MEDICAL POLICY
POLICY TITLE
GENETIC TESTING FOR HEREDITARY PANCREATITIS
POLICY NUMBER
MP-2.318
Original Issue Date (Created):
4/1/2014
Most Recent Review Date (Revised): 1/31/2017
Effective Date:
POLICY
RATIONALE
DISCLAIMER
POLICY HISTORY
3/1/2017
PRODUCT VARIATIONS
DEFINITIONS
CODING INFORMATION
APPENDIX
DESCRIPTION/BACKGROUND
BENEFIT VARIATIONS
REFERENCES
I. POLICY
Genetic testing for hereditary pancreatitis may be considered medically necessary for patients
aged 18 years and under with unexplained recurrent (>1 episode) acute or chronic pancreatitis
with documented elevated amylase or lipase.
Genetic testing for hereditary pancreatitis is considered investigational in all other situations.
There is insufficient evidence to support a conclusion concerning the health outcomes or benefits
associated with this procedure.
II. PRODUCT VARIATIONS
TOP
This policy is applicable to all programs and products administered by Capital BlueCross unless
otherwise indicated below.
FEP PPO*
* Refer to FEP Medical Policy Manual MP-2.04.99 Genetic Testing for Hereditary Pancreatitis
The FEP Medical Policy Manual can be found at: www.fepblue.org
III. DESCRIPTION/BACKGROUND
TOP
Acute and chronic pancreatitis (CP) is caused by trypsin activation within the pancreas, resulting
in autodigestion, inflammation, elevation of pancreatic enzymes in serum, and abdominal pain.
CP is defined as an ongoing inflammatory state associated with chronic/recurrent symptoms and
progression to exocrine and endocrine pancreatic insufficiency.
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Alcohol is the major etiologic factor in 80% of CP, which has a peak incidence in the 4th and 5th
decades of life. Gall stones, hypercalcemia, inflammatory bowel disease, autoimmune
pancreatitis, and peptic ulcer disease can also cause CP. About 20% of CP is idiopathic. A small
percentage of CP is categorized as HP, which usually begins with recurrent episodes of acute
pancreatitis in childhood and evolves into CP by age 20 years. Multiple family members may be
affected over several generations, and pedigree analysis often reveals an autosomal dominant
pattern of inheritance. Clinical presentation and family history alone are sometimes insufficient
to distinguish between idiopathic CP and hereditary pancreatitis, especially early in the course of
the disease. HP is a rare disorder, in 1997 there were about 1000 people with HP in the United
States.1
Genetic Determinants of HP
PRSS1 Mutations
In 1996, Whitcomb et al discovered that mutations of protease, serine, 1 (trypsin 1) (PRSS1) on
chromosome 7q35 cause HP. PRSS1 encodes cationic trypsinogen. Gain of function mutations of
the PRSS1 gene cause HP by prematurely and excessively converting trypsinogen to trypsin,
which then results in pancreatic autodigestion. Between 60% and 80% of people who have a
PRSS1 mutation will experience pancreatitis in their lifetimes; 30% to 40% will develop CP.
Most, but not all, people with a mutation of PRSS1 will have inherited it from one of their
parents. The proportion of HP caused by a spontaneous mutation of PRSS1 is unknown. In
families with 2 or more affected individuals in 2 or more generations, genetic testing shows that
most have a demonstrable PRSS1 mutation. In 60% to 100%, the mutation is detected by
sequencing technology (Sanger or next generation), and duplications of exons or the whole
PRSS1 gene are seen in about 6%. Two PRSS1 point mutations (p.Arg122His, p.Asn29Ile) are
most common, accounting for 90% of mutations in affected individuals. Over 40 other PRSS1
sequence variants have been found, but their clinical significance is uncertain. Pathogenic PRSS1
mutations are present in 10% or less of individuals with CP.2
Targeted analysis of exons 2 and 3, where the common mutations are found, or PRSS1
sequencing, are first-line tests, followed by duplication analysis. The general indications for
PRSS1 testing and emphasis on pre- and posttest genetic counseling have remained central
features of reviews and guidelines.1,3 However, several other genes have emerged as significant
contributors to both HP and CP. These include cystic fibrosis (CF) transmembrane conductance
regulator (CFTR) gene, serine peptidase inhibitor, Kazal type 1 (SPINK1) gene, chymotrypsin C
(CTRC) gene, and claudin-2 (CLDN-2) gene.
