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Cellular angiofibroma with atypia or sarcomatous transformation – case description with literature review

Introduction

Cellular angiofibroma (CAF) is a rare, benign, mesenchymal tumor. It occurs equally in men and women and occurs predominantly in the vulvo-vaginal region of middle-aged females or the inguino-scrotal location of older males. Clinically, it can easily be mistaken for a scrotal hernia. Sporadic cases occurring in the chest wall and retroperitoneum have been reported. It was first described by Nucci et al. in 1997 and then in 1998 by Laskin [1, 2]. Rare, atypical nuclear features have been reported in the histopathology of cellular angiofibroma [3]. Only one case of the scrotal cellular angiofibroma with prominent nuclear atypia has been reported to date [4]. We present a case of a 71-year-old male with a tumor attached to the spermatic cord showing the appearance of cellular angiofibroma. In addition, multiple scattered atypical cells were present.

Case report

A 71-year-old male was referred to the Bielanski Hospital in Warsaw, Poland, with a three months’ history of a slowly growing nodule in the right groin. The patient had right inguinal hernia repair in his childhood. At the time of admission to the hospital, ultrasound revealed a well-circumscribed, solid, highly vascularized, hypoechoic tumor mass measuring 5.8 cm in the largest dimension, attached to the spermatic cord. In addition, there was a small amount of fluid in the right scrotum. The patient underwent a right orchiectomy with the excision of the tumor together with a segment of the spermatic cord. Gross examination showed a well-circumscribed, solid, grey, glossy tumor measuring 6 × 4.5 × 4 cm which appeared to be attached to the spermatic cord. The testis and epididymis were grossly unremarkable. Microscopic examination of the tumor showed a spindle cell lesion with a loose, myxoid, partly collagenized stroma, numerous, prominent vessels with thick, partly hyalinized walls. Scattered atypical mononuclear and multinuclear cells were present. The microscopic images are presented in Figure 1 (A-F). The immunohistochemical studies showed: CD34 (+), desmin (+/–), S100 (–), SMA (–), HHF35 (–), Ki67 (10%).

Discussion

Cellular angiofibroma occurs equally in men and women in the inguino-scrotal and vulvo-vaginal region, respectively. Histologically, cases of CAF show a heterogeneous appearance. They range from lesions with myxoid stroma to tumors exhibiting collagenized stroma. The tumor cells are usually bland spindle to oval and epithelioid cells. Prominent vascular channels with thick hyalinized walls are characteristically present in all lesions. Interestingly, there is a morphologic, immunohistochemical and cytogenetic similarity between three lesions described as separate entities: cellular angiofibroma, spindle cell lipoma and extra-mammary myofibroblastoma. It is postulated that these three entities can be in fact a morphological spectrum of one type of neoplasm [5, 6]. Occasionally, the tumor shows scattered atypical cells with nuclear hyperchromasia, nuclear irregularity as well as multinuclear atypical cells. There are single cases with sarcomatous nodules in the otherwise typical cellular angiofibroma. The cases with atypical or sarcomatous features are designated as cellular angiofibroma with atypia or sarcomatous transformation (CAS). There has been only one series of 13 cases of CAS published to date [4]. The series included 11 females with lesions of the vulva, 1 female with a hip lesion and one 26-year-old male with a paratesticular tumor. We present in this article the case of a 71-year-old man with the tumor attached to the spermatic cord. The tumor shows an appearance of cellular angiofibroma with atypia as part of the spectrum of CAS morphology. The age of our patient is in the age range of CAF.

Immunohistochemistry of CAF has been evaluated in several studies. The tumor shows frequently CD34 positive staining. It is variably positive for smooth muscle actin and desmin. There is a negative staining with S100, caldesmon, pancytokeratin and CD31 [7, 8]. Our case showed a positive staining with CD34, focal positive staining with smooth muscle actin and was negative for desmin and S100.

Recent cytogenetic and molecular studies of CAF revealed, in a few reported cases, the loss of RB1 and FOXO1A1 genes due to the deletion of the 13q14 region [9-11].

Differential diagnosis of CAF includes aggressive angiomyxoma, angiomyofibroblastoma, solitary fibrous tumor and schwannoma. Aggressive angiomyxoma shows a less prominent vascular pattern than CAF and exhibits positive desmin staining. Solitary fibrous tumor has areas with the staghorn vascular pattern and dense collagenous stroma. Schwannoma shows characteristic nuclear palisading and is immunohistochemically S100 positive. Well-differentiated liposarcoma (WD-LPS) is the main differential diagnosis of cellular angiofibroma with atypia or sarcomatous transformation (CAS). Moreover, the inguino-scrotal region is one of the most common locations where WD-LPS can occur. It is difficult to distinguish CAS and WD-LPS or another type of sarcoma due to the presence of cells with prominent nuclear atypia. It appears that histological features characteristic of CAF in the lesion next to the CAS nodules or presence of scattered atypical cells among characteristic cellular angiofibroma appearance might help to reach the final diagnosis.

