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Hereditary & familial colorectal cancer
Identification, characteristics, surveillance
Kallenberg, F.G.J.
Publication date
2017
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Citation for published version (APA):
Kallenberg, F. G. J. (2017). Hereditary & familial colorectal cancer: Identification,
characteristics, surveillance.
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F.G.J. Kallenberg, B.A.J. Bastiaansen, C.Y. Nio, M.R. Soeters, M.A. Boermeester,
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adrenal lesIons In patIents wIth
(attenuated) famIlIal adenomatous
polyposIs and mutyh-assocIated
polyposIs
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A B S T R A C T
Background
The reported proportion of patients with familial adenomatous polyposis who have adrenal lesions varies between 7% and 13%, compared to 4% in the general population; the prevalence of adrenal lesions in patients with attenuated familial adenomatous polyposis and MUTYH-associated polyposis is unknown. Data on the clinical relevance and clinical course are limited.
Objective
We aimed to report on the frequency, characteristics and progression of adrenal lesions in polyposis patients.
Design
Historical cohort study.
Settings
The study was performed at the Academic Medical Center, Amsterdam.
Patients
All patients with familial adenomatous polyposis, attenuated familial adenomatous polyposis and MUTYH-associated polyposis were included. Medical records and imaging reports were analyzed for data on adrenal lesions. A radiologist reassessed all images. Patients had not routinely been screened for adrenal lesions.
Main outcome measures
The frequency, characteristics and progression of adrenal lesions in polyposis patients who underwent abdominal imaging. Findings were compared with a reference.
Results
A total of 39 adrenal lesions were identified in 23/90 patients with familial adenomatous polyposis (26%), 2/11 with attenuated familial adenomatous polyposis (18%) and 5/21 with MUTYH-associated polyposis (24%). Mean age at time of detection was 50.7 years (range
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17.1-83.3). Median lesion size at baseline was 1.4 cm (range 1.0-5.0) versus 1.7 cm (range 1.0-5.7) after a median of 3.5 years (range 1.0-11.4). Two patients were diagnosed with a hyperfunctioning lesion and four underwent adrenalectomy: three lesions appeared benign, one was oncocytic of uncertain malignant potential. The odds ratio for detecting at least one lesion in a polyposis patient versus reference was 6.2 (95% CI 3.2-12.3), with no significant differences in odds ratios between the three syndromes.
Limitations
Retrospective design.
Conclusion
Adrenal lesions are frequent in polyposis patients who undergo abdominal imaging. They seem to follow a benign and slowly progressive course and are mostly non-hyperfunctioning.
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I N T R O d u C T I O N
Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited syndrome, characterized by the presence of multiple colorectal adenomas. Several extra-colonic manifestations are also commonly identified in these patients. These include duodenal adenomas and, with a lifetime risk approaching 100% and a duodenal cancer risk up to 36%, screening and surveillance recommendations are typically provided.1-5 Less is known about
the prevalence and characteristics of other FAP-related manifestations, such as adrenal lesions.6-8
In the general population, adrenal lesions include a heterogeneous group of entities that can be benign or malignant and in some cases are hyperfunctioning.9 Non-hyperfunctioning
lesions can also become active over time and benign lesions could progress to malignant disease. Limited data indicate an increased risk of such lesions in patients with FAP, with a lifetime prevalence between 7 to 13%, compared to 4% in the general population.6-8, 10, 11 Data
on the clinical presentation and biological behavior of these lesions in patients with FAP are scarce and only two studies have reported on their follow-up.6, 8 As most patients with FAP now
undergo prophylactic colectomy, which prolongs survival, the incidence of adrenal lesions is likely to increase and their presence could become more clinically relevant. In addition, their detection is probably facilitated by the progressive use of abdominal imaging.
Before we can consider whether screening and surveillance for adrenal lesions is indicated for these patients, more information is needed.7, 10, 12 Whether patients with the related syndromes
attenuated FAP (AFAP) and MUTYH-associated polyposis (MAP) are also at risk has not yet been studied. We performed a historical cohort study in patients with FAP, AFAP and MAP, based on available records and images, and report on the frequency, characteristics and clinical progression of adrenal lesions.
