The College of American Pathologists outlines standardized testing and typing methods aimed at reducing diagnostic variability and improving outcomes for patients with this rare but serious disease.
Clinical laboratory leaders facing growing demand for precision diagnostics now have new guidance to support one of pathology’s most complex diagnostic challenges. The College of American Pathologists (CAP) has published an evidence-based guideline designed to standardize laboratory approaches to diagnosing amyloidosis, a rare but life-threatening condition that often goes undetected until advanced stages.
Amyloidosis occurs when abnormal amyloid proteins accumulate in tissues and organs, leading to progressive damage. Because symptoms can mimic other diseases and diagnostic techniques vary widely between laboratories, delays and misclassification have long been a concern. CAP’s new guideline aims to reduce that variability by defining best practices for amyloid detection, fibril protein typing, and specimen evaluation.
The recommendations were developed by a multidisciplinary expert panel that reviewed more than 4,000 peer-reviewed studies. The result is a practical framework intended to help pathologists select the most accurate testing strategies while improving consistency across laboratories.
“This guideline is meant to improve the consistency and accuracy of laboratory diagnoses for systemic amyloidosis,” said Dylan V. Miller, MD, FCAP, guideline co-chair.
Dylan V. Miller, MD, FCAP, guideline co-chair noted, “Clearer standards will support more reliable diagnoses and ultimately better outcomes for patients.” (Photo credit: American Board of Pathology)
Best Practices for Amyloid Detection and Typing
Among the recommendations, the guideline reinforces Congo red staining as the diagnostic standard for detecting amyloid, while noting that fluorescence microscopy may enhance sensitivity in laboratories where it is available. Cytology, including fat pad aspirates, may be appropriate for initial screening due to its minimally invasive nature, but the guideline cautions that such samples are often insufficient for definitive subtyping.
For amyloid protein identification, the panel recommends mass spectrometry as the most accurate and sensitive method, particularly in complex or ambiguous cases. CAP emphasizes that precise protein typing is essential, as treatment options and prognoses vary significantly depending on amyloid subtype.
“Amyloid science is advancing rapidly, with new imaging, typing, and therapies reshaping the field,” said Billie Fyfe-Kirschner, MD, FCAP, guideline co-chair. “For pathologists, staying current is essential to ensure accurate diagnoses and guide patient care.”
Rising Need for Advanced Diagnostics and Long-Term Planning
From a management perspective, the guideline underscores the growing importance of advanced diagnostic capabilities, including access to validated staining methods and mass spectrometry. For lab leaders, this may influence decisions around test menus, referral relationships, and investment in specialized technologies.
CAP plans to reassess the guideline at least every five years, or sooner if major scientific or clinical advances occur. As amyloidosis awareness increases and targeted therapies expand, laboratory accuracy will play an increasingly central role in patient outcomes.
For clinical laboratory leaders and pathologists, the new guideline provides a roadmap for improving diagnostic confidence, standardizing workflows, and aligning laboratory practices with evolving expectations for precision medicine.
Industry commenters point to a void since the federal government shuttered the Clinical Laboratory Improvement Advisory Committee
For readers wondering what has happened to the Clinical Laboratory Improvement Advisory Committee (CLIAC), the bottom line is the panel has been terminated, causing a significant void for the lab industry at the federal level.
Dark Daily’s sibling brands, including The Dark Report, G2 Intelligence, and Today’s Clinical Lab, have been exploring various aspects about the demise of CLIAC.
The Centers for Disease Control and Prevention (CDC) confirmed to G2 Intelligence that CLIAC was terminated as of March 31, citing an executive order from President Donald Trump intended to reduce federal advisory committees. The decision blindsided even those closest to CLIAC. Incoming committee chairman Jordan Laser, MD, revealed in an email to colleagues that he did not have more insight into CLIAC’s demise beyond media reports, G2 reported.
Since its founding in 1992, CLIAC has played an influential—though non-regulatory—role in shaping updates to the Clinical Laboratory Improvement Amendments of 1988 (CLIA). The committee brought together pathologists, lab directors, public health leaders, and representatives from federal agencies such as the CDC, Centers for Medicare and Medicaid Services, and Food and Drug Administration.
The federal government’s decision to eliminate CLIAC “risks stalling progress in laboratory medicine, which could ultimately hinder efforts to improve patient care,” CAP President Donald Karcher, MD, FCAP, told The Dark Report. (Photo copyright: College of American Pathologists.)
