Diagnostic accuracy of FNA to determine HPV status in HPV-associated oropharyngeal squamous cell carcinoma.

PURPOSE/OBJECTIVE(S): Accurate diagnosis of human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) affects prognosis and can alter the treatment plan. We evaluated the diagnostic accuracy of FNA biopsies to determine malignancy and HPV status in OPSCC at our institution. METHODS: Pathology samples from consecutive patients with pathologically confirmed HPV-associated OPSCC who underwent FNA of a cervical lymph node during initial diagnostic work-up were retrospectively analyzed between November 2015 and August 2021. RESULTS: Initial FNA was diagnostic for malignancy in 109/148 (73.6%) patients and non-diagnostic in 39/148 (26.4%). P16 staining of FNAs positive for malignancy showed: 54/109 (49.5%) p16 positive, 6/109 (5.5%) p16 negative, 49/109 (45.0%) p16 indeterminate. In patients with an initial non-diagnostic sampling or p16 indeterminate, repeat FNA was performed in 30/88 (34.1%) patients. Of the 30 repeat FNAs: 23/30 (76.7%) were diagnostic of malignancy and 7/30 (23.3%) remained non-diagnostic for malignancy. Of the 23 repeat FNAs diagnostic of malignancy: 16/23 (69.6%) were p16 positive and 7/23 (30.4%) were p16 indeterminate. In summary, 88/148 (59.5%) initial FNAs and 14/30 (46.7%) of repeat FNAs were non-diagnostic of malignancy or p16 indeterminate. Final yield of FNA biopsies (initial and first repeat FNA) to diagnose malignancy and p16 status was 70/148 (47.3%). CONCLUSIONS: Fine needle aspirations of lymph nodes in patients with HPV-associated OPSCC are frequently non-diagnostic for malignancy or indeterminate for p16 status, requiring repeat FNA or biopsy of the primary site. This can potentially cause treatment delay and increase morbidity and cost to the patient.

Twin/Multiple Gestations With a Hydatidiform Mole: Clinicopathologic Analysis of 21 Cases With Emphasis on Molecular Genotyping and Parental Contribution.

Complete hydatidiform moles (CHMs) and partial hydatidiform moles (PHMs) are abnormal gestations characterized by vesicular chorionic villi accompanied by variable trophoblastic hyperplasia, with or without embryonic development. CHMs are purely androgenetic (only paternal [P] chromosome complements), mostly homozygous/monospermic (~85%) but occasionally heterozygous/dispermic, whereas PHMs are overwhelmingly diandric triploid (2 paternal [P] and 1 maternal [M] chromosome complements) and heterozygous/dispermic (>95%). The presence of a fetus in a molar pregnancy usually indicates a PHM rather than a CHM; however, CHMs and PHMs rarely can be associated with a viable fetus or a nonmolar abortus in twin pregnancies and rare multiple gestation molar pregnancies have been reported. A "one-oocyte-model," with diploidization of dispermic triploid zygotes, has been proposed for twin CHM with coexisting fetus, and a "two-oocyte-model" has been proposed for twin PHM with coexisting fetus. Among 2447 products of conception specimens, we identified 21 cases of twin/multiple gestations with a molar component, including 20 CHMs (17 twins, 2 triplets, 1 quintuplet) and 1 PHM (twin). P57 immunohistochemistry was performed on all; DNA genotyping of molar and nonmolar components was performed on 9 twin CHMs, 1 triplet CHM, 1 quintuplet CHM, and 1 twin PHM. All CHM components were p57-negative and those genotyped were purely androgenetic. Twin CHMs had genotypes of P1M1+P2P2 in 5, P1M1+P1P1 in 1, and P1M1+P2P3 in 1, consistent with involvement of 1 oocyte and from 1 to 3 sperm-most commonly a homozygous CHM but involving 2 sperm in the whole conception-and compatible with a "one-oocyte-model." The triplet CHM was P1M1+P1P1+P2M2 and the quintuplet CHM was P1M1+P2M2+P2M2+P3M3+P4P4, consistent with involvement of 2 sperm and at least 2 oocytes for the triplet and 4 sperm and at least 3 oocytes for the quintuplet. The twin PHM had a P1M1+P2P3M2 genotype, consistent with involvement of 2 oocytes and 3 sperm. p57 immunohistochemistry is highly reliable for diagnosis of CHMs in twin/multiple gestations. Refined diagnosis of molar twin/multiple gestations is best accomplished by correlating morphology, p57 immunohistochemistry, and molecular genotyping, with the latter clarifying zygosity/parental chromosome complement contributions to these conceptions.

