Education and diversity in cytopathology: Past, present, and future.

Diversity, equity, and inclusion is a powerful goal which many of us strive toward in medicine, both in patient care and administrative leadership. As the world evolves, the practice of medicine must evolve with it. We are cognizant of the importance of the history of our medical specialties. If we do not acknowledge all parts of our history, we are doomed to repeat it. This special issue is unique and unlike anything that has previously been published in Diagnostic Cytopathology. This issue looks at some of the history of cytopathology. This historical review is followed by some of the present state of cytopathology. There are insights into global cytopathology. The final portion of this issue examines the critical need for cytotechnology schools in the United States. All of these areas are critical to the past, present, and future of cytopathology.

Single nucleotide polymorphism (SNP) chromosomal microarray as a diagnostic tool for mucinous tubular and spindle cell carcinoma: A validation study.

Mucinous tubular and spindle cell carcinoma (MTSCC) shows significant overlap with papillary renal cell carcinoma (PRCC), and harbor recurrent copy-number alterations (CNA). We evaluated 16 RCC with features suggestive of MTSCC using chromosomal microarrays. The cohort was comprised of 8 females and males, each, with an age range of 33-79 years (median, 59), and a tumor size range of 3.4-15.5 cm (median, 5.0). Half the tumors were high-grade (8/16, 50%) with features such as necrosis, marked cytologic atypia, and sarcomatoid differentiation, and 5/16 (31%) were high stage (≥pT3a). Three (of 16, 19%) cases had a predominant (>95%) spindle cell component, whereas 5/16 (31%) were composed of a predominant (>95%) epithelial component. Most cases (12/16, 75%) exhibited a myxoid background and/or extravasated mucin, at least focally. Twelve (of 16, 75%) cases demonstrated CNA diagnostic of MTSCC (losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22). In addition, 2 high-grade tumors showed loss of CDKN2A/B, and gain of 1q, respectively, both of which are associated with aggressive behavior. Three (of 16, 19%) cases, demonstrated nonspecific CNA, and did not meet diagnostic criteria for established RCC subtypes. One (of 16, 6%) low-grade epithelial predominant tumor (biopsy) demonstrated characteristic gains of 7, 17, and loss of Y, diagnostic of PRCC. MTSCC can be a morphologically heterogenous tumor. Our study validates the detection of characteristic chromosomal CNA for diagnostic use that may be useful in challenging cases with unusual spindle cell or epithelial predominant features, as well as in high-grade tumors.

PlasmaBlade-assisted surgical septal myectomy: technique and our experience.

Background: The pulsed-electron avalanche knife (PEAK) PlasmaBlade provides an atraumatic, scalpel-like cutting precision and electrocautery-like hemostasis. PlasmaBlade operates near body temperature, and its long, thin, and malleable tip can overcome the limitations of a surgical knife. In this study, we aimed to evaluate our clinical experience and histopathological outcomes of septal myectomy using PlasmaBlade. Methods: Electronic medical records were reviewed for preoperative, operative, and follow-up data of the patients who underwent septal myectomy using PEAK PlasmaBlade at our institute between January 2019 and December 2022. Histopathology of the myectomy specimens was reviewed for the depth of muscle necrosis and compared with the left atrial appendage (LAA) specimen. Results: Twenty-nine patients underwent septal myectomy using the PEAK PlasmaBlade. No mortality was reported. The mean age was 60.6 ± 12.5 years, and 58.6% of patients were male. Peak left ventricular outflow tract (LVOT) gradients were 40.5 ± 34.9 mmHg at rest and 56.5 ± 34.9 mmHg after provocation. Concomitant procedures performed were LAA ligation in 20 (69.0%), aortic valve replacement in 5 (17.2%), and coronary artery bypass grafting in 3 (10.3%) patients. Postoperative complications were complete heart block in one (3.4%) and ventricular septal defect in two (6.9%) patients. Both the ventricular septal defects were identified intraoperatively and repaired. Histopathology of myectomy specimens demonstrated cautery artifact limited to <50 µm depth compared to >1,000 µm with conventional electrocautery. At a mean follow-up of 8.4 ± 10.3 months, the mean LVOT gradient was 4.4 ± 5.8 mmHg at rest and 9.5 ± 3.3 mmHg after provocation. All patients were alive and in New York Heart Association class I/II. No patient developed complications or required reintervention or reoperation. Conclusion: Adequate septal myectomy can be precisely and safely performed using the PEAK PlasmaBlade with minimal collateral damage.

