Desmoid tumors – a characterization of patients seen at Mayo Clinic 1976–1999 Taya Fallen 1 , Marcia Wilson 2 , Bruce Morlan 3 and Noralane M Lindor 2 1 Cancer Genetics Program, Department of Medicine, Division of Hematology/Oncology, Northwestern Medical Faculty Foundation, Chicago, IL, USA; 2 Familial Cancer Program, Department of Medical Genetics, Mayo Clinic, Rochester, MN, USA; 3 Cancer Center Statistics, Mayo Clinic, Rochester, MN, USA Received 3 November 2005; accepted in revised form 8 December 2005 Key words: desmoid, desmoid tumors, familial adenomatous polyposis (FAP), FAP risk assessment, hereditary colorectal cancer Abstract Desmoid tumors occur with high frequency in individuals with Familial Adenomatous Polyposis (FAP). Because of this, individuals developing desmoid tumors may be referred for genetic risk assessment. Determining whether a person has a FAP-related desmoid tumor or a sporadic desmoid can be challenging. We sought to characterize the patients who were seen at our institution to determine if there were clinical differences in presentation between FAP- associated and sporadic desmoid tumors. We searched the Mayo Clinic-modified H-ICDA (Hospital adaptation of the International Classification of Diseases) diagnostic codes for all diagnoses of desmoid tumors in patients seen between 1976 and 1999. Charts were reviewed to determine accuracy of diagnosis, age when seen, gender, site of tumor, and presence of polyposis. A total of 454 patients (174 males and 280 females) met the search criterion. Of the 447 patients on whom all data was obtained, 70 had FAP and 377 had no evidence of FAP. The female/male ratio for FAP cases was 1.12 compared to female/male ratio of 1.71 for non-FAP cases. (P = 0.17). Location of development of desmoid tumors was correlated with but not specific for distinguishing FAP from non-FAP desmoids. Abdominal desmoids comprised the majority of FAP desmoids and extra-abdominal desmoids comprised the majority of non-FAP desmoids (P<0.001) but age was not a discriminating factor. Using Bayesian analysis, we demonstrate how these findings can assist genetic professionals in their evaluation of patients with desmoid tumors by providing prior probabilities of FAP based upon clinical presentation. Abbreviations: AFAP: attenuated familial adenomatous polyposis; APC gene: adenomatous polyposis coli gene; FAP: familial adenomatous polyposis; H-IDCA: Hospital adaptation of the International Classification of Dis- eases, adapted for the United States Background Desmoid tumors are locally aggressive but histologically benign neoplasms that are often classified as deep fibromatoses [1]. Despite their non-malignant classifica- tion, the common finding of local infiltration and risk of recurrence following excision leads to a significant increase in morbidity and mortality. Desmoids can occur at the site of any fascia, but they commonly develop at the muscle. Multiple studies have shown that 37–50% occur in the abdominal region [2–5]. The shoulder girdle, chest wall and inguinal regions are the most prevalent extra-abdominal sites. Sporadic desmoid tumors are very rare, estimated to occur in two to five persons per million per year. They account for approximately 0.03% of all neoplasms [6]. In contrast, desmoid tumors form in 3.5–32% of individuals with the autosomal dominant disorder, Familial Adenomatous Polyposis (FAP). Using an FAP desmoid risk of 32%, leads to up to a relative risk of 1067 compared to the general population [7–13]. Desmoids can be found at any age and have been documented from infancy to 67 years [14, 15]. There appears to be a higher incidence of desmoids diagnosed in women, particularly of reproductive age [2–4, 10, 11]. However, the magnitude of the female to male ratio is Correspondence to: Noralane Lindor, MD, Department of Medical Genetics, E7B Mayo Clinic, Rochester, MN 55905, USA. Tel.: +1-507-284- 3750; Fax: +1-507-284-1067; E-mail: [email protected] Familial Cancer (2006) 5:191–194 Ó Springer 2006 DOI 10.1007/s10689-005-5959-5
Desmoid tumors – a characterization of patients seen at Mayo Clinic 1976–1999
Dec 16, 2022
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Desmoid tumors – a characterization of patients seen at Mayo Clinic 1976–1999
Taya Fallen1, Marcia Wilson2, Bruce Morlan3 and Noralane M Lindor2 1Cancer Genetics Program, Department of Medicine, Division of Hematology/Oncology, Northwestern Medical Faculty Foundation, Chicago, IL, USA; 2Familial Cancer Program, Department of Medical Genetics, Mayo Clinic, Rochester, MN, USA; 3Cancer Center Statistics, Mayo Clinic, Rochester, MN, USA
Received 3 November 2005; accepted in revised form 8 December 2005
Key words: desmoid, desmoid tumors, familial adenomatous polyposis (FAP), FAP risk assessment, hereditary colorectal cancer
Abstract
Desmoid tumors occur with high frequency in individuals with Familial Adenomatous Polyposis (FAP). Because of this, individuals developing desmoid tumors may be referred for genetic risk assessment. Determining whether a person has a FAP-related desmoid tumor or a sporadic desmoid can be challenging. We sought to characterize the patients who were seen at our institution to determine if there were clinical differences in presentation between FAP- associated and sporadic desmoid tumors. We searched the Mayo Clinic-modified H-ICDA (Hospital adaptation of the International Classification of Diseases) diagnostic codes for all diagnoses of desmoid tumors in patients seen between 1976 and 1999. Charts were reviewed to determine accuracy of diagnosis, age when seen, gender, site of tumor, and presence of polyposis. A total of 454 patients (174 males and 280 females) met the search criterion. Of the 447 patients on whom all data was obtained, 70 had FAP and 377 had no evidence of FAP. The female/male ratio for FAP cases was 1.12 compared to female/male ratio of 1.71 for non-FAP cases. (P = 0.17). Location of development of desmoid tumors was correlated with but not specific for distinguishing FAP from non-FAP desmoids. Abdominal desmoids comprised the majority of FAP desmoids and extra-abdominal desmoids comprised the majority of non-FAP desmoids (P<0.001) but age was not a discriminating factor. Using Bayesian analysis, we demonstrate how these findings can assist genetic professionals in their evaluation of patients with desmoid tumors by providing prior probabilities of FAP based upon clinical presentation.