CFTR Mutations
Autosomal recessive mutations of CFTR cause CF, a chronic disease with onset in childhood that
causes severe sinopulmonary disease and numerous gastrointestinal abnormalities. The signs and
symptoms of CF can vary widely. On rare occasions, an affected individual may have mild
pulmonary disease, pancreatic exocrine sufficiency, and may present with acute, recurrent acute,
or CP.1 Individuals with heterozygous mutations of the CFTR gene (CF carriers) have a 3- to 4-
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fold increased risk for CP. Individuals with 2 CFTR mutations (homozygotes or compound
heterozygotes) will benefit from CF-specific evaluations, therapies, and genetic counseling.
SPINK Mutations
The SPINK gene encodes a protein that binds to trypsin and thereby inhibits its activity.
Mutations in SPINK are not associated with acute pancreatitis but are found, primarily as
modifiers, in recurrent acute pancreatitis and seem to promote the development of CP, including
for individuals with compound heterozygous mutations of the CFTR gene. Autosomal recessive
familial pancreatitis may be caused by homozygous or compound heterozygous SPINK
mutations.4
CTRC Mutations
CTRC is important for the degradation of trypsin and trypsinogen, and 2 mutations (p.R254W
and p.K247_R254del) are associated with increased risk for idiopathic CP (odds ratio [OR], 4.6),
alcoholic pancreatitis (OR=4.2), and tropical pancreatitis (OR=13.6).5
CLDN2 Mutations
CLDN2 encodes a member of the claudin protein family, which acts as an integral membrane
protein at tight junctions and has tissue-specific expression. Several single nucleotide
polymorphisms in CLDN2 have been associated with CP.
Genetic Testing for Mutations Associated With HP
Testing for mutations associated with HP are typically done by direct sequence analysis or nextgeneration sequencing (NGS). A number of laboratories offer testing for the relevant genes,
either individually or as genetic panels. For example, Arup Laboratories (Salt Lake City, UT)
offers a Pancreatitis Panel, which includes direct (Sanger) sequencing of CFTR, CTRC, PRSS1,
and SPINK.6 Prevention Genetics (Marshfield, WI) offers a Chronic Pancreatitis NextGen
Sequencing Panel, which includes NGS of CASR, CFTR, CTRC, PRSS1, and SPINK1.7
Regulatory Status
Clinical laboratories may develop and validate tests in-house and market them as a laboratory
service; laboratory-developed tests (LDTs) must meet the general regulatory standards of the
Clinical Improvement Act (CLIA). Genetic testing for hereditary pancreatitis is available under
the auspices of CLIA. Laboratories that offer LDTs must be licensed by CIA for highcomplexity testing. To date, the U.S. Food and Drug Administration has chosen not to require
any regulatory review of these tests.
IV. RATIONALE
TOP
This evidence review was created in August 2013 and updated periodically with literature
reviews, most recently through July 8, 2015 (see Appendix Table 1 for genetic testing
categories).
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Analytic Validity
Testing for mutations in the protease, serine, 1 (trypsin 1) (PRSS1), serine peptidase inhibitor
(SPINK), and cystic fibrosis (CF) transmembrane conductance regulator (CFTR) genes is usually
done by direct sequence analysis, which is the criterion standard for detecting a mutation that is
present and/or excluding a mutation that is absent. Testing can also be done by next-generation
sequencing, which has an accuracy that approaches that of direct sequencing. In patients who test
negative by either of these methods, duplication/deletion analysis may be performed to detect
copy number variations. These genetic testing methods are considered to have high analytic
validity.