M A T E R I A L A N d M E T h O d S
Study population
A medical chart review was performed to identify all patients with FAP, AFAP and MAP (below referred to as “polyposis patients”) attending the Hereditary Cancer Clinic at the Academic Medical Center in Amsterdam, The Netherlands, between 1985 and May 2015. Diagnoses of FAP and AFAP had been established genetically based on the presence of an APC-gene mutation, or clinically, by the presence of >100 (FAP) or 10-100 (AFAP) colorectal adenomas. All patients with MAP had a biallelic germline MUTYH mutation.
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Identification, characteristics and progression of adrenal lesions
In our center we do not routinely screen for adrenal lesions but abdominal imaging may be performed for other indications. For all known polyposis patients, medical records and relevant imaging were reviewed in search for evidence of adrenal lesions. Imaging modalities were considered relevant if the adrenal glands had been completely and clearly visualized. This means only positron emission tomography-computed tomography (PET-CT), computed tomography (CT) and magnetic resonance imaging (MRI) images were included. In case the adrenal glands were not described in the original imaging reports, an experienced radiologist (more than 20 years of experience with abdominal cross-sectional imaging) reviewed the scans for adrenal assessment.
An adrenal lesion was defined as a focal lesion of at least one centimeter.13 For all identified
lesions, scans were reviewed and described by the radiologist using standardized characteristics.11 A lesion was classified as benign in case of identification of sharp margins,
homogeneous density and, if available, homogeneous contrast uptake, a maximum diameter of less than 3.5 centimeter, a growth rate of less than 5 millimeters per year. A lesion was classified as an adenoma in case of CT attenuation values of less than 10 Houndsfield units (HU) (on plain CT), a signal drop in out-of-phase sequence in case of MRI, or an absolute washout of at least 60% after intravenous contrast (if performed). Other criteria for a benign lesion were absence of necrosis, hemorrhage or calcification. Growth rate was reported if follow-up imaging had been performed after one year or more and was calculated as change per year. Changes in size of 2 mm or more were considered clinically significant.
Hormonal activity & histopathology
Data on endocrine testing for hormonal activity (e.g. dexamethasone suppression tests, assessment of plasma and urine levels of metanephrines), when available, were retrieved from medical records. Data on histopathology of operated lesions were collected from patient files.
Reference group comparison
For comparison, we collected information on patients who had participated in the multicenter OPTIMA imaging study.14 This study compared the diagnostic accuracy of imaging strategies in
patients with non-traumatic acute abdominal pain. Between 2005 and 2006, 1,021 consenting patients presenting at the emergency department of one of six hospitals (including our center), underwent a plain chest and abdominal radiograph, abdominal ultrasound and CT scan. For our analyses, the CT scan reports of all 298 patients presenting at the Academic Medical Center
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were scrutinized for adrenal lesions. In case adrenal lesions were mentioned or adrenal glands were not described, the study radiologist reviewed the scans.
Statistical analysis
We compared demographic data between groups using the Chi square test, Fisher’s exact test, Mann-Whitney U test or unpaired t-test statistics, depending on the type of variable. To compare ages of those with and without adrenal lesions, the age at the time of the last performed imaging was used in polyposis patients without adrenal lesions. For those with polyposis and adrenal lesions, the age at time of first detection of an adrenal lesion was used. In all comparisons, p-values smaller than 0.05 were considered to indicate statistically significant differences. A logistic regression analysis was performed to evaluate the conditional association of adrenal lesions and polyposis, using the data from the reference group while adjusting for the confounders age and sex. In this analysis, the detection of one or more lesions was the dependent variable, and polyposis, age and sex were independent variables. Associations are presented as odds ratios with 95 % confidence intervals (95% CI). All analyses were performed using SPSS statistical software version 23 (IBM SPSS, Chicago, IL, USA).
Ethical considerations
The images of polyposis patients had been used for patient care, and according to Dutch law, no additional consent is needed for these anonymized analyses. All OPTIMA participants had provided written informed consent. The current study was carried out in accordance with the Helsinki Declaration.15
R E S u L T S
Study group
A total number of 200 patients with FAP, 37 with AFAP and 32 with MAP were identified at our clinic. Of those, 90/200 (45%) with FAP, 11/37 (30%) with AFAP and 21/32 (66%) with MAP had undergone relevant imaging between 1995 and 2015.