Abbreviations: AFAP: attenuated familial adenomatous polyposis; APC gene: adenomatous polyposis coli gene; FAP: familial adenomatous polyposis; H-IDCA: Hospital adaptation of the International Classification of Dis- eases, adapted for the United States
Background
Desmoid tumors are locally aggressive but histologically benign neoplasms that are often classified as deep fibromatoses [1]. Despite their non-malignant classifica- tion, the common finding of local infiltration and risk of recurrence following excision leads to a significant increase in morbidity and mortality.
Desmoids can occur at the site of any fascia, but they commonly develop at the muscle. Multiple studies have shown that 37–50% occur in the abdominal region [2–5]. The shoulder girdle, chest wall and inguinal regions are the most prevalent extra-abdominal sites.
Sporadic desmoid tumors are very rare, estimated to occur in two to five persons per million per year. They account for approximately 0.03% of all neoplasms [6]. In contrast, desmoid tumors form in 3.5–32% of individuals with the autosomal dominant disorder, Familial Adenomatous Polyposis (FAP). Using an FAP desmoid risk of 32%, leads to up to a relative risk of 1067 compared to the general population [7–13].
Desmoids can be found at any age and have been documented from infancy to 67 years [14, 15]. There appears to be a higher incidence of desmoids diagnosed in women, particularly of reproductive age [2–4, 10, 11]. However, the magnitude of the female to male ratio is
Correspondence to: Noralane Lindor, MD, Department of Medical Genetics, E7B Mayo Clinic, Rochester, MN 55905, USA. Tel.: +1-507-284- 3750; Fax: +1-507-284-1067; E-mail: [email protected]
Familial Cancer (2006) 5:191–194 Springer 2006 DOI 10.1007/s10689-005-5959-5
debated. The role of gender with respect to desmoid tumor development in the FAP population is also controversial.
Little has been written comparing the desmoids that arise in patients with FAP with those that arise appar- ently sporadically. Health professionals evaluating iso- lated cases of desmoid tumors in otherwise healthy appearing individuals face a challenge in determining prior probability of FAP, future disease potential and the need for further clinical evaluation or genetic testing. We were interested in determining if there were differences in the presentations of desmoid tumors with respect to gender, age, or tumor site that might help distinguish patients with desmoid tumors in FAP compared to non- FAP-associated desmoid tumors.We also were interested in understanding the proportion of desmoid tumors seen at this tertiary care institution that were FAP-related.
Methods
We searched the Mayo Clinic-modified H-ICDA (Hos- pital adaptation of the International Classification of Disease for the United States) diagnostic codes for all diagnoses of desmoid tumors in patients seen between l976 and 1999. Charts were reviewed to determine the accuracy of diagnosis, age when first seen for desmoid consultation at Mayo Clinic, gender, site of tumor, and presence of polyposis or colon cancer in the patients or their relatives. We cannot be sure that some patients considered to have sporadic disease might not have had undiagnosed or undocumented FAP.
Results
A total of 454 patients comprising 174 males and 280 females met this search criterion. Seven patients (two males and five females) were excluded from analysis due to incomplete data or inability to categorize tumor location. Of the remaining 447 patients (172 males and 275 females), 70 had FAP (15.7%) and 377 had no evidence of FAP. The previously reported predomi- nance of desmoids among women versus males was seen in our study population (61.5% versus 38.5%). Of the male cases, 19.2% had FAP compared to 13.5% of the female cases. Thus, the female/male ratio for FAP cases was 1.12 compared to the female/male ratio of 1.71 for non-FAP cases, suggesting a more equal distribution of desmoids among males and females with FAP. How- ever, this finding was not statistically significant (P=0.17). These data are summarized in Table 1.
Approximately 67% of the desmoids diagnosed in individuals with FAP were in the abdomen, whereas just 11% of the desmoids diagnosed in non-FAP patients were in the abdomen. In contrast, limb desmoids were diagnosed in 34.7% of non-FAP patients and just 1.4% of FAP patients. Overall, abdominal desmoids com- prised the majority of FAP desmoids and extra-abdom- inal desmoids comprised the majority of non-FAP desmoids (P<0.001) (Table 2).
The average ages of desmoid tumor consultation ranged from approximately age 34–40. There were no significant differences in ages between development of desmoids in FAP and non-FAP settings (Table 3).
