Pancreaticobiliary Cytology Practice in 2021: Results of a College of American Pathologists Survey.

CONTEXT.­: The College of American Pathologists (CAP) surveys provide national benchmarks of pathology practice. OBJECTIVE.­: To investigate pancreaticobiliary cytology practice in domestic and international laboratories in 2021. DESIGN.­: We analyzed data from the CAP Pancreaticobiliary Cytology Practice Supplemental Questionnaire that was distributed to laboratories participating in the 2021 CAP Nongynecologic Cytopathology Education Program. RESULTS.­: Ninety-three percent (567 of 612) of respondent laboratories routinely evaluated pancreaticobiliary cytology specimens. Biliary brushing (85%) was the most common pancreaticobiliary cytology specimen evaluated, followed by pancreatic fine-needle aspiration (79%). The most used sampling methods reported by 235 laboratories were 22-gauge needle for fine-needle aspiration (62%) and SharkCore needle for fine-needle biopsy (27%). Cell block was the most used slide preparation method (76%), followed by liquid-based cytology (59%) for pancreatic cystic lesions. Up to 95% (303 of 320) of laboratories performed rapid on-site evaluation (ROSE) on pancreatic solid lesions, while 56% (180 of 320) performed ROSE for cystic lesions. Thirty-six percent (193 of 530) of laboratories used the Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology in 2021. Among all institution types, significant differences in specimen volume, specimen type, ROSE practice, and case sign-out were identified. Additionally, significant differences in specimen type, slide preparation, and ROSE practice were found. CONCLUSIONS.­: This is the first survey from the CAP to investigate pancreaticobiliary cytology practice. The findings reveal significant differences among institution types and between domestic and international laboratories. These data provide a baseline for future studies in a variety of practice settings.

Shape-Sensing Robotic-Assisted Bronchoscopy with Concurrent use of Radial Endobronchial Ultrasound and Cone Beam Computed Tomography in the Evaluation of Pulmonary Lesions.

PURPOSE: Lung nodules are a common radiographic finding. Non-surgical biopsy is recommended in patients with moderate or high pretest probability for malignancy. Shape-sensing robotic-assisted bronchoscopy (ssRAB) combined with radial endobronchial ultrasound (r-EBUS) and cone beam computed tomography (CBCT) is a new approach to sample pulmonary lesions. Limited data are available regarding the diagnostic accuracy of combined ssRAB with r-EBUS and CBCT. METHODS: We conducted a retrospective analysis of the first 200 biopsy procedures of 209 lung lesions using ssRAB, r-EBUS, and CBCT at UT Southwestern Medical Center in Dallas, Texas. Outcomes were based on pathology interpretations of samples taken during ssRAB, clinical and radiographic follow-up, and/or additional sampling. RESULTS: The mean largest lesion dimension was 22.6 ± 13.3 mm with a median of 19 mm (range 7 to 73 mm). The prevalence of malignancy in our data was 64.1%. The diagnostic accuracy of ssRAB combined with advanced imaging was 91.4% (CI 86.7-94.8%). Sensitivity was 87.3% (CI 80.5-92.4%) with a specificity of 98.7% (CI 92.8-100%). The negative and positive predictive values were 81.3% and 99.2%. The rate of non-diagnostic sampling was 11% (23/209 samples). The only complication was pneumothorax in 1% (2/200 procedures), with 0.5% requiring a chest tube. CONCLUSION: Our results of the combined use of ssRAB with r-EBUS and CBCT to sample pulmonary lesions suggest a high diagnostic accuracy for malignant lesions with reasonably high sensitivity and negative predictive values. The procedure is safe with a low rate of complications.

Oxidized Regenerated Cellulose (Surgicel®) on Cytology/Histology.

