Leydig cell tumors of the testis with unusual features: adipose differentiation,calcification with ossification,and spindle-shaped tumor cells

We report 19 Leydig cell tumors (LCTs) of the testis with adipose differentiation (n = 12) and/or spindle cell growth (n = 8) in patients 28-70 years of age; three tumors with adipose differentiation showed psammomatous calcifications, two of which also had foci of ossification. In eight tumors fat-like cells apparently derived from lipid accumulation within neoplastic Leydig cells and appeared as focal to prominent clusters in a background of vacuolated, neoplastic Leydig cells. The fat-like cells were usually immunoreactive for Leydig cell markers (inhibin-alpha, calretinin, and melan-A) but were typically strongly positive for the adipose tissue marker, S-100 protein, supporting a hybrid cell phenotype. Four tumors had fat of stromal derivation. In two of these there were intermixed mature adipocytes, but in two others only lipoblastic cells were present. These four tumors lacked vacuolated, neoplastic Leydig cells, and the fat cells in the single case studied were negative for inhibin-alpha and melan-A but positive for S-100. Three of the 12 LCTs with adipose differentiation were clinically malignant, and each had several of the established malignant features. Eight tumors with spindle cells occurred in men 34-70 years of age. Two tumors had ill-defined fascicles of spindle cells, and three showed prominent edematous to myxoid areas with spindle-shaped tumor cells. Two additional tumors had a fibroma-like spindled component that blended with islands of more plump, polygonal to spindle-shaped Leydig cells. Finally, one tumor had foci resembling an unclassified sarcoma that merged with conventional LCT; the spindle cell component in this case did not react for Leydig cell markers in contrast to the spindle cells in five of the six other cases in which immunostains were performed. Spindle cell differentiation, by itself, did not appear to have prognostic significance. Of the six patients with available follow-up, two developed metastases, but their tumors had malignant features apart from spindle cells; the remaining four patients were disease free at a mean of 3.6 years. Awareness of these unusual patterns in LCTs may prevent misinterpretation of fat admixed with neoplastic Leydig cells as evidence of extratesticular growth (a criterion for malignant LCT) may help avoid misdiagnosis of a LCT as a testicular "tumor" of the adrenogenital syndrome (which may contain fat) and may prevent misdiagnosis of a LCT with spindle cells as a sarcoma or unclassified sex cord-stromal tumor.     

Expression of CD56 and WT1 in ovarian stroma and ovarian stromal tumors

The immunophenotype of ovarian stroma and spindle cell tumors derived from ovarian stroma has not been well studied. We studied the expression of CD56, WT1, estrogen receptor-beta (ER-beta), progesterone receptor (PR), smooth muscle actin, S-100, CD34, and muscle specific actin in 16 normal ovaries, 17 ovarian fibromas, 11 ovarian cellular fibromas, 10 ovarian fibrothecomas, and 11 ovarian leiomyomas. In addition, we studied CD56 and WT1 expression in 7 cases of normal endometrium, 8 uterine smooth muscle tumors, 5 endometrial stromal tumors and 64 nongynecologic (GYN) spindle cell sarcomas. All normal ovaries, ovarian fibromas, fibrothecomas, and ovarian leiomyomas were positive for CD56 and WT1. Most of the normal ovaries, ovarian fibromas, ovarian fibrothecomas, and ovarian leiomyomata also expressed ER-beta and PR. Eight of 17 ovarian fibromas, 5 of 11 ovarian cellular fibromas, and 4 of 10 ovarian fibrothecoma with focal fibroblastic differentiation were positive for smooth muscle actin. A few cases of these tumors also expressed S-100 and CD34. Only rare cases of non-GYN spindle cell sarcomas expressed WT1. Our study results show that ovarian fibromas, fibrothecomas, and leiomyomas have a similar immunophenotype (positive for CD56, WT1, ER-beta, and PR) to that of ovarian stromal cells, supporting an ovarian stromal origin for these neoplasms. However, unlike normal ovarian stromal cells, ovarian fibromas, fibrothecomas, and leiomyomas can also show fibroblastic, smooth muscle, Schwannian, and solitary fibrous tumorlike differentiation. WT1 is a fairly specific marker for spindle cell tumors of gynecologic organs, including ovarian spindle cell tumors, endometrial stromal tumors, and uterine smooth muscle tumors. Non-GYN spindle cell sarcomas rarely express WT1. CD56 is strongly expressed in ovarian stromal cells but not in endometrial stromal cells. CD56 is often expressed by a wide variety of spindle cell sarcomas, thus, it has no value in differentiating GYN from non-GYN spindle cell tumors.     

