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Cellular angiofibroma of the vulva: a poorly known entity, a case report and literature review
BMC Clinical Pathology volume 16, Article number: 8 (2016)
Cellular angiofibroma represents a newly described, site specific tumor. Histologically, CAF is a benign mesenchymal neoplasm characterized by two principal components: bland spindle cells and prominent small to medium-sized vessels with mural hyalinization. The indolent nature of the lesion is underscored by the uniformity of its constituent stromal cells, and their lack of nuclear atypia. Characterization by immunohistochemistry is helpful distinguishing Cellular angiofibroma from other mesenchymal lesions.
We report the case of a 37-year-old woman, presenting with a painless nodule involving the vulva. This lesion had gradually increased in size; a simple excision was performed, and follow up was unremarkable. Gross examination showed a well circumscribed, firm tumor measuring 3× 3 × 2,5 cm. Histologically, the tumor was composed of uniform, short spindle-shaped cells, proliferating in an edematous to fibrous stroma and numerous small to medium-sized thick-walled vessels. A panel of immunohistochemical stains was performed, and confirmed the diagnosis of Cellular angiofibroma.
In this report we aim to describe the clinical, pathological and immunohistochemical features of this rare entity through a literature review, and to discuss other vulvar mesenchymal lesions.
Cellular angiofibroma (CAF) is a rare benign mesenchymal lesion with a predilection for the genitourinary region. First described in 1997 , CAF is characterized by a spindle cell component and abundant small- to medium-sized thick-walled vessels . Cases in males have been previously named “angiomyofibroblastoma-like tumor”. Besides two small series, cellular angiofibroma has been described only in isolated case reports, we found only 68 patients with genital CAF (Table 1) [3, 4]. To date, this last condition still remains a poorly known lesion that needs further investigations to closely define its clinical and pathological features.
We report a case of cellular angiofibroma, for which the clinical diagnosis was Bartholin’s glandular cyst.
A healthy 37-year-old woman consulted for an asymptomatic vulvar nodule of 6 years duration. She was concerned because it had progressively enlarged over the last few months. There was no history of pain or bleeding. Local and colposcopic examinations revealed a 3,5 cm freely mobile non reducible nodule located in the left labia majora. Ultrasonography showed a superficial, well-demarcated, solid soft tissue tumor. A well circumscribed lesion measuring 3 cm in diameter was excised with a rim of normal tissue. Gross examination showed a well circumscribed, solid, whitish, glossy tumor measuring 3× 3 × 2,5 cm. Microscopically, the tumor was well circumscribed, surrounded by a fibrous pseudocapsule. On low-power examination, hypocellular and hypercellular areas, composed of uniform, short spindle-shaped cells, proliferating in an edematous to fibrous stroma (Fig. 1). Numerous small to medium-sized thick-walled vessels were also seen (Fig. 2). Mature adipocytes were noted in the periphery in small clusters. There was no necrosis and few or no mitotic figures (Fig. 3). Immunohistochemical staining was positive for vimentin, CD34 (Fig. 4), focally for actin, and negative for protein S-100, and desmin. These findings are consistent with the diagnosis of cellular angiofibroma. At 14 months postoperatively, the patient is doing well with no signs of recurrence.
Tumors primarily arising from the vulvo-vaginal area are relatively rare and they include soft tissue specific and non-specific tumors, as well as a spectrum of fibro-epithelial tumors [5, 6]. Cellular angiofibroma is an uncommon benign mesenchymal neoplasm, originally described in the genital region, and occurs equally in both genders . A marked predilection for the vulva is observed , our review of the literature yielded 68 cases reported, involving the female genital tract (Table 1). Women are affected most often in the fifth decade, whereas males are mainly in the seventh decade . Clinically, cellular angiofibroma is often mistaken for a Bartholin gland, labial, or submucosal cyst .
Etiopathologically, some authors suggested that these lesions are stem cell–derived, with a capacity for adipose and myofibroblastic differentiation in accordance with the influence of hormones, microenvironments, cytokines and growth factors .
Histologically, CAF is typically well circumscribed, composed of two principal components: bland spindle cells and prominent small to medium-sized vessels with mural hyalinization . The spindle cells are arranged in short intersecting fascicles lying between short bundles of wispy collagen . Hypocellular areas can be seen, often associated with stromal edema or hyalinization. Typically, significant pleomorphism and abnormal mitoses were absent . The accompanying blood vessels tend to be thick-walled and even hyalinized . Mature individual or small clusters of adipocytes can be present, most often located in the periphery of the lesion [2, 3]. Fletcher et al. recently have reported a study of 13 cases of cellular angiofibroma with atypia and sarcomatous transformation . The sarcomatous component can show variable features (atypical lipomatous tumor, pleomorphic liposarcoma, and pleomorphic sarcoma). This phenomenon seems not to predispose to recurrence based on limited clinical follow-up available [2, 11].
