Aggressive angiomyxoma: a clinicopathological and immunohistochemical study of 11 cases with long-term follow-up.
OBJECTIVE
To report the clinicopathological and immunohistochemical features and longer term biological behaviour of aggressive angiomyxoma, an uncommon mesenchymal neoplasm occurring predominantly in the pelvi-perineal region of adults. Using immunohistochemistry, possible overexpression of CDK4 and MDM2 was analysed, which might point to (cyto)genetic alteration(s) in chromosome region 12q13-15, an area reported to be altered in this tumour entity.


RESULTS
Cases (n=11) of aggressive angiomyxoma were retrieved from the consultation files of the Comprehensive Cancer Centre of the Middle Netherlands (IKMN) panel for soft tissue tumours. Clinical and follow-up information were obtained, and immunohistochemical analysis was performed using antibodies directed against vimentin, cytokeratin AE1/AE3, desmin, alpha-smooth-muscle actin, CD34, S-100 protein, oestrogen receptors, CDK4 and MDM2. Five patients were female (age range 24-47 years; median 39 years), and six patients were male (age range 36-69 years; median 44.5 years). Of 11 cases, 10 arose in the pelvi-perineal area and 1 arose in the abdominal cavity in close relation to the bladder. Morphology was consistent with previous reports of this entity. Immunohistochemically, 8 of 11 cases were desmin positive (5 of 5 positive in females; 3 of 6 positive in males), 6 of 11 cases were positive for alpha-smooth-muscle actin, 5 of 11 cases were CD34 positive, 11 of 11 cases, irrespective of gender, were positive for oestrogen receptors and 3 of 11 cases were positive for cytokeratin AE1/AE3. Strong, diffuse nuclear positivity for CDK4 expression was present in all 6 cases tested, while only 1 of 11 cases tested for MDM2 showed weak focal positivity. Clinical follow-up in all cases (range 1-216 months; median 72 months) showed one local recurrence (9%) after 36 months. No metastases or tumour-related deaths were noted.


CONCLUSIONS
The sex distribution of cases reported in this study was roughly equal, in contrast to previous reports emphasising the predominance of this tumour in females. Our study confirms the local aggressive nature of aggressive angiomyxoma, although our local recurrence rate is lower than previous reports (9% versus 36-72%); no metastases and/or disease-related patient deaths were documented. All cases arising in females were positive for desmin, while three of the six cases arising in males were negative for desmin, supporting previous findings and indicating that the lesion may be somewhat different in males. The strong diffuse positivity for CDK4 in all six cases tested goes some way in implicating CDK4, either directly or indirectly, in tumourigenesis. The negative immunostaining for MDM2 would argue against functional amplification of this gene.
van Roggen
J F Graadt
JF
Department of Pathology, Leiden University Medical Centre, Building I, L1-Q, P.O. Box 9600, 2300RC, Leiden, The Netherlands.
van Unnik
J A M
JA
Briaire-de Bruijn
I H
IH
Hogendoorn
P C W
PC
D000199:Actins / Q000032:analysis; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000032:analysis; D003893:Desmin / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009232:Myxoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology*; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D009687:Nuclear Proteins / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D051736:Proto-Oncogene Proteins c-mdm2; D011960:Receptors, Estrogen / Q000032:analysis; D012727:Sex Characteristics
D000199:Actins; D018952:Antigens, CD34; D003893:Desmin; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D011960:Receptors, Estrogen; D007633:Keratins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases
Histopathology. 1999 Oct;35(4):291-312
10564384
Cancer Genet Cytogenet. 1996 Jul 1;89(1):61-4
8689613
Hum Pathol. 1985 Jun;16(6):621-8
3997139
N Engl J Med. 1999 Dec 2;341(23):1772
10610453
Am J Surg Pathol. 1992 Nov;16(11):1059-65
1471726
Am J Clin Pathol. 1995 Oct;104(4):391-6
7572787
Genes Chromosomes Cancer. 1998 Nov;23(3):203-12
9790500
Genes Chromosomes Cancer. 2001 Oct;32(2):172-6
11550285
Nat Genet. 1995 Aug;10(4):436-44
7670494
Hum Pathol. 2003 Oct;34(10):1072-4
14608546
Am J Clin Pathol. 1998 Mar;109(3):251-61
9495195
Am J Surg Pathol. 1983 Jul;7(5):463-75
6684403
Am J Pathol. 1998 Feb;152(2):431-5
9466569
Histopathology. 1997 Jan;30(1):3-10
9023551
Cancer. 1996 Jul 1;78(1):79-90
8646730