Evaluation of abnormal gallbladder imaging findings: Surgical management and pathologic correlations in early-stage gallbladder cancer.

Gallbladder cancer is a rare but potentially fatal disease. It is often asymptomatic in early stages and is frequently found incidentally or during the workup for benign biliary disease. We present two patients who each had suspicious gallbladder imaging findings and highlight their differences on radiologic and pathologic examination.

Case of Primary Hepatic Angiosarcoma Presenting With Jaundice and Infiltrative Liver Masses.

Primary hepatic angiosarcoma (PHA) is a rare and aggressive mesenchymal liver tumor with a poor prognosis and high mortality. Treatment options are limited to palliative chemotherapy with surgical resection reserved for the few cases that present early. We present a case of a patient who presented with jaundice and elevated liver enzymes. Imaging identified a diffusely heterogeneous liver consistent with cirrhosis, findings of portal hypertension, and 2 ill-defined liver lesions. Biopsy results confirmed PHA. Primary hepatic angiosarcoma does not have a typical presentation but should be considered for any patient presenting with an infiltrative liver mass.

Effects of COVID-19 pandemic on cytology: specimen adequacy in fine-needle aspiration of palpable head and neck masses.

INTRODUCTION: At our institution, palpation-guided fine-needle aspiration (FNA) is performed by the cytopathology service on an outpatient basis at the request of otolaryngologist surgeons. The aim of this study is to assess the effect of COVID lockdown measures on our FNA service with specific focus on adequacy rates. MATERIALS AND METHODS: All palpation-guided FNA performed in 2019 to 2020 were identified in our pathology database. Adequacy rates were compared for 3 time periods in 2020: pre-COVID, lockdown, and post-lockdown. RESULTS: In 2019, 121 FNAs were performed with 98% (119 of 121) obtained by pathology and only 2% (2 of 121) obtained by surgeons. In 2020, 89 FNAs were performed with 45% (40 of 89) collected by pathologists and 55% (49 of 89) by surgeons. During the pre-COVID period of 2020, 27 FNAs were collected, 85% (23 of 27) by pathologists, 8.7% of these (2 of 23) were nondiagnostic. Of the 4 FNAs performed by surgeons, all were positive for malignancy. During COVID lockdown all 24 FNAs were performed by surgeons with a 50% (12 of 24) nondiagnostic rate. Post-lockdown, with FNA referrals still below pre-COVID levels, surgeons performed 55.3% (21 of 38) of FNAs with 28.6% (6 of 21) non-diagnostic, while pathology performed 44.7% (17 of 38) with an 11.8% (2 of 17) nondiagnostic rate. CONCLUSIONS: Our FNA service noted significant changes in 2020 as a result of the COVID pandemic. Nondiagnostic rates were significantly increased in 2020 compared with 2019, primarily due to a shift to majority surgeon-performed palpation-guided FNA in the absence of cytopathology service during the lockdown period.

Mimics of hepatocellular carcinoma: a review and an approach to avoiding histopathological diagnostic missteps.

Hepatocellular carcinoma (HCC) is one of the commonest carcinomas and leading causes of cancer-related death. Although, in patients with cirrhosis, radiologic diagnosis has improved significantly over the years, needle biopsy and histopathological assessment remains an important diagnostic modality. Most importantly, histopathological diagnosis is essential in patients with contending extrahepatic primaries, those with no known HCC risk factors, patients with ambiguous radiological features, and many other clinical contexts. Helpful features such as high serum alpha-fetoprotein (AFP) serologies are known to be present in many other tumor (including but not only HCC) and nontumor contexts and therefore not only lack sufficient diagnostic specificity for HCC but also create the potential to overlook non-HCC AFP-producing tumors, of which there are many. Therefore, using clinical examples and other examples from the medical literature, this review discusses several clinical and histological mimics of HCC and proffers an approach for practicing pathologists geared toward avoiding missteps.

