Telecytology validation: is there a recipe for everybody?

INTRODUCTION: Telecytology offers a suitable solution to the cost and time efficiency questions on rapid onsite evaluation (ROSE). An increasing number of institutions are adopting new telecytology systems to meet the increasing ROSE requests, although there is no agreement on the details of how a telecytology validation study needs to be conducted. We propose a standardized approach for telecytology validation studies that could be done in a variety of practices. MATERIALS AND METHODS: Consecutive cases from 6 months prior were chosen to reflect a case mix comparable to real life. A fellow assessed the slides at the ROSE site while 6 cytopathology faculty convened in a conference room with a television screen, and noted the adequacy, diagnostic category, and specific diagnoses. All participants were blinded to the original adequacy assessment and final diagnoses. For each case, evaluation time and the slides counts were noted. RESULTS: Fine-needle aspiration specimens from 52 patients were included in the study. Of these, 13 cases were used in the first "test" session. The adequacy concordance rates ranged between 92.3% and 100%, with an overall concordance rate of 94.8%. The diagnostic category concordance rates ranged between 90.3% and 95.5%, with an overall concordance rate of 91.9%. The specific diagnosis concordance rates ranged between 84.6% and 92.9%, with an overall concordance rate of 88.1%. CONCLUSIONS: Validation of telecytology requires a standardized approach just like any other new technology. In this study, we propose an efficient and accurate method for cytopathology departments of various case volumes to conduct telecytology validation studies.

Malignant Gastrointestinal Neuroectodermal Tumor (GNET) with Prolonged Disease-Free Survival after Platinum-Based Chemotherapy.

Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare disease with a handful of cases described in literature. GNET has only become a well-known/widely accepted entity in the recent years, but it is still not listed in the database of rare diseases. Due to the rarity of disease, there are no guidelines on standard therapeutic approaches in the adjuvant or metastatic setting. Here, we describe a unique case of GNET with a 7-year disease-free survival following adjuvant cisplatin and etoposide chemotherapy. This is the longest disease-free survival that has ever been described in literature and may support using this combination in a larger cohort of patients in the context of a global clinical trial. We will also review the histopathologic features of GNET and potential therapeutic options in the metastatic setting.

The utilization and utility of immunostains in body fluid cytology.

BACKGROUND: Body fluid cytology (BFC) is an important tool in the diagnosis and staging of malignancy and is aided by the judicious use of immunohistochemistry (IHC). The aim of this study was to determine the usage rates of IHC stains in BFC, their type and indications, and their diagnostic impact. We also attempted to estimate the optimal rate of IHC use in BFC by comparing the entire laboratory's and each individual cytopathologist's IHC use rates with their respective indeterminate and malignant diagnosis rates. METHODS: We conducted a retrospective study of IHC stain use in BFC during a 5.5-year interval (2013-2018) and determined the laboratory's and each individual cytopathologist's IHC usage patterns according to the final diagnosis, site, and indications for their use. RESULTS: A total of 477 out of 4144 (11.5%) BFC cases had 2128 individual immunostains performed, with an average of 4.5 immunostains per case. Individual cytopathologists used IHC stains on 6.7% to 22% of their BFC cases. Pathologists with higher rates of IHC stain use than the laboratory's mean were less experienced and had higher rates of indeterminate but not of malignant diagnoses. The most common indication for the use of IHC stains was differentiating mesothelial from malignant cells. MOC31, calretinin, Ber-EP4, CD68, and D2-40 were the most commonly used of the 67 different IHC stains used in BFC. CONCLUSIONS: The laboratory's mean may represent the optimal IHC use rate, as higher IHC use rates did not lead to more diagnostic certainty or higher pickup rates of malignant cells.

Fine-needle aspiration specimens of 3 cases of intra-abdominal Rosai-Dorfman disease with comprehensive review of the literature.

INTRODUCTION: Rosai-Dorfman disease (RDD) is a rare usually self-limited non-Langerhans cell histiocytosis of unknown etiology. Nodal and extranodal RDD appear to represent distinct conditions with different molecular alterations and prognosis. They also pose different diagnostic challenges on biopsies and fine-needle aspiration (FNA) cytology. The aim of this study was to report on 3 cases of intra-abdominal RDD and perform an extensive review of the literature on FNA findings of RDD. MATERIALS AND METHODS: We reviewed FNA specimens from cases diagnosed histologically or cytologically as RDD during the past 10 years. We searched the PubMed and Google Scholar databases for cases of RDD sampled by FNA. RESULTS: We identified 3 cases of intra-abdominal RDD, involving the kidney, periportal lymph node, and pancreas. FNA of the latter was hypocellular with fibrosis and was nondiagnostic. FNA of the first 2 yielded hypercellular smears that were diagnosed as RDD due to the identification of emperipolesis occurring in large uni- or binucleated histiocytes with large nuclei, fine chromatin, and prominent nucleoli in smears and cell-block sections. Immunohistochemistry showed positive staining for S100 and CD68 and negative staining for CD1a. The large histiocytes with emperipolesis were more difficult to identify histologically and their demonstration required immunohistochemical stains. CONCLUSION: Our experience and an extensive review of the literature suggest that extranodal RDD can be diagnosed on FNA, and that the recognition of histiocytes with emperipolesis may be less challenging cytologically than histologically. The fibrosis frequently seen in extranodal RDD may lead to nondiagnostic aspirates, however.

Variation of cytopathologists' use of the indeterminate diagnostic categories "atypical" and "suspicious for malignancy" in the cytologic diagnosis of solid pancreatic lesions on endoscopic ultrasound-guided fine-needle aspirates.