Comments
We were interested to learn whether there might be clinical features that help distinguish desmoid tumors in FAP from the desmoid tumors that arise sporadically. Although statistically rare, determining the clinical differences between desmoids in these two settings would be of great benefit to genetic counselors and other health care providers. The results of this study indicate that the location of development of desmoid tumors is correlated with but not specific for distin- guishing FAP from non-FAP desmoids (P < 0.001). Abdominal desmoid tumors comprised the majority of FAP desmoids (67%) and extra-abdominal desmoids comprised the majority of non-FAP desmoids (89%).
Multiple studies have found a higher incidence of desmoids diagnosed in women, particularly of repro- ductive age. The magnitude of the female to male ratio is debated and has not been adequately studied within the FAP population. Our study noted a female predomi- nance of desmoid tumors for both FAP and non-FAP desmoids. The female/male ratio was closer to 1 in FAP than non-FAP patients (1.12 versus 1.71) but the difference was not significantly different (P=0.17).
Individuals with FAP have an average age of colo- rectal cancer onset of 39 years, which is almost three decades younger than the average age of colorectal cancer in the general population. Given the significant increased risk of desmoids among individuals with FAP, we were interested in the age of desmoid tumor formation among this same population. We found that the age at presentation was not significantly different between desmoid tumors in patients with FAP versus those without FAP seen at Mayo Clinic.
Genetic testing for FAP is available clinically. Approximately 80–90% of classically affected individ- uals will be found to carry an alteration in the APC gene located on chromosome number 5. The majority
Table 1. Frequency of desmoid tumors in male and female patients stratified by FAP versus non-FAP status.
Non-FAP (%) FAP (%) Total (%)
192 T. Fallen et al.
of affected individuals have a family history of colo- rectal cancer and polyposis, thereby assisting in the diagnosis of FAP in a family. However, it has estimated that up to 33% of affected individuals have de novo mutations within the APC gene and thus, no family history. A positive genetic test can resolve the question of whether or not a person presenting with a desmoid tumor has a causative APC gene mutation but a negative test alone is not reassuring. Similarly, a colon exam showing multiple adenomas can resolve this question, but because of the variable age of development of adenomas, a negative exam, especially at younger ages, is also not reassuring.
The cases of the attenuated form of FAP (AFAP), which is associated with mutations in the 3¢ and 5¢ ends of the APC gene, are especially challenging to diagnosis. Caspari et al. [16] found an association between desm- oid tumor formation and mutations in the 3¢ end of the APC gene, suggesting that individuals who develop desmoids may have less than the classical presentation of the disease. Given that individuals with FAP have up to a 100% risk of colorectal cancer and significant increased risk for additional malignancies throughout their lifetimes, making an accurate diagnosis in this population is essential.
Although age, gender and site do not individually provide much discrimination between FAP and non- FAP, we found the results of our study can be combined
and using Bayesian calculation can be used to estimate institution-specific probabilities that a person presenting with desmoid tumor does or does not have FAP. Examples of Bayesian calculations using our findings are shown in Tables 4 and 5. Using this data, we now have a much more useful tool for counseling patients on the likelihood that they do or do not have FAP. This type of risk assessment can help determine the need for genetic testing and colonoscopic screening in individuals presenting with an apparently isolated desmoid tumor.
These calculations assume that the desmoid cases presenting to Mayo Clinic between 1976 and 1999 are similar to those presenting currently. We have not proven that this is true, so this fact needs to be considered if results are being used for clinical purposes.
In addition, we cannot rule out the possibility that some of the individuals categorized as having sporadic desmoid tumors actually had undiagnosed FAP. Long- term follow up was not available on all patients included in this chart review-based study. Additional prospective studies will be needed to validate these findings through other centers.
Conclusions
We conducted a chart review of all patients who presented to Mayo Clinic between 1975 and 1999 with
Table 2. Frequency of site of desmoid tumor development in non-FAP and FAP patients stratified by site and gender.
Abdominal (%) Limb (%) Trunk (%) Total (%)
Female non-FAP 24 (10.1) 88 (37) 126 (53) 238
Male non-FAP 17 (12.2) 43 (30.9) 79 (56.8) 139
Total non-FAP 41 (10.9) 131 (34.7) 205 (54.4) 377
Female FAP 24 (64.9) 1 (2.7) 12 (32.4) 37
Male FAP 23 (69.7) 0 (0) 10 (30.3) 33
Total FAP 47 (67.1) 1 (1.4) 22 (31.4) 70
Table 3. Average age of diagnosis of desmoid tumors in non-FAP and FAP patients stratified by site and gender.
Abdominal Limb Trunk Average
Female non-FAP 35.8 31 30.4 33.8
Male non-FAP 38.4 30.9 39.4 36.6
Female FAP 42 34 39.4 37.6
Male FAP 39.4 na 40.3 40.3
Table 4. Bayesian calculation using desmoid data to calculate the likelihood that a man presenting with an abdominal desmoid tumor would
have FAP.