‘Critical Venue’ for Labs Has Been Eliminated
Industry groups are sounding alarms about what comes next. In an interview with Today’s Clinical Lab, Anthony Killeen, MD, PhD, president of the Association for Diagnostics and Laboratory Medicine (ADLM), said CLIAC was an important forum for medical lab scientists to discuss CLIA.
“[CLIAC] served as a critical venue for working through current problems with the rule and also for expert input on how new technologies—such as next-generation sequencing, digital pathology, and artificial intelligence-assisted diagnostics—should be assessed and integrated under CLIA,” Killeen said.
ADLM has formally urged Department of Health and Human Services Secretary Robert F. Kennedy, Jr. to reverse the CLIAC decision. In a May letter, the association emphasized that CLIAC’s work was funded entirely through user fees paid by clinical laboratories rather than taxpayer dollars—a point many in the lab industry say underscores CLIAC’s value.
CAP President Wonders about Future Communication Gaps
The Dark Report noted that the disbanding of CLIAC may cost labs time in certain cases, a commodity that few diagnostic settings have in abundance.
“The absence of this advisory body may lead to gaps in communication and slower response times in addressing [industry] challenges,” Donald Karcher, MD, FCAP, president of the College of American Pathologists (CAP), told The Dark Report.
The absence of CLIAC raises uncertainty for clinical labs because federal agencies have lost a prime source to gather specialized input on complex scientific and operational issues facing the lab industry. Dark Daily’s partner brands will continue to track this matter closely. If you’re not a subscriber, you can check out The Dark Report’s insider coverage with a 14-day free trial.
However, effective communication can bring more harmony to medical lab managers and scientists when it comes to compliance
Depending on how lab professionals view it, clinical laboratory regulations can be characterized as a series of checklists to fill out or an opportunity to grow an organization.
Leaning into the latter option will preserve regulatory compliance while also ensuring the operational health of the clinical laboratory.
At the Lab Manager Leadership Summit, Kelly VanBemmel, MS, MB(ASCP)CM (above) pressed attendees to open the lines of communication between bench scientists and lab managers when it comes to clinical laboratory regulations. (Photo copyright: Scott Wallask.)
‘There’s a Gap’ in How Both Sides View Regulatory Compliance
VanBemmel spent her presentation aiming to bridge the rift between how bench scientists look at clinical laboratory regulations compared to the views of medical lab managers.
“There’s a gap between how staff experience regulations and how management does,” she noted. “Staff typically think of compliance as a checklist to do their jobs.” Managers, however, need to understand a wider compliance picture. She illustrated her point by comparing views on the following regulatory bodies.
Staff understand that the FDA clears tests and devices for use in non-research environments, though not all consumables or equipment are in that setting.
Managers understand that the FDA develops rules and guidance for CLIA complexity categorization.
Communication Leads to Common Ground with Clinical Laboratory Regulations
Given the above differences among managers and staff, VanBemmel explained that both sides must frequently talk to each other to fill in the missing details.
“When you’re in the thick of regulations, communication becomes critical,” she said.
For example, bench staff may feel it is solely their manager’s responsibility to comply with clinical laboratory regulations. Savvy lab leaders will point out non-compliant conditions—such as diagnostic analyzer malfunctions and sample cross contamination—over which bench staff have direct control, helping workers better understand their responsibility when it comes to compliance.
On the other hand, lazy communication from managers to their bench scientists can stunt compliance efforts. She recalled a prior supervisor who often answered questions about regulations by asking: What does the standard operation procedure state?
“That answer wasn’t particularly helpful,” VanBemmel recalled. “That made me think that my supervisor didn’t understand nuance.”
Thorough communication builds greater trust, and seasoned clinical laboratory professionals of all ranks will quickly recognize the compliance benefits when the worker-manager relationship gels.
McGonnagle’s involvement with medical laboratory medicine spans five decades and 38 years of support for the nation’s anatomic pathologists and clinical laboratory professionals
The presentation was made in front of 950 attendees. During the presentation, several of McGonnagle’s peers described the multiple ways that he regularly supports the profession of clinical laboratory medicine.
In 1986, McGonnagle was engaged by the College of American Pathologists (CAP) to develop the concept of a new, tabloid-sized, color magazine to be called CAP Today. It was January 1987 when monthly publication of CAP Today formally commenced.
McGonnagle was again tapped by CAP to oversee production of another publication that was created in 1996. Since its inception, he has also been publisher of the Archives of Pathology and Laboratory Medicine.