Reprint of: lessons from histopathologic examination of nephrectomy specimens in patients with tuberous sclerosis complex: cysts, angiomyolipomas & renal cell carcinoma.

Renal manifestations in patients with tuberous sclerosis complex (TSC) include cysts, angiomyolipoma, and renal cell carcinoma. Unlike many hereditary predisposition syndromes, the spectrum of renal tumors in TSC patients (including both angiomyolipoma and renal cell carcinoma) is broad, with significant morphologic heterogeneity. An improved understanding of histopathologic findings in TSC patients and associated clinicopathologic correlates has significant implications not just in establishing a diagnosis of TSC, but also in the recognition of sporadic tumors occurring secondary to somatic alterations of TSC1/TSC2/MTOR pathway genes and accurate prognostication. In this review, we have discussed issues relevant to clinical management based on histopathologic findings in nephrectomy specimens from patients with TSC. This includes discussions related to screening for TSC, diagnosis of PKD1/TSC2 contiguous gene deletion syndrome, the morphologic spectrum of angiomyolipoma and renal epithelium-derived neoplasia, including the risk of disease progression.

Molecular and Immunophenotypic Correlates of Metastatic Epithelioid Angiomyolipoma Include Alterations of TP53, RB1, and ATRX.

CONTEXT.­: Epithelioid angiomyolipomas (eAMLs) are rare tumors of the kidney that occur in patients with tuberous sclerosis complex or in a sporadic setting; a subset of these tumors exhibit metastatic behavior. OBJECTIVE.­: To analyze molecular profiling data to identify pathogenic alterations in rare cases of metastatic eAML, and to identify immunohistochemistry (IHC)-based surrogate markers. DESIGN.­: Molecular profiling data from the American Association for Cancer Research GENIE registry was accessed for 23 patients with angiomyolipomas, and 9 of 16 patients with eAMLs in our institutional registry were evaluated with next-generation sequencing. IHC was performed to screen for alterations of P53, RB, and ATRX for all 16 institutional cases. RESULTS.­: Combined alterations of 5 tumor-suppressor genes (TP53, ATRX, RB1, APC, and NF1) were identified using next-generation sequencing in 7 of 8 (88%) patients with metastatic disease compared to a single patient with nonmetastatic disease (RB1 variant of uncertain significance; 1 of 24, 4%). No cases with abnormal IHC results were identified in 11 patients with nonmetastatic disease compared to 3 of 5 patients with metastatic disease. CONCLUSIONS.­: Our results show that the majority of metastatic eAMLs have mutations of 5 tumor-suppressor genes (TP53, ATRX, RB1, APC, and NF1), while these are rare in patients with nonmetastatic disease. Furthermore, IHC for P53, RB, and ATRX may serve as a screen for a subset of these alterations in resource-limited settings. These findings, if validated in larger data sets, have the potential to predict metastatic behavior in eAMLs.

Revisiting the cytologic features of autoimmune pancreatitis: An institutional experience.