Evaluation and Comparison of Performance Parameters and Impact of Telepathology and Operator Experience on Endobronchial and Endoscopic Ultrasound-Guided Fine-Needle Aspiration.

OBJECTIVES: Endobronchial ultrasound- and endoscopic ultrasound-guided fine-needle aspiration (EBUS-/EUS-FNA) are minimally invasive techniques of diagnosing and staging malignancies. The procedures are difficult to master, requiring specific feedback for optimizing yield. METHODS: Over 2 years, EBUS-/EUS-FNA cases were gathered using the institutional pathology database. Patient and specimen characteristics were collected from the pathology database and electronic medical record. RESULTS: In 2 years, 789 unique FNA specimens were collected (356 EBUS and 433 EUS specimens). The cohort and each subgroup had excellent performance, which was enhanced by telepathology. The discrepancy rate was satisfactorily low. Hematolymphoid neoplasms are overrepresented in discrepant EBUS cases. The malignancy rates of cytology diagnostic categories were comparable to the literature. CONCLUSIONS: Using diagnostic yield and concordance results allow for comprehensive evaluation of the entire process of EBUS-/EUS-FNAs. This study's findings can influence patient management, training methods, and interpretation of results, while also acting as a model for others to investigate their own sources of inadequacy, discrepancy, and training gaps.

Type 1 diabetes mellitus in patients with recurrent acute and chronic pancreatitis: A case series.

BACKGROUND/OBJECTIVES: Pancreatogenic diabetes mellitus has been assumed to result from non-immune beta cell destruction when the pancreas is replaced by fibrotic tissue secondary to acute and chronic pancreatitis. We hypothesize that recurrent episodes of pancreatic inflammation may increase the risk for developing ß-cell autoimmunity in susceptible individuals. METHODS: We describe 11 patients who had both recurrent acute and/or chronic pancreatitis and type 1 diabetes (T1D) requiring insulin therapy. RESULTS: All 11 patients had positive autoantibodies and 8 patients tested had minimal to undetectable (7/8) or moderate (1/8) stimulated C-peptide at 12 months after T1D onset. Three had biopsy confirmation of insulitis. CONCLUSIONS: These cases lend support to the theory that pancreatitis may increase risk for T1D. We postulate that the pro-inflammatory conditions of pancreatitis may increase posttranslational protein modifications of ß-cell antigens and neoepitope generation, which are potential initiating events for loss of ß-cell self-tolerance.

Changing Insulinoma Management Due to Incidentally Discovered Metastasis: A Case Report.

BACKGROUND Hypoglycemia is rare in individuals without drug-treated diabetes mellitus. In a seemingly well individual, the differential diagnosis of hypoglycemia narrows to 2 major categories: 1) accidental, surreptitious, or intentional hypoglycemia, or 2) endogenous hyperinsulinism (EHH). Insulinomas are the most common cause of EHH. Localization of insulinomas can be challenging, as most tumors are less than 2 cm in size and may be present in any part of the pancreas. In fact, almost 30% of neuroendocrine tumors (NET) cannot be located preoperatively by traditional imaging techniques such as computerized tomography (CT) or magnetic resonance imaging (MRI). CASE REPORT This report describes a case of metastatic insulinoma in a patient with a complex medical history. CT with contrast of the abdomen identified 1 lesion located in the pancreas body. Endoscopic ultrasound (EUS) identified an additional 3 to 4 hypoechoic lesions in the pancreatic neck and body. 68-Gallium Dotatate scanning identified 3 distinct lesions within the pancreas and a right posterior rib sclerotic lesion. CONCLUSIONS Reliance upon traditional imaging techniques (CT/MRI) for tumor localization would not have identified the multifocal pancreatic lesions and the metastatic bone lesion. Accurate identification of multifocal, metastatic insulinomas requires multiple imaging modalities, including first-line non-invasive imaging (CT or MRI) followed by second-line imaging (EUS or nuclear imaging).

Mediastinal ganglioneuroma diagnosed by transesophageal endoscopic ultrasound guided fine needle aspiration (EUS-FNA).

