Jeffrey H. Baybick, MD

The US Government Accountability Office (GAO) released a study on June 24, 2013, calling for "action" to address higher use of anatomic pathology services by providers who "self-refer" (i.e., those that have ownership positions in pathology labs). The report suggested that profit and not science drove utilization, including that of special stains. The relationship between luminal gastroenterology and pathology has been close since the beginning of flexible endoscopy and is inherent to excellent patient care and management.

As we began to diagnose predictive conditions (e.g., dysplasia) in addition to endpoint disease (e.g., cancer), the need for communication and closer cooperation became even more important. Endoscopists can help the pathologist with disease context and demographic information, allowing a more exact choice of histologic tools to aid diagnoses. In this article, I teamed up with a pathologist from a large independent GI group to explore these areas of potential controversy.

John I. Allen, M.D., M.B.A., AGAF, Special Section Editor

Gastroenterologists have long enjoyed a close working relationship with gastrointestinal (GI) pathologists as much of our endoscopic work is accompanied by biopsies. Excellent communication between the endoscopist and pathologist is critical for maximizing the diagnostic value of the biopsy and leads to an environment where the integrated team adds substantial value to patient health outcomes.¹

During the last decade, a number of community gastroenterologists have added pathology services to their practices as the enhanced communication resulting from such integration improves patient care in both qualitative and quantitative ways. For example, reduced time from biopsy to patient reporting minimizes the patient’s anxiety as they await results. The development of special GI pathology expertise within the practice aids the gastroenterologist in his/her understanding of the pathology report.²

Business arrangements for in-house pathology vary and are beyond the scope of this article. These will be covered in subsequent publications in the Practice Management Toolbox.

The Centers for Medicaid and Medicare Services (CMS) prohibit physicians from referring patients for designated health services delivered by entities in which they or a family member have a financial relationship. These proscriptions are commonly referred to as Stark Laws. Anatomic pathology services, with Healthcare Common Procedure Coding System (HCPCS) codes in the 883xx family, are an exempted service. The primary code is 88305 and encompasses any biopsy taken by endoscopy, colonoscopy, or sigmoidoscopy. Add-on codes for additional studies are 88312, 88313, and 88342.

In June 2013, the United States Government General Accountability Office (GAO) issued a report in response to requests from several Congressmen concerning the increased use of anatomic pathology services by providers who self-refer to pathology labs owned and operated by their practices.³ The report analyzed expenditures for Medicare Part B services by using the above stated HCPCS codes from 2007 to 2011. They found an increase of 5.9% annually, and the rate of anatomic pathology billing to Medicare from dermatology, urology, and GI practices that owned pathology labs was significantly higher compared with those practices that did not self-refer. Both the rate of biopsies (related to procedures) and the numbers of special stains were higher, leading the GAO to recommend that CMS both analyze these trends directly and potentially limit such self-referral. To date, the Secretary of Health and Human Services has rejected these recommendations.

Fellowship training in GI medicine encourages GI pathology training so that the gastroenterologist can understand the language of pathology. Even with this training, pathology reports can be confusing. The pathologist also needs to understand the language of the gastroenterologist. Incorporating pathologists within the practice helps translate the esoteric language of pathology into the clinical language of the gastroenterologist.

Treating a disease at its earliest manifestation is the most effective point of intervention. Therefore, an important objective of medicine is to find disease in its nascent form or, if it is neoplastic, in its precursor form before it is capable of spreading. Pathology evolved to identify and detect these early manifestations of disease. The transformation of pathology from a specialty that confirms a diagnosis after a disease is fully manifest to a specialty that identifies a population at risk conferred an additional mandate on the pathologist so that the pathologist is called on to make a diagnosis earlier and earlier in the diagnostic cascade. The integration of both specialties into a single team maximizes communication and minimizes confusion.

The diagnostic algorithm begins with the standard stain

The diagnostic algorithm for rendering a complete surgical pathology interpretation begins with the pathologist examining the initial slide stained with H&E. This stain differentiates cytoplasmic and nuclear detail and allows a morphologic interpretation (i.e., "what does the lesion look like?"). At this level, the pathologist uses heuristic rules of thumb to make an approximate diagnosis. The experienced and well-trained pathologist knows that morphology only gives an 80%-85% confidence level in diagnosis. To achieve diagnostic accuracy and reproducibility approaching 100%, the trained pathologist is expected to triage the specimen and determine the need for any additional studies. In this modern setting, heuristic rules of thumb that are based on morphology are anachronistic, whereas establishing the correct diagnosis is paramount. This need is recognized in CMS regulation 80.6.5 that allows the pathologist to use whatever special studies are necessary as long as certain criteria are met.⁴

The definition of special stains

"Special stain" is an expansive term used for both chargeable and nonchargeable studies. Chargeable special studies are defined as add-on studies. In fact, the most common special study is nonchargeable and is known as leveling the block. Leveling the block obtains additional slides stained with H&E to ensure that the tissue examined on the microscope slide is fully representative of the disease process. This service is considered to be part of the H&E diagnosis and is not compensated.

In the Capital Digestive Care LLC laboratory, additional levels on the block have increased the adenoma detection rate by approximately 2% (personal observation). In cases of malignancy, Capital Digestive Care often obtains 30 additional slides to ensure complete sampling of the lesion and preservation of precious tissue in case additional studies are necessary. These studies are used to evaluate site of origin, prognostic factors such as vascular invasion, and expression of mismatched repair proteins as surrogate markers to microsatellite instability lesions and Lynch syndrome.