Polyposis patients with adrenal lesions
In the 90 patients with FAP who had undergone relevant imaging at our clinic, one or more adrenal lesions were detected in 23 (26%) (Fig. 1, Fig. 2). In the 11 patients with AFAP, in 2 adrenal lesions were detected (18%); In MAP this number was 5 out of 21 patients (23%),
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all with a biallelic germline MUTYH mutation. All adrenal lesions were coincidental findings. Eighteen of 23 affected patients with FAP and both patients with AFAP had a germline APC mutation. When evaluating the results for those 82 patients with an APC-germline mutation only (combining FAP and AFAP and excluding patients with clinical FAP and AFAP) and who underwent relevant imaging, 20 (24%) had an adrenal lesion. Of the 16 patients without an APC or MUTYH mutation and relevant imaging, 5 of 12 with clinical FAP (42%) and none of 4 with clinical AFAP had an adrenal lesion. In three patients without adrenal lesions it was unknown if the diagnosis was made clinically or genetically.
Three patients with adrenal lesions and an APC mutation (of whom unknown if they were kin) shared an exon 3 splice site mutation, but no other common germline mutations were found. Of the 30 patients with adrenal lesions, 17 (57%) were male; mean age at time of detection was 50.7 years (range 17.1-83.3). Patients with FAP who had an adrenal lesion detected were significantly older than those without an adrenal lesion: 50.4 versus 40.0 years (p=0.007). There was no significant difference in sex distribution: 12/23 males with a lesion (52%) versus 39/67 without (58%; p=0.63). In AFAP and MAP patients no significant differences in age and sex were observed between those with and without adrenal lesions (Table 1).
Five patients had bilateral lesions and four had two unilateral lesions, resulting in a total number of 39 detected lesions. Median size of these lesions at first detection was 1.7 (range 1.0-5.0) cm. Other extra-colonic manifestations were present in 29 of the 30 patients with adrenal lesions. There were 26 patients with duodenal adenomas, 20 with fundic gland polyps, 6 with intra-abdominal desmoids, 1 with jejunal cancer and 1 with thyroid cancer. There was no significant
Figure 1. Image A shows a right adrenal lesion with absence of suspicious signs and HU value <10, thus most likely adenoma (black arrow). On the left side a renal cyst is visible next to a normal left adrenal gland. Image B shows an enlarged left adrenal gland with a small enhancing nodule and
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Figure 2. Flowchart showing polyposis patients with adrenal lesions, their characteristics and follow-up; *Therefore included in both ‘Approach’ arms
difference in the detection of desmoids, fundic gland polyps or duodenal adenomas between FAP patients with and those without adrenal lesions (p=0.77, p=0.33 and p=0.17 resp.), nor in AFAP and MAP patients.
Hormonal activity and adrenalectomies
In 17 of 30 patients with adrenal lesions, endocrine testing had been performed. In 15 of them, lesions appeared non-hyperfunctioning. Two FAP patients had a hyperfunctioning lesion (Fig. 2): one had subclinical primary hypercortisolism for which follow-up was recommended and one had primary hypercortisolism for which adrenalectomy was performed at age 44, with adenomatous histopathology after resection. Fourteen years later a contralateral lesion was identified incidentally and not resected. Three other patients also underwent adrenalectomy.
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One male MAP patient was diagnosed with multiple primary malignancies (pouch, lung and thyroid carcinoma and splenic angiosarcoma) and radiologic signs of adrenal metastasis (FDG uptake on PET-CT) at age 17. Histopathology after resection was inconclusive on a diagnosis of adenoma or hyperplasia. One patient with FAP was operated at age 60 due to the large size (4.3 cm), irregular aspect and calcifications in the adrenal lesion on CT, suggestive of a malignancy. In this patient histopathology also showed an adrenal adenoma. Another patient with FAP (female, 30 years) had two unilateral lesions of which one was 4.7 cm with a size change of more than 5 mm per year, inhomogeneous contrast uptake and signs of necrosis and bleeding. After resection, histopathology revealed an oncocytic lesion of uncertain malignant potential and three adenomas, for which 5-year surveillance with adrenal imaging was recommended.