BACKGROUND: Autoimmune pancreatitis (AIP) is a known mimicker of pancreatic ductal adenocarcinoma both clinically and radiologically. In this study, the authors present their institutional experience in diagnosing AIP on cytology and correlate results with the histologic findings. METHODS: A 14-year computerized search for patients who had histologically confirmed AIP with concurrent or prior cytology was performed. Clinical data, cytology findings, and surgical pathology results were reviewed for analysis. RESULTS: Eighteen patients were identified. The patients showed a male predominance, with a mean age of 59 years. Jaundice, weight loss, and abdominal pain were the most common clinical presentation. Five of 12 patients who were tested for serum immunoglobulin G4 had elevated levels. Cytologic findings of 16 cases that were available for review showed markedly inflamed fibrous stroma (54%) and cytologic atypia (50%). The final cytologic diagnoses were suspicious for adenocarcinoma (n = 1), atypical (n = 8), and benign/negative (n = 9). The corresponding surgical pathology diagnoses were classified as type 1 (n = 10), type 2 (n = 6), and AIP, not otherwise specified (n = 2). All type 2 AIP cases had at least atypical cytologic diagnoses, with one called suspicious for adenocarcinoma and another called adenocarcinoma at the time of rapid on-site evaluation. In contrast, eight of 10 type 1 AIP cases were negative/benign, and two of 10 were atypical. In these two atypical cases, the possibility of AIP was raised because of the presence of inflamed stroma. CONCLUSION: AIP is a pitfall in cytology because moderate-to-marked atypia can be present, especially in type 2 AIP. Because atypia can be severe, the presence of cellular fibrous stroma with lymphocytic stromal infiltrates and the integration of serum immunoglobulin G4 levels could be helpful in avoiding diagnostic overcall in AIP.

Oil Red O Staining of Pulmonary Macrophages in Bronchoalveolar Lavage Specimens Is Not Specific for Vaping-Associated Lung Injury.

OBJECTIVES: Oil Red O (ORO) positivity in bronchoalveolar lavage (BAL) fluid macrophages in the setting of e-cigarette, or vaping, product use-associated acute lung injury (EVALI) has been frequently requested by clinicians based on rare reports and subsequent US Centers for Disease Control and Prevention guidelines. The aim of this study was to determine the specificity of ORO staining in BAL specimens with disease states other than EVALI. METHODS: Consecutive BAL specimens (October-December 2019) were stained with ORO. The lipid-laden macrophage index (LLMI) was calculated for each case. RESULTS: We studied BAL samples from 50 patients. Indications for BAL were surveillance bronchoscopy for lung transplantation (27/50), suspected infection (12/50), sarcoidosis/suspected sarcoidosis (3/50), nodules or ground-glass opacities (3/50), hemoptysis (2/50), asthma or eosinophilic pneumonia (2/50), and idiopathic pulmonary fibrosis (1/50). ORO staining was seen in BAL fluid macrophages in 45 of 50 cases (focal in 18, moderate in 23, diffuse in 4); LLMI ranged from 0 to 218. Using a threshold of LLMI of 85 or higher as positive, ORO was positive in 7 of 50 (14%) cases (range, 85-218). CONCLUSIONS: ORO staining in BAL fluid macrophages is not specific for EVALI. Even when an LLMI of 85 or higher is used as a threshold for positivity, ORO positivity occurs in a significant subset of non-vaping-related cases.

Lessons from histopathologic examination of nephrectomy specimens in patients with tuberous sclerosis complex: cysts, angiomyolipomas, and renal cell carcinoma.

Renal manifestations in patients with tuberous sclerosis complex (TSC) include cysts, angiomyolipoma, and renal cell carcinoma. Unlike many hereditary predisposition syndromes, the spectrum of renal tumors in TSC patients (including both angiomyolipoma and renal cell carcinoma) is broad, with significant morphologic heterogeneity. An improved understanding of histopathologic findings in TSC patients and associated clinicopathologic correlates has significant implications not just in establishing a diagnosis of TSC, but also in the recognition of sporadic tumors occurring secondary to somatic alterations of TSC1/TSC2/MTOR pathway genes and accurate prognostication. In this review, we have discussed issues relevant to clinical management based on histopathologic findings in nephrectomy specimens from patients with TSC. This includes discussions related to screening for TSC, diagnosis of PKD1/TSC2 contiguous gene deletion syndrome, the morphologic spectrum of angiomyolipoma and renal epithelium-derived neoplasia, including the risk of disease progression.

