Clinical Outcomes After Endoscopic Management of Low-Risk and High-Risk T1a Esophageal Adenocarcinoma: A Multicenter Study.

INTRODUCTION: Endoscopic eradication therapy (EET) is standard of care for T1a esophageal adenocarcinoma (EAC). However, data on outcomes in high-risk T1a EAC are limited. We assessed and compared outcomes after EET of low-risk and high-risk T1a EAC, including intraluminal EAC recurrence, extraesophageal metastases, and overall survival. METHODS: Patients who underwent EET for T1a EAC at 3 referral Barrett's esophagus endotherapy units between 1996 and 2022 were included. Patients with submucosal invasion, positive deep margins, or metastases at initial diagnosis were excluded. High-risk T1a EAC was defined as T1a EAC with poor differentiation and/or lymphovascular invasion, with low-risk disease being defined without these features. All pathology was systematically assessed by expert gastrointestinal pathologists. Baseline and follow-up endoscopy and pathology data were abstracted. Time-to-event analyses were performed to compare outcomes between groups. RESULTS: One hundred eighty-eight patients with T1a EAC were included (high risk, n = 45; low risk, n = 143) with a median age of 70 years, and 84% were men. Groups were comparable for age, sex, Barrett's esophagus length, lesion size, and EET technique. Rates of delayed extraesophageal metastases (11.1% vs 1.4%) were significantly higher in the high-risk group ( P = 0.02). There was no significant difference in the rates of intraluminal EAC recurrence ( P = 0.79) and overall survival ( P = 0.73) between the 2 groups. DISCUSSION: Patients with high-risk T1a EAC undergoing successful EET had a substantially higher rate of extraesophageal metastases compared with those with low-risk T1a EAC on long-term follow-up. These data should be factored into discussions with patients while selecting treatment approaches. Additional prospective data in this area are critical.

A case-control autopsy series of liver pathology associated with novel coronavirus disease (COVID-19).

BACKGROUND: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for coronavirus disease 2019 (COVID-19) is most well-known for causing pulmonary injury, a significant proportion of patients experience hepatic dysfunction. The mechanism by which SARS-CoV2 causes liver injury is not fully understood. The goal of this study was to describe the hepatic pathology in a large cohort of deceased patients with COVID-19 as compared to a control group of deceased patients without COVID-19. METHODS: Consented autopsy cases at two institutions were searched for documentation of COVID-19 as a contributing cause of death. A group of consecutive consented autopsy cases during the same period, negative for SARS-CoV-2 infection, was used as a control group. The autopsy report and electronic medical records were reviewed for relevant clinicopathologic information. H&E-stained liver sections from both groups were examined for pertinent histologic features. Select cases underwent immunohistochemical staining for CD 68 and ACE2 and droplet digital polymerase chain reaction (ddPCR) assay for evaluation of SARS-CoV2 RNA. RESULTS: 48 COVID-19 positive patients (median age 73, M:F 3:1) and 40 COVID-19 negative control patients (median age 67.5, M:F 1.4:1) were included in the study. The COVID-19 positive group was significantly older and had a lower rate of alcoholism and malignancy, but there was no difference in other comorbidities. The COVID-19 positive group was more likely to have received steroids (75.6 % vs. 36.1 %, p < 0.001). Hepatic vascular changes were seen in a minority (10.6 %) of COVID-19 positive cases. When all patients were included, there were no significant histopathologic differences between groups, but when patients with chronic alcoholism were excluded, the COVID-19 positive group was significantly more likely to have steatosis (80.9 % vs. 50.0 %, p = 0.004) and lobular inflammation (45.7 % vs. 20.7 %, p = 0.03). Testing for viral RNA by ddPCR identified 2 of the 18 (11.1 %) COVID-19 positive cases to have SARS-CoV-2 RNA detected within the liver FFPE tissue. CONCLUSIONS: The most significant findings in the liver of COVID-19 positive patients were mild lobular inflammation and steatosis. The high rate of steroid therapy in this population may be a possible source of steatosis. Hepatic vascular alterations were only identified in a minority of patients and did not appear to play a predominant role in COVID-19 mediated hepatic injury. Low incidence of SARS-CoV-2 RNA positivity in liver tissue in our cohort suggests hepatic injury in the setting of COVID-19 may be secondary in nature.

Effects of Subnormothermic Regulated Hepatic Reperfusion on Mitochondrial and Transcriptomic Profiles in a Porcine Model.