Has FAP Does not have FAP
Prior probability (of all desmoids seen at Mayo Clinic) 16% 84%
Conditional probabilities
Abdominal site 47/70=67% 41/377=11%
Joint probability
Desmoid tumors 193
a diagnosis of desmoid tumor to obtain information to inform our counseling of patients presenting for genetic risk assessment because of a diagnosis of a desmoid tumor. Of the 447 patients on whom all study informa- tion was obtained, 15.6% had FAP and in 84.6% of cases, the desmoids were apparently sporadic. There were more females than males in both categories, although the sex distribution was more equal among the FAP-related cases. FAP-associated desmoids were much more likely to be abdominal in location than non- FAP desmoids. The mean ages at consultation, tumor site and gender were not individually useful in distin- guishing FAP-associated desmoids from non-FAP desmoids. However, using a Bayesian approach, condi- tioning on gender and tumor site was useful in estimat- ing the probability that a given individual may have FAP based on the specific experience of our institution. This has the potential to enable geneticists and genetic counselors to provide a more appropriate risk assess- ment regarding the likelihood of FAP, and therefore may impact the recommendation for FAP screening for those with the highest risks.
References
Ges Path 1998; 82: 75–82.
2. Posner MC, Shiu HM, Newsome JL et al. The desmoid tumor.
Not a benign disease. Arch Surg 1989; 124: 191–6.
3. Lopez R, Kemalyann, Moseley HS et al. Problems in diagnosis
and management of desmoid tumors. Am J Surg 1990; 159: 400–3.
4. Reitamo JJ, Pekka H, Nykri E. The desmoid tumor. Incidence,
sex, age, and anatomic distribution in the Finnish population. Am
J Clin Pathol 1982; 77: 665–73.
5. Einstein DM, Tagliabue JR, Desai RK. Abdominal desmoids: CT
findings in 25 patients. Am J Roentgenol 1991; 157: 275–9.
6. Kiel KD, Suit HD. Radiation therapy in the treatment of aggres-
sive fibromatosis (desmoid tumors). Cancer 1984; 54: 2051–5.
7. Naylor EW, Gardner EJ, Richards RC. Desmoid tumours and
mesenteric fibromatosis in Gardner’s syndrome. Arch Surg 1979;
114: 1181–5.
8. Jones IT, Jagelman DG, Fazio VW et al. Desmoid tumors in
familial polyposis coli. Am Surg 1986; 204: 94–7.
9. Bussey HI. Extracolonic lesions associated with polyposis coli.
Proc R Soc Med 1972; 65: 294.
10. Richards RC, Rogers SW, Gardner EJ. Spontaneous mesenteric
fibromatosis in Gardner’s syndrome. Cancer 1981; 47: 597–601.
11. Gurbaz AK, Giardiello FM, Petersen GM et al. Desmoid tumours
in familial adenomatous polyposis. Gut 1994; 35(3): 377–81.
12. Jarviren HJ. Desmoid disease as part of familial Adenomatous
polyposis coli. Acta Chir Scand 1987; 153: 374–83.
13. Lofti AM, Dozois RR, Gordon H et al. Mesenteric fibromatosis
complicating familial Adenomatous polyposis: predisposing fac-
tors and results of treatment. Int J Colorectal Dis 1989; 4: 30–6.
14. Halata MS, Miller J, Stone RK. Gardner syndrome. Early pre-
sentation with a desmoid tumor. Discovery of multiple colonic
polyps. Clin Pediatr 1989; 28: 538–540.
15. Brodsky JT, Gordan MS, Hajdu SI, Burt M. Desmoid tumors of
the chest wall. A locally recurrent problem. J Thorac Card Surg
1992; 104: 900–903.
16. Caspari R, Olschwang S, Friedl W et al. Familial adenomatous
polyposis: desmoid tumours and lack of ophthalmic lesions
(CHRPE) associated with APC mutations beyond codon 1444.
Hum Mol Genet 1995; 4: 337–40.
Table 5. Bayesian calculation using desmoid data to calculate the likelihood that a woman presenting with a desmoid tumor of the limb
would have FAP.
Has FAP Does not have FAP
Prior Probability (of all desmoids seen at Mayo Clinic) 16% 84%
Conditional probabilities
Joint probability
<< /ASCII85EncodePages false /AllowTransparency false /AutoPositionEPSFiles true /AutoRotatePages /None /Binding /Left /CalGrayProfile (None) /CalRGBProfile (sRGB IEC61966-2.1) /CalCMYKProfile (ISO Coated) /sRGBProfile (sRGB IEC61966-2.1) /CannotEmbedFontPolicy /Error /CompatibilityLevel 1.3 /CompressObjects /Off /CompressPages true /ConvertImagesToIndexed true /PassThroughJPEGImages true /CreateJDFFile false /CreateJobTicket false /DefaultRenderingIntent /Perceptual /DetectBlends true /ColorConversionStrategy /sRGB /DoThumbnails true /EmbedAllFonts true /EmbedJobOptions true /DSCReportingLevel 0 /SyntheticBoldness 1.00 /EmitDSCWarnings false /EndPage -1 /ImageMemory 524288 /LockDistillerParams true /MaxSubsetPct 100 /Optimize true /OPM 1 /ParseDSCComments true /ParseDSCCommentsForDocInfo true /PreserveCopyPage true /PreserveEPSInfo true /PreserveHalftoneInfo false /PreserveOPIComments false /PreserveOverprintSettings true /StartPage 1 /SubsetFonts false /TransferFunctionInfo /Apply /UCRandBGInfo /Preserve /UsePrologue false /ColorSettingsFile () /AlwaysEmbed [ true ] /NeverEmbed [ true ] /AntiAliasColorImages false /DownsampleColorImages true /ColorImageDownsampleType /Bicubic /ColorImageResolution 150 /ColorImageDepth -1 /ColorImageDownsampleThreshold 1.50000 /EncodeColorImages true /ColorImageFilter /DCTEncode /AutoFilterColorImages false /ColorImageAutoFilterStrategy /JPEG /ColorACSImageDict << /QFactor 0.76 /HSamples [2 1 1 2] /VSamples [2 1 1 2] >> /ColorImageDict << /QFactor 0.76 /HSamples [2 1 1 2] /VSamples [2 1 1 2] >> /JPEG2000ColorACSImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /JPEG2000ColorImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /AntiAliasGrayImages false /DownsampleGrayImages true /GrayImageDownsampleType /Bicubic /GrayImageResolution 150 /GrayImageDepth -1 /GrayImageDownsampleThreshold 1.50000 /EncodeGrayImages true /GrayImageFilter /DCTEncode /AutoFilterGrayImages true /GrayImageAutoFilterStrategy /JPEG /GrayACSImageDict << /QFactor 0.76 /HSamples [2 1 1 2] /VSamples [2 1 1 2] >> /GrayImageDict << /QFactor 0.15 /HSamples [1 1 1 1] /VSamples [1 1 1 1] >> /JPEG2000GrayACSImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /JPEG2000GrayImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /AntiAliasMonoImages false /DownsampleMonoImages true /MonoImageDownsampleType /Bicubic /MonoImageResolution 600 /MonoImageDepth -1 /MonoImageDownsampleThreshold 1.50000 /EncodeMonoImages true /MonoImageFilter /CCITTFaxEncode /MonoImageDict << /K -1 >> /AllowPSXObjects false /PDFX1aCheck false /PDFX3Check false /PDFXCompliantPDFOnly false /PDFXNoTrimBoxError true /PDFXTrimBoxToMediaBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXSetBleedBoxToMediaBox true /PDFXBleedBoxToTrimBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXOutputIntentProfile (None) /PDFXOutputCondition () /PDFXRegistryName (http://www.color.org?) /PDFXTrapped /False /Description << /DEU <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> /ENU <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> >> >> setdistillerparams << /HWResolution [2400 2400] /PageSize [2834.646 2834.646] >> setpagedevice
Taya Fallen1, Marcia Wilson2, Bruce Morlan3 and Noralane M Lindor2 1Cancer Genetics Program, Department of Medicine, Division of Hematology/Oncology, Northwestern Medical Faculty Foundation, Chicago, IL, USA; 2Familial Cancer Program, Department of Medical Genetics, Mayo Clinic, Rochester, MN, USA; 3Cancer Center Statistics, Mayo Clinic, Rochester, MN, USA
Received 3 November 2005; accepted in revised form 8 December 2005
Key words: desmoid, desmoid tumors, familial adenomatous polyposis (FAP), FAP risk assessment, hereditary colorectal cancer
Abstract
Desmoid tumors occur with high frequency in individuals with Familial Adenomatous Polyposis (FAP). Because of this, individuals developing desmoid tumors may be referred for genetic risk assessment. Determining whether a person has a FAP-related desmoid tumor or a sporadic desmoid can be challenging. We sought to characterize the patients who were seen at our institution to determine if there were clinical differences in presentation between FAP- associated and sporadic desmoid tumors. We searched the Mayo Clinic-modified H-ICDA (Hospital adaptation of the International Classification of Diseases) diagnostic codes for all diagnoses of desmoid tumors in patients seen between 1976 and 1999. Charts were reviewed to determine accuracy of diagnosis, age when seen, gender, site of tumor, and presence of polyposis. A total of 454 patients (174 males and 280 females) met the search criterion. Of the 447 patients on whom all data was obtained, 70 had FAP and 377 had no evidence of FAP. The female/male ratio for FAP cases was 1.12 compared to female/male ratio of 1.71 for non-FAP cases. (P = 0.17). Location of development of desmoid tumors was correlated with but not specific for distinguishing FAP from non-FAP desmoids. Abdominal desmoids comprised the majority of FAP desmoids and extra-abdominal desmoids comprised the majority of non-FAP desmoids (P<0.001) but age was not a discriminating factor. Using Bayesian analysis, we demonstrate how these findings can assist genetic professionals in their evaluation of patients with desmoid tumors by providing prior probabilities of FAP based upon clinical presentation.
Abbreviations: AFAP: attenuated familial adenomatous polyposis; APC gene: adenomatous polyposis coli gene; FAP: familial adenomatous polyposis; H-IDCA: Hospital adaptation of the International Classification of Dis- eases, adapted for the United States
Background
Desmoid tumors are locally aggressive but histologically benign neoplasms that are often classified as deep fibromatoses [1]. Despite their non-malignant classifica- tion, the common finding of local infiltration and risk of recurrence following excision leads to a significant increase in morbidity and mortality.
Desmoids can occur at the site of any fascia, but they commonly develop at the muscle. Multiple studies have shown that 37–50% occur in the abdominal region [2–5]. The shoulder girdle, chest wall and inguinal regions are the most prevalent extra-abdominal sites.
Sporadic desmoid tumors are very rare, estimated to occur in two to five persons per million per year. They account for approximately 0.03% of all neoplasms [6]. In contrast, desmoid tumors form in 3.5–32% of individuals with the autosomal dominant disorder, Familial Adenomatous Polyposis (FAP). Using an FAP desmoid risk of 32%, leads to up to a relative risk of 1067 compared to the general population [7–13].
