Indeterminate Thyroid Nodules and Advances in Molecular Pathology.

Thyroid cytology has in recent years been augmented by molecular testing for indeterminate lesions. Three commercial molecular tests are available which provide variable amounts of detail regarding the genetic alterations identified in a sample. This paper will describe these tests, as well as the common molecular drivers associated with papillary thyroid carcinoma (PTC) and follicular patterned lesions, in order to help the practicing pathologist and clinician better interpret the results of these tests and incorporate this information into their management of cytologically indeterminate thyroid lesions.

HPV Cotesting of Unsatisfactory Papanicolaou Tests: Implications for Follow-up Intervals.

OBJECTIVES: The 2019 American Society of Colposcopy and Cervical Pathology management guidelines recommend that patients with an unsatisfactory Papanicolaou (Pap) test (UPT) and negative human papillomavirus (HPV) cotest undergo repeat age-based screening in 2 to 4 months. The rationale is that a negative HPV test in the setting of an UPT may reflect an inadequate sample and therefore should not be interpreted as truly "negative." For patients 25 years and older who are cotested, if HPV is positive for the 16 or 18 genotypes, direct referral for colposcopy is recommended. Our study aimed to determine if a negative HPV cotest result is predictive of the absence of a high-grade squamous intraepithelial lesion (HSIL) and whether these patients may be called back for repeat testing at an interval longer than 2 to 4 months. METHODS: Follow-up cervical cytology and biopsy results in women with UPT and HPV cotests from January 2017 to December 2021 were collected. Original UPT and HPV cotest results were correlated with the follow-up Pap and biopsy results. RESULTS: There were 1,496 (2.28%) UPT cases out of 65,641 total Pap tests. Among the 1,496 UPT cases, 1,010 (67.5%) had HPV cotesting; 676 (45.1%) were followed by repeat Pap or biopsy within 4 months and 850 (56.8%) within 12 months. The total follow-up rate was 81%, with a range of 3 days to 36 months. The HSIL rate in HPV-positive cases was 5.7% (3/53) vs 0.4% (2/539) (P = .006) in HPV-negative cases. In UPT, HPV cotesting showed negative predictive values for low-grade and high-grade squamous intraepithelial lesion detection of 98.5% and 99.6%, respectively, while positive predictive values were 19% and 5.7%. CONCLUSIONS: A negative HPV cotest in individuals with UPT predicted the lack of HSIL in our study. Compliance with the recommended follow-up time of 2 to 4 months for women with UPT was low (45.1%). Our study suggests that women with UPT and negative HPV cotest may be safely called back at an interval longer than 4 months.

Molecular Profiles of Noninvasive, Minimally Invasive, and Invasive Follicular Patterned Thyroid Neoplasms with Papillary Nuclear Features.

Background: An increasing amount of data is being published, which risk-stratify thyroid tumors according to genetic signatures and histological morphology. Typically, follicular patterned lesions have been shown to harbor RAS-like mutations with more indolent behaviors. Our study aims to examine the extent of similarity among three groups of follicular patterned lesions with papillary nuclear features-noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) with capsular invasion and/or angioinvasion, and infiltrative follicular variant of papillary thyroid carcinoma (iFVPTC)-to help clarify whether NIFTP and EFVPTC represent a histological continuum and the degree to which the genomic landscape further separates higher risk follicular patterned tumors such as iFVPTC from more indolent ones (EFVPTC and NIFTP). Methods: ThyroSeq test results were compared for cases with histological NIFTP, EFVPTC, and iFVPTC in this retrospective study. Genetic drivers were subcategorized by level of aggressiveness. Gene expression alterations (GEAs) and copy number alterations (CNAs) were compared among the three histological groups. Results: NIFTP and EFVPTC cases displayed predominantly RAS-like alterations (100% and 75%, respectively) and RAS-like GEAs (55.2% and 47.2%, respectively), and many showed CNAs with 22q-loss. Despite a predominance of RAS-like alterations, EFVPTC cases showed molecular heterogeneity with significantly more intermediate and aggressive drivers (22.3% of cases) than NIFTP (0%) (p = 0.0068). iFVPTC cases displayed molecular profiles in between that of traditional follicular patterned lesions and classical papillary thyroid carcinoma, predominantly displaying intermediate and aggressive drivers (61.6%), which was significantly higher than that of EFVPTC (22.3%, p = 0.0158) and NIFTP (0%, p < 0.0001), illustrating the higher MAP kinase activity of iFVPTC. There was no significant difference, however, in comparing GEAs among the three histological groups. Conclusions: While follicular patterned lesions with papillary nuclear features overall tend to display RAS-like alterations, EFVPTC cases, followed by iFVPTC in this series, showed increasing proportions of more aggressive drivers. EFVPTC and NIFTP show much molecular overlap, with predominance of RAS-like alterations, suggesting that these tumors are part of a genetic continuum, while still ranked differentially. Preoperative molecular testing can potentially distinguish EFVPTC and iFVTPC from NIFTP based on a particular molecular signature, optimizing patient management.

