The International Nomenclature Project: An Update

One of the challenges for toxicologic pathologists is to translate the diverse range of morphologic changes that are observed in toxicity studies into a consistent and readily understood set of diagnostic terms to be tabulated and summarized in regulatory reports or peer-reviewed publications. Historically, there have been multiple efforts to provide uniform nomenclature for lesions observed in laboratory animals. These efforts began as early as 1973 and have culminated in various textbooks, workshop reports, and monographs. The efforts have typically focused on the rat and mouse and, in many cases, were limited to proliferative lesions. Many of the texts or documents that describe suggested nomenclature are either not widely available or are out of print.

To address this issue, members of the major societies of toxicologic pathology (JSTP, BSTP, ESTP, and STP) have been engaged in an international collaborative effort to codify and publish uniform nomenclature for both proliferative and non-proliferative lesions in laboratory rodents. Several features unique to this effort include (1) a truly international scope, (2) implementation of an open comment period allowing a wide group of toxicologic pathologists the opportunity to provide input, and (3) availability in a Web-based format.

The project goes under the acronym INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice). Project oversight is provided by the Global Editorial and Steering Committee (GESC), which consists of members from each of the major societies of toxicologic pathology. The most important components of the INHAND project are the Organ System Working Groups. Formation of these groups is coordinated by the GESC, and they consist of a global chairperson and members from each of the major societies of toxicologic pathology. The GESC actively seeks out organ system experts to serve on these groups. In addition, the GESC often accommodates requests from pathologists who volunteer for a specific organ working group.

The Organ System Working Groups have the responsibility to prepare the nomenclature guidelines for both proliferative and nonproliferative lesions of rats and mice for their assigned organ system. In addition to lesions that occur spontaneously, the groups are asked to determine if there are common, xenobiotic-induced lesions for which standardized nomenclature might be needed. The working groups draw heavily from existing nomenclature documents, Web sites, and publications including prior work of the Registry of Industrial Toxicology Animal-Data (RITA) and the Standardized System of Nomenclature and Diagnostic Criteria (SSNDC). For each diagnostic entity, the working group selects a preferred diagnosis and acceptable alternative diagnoses, provides diagnostic criteria and differential diagnosis, and prepares representative photomicrographs.

An important feature of the INHAND project is the access provided to the global open Registry Nomenclature Information System (goRENI; www.goreni.org) (Figure 1). Access is provided to all members of toxicologic pathology societies worldwide. Access is free but must be requested through the goRENI Web site (Figure 2). Once access is granted, pathologists can navigate by organ systems (Figure 3) and ultimately select a diagnosis they would like to view. Within the goRENI system, each diagnostic entity is referred to as a “manuscript.” An example is the written information, and photographic illustrations, provided for a bronchiolo-alveolar carcinoma as shown in Figure 4.

Once an organ working group has prepared a draft document, the nomenclature is placed on the goRENI Web site for review and discussion. Members of the contributing STPs are notified of the dates of the review period through their respective societies. Following the designated comment period, the working group revises the nomenclature documents and, in consultation with the GESC, finalizes the nomenclature for that organ system. Finalized nomenclature will be available to toxicologic pathologists in two forms: (1) electronic access via the goRENI Web site and (2) print-based publication in the toxicologic pathology journals. Due to the substantial costs associated with print-based publications, these publications will be rotated among the various toxicologic pathology journals, rather than all being published in each of the journals.

Given the international scope of the project and the range of organ systems to be covered, it is anticipated that this project will take several years to complete. To date, eight organ working groups have been formed, including Respiratory, Immune, Cardiovascular, Central Nervous System, Urinary, Liver, Male Reproductive, and Female Reproductive. The remaining seven organ working groups comprise Digestive, Special Senses, Endocrine, Musculoskeletal, Mammary Gland, Integument, and Soft Tissue. It is anticipated that these groups will initiate work during June 2009.

The first organ system that will be available is the Respiratory System. The draft nomenclature for this system was available for review and comment on the goRENI site during 2008, and the final version will be published in a supplementary “special issue” of Toxicologic Pathology. It is anticipated that at least two additional organ systems will have drafts for review and comment during 2009.

What can you do to support this effort?

1. Review and comment on draft nomenclature during the open comment periods. While the experts on the working groups are responsible for reaching consensus on challenging diagnoses, your input is extremely important in this process.

2. Most important, as more and more organ systems develop harmonized nomenclature, implement these diagnoses and associated diagnostic criteria in your daily practice of toxicologic pathology.

The GESC sincerely appreciates the efforts of all of those serving on the organ working groups, and we look forward to working with the toxicologic pathology community as additional organ systems are drafted, reviewed, and completed.