Cyto-histo correlation and false-negative urine: Before and after the Paris system for reporting urinary cytology.

BACKGROUND: The impact of implementing the Paris system (TPS) on the rate of discrepant cases in the negative for high-grade urothelial carcinoma (NHGUC) category that had a subsequent diagnosis of high-grade urothelial carcinoma (HGUC) on histology is not well studied. METHODS: We adopted TPS in May 2019. We searched discrepant cases with negative urine cytology 2017-2019 in our cyto-histo correlation database. The urine cytology and follow-up biopsy/resection were reviewed by a cytopathologist who also did Genitourinary (GU) Pathology subspecialty sign-out. Voided urine and instrumented urine were included in this study. RESULTS: There were total of 70 discrepant cases with negative cytology interpretation but HGUC on the subsequent biopsy or resected specimen. Following the TPS criteria, the rate of discrepant negative cytology cases increased from 6 cases between January 2017 and May 2019 to 64 cases after May 2019 when we adopted TPS. There were 2 discrepant negative cases in 2017, 3 cases in 2018, and 65 cases in 2019. Out of 65 cases in 2019, 64 cases were identified after May 2019. Additional 55 urine cytology slides were reviewed according to the TPS criteria, of which, the diagnoses remained unchanged in 45 (82%) cases and 10 (19%) cases were reassigned to either atypical or suspicious categories. The discrepancy was noted more on the instrumented urine and the upper tract urine. However, the false-negative rate rose faster in voided urine and lower tract urine. The risk of HGUC with the category of NHGUC was 0.03% in 2017, 0.05% in 2018, and 1.06% in 2019 at our institution. The increase in false-negative rate could not be attributed to a single cytopathologist. CONCLUSION: After adopting TPS for reporting urine cytology, there was an increase in HGUC from negative urine cytology which was subsequently confirmed on histology as cases of HGUC. The quality control of negative urines could be important monitoring the process when implementing TPS.

Signet-ring cells in pleural and peritoneal effusions identified on Wright stains - A diagnostic pitfall.

Objectives: Signet-ring cells (SRCs) in effusion specimens represent a diagnostic challenge. In this study, a consecutive series of pleural and peritoneal effusions with benign SRCs are examined and compared with malignant SRCs. Material and Methods: We reviewed consecutive Wright-stained serous effusion slides and searched for cases with SRCs. Corresponding ThinPrep slides and clinical histories were reviewed. Cytology cases with known signet-ring adenocarcinoma were retrieved and reviewed. Results: Four hundred Wright-stained serous effusions were reviewed. Eighteen cases were identified with SRC-like cells. Thirteen patients had liver cirrhosis, three patients had end-stage renal disease, one patient had a history of pancreatic adenocarcinoma, and one patient had endometrioid carcinoma. For the latter two patients, the primary tumor showed no histologic findings of signet-ring features. In all cases, no SRCs were found on the corresponding ThinPrep slides. Five cytology cases with malignant SRCs were reviewed. Benign SRCs have a uniformly pale and markedly distended cytoplasm, and the nuclei are thin and curved. The malignant SRCs showed larger non-curved nuclei and bubbly mucin-containing cytoplasm. Conclusion: Mesothelial cells and histiocytes can mimic signet-ring adenocarcinoma cells on Wright-stained slides. Correlation with ThinPrep specimens is necessary before reporting, as the SRCs typically are not present in ThinPrep preparations.

Cross-contamination in cytology processing: a review of current practice.