Clinical Validity
The clinical validity of genetic testing for hereditary pancreatitis (HP) refers to the mutation
detection rate in patients who have known HP.
There is a lack of published evidence on the percent of patients who are first identified as having
clinically defined HP and then tested for genetic mutations. Most studies that examine the
mutation detection rate use a population of patients with idiopathic chronic pancreatitis (CP) and
do not necessarily require that patients have a family history of CP. In other studies, cohorts of
patients with HP were defined by the presence of genetic mutations or family history, which
therefore may include patients with genetic mutations who do not have a family history of CP.
A summary of representative studies reporting the sensitivity and specificity of genetic testing in
patients with is included in Table 1.
Table 1. Summary of Studies Reporting the Clinical Validity of HP Gene Texting
Study
Population
Schwarzenberg
(2015)
(international)8
170 children, 76 with CP and 94 with
acute recurrent pancreatitis
Poddar (2015)
(India)9
68 children with pancreatitis (35.3%
acute, 32.3% acute recurrent, 32.3%
chronic); 25 healthy controls
253 patients with idiopathic CP
Masson (2014)
(France)10
Wang (2014)
(China)11
75 children with idiopathic CP
Ceppa (2013)
(U.S.)12
87 patients with HP, defined by known
genetic mutation or family history
Sultan (2012)
(U.S.)13
29 children with recurrent acute or CP
Genes
Tested
PRSS1
SPINK
CFTR
CTRC
PRSS1
SPINK
CFTR
PRSS1
SPINK
CFTR
CTRC
PRSS1
SPINK
CFTR
CTRC
CLDN2
PRSS1
SPINK
CFTR
PRSS1
SPINK
CFTR
Clinical Sensitivity
67% (51/76 with CP)
Clinical
Specificity
NR
44% (38/68)
96% (24/25)
 23.7% “causal”
mutation (60/253)
 24.5% “contributory”
mutation (62/253)
 66.7% (50/75)
(with PRSS1 or
SPINK mutations)
NR
NR
62% (54/87)
NR
79% (23/29)
NR
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Gasiorowska (2011)
(Poland)14
14 patients with idiopathic CP; 46
control patients without pancreatitis
PRSS1
SPINK
50% (7/14)
89%
(41/46)
Joergensen (2010)
(Denmark)15
122 patients with idiopathic pancreatitis
PRSS1
SPINK
CFTR
PRSS1
40% (49/122)
NR
68% (136/200)
NR
49% (185/381)
NR
8% (8/104)
NR
52% (60/115)
13% (46/349)
Rebours (2009)
(France)16
Keiles (2006)
(U.S.)17
200 patients with CP
389 patients with recurrent or CP
referred for genetic testing
PRSS1
SPINK
CFTR
PRSS1
Truninger (2001)
104 patients with CP
(Germany)18
Applebaum-Shapiro
115 patients with HP defined clinically; PRSS1
(2001) (U.S.)19
349 unaffected family members
CP: chronic pancreatitis; HP: hereditary pancreatitis; NR: not reported.
CP, chronic pancreatitis; HP, hereditary pancreatitis.
These data on clinical validity demonstrate that genetic mutations are common in patients with
CP. A very limited amount of evidence reports that genetic mutations are found in a small
percentage of patients without pancreatitis. However, the true clinical sensitivity and specificity
for genetic testing in cases of HP are uncertain for a number of reasons. First, the populations in
these studies are defined differently, with most not consisting of patients with clinically defined
HP. The populations are from different geographic regions, in which the prevalence of genetic
mutations may vary. Some of the studies mix adult and pediatric populations, while others report
on either adults or children. In the 2 studies that exclusively enrolled children, the rate of
mutation detection was generally higher than other studies (67% and 79%). Finally, mutations
tested for in these studies differ, with many studies not including all of the known genes that are
associated with HP.