Follow-up of non-resected adrenal lesions
In patients with non-resected lesions, follow-up imaging after at least 1 year was available in
Table 1. Differences in age and sex distribution amongst 90 patients with FAP, 11 with AFAP, 21 with MAP and 298 in a reference group, with and without adrenal lesions
Adrenal lesion No adrenal lesion P-value FAP
Number 23 (26%) 67 (74%)
Median age in years (range) 50.4 (27.3-83.3) 40.0 (2.0-77.8) 0.007a
Males 12 (52%) 39 (58%) 0.63b
AFAP
Number 2 (18%) 9 (82%)
Median age in years (range) 49.6 (46.7-52.5) 58.6 (37.0-72.7) 0.35a
Males 1 (50%) 5 (56%) 1.00b
MAP
Number 5 (24%) 16 (76%)
Median age in years (range) 51.2 (17.1-72.0) 58.3 (25.8-85.6) 0.32a
Males 4 (80%) 7 (44%) 0.31b
Reference group
Number 15 (5%) 283 (95%)
Median age in years (range) 52.1 (42.4-68.7) 43.8 (19.0-94.5) 0.031a
Males 9 (60%) 120 (42%) 0.19b
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(range 1.0-5.0) cm and at follow-up 1.6 (range 1.0-5.7) cm after a median of 3.5 (range 1.0-11.4) years. Of these 17 lesions, 9 remained stable, 7 progressed and 1 decreased in size. Median growth rate for those that progressed was 0.12 cm per year (range 0.03-0.31). During follow-up, 6 patients had died, all from other causes.
Imaging characteristics of non-resected adrenal lesions
In 8 of the 27 patients in whom the lesions were not resected, the lesions were classified as adenoma based on a HU value <10, a HU value ≥10 together with washout of ≥60%, or a signal drop in out-of-phase sequence in case of MRI, in the absence of suspicious signs.
In 9 other patients, adrenal lesions showed one or more imaging signs that raised suspicion of a malignant lesion. Four FAP patients had a lesion larger than 3.5 cm, two FAP patients had adrenal calcifications (including one with a large lesion size) and one patient with MAP had a lesion with a HU value >10 on a plain CT scan and wash-out on MRI of less than 60%. In three patients, a HU value > 10 was found based on a plain CT, but wash-out evaluation was not (yet) performed for further evaluation. None of them had other suspicious signs on imaging. Details of these patients can be found in Table 2.
The remaining 10 patients with non-resected lesions all underwent imaging with contrast enhancement, resulting in an unreliable HU value assessment. One patient underwent an MRI without out-of-phase sequence, so evaluation of signal drop could not be performed. None of these patients showed other signs suggestive of suspicious lesions.
Adrenal lesions in the reference group
The mean age in the reference group of 298 patients with non-traumatic acute abdominal pain was 46.9 years (range 19.0-94.5), compared to 46.7 (2.0-85.6) years in the 122 polyposis patients (90 FAP, 11 AFAP, 21 MAP) who had undergone relevant imaging (p=0.91; Table 3). There were fewer males in the reference group: 43% versus 56% in the polyposis group (p=0.02).
Significantly less patients had adrenal lesions identified in the reference group: 15 (5%), compared to the 30 in the polyposis group (25%). No significant differences were found in age and sex distribution between polyposis and reference group patients with adrenal lesions. In multivariable logistic regression, adjusting for age and sex, polyposis was found to be significantly associated with having an adrenal lesion detected, with an OR of 6.2 (95% CI 3.2-12.3; Table 4). There were no significant differences between the FAP, AFAP and MAP subgroups.