During last week’s Executive War College on Diagnostic, Laboratory, and Pathology Management in New Orleans, Bob McGonnagle (center right) was honored with a Lifetime Achievement Award for his 38 years as Publisher of CAP Today, along with his innumerable contributions to advancing the clinical laboratory and anatomic pathology professions. McGonnagle is joined by Robert Michel, founder of the Executive War College on his right; Al Lui, MD, of Innovative Pathology Medical Group on his far right; and Stan Schofield of Compass Group on his left. (Photo copyright: The Dark Report.)
38 Years as Publisher of CAP Today Magazine
But McGonnagle’s duties as publisher are just the starting point of the contributions McGonnagle has made to the House of Laboratory Medicine in the past 38 years. He is regularly seen at pathology and lab meetings, conferences, and workshops throughout the United States and overseas. As a speaker and moderator, he is much in demand. He is often asked to sit in during strategic retreats and think tanks organized by laboratory associations, lab organizations, and lab vendors.
During the presentation ceremony, three of McGonnagle’s peers offered insights and examples of his unstinting support of pathologists, lab managers, and companies serving medical laboratories. First to speak was Stan Schofield, Managing Principal at Compass Group and past CEO of NorDx Laboratories in Scarborough, Maine.
“Bob McGonnagle is excellent as a moderator for conferences, meetings, and conventions and will always say ‘yes’ when asked to serve,” Schofield observed. “He is quick to recognize and adapt to emerging issues. He processes information from various parts of the lab industry, then generates insights and information all can understand and use to the benefit of their respective labs and pathology groups.”
Next to speak was pathologist Al Lui, MD, President and Medical Director, at Innovative Pathology Medical Group in Torrance, California. Lui has been active on committees and initiatives of CAP for decades. “Recognition of Bob McGonnagle’s past and continuing contributions to the profession of pathology and laboratory medicine is long overdue,” he said.
McGonnagle as Farmer, Fan of Classical Music, and Oenophile
Lui then presented slides that showed the range of McGonnagle’s activities outside of his publishing responsibilities. For example, Bob is remote manager of two inherited family farms in Iowa that produce corn, soybeans, and cattle. His wife competes in equestrian events. They are wine aficionados and close personal friends with one of Napa Valley’s most respected vintners.
One key figure in McGonnagle’s publishing activities is the Editor of CAP TodaySherrie Rice. She has served in this role since 1987 and thus has collaborated with Bob for the 38 years of CAP Today’s publication. “His leadership of the periodicals department at the CAP has been brilliant and working alongside him for more than three decades has been the gift of a lifetime,” Rice noted.
Rice also described an underappreciated aspect of McGonnagle’s efforts as Publisher. “Bob constantly works to connect the IVD manufacturers and lab vendors with labs that need and benefit from these solutions,” she noted. “He is quick to recognize emerging technologies and help explain them with in-depth stories in CAP Today that help pathologists and lab managers better understand when such innovations are ready to be implemented.”
A Career That Spans Five Decades
As McGonnagle was handed his Lifetime Achievement Award, Robert Michel, Founder of the Executive War College and Editor-in-Chief of Dark Daily and its sister publication The Dark Report, made several observations. “Bob McGonnagle has all the hallmarks of a loyal friend. He is always willing to help and never asks for anything in return,” Michel noted. “He is discreet and trustworthy, with keen powers of observation and analysis. Our profession is blessed that his career and contributions have spanned five decades.”
All of Bob McGonnagle’s colleagues, friends, and associates are encouraged to use social media to send him congratulations and notes of appreciation for his 38 years of service as Publisher of CAP Today, and for his many contributions to the clinical laboratory and pathology professions.
Here are social media links where it would be appropriate to post comments about Bob McGonnagle, with best wishes, congratulations, and examples of his selfless support:
But even though the College of American Pathologists (CAP) and nine other organizations signed a December 12 stakeholder letter to leaders of key House and Senate committees urging passage of legislation that would enable some regulation of LDTs, the VALID Act was ultimately omitted from the year-end omnibus spending bill (H.R. 2617).
That may be due to pressure from organizations representing clinical laboratories and pathologists which lobbied hard against the bill.