A common situation where a special stain is useful is in the diagnosis of Helicobacter pylori infection. The use of special stains is not unique to Helicobacter. There is a legion of other diagnoses that require special stains to reveal them, differentiate them from mimics, confirm their existence, or eliminate them as a possibility. An exhaustive listing of special stains and their uses is beyond the scope of this article. However, anexample is the use of additional studies to differentiate various forms of peripheral nerve sheath tumors, or to differentiate hyperplastic polyps from serrated polyps, or in the classification of mature B-cell lymphomas, or the use of the homeobox antigen CDX2 to identify an adenocarcinoma as being of intestinal phenotype.

In seeking to detect Barrett’s esophagus, Harrison et al.⁴ recommend eight separate biopsies as the best chance to come to an accurate diagnosis of intestinal metaplasia. In many cases, it is difficult for an endoscopist to retrieve eight biopsies from patients in whom Barrett’s esophagus is suspected. The conscientious pathologist will perform extensive leveling of the block and use ancillary studies such as Alcian blue to highlight rare goblet cells or differentiate pseudogoblet cells from true goblet.⁵

The add-on study is chargeable if reported as "negative for" or "positive for" a particular diagnosis. As an example, the ancillary study for Helicobacter is correctly interpreted as positive for Helicobacter or negative for Helicobacter. The add-on confers the ability for precise classification of disease. The positive interpretation indicates Helicobacter as an etiology, and a negative interpretation excludes Helicobacter as an etiology. Many pathologists substitute the term noncontributory for "negative for." This is incorrect. Negative information contributes to the final diagnosis because it excludes diagnostic possibilities and therefore is contributory. If the ancillary study truly does not contribute to the final diagnosis, then the noncontributory service should not have been done and is nonchargeable.

Ancillary studies increase sensitivity and specificity

Traditionally, pathologists performed a gross examination and examined large segments of tissue and sampled areas that were abnormal to sight and touch. When biopsies are obtained by endoscopy, it is the gastroenterologist who performs the gross examination during endoscopy. In this setting, the pathologist is blind to the gross appearance of the lesion. Nevertheless, the pathologist is called on to render a complete interpretation and is dependent on the eyes and hands of the gastroenterologist to procure a diagnostic sample. It is evident that in the modern setting, such a sampling is inherently limited and requires the pathologist and gastroenterologist to work as an integrated team to render a complete interpretation.

In the best of circumstances, the biopsy is small and in some cases it is an incomplete representation of a disease process. The pathologist is under considerable pressure to arrive at a correct and timely diagnosis because his or her interpretation potentially has substantial consequences to patient care. Ancillary studies or special stains enhance the ability to finesse information out of a small biopsy. The small size and incompleteness of the biopsy often result in disagreements of interpretation by pathologists. It is not uncommon for the gastroenterologist to encounter disagreements among pathologists in biopsy interpretation. Special stains often minimize disagreements because there are objective standards by which opinions become fact.

Lack of gold standard

Pathology literature often documents large interobserver variability in which two or more pathologists cannot agree on the diagnosis. There is also intraobserver variability in which the same pathologist on different days may arrive at a different conclusion. As the diagnosis moves from overt manifestation of disease to subtle alterations indicating the likelihood of disease development, this interobserver variability increases, and it is evident that the likelihood of diagnostic error increases. As the pathologist moves further up the diagnostic stream and closer to the point of disease origin, the morphologic markers are often obscure and little differentiated and require increasingly powerful tools to extract information. These tools are known as add-on or special studies.

Barrett’s esophagus is surveyed to prevent the development of esophageal adenocarcinoma. The end point of Barrett’s esophagus surveillance is the establishment of low- or high-grade dysplasia, carcinoma in situ, or invasive carcinoma because these diagnoses lead to additional therapeutic interventions. It would seem evident that a process such as dysplasia, which has been established in pathology almost since its inception, would be well defined and the criteria well delineated. However, a seminal article on Barrett’s dysplasia showed that 12 leading GI pathologists from centers of excellence in Barrett’s esophagus showed a large interobserver variability for all non–high-grade dysplasia diagnoses even after there was a consensus conference as to what morphologic changes should be categorized as dysplasia. The results showed a 90% agreement if two diagnostic categories were used (negative or high-grade dysplasia vs. high-grade dysplasia or more significant lesion) and a 75% agreement if three diagnostic categories were used (BE, negative for dysplasia, BE indefinite for dysplasia or low-grade dysplasia, and BE with high-grade dysplasia or more significant lesion).

The authors also showed a "barbell distribution" of agreement in that there was fairly good agreement at the low and high end of the spectrum (negative for dysplasia and high-grade dysplasia) and very poor agreement in the middle ground between indefinite for dysplasia and low-grade dysplasia. Even so, they never reached a level of greater than 90% agreement.⁵

This inherent subjectivity to morphologic analysis means there is no gold standard. If no gold standard exists, then it is evident that comparison of diagnostic acumen between pathologists and institutions is meritless. These limitations have led pathologists to test various biomarkers or ancillary studies to help and increase accuracy and precision and to render reproducible diagnoses between pathologists. It is universally accepted that high-grade dysplasia is the best predictor of progression in Barrett’s esophagus to adenocarcinoma. However, the practical application of this standard is limited by the subjective nature of the criteria for establishing high-grade dysplasia and that some reactive conditions cannot be readily distinguished from high-grade dysplasia by histological assessment alone. Therefore, pathologists use biomarkers to distinguish dysplasia from its histological mimics and to help and grade the level of dysplasia.⁶

The problem of interobserver variability is not limited to Barrett’s esophagus but extends to colon cancer screening. For colon cancer screening, risk stratification is based on the size and morphology of the lesion. The gastroenterologist determines the size of the lesion at colonoscopy, and the pathologist then defines the morphology. There is no consensus among pathologists as to what constitutes high-grade dysplasia and villous morphology, and the endoscopic estimate of polyp size is unreliable.^7,8

The reason for errors and disagreement is the inherently subjective nature of pathology. The best way to resolve this dilemma is to bring more objective standards to bear and to establish a gold standard. One way of objectifying a subjective interpretation is to submit it to a binary "yes"/"no" test. This is the role of add-on studies.