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b le 2 . P at ie nt s w it h no n-re se ct ed a d re na l l es io ns w it h im ag in g si gn s su sp ic io us o f a m al ig na nt le si o n Pa ti en t G en d er Po ly p o si s A g e (y rs ) Ad re n al les io n s iz e (c m ) Su sp ic io us s ig n s o n s ca n C o m m en ts 1 M al e FA P 66 3. 6 C al ci fic at io n St ab le si ze a nd H U <1 0 o n pla in C T, t he re fo re n o in te rv en ti o n o r fo llo w -u p p er fo rm ed 2 M al e FA P 33 3. 6 -H U <1 0 o n pl ai n C T. P at ie nt is in su rv ei lla nc e, fo llo w -u p im ag in g no t ye t p er fo rm ed 3 M al e FA P 69 4. 5 - (b ut n o p la in C T p er fo rm ed ) Pa ti en t is in s ur ve ill an ce , fo llo w -u p im ag in g no t ye t p er fo rm ed 4 M al e FA P 73 5. 7 H et er o ge ne o us c o nt ra st u pt ak e, H U >1 0 o n pla in C T W as h-o ut o n M RI n o t p er fo rm ed . R ef er re d fo r su rg er y, b ut n o t o p er at ed d ue to s ev er e co m o rb id it ie s. A liv e af te r 3. 6 ye ar s o f fo llo w -u p 5 Fe m al e FA P 83 3. 1 C al ci fic at io ns ( no p la in C T p er fo rm ed ) D ue to h igh a ge n o in te rve nt io n o r fo llo w -u p p er fo rm ed 6 M al e M A P 43 3. 4 H U >1 0 o n pl ai n C T, w as h-o ut < 60 % o n M RI C T-gu id ed b io ps y at te m pt ed , b ut r ad io lo gi c w in do w in su ffi ci en t fo r bi o ps y. U nd er s ur ve ill an ce , f o llo w -u p im ag in g no t ye t p er fo rm ed 7 M al e FA P 34 1.9 , 1 .6 (u ni la te ra l) H U >1 0 o n pla in C T W as h-o ut o n M RI n o t p er fo rm ed . P at ie nt d ec ea se d, n o t re la te d to a dr en al le si o n 8 Fe m al e FA P 61 1. 7 H U >1 0 o n pla in C T W as h-o ut o n M RI n o t p er fo rm ed . P at ie nt d ec ea se d, n o t re la te d to a dr en al le si o n 9 M al e FA P 63 1. 5 H U >1 0 o n pl ai n C T W as h-o ut o n M RI n o t p er fo rm ed . P at ie nt r ef er re d el se w he re9
d I S C u S S I O N
Now that survival in patients with adenomatous polyposis is prolonged due to better diagnosis, treatment and surveillance options, extra-intestinal manifestations may become more clinically relevant. To optimize screening and surveillance strategies, more knowledge on extra-intestinal findings is needed. In this historical cohort study, we found that adrenal lesions are frequently identified in patients with adenomatous polyposis who undergo abdominal imaging: up to a quarter of patients with FAP, AFAP or MAP had at least one adrenal lesion, compared to one in 20 in a reference group. In polyposis patients, lesions were most likely to be detected around the age of 50 and most remained stable or exhibited slow growth after follow-up of
Table 4. Logistic regression analysis
Risk factor OR (95% CI) multivariablea
Age in yearsb 1.26 (1.07-1.48)
Age in years (squared)b 0.998 (0.996-0.999)
Male sex 1.37 (0.70-2.69) Polyposisc FAP AFAP MAP 6.23 (3.16-12.30)d 7.00 (3.39-14.48) 3.02 (0.59-15.59) 5.64 (1.75-18.23)
a OR calculated with a multivariable logistic regression model; dependent variable was detection of an adrenal lesion
b Quantitative variables are treated as such in the multivariable model c FAP, AFAP, MAP combined
d No significant differences between AFAP, FAP and MAP were found for this risk (p=0.55 using a Chi square test) Table 3. Characteristics of polyposis patients and reference group
FAP, AFAP, MAP Reference group P-value
Number 122a 298
Mean age in years (range) 46.7 (2.0-85.6) 46.9 (19.0-94.5) 0.91b
Males 68 (55.7%) 129 (43.3.%) 0.02c
Adrenal lesions, n
Males
Mean age in years (range)
30 (24.6%) 17 (56.7%) 50.7 (17.1-83.3) 15 (5.0%) 9 (60%) 53.0 (42.2-68.7) <0.001 c 0.81c 0.58b
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more than 3 years. Only 2 of 30 patients had a known hyperfunctioning lesion. Four lesions were resected, of which three appeared benign upon resection and one was oncocytic with uncertain malignant potential.
This cohort study is among the largest to evaluate the frequency, characteristics and long-term follow-up of adrenal lesions in patients with FAP, and the first in patients with AFAP and MAP. By revising imaging of all identified lesions we created a uniform description of these findings. Moreover, we could put our results into perspective by comparing them to a reference group, which has never been done before. Although the reference group did not reflect the general population, acute abdominal pain is most likely not a risk factor for adrenal lesions.