Increased Rate of ASCUS Diagnosis With Concomitant Request for High-Risk Human Papillomavirus Reflex Testing May Be Due to Cognitive Bias.

OBJECTIVES: To determine if concomitant high-risk human papillomavirus (HPV-HR) reflex testing may bias the cytologic interpretation of Papanicolaou (Pap) tests. METHODS: Percentage of atypical squamous cells of undetermined significance (ASCUS) and HPV-HR positivity was compared between Pap tests with HPV-HR cotesting and HPV-HR reflex testing for ASCUS, with subset analysis of cytopathologists' experience. RESULTS: ASCUS in the reflex group (41.5%) was significantly higher than the cotesting group (33.0%) (P = .02). There was no difference in HPV-HR positivity or ASCUS/squamous intraepithelial lesion (SIL) ratios between the two groups. The cytopathologists' experience inversely correlated with the proportion of ASCUS but did not explain the higher reflex group ASCUS. CONCLUSIONS: HPV-HR reflex testing may introduce bias in cytologic diagnosis, making it more likely that an ASCUS diagnosis is rendered. HPV-HR and ASCUS/SIL ratios were similar between the groups, so cytopathologist performance was not significantly affected. There was no effect of cytopathologists' experience.

Northern Italy in the American South: Assessing interobserver reliability within the Milan System for Reporting Salivary Gland Cytopathology.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has been proposed to standardize salivary gland fine-needle aspiration (FNA) diagnoses. This study assessed salivary gland FNA results and risk of malignancy (ROM) rates at the University of North Carolina as well as the interobserver reliability (IOR) of the atypia of undetermined significance (AUS) and salivary gland neoplasm of uncertain malignant potential (SUMP) categories. METHODS: The electronic medical record was searched for FNA cases from 2010 to 2017 with subsequent surgical resections. Histologic diagnosis was used for gold-standard comparison. The original cytologic results were then converted into MSRSGC categories (nondiagnostic, nonneoplastic, AUS, benign neoplasm, SUMP, suspicious, and malignant). For the assessment of IOR, 23 cases were selected with enrichment for cases diagnosed as AUS (n = 11) or SUMP (n = 9). Six boarded cytopathologists and 1 cytopathology fellow assessed representative slides and provided an MSRSGC diagnosis for each case. Fleiss' κ coefficients were calculated to determine IOR. RESULTS: The ROM was 33% for both AUS and SUMP cases; however, the risk of neoplasia was 56% for AUS cases and 100% for SUMP cases. Fleiss' κ for the AUS category was 0.217 (P < .05), and Fleiss' κ for the SUMP category was 0.024 (P = .74). CONCLUSIONS: In this study assessing the IOR of MSRSGC categories, fair agreement and slight agreement were found for the AUS and SUMP categories, respectively. Observers preferentially used the AUS or benign neoplasm category for SUMP cases, perhaps because of unfamiliarity with SUMP as a diagnostic option. The initial adoption of a new reporting system will require a quality assessment to ensure that the system is reliable and useful for clinicians. Cancer Cytopathol 2018;126:390-6. © 2018 American Cancer Society.

Correlation of rapid on-site evaluation with final diagnosis in the evaluation of renal lesions.

INTRODUCTION: Rapid on-site evaluation (ROSE) increases adequacy and diagnostic yield of cytology procedures and provides information for rapid clinical decisions. Cytology procedures with ROSE (fine-needle aspiration [FNA] and touch preparation with core biopsy [TP + CB]) are used to evaluate renal lesions, especially prior to concomitant ablation. MATERIALS AND METHODS: Consecutive image-guided procedures of FNA and TP + CB of renal lesions with ROSE were reviewed for a ten year period. ROSE diagnoses were correlated with final diagnoses and clinical course. Diagnoses were considered in five categories: positive, atypical/suspicious, nonspecific (including adequate, lesional, cellular, and oncocytic descriptors), negative, and nondiagnostic. Statistical analysis was performed using Fisher's exact test. RESULTS: A total of 209 procedures with 226 ROSE (73 FNA, 119 TP + CB, 17 FNA + TP + CB) were performed. FNAs had more nondiagnostic specimens than CBs by both ROSE and final diagnosis (19 of 90 versus 7 of 136 for ROSE [P = 0.0004], 15 of 90 versus 5 of 136 for final [P = 0.0013]). More FNAs than CBs were positive by ROSE (33 of 90 versus 23 of 136, P = 0.0009), with no difference in positive final diagnoses (66 of 90 versus 106 of 136, P = 0.43). Treatment following diagnosis included ablation (67, with 42 concomitant after ROSE), surgical resection (50), chemotherapy/radiation (42), re-biopsy (5), serial imaging (15), no treatment/other (15), and lost to follow up (15). CONCLUSIONS: All lesions with positive ROSE had positive final diagnoses. For cases with positive final diagnoses, ROSE diagnoses were relatively evenly distributed among positive, atypical/suspicious, and nonspecific. TP + CB had higher adequacy than FNA by both ROSE and final diagnosis, although FNAs more often had positive ROSE diagnoses.

