Guide for Combining Primary Tumors for Statistical Analysis in Rodent Carcinogenicity Studies.

The Tumor Combination Guide was created at the request of the U. S. Food and Drug Administration (FDA) by a Working Group of biopharmaceutical experts from international societies of toxicologic pathology, the Food and Drug Administration (FDA), and members of the Standard for Exchange of Nonclinical Data (SEND) initiative, to assist pharmacology/toxicology reviewers and biostatisticians in statistical analysis of nonclinical tumor data. The guide will also be useful to study and peer review pathologists in interpreting the tumor data. This guide provides a higher-level hierarchy of tumor types or categories correlating the tumor names from the International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) publications with those available in the NEOPLASM controlled terminology (CT) code list in SEND. The version of CT used in a study should be referenced in the nonclinical study data reviewer's guide (SDRG) (section 3.1) of electronic submissions to the FDA. The tumor combination guide instructions and examples are in a tabular format to make informed decisions for combining tumor data for statistical analysis. The strategy for combining tumor types for statistical analysis is based on scientific criteria gleaned from the current scientific literature; as SEND and INHAND terminology and information evolve, this guide will be updated.

The Corbett Targeted Coin Test: Reliability, criterion related validity, and normative data.

STUDY DESIGN: Clinical measurement. BACKGROUND: Many daily living tasks require in-hand manipulation (IHM). There is a gap in standardized assessment tools for measuring IHM. The Corbett Targeted Coin Test (CTCT) was designed to allow measurement of that fine motor skill. PURPOSE: 1) To evaluate the interrater, test-retest reliability, and validity of the CTCT, and 2) to establish adult norms for the CTCT. METHODS: Reliability and Validity - 30 participants (25 females, age range 21-45) were assessed with the Nine-Hole Peg test and CTCT consecutively by three researchers, then re-evaluated one week later on the CTCT; Reliability was determined using intraclass correlation (ICC2,k) between tests and across testers; Criterion-related validity was determined by comparing scores from nine-hole test and CTCT across testers using ICC2,k. Normative - 190 participants (147 females, age range 20-80) were assessed with the CTCT; mean and standard deviation for participants' scores were calculated by age groups and gender. RESULTS: Test-retest reliability: poor for the right hand (ICCs = -0.29 to 0.45), and poor-moderate for the left hand (ICCs = 0.17-0.56). Inter-rater reliability ranged from moderate to excellent (ICCs = 0.60-0.80). The agreement between CTCT scores and Nine-Hole Peg test was poor for the right (ICC = 0.02; 95% CI: [-0.06, 0.14]) and left hands (ICC = 0.06; 95% CI: [-0.08, 0.28]). CTCT normative data: 41-50 age group demonstrated the highest performance while the 71-80 age group demonstrated the lowest performance. Scores between genders were similar. DISCUSSION: The poor test-retest reliability of CTCT was probably due to practice effect, while interrater reliability indicated that the test can be administered by different testers without compromising the results. The poor validity between tools proves their different constructs. CONCLUSIONS: Use of the CTCT may add another dimension to assessment of dexterity and fine motor skills, specifically, in-hand manipulation, but needs further research on test-retest reliability.

Proceedings of the 2023 Division of Translational Toxicology Satellite Symposium.

The 2023 annual Division of Translational Toxicology (DTT) Satellite Symposium, entitled "Pathology Potpourri," was held in Summerlin, Nevada, at the Society of Toxicologic Pathology's 41st annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers' talks along with select images that were used by the audience for voting and discussion. Various lesions and topics covered during the symposium included induced and spontaneous neoplastic and nonneoplastic lesions in the mouse liver, infectious and proliferative lesions in nonhuman primates, interesting presentations of mononuclear cell infiltrates in various animal models and a complex oral tumor in a rat.

Immunohistochemical Characterization of Proliferative Lesions in the Thymus of Aging CD-1 Mice From Two Studies on the RITA Database, With Special Reference to the Perivascular Space.