The clinical significance of the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) category 5 thyroid nodules: Not as risky as we think?

BACKGROUND: Although the prevalence of thyroid nodules is high, few prove to be malignant. Based on sonographic features, the American College of Radiology Thyroid Imaging Reporting and Data System categorizes malignancy risk of thyroid nodules with associated management recommendations for each category level. Malignancy rates among nodules with a highly suspicious Thyroid Imaging Reporting and Data System category 5 warrant examination in the context of additional risk stratification tools, including cytopathology and molecular testing. METHODS: All patients who underwent fine-needle aspiration biopsy for Thyroid Imaging Reporting and Data System category 5 nodules from January 2018 to September 2021 in a large integrated academic health system were reviewed. Using the Bethesda System for Reporting Thyroid Cytopathology, categories V and VI were set as malignant. Molecular testing (ThyroSeq version 3; Rye Brook, NY) yielding ≥50% risk of malignancy was deemed positive and correlated with surgical pathology. RESULTS: A total of 496 Thyroid Imaging Reporting and Data System category 5 nodules were identified. On fine-needle aspiration cytopathology, 61 (12.3%) were malignant. The breakdown included Bethesda System for Reporting Thyroid Cytopathology I, 15 (3%); II, 362 (73%); III, 52 (10.5%); IV, 5 (1%); V, 6 (1.3%); and VI, 55 (11.1%). Of Bethesda System for Reporting Thyroid Cytopathology III/IV nodules with molecular testing (n = 53), 24.5% yielded positive results. In total, 42 (8.5%) nodules underwent surgical resection, most of which were Bethesda System for Reporting Thyroid Cytopathology VI (n = 26, 61.9%). Of excised nodules, 33 (78.6%) nodules were malignant, 6 (14.3%) benign, and 3 (7.1%) noninvasive follicular thyroid neoplasm with papillary-like nuclear features. All Thyroid Imaging Reporting and Data System category 5 nodules with malignant cytology (Bethesda System for Reporting Thyroid Cytopathology V/VI) that underwent surgery were malignant on histopathology. On average, the total Thyroid Imaging Reporting and Data System points were higher in malignant nodules compared with benign (9.3 vs 7.3; P = .015). Moreover, benign nodules more frequently received Thyroid Imaging Reporting and Data System points when the radiologist was unable to determine composition or echogenicity (33% vs 3% among malignant nodules; P = .01). CONCLUSION: Thyroid Imaging Reporting and Data System category 5 designation in thyroid nodules is associated with a lower risk of malignancy than previously reported. Benign and malignant nodules with Thyroid Imaging Reporting and Data System category 5 designation have discrepancies in certain Thyroid Imaging Reporting and Data System characteristics and individual points assigned, which may offer an opportunity for quality improvement and standardization measures in ultrasound reporting practices.

Repeat Fine-Needle Aspiration With Molecular Analysis in Management of Indeterminate Thyroid Nodules.