Liability

The pathologist is a physician subject to litigation as are all health care providers. The pathologist’s clinical counterpart shares the burden of the missed pathologic diagnosis. The use of ancillary studies increases the likelihood of a correct diagnosis and minimizes the likelihood of the missed or wrong diagnosis.

Conclusion

In the end, the eye sees what the mind knows, but what the mind knows and the eye sees are highly variable among many pathologists; and in some cases the result is a nonreproducible diagnosis. Clearly, this is not an acceptable state. If a diagnosis cannot be reproducibly rendered between pathologists in the same institution or between collaborative institutions, any study that relies on such diagnosis is inherently flawed. The pathologist, the clinician, and the patient should expect and demand the "right" or at least the "best" answer. However, this lack of reproducibility means that the patient who has their slides sent to a large number of institutions seeking the "right diagnosis" is on a fool’s errand. The objective information bought by ancillary studies achieves this goal in some cases. The failure to use ancillary studies fully may do the patient and the clinical community a gross disservice.

The GAO report showing possible overuse related to conflict of interest has initiated considerable interest, scrutiny, and conversation in Congress and CMS.¹

Recent reductions in the reimbursement for 88305 have tempered the need for further cost reductions (at the expense of pathologists and owners of laboratory services), but we can expect Congress to revisit this issue in the future. Our best defense for preservation of this Stark exemption is to practice evidence-based medicine where we can defend our decisions on the basis of patient needs and improved health outcomes.

References

1. Snover, D.C. Maximizing the value of the endoscopist-pathologist partnership in the management of colorectal polyps and carcinoma. Gastrointest. Endosc. Clin. N. Am. 2010;20:641-57.

2. Sarles, H. Gastrointestinal pathology: incorporating a GI pathology laboratory into your practice. Gastroenterol. Endoscopy News. 2011;June:1-4.

3. GAO 13-445 Medicare and Self-Referral of Anatomic Pathology Services. 2013. Available at: www.gao.gov/products/gao-13-445. Accessed September 22, 2013.

4. Harrison, R., Perry, I., Haddadin, W. et al. Detection of intestinal metaplasia in Barrett’s esophagus: an observational comparator study suggests the need for a minimum of eight biopsies. Am. J. Gastroenterol. 2007;102:1154-61.

5. Montgomery, E. Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation. Hum. Pathol. 2001;32:368-78.

6. Fels, Elliott D.R. and Fitzgerald, R.C. Molecular markers for Barrett’s esophagus and its progression to cancer. Curr. Opin. Gastroenterol. 2013;29:437-45.

7. Mahajan, D., Downs-Kelly, E., Liu, X. et al. Reproducibility of the villous component and high grade dysplasia in colorectal adenomas < 1 cm. Am. J. Surg. Pathol. 2013;37:427-33.

8. Eichenseer, P.J. Endoscopic miss-sizing of polyps changes colorectal cancer surveillance recommendations. Dis. Colon Rectum 2013;56:315-21.

Dr. Baybick is medical director of Capital Digestive Care, LLC, Laboratory Division, Bowie, Md.; Dr. Allen is professor of medicine, and clinical chief of gastroenterology and hepatology at the Yale School of Medicine, New Haven, Conn. The authors disclose no conflicts of interest.

Content from this column was originally published in the "Practice Management: The Road Ahead" section of Clinical Gastroenterology and Hepatology (2014;12:3-6).

"Practice Management Toolbox" provides key information and resources necessary for facing the unique challenges of today’s clinical practices.

Resources for Practical Application: To view additional online resources about this topic and to access our Coding Corner, visit, www.cghjournal.org/content/practice_management.

The US Government Accountability Office (GAO) released a study on June 24, 2013, calling for "action" to address higher use of anatomic pathology services by providers who "self-refer" (i.e., those that have ownership positions in pathology labs). The report suggested that profit and not science drove utilization, including that of special stains. The relationship between luminal gastroenterology and pathology has been close since the beginning of flexible endoscopy and is inherent to excellent patient care and management.

As we began to diagnose predictive conditions (e.g., dysplasia) in addition to endpoint disease (e.g., cancer), the need for communication and closer cooperation became even more important. Endoscopists can help the pathologist with disease context and demographic information, allowing a more exact choice of histologic tools to aid diagnoses. In this article, I teamed up with a pathologist from a large independent GI group to explore these areas of potential controversy.

John I. Allen, M.D., M.B.A., AGAF, Special Section Editor

Gastroenterologists have long enjoyed a close working relationship with gastrointestinal (GI) pathologists as much of our endoscopic work is accompanied by biopsies. Excellent communication between the endoscopist and pathologist is critical for maximizing the diagnostic value of the biopsy and leads to an environment where the integrated team adds substantial value to patient health outcomes.¹

During the last decade, a number of community gastroenterologists have added pathology services to their practices as the enhanced communication resulting from such integration improves patient care in both qualitative and quantitative ways. For example, reduced time from biopsy to patient reporting minimizes the patient’s anxiety as they await results. The development of special GI pathology expertise within the practice aids the gastroenterologist in his/her understanding of the pathology report.²

Business arrangements for in-house pathology vary and are beyond the scope of this article. These will be covered in subsequent publications in the Practice Management Toolbox.

The Centers for Medicaid and Medicare Services (CMS) prohibit physicians from referring patients for designated health services delivered by entities in which they or a family member have a financial relationship. These proscriptions are commonly referred to as Stark Laws. Anatomic pathology services, with Healthcare Common Procedure Coding System (HCPCS) codes in the 883xx family, are an exempted service. The primary code is 88305 and encompasses any biopsy taken by endoscopy, colonoscopy, or sigmoidoscopy. Add-on codes for additional studies are 88312, 88313, and 88342.

