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.

EMG-driven shared human-robot compliant control for in-hand object manipulation in hand prostheses.

Objective. The limited functionality of hand prostheses remains one of the main reasons behind the lack of its wide adoption by amputees. Indeed, while commercial prostheses can perform a reasonable number of grasps, they are often inadequate for manipulating the object once in hand. This lack of dexterity drastically restricts the utility of prosthetic hands. We aim at investigating a novel shared control strategy that combines autonomous control of forces exerted by a robotic hand with electromyographic (EMG) decoding to perform robust in-hand object manipulation.Approach. We conduct a three-day long longitudinal study with eight healthy subjects controlling a 16-degrees-of-freedom robotic hand to insert objects in boxes of various orientations. EMG decoding from forearm muscles enables subjects to move, proportionally and simultaneously, the fingers of the robotic hand. The desired object rotation is inferred using two EMG electrodes placed on the shoulder that record the activity of muscles responsible for elevation and depression. During the object interaction phase, the autonomous controller stabilizes and rotates the object to achieve the desired pose. In this study, we compare an incremental and a proportional shoulder-decoding method in combination with two state machine interfaces offering different levels of assistance.Main results. Results indicate that robotic assistance reduces the number of failures by41%and, when combined with an incremental shoulder EMG decoding, leads to faster task completion time (median = 16.9 s), compared to other control conditions. Training to use the assistive device is fast. After one session of practice, all subjects managed to achieve tasks with50%less failures.Significance. Shared control approaches that give some authority to an autonomous controller on-board the prosthesis are an alternative to control schemes relying on EMG decoding alone. This may improve the dexterity and versatility of robotic prosthetic hands for people with trans-radial amputation. By delegating control of forces to the prosthesis' on-board control, one speeds up reaction time and improves the precision of force control. Such a shared control mechanism may enable amputees to perform fine insertion tasks solely using their prosthetic hands. This may restore some of the functionality of the disabled arm.

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.

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.

Bioinspired High-Degrees of Freedom Soft Robotic Glove for Restoring Versatile and Comfortable Manipulation.

The human hand is one of the most complex and compact grippers that has arisen as a product of natural genetic engineering; it is highly versatile, as it handles power and precision tasks. Since proper contact points and force directions are required to ensure versatility and secure a stable grip on an object, there must be a large workspace and controllable tip force directions for the digits. Although they are important, many individuals with neuromuscular diseases experience loss of these features. Thus, we propose a high-degree-of-freedom (DOF) soft robotic glove inspired by the anatomical features of human hands. The mechanism for adjusting the position and force direction of each tip is based on the structure of the extrinsic and intrinsic muscle-tendon units. The large thumb workspace was achieved by assisting opposition/reposition and flexion/extension to enable various grasping postures. A bidirectional actuation control mechanism with a cable-actuated agonist and an elastomer antagonist increased the assisted DOF and maintained compactness. The kinematic and kinetic performances of our device were evaluated by performing tests with eight stroke survivors. The thumb workspace increased by 43%, 207%, and 248% in the distal-proximal, dorsal-palmar, and radial-ulnar directions, respectively. The pinching shear force decreased by 54% and 45% for the nonthumb digits and thumb, respectively. These device-assisted improvements allowed objects to be stably grasped and manipulated in various postures. The novel device can assist individuals with impaired hand function to improve their grasping performance. Clinical Research Information Service (CRIS) Registration Number: KCT0004855.

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.

Using Tactile Sensing to Improve the Sample Efficiency and Performance of Deep Deterministic Policy Gradients for Simulated In-Hand Manipulation Tasks.

Deep Reinforcement Learning techniques demonstrate advances in the domain of robotics. One of the limiting factors is a large number of interaction samples usually required for training in simulated and real-world environments. In this work, we demonstrate for a set of simulated dexterous in-hand object manipulation tasks that tactile information can substantially increase sample efficiency for training (by up to more than threefold). We also observe an improvement in performance (up to 46%) after adding tactile information. To examine the role of tactile-sensor parameters in these improvements, we included experiments with varied sensor-measurement accuracy (ground truth continuous values, noisy continuous values, Boolean values), and varied spatial resolution of the tactile sensors (927 sensors, 92 sensors, and 16 pooled sensor areas in the hand). To facilitate further studies and comparisons, we make these touch-sensor extensions available as a part of the OpenAI Gym Shadow-Dexterous-Hand robotics environments.

Sensor-Less and Control-Less Underactuated Grippers With Pull-In Mechanisms for Grasping Various Objects.

This paper proposes an underactuated grippers mechanism that grasps and pulls in different types of objects. These two movements are generated by only a single actuator while two independent actuators are used in conventional grippers. To demonstrate this principle, we have developed two kinds of gripper by different driving systems: one is driven by a DC motor with planetary gear reducers and another is driven by pneumatic actuators with branch tubes as a differential. Each pulling-in mechanism in the former one and the latter one is achieved by a belt-driven finger surface and a linear slider with an air cylinder, respectively. The motor-driven gripper with planetary gear reducers can pull-up the object after grasping. However, the object tends to fall when placing because it opens the finger before pushing out the object during the reversed movement. In addition, the closing speed and the picking-up speed of the fingers are slow due to the high reduction gear. To solve these drawbacks, a new pneumatic gripper by combining three valves, a speed control valve, a relief valve, and non-return valves, is proposed. The proposed pneumatic gripper is superior in the sense that it can perform pulling-up after grasping the object and opening the fingers after pushing-out the object. In the present paper, a design methodology of the different underactuated grippers that can not only grasp but also pull up objects is discussed. Then, to examine the performance of the grippers, experiments were conducted using various objects with different rigidity, shapes, size, and mass, which may be potentially available in real applications.

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.

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.

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/).

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.

Hierarchical Tactile-Based Control Decomposition of Dexterous In-Hand Manipulation Tasks.

In-hand manipulation and grasp adjustment with dexterous robotic hands is a complex problem that not only requires highly coordinated finger movements but also deals with interaction variability. The control problem becomes even more complex when introducing tactile information into the feedback loop. Traditional approaches do not consider tactile feedback and attempt to solve the problem either by relying on complex models that are not always readily available or by constraining the problem in order to make it more tractable. In this paper, we propose a hierarchical control approach where a higher level policy is learned through reinforcement learning, while low level controllers ensure grip stability throughout the manipulation action. The low level controllers are independent grip stabilization controllers based on tactile feedback. The independent controllers allow reinforcement learning approaches to explore the manipulation tasks state-action space in a more structured manner. We show that this structure allows learning the unconstrained task with RL methods that cannot learn it in a non-hierarchical setting. The low level controllers also provide an abstraction to the tactile sensors input, allowing transfer to real robot platforms. We show preliminary results of the transfer of policies trained in simulation to the real robot hand.

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.