OBJECTIVE: To analyze clinical outcomes in a series of indeterminate thyroid nodules (ITNs) with repeat fine-needle aspiration (FNA) biopsy and results of genomic classifier. STUDY DESIGN: Historical chart review. SETTING: Tertiary care center. METHODS: We reviewed FNA samples from subjects with Bethesda III or IV diagnoses from January 2015 to December 2018 at a single institution and selected those with repeat FNA and ThyroSeq testing of the same nodule. Patient demographics, Bethesda classifications, ThyroSeq results, treatment detail, and surgical pathology, when available, were analyzed. RESULTS: Ninety-six patients with cytologic diagnosis of ITN, repeat FNA, and ThyroSeq testing were identified. Following repeat FNA, 55 nodules (57%) remained ITN; 40 (42%) were reclassified as benign; and 1 (1%) was reclassified as suspicious for malignancy. In 31 patients with ThyroSeq analysis accompanying initial and repeat FNA, 26 (84%) had the same result on each, while 5 (16%) tested ThyroSeq positive following an initially negative result (κ = 0.24). Most nodules that were downgraded to Bethesda II on repeat FNA (37/40, 93%) were managed nonsurgically. Patients with ThyroSeq-positive results were treated with surgery more often (25/28, 89%) than patients with ThyroSeq-negative results (11/68, 16%; P < .0001). In excised nodules, the prevalence of malignancy and noninvasive follicular thyroid neoplasm with papillary-like nuclear features was 28% (n = 10) and 22% (n = 8), respectively, and all malignancies were low risk. CONCLUSION: In this case series, repeat FNA helped patients with ITNs avoid diagnostic surgery through reclassification to benign cytology. The risk of high-risk malignancy in ThyroSeq-positive nodules with repeat indeterminate cytology was low.

Proportion of Malignancy and Evaluation of Sonographic Features of Thyroid Nodules Classified as Highly Suspicious Using ACR TI-RADS Criteria.

OBJECTIVES: The reported malignancy rate of highly suspicious thyroid nodules based on the ACR TI-RADS criteria (TI-RADS category 5 [TR5]) varies widely. The objective of our study was to determine the rate of malignancy of TR5 nodules at our institution. We also aimed to determine the predictive values of individual sonographic features, as well as the correlation of total points assigned to a nodule and rate of malignancy. METHODS: Our single-institution retrospective study evaluated 450 TR5 nodules that had cytology results available, in 399 patients over a 1-year period. Sonographic features and total TI-RADS points were determined by the interpreting radiologist. Statistical analyses included logistic regression models to find factors associated with increased odds of malignancy, and computing sensitivity, specificity, positive and negative predictive values of various individual sonographic features. RESULTS: Of the 450 nodules, 95 (21.1%, 95% exact confidence interval 17.4-25.2%) were malignant. Each additional TI-RADS point increased the odds of malignancy (adjusted odds ratio 1.35, 95% confidence interval 1.13-1.60, P < .001). "Very hypoechoic" was the sonographic feature with the highest specificity and positive predictive value for malignancy (95.5 and 44.8%, respectively), while "punctate echogenic foci" had the lowest positive predictive value (20.0%). CONCLUSIONS: The rate of malignancy of TR5 nodules at our institution was 21.1%, which is lower than other malignancy rates reported in the literature. The total number of points assigned on the basis of the TI-RADS criteria was positively associated with malignancy, which indicates that TR5 should be viewed as a spectrum of risk.

Role of High-Risk HPV Testing in Papanicolaou Tests With Atypical Glandular Cells With and Without Concurrent Squamous Cell Abnormalities.

OBJECTIVES: Data on Papanicolaou (Pap) tests with atypical glandular cells (AGCs) with concurrent squamous cell abnormalities (AGC + Sq) are limited. We evaluated histologic outcomes and the role of high-risk human papillomavirus (HR-HPV) testing in this setting compared with AGCs without concurrent squamous cell abnormalities (AGC-alone). METHODS: This study used a retrospective cohort of patients with Pap test diagnoses of AGC + Sq and AGC-alone between October 2013 and August 2021. RESULTS: We included 287 Pap tests from 278 patients. The HR-HPV test was positive in 55% of AGC + Sq cases and 14% of AGC-alone cases (P < .0001). Most AGC + Sq cases displayed squamous lesions (41.5%) or were benign (41.5%) on histology, whereas AGC-alone cases were predominantly benign (72%) or extracervical neoplasms (18%). AGC + Sq cases showed higher rates of significant histologic lesions (P = .0001), which were associated with positive HR-HPV status (P = .0012). In AGC-alone cases, HR-HPV status was associated with significant histology only in patients 50 years of age or younger. In both groups, 20% or more of HR-HPV-negative patients harbored significant lesions. CONCLUSIONS: AGC + Sq represents a distinct group of patients. HR-HPV testing and patient age provide useful information in the evaluation of AGC, but triage based on HR-HPV testing is not recommended because of the potential for missing significant lesions.

