血管肌纤维母细胞瘤与侵袭性血管粘液瘤临床病理分析

目的：探讨血管肌纤维母细胞瘤（ＡＭＦＢ）的临床病理特点及与侵袭性血管粘液瘤（ＡＡ）的鉴别。方法：对５例ＡＭＦＢ和５例ＡＡ进行临床病理和免疫组化研究,对３例ＡＭＦＢ进行电镜观察。结果：ＡＭＦＢ位于外阴或腹股沟我,肿瘤边界清楚,大小０．８～４ｃｍ。光镜：肿瘤细胞呈梭形上皮样、束头及巢状排列,常围绕小至中等大小的薄壁血管周围。肿瘤有细胞密集区和细胞分散区。免疫组化：肿瘤细胞表达ｖｉｍｅｎｔｉｎ,ｄｅｓｍ     

Aggressive angiomyxoma: a second case of metastasis with patient's death

Aggressive angiomyxoma is a rare tumor that predominates in the female genital tract. Multiple relapses may occur in adjacent organs and tissues, but metastases have not been reported. We present a case of aggressive angiomyxoma in a young woman with multiple local recurrences that metastasized to the lungs, killing the patient. We document this case and report a similar one, found in the literature, of a postmenopausal woman with pulmonary and mediastinic metastases. These cases may expand the current concepts of potential behavior of aggressive angiomyxoma.     

Myxoid leiomyoma of the vulva mimicking aggressive angiomyxoma

A case of vulvar leiomyoma with extensive myxoid change in a 40 year old female is described. The tumor had a unique connection with a non-degenerative leiomyoma that compressed the rectum and the bladder. Scattered smooth muscle cells in a loose myxoid stroma were immunoreactive for desmin. Fibroblast-like spindle cells were immunoreactive for vimentin but not for desmin. The initial, although incorrect, pathological diagnosis of the tumor was aggressive angiomyxoma based on the similarity in both clinical and pathological aspects with this more invasive tumor. Myxoid vulvar leiomyoma should also be differentiated from angio-myoflbroblastoma. The key to the differential diagnosis is the presence of interlacing smooth muscle cells and an awareness of tendency toward myxoid change in vulvar leiomyomas.     

血管肌纤维母细胞瘤的临床病理和鉴别诊断

目的　探讨血管肌纤维母细胞瘤 (AMF)的临床病理特征和鉴别诊断。方法　通过 4例AMF的病理形态和免疫组化研究 ,结合复习文献总结AMF的临床病理特征和鉴别诊断。结果　肿瘤境界清楚 ,直径 <5cm ,瘤细胞梭形或卵圆形 ,常围绕血管排列 ,呈疏密交替分布特征。免疫表型 :desmin、SMA、vimentin、CD34、ER和PR阳性或部分阳性 ,而MSA、S 10 0蛋白、Mac387和CK均阴性。结论　AMF是一种主要发生于生育期女性外阴的良性软组织肿瘤 ,需与侵袭性血管黏液瘤、富细胞性血管纤维瘤等相鉴别     

Fine-needle aspiration cytology findings in a case of aggressive angiomyxoma: A case report and review of the literature

Aggressive angiomyxomas are uncommon but distinct soft-tissue neoplasms occurring predominantly in the pelvis and peritoneum of females, but they have occasionally been reported in association with inguinal hernias in males. Histologically, these neoplasms are characterized by a proliferation of spindle- or stellate-shaped cells widely separated by loose myxoid stroma in which is dispersed a prominent vascular component. The vascular component is comprised of large, thick-walled vessels that generally do not show an arborizing pattern. Mitotic activity has been exceedingly low in the cases reported. Because of their occurrence within the groin, these lesions may undergo fine-needle aspiration (FNA). Cytologic examination of this material will reveal hypocellular smears containing scattered spindle cells with bipolar cytoplasmic processes, as well as bland stellate cells. The nuclei are fusiform to oval with a bland chromatin pattern. The stromal cells lie in a background of watery myxoid material. While specific diagnosis by FNA is not possible, the recognition of this cytologic appearance should exclude lymphoproliferative processes as well as metastatic disease from the differential diagnosis. Careful attention to cytologic detail should also help exclude certain other myxoid neoplasms, especially myxoid liposarcoma. Once the myxoid stromal nature of the proliferation is recognized, a differential diagnosis of myxoid lesions can be considered along with a recommendation for open biopsy to establish the definitive diagnosis. Diagn. Cytopathol. 16:425–429, 1997. © 1997 Wiley-Liss, Inc.     

Aggressive angiomyxoma: a clinicopathological and immunohistochemical study of 11 cases with long-term follow-up

Aims 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.Methods and 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, -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 -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.     