INTRODUCTION: In patients with a history of malignancy, follow-up surveillance of lymph nodes (LNs) is required to evaluate for potential malignancy or infection. In some cases, the lymphadenopathy may be secondary to an intraprocedural hemostatic agent and/or related granulomatous reaction. CASE PRESENTATION: We present the case of an 80-year-old female with a remote past medical history of breast cancer status post-lumpectomy and chemoradiation. Twenty years later, a 2.4 cm pulmonary right middle lobe nodule was noted on imaging studies. She underwent bronchoscopy, cervical mediastinoscopy, and right middle lobe wedge resection. The final pathologic diagnosis was a pulmonary carcinoid tumor, and the excised mediastinal LN was negative for malignancy. A 10-month surveillance positron emission tomography scan showed new mildly avid mediastinal and right hilar LNs. The following endobronchial ultrasound-guided transbronchial needle aspiration showed unremarkable lymphoid elements in the enlarged 4R LN, while the station 7 LN demonstrated ample dense hyaline-like foreign material. Subsequent review of the cell block/biopsy and communication with the thoracic surgeon revealed that Surgicel® (or oxidized regenerated cellulose) was placed during surgery at the station 7 site. DISCUSSION/CONCLUSION: Assessment of the findings and based on the similar histologic appearance reported in previous cases associated with Surgicel® [Ann Thorac Med. 2017;12(1):55-6, Cancer Cytopathol. 2019;127(12):765-70, and Arch Bronconeumol. 2020;56(7):459-71], the station 7 acellular, amorphous, and hyaline-like exogenous material found in our case was interpreted as hemostatic agent compatible with Surgicel® (or oxidized regenerated cellulose). This case highlights the importance of cytologic/histologic recognition of hemostatic agents, specifically oxidized cellulose mesh.

Cdk5 drives formation of heterogeneous pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous population of neoplasms that arise from hormone-secreting islet cells of the pancreas and have increased markedly in incidence over the past four decades. Non-functional PanNETs, which occur more frequently than hormone-secreting tumors, are often not diagnosed until later stages of tumor development and have poorer prognoses. Development of successful therapeutics for PanNETs has been slow, partially due to a lack of diverse animal models for pre-clinical testing. Here, we report development of an inducible, conditional mouse model of PanNETs by using a bi-transgenic system for regulated expression of the aberrant activator of Cdk5, p25, specifically in ß-islet cells. This model produces a heterogeneous population of PanNETs that includes a subgroup of well-differentiated, non-functional tumors. Production of these tumors demonstrates the causative potential of aberrantly active Cdk5 for generation of PanNETs. Further, we show that human PanNETs express Cdk5 pathway components, are dependent on Cdk5 for growth, and share genetic and transcriptional overlap with the INS-p25OE model. The utility of this model is enhanced by the ability to form tumor-derived allografts. This new model of PanNETs will facilitate molecular delineation of Cdk5-dependent PanNETs and the development of new targeted therapeutics.

Low Molecular Weight Cytokeratin Immunostaining for Extrafollicular Reticulum Cells is an Effective Means of Separating Salivary Gland Tumor-Associated Lymphoid Proliferation from True Lymph Node Involvement.

Tumor-associated lymphoid proliferation (TALP) is a well-recognized lymphocytic reaction that is commonly associated with certain salivary gland tumors. A salivary carcinoma with TALP may be confused for true lymph node involvement by that tumor, constituting a potential pitfall in tumor staging that may result in unnecessary therapeutic intervention or erroneous prognostication for patients. True lymph nodes harbor populations of extrafollicular reticulum cells (ERCs), which can be highlighted by low molecular weight cytokeratin immunohistochemistry. We sought to determine whether low molecular weight cytokeratin Cam5.2 immunostaining may be utilized to differentiate true lymph node involvement by salivary gland tumors from TALP. The surgical pathology archives of the University of Texas Southwestern Medical Center was searched for cases of salivary gland neoplasms exhibiting either TALP or true lymph node involvement. Hematoxylin and eosin-stained sections were examined. Cases were classified on the basis of a definitive lymph node capsule and subcapsular sinus, as seen on routine histologic evaluation. Low molecular weight cytokeratin Cam5.2 immunostaining was performed and evaluated on all cases. Twenty-three salivary gland carcinomas with TALP and 16 carcinomas involving a lymph node (14 carcinomas metastatic to regional lymph nodes and 2 carcinomas arising from benign lymph node inclusions) were identified. Numerous Cam5.2-positive ERCs were identified within the nodal tissue of all true lymph nodes involved by carcinoma (16 of 16 cases), while Cam5.2-positive ERCs were completely absent in all cases of salivary gland lesions with TALP (0 of 23 cases) (100% vs. 0%, p < .0001, Fisher's Exact). Utilization of low molecular weight cytokeratin Cam 5.2 immunostaining for ERCs is a highly useful tool for distinguishing true lymph node involvement by salivary gland carcinomas from TALP. This strategy may be useful in identifying genuine nodal metastasis in histologically ambiguous cases, and to avoid erroneously upstaging tumor with TALP as nodal metastasis with the resulting prognostic and therapeutic implications. Moreover, low molecular weight cytokeratin immunostaining may be useful in confirming the rare examples of salivary gland tumors arising from intranodal salivary gland inclusions.