In June 2013, the United States Government General Accountability Office (GAO) issued a report in response to requests from several Congressmen concerning the increased use of anatomic pathology services by providers who self-refer to pathology labs owned and operated by their practices.³ The report analyzed expenditures for Medicare Part B services by using the above stated HCPCS codes from 2007 to 2011. They found an increase of 5.9% annually, and the rate of anatomic pathology billing to Medicare from dermatology, urology, and GI practices that owned pathology labs was significantly higher compared with those practices that did not self-refer. Both the rate of biopsies (related to procedures) and the numbers of special stains were higher, leading the GAO to recommend that CMS both analyze these trends directly and potentially limit such self-referral. To date, the Secretary of Health and Human Services has rejected these recommendations.

Fellowship training in GI medicine encourages GI pathology training so that the gastroenterologist can understand the language of pathology. Even with this training, pathology reports can be confusing. The pathologist also needs to understand the language of the gastroenterologist. Incorporating pathologists within the practice helps translate the esoteric language of pathology into the clinical language of the gastroenterologist.

Treating a disease at its earliest manifestation is the most effective point of intervention. Therefore, an important objective of medicine is to find disease in its nascent form or, if it is neoplastic, in its precursor form before it is capable of spreading. Pathology evolved to identify and detect these early manifestations of disease. The transformation of pathology from a specialty that confirms a diagnosis after a disease is fully manifest to a specialty that identifies a population at risk conferred an additional mandate on the pathologist so that the pathologist is called on to make a diagnosis earlier and earlier in the diagnostic cascade. The integration of both specialties into a single team maximizes communication and minimizes confusion.

The diagnostic algorithm begins with the standard stain

The diagnostic algorithm for rendering a complete surgical pathology interpretation begins with the pathologist examining the initial slide stained with H&E. This stain differentiates cytoplasmic and nuclear detail and allows a morphologic interpretation (i.e., "what does the lesion look like?"). At this level, the pathologist uses heuristic rules of thumb to make an approximate diagnosis. The experienced and well-trained pathologist knows that morphology only gives an 80%-85% confidence level in diagnosis. To achieve diagnostic accuracy and reproducibility approaching 100%, the trained pathologist is expected to triage the specimen and determine the need for any additional studies. In this modern setting, heuristic rules of thumb that are based on morphology are anachronistic, whereas establishing the correct diagnosis is paramount. This need is recognized in CMS regulation 80.6.5 that allows the pathologist to use whatever special studies are necessary as long as certain criteria are met.⁴

The definition of special stains

"Special stain" is an expansive term used for both chargeable and nonchargeable studies. Chargeable special studies are defined as add-on studies. In fact, the most common special study is nonchargeable and is known as leveling the block. Leveling the block obtains additional slides stained with H&E to ensure that the tissue examined on the microscope slide is fully representative of the disease process. This service is considered to be part of the H&E diagnosis and is not compensated.

In the Capital Digestive Care LLC laboratory, additional levels on the block have increased the adenoma detection rate by approximately 2% (personal observation). In cases of malignancy, Capital Digestive Care often obtains 30 additional slides to ensure complete sampling of the lesion and preservation of precious tissue in case additional studies are necessary. These studies are used to evaluate site of origin, prognostic factors such as vascular invasion, and expression of mismatched repair proteins as surrogate markers to microsatellite instability lesions and Lynch syndrome.

A common situation where a special stain is useful is in the diagnosis of Helicobacter pylori infection. The use of special stains is not unique to Helicobacter. There is a legion of other diagnoses that require special stains to reveal them, differentiate them from mimics, confirm their existence, or eliminate them as a possibility. An exhaustive listing of special stains and their uses is beyond the scope of this article. However, anexample is the use of additional studies to differentiate various forms of peripheral nerve sheath tumors, or to differentiate hyperplastic polyps from serrated polyps, or in the classification of mature B-cell lymphomas, or the use of the homeobox antigen CDX2 to identify an adenocarcinoma as being of intestinal phenotype.

In seeking to detect Barrett’s esophagus, Harrison et al.⁴ recommend eight separate biopsies as the best chance to come to an accurate diagnosis of intestinal metaplasia. In many cases, it is difficult for an endoscopist to retrieve eight biopsies from patients in whom Barrett’s esophagus is suspected. The conscientious pathologist will perform extensive leveling of the block and use ancillary studies such as Alcian blue to highlight rare goblet cells or differentiate pseudogoblet cells from true goblet.⁵

The add-on study is chargeable if reported as "negative for" or "positive for" a particular diagnosis. As an example, the ancillary study for Helicobacter is correctly interpreted as positive for Helicobacter or negative for Helicobacter. The add-on confers the ability for precise classification of disease. The positive interpretation indicates Helicobacter as an etiology, and a negative interpretation excludes Helicobacter as an etiology. Many pathologists substitute the term noncontributory for "negative for." This is incorrect. Negative information contributes to the final diagnosis because it excludes diagnostic possibilities and therefore is contributory. If the ancillary study truly does not contribute to the final diagnosis, then the noncontributory service should not have been done and is nonchargeable.

Ancillary studies increase sensitivity and specificity

Traditionally, pathologists performed a gross examination and examined large segments of tissue and sampled areas that were abnormal to sight and touch. When biopsies are obtained by endoscopy, it is the gastroenterologist who performs the gross examination during endoscopy. In this setting, the pathologist is blind to the gross appearance of the lesion. Nevertheless, the pathologist is called on to render a complete interpretation and is dependent on the eyes and hands of the gastroenterologist to procure a diagnostic sample. It is evident that in the modern setting, such a sampling is inherently limited and requires the pathologist and gastroenterologist to work as an integrated team to render a complete interpretation.

