Cellular angiofibroma is a rare benign mesenchymal tumour of middle-aged adults. This tumour is usually located in the vulvovaginal or inguinoscrotal region. This report describes the case of a patient with a 3.5 cm subcutaneous mass, 2 cm below the left anterior superior iliac spine. Grossly, the mass had tan-white cut surface with a 1.5 cm tan-yellow, whorled, well-delineated nodule. Histologically, the tumour was composed primarily of cytologically bland spindle cells set in a collagenous stroma, with multiple dilated vessels. Other areas showed an abrupt transition to hypercellular sarcomatous elements, including pleomorphic cells with high mitotic activity. The tumour cells were diffusely positive for vimentin and factor XIIIa, and weakly positive for CD34. The patient did not develop any recurrences or metastases, and expired 3 years later of metastatic poorly differentiated carcinoma of unknown origin. This is believed to be the first reported case of sarcomatous transformation in a cellular angiofibroma.
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Cellular angiofibroma is a rare mesenchymal tumour that was first described in 1997.1 The term “cellular angiofibroma” was coined by Nucci et al to emphasise the two principal components of this tumour: a proliferation of uniform, bland, spindled cells set in a collagenous stroma with numerous thick-walled and often hyalinised blood vessels.1 Subsequently, several similar cases have been reported, most of which occurred in the vulvovaginal or inguinoscrotal region,2 ,3 ,4 ,5 with rare cases described in the retroperitoneum and subcutaneous tissue of the chest.6 ,7 In 2004, Iwasa and Fletcher described a series of 51 cases of cellular angiofibroma to further characterise its clinicopathological and immunohistochemical features.3 All of the tumours showed the classical morphology without any significant nuclear atypia or abnormal mitosis. Sixty per cent of the cases expressed CD34, 21% expressed smooth muscle actin, and 8% were immunoreactive for desmin. S-100 protein was negative in all cases.
Since its original description, cellular angiofibroma has been known for its benign behaviour and lack of metastatic potential. A single case exhibited local recurrence 6 months after the original tumour had been resected.8 Herein, we report the first case of extragenital cellular angiofibroma with sarcomatous transformation.
A patient presented to his/her primary care physician complaining of a painless subcutaneous mass 2 cm below the left anterior–superior iliac spine. The patient was status post thyroidectomy and appendectomy for benign lesions. Otherwise, the past medical history was unremarkable. The clinical impression was that of a lipoma. The patient was referred to surgery and the mass was excised under local anaesthetic and sent to the surgical pathology department at Fletcher Allen Hospital, University of Vermont, for evaluation.
The soft tissue excision consisted of a 3.5×3.0×2.3 cm specimen with a predominantly tan-white and firm cut surface. Eccentrically located within this tissue was a tan-yellow, whorled, well-delineated nodule measuring 1.5 cm in greatest dimension; the nodule was entirely submitted for paraffin-embedded sections with routine H&E staining. Sections were cut at 5 μm thickness. Select tissue blocks were submitted for immunohistochemical studies for the following antibodies: vimentin (V9; Dako, Carpinteria, California, USA), factor XIIIa (polyclonal; Biogenex, San Ramon, California, USA), CD34 (MY10; Becton-Dickinson, Franklin Lakes, New Jersey, USA), keratin (AE1-AE3; Chemicon International, Temecula, California, USA), S-100 protein (polyclonal; Dako), α-smooth muscle actin (IA4; Sigma-Aldrich, St Louis, Missouri, USA), desmin (33; Biogenex), cytokeratin (CK)7 (OV-TL; Dako), CK20 (K520.8; Dako) and thyroid-transcription factor (8G7G3/1; Dako). All reagent performance characteristics have been optimised by the histology laboratory at Fletcher Allen Health Care. Positive and negative controls were performed and stained appropriately.