Responding to criticism of its stance on FDA oversight of LDTs, in a May 2022 open letter posted on the organization’s website, anatomic pathologist and CAP president Emily Volk, MD, said “we at the CAP have an honest difference of opinion with some other respected laboratory organizations. … We believe the VALID Act is the only viable piece of legislation addressing the LDT issue. … the VALID Act contains many provisions that are similar to policy the CAP has advocated for regarding the regulation of laboratory tests since 2009. Importantly, the current version includes explicit protections for pathologists and our ability to practice medicine without infringement from the Food and Drug Administration (FDA).” (Photo copyright: College of American Pathologists.)
Organizations on Both Sides Brought Pressure to Bear on Legislators
The AAMC and AMP were especially influential, Bucshon told ProPublica. In addition to spending hefty sums on lobbying, AMP urged its members to contact legislators directly and provided talking points, ProPublica reported.
“The academic medical centers and big medical centers are in every state,” Bucshon said. As major employers in many locales, they have “a pretty big voice,” he added.
Discussing CAP’s reasoning behind its support of the VALID Act in a May 26 open letter and podcast, CAP president Emily Volk, MD, said the Valid Act “creates a risk-based system of oversight utilizing three tiers—low, moderate and high risk—in order to target the attention of the FDA oversight.”
While acknowledging that it had room for improvement, she lauded the bill’s three-tier risk-based system, in which tests deemed to have the greatest risks would receive the highest level of scrutiny.
She also noted that the bill exempts existing LDTs from an FDA premarket review “unless there is a safety concern for patients.” It would also exempt “low-volume tests, modified tests, manual interpretation tests, and humanitarian tests,” she wrote.
In addition, the bill would “direct the FDA not to create regulations that are duplicative of regulation under CLIA,” she noted, and “would require the FDA to conduct public hearings on LDT oversight.”
Pros and Cons of the VALID Act
One concern raised by opponents relates to how the VALID Act addressed user fees paid by clinical laboratories to fund FDA compliance activities. But Volk wrote that any specific fees “would need to be approved by Congress in a future FDA user fee authorization bill after years of public input.”
During the May 2022 podcast, Volk also cast CAP’s support as a matter of recognizing political realities.
“We understand that support for FDA oversight of laboratory-developed tests or IVCTs is present on both sides of the aisle and in both houses of Congress,” she said. “In fact, it enjoys wide support among very influential patient advocacy groups.” These groups “are very sophisticated in their understanding of the issues with laboratory-developed tests, and they do have the ear of Congress. There are many in the laboratory community that believe the VALID Act goes too far, but I can tell you that many of these patient groups don’t believe it goes far enough and are actively pushing for even more restrictive paradigms.”
Also urging passage of the bill were former FDA commissioners Scott Gottlieb, MD, and Mark B. McClellan, MD, PhD. In a Dec. 5 opinion piece for STAT, they noted that “diagnostic technologies have undergone considerable advances in recent decades, owing to innovation in fields like genomics, proteomics, and data science.” However, they wrote, laws governing FDA oversight “have not kept pace,” placing the agency in a position of regulating tests based on where they are made—in a medical laboratory or by a manufacturer—instead of their “distinctive complexity or potential risks.”
In their May 22 letter, opponents of the legislation outlined broad areas of concern. They contended that it would create “an onerous and complex system that would radically alter the way that laboratory testing is regulated to the detriment of patient care.” And even though existing tests would be largely exempted from oversight, “the utility of these tests would diminish over time as the VALID Act puts overly restrictive constraints on how they can be modified.”
CLIA Regulation of LDTs also Under Scrutiny
The provision to avoid duplication with the Clinical Laboratory Improvement Amendments (CLIA) program—which currently has some regulatory oversight of LDTs and IVCTs—is “insufficient,” opponents added, “especially when other aspects of the legislation call for requirements and activities that lead to duplicative and unnecessary regulatory burden.”
Opponents to the VALID Act also argued that the definitions of high-, medium-, and low-risk test categories lacked clarity, stating that “the newly created definition of moderate risk appears to overlap with the definition of high risk.”
The opponents also took issue with the degree of discretion that the bill grants to the US Secretary of Health and Human Services. This will create “an unpredictable regulatory process and ambiguities in the significance of the policy,” they wrote, while urging the Senate committee to “narrow the discretion so that stakeholders may better evaluate and understand the implications of this legislation.”
Decades ago, clinical laboratory researchers were allowed to develop assays in tandem with clinicians that were intended to provide accurate diagnoses, earlier detection of disease, and help guide selection of therapies. Since the 1990s, however, an industry of investor-funded laboratory companies have brought proprietary LDTs to the national market. Many recognize that this falls outside the government’s original intent for encouragement of laboratory-developed tests to begin with.