Thymic lymphoid hyperplasia is a common age-related finding, which occurs particularly in female CD-1 mice. The main differential diagnoses are malignant lymphoma and thymoma. A systematic investigation of control groups from two carcinogenicity studies was performed including measurements of thymic size, and the immunohistochemistry (IHC) markers pan-Cytokeratin (pan-CK) for thymic epithelial cells; CD3 and CD45R/B220 for T and B lymphocytes, respectively; CD31 for endothelial cells; and F4/80 for macrophages. Thymoma can be differentiated by increased numbers of proliferating epithelial cells demonstrated by pan-CK IHC staining. Differentiation between lymphoid hyperplasia and lymphoma is more challenging as a mixture of B and T lymphocytes can be present in both findings. The present investigation showed that the thymic perivascular space is the compartment where the increased numbers of lymphocytes in hyperplasia are localized and not the medulla, as previously thought. The lymphoepithelial compartment is atrophic to the same extent in thymi diagnosed with age-related involution or lymphoid hyperplasia. Both diagnoses are thus related to variations in lymphoid cellularity of the nonepithelial perivascular space, which is continuous with the perithymic tissue. Likewise, lymphomas have a predilection to colonize the perivascular space and to spare the lymphoepithelial compartment.

Proceedings of the 2022 National Toxicology Program Satellite Symposium.

The 2022 annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri," was held in Austin, Texas at the Society of Toxicologic Pathology's 40th annual meeting during a half-day session on Sunday, June 19. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers' talks along with select images that were used by the audience for voting and discussion. Various lesions and topics covered during the symposium included induced and spontaneous neoplastic and nonneoplastic lesions in the mouse lung, spontaneous lesions in the reproductive tract of a female cynomolgus macaque, induced vascular lesions in a mouse asthma model and interesting case studies in a rhesus macaque, dog and genetically engineered mouse model.

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of the Dog.

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions) Project (www.toxpath.org/inhand.asp) is a joint initiative of the societies of toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying lesions observed in most tissues and organs from the dog used in nonclinical safety studies. Some of the lesions are illustrated by color photomicrographs. The standardized nomenclature presented in this document is also available electronically on the internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous lesions, lesions induced by exposure to test materials, and relevant infectious and parasitic lesions. A widely accepted and utilized international harmonization of nomenclature for lesions in laboratory animals will provide a common language among regulatory and scientific research organizations in different countries and increase and enrich international exchanges of information among toxicologists and pathologists.

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of the Minipig.

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions) Project (www.toxpath.org/inhand.asp) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in most tissues and organs from the minipig used in nonclinical safety studies. Some of the lesions are illustrated by color photomicrographs. The standardized nomenclature presented in this document is also available electronically on the internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous lesions as well as lesions induced by exposure to test materials. Relevant infectious and parasitic lesions are included as well. A widely accepted and utilized international harmonization of nomenclature for lesions in laboratory animals will provide a common language among regulatory and scientific research organizations in different countries and increase and enrich international exchanges of information among toxicologists and pathologists.

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of the Rabbit.

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions Project (www.toxpath.org/inhand.asp) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for proliferative and non-proliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in most tissues and organs from the laboratory rabbit used in nonclinical safety studies. Some of the lesions are illustrated by color photomicrographs. The standardized nomenclature presented in this document is also available electronically on the internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous lesions as well as lesions induced by exposure to test materials. Relevant infectious and parasitic lesions are included as well. A widely accepted and utilized international harmonization of nomenclature for lesions in laboratory animals will provide a common language among regulatory and scientific research organizations in different countries and increase and enrich international exchanges of information among toxicologists and pathologists.

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Non-proliferative and Proliferative Lesions of the Non-human Primate (M. fascicularis).

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions Project (www.toxpath.org/inhand.asp) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in most tissues and organs from the nonhuman primate used in nonclinical safety studies. Some of the lesions are illustrated by color photomicrographs. The standardized nomenclature presented in this document is also available electronically on the internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous lesions as well as lesions induced by exposure to test materials. Relevant infectious and parasitic lesions are included as well. A widely accepted and utilized international harmonization of nomenclature for lesions in laboratory animals will provide a common language among regulatory and scientific research organizations in different countries and increase and enrich international exchanges of information among toxicologists and pathologists.

Proliferative and Nonproliferative Lesions of the Rat and Mouse Central and Peripheral Nervous Systems: New and Revised INHAND Terms.