Desmoids can be found at any age and have been documented from infancy to 67 years [14, 15]. There appears to be a higher incidence of desmoids diagnosed in women, particularly of reproductive age [2–4, 10, 11]. However, the magnitude of the female to male ratio is
Correspondence to: Noralane Lindor, MD, Department of Medical Genetics, E7B Mayo Clinic, Rochester, MN 55905, USA. Tel.: +1-507-284- 3750; Fax: +1-507-284-1067; E-mail: [email protected]
Familial Cancer (2006) 5:191–194 Springer 2006 DOI 10.1007/s10689-005-5959-5
debated. The role of gender with respect to desmoid tumor development in the FAP population is also controversial.
Little has been written comparing the desmoids that arise in patients with FAP with those that arise appar- ently sporadically. Health professionals evaluating iso- lated cases of desmoid tumors in otherwise healthy appearing individuals face a challenge in determining prior probability of FAP, future disease potential and the need for further clinical evaluation or genetic testing. We were interested in determining if there were differences in the presentations of desmoid tumors with respect to gender, age, or tumor site that might help distinguish patients with desmoid tumors in FAP compared to non- FAP-associated desmoid tumors.We also were interested in understanding the proportion of desmoid tumors seen at this tertiary care institution that were FAP-related.
Methods
We searched the Mayo Clinic-modified H-ICDA (Hos- pital adaptation of the International Classification of Disease for the United States) diagnostic codes for all diagnoses of desmoid tumors in patients seen between l976 and 1999. Charts were reviewed to determine the accuracy of diagnosis, age when first seen for desmoid consultation at Mayo Clinic, gender, site of tumor, and presence of polyposis or colon cancer in the patients or their relatives. We cannot be sure that some patients considered to have sporadic disease might not have had undiagnosed or undocumented FAP.
Results
A total of 454 patients comprising 174 males and 280 females met this search criterion. Seven patients (two males and five females) were excluded from analysis due to incomplete data or inability to categorize tumor location. Of the remaining 447 patients (172 males and 275 females), 70 had FAP (15.7%) and 377 had no evidence of FAP. The previously reported predomi- nance of desmoids among women versus males was seen in our study population (61.5% versus 38.5%). Of the male cases, 19.2% had FAP compared to 13.5% of the female cases. Thus, the female/male ratio for FAP cases was 1.12 compared to the female/male ratio of 1.71 for non-FAP cases, suggesting a more equal distribution of desmoids among males and females with FAP. How- ever, this finding was not statistically significant (P=0.17). These data are summarized in Table 1.
Approximately 67% of the desmoids diagnosed in individuals with FAP were in the abdomen, whereas just 11% of the desmoids diagnosed in non-FAP patients were in the abdomen. In contrast, limb desmoids were diagnosed in 34.7% of non-FAP patients and just 1.4% of FAP patients. Overall, abdominal desmoids com- prised the majority of FAP desmoids and extra-abdom- inal desmoids comprised the majority of non-FAP desmoids (P<0.001) (Table 2).
The average ages of desmoid tumor consultation ranged from approximately age 34–40. There were no significant differences in ages between development of desmoids in FAP and non-FAP settings (Table 3).
Comments
We were interested to learn whether there might be clinical features that help distinguish desmoid tumors in FAP from the desmoid tumors that arise sporadically. Although statistically rare, determining the clinical differences between desmoids in these two settings would be of great benefit to genetic counselors and other health care providers. The results of this study indicate that the location of development of desmoid tumors is correlated with but not specific for distin- guishing FAP from non-FAP desmoids (P < 0.001). Abdominal desmoid tumors comprised the majority of FAP desmoids (67%) and extra-abdominal desmoids comprised the majority of non-FAP desmoids (89%).
Multiple studies have found a higher incidence of desmoids diagnosed in women, particularly of repro- ductive age. The magnitude of the female to male ratio is debated and has not been adequately studied within the FAP population. Our study noted a female predomi- nance of desmoid tumors for both FAP and non-FAP desmoids. The female/male ratio was closer to 1 in FAP than non-FAP patients (1.12 versus 1.71) but the difference was not significantly different (P=0.17).
Individuals with FAP have an average age of colo- rectal cancer onset of 39 years, which is almost three decades younger than the average age of colorectal cancer in the general population. Given the significant increased risk of desmoids among individuals with FAP, we were interested in the age of desmoid tumor formation among this same population. We found that the age at presentation was not significantly different between desmoid tumors in patients with FAP versus those without FAP seen at Mayo Clinic.
Genetic testing for FAP is available clinically. Approximately 80–90% of classically affected individ- uals will be found to carry an alteration in the APC gene located on chromosome number 5. The majority
Table 1. Frequency of desmoid tumors in male and female patients stratified by FAP versus non-FAP status.
Non-FAP (%) FAP (%) Total (%)
192 T. Fallen et al.
of affected individuals have a family history of colo- rectal cancer and polyposis, thereby assisting in the diagnosis of FAP in a family. However, it has estimated that up to 33% of affected individuals have de novo mutations within the APC gene and thus, no family history. A positive genetic test can resolve the question of whether or not a person presenting with a desmoid tumor has a causative APC gene mutation but a negative test alone is not reassuring. Similarly, a colon exam showing multiple adenomas can resolve this question, but because of the variable age of development of adenomas, a negative exam, especially at younger ages, is also not reassuring.