Indeterminate cytologic diagnoses in endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNA) of solid pancreatic lesions include the diagnostic categories "atypical" (ATY) and "suspicious for malignancy" (SUSP), which are used at variable rates and are associated with variable underlying risk of malignancy. The aim of this study was to determine individual cytopathologists' rates of indeterminate diagnoses in EUS-FNA of solid pancreatic lesions and their relationship to cytopathologists' experience and volume of pancreatic EUS-FNA examined, as well as the potential impact of departmental consensus review on indeterminate diagnoses. DESIGN: The diagnostic rates of ATY and SUSP and their underlying risk of malignancy were calculated for six cytopathologists who diagnosed 1,114 of 1,225 EUS-FNA of solid pancreatic lesions from 1/1/2001 to 9/15/2014, and were then compared for the periods before and after the implementation of departmental consensus review during 2009. RESULTS: The six cytopathologists diagnosed 10% of cases as indeterminate; 82 (7.4%) as "atypical" and 29 (2.6%) as "suspicious". The individual cytopathologists' indeterminate diagnosis rates varied twofold (6.67-12.80%) and did not correlate with their experience, total or annual volume of EUS-FNAs. Of the 56/99 (56.57%) cases with follow-up, the underlying rate of malignancy was 47% (35/75; for "atypical" and 87.5% (21/24); for "suspicious"). The underlying rates of malignancy were 33-67% for "atypical" and 80-100% for "suspicious" diagnoses made by individual cytopathologists. The rate of indeterminate diagnoses decreased from 11.55 to 7.88% after the implementation of departmental consensus review. CONCLUSION: Individual cytopathologists' rates of indeterminate diagnoses and their significance vary; however, consensus review is helpful in reducing these rates. Diagn. Cytopathol. 2017;45:3-13. © 2016 Wiley Periodicals, Inc.

Mixed acinar-neuroendocrine-ductal carcinoma of the pancreas: a tale of three lineages.

Most pancreatic cancers arise from a single cell type, although mixed pancreatic carcinomas represent a rare exception. The rarity of these aggressive malignancies and the limitations of fine-needle aspiration (FNA) pose significant barriers to diagnosis and appropriate management. We report a case of a 54-year-old man presenting with abdominal pain, jaundice and a hypodense lesion within the uncinate process on CT. FNA suggested poorly differentiated adenocarcinoma, which was subsequently resected via pancreaticoduodenectomy. Pathological analysis yielded diagnosis of invasive mixed acinar-neuroendocrine-ductal pancreatic carcinoma. Given the rare and deadly nature of these tumours, clinicians must be aware of their pathophysiology and do practice with a high degree of clinical suspicion, when appropriate. Surgical resection and thorough pathological analysis with immunohistochemical staining and electron microscopy remain the standards of care for mixed pancreatic tumours without gross evidence of metastasis. Diligent characterisation of the presentation and histological findings associated with these neoplasms should continue in order to promote optimal diagnostic and therapeutic strategies.

Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) of the pancreas: second case report.

INTRODUCTION: Rosai-Dorfman disease (RDD), originally described as sinus histiocytosis with massive lymphadenopathy, is a rare histiocytic proliferative disorder with a distinctive microscopic appearance. It formerly was thought to be a process limited to lymph nodes, yet RDD has been documented to occur in many organ systems, notably the bone, skin, soft tissue, central nervous system, eye and orbit, and upper respiratory tract. The digestive system, however, is affected only exceptionally, with this being only the second documented case involving the pancreas. CASE DESCRIPTION: In this case report, we present a case of a 63-year-old African-American female who was found to have a pancreatic head mass and right middle lobe pleural nodule during evaluation for obstructive jaundice. DISCUSSION AND CONCLUSION: She underwent a Whipple procedure. Her pathology of both the pancreatic mass and RML lung wedge resection showed sinus histiocytosis with massive lymphadenopathy, along with extensive fibrosis intertwined with nodular mixed inflammatory infiltrate. The histiocytes characteristically showed "emperipolesis," in which lymphocytes had penetrated the cytoplasm and remained viable within the histiocytes (lymphocytes continued to have free movement in the histiocyte). In addition, the histiocytic cells were positive with S-100 protein and CD68, hallmarks of RDD. Although rare, Rosai-Dorfman disease should be considered in the differential diagnosis of patients presenting with pancreatic and/or lung nodules, especially when biopsy or cytology results report atypical inflammatory findings.

The serotonin-1A agonist ipsapirone prevents ethanol-associated death of total rhombencephalic neurons and prevents the reduction of fetal serotonin neurons.

Previously, this laboratory showed that in utero and in vitro ethanol exposure significantly reduces developing serotonin (5-HT) neurons and that treatment with a 5-HT1A agonist such as buspirone or ipsapirone prevents the ethanol-associated loss. The present study investigated whether ethanol decreases fetal rhombencephalic neurons, including 5-HT neurons, by causing apoptosis. We also investigated whether ipsapirone prevents the ethanol-associated deficit of fetal rhombencephalic neurons by reducing apoptosis. The results of these studies strongly suggest that the ethanol-associated reduction in fetal rhombencephalic neurons that accompanies both in utero and in vitro exposure to physiological concentrations of ethanol is associated with increased apoptosis in these neurons. A physiological concentration of ethanol (i.e., 50 mM) increases apoptosis in fetal rhombencephalic neurons and decreases the number 5-HT neurons. It also appears that the 5-HT1A agonist ipsapirone provides neuroprotection to these neurons by reducing apoptosis. Another mechanism by which ethanol-associated apoptosis can be blocked is by including serum proteins in the media at a concentration of 1% or higher; this concentration of serum proteins is high in comparison to the protein concentration in cerebrospinal fluid.