Lung Nodule with Increasing Fluorodeoxyglucose Uptake in a Patient with a History of Lung Carcinoma and Talc Pleurodesis Evaluated by EBUS-TBNA On-Site Assessment.

BACKGROUND: Fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan is an indicator of potential malignancy or infection. Patients with a history of talc pleurodesis can develop pleural or lung parenchymal nodules/talcomas. In these patients, talc-associated (non-malignancy-related) FDG uptake may occur over years. CASE REPORT: A 66-year-old female presented with a past medical history significant for resected non-small-cell lung cancer and was treated with chemotherapy/radiation. The referring physician indicated that she subsequently developed benign pleural effusions and had talc pleurodesis to limit recurrence. The patient was referred to our institution for endobronchial ultrasound-guided transbronchial fine-needle aspiration (EBUS-TBNA) due to a new left upper lobe nodule with increasing FDG uptake on follow-up interval PET performed at the referring institution. On-site cytologic evaluation showed no evidence of malignancy, but found refractile foreign material, consistent with the presence of talc particles. CONCLUSION: This case presents the importance of cytologic recognition of talc particles during on-site evaluation and discusses the phenomenon of increasing PET-FDG uptake associated with talc pleurodesis.

Pleural fluid extramedullary hematopoiesis case report with review of the literature.

Extramedullary hematopoiesis (EMH) is the trilineage formation of normal blood cells outside of the bone marrow. While predominantly seen in the spleen and liver, EMH rarely occurs in serous effusions. Accurate diagnosis requires recognition of megakaryocytes and other precursor hematopoietic elements. We present a case of pleural fluid EMH in a patient with primary myelofibrosis and developing leukemia, with a review of the literature, prognostic implications and diagnostic challenges.

Lymphangioleiomyomatosis diagnosed by effusion cytology: A case report.

Lymphangioleiomyomatosis (LAM) is a rare lung disease traditionally affecting women during their childbearing years. It can be sporadic or be associated with tuberous sclerosis syndrome. It is usually manifested in the lungs, kidneys, and/or lymphatic system. It consists of an overgrowth of abnormal smooth muscle-like cells, usually along the bronchovascular structures, resulting in the formation of cysts and the destruction of the lung parenchyma. We present the case of a 43-year-old woman with a history of pleural effusion and dyspnea. A computed tomographic scan revealed a mediastinal mass, chylothorax, and multiple pulmonary cysts. A diagnosis of LAM was rendered on a pleural fluid sample.

Central portalization correlates with fibrosis but not with risk factors for nonalcoholic steatohepatitis in steatotic chronic hepatitis C.

Concomitant steatosis in chronic hepatitis C is associated with fibrosis and unfavorable treatment outcome. Central zone injury in nonalcoholic steatohepatitis (NASH) manifests as central portalization, with centrizonal microvessels and ductular reaction. We investigated whether central portalization in steatotic HCV biopsies would identify patients with metabolic risk factors for NASH. Liver biopsies with chronic hepatitis C and >10% steatosis (n = 65) were evaluated for the degree of steatosis, zonation of steatosis, fibrosis, and nonalcoholic fatty liver disease (NAFLD) activity score. The presence of centrizonal microvessels, sinusoidal capillarization, ductular reaction, and CK7 positive intermediate-phenotype hepatocytes were evaluated by CD34 and CK7 immunostain. The degree of steatosis and fibrosis showed a positive correlation. Additional positive correlations were noted between centrizonal angiogenesis and NAFLD activity score and central portalization and fibrosis. However, neither central portalization nor zonation of steatosis identified patients with metabolic risk factors for NASH. Therefore, central portalization cannot be used as a surrogate marker to identify patients with metabolic risk factors for NASH in steatotic HCV biopsies. The mechanism of centrizonal injury in steatotic HCV hepatitis is not solely attributable to the metabolic risk factors for NASH.

Cytology specimens offer an effective alternative to formalin-fixed tissue as demonstrated by novel automated detection for ALK break-apart FISH testing and immunohistochemistry in lung adenocarcinoma.