The cases of the attenuated form of FAP (AFAP), which is associated with mutations in the 3¢ and 5¢ ends of the APC gene, are especially challenging to diagnosis. Caspari et al. [16] found an association between desm- oid tumor formation and mutations in the 3¢ end of the APC gene, suggesting that individuals who develop desmoids may have less than the classical presentation of the disease. Given that individuals with FAP have up to a 100% risk of colorectal cancer and significant increased risk for additional malignancies throughout their lifetimes, making an accurate diagnosis in this population is essential.
Although age, gender and site do not individually provide much discrimination between FAP and non- FAP, we found the results of our study can be combined
and using Bayesian calculation can be used to estimate institution-specific probabilities that a person presenting with desmoid tumor does or does not have FAP. Examples of Bayesian calculations using our findings are shown in Tables 4 and 5. Using this data, we now have a much more useful tool for counseling patients on the likelihood that they do or do not have FAP. This type of risk assessment can help determine the need for genetic testing and colonoscopic screening in individuals presenting with an apparently isolated desmoid tumor.
These calculations assume that the desmoid cases presenting to Mayo Clinic between 1976 and 1999 are similar to those presenting currently. We have not proven that this is true, so this fact needs to be considered if results are being used for clinical purposes.
In addition, we cannot rule out the possibility that some of the individuals categorized as having sporadic desmoid tumors actually had undiagnosed FAP. Long- term follow up was not available on all patients included in this chart review-based study. Additional prospective studies will be needed to validate these findings through other centers.
Conclusions
We conducted a chart review of all patients who presented to Mayo Clinic between 1975 and 1999 with
Table 2. Frequency of site of desmoid tumor development in non-FAP and FAP patients stratified by site and gender.
Abdominal (%) Limb (%) Trunk (%) Total (%)
Female non-FAP 24 (10.1) 88 (37) 126 (53) 238
Male non-FAP 17 (12.2) 43 (30.9) 79 (56.8) 139
Total non-FAP 41 (10.9) 131 (34.7) 205 (54.4) 377
Female FAP 24 (64.9) 1 (2.7) 12 (32.4) 37
Male FAP 23 (69.7) 0 (0) 10 (30.3) 33
Total FAP 47 (67.1) 1 (1.4) 22 (31.4) 70
Table 3. Average age of diagnosis of desmoid tumors in non-FAP and FAP patients stratified by site and gender.
Abdominal Limb Trunk Average
Female non-FAP 35.8 31 30.4 33.8
Male non-FAP 38.4 30.9 39.4 36.6
Female FAP 42 34 39.4 37.6
Male FAP 39.4 na 40.3 40.3
Table 4. Bayesian calculation using desmoid data to calculate the likelihood that a man presenting with an abdominal desmoid tumor would
have FAP.
Has FAP Does not have FAP
Prior probability (of all desmoids seen at Mayo Clinic) 16% 84%
Conditional probabilities
Abdominal site 47/70=67% 41/377=11%
Joint probability
Desmoid tumors 193
a diagnosis of desmoid tumor to obtain information to inform our counseling of patients presenting for genetic risk assessment because of a diagnosis of a desmoid tumor. Of the 447 patients on whom all study informa- tion was obtained, 15.6% had FAP and in 84.6% of cases, the desmoids were apparently sporadic. There were more females than males in both categories, although the sex distribution was more equal among the FAP-related cases. FAP-associated desmoids were much more likely to be abdominal in location than non- FAP desmoids. The mean ages at consultation, tumor site and gender were not individually useful in distin- guishing FAP-associated desmoids from non-FAP desmoids. However, using a Bayesian approach, condi- tioning on gender and tumor site was useful in estimat- ing the probability that a given individual may have FAP based on the specific experience of our institution. This has the potential to enable geneticists and genetic counselors to provide a more appropriate risk assess- ment regarding the likelihood of FAP, and therefore may impact the recommendation for FAP screening for those with the highest risks.
References
Ges Path 1998; 82: 75–82.
2. Posner MC, Shiu HM, Newsome JL et al. The desmoid tumor.
Not a benign disease. Arch Surg 1989; 124: 191–6.
3. Lopez R, Kemalyann, Moseley HS et al. Problems in diagnosis
and management of desmoid tumors. Am J Surg 1990; 159: 400–3.
4. Reitamo JJ, Pekka H, Nykri E. The desmoid tumor. Incidence,
sex, age, and anatomic distribution in the Finnish population. Am
J Clin Pathol 1982; 77: 665–73.
5. Einstein DM, Tagliabue JR, Desai RK. Abdominal desmoids: CT
findings in 25 patients. Am J Roentgenol 1991; 157: 275–9.
6. Kiel KD, Suit HD. Radiation therapy in the treatment of aggres-
sive fibromatosis (desmoid tumors). Cancer 1984; 54: 2051–5.
7. Naylor EW, Gardner EJ, Richards RC. Desmoid tumours and
mesenteric fibromatosis in Gardner’s syndrome. Arch Surg 1979;
114: 1181–5.
8. Jones IT, Jagelman DG, Fazio VW et al. Desmoid tumors in
familial polyposis coli. Am Surg 1986; 204: 94–7.
9. Bussey HI. Extracolonic lesions associated with polyposis coli.
Proc R Soc Med 1972; 65: 294.
10. Richards RC, Rogers SW, Gardner EJ. Spontaneous mesenteric
fibromatosis in Gardner’s syndrome. Cancer 1981; 47: 597–601.