Postoperative radiotherapy for diffuse pigmented villonodular synovitis of the temporomandibular joint.

BACKGROUND: Pigmented villonodular synovitis (PVNS) is a rare/benign condition of the synovial joint lining. It most commonly presents in the knee but has also been reported to occur in the temporomandibular joint (TMJ). Although there are several series reporting the use of postoperative radiotherapy (PORT) for extremity PVNS, there is scant literature on the use of PORT for PVNS of the TMJ. METHODS: We conducted a literature review for case reports related to PVNS of the TMJ and discuss two additional cases treated with surgery and PORT. RESULTS: 71 cases were found in the literature. 89% were the diffuse subtype. 92% had primary surgery and 7% had PORT. 68% were locally controlled. Both patients treated at our institution are locally controlled. CONCLUSIONS: PVNS of the TMJ is a rare entity. Surgery is the mainstay of treatment but PORT may be useful for local control of extensive tumors or positive margins.

Isolated myxoma of the external auditory canal.

The majority of neoplasms within the external auditory canal are benign. Management of these primary tumors and their local recurrences are discussed herein. We present a case of an isolated myxoma of the external auditory canal with a review of the common histopathological and radiographic features. Although rare, this highlights the possibility of encountering benign tumor types that carry associated morbidity or mortality due to manifestations outside of the head and neck.

Utility of fine-needle aspiration and core biopsy with touch preparation in the diagnosis of renal lesions.

BACKGROUND: Cytologic evaluation by fine-needle aspiration (FNA) and core biopsy (CB) with touch preparation (TP) is used in the diagnosis of renal lesions. METHODS: Consecutive image-guided FNA and CB, with or without TP, of renal lesions were reviewed. The cytology diagnoses were correlated with the radiology, surgical specimens, and clinical course. RESULTS: A total of 154 procedures (76 FNA, 17 FNA+CB, 46 CB+TP, 15 FNA+CB+TP) were performed for lesions with benign (21), malignant (123), or indeterminate (10) radiology. Specimen adequacy was satisfactory in 86% of FNAs (93 of 108), 95% of TPs (58 of 61), and 94% of CBs (73 of 78), and is statistically significant for CB with or without TP versus FNA (P = .045). In the subset with concerning radiology (n = 133), specimen adequacy was satisfactory in 83% of FNAs (72 of 87), 95% of TPs (58 of 61), and 94% of CBs (73 of 78) (P = .006 for CB ± TP versus FNA), and procedures were diagnostic in 79% of FNAs (69 of 87), 90% of 61 TPs (55 of 61) and 90% of CBs (70 of 78) (P = .02 for CB ± TP versus FNA). Renal cell carcinoma subtype was reported in 63% of FNA (19 of 30) versus 88% of CB ± TP (43 of 49) (P = .01), and Fuhrman nuclear grade was reported only on CB. The cytology diagnoses correlated with surgical specimens in 94% (33 of 35). The most common treatment was ablation of small (3.0 ± 1.3 cm) masses (n = 47). CONCLUSIONS: Compared with FNA, CB and TP have higher adequacy and diagnostic yield and provide more diagnostic information. Cytology diagnoses are highly accurate when correlated to surgical specimens.

Mucoepidermoid carcinoma of the parotid as a secondary malignancy after chemotherapy in a child with neuroblastoma.