In the best of circumstances, the biopsy is small and in some cases it is an incomplete representation of a disease process. The pathologist is under considerable pressure to arrive at a correct and timely diagnosis because his or her interpretation potentially has substantial consequences to patient care. Ancillary studies or special stains enhance the ability to finesse information out of a small biopsy. The small size and incompleteness of the biopsy often result in disagreements of interpretation by pathologists. It is not uncommon for the gastroenterologist to encounter disagreements among pathologists in biopsy interpretation. Special stains often minimize disagreements because there are objective standards by which opinions become fact.

Lack of gold standard

Pathology literature often documents large interobserver variability in which two or more pathologists cannot agree on the diagnosis. There is also intraobserver variability in which the same pathologist on different days may arrive at a different conclusion. As the diagnosis moves from overt manifestation of disease to subtle alterations indicating the likelihood of disease development, this interobserver variability increases, and it is evident that the likelihood of diagnostic error increases. As the pathologist moves further up the diagnostic stream and closer to the point of disease origin, the morphologic markers are often obscure and little differentiated and require increasingly powerful tools to extract information. These tools are known as add-on or special studies.

Barrett’s esophagus is surveyed to prevent the development of esophageal adenocarcinoma. The end point of Barrett’s esophagus surveillance is the establishment of low- or high-grade dysplasia, carcinoma in situ, or invasive carcinoma because these diagnoses lead to additional therapeutic interventions. It would seem evident that a process such as dysplasia, which has been established in pathology almost since its inception, would be well defined and the criteria well delineated. However, a seminal article on Barrett’s dysplasia showed that 12 leading GI pathologists from centers of excellence in Barrett’s esophagus showed a large interobserver variability for all non–high-grade dysplasia diagnoses even after there was a consensus conference as to what morphologic changes should be categorized as dysplasia. The results showed a 90% agreement if two diagnostic categories were used (negative or high-grade dysplasia vs. high-grade dysplasia or more significant lesion) and a 75% agreement if three diagnostic categories were used (BE, negative for dysplasia, BE indefinite for dysplasia or low-grade dysplasia, and BE with high-grade dysplasia or more significant lesion).

The authors also showed a "barbell distribution" of agreement in that there was fairly good agreement at the low and high end of the spectrum (negative for dysplasia and high-grade dysplasia) and very poor agreement in the middle ground between indefinite for dysplasia and low-grade dysplasia. Even so, they never reached a level of greater than 90% agreement.⁵

This inherent subjectivity to morphologic analysis means there is no gold standard. If no gold standard exists, then it is evident that comparison of diagnostic acumen between pathologists and institutions is meritless. These limitations have led pathologists to test various biomarkers or ancillary studies to help and increase accuracy and precision and to render reproducible diagnoses between pathologists. It is universally accepted that high-grade dysplasia is the best predictor of progression in Barrett’s esophagus to adenocarcinoma. However, the practical application of this standard is limited by the subjective nature of the criteria for establishing high-grade dysplasia and that some reactive conditions cannot be readily distinguished from high-grade dysplasia by histological assessment alone. Therefore, pathologists use biomarkers to distinguish dysplasia from its histological mimics and to help and grade the level of dysplasia.⁶

The problem of interobserver variability is not limited to Barrett’s esophagus but extends to colon cancer screening. For colon cancer screening, risk stratification is based on the size and morphology of the lesion. The gastroenterologist determines the size of the lesion at colonoscopy, and the pathologist then defines the morphology. There is no consensus among pathologists as to what constitutes high-grade dysplasia and villous morphology, and the endoscopic estimate of polyp size is unreliable.^7,8

The reason for errors and disagreement is the inherently subjective nature of pathology. The best way to resolve this dilemma is to bring more objective standards to bear and to establish a gold standard. One way of objectifying a subjective interpretation is to submit it to a binary "yes"/"no" test. This is the role of add-on studies.

Liability

The pathologist is a physician subject to litigation as are all health care providers. The pathologist’s clinical counterpart shares the burden of the missed pathologic diagnosis. The use of ancillary studies increases the likelihood of a correct diagnosis and minimizes the likelihood of the missed or wrong diagnosis.

Conclusion

In the end, the eye sees what the mind knows, but what the mind knows and the eye sees are highly variable among many pathologists; and in some cases the result is a nonreproducible diagnosis. Clearly, this is not an acceptable state. If a diagnosis cannot be reproducibly rendered between pathologists in the same institution or between collaborative institutions, any study that relies on such diagnosis is inherently flawed. The pathologist, the clinician, and the patient should expect and demand the "right" or at least the "best" answer. However, this lack of reproducibility means that the patient who has their slides sent to a large number of institutions seeking the "right diagnosis" is on a fool’s errand. The objective information bought by ancillary studies achieves this goal in some cases. The failure to use ancillary studies fully may do the patient and the clinical community a gross disservice.

The GAO report showing possible overuse related to conflict of interest has initiated considerable interest, scrutiny, and conversation in Congress and CMS.¹

Recent reductions in the reimbursement for 88305 have tempered the need for further cost reductions (at the expense of pathologists and owners of laboratory services), but we can expect Congress to revisit this issue in the future. Our best defense for preservation of this Stark exemption is to practice evidence-based medicine where we can defend our decisions on the basis of patient needs and improved health outcomes.

References

1. Snover, D.C. Maximizing the value of the endoscopist-pathologist partnership in the management of colorectal polyps and carcinoma. Gastrointest. Endosc. Clin. N. Am. 2010;20:641-57.

