Cellular angiofibroma is genetically similar to spindle cell lipoma: a case report

Cellular angiofibroma is a benign mesenchymal neoplasm of female and male genital tract composed of prominent vasculature and stromal spindle cells, often with admixture of adipose tissue. The tumor has histomorphologic similarities to angiomyofibroblastoma and spindle cell lipoma. Herein we describe a tumor arising in the perineal region of a 60-year-old man with morphological and immunohistochemical features of cellular angiofibroma and showing cytogenetic characteristics similar to spindle cell lipoma. To our knowledge, this is the first report of cytogenetic changes in cellular angiofibroma. The genetic overlap of these entities supports their origin from the same mesenchymal stem cell.     

Leiomyomatous nodules in a cellular angiofibroma: a hitherto unreported finding

Cellular angiofibroma is a benign tumor of the superficial soft tissues of the vulvovaginal and inguinoscrotal regions of adult patients. Histologically, it is characterized by bland spindle cells arranged without any pattern in a stroma with thin collagen fibrils and evenly distributed small- to medium-sized blood vessels with hyalinized walls. The case of a 44-year-old female with a perineal cellular angiofibroma containing small leiomyomatous nodules is described in this case report. These nodules could probably be originated from smooth muscle differentiation of the spindle cell component of an otherwise conventional cellular angiofibroma. To our knowledge, the finding of distinct leiomyomatous nodules within a cellular angiofibroma has not been previously reported.     

Cellular angiofibroma of the vulva: a poorly known entity,a case report and literature review

Background

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.

Case presentation

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.

Conclusion

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.

     

Evidence for an association between increased oxidative stress and derangement of FOXO1 signaling in tumorigenesis of a cellular angiofibroma with monoallelic 13q14: a case report

Cellular angiofibroma (CAF) is a rare soft tissue tumor characterized by random arrangement of spindle tumor cells in the stroma with short collagen bundles and thick- and hyalinized small vessels. CAFs share histological characteristics with spindle cell lipomas and mammary type myofibroblastomas. Because these tumors harbor monoallelic 13q14, common genetic and molecular mechanism for tumorigenesis is presumed. In this study, we reported a case of CAF in a 69-year-old man with monoallelic 13q14. Immunohistochemical analysis revealed that FOXO1, which is located in chromosome 13q14, was not expressed in the tumor. We also detected oxidative stress markers and found p38 MAPK activation, which is often induced by cellular stressors such as reactive oxygen species (ROS). Because FOXO1 induces the expression of genes encoding enzymes that generate antioxidants, oxidative stress induced by loss of FOXO1 expression may be common among CAFs, spindle cell lipomas, and mammary type myofibroblastomas.     

Solitary fibrous tumor: is there a molecular relationship with cellular angiofibroma, spindle cell lipoma, and mammary-type myofibroblastoma?

Solitary fibrous tumor (SFT) is a mesenchymal tumor characterized by ovoid cells, branching blood vessels, stromal hyalinization, and CD34 immunoreactivity. Studies have shown loss of 13q in a group of morphologically similar entities, including cellular angiofibroma, mammary-type myofibroblastoma, and spindle cell lipoma. The histologic and immunophenotypic overlap between SFT and the latter group of tumors suggests that these tumors may be genetically linked. We tested a group of 40 SFTs to assess for loss of RB1 (13q14) by fluorescence in situ hybridization (FISH). All 38 SFTs with evaluable signals failed to show loss of RB1 (13q14) by FISH. All cases of cellular angiofibroma (1/1), spindle cell lipoma (6/6), and mammary-type myofibroblastoma (4/4), which were used as a control group, showed monoallelic or biallelic loss of RB1. The absence of RB1 loss in SFTs suggests that they are not related to cellular angiofibroma, mammary-type myofibroblastoma, or spindle cell lipoma.     