Other studies have reported on the rates of genetic mutations among populations of patients who
were identified using less selective criteria, such as patients with isolated unexplained or
recurrent acute pancreatitis or unexplained CP. Ballard et al reported results of a retrospective
cohort study of 370 adults with unexplained pancreatitis, including recurrent acute pancreatitis,
CP, or symptoms consistent with CP, who underwent pancreas-specific genetic testing at a single
center.20 Although 67 patients (18.1%) had any mutation detected, only 24 of these (6.4%) were
found to have high-risk mutations, defined as (1) a single copy mutation of PRSS1, (2)
homozygous mutations of CFTR, SPINK1, or CTRC, or (3) compound heterozygous mutations
of CFTR, SPINK, and/or CTRC. High-risk mutations were more likely to be detected in patients
who underwent complete gene sequencing methods compared with those who had targeted
mutation testing methods. In a case-control study, Rai et el reported that SPINK1 mutations were
found in 12.0% of 183 patients with acute pancreatitis, compared with 2.4% of 168 controls
(p=0.006).21 In a cohort study of 67 patients with acute recurrent pancreatitis of unknown
etiology, Werlin et al reported that 34% of patients had a mutation in at least one gene associated
with HP.22
The mutation detection rate for children with CP appears to be higher than for adults. Similarly,
the proportion of patients with acute pancreatitis attributable to genetic causes is higher among
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younger patients. In a group of 309 subjects with acute pancreatitis, patients aged 35 and
younger (n=66) were more likely to have a genetic cause of pancreatitis identified (10% vs 1.5%,
p=0.003).23
Section Summary: Clinical Validity for Testing for Mutations Associated With HP
A number of studies report the mutation detection rate in various populations of patients with
CP, but few studies enroll a population of patients with clinically defined HP. Therefore, the true
clinical sensitivity and specificity cannot be determined. In studies that report on children, the
detection rates are generally higher than other studies, suggesting that the mutation detection rate
may be higher in children than in adults.
Clinical Utility
Potential types of clinical utility for testing of genes associated with HP include confirmation of
the diagnosis of HP, predictive testing in asymptomatic relatives, and prognostic testing to
determine the course of the disease. In each case, demonstration of clinical utility depends on
whether identification of a genetic defect leads to changes in medical and/or surgical
management options, and whether these changes lead to improved health outcomes.
Preconception (carrier) testing and prenatal (in utero) testing can also be performed, but are not
addressed in this literature review.
Diagnostic Testing
There are no direct outcome data regarding the clinical utility of testing for confirmation of HP
(i.e., there are no studies that report outcome data in patients who have been tested for HP
compared with patients who have not been tested).
Confirmatory testing can be performed in patients who experience acute pancreatitis that is
otherwise unexplained, for recurrent acute pancreatitis of unclear cause, and/or for idiopathic CP.
In all of these scenarios, a substantial percentage of patients will be found to have a genetic
defect, thereby confirming the diagnosis of HP. Most treatments for the pain, maldigestion, and
diabetes caused by HP are fundamentally the same as for other types of CP. Therefore, if a
deleterious mutation associated with HP is found, treatment for CP is unlikely to change.
Interventions for CP include a low-fat diet with multiple small meals, maintenance of good
hydration, use of antioxidants, and avoidance of smoking and alcohol use. While all of these
interventions may alter the natural history of the disease, there is no evidence that the impact
differs for HP compared with other etiologies of CP.
Calcium channel blockers are currently being investigated as a potential treatment for HP. One
small uncontrolled trial of amlodipine in 9 patients was identified in the literature.24 This trial
included patients 6 years or older who had CP and a known PRSS1 mutation. Treatment was
continued for up to 11 weeks, and 4 patients successfully completed the full course of treatment.
All 4 patients reported decreased symptoms, and 3 of the 4 patients had improved scores on the
36-Item Short-Form Health Survey outcome instrument. There were no differences before and
after treatment in blood pressure, laboratory tests, or physical exam.