OBJECTIVE: We sought to investigate the biological effects of pre-reperfusion treatments of the liver after warm and cold ischemic injuries in a porcine donation after circulatory death model. SUMMARY OF BACKGROUND DATA: Donation after circulatory death represents a severe form of liver ischemia and reperfusion injury that has a profound impact on graft function after liver transplantation. METHODS: Twenty donor pig livers underwent 60 minutes of in situ warm ischemia after circulatory arrest and 120 minutes of cold static preservation prior to simulated transplantation using an ex vivo perfusion machine. Four reperfusion treatments were compared: Control-Normothermic (N), Control- Subnormothermic (S), regulated hepatic reperfusion (RHR)-N, and RHR-S (n = 5 each). The biochemical, metabolic, and transcriptomic profiles, as well as mitochondrial function were analyzed. RESULTS: Compared to the other groups, RHR-S treated group showed significantly lower post-reperfusion aspartate aminotransferase levels in the reperfusion effluent and histologic findings of hepatocyte viability and lesser degree of congestion and necrosis. RHR-S resulted in a significantly higher mitochondrial respiratory control index and calcium retention capacity. Transcriptomic profile analysis showed that treatment with RHR-S activated cell survival and viability, cellular homeostasis as well as other biological functions involved in tissue repair such as cytoskeleton or cytoplasm organization, cell migration, transcription, and microtubule dynamics. Furthermore, RHR-S inhibited organismal death, morbidity and mortality, necrosis, and apoptosis. CONCLUSION: Subnormothermic RHR mitigates IRI and preserves hepatic mitochondrial function after warm and cold hepatic ischemia. This organ resuscitative therapy may also trigger the activation of protective genes against IRI. Sub- normothermic RHR has potential applicability to clinical liver transplantation.

Long-term outcomes following successful endoscopic treatment of T1 esophageal adenocarcinoma: a multicenter cohort study.

BACKGROUND AND AIMS: Endoscopic eradication therapy (EET) is guideline endorsed for management of early-stage (T1) esophageal adenocarcinoma (EAC). Patients with baseline high-grade dysplasia (HGD) and EAC are at highest risk of recurrence after successful EET, but limited data exist on long-term (>5 year) recurrence outcomes. Our aim was to assess the incidence and predictors of long-term recurrence in a multicenter cohort of patients with T1 EAC treated with EET. METHODS: Patients with T1 EAC achieving successful endoscopic cancer eradication with a minimum of 5 years' clinical follow-up were included. The primary outcome was neoplastic recurrence, defined as dysplasia or EAC, and it was characterized as early (<2 years), intermediate (2-5 years), or late (>5 years). Predictors of recurrence were assessed by time to event analysis. RESULTS: A total of 84 T1 EAC patients (75 T1a, 9 T1b) with a median 9.1 years (range, 5.1-18.3 years) of follow-up were included. The overall incidence of neoplastic recurrence was 2.0 per 100 person-years of follow-up. Seven recurrences (3 dysplasia, 4 EAC) occurred after 5 years of EAC remission. Overall, 88% of recurrences were treated successfully endoscopically. EAC recurrence-related mortality occurred in 3 patients at a median of 5.2 years from EAC remission. Complete eradication of intestinal metaplasia was independently associated with reduced recurrence (hazard ratio, .13). CONCLUSIONS: Following successful EET of T1 EAC, neoplastic recurrence occurred after 5 years in 8.3% of cases. Careful long-term surveillance should be continued in this patient population. Complete eradication of intestinal metaplasia should be the therapeutic end point for EET.