Secondary neoplasms are not reported frequently after neuroblastoma, which until recently was a cancer with limited long-term survival. Although salivary gland tumors in children and adolescents may be idiopathic, they are seen more often after head and neck radiation. We report a child with stage 4 neuroblastoma treated with high-dose multiagent chemotherapy without radiation therapy to his neck who, within 1 year of treatment, developed a low-grade but large and locally aggressive mucoepidermoid carcinoma of his parotid gland further characterized by a t(11;19)(q21;p13.1). Our patient extends the spectrum of secondary neoplasms after neuroblastoma.

Absence of hyperlipidemia in LDL receptor-deficient mice having apolipoprotein B100 without the putative receptor-binding sequences.

OBJECTIVE: To examine the effects of apoB100 structure, specifically a mutation in the LDLr binding region, on the production of LDL and development of atherosclerosis in vivo. METHODS AND RESULTS: Ldlr(-/-)Apobec1(-/-) mice lacking the LDLR and apoB editing enzyme accumulated LDL in plasma and developed severe atherosclerosis when they had wild-type apoB100. In marked contrast, in Ldlr(-/-)Apobec1(-/-) mice carrying the Apob100-beta mutation, in the 2 putative LDLR-binding domains of apoB prevented both LDL accumulation and atherosclerosis. Intestinal absorption of lipids and triglyceride secretion from the liver were not affected. However, the VLDL particles with apoB100-beta were larger in volume by about 70%, and carried approximately four times as much apoE per particle. ApoB100-beta synthesis rate in the primary hepatocytes was normal, but its intracellular degradation was enhanced. Additionally, mutant apoB100 VLDL cleared from the circulation more quickly in vivo through apoE-LRP-mediated mechanism than VLDL with wild-type apoB100. In contrast, uptake of the 2 VLDL by macrophages were not different. CONCLUSIONS: While conformational change to apoB100 during conversion of VLDL to LDL exposes LDLR binding domains and facilitates LDLR-mediated lipoprotein clearance, it may also inhibit LRP-mediated VLDL uptake and contribute to LDL accumulation in familial hypercholesterolemia.

Life, death, and the risk of transfusion: a university hospital experience.

BACKGROUND: Frequently one encounters donor recruitment statements like ". . . about 90 percent of American adults will need at least one blood transfusion in the course of a lifetime." To assess the validity of such statements, the lifetime transfusion rate of patients dying in our tertiary-care hospital was determined. It would be expected that patients dying in a tertiary-care, Level 1 trauma center university hospital would have one of the highest transfusion rates. STUDY DESIGN AND METHODS: A retrospective review of blood bank and electronic clinical records was conducted for all patients who expired at our institution from January 1, 2004, through December 31, 2004. Stillborn infants were excluded from analysis. The rate of transfusion was stratified by age and sex. RESULTS: A total of 906 patients expired in 2004 at our institution. Of these, 35 were excluded (stillborn infants), leaving 871 patients for analysis. After review of blood bank records, 591 patients received blood products (67.9%). An additional 27 patients (3.1%) had a possible transfusion at another institution as the clinical record indicated complex surgical history. Only 253 patients (29.0%) did not have a documented transfusion event. Individuals who died before the age of 31 had the highest rates of transfusion (p < 0.001, Fisher's exact test, two-sided). CONCLUSIONS: The majority of patients who expire at our institution have a history of transfusion (67.9%-71.0%). Patients who die before the age of 31 have the highest rate of transfusion.

Diagnosis of human congenital cytomegalovirus infection by amplification of viral DNA from dried blood spots on perinatal cards.

Congenital human cytomegalovirus (HCMV) infection affects 1% of children and is the most common infectious cause of sensorineural hearing loss. Due to the difficulty of diagnosing deafness and other neurological disorders in infants, affected individuals may not be recognized until much later when active infection has resolved and culture is no longer informative. To overcome this problem, congenital HCMV infection was diagnosed retrospectively by testing residual blood samples collected from newborns and dried on perinatal cards as part of the North Carolina Newborn Screening Program. We modified the Qiagen method for purifying DNA from dried blood spots to increase the sample size and recovery of the lysate. A multiplex, real-time TaqMan polymerase chain reaction assay on an ABI 7900 instrument measured a highly conserved segment of the HCMV polymerase gene and the APOB human control gene. HCMV DNA was detected in blood dried on perinatal cards from all seven infants with culture-proven congenital infection, and all 24 negative control cases lacked detectable HCMV DNA. Our findings suggest that it is possible to diagnose congenital HCMV infection using dried blood collected up to 20 months earlier. Further studies are warranted on patients with hearing loss or other neurological deficits to determine the percentage that is attributable to congenital HCMV infection.