Total pancreatectomy with islet cell transplantation (or total pancreatectomy with islet
autotransplantation [TP-IAT]) has been investigated in CP or recurrent acute pancreatitis,
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particularly as a treatment for intractable pain in patients with impaired quality of life in whom
medical, endoscopic, or prior surgical treatment have failed. However, questions remain about
the best timing of surgery, selection of candidates, evaluation of outcomes, and follow-up.25
Chinnakotla et al conducted a retrospective study that compared outcomes after TP-IAT for
patients with HP or familial pancreatitis compared with other causes of CP among 484 patients
treated at a single institution from 1977 to 2012, 80 of whom had HP.26 Genetic testing was not
available for all patients with suspected HP. Multiple causes of HP or familial pancreatitis were
included: 38 with PRSS1 mutations; 9 with SPINK1 mutations; 14 with CFTR mutations; and 19
with familial pancreatitis without a mutation specified. Patients with HP were younger at the
time of TP-IAT (mean age, 21.9 years vs 37.9 years in nonhereditary CP, p<0.001), but had a
longer history of pancreatitis (mean, 10.1 years vs 6.4 years in nonhereditary CP, p<0.001). Pain
scores significantly improved after TP-IAT (p<0.001), with no significant differences between
HP and nonhereditary CP.
Predictive Testing
Predictive testing can be performed in asymptomatic relatives of patients with known HP to
determine the likelihood of CP. For this population, no direct evidence was identified that
compared outcomes in patients tested for genetic mutations compared with patients not tested for
genetic mutations. It is possible that at-risk relatives who are identified with genetic mutations
may alter lifestyle factors such as diet, smoking and alcohol use, and this may delay the onset or
prevent CP. However, evidence on this question is lacking, so that conclusions cannot be made
on whether testing of asymptomatic family members of patients with HP improves outcomes.
Prognostic Testing
Several studies were identified that examined whether the severity and/or natural history of CP
differs in patients with and without genetic mutations. A number of studies have reported that
patients with HP have an earlier age of onset compared with patients with other etiologies of
CP.27 Other studies have examined whether the severity and natural history differs for patients
with HP, but these studies have not reported consistent findings. Some studies have reported that
the progression of disease is slower in patients with HP27-29 and that surgical intervention is
required less often for patients with HP.28 However, 1 study also reported that the cumulative
risk for exocrine failure was more than twice as high for patients with genetic mutations
compared with patients without mutations.29 In another small study that compared the clinical
course of patients with HP to those with alcoholic CP, most clinical manifestations were similar,
but patients with HP had a higher rate of pseudocysts.30
Individuals with CP due to HP, like others with CP, are at increased risk for pancreatic cancer. In
a survey of 246 patients with HP from 10 countries, the cumulative risk of pancreatic cancer by
age 70 was estimated to be 40%.31 In a series of 200 patients with HP from France, the
cumulative incidence of pancreatic cancer at 50 years was 11% for men and 85% for women. At
75 years of age, the cumulative risk was 49% for men and 55% for women. There was no
evidence identified that the risk of pancreatic cancer differs for patients with HP compared with
patients with other forms of CP.
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Screening for pancreatic cancer with computed tomography scanning, endoscopic ultrasound,
and/or endoscopic retrograde cholangiopancreatography has been recommended for patients with
CP irrespective of etiology,32,33 but close surveillance has not yet been demonstrated to improve
long-term survival for any of these methods in patients with CP.