COVID-19-Associated Nonocclusive Fibrin Microthrombi in the Heart.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant clinical presentation, coronavirus disease 2019 (COVID-19), is an emergent cause of mortality worldwide. Cardiac complications secondary to this infection are common; however, the underlying mechanisms of such remain unclear. A detailed cardiac evaluation of a series of individuals with COVID-19 undergoing postmortem evaluation is provided, with 4 aims: (1) describe the pathological spectrum of the myocardium; (2) compare with an alternate viral illness; (3) investigate angiotensin-converting enzyme 2 expression; and (4) provide the first description of the cardiac findings in patients with cleared infection. METHODS: Study cases were identified from institutional files and included COVID-19 (n=15: 12 active, 3 cleared), influenza A/B (n=6), and nonvirally mediated deaths (n=6). Salient information was abstracted from the medical record. Light microscopic findings were recorded. An angiotensin-converting enzyme 2 immunohistochemical H-score was compared across cases. Viral detection encompassed SARS-CoV-2 immunohistochemistry, ultrastructural examination, and droplet digital polymerase chain reaction. RESULTS: Male sex was more common in the COVID-19 group (P=0.05). Nonocclusive fibrin microthrombi (without ischemic injury) were identified in 16 cases (12 COVID-19, 2 influenza, and 2 controls) and were more common in the active COVID-19 cohort (P=0.006). Four active COVID-19 cases showed focal myocarditis, whereas 1 case of cleared COVID-19 showed extensive disease. Arteriolar angiotensin-converting enzyme 2 endothelial expression was lower in COVID-19 cases than in controls (P=0.004). Angiotensin-converting enzyme 2 myocardial expression did not differ by disease category, sex, age, or number of patient comorbidities (P=0.69, P=1.00, P=0.46, P=0.65, respectively). SARS-CoV-2 immunohistochemistry showed nonspecific staining, whereas ultrastructural examination and droplet digital polymerase chain reaction were negative for viral presence. Four patients (26.7%) with COVID-19 had underlying cardiac amyloidosis. Cases with cleared infection had variable presentations. CONCLUSIONS: This detailed histopathologic, immunohistochemical, ultrastructural, and molecular cardiac series showed no definitive evidence of direct myocardial infection. COVID-19 cases frequently have cardiac fibrin microthrombi, without universal acute ischemic injury. Moreover, myocarditis is present in 33.3% of patients with active and cleared COVID-19 but is usually limited in extent. Histological features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.

Clinical, Endoscopic, and Histopathology Features of Esophageal Graft-vs-Host Disease.

INTRODUCTION: To describe the clinical, endoscopic, and histopathology features of esophageal graft-vs-host disease (GVHD). METHODS: Patients with biopsy-proven esophageal GVHD diagnosed at Mayo Clinic between 2000 and 2021 were included. RESULTS: In 43 esophageal patients, other organ GVHD was present in 58% before and 86% at esophageal GVHD diagnosis. Esophageal specific symptoms were uncommon (dysphagia 26% and odynophagia/heartburn 5%). Esophagogastroduodenoscopy was abnormal in 72% patients demonstrating erosive esophagitis, ulceration, desquamation, or rings/furrows in a diffuse or focal pattern. DISCUSSION: There should be a low threshold for esophageal biopsies for GVHD because esophageal symptoms and endoscopic findings may be nonspecific or absent.

Multi-institutional development and validation of a novel histologic grading system for colonic graft-versus-host disease.

Graft-versus-host disease (GVHD) remains a major complication for patients who have undergone hematopoietic stem cell transplantation. The Lerner system is the most widely used histologic grading score for gastrointestinal GVHD but its clinic utility is debated. The aim of our study was to develop a novel histologic grading system for gastrointestinal GVHD that incorporates independent evaluation of both apoptotic counts and crypt destruction. Colonic biopsies taken to assess for GVHD were retrospectively assessed for: Crypt damage (No crypt dropout or ulceration-0; crypt dropout without ulceration-1; ulceration-2) and crypt apoptotic counts (No apoptosis-0; 1-6 apoptotic bodies per 10 contiguous crypts-1; >6apoptotic bodies per 10 contiguous crypts-2). The two scores were added together to get an overall grade (0-4). Alternative apoptotic cutoff points were examined. An apoptotic cutoff of >9 apoptotic bodies per 10 contiguous crypts marginally improved the area under the curve (AUC), but the AUCs from the resulting novel grade calculations were not significantly different (p = 0.10). Lerner grading was also applied. The study group consisted of an initial analysis cohort (n = 191) and a second validation cohort from a separate institution (n = 97). In the initial analysis cohort, our histologic grading system provided prognostic stratification for GVHD-related death within 6 months (p = 0.0004, AUC = 0.705). The Lerner system performed similarly in terms of providing prognostic stratification for GVHD-related death (p = 0.0001, AUC = 0.707). In the external validation cohort, our histologic grading system was not associated with GVHD-related death (p = 0.14, AUC = 0.621), but the Lerner system was associated with GVHD-related death (p = 0.048, AUC = 0.663). While our grading system may have some advantages compared to the Lerner system, due to lack of reproducibility we do not currently recommend widespread adoption of this system. Nonetheless, we present a standardized tool for assessing both apoptosis and crypt damage. Future studies assessing alternative histologic grading systems with external validation and further examination the lower apoptotic threshold for GVHD diagnosis are warranted.