Immunohistochemically, the tumor cells consistently are vimentin positive . The expression of CD34 is seen in 60 % . Characteristically, they do not express S-100 protein, actin, desmin, or EMA, although a discrete staining for the last three markers has been reported [3, 9]. Lastly, the tumor cells have been found to be estrogen (ER) and progesterone receptor (PR) positive. However, the significance of the positive estrogen and progesterone receptors in CAF is unknown . In fact, a subset of mesenchymal cells of the distal female genital tract normally expresses estrogen and progesterone receptor and, the neoplastic cells arising from the vulva, may also show immunoreactivity for ER and/or PR . Thus, ER or PR immunoreactivity cannot be used to distinguish CAF and its histological mimics 
No specific chromosomal abnormality is found in CAF, although cytogenetic analysis revealed, in a few reported cases, the loss of RB1 and FOXO1A1 genes due to the deletion of the 13q14 region . This typical loss of genetic material is also shared by myofibroblastoma .
CAF, myofibroblastoma and angiomyofibroblastoma are usually considered as specific soft tissue tumors of the vulvo-vaginal area . These tumors may show overlapping morphological, immunohistochemical and cytogenetic features, and thus differential diagnosis is mandatory [17, 15].
Clinically, the age of onset of CAF occurs approximately 10 years later in life than aggressive angiomyxoma, myofibroblastoma and angiomyofibroblastoma . Histologically, aggressive angiomyxoma is poorly circumscribed, typically infiltrates adjacent soft tissue, and characterized by being composed of relatively uniform spindle cells, embedded in a myxoid matrix . AMF is a benign tumor which belongs to the category of the “stromal tumors of the lower female genital tract”, together with cellular angiofibroma and myofibroblastoma . It is characterized by the presence of multinucleate cells and epithelioid or plasmacytoid cells which tend to aggregate around blood vessels which are thin-walled . However recent cytogenetic analyses have shown that only CAF and myofibroblastoma are genetically related lesions because angiomyofibroblastoma lacks 13q14 deletion .
Myofibroblastoma is composed of ovoid- to spindle- or stellate-shaped cells, arranged in a variety of architectural patterns and set in a finely collagenous stroma. Hyalinized blood vessels are a diagnostic clue helpful in distinguishing cellular angiofibroma from myofibroblastoma .
Based on morphological, immunohistochemical and cytogenetic analyses, it has been postulated that CAF and myofibroblastoma of the lower female genital tract are closely related lesions that form a continuous spectrum of a single entity with different morphologic presentations, likely arising from a common precursor mesenchymal cell .
Other neoplasms that are not specific to the vulva, such as solitary fibrous tumour, spindle cell lipoma, smooth muscle tumours, nerve sheath tumours, and perineurioma, also enter into the differential diagnosis .
Spindle cell lipoma is composed of brightly, eosinophilic ropy and refractile stromal collagen bands with fewer capillary-sized thin-walled vessels, compared with palely eosinophilic and wispy collagen fibers associated with numerous thick-walled vessels in CAF [3, 18]. Solitary fibrous tumor (SFT) can be differentiated by the presence of thin-walled branching vascular pattern that may be described as hemangiopericytoma-like vessels, and dense collagen bundles [12, 23]. SFT shows positivity for CD34, CD99, bcl-2, and ER and/or PR, and negativity for SMA and desmin .
Other mesenchymal lesions (schwannoma, perineurioma and leiomyoma) can be ruled out in accordance with the histology and immunohistochemistry .
CAF behaves in a benign fashion and local excision with clear margins is the treatment of choice. This lesion shows no tendency for metastasis based on the limited clinical follow-up available [2, 3, 7]. However, there is one case of recurrent CAF, reported by McCluggage et al., in which a 49-year-old woman had recurrent swelling develop at the site of the previous excision 6 months later . Our patient is well without evidence of local recurrence 20 months after excision.
CAF represents a rare distinct clinico-pathological condition, that pathologists should be aware of morphological variation (Atypia and Sarcomatous transformation) to prevent diagnostic errors and therefore an aggressive therapy. As far as we are aware, no case of metastatic CAF has been described.
AMF, Angiomyofibroblastoma; CAF, Cellular angiofibroma; EMA, Epithelial membrane antigen; ER, estrogen receptor; PR, progesterone receptor.
Nucci MR, Granter SR, Fletcher CD. Cellular angiofibroma: a benign neoplasm distinct from angiomyofibroblastoma and spindle cell lipoma. Am J Surg Pathol. 1997;21(6):636–44.
Val-Bernal JF, Azueta A, Parra A, Mediavilla E, Zubillaga S. Paratesticular cellular angiofibroma with atypical (bizarre) cells: case report and literature review. Pathol Res Pract. 2013;209(6):388–92.
Iwasa Y, Fletcher CD. Cellular angiofibroma: clinicopathologic and immunohistochemical analysis of 51 cases. Am J Surg Pathol. 2004;28(11):1426–35.
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(1):82–9.
McCluggage WG. Recent developments in vulvovaginal pathology. Histopathology. 2009;54(2):156–73.