Aggressive angiomyxoma: an ultrastructural study of four cases

The histogenesis of the aggressive angiomyxoma of the vulvo-vaginal region was studied. Four cases of aggressive angiomyxoma were examined by using light microscopy, electron microscopy, and immunohistochemistry. Myofibroblastic from smooth muscle cell differentiation was distinguished by paying close attention to the structures of the neoplastic cell membrane. Aggressive angiomyxomas exhibit subtle features of smooth muscle differentiation, suggesting that the neoplastic cells differentiate from a multipotent perivascular cell.     

Hepatoblastoma: an immunohistochemical and ultrastructural study

The ultrastructural and immunohistochemical features of 19 hepatoblastomas were examined to evaluate the phenotypic expressivity of this solid embryonic neoplasm of childhood. Electron microscopy confirmed the embryonal and fetal characteristics of the neoplastic hepatocytes, but in addition, cells with features intermediate between these two cell types were identified. Dense bundles of collagen corresponding to the osteoid-like material by light microscopy surrounded nests of cells; the cells within this matrix stained for epithelial membrane antigen and vimentin and focally for cytokeratin, and they showed ultrastructural features of epithelial cells. The two cases of small cell hepatoblastoma reacted positively for vimentin and cytokeratin; the remaining 17 cases were immunoreactive for cytokeratin and alpha-fetoprotein, and some also for alpha 1-antitrypsin, ferritin, and vimentin. A histogenetic scheme based on our findings is proposed to explain the divergent morphologic features of this neoplasm.     

Maxillary aggressive angiomyxoma showing ineffective to radiotherapy: a rare case report and review of literature

Aggressive angiomyxoma, mostly originating in the female pelvis and peritoneum or in the male analogous sites, is a rare mesenchymal neoplasm characterized with infiltrative growth to adjacent tissue and local recurrence after primary excision. Herein, we report a case of aggressive angiomyxoma of maxilla in a 60-year-old male patient for its rarity. The patient presented with a one-year history of progressively enlarging maxillary mass on left side. Before referred to our hospital, he was given a biopsy and diagnosed as aggressive angiomyxoma by immunohistochemical staining. After that, he underwent 60Gy radiotherapy. Unfortunately, CT scan showed bigger mass infiltrated to adjacent facial soft tissues and bones compared with that of before radiotherapy. Besides that, he began to suffer with ingravescent headache. The mass was surgically removed and the diagnosis was confirmed by immunohistology in our hospital. As a case of aggressive angiomyxoma occurred in a rare site and experienced an ongoing growth in spite of radiotherapy, its characteristics was discussed with a brief literature review, which may aid further understanding of aggressive angiomyoma.     

Hepatoblastomas: an ultrastructural and immunohistochemical study.

Seven hepatoblastomas were studied by electron microscopy, and four of these were studied by immunohistochemistry. Five tumors were purely epithelial, and two were mixed epithelial-mesenchymal. They showed a spectrum of cellular differentiation ranging from primitive epithelial cells to differentiated cells resembling adult hepatocytes. Glycogen, lipid, basal lamina, and canaliculi were present in all cases. Mitochondria with large, membrane-bound, amorphous inclusions were present in one tumor, and large, complex, basal cell processes were present in two tumors. Ultrastructural features most characteristic of hepatocytes were most common in fetal type hepatoblastomas. Immunoreactive chromogranin cells were present in two tumors, one of which also contained immunoreactive somatostatin cells. The somatostatin-positive tumor had cells with granules resembling those seen in somatostatin-containing cells of normal pancreas and somatostatin-containing neuroendocrine carcinomas. Other immunoreactive substances were present, including alpha 1-antitrypsin (four cases), vimentin (embryonal cells in four cases; fetal cells in three cases), low-molecular weight cytokeratin (embryonal cells in three cases; fetal cells in four cases), and high-molecular weight cytokeratin (embryonal cells in one case; fetal cells in two cases). Osteoidlike material was positive for epithelial membrane antigen, vimentin, and S-100 protein.     

Synovial sarcoma: an immunohistochemical and ultrastructural study

Thirty-nine primary synovial sarcomas (15 biphasic, 24 monophasic), and 19 metastatic synovial sarcomas were studied with a battery of antibodies directed to keratin, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), vimentin, desmin, muscle-specific actin, smooth muscle actin, S-100 protein, Leu-7, chromogranin A, laminin, collagen IV, Ulex europaeus agglutinin I (UEAI), and the HMB-45 antimelanoma antibody. Twenty-two primary and 18 metastatic synovial sarcomas were also examined by electron microscopy. Epithelial and/or spindle cells in every biphasic tumor, primary and metastatic, reacted for keratin and EMA, but only six primary tumors (five biphasic and one monophasic) showed weak reactivity for CEA which, in the biphasic tumors, was confined to the epithelial component. Of the monophasic tumors, 15 primary (63%) and four metastatic (25%) stained for keratin, whereas seven primary (29%) and two metastatic (13%) tumors reacted for EMA. Only one primary monophasic synovial sarcoma stained for CEA. Tumors that stained for EMA or CEA also stained for keratin which is, therefore, the most useful epithelial marker. Immunostaining for epithelial markers, UEAI, collagen IV, and laminin serves to delineate the epithelial component when it is obscure in routine sections. Electron microscopy facilitates the diagnosis when epithelial markers are not expressed and aids in separating monophasic synovial sarcomas from other sarcomas that they resemble by light microscopy.     