INTRODUCTION: New cytopreparatory technologies decrease the need for direct smears in favor of an increased use of liquid-based cytology methods. Despite these practice changes, Clinical Laboratory Improvement Amendments continue to require that cytopathology laboratories have procedures to prevent cross-contamination (CC). While the incidence of CC is not well documented, specific cytologic preparations and specimens with a high potential for CC have not been generally defined by professional guidelines or consensus. The American Society of Cytopathology Clinical Practice Committee surveyed cytology practitioners to better understand current practice related to CC in cytology. MATERIALS AND METHODS: The survey focused on four topics: (1) practice settings and demographic data; (2) current practice for meeting CC requirements; (3) practice for rapid on-site evaluation; and (4) preparation types considered high risk for CC. The survey was sent to all American Society of Cytopathology and American Society for Cytotechnology members from July 1 to August 14, 2020. RESULTS: Ninety-eight percent of laboratories had a written CC policy, with 66.18% of the policies addressing rapid on-site evaluation CC procedures. Documented cases of CC were rare. Alcohol-fixed, direct smears of Pap-stained fluids were deemed the most likely to be impacted by CC. Cell block contamination during the histologic processing were reported by 56.20% of respondents. CONCLUSIONS: Changes in practice has resulted in decreased preparation types associated with a high potential for CC. Laboratories should follow a risk-based approach to define these cases. Knowledge of practice patterns among laboratories can guide the development and refinement of policy and procedures.

The Paris System for Reporting Urinary Cytology: A Meta-Analysis.

The Paris System (TPS) for Reporting Urinary Cytology is a standardized, evidence-based reporting system, comprising seven diagnostic categories: nondiagnostic, negative for high-grade urothelial carcinoma (NHGUC), atypical urothelial cells (AUC), suspicious for high-grade urothelial carcinoma (SHGUC), HGUC, low-grade urothelial neoplasm (LGUN), and other malignancies. This study aimed to calculate the pooled risk of high-grade malignancy (ROHM) of each category and demonstrate the diagnostic accuracy of urine cytology reported with TPS. Four databases (PubMed, Embase, Scopus, Web of Science) were searched. Specific inclusion and exclusion criteria were applied, while data were extracted and analyzed both qualitatively and quantitatively. The pooled ROHM was 17.70% for the nondiagnostic category (95% CI, 0.0650; 0.3997), 13.04% for the NHGUC (95% CI, 0.0932; 0.1796), 38.65% for the AUC (95% CI, 0.3042; 0.4759), 12.45% for the LGUN (95% CI, 0.0431; 0.3101), 76.89 for the SHGUC (95% CI, 0.7063; 0.8216), and 91.79% for the HGUC and other malignancies (95% CI, 0.8722; 0.9482). A summary ROC curve was created and the Area Under the Curve (AUC) was 0.849, while the pooled sensitivity was 0.669 (95% CI, 0.589; 0.741) and false-positive rate was 0.101 (95% CI, 0.063; 0.158). In addition, the pooled DOR of the included studies was 21.258 (95% CI, 14.336; 31.522). TPS assigns each sample into a diagnostic category linked with a specific ROHM, guiding clinical management.

Diagnostic Performance of Pancreatic Cytology with the Papanicolaou Society of Cytopathology System: A Systematic Review, before Shifting into the Upcoming WHO International System.

The Papanicolaou Society of Cytopathology (PSC) reporting system classifies pancreatobiliary samples into six categories (I-VI), providing guidance for personalized management. As the World Health Organization (WHO) has been preparing an updated reporting system for pancreatobiliary cytopathology, this systematic review aimed to evaluate the risk of malignancy (ROM) of each PSC category, also the sensitivity and specificity of pancreatic FNA cytology using the current PSC system. Five databases were investigated with a predefined search algorithm. Inclusion and exclusion criteria were applied to select the eligible studies for subsequent data extraction. A study quality assessment was also performed. Eight studies were included in the qualitative analysis. The ROM of the PSC categories I, II, III, IV, V, VI were in the ranges of 8-50%, 0-40%, 28-100%, 0-31%, 82-100%, and 97-100%, respectively. Notably, the ROM IVB ("neoplastic-benign") subcategory showed a 0% ROM. Four of the included studies reported separately the ROMs for the IVO subcategory ("neoplastic-other"; its overall ROM ranged from 0 to 34%) with low (LGA) and high-grade atypia (HGA). ROM for LGA ranged from 4.3 to 19%, whereas ROM for HGA from 64 to 95.2%. When the subcategory IVO with HGA was considered as cytologically positive, together with the categories V and VI, there was a higher sensitivity of pancreatic cytology, at minimal expense of the specificity. Evidence suggests the proposed WHO international system changes-shifting the IVB entities into the "benign/negative for malignancy" category and establishing two new categories, the "pancreatic neoplasm, low-risk/grade" and "pancreatic neoplasm, high-risk/grade"-could stratify pancreatic neoplasms more effectively than the current PSC system.