Development of a deep learning model for the histologic diagnosis of dysplasia in Barrett's esophagus.

BACKGROUND AND AIMS: The risk of progression in Barrett's esophagus (BE) increases with development of dysplasia. There is a critical need to improve the diagnosis of BE dysplasia, given substantial interobserver disagreement among expert pathologists and overdiagnosis of dysplasia by community pathologists. We developed a deep learning model to predict dysplasia grade on whole-slide imaging. METHODS: We digitized nondysplastic BE (NDBE), low-grade dysplasia (LGD), and high-grade dysplasia (HGD) histology slides. Two expert pathologists confirmed all histology and digitally annotated areas of dysplasia. Training, validation, and test sets were created (by a random 70/20/10 split). We used an ensemble approach combining a "you only look once" model to identify regions of interest and histology class (NDBE, LGD, or HGD) followed by a ResNet101 model pretrained on ImageNet applied to the regions of interest. Diagnostic performance was determined for the whole slide. RESULTS: We included slides from 542 patients (164 NDBE, 226 LGD, and 152 HGD) yielding 8596 bounding boxes in the training set, 1946 bounding boxes in the validation set, and 840 boxes in the test set. When the ensemble model was used, sensitivity and specificity for LGD was 81.3% and 100%, respectively, and >90% for NDBE and HGD. The overall positive predictive value and sensitivity metric (calculated as F1 score) was .91 for NDBE, .90 for LGD, and 1.0 for HGD. CONCLUSIONS: We successfully trained and validated a deep learning model to accurately identify dysplasia on whole-slide images. This model can potentially help improve the histologic diagnosis of BE dysplasia and the appropriate application of endoscopic therapy.

Mammary analogue secretory carcinoma: A challenging case arising in a young man with radiation exposure.

Mammary Analogue Secretory Carcinoma (MASC) is a recently described salivary gland tumor frequently sampled via fine-needle aspiration. The cytologic features of MASC are not entirely distinctive and can simulate acinic cell carcinoma, but the tumor harbors an ETV6 gene rearrangement resulting in an ETV6-NTRK3 fusion gene. We present a case of MASC arising in a 31 year old man with a history of multiple radio-embolization procedures.

Desmoid fibromatosis involving the pancreas: A retrospective case series with clinical, cytopathologic and radiologic correlation.

Desmoid-type fibromatosis (desmoid tumors) which involve the pancreas is an infrequent diagnosis which clinically can mimic both neoplastic and non-neoplastic lesions of the pancreas. The cytologic features of loosely cohesive cytologically bland (myo)fibroblastic cells are non-specific, however the long fascicular growth pattern and the presence of ß-catenin mutation with positive nuclear immunohistochemical staining or molecular testing allows for definitive diagnosis. While many previously reported desmoid tumors of the pancreas have been surgically resected, conservative management with a "watch and wait" approach is also an effective mode of management for these tumors. Herein, we report the largest case series of pancreatic desmoid tumors with clinical, cytopathologic, and radiologic correlation.

Suicide by Gaseous Displacement of Atmospheric Oxygen With Carbon Dioxide From Dry Ice Sublimation.

ABSTRACT: Deaths from gaseous substances can occur from exposure to toxic gases or from accumulation of nontoxic gases that displace oxygen. We present a 38-year-old man with no known medical history, who was found deceased in a small bathroom with blankets and towels shoved under the door from the inside.At autopsy, the decedent was found to be in a moderate state of decomposition. There was mild pulmonary congestion, with no other significant findings. Standard postmortem toxicology on femoral blood was noncontributory.A search of the decedent's cell phone revealed statements and internet searches regarding carbon dioxide (CO 2 ) and asphyxia using dry ice. A journal entry also outlined a suicide plan using large amounts of dry ice, which was enacted by placing a laundry basket of dry ice into a bathtub containing water. Based on the investigation, the cause of death was determined to be asphyxia from displacement of oxygen with CO 2 .Dry ice sublimates into gaseous CO 2 , which quickly accumulates, with concentrations of 10% or more, rapidly becoming life-threatening. There are no pathognomonic autopsy findings seen in CO 2 -related asphyxia. In these circumstances, scene investigation is the most important factor in determining cause of death.