Harmonization of diagnostic terminology used during the histopathologic analysis of rodent tissue sections from nonclinical toxicity studies will improve the consistency of data sets produced by laboratories located around the world. The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a cooperative enterprise of 4 major societies of toxicologic pathology to develop a globally accepted standard vocabulary for proliferative and nonproliferative lesions in rodents. A prior manuscript (Toxicol Pathol 2012;40[4 Suppl]:87S-157S) defined multiple diagnostic terms for toxicant-induced lesions, common spontaneous and age-related changes, and principal confounding artifacts in the rat and mouse central nervous system (CNS) and peripheral nervous system (PNS). The current article defines 9 new diagnostic terms and updates 2 previous terms for findings in the rodent CNS and PNS, the need for which has become evident in the years since the publication of the initial INHAND nomenclature for findings in rodent neural tissues. The nomenclature presented in this document is also available electronically on the Internet at the goRENI website (http://www.goreni.org/).

Sensing form - finger gaiting as key to tactile object exploration - a data glove analysis of a prototypical daily task.

BACKGROUND: Motor hand skill and associated dexterity is important for meeting the challenges of daily activity and an important resource post-stroke. In this context, the present study investigated the finger movements of right-handed subjects during tactile manipulation of a cuboid, a prototypical task underlying tactile exploration. During one motor act, the thumb and fingers of one hand surround the cuboid in a continuous and regular manner. While the object is moved by the guiding thumb, the opposed supporting fingers are replaced once they reach their joint limits by free fingers, a mechanism termed finger gaiting. METHODS: For both hands of 22 subjects, we acquired the time series of consecutive manipulations of a cuboid at a frequency of 1 Hz, using a digital data glove consisting of 29 sensors. Using principle component analysis, we decomposed the short action into motor patterns related to successive manipulations of the cuboid. The components purport to represent changing grasp configurations involving the stabilizing fingers and guiding thumb. The temporal features of the components permits testing whether the distinct configurations occur at the frequency of 1 Hz, i.e. within the time window of 1 s, and, thus, taxonomic classification of the manipulation as finger gaiting. RESULTS: The fraction of variance described by the principal components indicated that three components described the salient features of the single motor acts for each hand. Striking in the finger patterns was the prominent and varying roles of the MCP and PIP joints of the fingers, and the CMC joint of the thumb. An important aspect of the three components was their representation of distinct finger configurations within the same motor act. Principal component and graph theory analysis confirmed modular, functionally synchronous action of the involved joints. The computation of finger trajectories in one subject illustrated the workspace of the task, which differed for the right and left hands. CONCLUSION: In this task one complex motor act of 1 s duration could be described by three elementary and hierarchically ordered grasp configurations occurring at the prescribed frequency of 1 Hz. Therefore, these configurations represent finger gaiting, described until now only in artificial systems, as the principal mechanism underlying this prototypical task. TRIAL REGISTRATION: clinicaltrials.gov, NCT02865642 , registered 12 August 2016.

Grip Stabilization through Independent Finger Tactile Feedback Control.

Grip force control during robotic in-hand manipulation is usually modeled as a monolithic task, where complex controllers consider the placement of all fingers and the contact states between each finger and the gripped object in order to compute the necessary forces to be applied by each finger. Such approaches normally rely on object and contact models and do not generalize well to novel manipulation tasks. Here, we propose a modular grip stabilization method based on a proposition that explains how humans achieve grasp stability. In this biomimetic approach, independent tactile grip stabilization controllers ensure that slip does not occur locally at the engaged robot fingers. Local slip is predicted from the tactile signals of each fingertip sensor i.e., BioTac and BioTac SP by Syntouch. We show that stable grasps emerge without any form of central communication when such independent controllers are engaged in the control of multi-digit robotic hands. The resulting grasps are resistant to external perturbations while ensuring stable grips on a wide variety of objects.

Relationship between screen-time and hand function, play and sensory processing in children without disabilities aged 4-7 years: A exploratory study.