Proliferative myositis. An immunohistochemical and ultrastructural study

We studied four cases of proliferative myositis by the avidin-biotin-peroxidase complex technique, using a panel of 12 antibodies, and by electron microscopy. The aim was to clarify the nature of their constituent cells, specifically the giant ganglion-like cells and spindle cells, and to discuss the implications for histogenesis. In all cases, both cell types showed positive cytoplasmic staining with antibodies to vimentin, actin (C4), and alpha-smooth muscle actin-1, but in only one was there positive staining with desmin. No staining was obtained with factor XIIIa, muramidase, alpha-1-antitrypsin, myoglobin, S-100 protein, CAM 5.2, factor VIII-related antigen, or neuron-specific enolase. By electron microscopy, both types of cells were seen to contain numerous thin filaments, dense bodies, coated and pinocytotic vesicles, active and dilated rough endoplasmic reticulum, few microvilli, and incomplete desmosomal junctions. Our findings imply a myofibroblastic nature for the giant ganglion-like cells and spindle cells. Our observations also support the hypothesis that they are derived from a pericytic cell.     

Predictors of malignant behaviour in gastrointestinal stromal tumours: a clinicopathological study of 34 cases.

OBJECTIVE: The clinicopathological features of gastrointestinal (GI) stromal tumours were analysed to find out the features that influence prognosis in these neoplasms. DESIGN: Retrospective study. SETTING: University Hospital, Spain. SUBJECTS: Review of clinical records and analysis of a series of GI stromal tumours classified in three groups: benign = 7 leiomyomas, malignant or potentially malignant = 16 combined smooth muscle-neural tumours, and 2 miscellaneous, and definitely malignant = 1 leiomyosarcoma and 8 gastrointestinal autonomic nerve tumours. MAIN OUTCOME MEASURES: Electron microscopy and immunohistochemical staining for vimentin, smooth muscle actin, muscle specific actin, desmin, S-100 protein, neuronal specific enolase, chromogranin A, synaptophysin, CD34, CD117 (c-kit), Bcl-2, and Ki-67. RESULTS: We found significant differences (p < 0.0001) between the median (P25, P75) size of tumours in the benign group 2.0 (1.2, 3.5) and in the potentially 7.5 (4.0, 13.0) and definitely 5.0 (4.0,6.5) malignant groups. The percentage of mitoses was lower (p = 0.003) in the benign group 0.4 (0.5) than in the other groups 2.0 (1.0, 5.0). Immunoreactivity for CD117 in leiomyomas was an unexpected finding; this showed a different staining pattern from the diffuse and homogeneous staining in GI stromal tumours. In addition, the MIB-1 proliferation index differentiated (p = 0.002) between the benign group 1.5 (1.0, 2.5) and the other two groups 7.0 (3.0, 11.0). CONCLUSIONS: These findings support the idea that GI stromal tumours form a heterogeneous group of neoplasms in which large size, presence of necrosis, and a high proliferative index (mitotic rate or MIB-1 index, or both) are good predictors of malignant behaviour.     

Fat suction versus abdominoplasty

The author describes his fat-suction technique for the treatment of abdominal adiposity. He stresses the importance of the proper selection of patients prior to surgery and the indications for such surgery, analyzing especially the accumulation of subcutaneous adiposity and muscular flaccidity. He divides surgical techniques into four separate groups: isolated fat suction; fat suction associated with infraumbilical cutaneous resection; fat suction associated with conventional abdominoplasty; and, conventional abdominoplasty. The criteria of indications for each separate procedure are strongly emphasized.     