Desmoplastic cerebral astrocytomas of infancy: A histopathologic, immunohistochemical, ultrastructural, and molecular genetic study

The desmoplastic cerebral astrocytoma of infancy (DCAI) is a rare tumor that presents as a large hemispheric mass in infants. Despite an ominous histologic picture that may resemble a sarcoma, the tumor is astrocytic and has a good prognosis. We present two cases of DCAI, with histopathologic, immunohistochemical, ultrastructural, and molecular genetic data, and draw the following conclusions: (1) the diagnosis of DCAI requires a high index of suspicion and immunohistochemical or ultrastructural proof of astrocytic differentiation; (2) the data argue against nosologically equating these tumors with the desmoplastic infantile ganglioglioma, pleomorphic xanthoastrocytoma, or gliofibroma; (3) the components of the extensive tumor basal lamina may be elaborated by the tumor cells themselves and may contribute in an autocrine fashion to the slow growth of these lesions; and (4) if the lack of allelic loss on chromosomes 17p (including the p53 tumor suppressor gene locus) and 10 seen in our cases is found in other cases of DCAI, this may further distinguish the DCAI from other astrocytomas.     

Androgen insensitivity syndrome: an immunohistochemical, ultrastructural, and morphometric study

OBJECTIVE: To evaluate the morphometric, immunohistochemical, and ultrastructural lesions of the testes in prepubertal and adult patients with androgen insensitivity syndrome. METHODS: We examined the testicular biopsy using immunohistochemistry for vimentin, smooth muscle actin, and collagen IV antigens. Quantification of seminiferous tubules and testicular interstitium was performed in prepubertal and adult patients with androgen insensitivity syndrome and results were compared with normal testes from both infants and adults. RESULTS: The adult testes presented nodular and diffuse lesions that consisted of Sertoli-cell-only seminiferous tubules. Two types of Sertoli cells could be distinguished, namely, immature vimentin-positive Sertoli cells and nearly mature Sertoli cells. In the nodules, the lamina propria was thin and contained a scant number of actin-positive peritubular cells. Leydig cells were hyperplastic. The prepubertal patients showed only diffuse lesions characterized by Sertoli cell hyperplasia, decreased germ cell numbers, and a discontinuous immunoreaction to collagen IV. CONCLUSIONS: The testicular lesions in androgen insensitivity syndrome are probably caused by primary alterations that begin during gestation. These lesions become progressively more pronounced at puberty, when the nodular lesion pattern (adenomas) is completely developed.     

Understanding the origin,activation and regulation of matrix‐producing myofibroblasts for treatment of fibrotic disease

Fibrosis and scar formation results from chronic progressive injury in virtually every tissue and affects a growing number of people around the world. Myofibroblasts drive fibrosis, and recent work has demonstrated that mesenchymal cells, including pericytes and perivascular fibroblasts, are their main progenitors. Understanding the cellular mechanisms of pericyte/fibroblast‐to‐myofibroblast transition, myofibroblast proliferation and the key signalling pathways that regulate these processes is essential to develop novel targeted therapeutics for the growing patient population suffering from solid organ fibrosis. In this review, we summarize the current knowledge about different progenitor cells of myofibroblasts, discuss major pathways that regulate their transdifferentiation and discuss the current status of novel targeted anti‐fibrotic therapeutics in development. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Angiomyofibroblastoma of the vulva: A clinicopathologic study of seven cases

A clinicopathologic and immunohistochemical review was made of seven cases of angiomyofibroblastoma. The patients were middle-aged women who had a slowly growing mass, measuring 1.5–6 cm in maximum dimension, located sub-cutaneously in the vulva. The tumors were well-demarcated and characterized by well-vascularized, alternating hyper-cellular and hypocellular edematous areas composed of bland, plump spindle- or oval-shaped stromal cells frequently aggregated around small blood vessels. An epithelioid appearance of the stromal cells was seen in two cases. Immunohistochemically, the stromal cells were consistently positive for vimentin and desmin, but negative for muscle specific actin, a-smooth muscle actin, myosin, cytokeratins, S-100 protein or von Willebrand factor. Ultrastructurally, the plump stromal cells had a small amount of peripherally located rough endoplasmic reticulum, numerous pinocytotic vesicles and abundant intermediate filaments, on which immunogold probes for desmin were localized, whereas fine filaments were few and there were no electron dense plaques. Thus, while the proliferating stromal cells expressed an immunohistochemical profile of peculiar myoid differentiation, ultrastructural findings differed from those of smooth muscle cells or those seen in typical myofibroblasts. At 1–4 years after surgery, there was no evidence of recurrence.     