Section Summary: Clinical Utility for Testing for Mutations Associated With HP
The evidence on clinical utility does not support an improvement in health outcomes associated
with genetic testing. For diagnostic testing, there is a lack of evidence that genetic testing leads
to management changes. Several treatments for CP, including calcium channel blockers and TPIAT, are under investigation; however, the evidence to date is insufficient to determine whether
patients with HP respond differently to such treatments than other patients with CP. For
prognostic testing, there have been some differences reported regarding the natural course of CP
in patients with and without genetic mutations. The age of onset is consistently younger, and the
progression of disease may be slower, but it is not possible to conclude whether the overall
severity of disease or need for surgical intervention differs. The risk of pancreatic cancer is high
for patients with HP, but no evidence was identified that establishes whether the risk of cancer is
greater for patients with HP compared with other etiologies of CP. For testing asymptomatic, atrisk family members, there is a lack of evidence that genetic testing leads to interventions that
delay or prevent the onset of pancreatitis.
Summary of Evidence
The evidence for the use of genetic testing for mutations associated with hereditary pancreatitis
(HP) among patients with chronic pancreatitis (CP) or recurrent acute pancreatitis in adulthood
or childhood includes cohort and case-control studies that evaluate the yield of genetic testing
(clinical validity). Relevant outcomes are test accuracy, symptoms, change in disease status,
morbid events, and hospitalizations. Numerous studies demonstrate that genetic mutations are
found in a large percentage of patients with idiopathic CP. However, these studies are limited by
wide variations in the patient populations and genes tested; as a result, it is not possible to
determine the true prevalence of HP among patients with idiopathic CP, nor the sensitivity and
specificity of genetic testing (clinical validity) in patients with a familial pattern of disease. The
clinical utility of testing has not been demonstrated empirically. While testing can confirm the
diagnosis of HP, there is no evidence that treatment is altered by testing or that health outcomes
are improved. Similarly, predictive testing of at-risk relatives and prognostic testing have not
been shown to improve outcomes. Predictive testing can better define the risk of developing CP,
but there is no evidence that early interventions based on genetic testing alter the prevalence or
course of disease. The prognosis of HP may differ from other etiologies of CP, but this evidence
is mixed and there are no changes in management that result from refining the prognosis of CP.
Overall, direct evidence of improved health outcomes following use of genetic testing for HP
lacking. The changes in clinical management that would occur as a result of testing are not welldefined. The evidence is insufficient to determine the effects of the technology on health
outcomes.
The evidence for the use of genetic testing for mutations associated with HP among
asymptomatic individuals with family members with HP includes a very limited number of
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studies. Relevant outcomes are test accuracy, symptoms, change in disease status, morbid events,
and hospitalizations. No direct evidence was identified that compared outcomes in patients tested
for genetic mutations compared with patients not tested for genetic mutations. It is possible that
at-risk relatives who are identified with genetic mutations may alter lifestyle factors such as diet,
smoking, and alcohol use, and this may delay the onset or prevent CP. Direct evidence of
improved health outcomes following the use of genetic testing for HP in at-risk family members
is lacking. The changes in clinical management that would occur as a result of testing are not
well-defined. The evidence is insufficient to determine the effects of the technology on health
outcomes.
Clinical Input Received From Physician Specialty Societies and Academic Medical Centers
While the various physician specialty societies and academic medical centers may collaborate
with and make recommendations during this process through the provision of appropriate
reviewers, input received does not represent an endorsement or position statement by the
physician specialty societies or academic medical centers, unless otherwise noted.
In response to requests, input was received from 4 academic medical centers (one of which
provided 2 responses) and 2 specialty medical societies (one of which provided 2 responses)
when this policy was under review in 2014, with specific focus on testing in children. There was
consensus among reviewers that genetic testing for HP is medically necessary in children.
Practice Guidelines and Position Statements
American College of Medical Genetics
The American College of Medical Genetics issued a policy statement on laboratory standards
and guidelines for population-based cystic fibrosis (CF) carrier screening in 2001,34 which were
updated in 200435 and reaffirmed in 2013.36 These guidelines provide recommendations about
specific mutation testing in CF, but do not specifically address genetic testing for suspected HP.