Liver fluke eggs in bile duct brush cytology: An unexpected diagnosis during evaluation of a biliary stricture.

Clonorchis sinensis, a liver fluke parasite, infects humans through ingestion of raw or undercooked fish, crabs, or crayfish in endemic areas where the parasite is found. Clonorchis sinensis infects the liver, gallbladder, and bile duct in humans, causing Clonorichiasis. Although the majority of patients are asymptomatic, long-lasting infections may cause severe disease. Without treatment, human infection may persist for the parasite's lifespan (25-30 years). Pathologic diagnosis can be challenging as sampling may demonstrate limited cellularity with minuscule eggs that may be overlooked. Here, we report a rare case of liver fluke eggs diagnosed in bile duct brush cytology.

The Milan System for Reporting Salivary Gland Cytopathology.

OBJECTIVES: Our study assesses whether the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) offers any benefit over the original cytology classification, and measures interobserver agreement. METHODS: Four cytopathologists retrospectively blindly classified preoperative cytology by MSRSGC from 101 resected salivary tumors. Consensus MSRSGC diagnoses were correlated with surgical pathology diagnoses and compared with the original cytology classification. Diagnostic parameters were calculated for both systems. Interobserver variability was assessed. RESULTS: The original cytology classification vs MSRSGC had sensitivity, specificity, positive predictive value, and negative predictive value of 75.0% vs 78.3%, 97.1% vs 98.0%, 91.2% vs 94.7%, and 90.1% vs 90.0%, respectively. The original cytology classification risk of neoplasm (RON) was 91.7% for "negative for malignancy" and 100.0% for other categories. The MSRSGC RON was 71.4% in category II (nonneoplastic) and 100.0% in all other categories. The original cytology classification risk of malignancy (ROM) ranged from 0.0% for "atypical" to 100.0% for "positive for malignancy." The MSRSGC ROM ranged from 0.0% in categories I (nondiagnostic) and III (nonneoplastic) to 100.0% in category VI (malignant). Weighted agreement using the MSRSGC was 92% (Gwet AC1, 0.84); unweighted agreement was 69% (Gwet AC1, 0.64). MSRSGC category IVA (benign neoplasm) was most likely to show interobserver agreement, with complete agreement in 67% of cases. CONCLUSIONS: The MSRSGC performs similarly to the original cytology classification and shows relatively high interobserver agreement.

Evaluation of ACR TI-RADS cytologically indeterminate thyroid nodules and molecular profiles: a single-institutional experience.

INTRODUCTION: The American College of Radiology (ACR) Thyroid Imaging Reporting and Data Systems (TI-RADS) was developed to standardize thyroid ultrasound reports and predict the likelihood of malignancy. In our study, we aimed to correlate indeterminate thyroid fine needle aspiration cytology cases with preceding ultrasound (US) ACR TI-RADS scores and concurrent molecular testing results to examine how well the use of the ACR TI-RADS in our institution predicted which patients with indeterminate cytology might harbor molecular alterations. MATERIALS AND METHODS: We performed a retrospective review of thyroid nodules. Patients with US reports that included TI-RADS scores, fine needle aspiration specimens with indeterminate cytology (Bethesda class III-V), and molecular testing results were included. RESULTS: A total of 46 indeterminate cytology cases had had preceding US reports with TI-RADS scores and molecular testing (Bethesda class III, n = 37; Bethesda class IV, n = 6; Bethesda class V, n = 3). Most of the indeterminate cases had had a TI-RADS score of TR4 (31 of 46; 67.39%) or TR5 (9 of 46; 19.57%). RAS mutations were the most common alteration (n = 12). Of the 46 cases, 22 (47.85%) showed no alterations. Ten cases proceeded to surgery, of which seven displayed malignancies. CONCLUSIONS: Molecular testing in cytologically indeterminate thyroid nodules provided valuable information for TR4 and TR5 lesions; however, the TR2 and TR3 lesions often had no molecular alterations. These findings highlight the potential value of including US imaging features when assessing the significance of indeterminate cytology findings.

Do ACR TI-RADS scores demonstrate unique thyroid molecular profiles?