INTRODUCTION: Screen-time has become a regular occupation for young children at home and school, with little evidence of its impact on children's developmental skills. This study explored the association between children's screen-time, fine motor, in-hand manipulation (IHM), visual-motor integration (VMI), sensory processing (SP) and parent-reported play skills. METHOD: The fine motor, IHM, VMI, SP and play skills of a sample of 25 Australian children without disabilities (M age = 6.2 years, SD = 1.03; 64% girls) were assessed using the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition, Test of In-Hand Manipulation-Revised, Berry Buktenica Developmental Test of Visual-Motor Integration Sixth Edition, Sensory Processing Measure-Home Form and Pretend Play Enjoyment Developmental Checklist (PPEDC). Parents completed a week-long log of their child's screen-time. Spearman's rho correlations and linear regressions with bootstrapping were used for data analysis. RESULTS: Statistically significant moderate level negative correlations were found between Total Screen-Time (TST) and VMI skills (r = -.67, p < .01); Interactive Screen-Time and IHM abilities (r = -.46, p < .05) and TST and bilateral coordination skills (r = -.42, p < .05). There were significant negative correlations between SP ability and both TST (r = -.53, p < .01) and Watching Screen-Time (r = -.66, p < .01). When the PPEDC Object Substitution variable was entered into a regression model as a co-variate of hand function, it appeared to lessen the impact of TST as an independent predictor variable of children's VMI and bilateral coordination skills (p < .23 and p < .61). CONCLUSION: Playing with toys and using object substitution in play (e.g. a child uses an object for something else other than its intended use when playing with it) potentially appear to be a moderating factor of the impact of children's screen-time on their bilateral coordination and VMI skills. Clinicians can encourage children's active and dynamic involvement in games and play pursuits to counteract the potential impact of increased use of devices that involve screen-time.

Proceedings of the 2019 National Toxicology Program Satellite Symposium.

The 2019 annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri," was held in Raleigh, North Carolina, at the Society of Toxicologic Pathology's 38th annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers' talks along with select images that were used by the audience for voting and discussion. Various lesions and topics covered during the symposium included aging mouse lesions from various strains, as well as the following lesions from various rat strains: rete testis sperm granuloma/fibrosis, ovarian cystadenocarcinoma, retro-orbital schwannoma, periductal cholangiofibrosis of the liver and pancreas, pars distalis hypertrophy, chronic progressive nephropathy, and renal tubule regeneration. Other cases included polyovular follicles in young beagle dogs and a fungal blood smear contaminant. One series of cases challenged the audience to consider how immunohistochemistry may improve the diagnosis of some tumors. Interesting retinal lesions from a rhesus macaque emphasized the difficulty in determining the etiology of any particular retinal lesion due to the retina's similar response to vascular injury. Finally, a series of lesions from the International Harmonization of Nomenclature and Diagnostic Criteria Non-Rodent Fish Working Group were presented.

Nonproliferative and Proliferative Lesions of the Rat and Mouse Hematolymphoid System.

The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative changes in rats and mice. The purpose of this publication is to provide a standardized nomenclature for classifying changes observed in the hematolymphoid organs, including the bone marrow, thymus, spleen, lymph nodes, mucosa-associated lymphoid tissues, and other lymphoid tissues (serosa-associated lymphoid clusters and tertiary lymphoid structures) with color photomicrographs illustrating examples of the lesions. Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous lesions as well as lesions induced by exposure to test materials. The nomenclature for these organs is divided into 3 terminologies: descriptive, conventional, and enhanced. Three terms are listed for each diagnosis. The rationale for this approach and guidance for its application to toxicologic pathology are described in detail below.

Estimating the Orientation of Objects from Tactile Sensing Data Using Machine Learning Methods and Visual Frames of Reference.

Underactuated hands are useful tools for robotic in-hand manipulation tasks due to their capability to seamlessly adapt to unknown objects. To enable robots using such hands to achieve and maintain stable grasping conditions even under external disturbances while keeping track of an in-hand object's state requires learning object-tactile sensing data relationships. The human somatosensory system combines visual and tactile sensing information in their "What and Where" subsystem to achieve high levels of manipulation skills. The present paper proposes an approach for estimating the pose of in-hand objects combining tactile sensing data and visual frames of reference like the human "What and Where" subsystem. The system proposed here uses machine learning methods to estimate the orientation of in-hand objects from the data gathered by tactile sensors mounted on the phalanges of underactuated fingers. While tactile sensing provides local information about objects during in-hand manipulation, a vision system generates egocentric and allocentric frames of reference. A dual fuzzy logic controller was developed to achieve and sustain stable grasping conditions autonomously while forces were applied to in-hand objects to expose the system to different object configurations. Two sets of experiments were used to explore the system capabilities. On the first set, external forces changed the orientation of objects while the fuzzy controller kept objects in-hand for tactile and visual data collection for five machine learning estimators. Among these estimators, the ridge regressor achieved an average mean squared error of 0.077 ∘ . On the second set of experiments, one of the underactuated fingers performed open-loop object rotations and data recorded were supplied to the same set of estimators. In this scenario, the Multilayer perceptron (MLP) neural network achieved the lowest mean squared error of 0.067 ∘ .

Brief Synopsis: Review of Renal Tubule and Interstitial Anatomy and Physiology and Renal INHAND, SEND, and DIKI Nomenclature.

