) of patients had at least 1 follow-up colposcopic biopsy; 18% had HSIL on follow-up, including 20% of hrHPV+ and 12% of hrHPV-. HSIL at biopsy was most common when HPV16/18 was present (32%) and when multiple subtypes were detected (46%) versus when non-16, non-18 hrHPV alone was present (16%) or hrHPV was negative (12%). Of those hrHPV-, 5 of 22 (23%) with a prior screening abnormality had HSIL versus 1 of 27 (4%) for those without prior abnormalities. Follow-up occurred more commonly for hrHPV+ cotests (82%) than hrHPV- cotests (54%). No differences in follow-up rate based on hrHPV genotyping was seen. CONCLUSIONS: The highest HSIL rates were seen when HPV16/18 was present (32%). HSIL rates were similar for those hrHPV- (12%) and non-16, non-18 hrHPV+ (16%). Follow-up was more common for those hrHPV+, but genotype results did not impact follow-up rates. Past screening results may impact risk of HSIL for hrHPV- cases.

Fine-Needle Aspiration Cytology of Cellular Basaloid Neoplasms of the Salivary Gland.

CONTEXT.­: Cellular basaloid neoplasms of the salivary gland represent a diverse group of benign and malignant neoplasms with significant cytomorphologic overlap on fine-needle aspiration cytology. All are marked by the presence of monotonous and usually bland basaloid epithelium. Distinction between basaloid neoplasms on fine-needle aspiration cytology is based on the presence or absence of additional features, including a second cell population (eg, myoepithelial cells), an acellular stromal component, and/or cytologic atypia within the basaloid epithelium. This review highlights the cytomorphologic features of the most common cellular basaloid neoplasms of the salivary gland, with an emphasis on classification and subclassification within the Milan System. OBJECTIVE.­: To provide a comprehensive review of the cytologic features of basaloid epithelial neoplasms of the salivary gland, with an emphasis on classification within the Milan System for Reporting Salivary Gland Cytopathology. DATA SOURCES.­: Peer-reviewed literature, recent textbooks, and personal experiences of the author. CONCLUSIONS.­: Some basaloid neoplasms, in particular pleomorphic adenomas and adenoid cystic carcinomas, may have characteristic findings on fine-needle aspiration that allow for definitive diagnosis. In other cases, however, fine-needle aspiration can confirm a neoplastic basaloid process, but specific classification of a benign or malignant neoplasm cannot be rendered. The Milan System for Reporting Salivary Gland Cytopathology acknowledges this difficulty, and recommends benign or malignant classification only when definitive diagnostic features of a specific neoplasm are present. For indeterminate cases, the subcategorization of salivary neoplasm of uncertain malignant potential is recommended.

Malignant risk of indeterminate pediatric thyroid nodules-An institutional experience.

BACKGROUND: Few studies focus on pediatric thyroid nodules categorized under indeterminate diagnostic categories. The current study was conducted to assess the risk of malignancy of indeterminate pediatric thyroid nodules. METHODS: A search of the institutional electronic pathology database from 01/2011 to 09/2018 was performed to identify pediatric (<21 years old) thyroid nodules that were interpreted as follicular lesion of undetermined significance (FLUS), suspicious for follicular neoplasm (SFN), or suspicious for malignancy (SFM) and subsequently managed with surgery, repeat fine-needle aspiration (FNA), or ≥ 6 months of clinical/imaging monitoring. Results of follow-up (F/U) surgical resections and repeat FNA/Afirma tests, and clinical and radiologic data were collected. RESULTS: We identified 46 cases from 42 patients (11-20 years old, 33 females and 9 males), including 30 FLUS, 10 SFN, and 6 SFM. Twenty-five FLUS, ten SFN, and six SFM cases underwent surgery. The histology revealed carcinomas in 36% of FLUS, 20% of SFN, and 100% of SFM categories; follicular adenomas in 32% of FLUS and 80% of SFN categories; and benign nodules in 32% of FLUS category. All five nonsurgically treated FLUS cases were considered benign based on the findings of repeat FNA/Afirma tests (n = 3, 3-22 months F/U) or clinical/radiologic exams (n = 2, 8-12 months F/U). CONCLUSIONS: Based on a limited study cohort, malignancy was identified in 36%, 20%, and 100% of surgically managed pediatric thyroid nodules categorized as FLUS, SFN, and SFM, respectively; suggesting a markedly higher malignant rate than the implied malignant risk for FLUS and SFM categories in adults.