European Consensus Conference
A 2001 European Consensus Conference developed guidelines for genetic testing of the PRSS1
gene, genetic counseling, and consent for genetic testing for HP.37 The recommended indications
for symptomatic patients included:




Recurrent (2 or more separate, documented episodes with hyperamylasemia) attacks of
acute pancreatitis for which there is no explanation
Unexplained chronic pancreatitis
A family history of pancreatitis in a first- or second-degree relative
Unexplained pancreatitis in a child – if recurrent or requiring hospitalization
Predictive genetic testing, defined as genetic testing in an asymptomatic “at-risk” relative of an
individual proven to have HP, was considered more complex. Candidates for predictive testing
should be a first-degree relative of an individual with a well-defined HP gene mutation, capable
of informed consent, and able to demonstrate an understanding of autosomal dominant
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inheritance, incomplete penetrance, variable expressivity, and the natural history of HP. Written
informed consent must be documented before the genetic test is performed.
U.S. Preventive Services Task Force Recommendations
Not applicable.
Medicare National Coverage
There is no national coverage determination (NCD).
V. DEFINITIONS
TOP
N/A
VI. BENEFIT VARIATIONS
TOP
The existence of this medical policy does not mean that this service is a covered benefit under
the member's contract. Benefit determinations should be based in all cases on the applicable
contract language. Medical policies do not constitute a description of benefits. A member’s
individual or group customer benefits govern which services are covered, which are excluded,
and which are subject to benefit limits and which require preauthorization. Members and
providers should consult the member’s benefit information or contact Capital for benefit
information.
VII. DISCLAIMER
TOP
Capital’s medical policies are developed to assist in administering a member’s benefits, do not constitute medical
advice and are subject to change. Treating providers are solely responsible for medical advice and treatment of
members. Members should discuss any medical policy related to their coverage or condition with their provider
and consult their benefit information to determine if the service is covered. If there is a discrepancy between this
medical policy and a member’s benefit information, the benefit information will govern. Capital considers the
information contained in this medical policy to be proprietary and it may only be disseminated as permitted by
law.
VIII. CODING INFORMATION
TOP
Note: This list of codes may not be all-inclusive, and codes are subject to change at any time. The
identification of a code in this section does not denote coverage as coverage is determined by the terms
of member benefit information. In addition, not all covered services are eligible for separate
reimbursement.
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Covered when medically necessary:
CPT Codes®
81401
81404
81222
81223
81479
Current Procedural Terminology (CPT) copyrighted by American Medical Association. All Rights Reserved.
ICD-10-CM
Diagnosis
Description
Codes
K85.00
K85.01
K85.02
K85.10
K85.11
K85.12
K85.20
K85.21
K85.22
K85.30
K85.31
K85.32
K85.80
K85.81
K85.82
K86.1
Idiopathic acute pancreatitis without necrosis or infection
Idiopathic acute pancreatitis with uninfected necrosis
Idiopathic acute pancreatitis with infected necrosis
Biliary acute pancreatitis without necrosis or infection
Biliary acute pancreatitis with uninfected necrosis
Biliary acute pancreatitis with infected necrosis
Alcohol induced acute pancreatitis without necrosis or infection
Alcohol induced acute pancreatitis with uninfected necrosis
Alcohol induced acute pancreatitis with infected necrosis
Drug induced acute pancreatitis without necrosis or infection
Drug induced acute pancreatitis with uninfected necrosis
Drug induced acute pancreatitis with infected necrosis
Other acute pancreatitis without necrosis or infection
Other acute pancreatitis with uninfected necrosis
Other acute pancreatitis with infected necrosis
Other chronic pancreatitis
*If applicable, please see Medicare LCD or NCD for additional covered diagnoses.
IX. REFERENCES
TOP
1. Solomon S, Whitcomb, D.C., LaRusch, J, et al. PRSS1-Related Hereditary Pancreatitis.
GeneReviews 2012. Accessed June 10,2015.