PURPOSE: The present study aimed to examine the molecular profiles of cytologically indeterminate thyroid nodules stratified by American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) categories and to determine whether certain ultrasonographic features display particular molecular alterations. METHODS: A retrospective review was conducted of cases from January 1, 2016 to April 1, 2018. Cases with in-house ultrasonography, fine-needle aspiration Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) diagnoses, molecular testing, and surgery were included. All cases were diagnosed as TBSRTC indeterminate categories. The ultrasound studies were retrospectively reviewed and assigned TI-RADS scores (TR1-TR5) by board-certified radiologists. The final diagnoses were determined based on the surgical resection pathology. Binary logistic regression analysis was used to study whether demographic characteristics, TI-RADS levels, and TBSRTC diagnoses were associated with ThyroSeq molecular results. RESULTS: Eighty-one cases met the inclusion criteria. RAS mutations were the most common alteration across all TI-RADS categories (TR2 2/2; TR3 10/19, TR4 13/44, and TR5 8/16), and did not stratify with any particular TI-RADS category. Only TR4 and TR5 categories displayed more aggressive mutations such as BRAFV600E and TERT. ThyroSeq results were positively correlated with thyroid malignancy when non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was categorized in the malignant category (odds ratio [OR], 6.859; P<0.01), but not when NIFTP was removed from the malignancy category. Echogenicity scores were found to be negatively correlated with ThyroSeq results in thyroid nodules (OR, 0.162; P<0.01). CONCLUSION: Higher-risk molecular alterations tended to stratify with the higher TI-RADS categories.

Ganglioneuroma on fine needle aspiration cytology: Case series and review of the literature.

We report two cases of an uncommon benign lesion, retroperitoneal ganglioneuroma, first diagnosed on fine needle aspiration (FNA) cytology. Our first case presented with nausea, constipation, vomiting, and neutropenia after three cycles of chemotherapy for breast cancer treatment, while our second patient presented with seemingly unprovoked abdominal pain and progressive neuropathy. Both underwent computed tomography (CT) scans, in which a soft tissue mass was found in the retroperitoneal space in each patient. An endoscopic ultrasound guided (EUS) FNA was performed on both patients, and as a result, the masses were diagnosed as retroperitoneal ganglioneuromas. As retroperitoneal ganglioneuromas have low incidence of proliferation, invasive surgery was avoided in favor of routine follow-up imaging. Cytologically, both masses showed large, scattered ganglion cells with abundant cytoplasm and large nuclei against a background of wavy spindle cells with elongated nuclei. Histologically, both were positive for S-100. When an EUSFNA is performed and quality material is collected, a diagnosis of retroperitoneal ganglioneuroma may be established, preventing invasive surgery and its accompanying risks in favor of routine follow-up imaging.

Predictive Value of a Genomic Classifier in Indeterminate Thyroid Nodules Based on Nodule Size.

Importance: Genomic classifiers were developed to better guide clinicians in the treatment of indeterminate thyroid nodules (ITNs). To our knowledge, whether there is variation in the diagnostic accuracy of these tests depending on ITN size has not been previously studied. Objective: To analyze the diagnostic performance of a genomic classifier in relation to ITN size. Design, Setting, and Participants: A case series study with medical records review was conducted including all patients with a cytologic diagnosis of ITN managed with genomic classifier testing and surgery from January 2015 to December 2018 at NYU Langone Health. Demographics, ITN characteristics, genomic profiles, treatment, and final pathologic findings were recorded. Data analysis was conducted from March to April 2021. Main Outcomes and Measures: The primary aim was to assess the positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of a genomic classifier test (ThyroSeq) in relation to ITN size (<2, 2-4, and >4 cm). The secondary aim was to investigate the risk of cancer associated with genetic signatures. Results: Of the 212 patients with 218 ITNs, 158 (74.5%) were women; median (SD) age was 49 (15.6) years. Genomic classifier results were positive in 173 ITNs (79.4%) treated with surgery. In this group of 173 positive ITNs, 46 (26.6%) were malignant on final pathologic testing. Overall, the observed cancer prevalence in the population was 23.9% (52 ITNs). In 45 ITNs that underwent surgery despite a negative genomic classifier interpretation, 6 (13.3%) were malignant. The PPV of a positive test was 27% and the NPV was 87%. The PPV and NPV findings improved as the ITN size increased (<2 cm [n = 98]: PPV, 25%; NPV, 79% vs >4 cm [n = 33]: PPV, 50%; NPV, 89%). Test specificity was higher in larger ITNs (<2 cm: 15% vs >4 cm: 40%; P = .01). Isolated RAS sequence variations were the most common variant identified in malignant nodules (11 [21.1%] of all ITNs), followed by BRAF variants (7 [13.5%] of all ITNs). Conclusions and Relevance: In this case series, the performance of the ThyroSeq test improved for larger ITNs. The risk of cancer in large ITNs with negative test results was low. These data suggest that, in genomic classifier-negative ITNs larger than 4 cm, initial management of thyroid lobectomy may be sufficient.