Histologically, the tumour was primarily composed of cytologically bland spindle cells set in a collagenous stroma, with a proliferation of small to medium-sized dilated vessels with variably hyalinised walls (fig 1). Present in these areas, were scattered, somewhat atypical cells. Other areas showed an abrupt transition to hypercellular sarcomatous elements (fig 2), including pleomorphic cells with readily identified mitotic figures (fig 3). Immunohistochemically, the tumour cells were diffusely positive for vimentin and factor XIIIa, with weak focal positivity for CD34. Keratin AE1-AE3, S-100 protein, smooth muscle actin and desmin were all negative in both components. The resection margins of the initial excision were positive, and a subsequent wide re-excision approximately 1 month later showed no residual tumour. The patient had been free of disease recurrence and metastases for 27 months when (s)he started complaining of severe persistent headaches and neck pain. MRI tests revealed brain and cervical spine lesions, as well as apical lung lesion. Fine needle aspiration (FNA) of the lung lesion was positive for poorly differentiated malignant cells. The cells were highly pleomorphic with some resemblance to the sarcomatous cells. Due to the overlapping morphological features between the two specimens, a panel of immunocytochemistry was performed to distinguish a second primary from a metastatic sarcoma. The malignant cells depicted in the FNA specimen showed diffuse strong positivity for CK7 and focal but strong positivity for CK20, while the sarcoma cells were negative for both markers. Additionally, thyroid transcription factor-1, vimentin and factor XIIIa (the latter two were strongly positive in the sarcoma cells) were all negative in the FNA specimen. Although the immunocytochemical features excluded the possibility of metastatic sarcoma, it failed to identify the primary origin of the carcinoma. Furthermore, the patient developed biopsy-proven, subcutaneous metastases that were morphologically identical to the carcinoma cells. The patient was treated with palliative radiotherapy until (s)he expired 1 year later (3 years after the original diagnosis of sarcoma).
Cellular angiofibroma is a rare soft tissue tumour that was originally described in the vulvovaginal or inguinoscrotal region of middle-aged adults.1 Although most cases exhibit the classically described histological features, some have been reported to exhibit unusual features, including a haemangiopericytoma-like pattern, admixed adipose tissue, stromal mast cells and lymphoid aggregates, scattered multinucleated cells, as well as hypocellular hyalinised and myxoid areas.4 One case was reported to exhibit focal areas of marked cellular atypia reminiscent of symplastic change within a uterine leiomyoma,4 while another containing small leiomyomatous nodules has been recently described.9
In the vulvovaginal area, these tumours show overlapping morphological and immunophenotypical features with other mesenchymal lesions that occur at this site; these lesions include superficial myofibroblastoma and angiomyofibroblastoma. These neoplasms are almost always positive for oestrogen and progesterone receptors, suggesting that they all arise from the hormone-receptor-positive subepithelial mesenchymal layer within the lower female genital tract.10 Further, a molecular study performed on two cases of cellular angiofibroma demonstrated deletion of chromosome 13q14 region in one case and monoallelic loss in the other one.11 This finding suggests a genetic relationship with spindle cell lipoma and extramammary myofibroblastoma, which have also been shown to exhibit loss of 13q region. Interestingly, sarcomatous transformation has also been reported in vulvar angiomyofibroblastoma,10 providing further evidence to the link between these tumours.
To our knowledge, this represents the first reported case of sarcomatous transformation in a cellular angiofibroma. Although the significance of this finding is unclear, documentation of malignant transformation in this benign lesion is important, and additional cases are necessary to elucidate the prevalence and implications of this finding.
This report describes an unusual case of an extragenital cellular angiofibroma.
Cellular areas with marked pleomorphism, atypia and mitosis were present, consistent with sarcomatous transformation; this finding has not been previously described in cellular angiofibromas.
The patient was disease free for 27 months and died of a second malignancy.
The implication of this finding in cellular angiofibroma is unknown.
The authors would like to thank Dr Christopher Fletcher at Brigham and Women’s Hospital, Harvard Medical School, for providing consultation on this case.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.