2. Whitcomb DC. Value of genetic testing in the management of pancreatitis. Gut. Nov
2004;53(11):1710-1717. PMID 15479696
3. Fink EN, Kant JA, Whitcomb DC. Genetic counseling for nonsyndromic pancreatitis.
Gastroenterol Clin North Am. Jun 2007;36(2):325-333, ix. PMID 17533082
4. Whitcomb DC. Framework for interpretation of genetic variations in pancreatitis patients.
Front Physiol. 2012;3:440. PMID 23230421
5. Rosendahl J, Witt H, Szmola R, et al. Chymotrypsin C (CTRC) variants that diminish activity
or secretion are associated with chronic pancreatitis. Nat Genet. Jan 2008;40(1):78-82.
PMID 18059268
6. Arup Laboratories LTD. Pancreatitis, Panel (CFTR, CTRC, PRSS1, SPINK1) Sequencing.
http://ltd.aruplab.com/tests/pub/2010876. Accessed July 13, 2015.
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7. Prevention Genetics. Chronic Pancreatitis NextGen Sequencing (NGS) Panel. 2014;
https://www.preventiongenetics.com/clinical-dna-testing/test/chronic-pancreatitis-nextgensequencing-ngs-panel/2452/. Accessed July 13, 2015.
8. Schwarzenberg SJ, Bellin M, Husain SZ, et al. Pediatric chronic pancreatitis is associated
with genetic risk factors and substantial disease burden. J Pediatr. Apr 2015;166(4):890-896
e891. PMID 25556020
9. Poddar U, Yachha SK, Mathias A, et al. Genetic predisposition and its impact on natural
history of idiopathic acute and acute recurrent pancreatitis in children. Dig Liver Dis. Apr
25 2015. PMID 25981744
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Active List
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https://www.acmg.net/ACMG/Publications/Practice_Guidelines/ACMG/Publications/Practic
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X. POLICY HISTORY
MP 2.318
TOP
CAC 11/26/13 New Policy. BCBSA adopted. Genetic testing for hereditary
pancreatitis is considered investigational. Coded.
7/24/14 Administrative change for the Medicare variation - For Novitas
MAC jurisdictions, the LCD has been assigned a new number. Biomarkers
for Oncology LCD changed from L33124 to L34796
11/18/14 Administrative change. Medicare variation removed.
CAC 1/27/15 Minor revision. Policy statements changed to indicate that
genetic testing for hereditary pancreatitis may be considered medically
necessary for children. FEP variation added to refer to the FEP medical
policy manual. Policy coded for medically necessary indications.
CAC 1/26/16 Consensus review. No change to policy statements.
References and rationale updated. Coding reviewed.
Administrative Update 11/10/16 Variation reformatting
Administrative Update 1/1/17 New diagnosis codes added effective
10/1/16
CAC 1/31/17 Consensus review. No changes to the policy statements.
References and rationale updated. Appendix added. Coding reviewed.
Top
Health care benefit programs issued or administered by Capital BlueCross and/or its subsidiaries, Capital Advantage Insurance
Company®, Capital Advantage Assurance Company® and Keystone Health Plan® Central. Independent licensees of the
BlueCross BlueShield Association. Communications issued by Capital BlueCross in its capacity as administrator of programs
and provider relations for all companies.
Appendix Table 1. Categories of Genetic Testing Addressed in this policy
Category
1. Testing of an affected individual’s germline to benefit the individual
1a. Diagnostic
1b. Prognostic
1c. Therapeutic
2. Testing cancer cells from an affected individual to benefit the individual
2a. Diagnostic
2b. Prognostic
Addressed
X
X
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2c. Therapeutic
3. Testing an asymptomatic individual to determine future risk of disease
4. Testing of an affected individual’s germline to benefit family members
5. Reproductive testing
5a. Carrier testing: preconception
5b. Carrier testing: prenatal
5c. In utero testing: aneuploidy
5d. In utero testing: mutations
5e. In utero testing: other
X
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