Esophageal Epidermoid Metaplasia: Clinical Characteristics and Risk of Esophageal Squamous Neoplasia.

INTRODUCTION: Esophageal epidermoid metaplasia (EEM) is a rare disease. METHODS: Patients with EEM diagnosed between 2014 and 2020 were reviewed. RESULTS: Forty EEM cases were identified. EEM occurred in 9 (23%) patients before, concordant, or after esophageal squamous cell carcinoma (ESCC). EEM was associated with previous esophageal lichen planus in 5 patients, Barrett's esophagus 7, and esophageal adenocarcinoma 1. EEM was focal in 28 (70%) or diffuse in 12 (30%) and not detected in 45% on recent previous endoscopy. DISCUSSION: EEM is a premalignant underrecognized condition associated with multiple conditions. Close follow-up or endoscopic treatment may be warranted because of its ESCC association.

Malignant gastrointestinal neuroectodermal tumor: Cytologic, histologic, immunohistochemical, and molecular pitfalls.

Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare malignant primary gastrointestinal mesenchymal tumor which can be diagnosed via fine-needle aspiration (FNA) cytology. In the context of FNA, the diagnosis requires a cell block and the use of significant resources including immunohistochemical stains and molecular testing. The differential diagnosis of GNET includes clear cell sarcoma (CCS), gastrointestinal stromal tumor (GIST), gastric schwannoma, metastatic melanoma, malignant perivascular epithelioid cell tumor (PEComa) and granular cell tumor, among others. Here we describe a case which was initially diagnosed as malignant granular cell tumor by FNA which was later revised to GNET following the finding of an EWSR1-ATF1 fusion gene rearrangement.

Importance of Normalization of CA19-9 Levels Following Neoadjuvant Therapy in Patients With Localized Pancreatic Cancer.

OBJECTIVE: Carbohydrate antigen 19-9 (CA19-9) is a prognostic marker for patients with pancreatic cancer (PC), but its value as a treatment biomarker is unclear. SUMMARY BACKGROUND DATA: Although CA19-9 is an established prognostic marker for patients with PC, it is unclear how CA19-9 monitoring should be used to guide multimodality treatment and what level of change in CA19-9 constitutes a meaningful treatment response. METHODS: CA19-9 measurements at diagnosis (pretx), after completion of all planned neoadjuvant therapy (preop), and after surgery (postop) were analyzed in patients with localized PC who had an elevated CA19-9 (≥35 U/dL) at diagnosis. Patients were classified by: 1) quartiles of pretx CA19-9 (Q1-4); 2) proportional changes in CA19-9 (ΔCA19-9) after the completion of neoadjuvant therapy; 3) normalization (CA19-9 <35 U/dL) of preop CA19-9; and 4) normalization of postop CA19-9. RESULTS: Among 131 patients, the median overall survival (OS) was 30 months; 68 months for the 33 patients in Q1 of pretx CA19-9 (<80 U/dL) compared with 25 months for the 98 patients in Q2-4 (P = 0.03). For the 98 patients in Q2-4, preop CA19-9 declined (from pretx) in 86 (88%), but there was no association between the magnitude of ΔCA19-9 and OS (P = 0.77). Median OS of the 98 patients who did (n = 29) or did not (n = 69) normalize their preop CA19-9 were 46 and 23 months, respectively (P = 0.02). Of the 69 patients with an elevated preop CA19-9, 32 (46%) normalized their postop CA19-9. Failure to normalize preop or postop CA19-9 was associated with a 2.77-fold and 4.03-fold increased risk of death, respectively (P < 0.003) as compared with patients with normal preop CA19-9. CONCLUSIONS: Following neoadjuvant therapy, normalization of CA19-9, rather than the magnitude of change, is the strongest prognostic marker for long-term survival.

Evaluation of the lower histologic threshold for gastric graft versus host disease.