Gastric glomus tumor diagnosed by fine needle aspiration of the stomach: A report of two cases and review of the literature.

Glomus tumors make up 1% of stromal tumors of the stomach. Radiologic diagnosis of glomus tumors can be challenging as they share imaging characteristics with other neuroendocrine tumors and gastrointestinal stromal tumors. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been reported as a useful method for the evaluation of gastrointestinal lesions. We report two cases of gastric glomus tumors in which EUS-FNA diagnosis was challenging. Cytologically, neoplastic cells were round to oval, uniform, bland appearing epithelioid cells with delicate chromatin and inconspicuous to vague nucleoli. Both samples lacked worrisome features such as high nuclear grade, high mitotic rate, and necrosis. Neoplastic cells were negative for Cam5.2 and AE1/AE3 with focal expression of synaptophysin in one of the cases. A definitive diagnosis was not made based on FNA. Familiarity with glomus tumors in the GI system and procurement of adequate material for cell block allowing the use of immunohistochemistry may allow an accurate preoperative diagnosis.

Effusion fluid cytology and COVID-19 infection.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for coronavirus disease 2019 (COVID-19), is known to cause severe respiratory infections with occasional accompanying pleural effusion (PE), pericardial effusion (PCE), or peritoneal effusion (PTE). The effect of COVID-19 on effusion cytology is not yet known. This study aimed to examine the cytomorphologic features and workup of effusion fluids in patients with active COVID-19 infection versus those in recovery. METHODS: PE (n = 15), PCE (n = 1), and PTE samples (n = 20) from hospitalized patients with a SARS-CoV-2 infection (from June 1, 2020, to December 30, 2020) were reviewed. Effusion fluids with metastatic carcinoma were excluded. Differential cell counts, cytomorphology, and relevant immunostains for effusion fluids were retrospectively evaluated and compared between patients with active infection (positive on a SARS-CoV-2 nucleic acid amplification test [NAAT] within 2 months; n = 23) and those in the recovery phase from COVID-19 (negative on a SARS-CoV-2 NAAT for >2 months; n = 13). RESULTS: The cytology diagnoses were negative for malignancy (n = 31), atypical (n = 4), and suspicious for malignancy (n = 1). Active infection cases showed more atypical mesothelial cells than recovery cases (P < .05); some had enlarged nuclei, prominent nucleoli, occasional multinucleation, and bizarre nuclei. Immunostains were performed more often in active infection cases than recovery cases (47.8% vs 7.7%; P < .05). Differential cell counts (available for 28 cases) showed no significant differences between the active infection and recovery groups. CONCLUSIONS: This study found atypical and bizarre mesothelial cells more often in effusions of cases with active COVID-19 infection in comparison with patients in recovery. It is important for cytopathologists to become familiar with the cytomorphologic effects of SARS-CoV-2 on effusion cytology so that these cases can be properly triaged.

Myopericytoma of the Parotid and Molecular Profiling: Report of a Rare Case and Review of the Literature.

Myopericytomas are uncommon tumors defined by their round to spindle shaped cells often arranged in a concentric pattern of perivascular growth. They are typically well-circumscribed, nodular, slow-growing lesions that occur in the soft tissue of the extremities. Here, we present a 30-year-old female with a 2.4 cm myopericytoma occurring in the deep lobe of the parotid gland. The diagnosis was made with detailed histopathologic and immunohistochemical findings and positive identification of the specific mutation for PDGFRß p.Asp666Lys by next generation sequencing (NGS). This is the first case report of a parotid myopericytoma with a genetic testing that shows a particular mutation that has been linked to myopericytomatosis.