2. Sarles, H. Gastrointestinal pathology: incorporating a GI pathology laboratory into your practice. Gastroenterol. Endoscopy News. 2011;June:1-4.

3. GAO 13-445 Medicare and Self-Referral of Anatomic Pathology Services. 2013. Available at: www.gao.gov/products/gao-13-445. Accessed September 22, 2013.

4. Harrison, R., Perry, I., Haddadin, W. et al. Detection of intestinal metaplasia in Barrett’s esophagus: an observational comparator study suggests the need for a minimum of eight biopsies. Am. J. Gastroenterol. 2007;102:1154-61.

5. Montgomery, E. Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation. Hum. Pathol. 2001;32:368-78.

6. Fels, Elliott D.R. and Fitzgerald, R.C. Molecular markers for Barrett’s esophagus and its progression to cancer. Curr. Opin. Gastroenterol. 2013;29:437-45.

7. Mahajan, D., Downs-Kelly, E., Liu, X. et al. Reproducibility of the villous component and high grade dysplasia in colorectal adenomas < 1 cm. Am. J. Surg. Pathol. 2013;37:427-33.

8. Eichenseer, P.J. Endoscopic miss-sizing of polyps changes colorectal cancer surveillance recommendations. Dis. Colon Rectum 2013;56:315-21.

Dr. Baybick is medical director of Capital Digestive Care, LLC, Laboratory Division, Bowie, Md.; Dr. Allen is professor of medicine, and clinical chief of gastroenterology and hepatology at the Yale School of Medicine, New Haven, Conn. The authors disclose no conflicts of interest.

Content from this column was originally published in the "Practice Management: The Road Ahead" section of Clinical Gastroenterology and Hepatology (2014;12:3-6).

"Practice Management Toolbox" provides key information and resources necessary for facing the unique challenges of today’s clinical practices.

Resources for Practical Application: To view additional online resources about this topic and to access our Coding Corner, visit, www.cghjournal.org/content/practice_management.

The US Government Accountability Office (GAO) released a study on June 24, 2013, calling for "action" to address higher use of anatomic pathology services by providers who "self-refer" (i.e., those that have ownership positions in pathology labs). The report suggested that profit and not science drove utilization, including that of special stains. The relationship between luminal gastroenterology and pathology has been close since the beginning of flexible endoscopy and is inherent to excellent patient care and management.

As we began to diagnose predictive conditions (e.g., dysplasia) in addition to endpoint disease (e.g., cancer), the need for communication and closer cooperation became even more important. Endoscopists can help the pathologist with disease context and demographic information, allowing a more exact choice of histologic tools to aid diagnoses. In this article, I teamed up with a pathologist from a large independent GI group to explore these areas of potential controversy.

John I. Allen, M.D., M.B.A., AGAF, Special Section Editor

Gastroenterologists have long enjoyed a close working relationship with gastrointestinal (GI) pathologists as much of our endoscopic work is accompanied by biopsies. Excellent communication between the endoscopist and pathologist is critical for maximizing the diagnostic value of the biopsy and leads to an environment where the integrated team adds substantial value to patient health outcomes.¹

During the last decade, a number of community gastroenterologists have added pathology services to their practices as the enhanced communication resulting from such integration improves patient care in both qualitative and quantitative ways. For example, reduced time from biopsy to patient reporting minimizes the patient’s anxiety as they await results. The development of special GI pathology expertise within the practice aids the gastroenterologist in his/her understanding of the pathology report.²

Business arrangements for in-house pathology vary and are beyond the scope of this article. These will be covered in subsequent publications in the Practice Management Toolbox.

The Centers for Medicaid and Medicare Services (CMS) prohibit physicians from referring patients for designated health services delivered by entities in which they or a family member have a financial relationship. These proscriptions are commonly referred to as Stark Laws. Anatomic pathology services, with Healthcare Common Procedure Coding System (HCPCS) codes in the 883xx family, are an exempted service. The primary code is 88305 and encompasses any biopsy taken by endoscopy, colonoscopy, or sigmoidoscopy. Add-on codes for additional studies are 88312, 88313, and 88342.

In June 2013, the United States Government General Accountability Office (GAO) issued a report in response to requests from several Congressmen concerning the increased use of anatomic pathology services by providers who self-refer to pathology labs owned and operated by their practices.³ The report analyzed expenditures for Medicare Part B services by using the above stated HCPCS codes from 2007 to 2011. They found an increase of 5.9% annually, and the rate of anatomic pathology billing to Medicare from dermatology, urology, and GI practices that owned pathology labs was significantly higher compared with those practices that did not self-refer. Both the rate of biopsies (related to procedures) and the numbers of special stains were higher, leading the GAO to recommend that CMS both analyze these trends directly and potentially limit such self-referral. To date, the Secretary of Health and Human Services has rejected these recommendations.

Fellowship training in GI medicine encourages GI pathology training so that the gastroenterologist can understand the language of pathology. Even with this training, pathology reports can be confusing. The pathologist also needs to understand the language of the gastroenterologist. Incorporating pathologists within the practice helps translate the esoteric language of pathology into the clinical language of the gastroenterologist.

Treating a disease at its earliest manifestation is the most effective point of intervention. Therefore, an important objective of medicine is to find disease in its nascent form or, if it is neoplastic, in its precursor form before it is capable of spreading. Pathology evolved to identify and detect these early manifestations of disease. The transformation of pathology from a specialty that confirms a diagnosis after a disease is fully manifest to a specialty that identifies a population at risk conferred an additional mandate on the pathologist so that the pathologist is called on to make a diagnosis earlier and earlier in the diagnostic cascade. The integration of both specialties into a single team maximizes communication and minimizes confusion.