Kazakov DV, Spagnolo DV, Stewart CJ, Thompson J, Agaimy A, Magro G, Bisceglia M, Vazmitel M, Kacerovska D, Kutzner H, Mukensnabl P, Michal M. Fibroadenoma and phyllodes tumors of anogenital mammary-like glands: a series of 13 neoplasms in 12 cases, including mammary-type juvenile fibroadenoma, fibroadenoma with lactation changes, and neurofibromatosis-associated pseudoangiomatous stromal hyperplasia with multinucleated giant cells. Am J Surg Pathol. 2010;34:95–103.
Kerkuta R, Kennedy CM, Benda JA, Galask RP. Vulvar cellular angiofibroma: a case report. Am J Obstet Gynecol. 2005;193(5):1750–2.
Micheletti AM, Silva AC, Nascimento AG, Da Silva CS, Murta EF, Adad SJ. Cellular angiofibroma of the vulva: case report with clinicopathological and immunohistochemistry study. Sao Paulo Med J. 2005;123(5):250–2.
Dargent JL, de Saint AN, Galdón MG, Valaeys V, Cornut P, Noël JC. Cellular angiofibroma of the vulva: a clinicopathological study of two cases with documentation of some unusual features and review of the literature. J Cutan Pathol. 2003;30(6):405–11.
Lane JE, Walker AN, Mullis Jr EN, Etheridge JG. Cellular angiofibroma of the vulva. Gynecol Oncol. 2001;81(2):326–9.
Chen E, Fletcher CD. Cellular angiofibroma with atypia or sarcomatous transformation: clinicopathologic analysis of 13 cases. Am J Surg Pathol. 2010;34(5):707–14.
Mandato VD, Santagni S, Cavazza A, Aguzzoli L, Abrate M, La Sala GB. Cellular angiofibroma in women: a review of the literature. Diagn Pathol. 2015;(19)10:114.
Lourenço C, Oliveira N, Ramos F, Ferreira I, Oliveira M. Aggressive angiomyxoma of the vagina: a case report. Rev Bras Ginecol Obstet. 2013;35(12):575–82.
Ptaszyński K, Szumera-Ciećkiewicz A, Bartczak A. Cellular angiofibroma with atypia or sarcomatous transformation - case description with literature review. Pol J Pathol. 2012;63(3):207–11.
Magro G, et al. Vulvovaginal myofibroblastoma: expanding the morphological and immunohistochemical spectrum. A clinicopathologic study of 10 cases. Hum Pathol. 2012;43(2):243-53.
McCluggage WG. A review and update of morphologically bland vulvovaginal mesenchymal lesions. Int J Gynecol Pathol. 2005;24(1):26-38.
Dufau JP, Soulard R, Gros P. Cellular angiofibroma, angiomyofibroblastoma and aggressive angiomyxoma: members of a spectrum of genital stromal tumours?. Ann Pathol. 2002;22(3):241-3.
Curry JL, Olejnik JL, Wojcik EM. Cellular angiofibroma of the vulva with DNA ploidy analysis. Int J Gynecol Pathol. 2001;20(2):200-3.
Magro G, et al. Mammary and vaginal myofibroblastomas are genetically related lesions: fluorescence in situ hybridization analysis shows deletion of 13q14 region. Hum Pathol. 2012;43(11):1887-93.
Magro G et al. Vulvovaginal angiomyofibroblastomas morphologic, immunohistochemical, and fluorescence in situ hybridization analysis for deletion of 13q14 region. Hum Pathol. 2014;45(8):1647-55).
McCluggage WG, Ganesan R, Hirschowitz L, Rollason TP. Cellular angiofibroma and related fibromatous lesions of the vulva: report of a series of cases with a morphological spectrum wider than previously described. Histopathology. 2004;45(4):360-8.
McCluggage WG, Perenyei M, Irwin ST. Recurrent cellular angiofibroma of the vulva. J Clin Pathol. 2002;55(6):477-9.
Fletcher CDM, Bridge JA, Hogendoorn PCW et al Classification of Tumours of Soft Tissue and Bone 4th edn. IARC Press: Lyon, France, 2013, p :80-82.
Mosquera JM, Fletcher CD. Expanding the spectrum of malignant progression in solitary fibrous tumors: a study of 8 cases with a discrete anaplastic component--is this dedifferentiated SFT?. Am J Surg Pathol. 2009;33(9):1314-21.
Colombat M, Liard-Meillon ME, de Saint-Maur P, Sevestre H, Gontier MF. L’angiofibrome cellulaire, une tumeur vulvaire rare: à propos d’un cas. Ann Pathol 2001;21:145.
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MK analyzed and interpreted the patient data, drafted the manuscript and made the figures. NL and ZA performed the histological examination, proposed the study, supervised MK and revised the manuscript. AM and LR have made substantial contributions to analysis and interpretation of patient data. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
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Khmou, M., Lamalmi, N., Malihy, A. et al. Cellular angiofibroma of the vulva: a poorly known entity, a case report and literature review. BMC Clin Pathol 16, 8 (2016) doi:10.1186/s12907-016-0030-z
- Cellular angiofibroma
- Mesenchymal tumors