Growth hormone secreting pituitary carcinomas: Case report and review of literature.

OBJECTIVE: Pituitary carcinoma is a rare tumor, defined as a tumor of adenohypophyseal cells with systemic or craniospinal metastasis. We present a case of a growth hormone (GH)-secreting pituitary carcinoma with a review of literature to better characterize this disease. DESIGN: Case report and literature review of 25 cases of GH-secreting pituitary carcinomas RESULTS: The age of diagnosis of GH-secreting carcinomas ranged 24-69 years old with a mean age of 44.4 with 52% of cases present in females. Mean latency period between diagnosis of acromegaly and transition to pituitary carcinoma was 11.4 years with mean survival being 3.4 years. CONCLUSION: Growth hormone (GH)-secreting pituitary carcinomas are rare and hard to distinguish from aggressive pituitary adenomas. From review of literature, treatment options include debulking surgery, radiotherapy, or chemotherapy with dismal outcomes. There are no diagnostic markers or features which can predict metastatic progression of these tumors. Future studies with genomic landscapes and relevant tumor markers are needed to identify pituitary tumors most likely to metastasize.

p16 immunostaining in fine-needle aspirations of the head and neck: determining the optimal positivity threshold in HPV-related squamous cell cancer.

INTRODUCTION: There is no consensus for interpretation of p16 immunohistochemistry (IHC) in cytology preparations. Our study aims to assess p16 IHC staining in formalin-fixed cytology cell blocks (CBs) from head and neck squamous cell carcinoma (HNSCC) fine-needle aspiration (FNA) specimens in comparison with surgical pathology p16 staining and to determine the reproducibility of p16 IHC scoring in CBs. METHODS: A total of 40 FNAs from 2014 to 2019 of HNSCC with p16 IHC were obtained. CB p16 staining was scored independently by 5 cytopathologists as interval percentages of tumor cell positivity. Receiver operating characteristic (ROC) curves were examined to determine optimal cutoffs for each pathologist based on sensitivity and specificity values. Gwet's coefficient (AC1) was calculated to assess inter-rater reliability. RESULTS: Greater than 10% was the lowest threshold to reach 100% specificity with high sensitivity (55%-84%) in all 5 raters. Rater performances were similar, with areas under the curve (AUCs) ranging from 0.89 to 0.95. Using the >10% threshold, Gwet's AC1 = 0.72 (95% CI: 0.56-0.89). Diagnostic performance improved further when low-cellularity cases were excluded, with AUC ranging from 0.94 to 0.99 and Gwet's AC1 = 0.79 (95% CI: 0.61-0.98). CONCLUSION: p16 IHC performed on cytology CBs can serve as a surrogate marker for the detection of HPV with high sensitivity and specificity levels. Using a threshold lower than that recommended for surgical pathology for the interpretation of p16 positivity may be appropriate for FNA cytology CB preparations. All cytopathologists in our study displayed reproducible high sensitivity and specificity values at the >10% threshold.

Lessons Learned From an Anatomic Pathology Department in a Large Academic Medical Center at the Epicenter of COVID-19.

Many state-wide, city-wide, and hospital-wide changes have been implemented due to the ongoing COVID-19 crisis. We describe lessons learned in an anatomic pathology division at a tertiary care center during the peak of the COVID-19 pandemic in the hopes that knowledge of our experiences can benefit other pathology departments as they encounter this pandemic. Five categories that are critical in strategic planning for the COVID-19 pandemic are discussed: workload, departmental policy revisions, impact on faculty, workforce staffing, and impact on educational programs, including residency and fellowship training. Although the volume of COVID-19 testing had grown placing increased demands on the clinical pathology laboratory, the volume of anatomic pathology cases had declined during the COVID-19 peak. Lessons learned were widespread including changes in the anatomic pathology workflow due to declining surgical and cytologic case volumes and increases in autopsy requests. Modifications were required in gross room policies, levels of personal protective equipment, and workforce. Travel and meeting policies were impacted. Adaptations to residency and fellowship programs were vast and included innovations in didactic and interactive education. We must learn from our experiences thus far in order to move forward, and we hope that our experiences in an anatomic pathology department in the epicenter of the COVID-19 pandemic can help other pathology departments across the country.