The diagnostic algorithm begins with the standard stain

The diagnostic algorithm for rendering a complete surgical pathology interpretation begins with the pathologist examining the initial slide stained with H&E. This stain differentiates cytoplasmic and nuclear detail and allows a morphologic interpretation (i.e., "what does the lesion look like?"). At this level, the pathologist uses heuristic rules of thumb to make an approximate diagnosis. The experienced and well-trained pathologist knows that morphology only gives an 80%-85% confidence level in diagnosis. To achieve diagnostic accuracy and reproducibility approaching 100%, the trained pathologist is expected to triage the specimen and determine the need for any additional studies. In this modern setting, heuristic rules of thumb that are based on morphology are anachronistic, whereas establishing the correct diagnosis is paramount. This need is recognized in CMS regulation 80.6.5 that allows the pathologist to use whatever special studies are necessary as long as certain criteria are met.⁴

The definition of special stains

"Special stain" is an expansive term used for both chargeable and nonchargeable studies. Chargeable special studies are defined as add-on studies. In fact, the most common special study is nonchargeable and is known as leveling the block. Leveling the block obtains additional slides stained with H&E to ensure that the tissue examined on the microscope slide is fully representative of the disease process. This service is considered to be part of the H&E diagnosis and is not compensated.

In the Capital Digestive Care LLC laboratory, additional levels on the block have increased the adenoma detection rate by approximately 2% (personal observation). In cases of malignancy, Capital Digestive Care often obtains 30 additional slides to ensure complete sampling of the lesion and preservation of precious tissue in case additional studies are necessary. These studies are used to evaluate site of origin, prognostic factors such as vascular invasion, and expression of mismatched repair proteins as surrogate markers to microsatellite instability lesions and Lynch syndrome.

A common situation where a special stain is useful is in the diagnosis of Helicobacter pylori infection. The use of special stains is not unique to Helicobacter. There is a legion of other diagnoses that require special stains to reveal them, differentiate them from mimics, confirm their existence, or eliminate them as a possibility. An exhaustive listing of special stains and their uses is beyond the scope of this article. However, anexample is the use of additional studies to differentiate various forms of peripheral nerve sheath tumors, or to differentiate hyperplastic polyps from serrated polyps, or in the classification of mature B-cell lymphomas, or the use of the homeobox antigen CDX2 to identify an adenocarcinoma as being of intestinal phenotype.

In seeking to detect Barrett’s esophagus, Harrison et al.⁴ recommend eight separate biopsies as the best chance to come to an accurate diagnosis of intestinal metaplasia. In many cases, it is difficult for an endoscopist to retrieve eight biopsies from patients in whom Barrett’s esophagus is suspected. The conscientious pathologist will perform extensive leveling of the block and use ancillary studies such as Alcian blue to highlight rare goblet cells or differentiate pseudogoblet cells from true goblet.⁵

The add-on study is chargeable if reported as "negative for" or "positive for" a particular diagnosis. As an example, the ancillary study for Helicobacter is correctly interpreted as positive for Helicobacter or negative for Helicobacter. The add-on confers the ability for precise classification of disease. The positive interpretation indicates Helicobacter as an etiology, and a negative interpretation excludes Helicobacter as an etiology. Many pathologists substitute the term noncontributory for "negative for." This is incorrect. Negative information contributes to the final diagnosis because it excludes diagnostic possibilities and therefore is contributory. If the ancillary study truly does not contribute to the final diagnosis, then the noncontributory service should not have been done and is nonchargeable.

Ancillary studies increase sensitivity and specificity

Traditionally, pathologists performed a gross examination and examined large segments of tissue and sampled areas that were abnormal to sight and touch. When biopsies are obtained by endoscopy, it is the gastroenterologist who performs the gross examination during endoscopy. In this setting, the pathologist is blind to the gross appearance of the lesion. Nevertheless, the pathologist is called on to render a complete interpretation and is dependent on the eyes and hands of the gastroenterologist to procure a diagnostic sample. It is evident that in the modern setting, such a sampling is inherently limited and requires the pathologist and gastroenterologist to work as an integrated team to render a complete interpretation.

In the best of circumstances, the biopsy is small and in some cases it is an incomplete representation of a disease process. The pathologist is under considerable pressure to arrive at a correct and timely diagnosis because his or her interpretation potentially has substantial consequences to patient care. Ancillary studies or special stains enhance the ability to finesse information out of a small biopsy. The small size and incompleteness of the biopsy often result in disagreements of interpretation by pathologists. It is not uncommon for the gastroenterologist to encounter disagreements among pathologists in biopsy interpretation. Special stains often minimize disagreements because there are objective standards by which opinions become fact.

Lack of gold standard

Pathology literature often documents large interobserver variability in which two or more pathologists cannot agree on the diagnosis. There is also intraobserver variability in which the same pathologist on different days may arrive at a different conclusion. As the diagnosis moves from overt manifestation of disease to subtle alterations indicating the likelihood of disease development, this interobserver variability increases, and it is evident that the likelihood of diagnostic error increases. As the pathologist moves further up the diagnostic stream and closer to the point of disease origin, the morphologic markers are often obscure and little differentiated and require increasingly powerful tools to extract information. These tools are known as add-on or special studies.

Barrett’s esophagus is surveyed to prevent the development of esophageal adenocarcinoma. The end point of Barrett’s esophagus surveillance is the establishment of low- or high-grade dysplasia, carcinoma in situ, or invasive carcinoma because these diagnoses lead to additional therapeutic interventions. It would seem evident that a process such as dysplasia, which has been established in pathology almost since its inception, would be well defined and the criteria well delineated. However, a seminal article on Barrett’s dysplasia showed that 12 leading GI pathologists from centers of excellence in Barrett’s esophagus showed a large interobserver variability for all non–high-grade dysplasia diagnoses even after there was a consensus conference as to what morphologic changes should be categorized as dysplasia. The results showed a 90% agreement if two diagnostic categories were used (negative or high-grade dysplasia vs. high-grade dysplasia or more significant lesion) and a 75% agreement if three diagnostic categories were used (BE, negative for dysplasia, BE indefinite for dysplasia or low-grade dysplasia, and BE with high-grade dysplasia or more significant lesion).