Myeloid Sarcoma Involving the Testis in Adults: Clonal Evolution of Acute Myeloid Leukemia.

To describe the clinical, histologic, immunophenotypic, and genetic characteristics of myeloid sarcoma (MS) diagnosed in the testes of adults, 3 cases were identified, and information on their presentation, clinical features, treatment, and outcome was retrieved from the medical records. In addition, histologic, immunophenotypic, and molecular characteristics were reviewed. This showed that all patients had a previous history of acute myeloid leukemia (AML), in 2 cases diagnosed >10 years before the testicular lesions. In 1 case, there was bilateral involvement, while in 2, involvement was unilateral. The neoplastic cells showed evidence of cytogenetic/molecular clonal evolution in all cases, 1 of which also had significant immunophenotypic changes. A mutational profile including NPM1 p.Trp288Cysfs*12, IDH1 p.Arg132His NRAS p.Gly12Asp was seen in 2 of the 3 cases. Concurrent bone marrow involvement by a myeloid neoplasm was diagnosed in 2 patients, in 1, there was AML in the second 8% blasts. These patients progressed rapidly after MS and had a dismal outcome. The patient with no concurrent bone marrow disease had a favorable outcome. In conclusion, MS involving the testes of adults is a rare event, and it may represent the clonal evolution of AML.

A Modern Assessment of Cancer Risk in Adrenal Incidentalomas: Analysis of 2219 Patients.

OBJECTIVE: The aim of this study was to analyze the incidence of and risk factors for adrenocortical carcinoma (ACC) in adrenal incidentaloma (AI). SUMMARY OF BACKGROUND DATA: AI guidelines are based on data obtained with old-generation imaging and predominantly use tumor size to stratify risk for ACC. There is a need to analyze the incidence and risk factors from a contemporary series. METHODS: This is a retrospective review of 2219 AIs that were either surgically removed or nonoperatively monitored for ≥12 months between 2000 and 2017. Multivariate logistic regression was performed to define risk factors. ROC curves constructed to determine optimal size and attenuation cut-offs for ACC. RESULTS: 16.8% of AIs underwent upfront surgery and rest initial nonoperative management. Of conservatively managed patients, an additional 7.7% subsequently required adrenalectomy. Overall, ACC incidence in AI was 1.7%. ACC rates by size were 0.1%, 2.4%, and 19.5% for AIs of <4, 4 to 6, and >6 cm, respectively. The optimal size cut-off for ACC in AI was 4.6 cm. ACC risks by Hounsfield density were 0%, 0.5%, and 6.3% for lesions of <10, 10 to 20, and >20 HU, with an optimal cut-off of 20 HU to diagnose ACC. 15.5% of all AIs and 19.2% of ACCs were hormonally active. Male sex, large tumor size, high Hounsfield density, and >0.6 cm/year growth were independent risk factors for ACC. CONCLUSION: This contemporary analysis demonstrates that ACC risk per size in AI is less than previously reported. Given these findings, modern management of AIs should not be based just on size, but a combination of thorough hormonal evaluation and imaging characteristics.

SMARCA4-Deficient Undifferentiated Tumor Diagnosed on Adrenal Sampling.