BACKGROUND: Minimally invasive sampling by cytology or core needle biopsy often provides an initial diagnosis for treatment in patients with lung nodules. From these limited specimens, multiple molecular studies are frequently requested. Current guidelines from the US Food and Drug Administration recommend using formalin-fixed paraffin-embedded tissue sections for the detection of anaplastic lymphoma kinase (ALK) gene rearrangement by fluorescence in situ hybridization (FISH). The authors compared alcohol-fixed and formalin-fixed cytology specimens using a novel automated detection for ALK rearrangements by FISH and immunohistochemistry (IHC). METHODS: ALK FISH testing was performed on 129 lung adenocarcinomas from 71 cytology cases and 58 biopsy/resection specimens using Papanicolaou staining with integrated cytomorphology. IHC with the ALK D5F3 antibody was performed on cases with residual material (88 of 129 cases). RESULTS: The mean age of the patients was 66 years; there were 62 women and 67 men. ALK gene rearrangement was present in 4% of cytology specimens (3 of 71 specimens) and 7% of surgical specimens (4 of 58 specimens). FISH in 13 cases was technically unsuccessful. Of the 7 FISH-positive cases, only 2 cytology cases (4%) and 2 surgical cases (6%) were found to be positive with the ALK antibody, demonstrating 80% concordance. The one case found to be negative for ALK by IHC demonstrated a variant rearrangement of the ALK 2p23 gene locus by FISH. CONCLUSIONS: The results of the current study validate the usefulness of alcohol-fixed and/or formalin-fixed cytology specimens for ALK rearrangement by a novel automated FISH method. IHC using the D5F3 antibody for ALK is specific in this limited cohort. The authors also demonstrated that alcohol-fixed cytology specimens can be used for ALK rearrangement by automated FISH, alone or in conjunction with IHC.

The triage efficacy of fine needle aspiration biopsy for follicular variant of papillary thyroid carcinoma using the Bethesda reporting guidelines.

Diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC) by ultrasound-guided fine-needle aspiration (FNA) is challenging. In this retrospective review, we evaluated triage efficacy (i.e., potential for triggering surgical intervention) in 44 archived FNA biopsies of surgically confirmed FVPTC obtained between December 2006 and December 2008. We compared the original FNA diagnoses with reclassified diagnoses based on 2007 National Cancer Institute (NCI)/Bethesda recommendations, and reviewed FNA cytologic features. Original FNA diagnoses included colloid nodule (7%, 3/44), atypical follicular cells (5%, 2/44), follicular lesion (11%, 5/44), follicular neoplasm (16%, 7/44), suspicious for malignancy/PTC (27%, 12/44), and papillary thyroid carcinoma (34%, 15/44). Reclassified diagnoses included indeterminate (5%, 2/44), colloid nodule (7%, 3/44), atypical cells of undetermined significance [ACUS] (7%, 3/44), Hurthle cell neoplasm (2%, 1/44), follicular neoplasm (7%, 3/44), suspicious for malignancy/PTC (25%, 11/44), and PTC (48%, 21/44). Triage efficacy was 77% (34/44) for original diagnoses versus 82% (36/44) for reclassified FNA diagnoses. We frequently observed cytologic features of PTC, such as nuclear grooves and fine chromatin; conversely, intranuclear inclusions, though present in 77% cases, were scant. Our review findings suggest that lack of characteristic cytologic features of PTC,coexistence with other thyroid lesions, and small tumor size arethe major obstacles to FNA diagnosis of FVPTC. Reclassification of thyroid FNA diagnoses does not significantly improve triage efficacy. Furthermore, FNA diagnoses of follicular neoplasm and suspicious for malignancy are valuable in patients with FVPTC because they trigger triage toward surgical intervention.

Cervista HR and HPV 16/18 assays vs hybrid capture 2 assay: outcome comparison in women with negative cervical cytology.

Sensitive and specific assays for human papillomavirus (HPV) are essential for patient management. In this study, we directly compared the efficacy of the Hybrid Capture 2 (HC2; Qiagen, Valencia, CA) and Cervista assays (Hologic, Madison, WI). Consecutive cervical cytology specimens (n = 601) were tested using HC2, Cervista HR, and Cervista HPV 16/18 with analysis of only cytology-negative cases (n = 533). Results indicated no significant difference (P = .458) in prevalence rates between HC2 (7.5%) and Cervista HR (8.5%). The Cervista 16/18 prevalence was 1.6%. The negative percentage of agreement was 95.1% (468/492) vs a 70% (28/40) positive percentage of agreement. No false-negative results were detected by the Cervista internal DNA control. Our data show 29 discordant positive results (12 HC2 and 17 Cervista HR), suggesting some women with negative cytology may be triaged for unnecessary follow-up with either assay. For clinical screening, Cervista HR and HC2 are comparable and, by extension, should provide excellent negative predictive value for histologically relevant disease.