Data regarding the lower diagnostic threshold for gastric graft-versus-host disease is lacking. The aim of this study was to review a cohort of gastric biopsies taken to evaluate for graft-versus-host disease, and to correlate histologic findings with clinical and endoscopic evidence of graft-versus-host disease as well as biopsy findings from other locations to define a lower diagnostic threshold for gastric graft-versus-host disease. Gastric biopsies were evaluated for the maximum number of apoptotic bodies per 10 contiguous gastric pits, presence of ≥1 apoptotic body per biopsy (NIH criteria), and presence of gastric pit dropout and/or ulceration. To evaluate histologic specificity, sixty gastric biopsies from non-stem cell transplant patients were selected as a control group. Clinical information was collected from chart review. The study group consisted of 65 gastric biopsies from 52 stem cell transplant patients. The mean apoptotic count per 10 contiguous gastric pits for stem cell transplant biopsies was 1.8 (range 0-8) and for control cases 1.0 (range 0-5). Nineteen stem cell transplant biopsies (29%) had ≥1 apoptotic body per biopsy and only a single case had >6 apoptotic bodies per 10 contiguous gastric pits. When the NIH guidelines were combined with presence of at least two apoptotic bodies per 10 contiguous gastric pits, this cutoff point was significantly associated with treatment for graft-versus-host disease (OR = 9.4, 95% CI = 1.7-176.7, p = 0.04) and evidence of extraintestinal graft-versus-host disease (OR = 3.2, 95% CI = 1.1-10.7, p = 0.04). The diagnostic specificity for our proposed cutoff value is 94%. We present criteria for the lower diagnostic threshold of gastric graft-versus-host disease, which uses a lower apoptotic cutoff value than has been utilized in colonic biopsies. Although sensitivity remains a challenge for gastric graft-versus-host disease biopsies, this newly proposed cutoff provides higher specificity than NIH guidelines alone and better correlates with clinical evidence of graft-versus-host disease.

Smooth muscle tumors of the gastrointestinal tract: an analysis of prognostic features in 407 cases.

Smooth muscle tumors represent the second most common mural mesenchymal neoplasm in the gastrointestinal tract, but established criteria for prognostic assessment of these tumors are lacking. A large cohort of surgically resected intramural gastrointestinal smooth muscle tumors from 31 institutions was analyzed to identify potential prognostic features. Pathologic features were assessed by expert gastrointestinal and/or soft tissue pathologists at each center. Immunohistochemical confirmation was required. A total of 407 cases from the esophagus (n = 97, 24%), stomach (n = 180, 44%), small bowel (n = 74, 18%), and colorectum (n = 56, 14%) were identified. Patients ranged in age from 19 to 92 years (mean 55 years), with a slight female predominance (57%). Mean tumor size was 5.4 cm, with the largest tumor measuring 29 cm. Disease progression following surgery, defined as local recurrence, metastasis, or disease-related death, occurred in 56 patients (14%). Colorectal tumors were most likely to progress, followed by small bowel and gastric tumors. None of the esophageal tumors in this series progressed. Receiver operator characteristic analysis identified optimal cutoffs of 9.8 cm and 3 mitoses/5 mm2 for discriminating between progressive and non-progressive tumors. Histologic features strongly associated with progression by univariate analysis included moderate-to-severe atypia, high cellularity, abnormal differentiation (defined as differentiation not closely resembling that of normal smooth muscle), tumor necrosis, mucosal ulceration, lamina propria involvement, and serosal involvement (P < 0.0001 for all features). Age, sex, and margin status were not significantly associated with progression (P = 0.23, 0.82, and 0.07, respectively). A risk assessment table was created based on tumor site, size, and mitotic count, and Kaplan-Meier plots of progression-free survival for each subgroup revealed progression-based tiers. Based on our findings, it appears that nonesophageal gastrointestinal smooth muscle tumors measuring >10 cm and/or showing ≥3 mitoses/5 mm2 may behave aggressively, and therefore close clinical follow-up is recommended in these cases.

Lymphoepithelial cyst of the pancreas: A challenging diagnosis on fine needle aspiration.

Lymphoepithelial cysts (LECs) of the pancreas are rare, benign pancreatic cysts comprising approximately 0.5% of all pancreatic cysts. They occur predominantly in men in the 5th and 6th decades of life. LECs are true cysts lined by stratified squamous epithelium with adjacent subepithelial lymphoid tissue. They range in size from 1.2 to 17 cm (mean size 4.6 cm) and can arise in any part of the pancreas. 1 LEC resembles other benign and malignant pancreatic cysts clinically and radiologically. The cytomorphologic features of LECs have been described in a small number of case reports and it has been indicated that features may overlap with other benign and malignant pancreatic lesions. Herein, we report clinical, radiological, cytological and histopathological features of a pancreatic LEC in a 62-year-old male.

Intraductal papillary squamous neoplasm of the pancreas: Cyto-histologic correlation of a novel entity.