This article provides a synopsis of the first two presentations from the second scientific session of the 37th Annual Symposium of the Society of Toxicologic Pathology in Indianapolis, Indiana, on June 18, 2018; the session focused on acute kidney injury. The first presentation, given by Dr. Kevin McDorman, focused on "Fundamentals of Renal Tubule and Interstitial Anatomy and Physiology." Several common background findings from toxicity studies were additionally discussed. Lastly, factors that impact the relevance and usefulness of historical control data, such as quality and consistency of histopathology, were discussed. The second presentation, given by Dr. Torrie Crabbs, provided a review of International Harmonization of Nomenclature and Diagnostic Criteria (INHAND), Standard for Exchange of Nonclinical Data (SEND), and drug-induced kidney injury (DIKI) nomenclature. INHAND is a global collaborative project that provides internationally accepted standardized nomenclature and diagnostic criteria for proliferative and nonproliferative changes in laboratory animals in toxicity and carcinogenicity studies. SEND is currently a required standard for data submission to the Food and Drug Administration (FDA). Since the FDA has indicated its preference for INHAND nomenclature, SEND will predominately use INHAND terminology; thus, familiarity with INHAND terminology is critical for toxicologic pathologists. The diagnostic features of three common DIKI findings, in addition to several complicated INHAND terminologies, were reviewed.

Acute Kidney Injury (AKI)-The Toxicologic Pathologist's Constant Companion.

This article provides a brief overview of the second scientific session of the 37th Annual Symposium of the Society of Toxicologic Pathology in Indianapolis, Indiana, on June 18, 2018. The session was entitled "Acute Kidney Injury (AKI): The Toxicologic Pathologist's Constant Companion" and was co-chaired by Drs. Zaher Radi and Torrie Crabbs. The fundamentals of tubule and interstitial anatomy were covered by Dr. Kevin McDorman, followed by a review of International Harmonization of Nomenclature and Diagnostic Criteria, Standard for Exchange of Nonclinical Data, and Drug-Induced Kidney Injury terminology, which was presented by Dr. Torrie Crabbs. Dr. Bruce Molitoris gave a talk on renal hemodynamics, microcirculation, and ischemia. Advances and challenges on new therapies and clinical targets of AKI were presented by Dr. Brad Rovin, and the session ended with a review from Dr. Zaher Radi on immunopathology of AKI.

Best Practice Approach for Assessment of Microchip-associated Tumors in Preclinical Safety Studies: Position of the Registry of Industrial Toxicology Animal-data (RITA).

Microchip (passive radio-frequency identification device) implantation is a common and widely employed means of animal identification in laboratory animal facilities. However, these devices have been associated with tumors of the skin and subcutis in rodents. While microchip-associated tumors are rare, they pose a challenge for accurate diagnosis and documentation in preclinical toxicity studies. Documentation of these tumors should differentiate microchip-associated lesions with spontaneously occurring or test article-induced tumors. Standardizing criteria for microchip-associated lesions will aid the diagnostic process and allow for preclinical regulatory standardization. To this end, the Registry of Industrial Toxicology Animal-data have developed clear recommendations for diagnosis and documentation of microchip-associated lesions.

Proceedings of the 2018 National Toxicology Program Satellite Symposium.

The 2018 annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri," was held in Indianapolis, Indiana, at the Society of Toxicologic Pathology's 37th annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers' talks along with select images that were used by the audience for voting and discussion. Various lesions and other topics covered during the symposium included seminiferous tubule dysgenesis in rats, ameloblast and odontoblast degeneration/necrosis in a Sprague Dawley rat, intestinal leiomyositis in a beagle dog, gallbladder mucinous hyperplasia, focus of hepatocellular alteration and bile duct alteration in otters, renal tubule cytoplasmic vacuolation with basophilic granules in mice treated swith antisense oligonucleotide therapy, a uterine choriocarcinoma in a rhesus macaque, and rete ovarii proliferative ovarian lesions in various aged rat strains. One particularly provocative lesion was a malignant neoplastic proliferation in the renal pelvic region of a cynomolgus macaque from a 21-day study. Additional challenging lesions included thyroid proliferative lesions in zebra fish and gross findings in fish larvae during routine chemical screening. The Rabbit and Minipig International Harmonization of Nomenclature and Diagnostic Criteria Organ Working Groups also presented a series of challenging lesions.