Angiomyofibroblastoma-like tumor (lipomatous variant) of the inguinal region of a male patient

A case of angiomyofibroblastoma-like tumor (lipomatous variant) that arose in the subcutis of the inguinal region of a 45-year-old man is presented. The maximum dimension of the tumor measured 39 mm and it was well circumscribed. Histopathological examination revealed a close admixture of plump spindle or stellate cells and mature adipocytes. These were arranged haphazardly or formed interconnecting thin cellular trabeculae on the myxoid or edematous background. The tumor was highly vascularized and contained a moderate amount of collagen fibers. Immunohistochemically, the tumor cells were positive for vimentin, CD34 and the estrogen receptor, but negative for alpha-smooth muscle actin and desmin. The differential diagnosis between the lipomatous variant of angiomyofibroblastoma and cellular angiofibroma or spindle cell lipoma is discussed, and the pathogenetic hypotheses about the occurrence of mature adipocytes within benign fibroblastic or myofibroblastic neoplasms are mentioned briefly. It is important for surgical pathologists to be acquainted with the occasional presence of adipocytes in these neoplasms to avoid misinterpretation.     

Extragenital subcutaneous cellular angiofibroma. Case report

Cellular angiofibroma (CAF) is a rare distinctive mesenchymal neoplasm that occurs almost exclusively in the genital area. We report the case of a 38-year-old woman who presented with an asymptomatic subcutaneous mass, 3.5 cm in diameter, located in the left hypochondrium, which had progressively enlarged during the previous 6 months. The lesion was completely excised. No recurrence was observed 3 months after the excision. A review of the literature--and including the present report--revealed five cases (three men and two women) with location outside the urogenital tract. Mean age was 57 (range 38-78) years; mean 41 years for women and 68 years for men. Average tumor size was 9 (range 3.5-25) cm; mean 5 cm for women and 12 cm for men. Tumors were located in the superficial soft tissue of the trunk, except for one case in the retroperitoneum. Mean follow-up was 29 (range 3-102) months, and no patient developed recurrence or metastasis. Extragenital CAF, except for location, shows similar clinicopathological features to genital CAF. Simple tumorectomy appears to be adequate treatment. Morphologically, CAF is closely related to spindle cell lipoma.     

The spectrum of histologic growth patterns in benign and malignant fibrous tumors of the pleura.

A review of the histologic growth patterns in 50 cases of benign and malignant fibrous tumors of the pleura (localized or solitary fibrous tumor, fibrous mesothelioma) is presented. Two major histologic growth patterns were observed admixed in various proportions: solid spindle and diffuse sclerosing. The solid spindle growth pattern assumed various configurations, including fascicular areas, storiform and herringbone formations, angiofibroma and hemangiopericytoma-like areas, synovial sarcoma-like areas, and neural-type palisading, thus simulating a variety of soft-tissue neoplasms. The diffuse sclerosing pattern, although rarely assuming a dominant role, was present in varying proportions in virtually all cases. In areas with extensive sclerosis, focal degeneration of collagen simulating tumor necrosis was often present. Other less frequently observed features were the formation of "amianthoid" fibers, multinucleated giant cells, and foci of metaplastic ossification. On ultrastructural and immunohistochemical examination, the tumor cells showed nondistinct features. Due to the extreme variability in morphologic appearances and the lack of distinctive ultrastructural or immunohistochemical characteristics, these tumors can pose a significant diagnostic problem. Familiarity with their histologic appearances and correlation with the gross findings and clinical setting are essential for arriving at the correct diagnosis.     

Mixed tumor of the vagina: a case report

We report a case of mixed tumor arising in the lower vaginal wall. The patient was a 20-yr-old nullipararous woman. The tumor was relatively well-defined with expansile margin, and showed solid sheets or fascicles of stromal-type spindle cells and ovoid epithelial cells with sparsely scattered nests of mature squamous epithelium and glands lined by mucinous epithelium. Cellular atypia was not conspicuous, however, mitosis was counted upto 6 per 10 high power fields. We examined this tumor immunohistochemically and ultrastructurally and reviewed the articles to identify the histogenesis. Positive reaction for vimenin and cytokeratin of stromaltype spindle cells and presence of desmosome-like structures and tonofilaments on electron microscopic examination suggested the epithelial origin of the stromaltype spindle cells.     