OBJECTIVES: SMARCA4-deficient undifferentiated tumor has distinct clinicopathologic features. We describe our experience with primary diagnosis on adrenal sampling. METHODS: We collected six SMARCA4-deficient undifferentiated tumors diagnosed on adrenal sampling. Immunostains for SMARCA4, SF-1, inhibin, calretinin, S-100 protein, EMA, and TTF-1 were performed. A control group of 63 primary adrenocortical tumors was also immunostained. RESULTS: Patients included four men and two women (aged 52-77 years). Five had unilateral adrenal masses and one bilateral (range, 2.4-9.6 cm). Five had pulmonary masses, and one had a midline mediastinal mass. All cases had a monotonous epithelioid appearance and variable rhabdoid morphology. Immunophenotypically, all six cases had loss of nuclear SMARCA4 expression and no staining for SF-1, inhibin, calretinin, or S-100 protein. Variable EMA immunoreactivity was present in four of six cases and focal nuclear TTF-1 expression in one of six. All 63 adrenocortical neoplasms had retained nuclear SMARCA4 expression. CONCLUSIONS: SMARCA4-deficient undifferentiated tumor may present in the adrenal gland, and this series likely represents metastases from thoracic primaries. Because of the frequent absence of lineage marker expression, knowledge of the characteristic clinical presentation, the rhabdoid morphology, and the typical immunophenotype (loss of SMARCA4/BRG1) allow for appropriate distinction from adrenocortical carcinoma.

A critical analysis of laparoscopic and open approaches to sporadic pancreatic insulinoma resection in the modern era.

BACKGROUND: A single center experience with sporadic pancreatic insulinoma was analyzed to develop an algorithm for modern surgical management. METHODS: Thirty-four patients undergoing surgery from 2001 to 2019 were reviewed. RESULTS: The majority underwent enucleation (10 laparoscopic, 15 open). Laparoscopy was performed in 22 patients with conversion to open in 11, mostly related to the proximity of the tumor to the pancreatic duct (n = 4). Tumors on the anterior and posterior surface of the pancreas in all anatomic locations were completed with laparoscopic enucleation. Overall, the clinically-relevant postoperative pancreatic fistula (CR-POPF) rate was 21%, with no difference between laparoscopic versus open enucleation (10% vs 20%, p = 0.50) or enucleation versus resection (16% vs 33%, p = 0.27). Laparoscopic enucleation had shorter median hospital length of stay (LOS) compared with open (4 vs 7 days, p = 0.02). CONCLUSIONS: Laparoscopic enucleation does not increase the CR-POPF risk and provides an advantage with a shorter hospital LOS in select patients. Tumor location and relationship to the pancreatic duct guide surgical decision-making. These findings highlight tumor-specific criteria that would benefit from a minimally invasive approach.

Papillary Renal Cell Carcinoma With Microcystic Architecture Is Strongly Associated With Extrarenal Invasion and Metastatic Disease.