We correlate the cytologic and histologic features of a squamous-lined pancreatic cystic lesion with a complex papillary architecture and an associated KRAS mutation, which to our knowledge has not been previously described. A 69 year-old woman presented with intermittent left upper quadrant pain. CT imaging revealed a 1 cm solid lesion in the pancreatic tail with peripheral calcification. Endoscopic ultrasound-guided fine needle biopsy showed a proliferation of epithelial cells with fibrovascular cores. An immunohistochemical stain for p40 was positive in the lesional cells. A distal pancreatectomy revealed a unilocular, cystic, well-circumscribed, soft and friable mass measuring 1.0 × 1.0 × 0.8 cm. Histologically, the cyst was lined by nonkeratinizing stratified squamous epithelium with a complex papillary architecture, filling the cyst lumen. Molecular sequencing revealed a KRAS G12V missense mutation. While the lesion shared some histologic features with the previously described "squamoid cyst of the pancreatic ducts", the complex papillary architecture and presence of a KRAS mutation are unique to the entity we describe herein and we propose the name "intraductal papillary squamous neoplasm of the pancreas." Reporting the cytomorphologic features of this novel entity may help in identification of similar lesions and understanding of the clinicopathologic significance.

Gross tumor size using the AJCC 8th ed. T staging criteria does not provide prognostic stratification for neoadjuvant treated pancreatic ductal adenocarcinoma.

The 8th edition AJCC T stage criteria for pancreatic ductal adenocarcinoma (PDAC) are now size based. These criteria provide better prognostic stratification in patients without neoadjuvant therapy. Our aim was to determine if gross tumor size is prognostically significant using the 8th ed. staging criteria for neoadjuvant treated PDAC. The study included 289 patients who underwent resection for PDAC following neoadjuvant therapy. By AJCC 7th ed., there were 12 (4.2%) ypT0, 32 (11.1%) ypT1, 64 (22.1%) ypT2, and 181 (62.6%) ypT3 patients. By AJCC 8th ed., there were 12 (4.2%) ypT0, 74 (25.6%) ypT1 (6 ypT1a, 1 ypT1b, 67 ypT1c), 161 (55.7%) ypT2, and 42 (14.5%) ypT3 patients. 182 patients had negative lymph nodes and 107 had positive lymph nodes. 77 patients were ypN1 and 30 were ypN2 by 8th ed. criteria. 7th ed. T stage significantly correlated with OS (p = 0.048), while 8th ed. T stage did not correlate with OS (p = 0.13). In ypN0 patients, neither the 7th ed. or 8th ed. T stages significantly correlated with patient OS (p = 0.065 and 0.26, respectively). Higher 7th ed. T stage correlated with lymph node status (p ≤ 0.001) more strongly than 8th ed. T stage (p = 0.04). 7th ed. and 8th ed. N stage correlated with OS (p = 0.004 and p = 0.0002, respectively). By 8th ed. AJCC staging criteria, gross tumor size does not provide good prognostic stratification in neoadjuvant therapy PDAC. Mapped grossing techniques combining gross and microscopic examination to determine tumor size may provide more accurate staging of neoadjuvant treated tumors.

Coexisting pancreatic serous cystadenoma and pancreatic ductal adenocarcinoma: A cytological-pathologic correlation with literature review.

Pancreatic serous cystadenoma (SCA) is a benign neoplastic lesion with a distinctive gross and microscopic appearance consisting of numerous thin-walled cysts lined by uniform epithelial cells with clear cytoplasm and small nuclei. The vast majority of serous cystadenomas are benign. Pancreatic SCA has rarely been reported in association with other pancreatic lesions. We present a challenging case in which a cystic and solid pancreatic mass was identified on imaging studies. FNA was performed and showed clusters of atypical cells with significant nuclear pleomorphism (>4:1), disorganized, overlapping nuclei, and prominent nucleoli. The FNA diagnosis was positive for malignancy, consistent with adenocarcinoma. The patient underwent neoadjuvant therapy and pancreaticoduodenectomy. Final pathology showed a serous cystadenoma associated with small foci of high-grade PanIN. The lack of invasive adenocarcinoma in the resection specimen was most likely due to complete response of the tumor to neoadjuvant chemoradiation therapy, but it is also possible that only high-grade PanIN was present initially. To our knowledge, this is the first reported case of SCA and high grade PanIN/PDAC that was assessed by FNA. We discuss the cytologic differential diagnosis and how to avoid potential pitfalls highlighted by this case.