Angiomyofibroblastoma and aggressive angiomyxoma: two benign mesenchymal neoplasms of the female genital tract. An immunohistochemical study

We describe a rare case of angiomyofibroblastoma (AMF) of the vulva and one case of aggressive angiomyxoma (AAM) of the pelvic region and, with the help of an extensive revision of the literature, we attempt to define their histogenesis and peculiar biological behaviour by an immunohistological evaluation. Our results indicate that AAM, which is characterized by the presence of a high content of glycosaminoglycans in the stroma, expresses uniformly vimentin and hyaluronate receptor CD44, and heterogeneously muscle specific actin (MSA) and desmin, while AMF displays a positive reaction for vimentin, desmin and laminin, and only a weak and heterogeneous positivity for CD44. Both AMF and AAM showed no immunohistochemical reactivity for alpha-smooth muscle actin (ASMA), myoglobin, cytokeratin, collagen type IV, CD68 and S-100. The stromal cells of AAM were negative for laminin. These findings support the suggestion of an origin of the two entities by a common myofibroblastic progenitor, which normally occurs in the lower female genital tract and subsequently undergoes a neoplastic transformation. The expression of CD44 by AAM, which has never been reported before, could be responsible for its more aggressive behaviour, because this receptor is able to mediate migration of neoplastic cells on a hyaluronate rich extracellular matrix. It is speculated that the neoplastic cell of the AAM and AMF of the vulva is a specific myofibroblast which probably arises from undifferentiated mesenchymal cells normally occurring in the lower female genital tract.     

Reactive hyperplasia of vascular pericytes in meningioma: immunohistochemical and ultrastructural studies of two cases

An isolated proliferation of pericytes is a unique vascular reaction seen almost exclusively in the stroma of secretory meningioma. We report the results of immunohistochemical and ultrastructural studies of a pericytic proliferation that was found in two cases of meningioma (a secretory meningioma of the sphenoid ridge and a parasagittal atypical meningioma showing predominantly fibroblastic features). Pericytes had hyperchromatic nuclei and scant cytoplasm, and showed stratification or formed small clusters within the walls of small blood vessels. They occasionally showed close contact with pseudopsammoma bodies in secretory meningioma. Pericytes showed immunoreactivity for α-smooth muscle actin but were not immunoreactive for desmin. They also exhibited characteristic ultrastructural features of pericytes, including the presence of microfilaments and abundant pinocytotic vesicles, and investment by the basal lamina. This isolated pericytic proliferation is likely a peculiar response of the vascular wall, probably induced by some cytokines secreted from neoplastic meningothelial cells. The close contact of proliferating pericytes with pseudopsammoma bodies suggests a close pathogenetic association between them. The occurrence of pericytic proliferation that was found in our second case (atypical meningioma with predominantly fibroblastic features) is exceptional and has not been documented to date.     

Soft-tissue and meningeal hemangiopericytomas: an immunohistochemical and ultrastructural study

The debate on the nosologic position of hemangiopericytomas of the meninges has been based mainly on light microscopic and ultrastructural considerations; recent immunohistochemical studies have yielded controversial results. We have used a panel of antibodies to vimentin, desmin, actin, S100 protein, epithelial membrane antigen, cytokeratins, Leu-7, factor VIII-related antigen and type IV collagen to compare the immunophenotype of 10 soft-tissue and seven meningeal hemangiopericytomas. The immunophenotypic profile of these tumors is identical, and differs from that of meningiomas in that epithelial membrane antigen and cytokeratin are not present. The vascular pattern occurring in some meningiomas can simulate true hemangiopericytomas of the meninges. Immunohistochemical studies should allow their distinction in each instance. Meningeal and soft-tissue hemangiopericytomas display similar ultrastructural features.     

Fibrous hamartoma of infancy: an immunohistochemical and ultrastructural study

Fibrous hamartoma of infancy is an uncommon lesion of uncertain histogenesis. Three cases were studied by light microscopy, electron microscopy, and immunohistochemistry. Two histologic variants are presented. Ultrastructurally, fibroblasts and myofibroblasts were found in the fascicular-fibroblastic areas while primitive mesenchymal cells were found in the immature-appearing regions. Vimentin positivity was noted in both areas, whereas desmin and actin positivity was found mainly in the fascicular-fibroblastic regions. The lesion appears to fulfill the criteria for its characterization as "hamartoma."