Ganglioneuromas are rare benign tumors that arise from the sympathetic nerve fibers and represent the final maturation stage of neuroblast tumors. The most common sites of involvement in the body include posterior mediastinum, followed by retroperitoneum, adrenal gland, and soft tissues of the head and neck. In the mediastinum, this tumor is most frequently located in posterior compartment, together with other neurogenic tumors. The reports of mediastinal ganglioneuroma diagnosed by fine needle aspiration (FNA), especially endoscopic ultrasound-guided FNA (EUS-FNA) are very sparse. We describe the clinical, radiologic, cytologic, gross and histologic features of mediastinal ganglioneuroma diagnosed by transesophageal endoscopic ultrasound-guided fine needle aspiration.

Oncocytic features in salivary duct carcinoma, a potential pitfall for misdiagnosis as Warthin tumor in fine needle aspiration specimens: A cytomorphologic analysis of 14 cases.

BACKGROUND: Salivary duct carcinoma (SDC) is an uncommon and highly aggressive primary salivary gland neoplasm. Cytomorphologic features of SDC include cellular smears, nuclear atypia, prominent nucleoli, cribriform and papillary architecture, and background necrosis. The presence of oncocytic features has been described but not adequately characterized in the current literature. METHOD: This study cohort consisted of 14 cases of histologically proven SDC with previous salivary gland fine needle aspiration (FNA). The cytologic material of each case was semi-quantitatively analyzed and evaluated for various cytomorphologic, architectural, and background features. RESULTS: Twelve SDCs were located in the parotid gland and two in the submandibular gland. In two cases the initial cytologic diagnoses was Warthin tumor or favor Warthin tumor. Moderate to marked degree of oncocytic changes were noted in all cases except one case. Nuclear atypia was variable with most cases exhibiting moderate to high-grade nuclear features, while four cases demonstrated low-grade nuclear cytomorphology. Cytoplasmic vacuolation was seen in nine cases and variable amount of background necrosis was observed in eight cases. Cribriform and papillary architecture was recognized in only six cases. Background lymphocytes were absent in all but one case. CONCLUSIONS: Precise diagnosis of SDC based on cytomorphologic features alone can be challenging. Oncocytic change is one of the most consistent features observed in this case series and when associated with less pronounced cytologic atypia, can potentially lead to misdiagnosis as Warthin tumor. SDC should be considered in the differential diagnosis of oncocytic salivary gland neoplasms where precise diagnosis is not possible.

Case report of synchronous post-lung transplant colon cancers in the era of colorectal cancer screening recommendations in cystic fibrosis: screening "too early" before it's too late.

BACKGROUND: The increasing life expectancy of individuals with Cystic Fibrosis (CF) is likely to be associated with new age-related challenges, colorectal cancer (CRC) most notably; recent consensus recommendations for CRC screening published in 2018 represent an important early step in addressing the emerging awareness of CF as a gastrointestinal cancer syndrome. These recommendations, however, need to be further refined based on more systematic data. We discuss an illustrative first-ever case of synchronous CRC arising in a post-lung transplant individual with CF within the recommended surveillance interval after a well-documented prior normal colonoscopy. CASE PRESENTATION: A 51-year-old female individual with homozygous F508del CF, presents to clinic with abdominal discomfort and intermittent blood in stools. She had previously undergone bilateral lung transplantation 18 years earlier, as well as two kidney transplants related to immunosuppression-related nephrotoxicity. A diagnostic colonoscopy was performed which revealed the presence of two separate synchronous colon cancers in the cecum and transverse colon; she had undergone a colonoscopy three years prior to this exam which was structurally normal. Endoscopic quality indicators, including a good quality bowel preparation, colonoscopic withdrawal time > 12 min, and quarterly Adenoma Detection Rate (ADR) ranging from 50 to 70% for both male and female patients for the endoscopist from both colonoscopic exams, as well as secondary retrospective comparative review of the pertinent case images, diminish the risk for a "missed" cancer or advanced lesion on the index exam. These cancers did not demonstrate any immunohistochemical features suggestive of Lynch Syndrome, though the rapid progression to cancer within the surveillance interval (possibly non-polypoid in nature) is similar. This cancer presentation within the newly-established recommended colon cancer screening interval warrants concern. CONCLUSIONS: This case prompts serious discussion regarding the length of surveillance intervals in the post-transplant CF population (a population at 20-30 times greater risk for CRC compared to the general non-CF population), as well as the importance of documenting endoscopic quality benchmarks, particularly if a narrative of interval CRC development continues to develop with further prospective monitoring and multi-center experience.