Due to the character of this study, several limitations need to be acknowledged. The actual number included is relatively small, which limits the precision of our estimates. Furthermore, as patients were not routinely screened for adrenal lesions, we could only report the detection date of adrenal lesions instead of the date when lesions developed. The differences in age at detection might therefore also reflect the timing of execution of the radiological examination. Thirdly, both enhanced and unenhanced CT scans and regular MRI scans were used. As a consequence, several uncertainties regarding the radiologic etiology of lesions remain. However, in most cases this involved uncertainties in furthermore non-suspicious lesions. Similarly, not all lesions with suspicious aspects on imaging were resected, and therefore their histologic etiology is yet unknown. None of these patients is known to have developed clinical signs of an adrenocortical carcinoma. Another limitation is that hormonal testing has not yet been done in all patients, which could have led to an underestimation of the number of hyperfunctioning lesions. Another factor that could influence our results is that the majority of polyposis patients, both with and without adrenal lesions, had extra-colonic manifestations such as desmoids. As was previously suggested, there might be an association between desmoids and adrenal lesions, which could have led to an overestimation of our findings.6, 7, 16
We could also not evaluate if family clustering occurred, as family history on adrenal lesions was not routinely collected. Neither do we know if included patients were kin. However, a previous study did not find signs of familial susceptibility.8
The prevalence of lesions we found is higher than reported in two previous studies.6, 7 Marchesa
et al retrospectively evaluated the frequency of adrenal lesions in 162 FAP patients who had undergone an abdominal CT scan for several indications and reported an incidentaloma prevalence of 7.4%.6 In a prospective study by Smith et al, 13% of 107 FAP patients were found to
have an adrenal lesion on a screening CT.7 Both studies were performed in the nineties, which
might explain the lower prevalence; evolving imaging techniques have made it more likely to identify incidentalomas over the last decades. Moreover, the risk of adrenal lesions increases with age.11, 17 As FAP patients in our study were older than screened patients in the study by
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Smith et al, this could explain why prevalence was higher in our study. A final explanation for these differences could be that we only included patients who had undergone abdominal imaging, which could have led to selection bias. The frequency of patients with adrenal lesions as a proportion of all polyposis patients, including those without imaging, would be 11% (30 in 269 patients). However, it is unlikely that none of the patients without abdominal imaging had an adrenal lesion, as these are usually incidental asymptomatic findings and the proportion in those patients would be at least 4% as found in the general population.
Despite these differences, it seems clear that risks are significantly elevated compared to the general population. In healthy persons, the prevalence of CT-detected incidentalomas is about 4%, which was confirmed in our reference group, and increasing to 7% in patients over 70 years of age.11, 17 In the general population, these lesions are found more frequently in
women, which is probably the result of referral bias.18, 19 We did not find such a female preference
in polyposis patients.
The majority (18/23) of FAP and all AFAP patients with an adrenal lesion had a genetically proven syndrome whereas others had a phenotypical syndrome. This is in line with findings by Will et al, who also reported that the majority (22/30) of their FAP patients with an adrenal lesion had an APC mutation.8 When selecting only patients with an APC mutation, we found that a similar
proportion (24%) had adrenal lesions. Whether the risk of adrenal lesions is due to the APC mutation is not clear, based on this study, as the group of patients without a mutation was too small to compare findings.
One study has shown that biallelic APC inactivation mediates activation of the Wnt/β-catenin pathway in the adrenal lesions of patients with FAP and several genetic mutations could be related to developing multiple and bilateral adrenal adenomas, although data are conflicting.4, 8, 12
The distribution of germline mutations in our patients seemed similar to that of a general population of FAP patients and therefore no clear genotype-phenotype correlation in FAP patients with adrenal lesions was present in our cohort.
We did not find evidence of phaeochromocytomas, adrenocortical carcinomas or other non-adenomatous etiologies in our patients, which is in line with the fact that to date only a few cases of adrenocortical cancer and phaeochromocytomas in patients with FAP have been described.6, 8, 12, 19-24 Regarding the follow-up of lesions in patients with FAP, we found that half of
the lesions remained stable and the other half minimally progressed after a median follow-up of nearly 4 years. This slow progression was confirmed in another study by Will et al, with a follow-up of 113 months, demonstrating a growth rate of 1.35 mm per year compared to 1.2 mm in our study, which could imply that adrenal lesions were present several years before their detection.8
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How should we interpret our findings and what is the clinical significance? We believe our results can help to determine if, how and when screening and surveillance for adrenal lesions should be performed in polyposis patients. Based on our findings it seems that adrenal lesions in these patients probably follow a benign and slowly progressive course, are mostly non-hyperfunctioning and do not lead to mortality. Despite the higher frequency, active screening for these lesions therefore does not seem indicated but once detected, we suggest surveillance and treatment recommendations similar to those for the general population, as previously proposed in a management schema by Will et al.8 We give similar recommendations to patients
with AFAP and MAP, although data are limited. To fill the remaining gaps in our knowledge, more long-term follow-up studies are needed in patients with adrenal lesions representing all polyposis subtypes, preferably with repetitive hormonal testing and appropriate imaging.
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