11. Gurbaz AK, Giardiello FM, Petersen GM et al. Desmoid tumours
in familial adenomatous polyposis. Gut 1994; 35(3): 377–81.
12. Jarviren HJ. Desmoid disease as part of familial Adenomatous
polyposis coli. Acta Chir Scand 1987; 153: 374–83.
13. Lofti AM, Dozois RR, Gordon H et al. Mesenteric fibromatosis
complicating familial Adenomatous polyposis: predisposing fac-
tors and results of treatment. Int J Colorectal Dis 1989; 4: 30–6.
14. Halata MS, Miller J, Stone RK. Gardner syndrome. Early pre-
sentation with a desmoid tumor. Discovery of multiple colonic
polyps. Clin Pediatr 1989; 28: 538–540.
15. Brodsky JT, Gordan MS, Hajdu SI, Burt M. Desmoid tumors of
the chest wall. A locally recurrent problem. J Thorac Card Surg
1992; 104: 900–903.
16. Caspari R, Olschwang S, Friedl W et al. Familial adenomatous
polyposis: desmoid tumours and lack of ophthalmic lesions
(CHRPE) associated with APC mutations beyond codon 1444.
Hum Mol Genet 1995; 4: 337–40.
Table 5. Bayesian calculation using desmoid data to calculate the likelihood that a woman presenting with a desmoid tumor of the limb
would have FAP.
Has FAP Does not have FAP
Prior Probability (of all desmoids seen at Mayo Clinic) 16% 84%
Conditional probabilities
Joint probability
<< /ASCII85EncodePages false /AllowTransparency false /AutoPositionEPSFiles true /AutoRotatePages /None /Binding /Left /CalGrayProfile (None) /CalRGBProfile (sRGB IEC61966-2.1) /CalCMYKProfile (ISO Coated) /sRGBProfile (sRGB IEC61966-2.1) /CannotEmbedFontPolicy /Error /CompatibilityLevel 1.3 /CompressObjects /Off /CompressPages true /ConvertImagesToIndexed true /PassThroughJPEGImages true /CreateJDFFile false /CreateJobTicket false /DefaultRenderingIntent /Perceptual /DetectBlends true /ColorConversionStrategy /sRGB /DoThumbnails true /EmbedAllFonts true /EmbedJobOptions true /DSCReportingLevel 0 /SyntheticBoldness 1.00 /EmitDSCWarnings false /EndPage -1 /ImageMemory 524288 /LockDistillerParams true /MaxSubsetPct 100 /Optimize true /OPM 1 /ParseDSCComments true /ParseDSCCommentsForDocInfo true /PreserveCopyPage true /PreserveEPSInfo true /PreserveHalftoneInfo false /PreserveOPIComments false /PreserveOverprintSettings true /StartPage 1 /SubsetFonts false /TransferFunctionInfo /Apply /UCRandBGInfo /Preserve /UsePrologue false /ColorSettingsFile () /AlwaysEmbed [ true ] /NeverEmbed [ true ] /AntiAliasColorImages false /DownsampleColorImages true /ColorImageDownsampleType /Bicubic /ColorImageResolution 150 /ColorImageDepth -1 /ColorImageDownsampleThreshold 1.50000 /EncodeColorImages true /ColorImageFilter /DCTEncode /AutoFilterColorImages false /ColorImageAutoFilterStrategy /JPEG /ColorACSImageDict << /QFactor 0.76 /HSamples [2 1 1 2] /VSamples [2 1 1 2] >> /ColorImageDict << /QFactor 0.76 /HSamples [2 1 1 2] /VSamples [2 1 1 2] >> /JPEG2000ColorACSImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /JPEG2000ColorImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /AntiAliasGrayImages false /DownsampleGrayImages true /GrayImageDownsampleType /Bicubic /GrayImageResolution 150 /GrayImageDepth -1 /GrayImageDownsampleThreshold 1.50000 /EncodeGrayImages true /GrayImageFilter /DCTEncode /AutoFilterGrayImages true /GrayImageAutoFilterStrategy /JPEG /GrayACSImageDict << /QFactor 0.76 /HSamples [2 1 1 2] /VSamples [2 1 1 2] >> /GrayImageDict << /QFactor 0.15 /HSamples [1 1 1 1] /VSamples [1 1 1 1] >> /JPEG2000GrayACSImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /JPEG2000GrayImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /AntiAliasMonoImages false /DownsampleMonoImages true /MonoImageDownsampleType /Bicubic /MonoImageResolution 600 /MonoImageDepth -1 /MonoImageDownsampleThreshold 1.50000 /EncodeMonoImages true /MonoImageFilter /CCITTFaxEncode /MonoImageDict << /K -1 >> /AllowPSXObjects false /PDFX1aCheck false /PDFX3Check false /PDFXCompliantPDFOnly false /PDFXNoTrimBoxError true /PDFXTrimBoxToMediaBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXSetBleedBoxToMediaBox true /PDFXBleedBoxToTrimBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXOutputIntentProfile (None) /PDFXOutputCondition () /PDFXRegistryName (http://www.color.org?) /PDFXTrapped /False /Description << /DEU <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> /ENU <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> >> >> setdistillerparams << /HWResolution [2400 2400] /PageSize [2834.646 2834.646] >> setpagedevice
Related Documents