Disseminated Hormographiella aspergillata Infection with Lung and Brain Involvement after Allogenic Hematopoietic Stem-Cell Transplantation in a 54-Year-Old Man.

Hormographiella is a rare fungal pathogen in humans; however, case reports have described disseminated infection in immunocompromised hosts. This pathogen has been described to yield poor prognosis in patients who harbor it. Herein, we present a case report of autopsy-proven disseminated Hormographiella aspergillata infection, confirmed by DNA sequencing, in a patient experiencing a relapse of leukemia. This 54-year-old Caucasian man with chronic myelogenous leukemia (CML) that had been diagnosed in 1989, after having received a hematopoietic cell allotransplant from a compatible sibling donor, had B-cell lymphoid-blast phase of CML in April of 2013, with multiple relapses. His most recent relapse was in September of 2016, when bone marrow biopsy showed 90% blasts. The results of bronchoalveolar lavage (BAL) cultures were positive for filamentous fungus infection. The patient developed encephalopathy and worsening respiratory statusand tachycardia with flutter and hypotension, which resulted in his death. At autopsy, bilateral pleural effusions, multiple right pleural nodules, and subarachnoid hemorrhage were noted. Angioinvasive hyphal fungi were found in the right frontal lobe of the brain and the right upper lobe of the lung. Morphologically, the fungi had multiseptate, branching hyphae. The bronchoalveolar lavage specimen grew a fungus for which the colony morphologic characteristics and microscopic features were compatible with a Hormographiella species. H. aspergillata from the bronchoalveolar lavage was further identified by sequencing the D2 hypervariable region of the large-subunit (LSU) ribosomal DNA gene and the full internal transcribed spacer (ITS) regions.

Patterns of Immunohistochemistry Utilization in Metastases to the Liver.

Immunohistochemistry (IHC) is a well-established morphology adjunct enabling pathologists to make accurate diagnoses. Metastases to the liver is a common scenario where pathologists may rely heavily on IHC in their interpretation. We conducted this study to audit the patterns of IHC utilization in malignant liver biopsies in 3 practice types (academic, community, and expert) as an initial step toward developing best practice guidelines. A total of 1100 specimens were analyzed and the association between the availability of history of other malignancies and the practice type on IHC utilization was studied. Community pathologists were twice as likely to use IHC and to use more markers per case than academic pathologists or the expert pathologist. When history of another malignancy was available, pathologists were not only 1.5 times more likely to use IHC but they also used more markers per case. IHC was still deemed necessary to reach the diagnosis in 67% of cases with a given history of other malignancy. This study described several variables for consideration in our effort to develop IHC utilization guidelines and its results quantify the variance noted among practice types.

Incidental Neuroendocrine Tumor Discovered After Total Pancreatectomy Intended for Islet Autotransplantation: Important Considerations for Surgical Decision-Making.

Total pancreatectomy (TP) is a treatment option for patients experiencing chronic pancreatitis (CP) refractory to medical management. Patients who are candidates for TP benefit from islet autotransplantation (IAT), which preserves available ß-cell mass and thereby reduces the risk of brittle diabetes. Malignancy is an absolute contraindication for IAT to prevent the transplantation of occult malignant cells. We present the case of a patient with CP who was approved to undergo TP with IAT (TPIAT) but was intraoperatively discovered to have a pancreatic neuroendocrine tumor. The case illustrates a number of important surgical decision-making considerations for patients undergoing TPIAT and should help guide surgeons should they be presented with this clinical scenario. We stress the importance of vigilance for possible malignancy and to consider an intraoperative biopsy to further investigate unexpected findings that might represent an occult pancreatic malignancy in patients with CP undergoing TPIAT.