Papillary renal cell carcinoma (PRCC) is well-recognized as a morphologically and molecularly heterogenous group of kidney tumors with variable clinical behavior. Our goal was to analyze a unique histologic pattern of PRCC we have observed in routine practice to evaluate for potential clinical significance or distinct molecular signature. We identified 42 cases of PRCC showing a morphologically distinct architecture characterized by numerous epithelial-lined cysts containing the papillary tumor (herein called "microcysts"), which are typically separated by fibrous stroma. Of the initial 42 case test set with microcystic features, 23 (55%) were stage pT3a or higher. Most tumors had strong and diffuse cytoplasmic immunoreactivity for CK7 (93%, 37/40) and AMACR (100%, 40/40). Fumarate hydratase staining was retained in all cases tested (39/39). We performed next-generation sequencing on 15 of these cases with available tissue and identified chromosomal alterations commonly reported in historically "type 1" PRCC, notably multiple chromosomal gains, particularly of chromosomes 7 and 17, and MET alterations. However, alterations in pathways associated with more aggressive behavior (including SETD2, CDKN2A, and members of the NRF pathway) were also identified in 6 of 15 cases tested (40%). Given this molecular and immunophenotypic data, we subsequently reviewed an additional group of 60 consecutive pT2b-pT3 PRCCs to allow for comparisons between cases with and without microcysts, to assess for potential associations with other recently described histologic patterns (ie, "unfavorable architecture": micropapillary, solid, and hobnail), and to assess interobserver reproducibility for diagnosing architectural patterns and grade. Of the total combined 102 PRCCs, 67 (66%) had microcystic architecture within the intrarenal component but were commonly admixed with other patterns (39% had micropapillary, 31% solid, and 31% hobnail). Twenty-seven cases (26%) had metastatic disease, and 24 of these 27 (89%) had microcystic architecture in the intrarenal tumor. Within the pT3 subset, 21 of 22 cases with metastases (95%) had extrarenal invasion as either individual microcysts in renal sinus fat or aggregates of microcysts bulging beyond the confines of the capsule. Backward elimination and stepwise regression methods to detect features significantly associated with adverse outcome identified solid architecture (hazard ratio [HR]: 6.3; confidence interval [CI]: 2.1-18.8; P=0.001), hobnail architecture (HR: 5.3; CI: 1.7-16.7; P=0.004), and microcystic architecture at the tumor-stromal interface (HR: 4.2; CI: 1.1-16.7; P=0.036) as strongest. Of architectural patterns and grade, the microcystic pattern had a substantial interobserver agreement (κ score=0.795) that was highest among the 6 observers. In summary, PRCCs with microcystic architecture represents a subset of historically "type 1" PRCC with a predilection for morphologically distinctive extrarenal involvement and metastatic disease. Microcysts co-vary with other "unfavorable" architectural patterns also associated with higher risk for aggressive disease (ie, micropapillary, hobnail, and solid), but microcysts were more common and have superior interobserver reproducibility. These findings suggest that microcystic PRCC should be recognized as a potentially aggressive histologic pattern of growth in PRCC.

Spindle cell neoplasms of the upper gastrointestinal tract, hepatobiliary tract, and pancreas by fine needle aspiration: A single institutional experience of 15 years with follow-up data.

BACKGROUND: The diagnosis of spindle cell neoplasms (SCN) of the upper gastrointestinal (GI) tract, hepatobiliary tract, and pancreas detected by fine needle aspiration (FNA) is challenging. We describe a single-center experience of these samples with follow-up data and characterization of the morphologic findings. METHODS: We retrospectively reviewed pathology records for all FNAs diagnostic for or suggestive of SCN on esophagus, stomach, small bowel, liver, and pancreas in a 15 year period. All cases with at least 6 month follow-up were included. Surgical material (biopsy or resection) was the diagnostic gold standard. All FNAs with subsequent surgical specimens were reviewed and assessed for cellularity, architectural features, and nuclear features. RESULTS: In 15 years, 5101 FNAs of the upper GI tract, hepatobiliary tract, and pancreas were performed. SCN was diagnosed in 98 (2%) patients. Seventy-two patients had definitive pathologic diagnoses: 68 were neoplastic and four were non-neoplastic. Cytomorphologic review in relationship to final diagnosis revealed three statistically significant features: low cellularity favors a benign process (P = .00544), epithelioid nuclear morphology favors malignancy (P = .00278), and identification of perinuclear vacuoles favors a diagnosis of GIST over non-GIST SCN (P = .04236). CONCLUSIONS: Among cases with follow-up, final pathologic diagnoses were SCN in 94% of cases diagnosed as SCN on FNA of upper GI, hepatobiliary tract, and pancreas. Although some cytomorphologic criteria are more suggestive of malignancy, arriving at a specific diagnosis relies on collaboration of clinical, radiologic, cytomorphologic, and immunohistochemical data.