Angiofibroma of soft tissue with fibrohistiocytic features and intratumor genetic heterogeneity of NCOA2 gene rearrangement revealed by chromogenic in situ hybridization: A case report

Angiofibroma of soft tissue is a recently described soft tissue tumor that is characterized by fibroblastic spindle tumor cells with arborizing capillary proliferation. Cytogenetically, it harbors a specific fusion gene involving the nuclear receptor coactivator 2 (NCOA2) gene. We report here additional new pathological and cytogenetic features. A soft tissue tumor in the left thigh of 73‐year‐old female was investigated. Microscopically, histiocytoid tumor cells were scattered in an edematous background with branching capillary proliferation. Immunohistochemically, we identified that the tumor cells were positive for histiocytic markers such as CD68 and CD163. Rearrangement of the NCOA2 gene was detected successfully by chromogenic in situ hybridization; however, abnormal signal patterns were observed in only a small subset of tumor cells. Unlike typical tumors with bland spindle cells, the present tumor needs to be distinguished from myxoid, dendritic and clear cell tumors. This case may suggest that angiofibroma of soft tissue is not in the center of the fibroblastic/myofibroblastic tumor group, but rather shows a fibrohistiocytic nature. We also found intratumor genetic heterogeneity, which is uncommon for a translocation‐associated tumor. Therefore, careful evaluation is required to detect the gene rearrangement in this tumor entity.     

Steroid hormone receptor expression in nasopharyngeal angiofibromas. Consistent expression of estrogen receptor beta

Nasopharyngeal angiofibroma is an uncommon tumor arising in adolescent males, suggesting that the tumor may be hormonally responsive. Previous studies have found androgen receptor (AR) expression but variable expression of estrogen receptor (ER). The recently described ss receptor for estrogen has not been analyzed in angiofibroma. We analyzed 13 cases of nasal angiofibroma by immunohistochemical analysis for the presence of ARs, progesterone receptors (PR), and ER-a and ER-ss. All 13 cases were positive for ER-ss, in stromal pericytic and endothelial cells, and 12 of 13 stained strongly. Five cases were positive for AR in stromal cells, most staining weakly, and with no staining in endothelial or pericytic cells. None of the cases displayed staining for ER-a or PR. The findings confirm that nasopharyngeal angiofibromas express ER and suggest that new modulators of ER-ss activity may provide an alternative therapy for these lesions.     

Para-testicular cellular angiofibroma: a rare tumour in a male renal transplant patient

Cellular angiofibroma is a rare, benign, mesenchymal neoplasm that should be distinguished from other more aggressive mesenchymal lesions. A 32-year-old male presented with a painless para-testicular mass. Pathological examination showed features characteristic of cellular angiofibroma. He had a history of renal transplantation and was on immunosuppressive drugs. The pathogenesis of cellular angiofibroma is largely undetermined. The role of immunosuppressive therapy in the genesis of this tumour awaits further analysis.     

Extraorbital giant cell angiofibroma

We describe a case of giant cell angiofibroma (GCA) in extraorbital location. A 47-year-old man developed a subcutaneous tumor on the forearm, which measured 6 cm in diameter and was well demarcated. Histologically, small-sized vessels similar to arterioles, sometimes with a hyalinized wall, were regularly distributed throughout the tumor tissue. Lesional cells were oval and spindle in shape with pale eosinophilic cytoplasm and plump nuclei with clumped chromatin. In addition, larger bizarre cells with lobulated hyperchromatic nucleus were randomly admixed. Areas with a sieve-like pattern contained small slit-like spaces or larger pseudocystic spaces lined by tumor cells with an admixture of bizarre cells. Both mononuclear and bizarre lesional cells expressed strongly and diffusely vimentin and CD34. Negative reactions were with cytokeratins, bcl-2, desmin, actin, VWF, S100, alpha-1-antitrypsin, CD99, lysozyme and FXIIIa. Our finding confirms that GCA is a benign neoplasm not necessarily confined to orbital location. The patient did well without recurrence after 13 months of follow-up.     