Efficacy of endoscopic-guided fine-needle aspiration in the diagnosis of gastrointestinal spindle cell tumors.

BACKGROUND: Spindle cell neoplasms of the gastrointestinal (GI) tract constitute a wide group of lesions that may raise diagnostic difficulties on hematoxylin-eosin-stained slides. Appropriate endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) technique with sufficient cell block material for immunohistochemistry (IHC) can lead to accurate diagnosis. METHODS: This is a retrospective study of 29 cases obtained from our institution's records over a five-year period (2011-2015). Cytomorphology, histology (when available), IHC, FNA procedure details, imaging characteristics, and clinical history were reviewed. Rapid onsite evaluation (ROSE) was used in all cases. Cytologic samples were correlated with surgical pathology resection specimens when available. RESULTS: Eighteen GI stromal tumors, six leiomyomas, two schwannomas, and one granular cell tumor were analyzed; two cases were not amenable for a definitive diagnosis: one showed fragments of smooth muscle not otherwise specified (smooth muscle vs. leiomyoma) and the other one was insufficient for diagnosis. Locations included stomach, esophagus, duodenum, and colon. EUS-FNA was performed with different gauge needles. Total number of passes ranged between two and nine. We found no evidence that larger-sized needles are superior in procuring adequate lesional tissue. Cell block material was stained with various antibodies. Fourteen surgical resection specimens available showed 100% correlation between cytology and histology. None of the neoplasms recurred until now; one patient succumbed to known esophageal squamous cell carcinoma. CONCLUSION: FNA is a pivotal and inexpensive method for rapid evaluation of GI spindle cell tumors and should be used widely in the attempt to avoid unnecessary surgery. Size of needle used for EUS-FNA does not seem to influence the yield of lesional tissue; rather, ROSE can guide the number of passes and subsequently lead to an adequate cell block.

Pancreatic involvement by metastasizing neoplasms as determined by endoscopic ultrasound-guided fine needle aspiration: A clinicopathologic characterization.

BACKGROUND: Pancreatic tumors often represent primary neoplasms, however organ involvement with metastatic disease can occur. The use of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) to determine the underlying pathology provides guidance of clinical management. METHODS: 25 cases were identified in a retrospective review of our institution's records from 2006 to 2016. Clinical parameters and prognosis are described. RESULTS: Metastatic lesions to the pancreas diagnosed by EUS-FNA accounted for 4.2% of all pancreatic neoplastic diagnoses, each lesion had a median greatest dimension of 1.5 cm, were most often located in the head of the pancreas, and by EUS were typically hypoechoic masses with variably defined borders. Patients were of a median age of 64 years old at diagnosis of the metastatic lesion(s) and the mean interval from primary diagnosis to the diagnosis of metastasis to the pancreas was 58.7 months (95% confidence interval, CI, 35.4 to 82.0 months). The rates of 24-month overall survival after diagnoses of metastatic renal cell carcinoma or all other neoplasms to the pancreas were 90% and 7% respectively. The origin of the neoplasms included the kidney (n = 10), colon (n = 4), ovary (n = 3), lung (n = 2), et al. Smear-based cytomorphology, and a combination of histomorphology and immunohistochemical studies from cell block preparations showed features consistent with the neoplasm of derivation. CONCLUSION: Metastases to the pancreas can be diagnosed via EUS-FNA, with enough specimen to conduct immunohistochemical studies if necessary to delineate origin. The determination of metastatic disease to the pancreas alters management and prognosis of the patient. Diagn. Cytopathol. 2017;45:418-425. © 2017 Wiley Periodicals, Inc.