Cellular angiofibroma behaves in a benign fashion and the surgical excision is a treatment of choice. All cases of CAS published by Chen et al. had a favorable prognosis according to follow-up information [4]. There were no cases of metastatic disease; no evidence of recurrence has been noted. One patient died of the metastatic carcinoma of unknown primary origin. In our case, six months after diagnosis, there have not been any signs and symptoms of the recurrence or metastasis in our case.

Table I presents a summary of the literature review which includes a presentation of all cases of CAS reported to date [1-15].

References

 1. Nucci MR, Granter SR, Fletcher CD. Cellular angiofibroma: a benign neoplasm distinct from angiomyofibroblastoma and spindle cell lipoma. Am J Surg Pathol 1997; 21: 636-644.

 2. Laskin WB, Fetsch JF, Mostofi FK. Angiomyofibroblastoma like tumor of the male genital tract. Analysis of 11 cases with comparison to female angiomyofibroblastoma and spindle cell lipoma. Am J Surg Pathol 1998; 22: 6-16.

 3. Kandil DH, Kida M, Laub DR, Cooper K. Sarcomatous transformation in a cellular angiofibroma: a case report. J Clin Pathol 2009; 62: 945-947.

 4. Chen E, Fletcher CD. Cellular angiofibroma with atypia or sarcomatous transformation: clinicopathologic analysis of 13 cases. Am J Surg Pathol 2010; 34: 707-714.

 5. Flucke U, van Krieken JH, Mentzel T. Cellular angiofibroma: analysis of 25 cases emphasizing its relationship to spindle cell lipoma and mammary-type myofibroblastoma. Mod Pathol 2011; 24: 82-89.

 6. Fritchie KJ, Carver P, Sun Y, et al. Solitary fibrous tumor: is there a molecular relationship with cellular angiofibroma, spindle cell lipoma, and mammary-type myofibroblastoma? Am J Clin Pathol 2012; 137: 963-970.

 7. Kairi-Vassilatou E, Dastamani C, Vouza E, et al. Angiomyofibroblastoma of the vulva: a clinicopathological and immunohistochemical analysis of a rare benign mesenchymal tumor. Eur J Gynaecol Oncol 2011; 32: 353-355.

 8. Iwasa Y, Fletcher CD. Cellular angiofibroma: clinicopathologic and immunohistochemical analysis of 51 cases. Am J Surg Pathol 2004; 28: 1426-1435.

 9. Chen BJ, Marin~o-Enríquez A, Fletcher CD, Hornick JL. Loss of retinoblastoma protein expression in spindle cell/pleomorphic lipomas and cytogenetically related tumors: an immunohistochemical study with diagnostic implications. Am J Surg Pathol 2012; 36: 1119-1128.

10. Maggiani F, Debiec-Rychter M, Vanbockrijck M, Sciot R. Cellular angiofibroma: another mesenchymal tumour with 13q14 involvement, suggesting a link with spindle cell lipoma and

(extra)-mammary myofibroblastoma. Histopathology 2007; 51: 410-412.

11. Magro G, Righi A, Casorzo L, et al. Mammary and vaginal myofibroblastomas are genetically related lesions: fluorescence in situ hybridization analysis shows deletion of 13q14 region. Hum Pathol 2012 May 9 [Epub ahead of print].

12. Dikaiakos P, Zizi-Sermpetzoglou A, Rizos S, Marinis A. Angiofibroma of the spermatic cord: a case report and a review of the literature. J Med Case Rep 2011; 5: 423.

13. Sabah M, Mohan P, Kay E. Para-testicular cellular angiofibroma: a rare tumour in a male renal transplant patient. Virchows Arch 2006; 449: 489-492.

14. Samaratunga H, Fitzpatrick P. Cellular angiofibroma of the scrotum. Pathology 2008; 40: 330-333.

15. Koo PJ, Goykhman I, Lembert L, Nunes LW. MRI features of cellular angiomyofibroma with pathologic correlation. J Magn Reson Imaging 2009; 29: 1195-1198.



Address for correspondence



Konrad Ptaszyński



Department of Pathology

Medical Centre for Postgraduate Education and Bielanski Hospital

ul. Marymoncka 99

02-813 Warsaw

e-mail: konrad.ptaszynski@cmkp.edu.pl