Extraorbital giant cell angiofibroma.

A number of intriguing fibrovascular mesenchymal proliferations with benign or low grade malignant potential have recently been described. Giant cell angiofibroma was introduced as an entity by Dei Tos et al. in 1995 and initially considered to be a lesion of the orbit. We describe an extraorbital example, indicating that giant cell angiofibroma is not confined to the orbit. Immunologically, giant cell angiofibroma is positive for CD 34, bcl-2 and vimentin, and negative for epithelial and muscle markers, and S-100. The tumor shares several morphological and immunological properties with giant cell fibroblastoma and solitary fibrous tumor, yet it features a histology sufficiently characteristic to allow its categorization as a separate entity. The recommended treatment is complete but conservative excision. Metastases have not been reported.     

Human immunodeficiency virus-associated oral Kaposi's sarcoma. A heterogeneous cell population dominated by spindle-shaped endothelial cells.

Cell lineage and cell function antigens were studied immunohistochemically in human immunodeficiency virus-associated oral Kaposi's sarcoma to provide insight into tumor pathogenesis. All tumors were composed predominantly of spindle cells that expressed endothelium-associated antigens, CD34 and CD36 (factor VIII-related antigen was expressed by considerably fewer numbers of tumor cells). Infrequently, spindle tumor cells also expressed actin. Factor XIIIa positive spindle and dendritic stromal cells comprised up to 9% of the tumor cell population. Other spindle and dendritic cells expressing macrophage-associated antigen, CD68, accounted for up to 15% of the tumor cells. Mast cells occurred frequently within and around tumors. Leukocyte function antigen (CD18) was expressed by approximately 13% of tumor cells, and its ligand, intercellular adhesion molecule (ICAM), was expressed by some tumor-associated capillaries (which also expressed endothelial leukocyte adhesion molecule, ELAM) and occasional stromal cells. Staining for proliferating cell nuclear antigen was noted in both interstitial and vascular lining cells. All tumors were non-reactive for human Papillomavirus antigen and HIV p24 antigen. Oral KS is a heterogeneous cellular proliferation composed predominantly of endothelial or endothelium-related spindle cells. Other spindle/dendritic (XIIIa-positive and CD68-positive) cells and mast cells are also present and may contribute to tumor development. ICAM and ELAM expression within tumors may assist infiltration of macrophages and other inflammatory cells into these lesions.     

Extrathoracic solitary fibrous tumors: their histological variability and potentially aggressive behavior

The histological variability of solitary fibrous tumors may contribute to the difficulty in diagnosing these neoplasms, especially when they arise in extrathoracic sites. Like intrathoracic lesions, the behavior of extrathoracic solitary fibrous tumors is currently unpredictable because these types of tumor have only recently been recognized. This study therefore was undertaken to examine the clinical behavior and histological, immunohistochemical, and ultrastructural features of 24 extrathoracic solitary fibrous tumors with long-term follow-up. The patients comprised 10 men and 14 women, between 30 and 85 years of age (mean, 51 years). Ten tumors were located in the retroperitoneum or pelvis, 5 in the trunk, 4 in the extremities, 2 in the orbital region, and 1 each in the kidney, uterine cervix, and meninges. All of the tumors showed a classic morphological appearance, diffuse and strong immunoreactivity for both vimentin and CD34, and variable reactivity for bcl-2. All 7 cases examined ultrastructurally contained fibroblasts and myofibroblasts. Six tumors contained multinucleated giant cells, and in 4 cases these lined pseudovascular spaces with mononuclear cells, thus resembling giant cell angiofibroma and giant cell fibroblastoma. Other potentially similar spindle cell neoplasms mixed with adipose tissue, such as dendritic fibromyxolipoma, lipomatous hemangiopericytoma, cellular angiofibroma, and spindle cell lipoma, were considered in the differential diagnosis. One tumor displayed atypical histological features in the form of increased cellularity and nuclear pleomorphism, but this patient has remained free of disease for 14 years. Another 2 patients developed local recurrences at 6 months and 5 years, and a further patient developed pulmonary metastases that were diagnosed after 7 years. These tumors lacked any atypical histological features in the primary lesions. No patient has so far died of the disease. In conclusion, most extrathoracic solitary fibrous tumors appear to pursue a benign course, although, because some have the potential to recur or metastasize, careful long-term follow-up is necessary for all patients.     