The authors also showed a "barbell distribution" of agreement in that there was fairly good agreement at the low and high end of the spectrum (negative for dysplasia and high-grade dysplasia) and very poor agreement in the middle ground between indefinite for dysplasia and low-grade dysplasia. Even so, they never reached a level of greater than 90% agreement.⁵

This inherent subjectivity to morphologic analysis means there is no gold standard. If no gold standard exists, then it is evident that comparison of diagnostic acumen between pathologists and institutions is meritless. These limitations have led pathologists to test various biomarkers or ancillary studies to help and increase accuracy and precision and to render reproducible diagnoses between pathologists. It is universally accepted that high-grade dysplasia is the best predictor of progression in Barrett’s esophagus to adenocarcinoma. However, the practical application of this standard is limited by the subjective nature of the criteria for establishing high-grade dysplasia and that some reactive conditions cannot be readily distinguished from high-grade dysplasia by histological assessment alone. Therefore, pathologists use biomarkers to distinguish dysplasia from its histological mimics and to help and grade the level of dysplasia.⁶

The problem of interobserver variability is not limited to Barrett’s esophagus but extends to colon cancer screening. For colon cancer screening, risk stratification is based on the size and morphology of the lesion. The gastroenterologist determines the size of the lesion at colonoscopy, and the pathologist then defines the morphology. There is no consensus among pathologists as to what constitutes high-grade dysplasia and villous morphology, and the endoscopic estimate of polyp size is unreliable.^7,8

The reason for errors and disagreement is the inherently subjective nature of pathology. The best way to resolve this dilemma is to bring more objective standards to bear and to establish a gold standard. One way of objectifying a subjective interpretation is to submit it to a binary "yes"/"no" test. This is the role of add-on studies.

Liability

The pathologist is a physician subject to litigation as are all health care providers. The pathologist’s clinical counterpart shares the burden of the missed pathologic diagnosis. The use of ancillary studies increases the likelihood of a correct diagnosis and minimizes the likelihood of the missed or wrong diagnosis.

Conclusion

In the end, the eye sees what the mind knows, but what the mind knows and the eye sees are highly variable among many pathologists; and in some cases the result is a nonreproducible diagnosis. Clearly, this is not an acceptable state. If a diagnosis cannot be reproducibly rendered between pathologists in the same institution or between collaborative institutions, any study that relies on such diagnosis is inherently flawed. The pathologist, the clinician, and the patient should expect and demand the "right" or at least the "best" answer. However, this lack of reproducibility means that the patient who has their slides sent to a large number of institutions seeking the "right diagnosis" is on a fool’s errand. The objective information bought by ancillary studies achieves this goal in some cases. The failure to use ancillary studies fully may do the patient and the clinical community a gross disservice.

The GAO report showing possible overuse related to conflict of interest has initiated considerable interest, scrutiny, and conversation in Congress and CMS.¹

Recent reductions in the reimbursement for 88305 have tempered the need for further cost reductions (at the expense of pathologists and owners of laboratory services), but we can expect Congress to revisit this issue in the future. Our best defense for preservation of this Stark exemption is to practice evidence-based medicine where we can defend our decisions on the basis of patient needs and improved health outcomes.

References

1. Snover, D.C. Maximizing the value of the endoscopist-pathologist partnership in the management of colorectal polyps and carcinoma. Gastrointest. Endosc. Clin. N. Am. 2010;20:641-57.

2. Sarles, H. Gastrointestinal pathology: incorporating a GI pathology laboratory into your practice. Gastroenterol. Endoscopy News. 2011;June:1-4.

3. GAO 13-445 Medicare and Self-Referral of Anatomic Pathology Services. 2013. Available at: www.gao.gov/products/gao-13-445. Accessed September 22, 2013.

4. Harrison, R., Perry, I., Haddadin, W. et al. Detection of intestinal metaplasia in Barrett’s esophagus: an observational comparator study suggests the need for a minimum of eight biopsies. Am. J. Gastroenterol. 2007;102:1154-61.

5. Montgomery, E. Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation. Hum. Pathol. 2001;32:368-78.

6. Fels, Elliott D.R. and Fitzgerald, R.C. Molecular markers for Barrett’s esophagus and its progression to cancer. Curr. Opin. Gastroenterol. 2013;29:437-45.

7. Mahajan, D., Downs-Kelly, E., Liu, X. et al. Reproducibility of the villous component and high grade dysplasia in colorectal adenomas < 1 cm. Am. J. Surg. Pathol. 2013;37:427-33.

8. Eichenseer, P.J. Endoscopic miss-sizing of polyps changes colorectal cancer surveillance recommendations. Dis. Colon Rectum 2013;56:315-21.

Dr. Baybick is medical director of Capital Digestive Care, LLC, Laboratory Division, Bowie, Md.; Dr. Allen is professor of medicine, and clinical chief of gastroenterology and hepatology at the Yale School of Medicine, New Haven, Conn. The authors disclose no conflicts of interest.

Content from this column was originally published in the "Practice Management: The Road Ahead" section of Clinical Gastroenterology and Hepatology (2014;12:3-6).

"Practice Management Toolbox" provides key information and resources necessary for facing the unique challenges of today’s clinical practices.

Resources for Practical Application: To view additional online resources about this topic and to access our Coding Corner, visit, www.cghjournal.org/content/practice_management.