Solitary fibrous tumor of the mammary gland: a potential pitfall in breast pathology

We report three cases of solitary fibrous tumor of the breast. The patients were adult to elderly women and complained of a slowly but relentless growing lump. The tumors were fairly circumscribed and cured by means of lumpectomy or, in one case, simple mastectomy. Histologically, they featured the customary "patternless pattern" of short spindle cells haphazardly arranged in fascicles within a collagenized or myxoid ground substance. In two cases, a prominent hemangiopericytic arrangement of tumor cells around a rich vascular framework could be noticed. Cellular areas were often present and showed nuclear overlapping, clumping of chromatin, and a brisk mitotic activity. No atypical mitosis was recognized. Tumor cells were immunoreactive for CD34, bcl2, and vimentin only. On follow-up there was no evidence of either local recurrence or distant metastases. Solitary fibrous tumors of the breast may represent a significant diagnostic problem because of the close mimicry to numerous benign and malignant mammary lesions composed of spindle cells; diagnostic clues may be further obscured in cellular and actively proliferating tumors. A brief overview of mammary solitary fibrous tumor taxonomy along with the principal differential diagnoses within the breast is presented.     

Angiofibroma of soft tissue: clinicopathologic study of 2 cases of a recently characterized benign soft tissue tumor

Angiofibroma of soft tissue is a very recently characterized, histologically distinctive benign mesenchymal neoplasm of unknown cellular origin composed of 2 principal components, the spindle cell component and very prominent stromal vasculatures. It usually occurs in middle-aged adults, with a female predominance. Herein, we describe the clinical and pathologic details of 2 other examples of this benign tumor. Both patients were middle-aged male and presented with a slow-growing, painless mass located in the deep-seated soft tissue of thigh and left posterior neck region, respectively. Grossly, both tumors were well-demarcated, partial encapsulated of a grayish-white color with firm consistence. Histologically, one case showed morphology otherwise identical to those have been described before, whereas the other case showed in areas being more cellular than most examples of this subtype tumor had, with the lesional cells frequently exhibiting short fascicular, vaguely storiform and occasionally swirling arrangements, which posed a challenging differential diagnosis. Immunostains performed on both tumors did not confirm any specific cell differentiation with lesional cells only reactive for vimentin and focally desmin and negative for all the other markers tested. This report serves to broaden the morphologic spectrum of angiofibroma of soft tumor. Awareness of this tumor is important to prevent misdiagnosis as other more aggressive soft tissue tumor.     

A case of adenocarcinoma of the lung with a spindle cell component.

We report a 60-year-old man, who was admitted to the hospital with complaints of cough and sputum. His chest x-ray showed an abnormal mass in the right upper lobe. After admission he noticed the painful gingival tumor. Right upper lobectomy and resection of the gingival tumor were performed. Their histological features showed that the tumor consisted of a papillary and tubular adenocarcinoma mixed with a component of spindle cells. Immunohistochemical study demonstrated a positive reaction in the epithelial component for keratin and epithelial membrane antigen, and not only these epithelial markers but also vimentin were expressed in some spindle tumor cells. Electron microscopic study confirmed the biphasic pattern, showing gland formation and undifferentiated cells. We diagnose this case as adenocarcinoma of the lung with a spindle cell component and the gingival tumor was metastatic. Autopsy showed that metastatic lesions were found in the left adrenal gland and in the left kidney. The tumor cells in the left adrenal gland were composed of spindle cells and the tumor in the left kidney showed gland formation. Immunohistochemical and electron microscopic findings of surgical and autopsy specimen suggest that this tumor is of epithelial origin, and the spindle cells are derived from immature mesenchymal cell transformation of epithelial cells.