Adipose tissues differentiated by adipose-derived stem cells harvested from transgenic mice

Objective: To induce adipocyte differentiation in vitro by adipose-derived stromal cells (ASCs) harvested from transgenic mice with green fluorescent protein (GFP) and assess the possibility of constructing adipose tissues via attachment of ASCs to typeⅡcollagen scaffolds. Methods: Inguinal fat pads from GFP transgenic mice were digested by enzymes for isolation of ASCs (primary culture). After expansion to three passages of ASCs, the cells were incubated in an adipogenic medium for two weeks, and the adipocyte differentiation by ASCs in vitro was assessed by morphological observation and Oil Red O staining. Then they were attached to collagen scaffolds and co-cultured for 12 hours, followed by hypodermic implantation to the dorsal skin of nude mice for 2 months. The newly-formed tissues were detected by HE staining. Results: The cultured primary stem cells were fibroblast-like and showed active proliferation. After being incubated in an adipocyte differentiation medium, the lipid droplets in the cytoplasm accumulated gradually and finally developed into mature adipocytes, which showed positive in Oil Red O staining. A 0. 5-cm3 new tissue clot was found under the dorsal skin of the nude mice and it was confirmed as mature adipose tissues by fluorescent observation and HE staining. Conclusions: ASCs can successfully differentiate adipose tissues into mature adipocytes, which exhibit an adipocyte-like morphology and express as intracytoplasmic lipid droplets. It is an efficient model of adipose tissues engineered with ASCs and type I collagen scaffolds.     

人脂肪干细胞的体外培养鉴定及分化特性

目的：在体外从脂肪块中分离出脂肪干细胞（adipose derived stem/stromal cells,ASCs）,对其进行形态观察、干细胞鉴定、增殖和分化能力检测。方法：将腹部取皮术的皮下脂肪利用胶原酶消化法,进行体外分离培养,取第3代的细胞进行细胞爬片HE染色、流式鉴定、MTT、细胞周期检测等,利用成脂和成骨培养液诱导,油红O和茜素红染色鉴定诱导结果。结果：原代培养第1次换液时细胞多呈多角形和短梭形,第3代ASCs细胞爬片HE染色显示形态多为长梭形,呈漩涡状生长;流式鉴定显示：CD29＋,CD31-,CD34-,CD44＋,CD45-,CD49＋,CD106-,CD133-;MTT显示ASCs生长增殖活性强;细胞周期检测结果显示：G1=86.8%,G2=8.77%;成脂诱导后油红O染色阳性,对照组为阴性;成骨诱导后茜素红染色阳性,对照组为阴性。结论：人ASCs具有贴壁生长、多向分化以及干细胞表型等特征,且生长增殖活性强,是一种很有应用前景的间充质干细胞。     

Divergent myoid, neuroendocrine, and perineural differentiation in a nasal tumor of a patient with Carney complex

A 39-year-old woman with Carney complex presented with a stroke of undetermined etiology. Computed tomography showed bilateral thalamic infarctions and also an unsuspected multicompartmental cystic neoplasm that had eroded the anterior clivus and extended forward into the nasopharynx. Histologically, the mass appeared benign and was composed of spindle cells and multiple foci of striated muscle. Immunohistochemically, the spindle cells were strongly reactive for S-100 protein and to a lesser extent for CD57, collagen IV, neuron-specific enolase, smooth muscle actin, epithelial membrane antigen, and glut-1. The striated muscle cells were positive for desmin and myogenin. The MIB-1 labeling index was 0.5%. Ultrastructural examination was necessary to reveal the full extent of divergent differentiation. Ultrastructurally, the spindle cells showed divergent differentiation along several cell lines, including smooth muscle, neuroendocrine, hybrid smooth muscle-neuroendocrine, perineural-like cells, and striated muscle. The occurrence of this unique lesion in a patient with the Carney complex raises the possibility that it may be a rare component of the syndrome.     

Papillary glioneuronal tumor with highly degenerative pseudopapillary structure accompanied by specific abortive glial cells: a case report

Recently, unusual examples of tumors of the mixed glioneuronal type have been reported, including the papillary glioneuronal tumor (PGNT). A 23-year-old woman with a 2-3 months history of headache and insomnia presented with a tumor. Neuroimaging showed a right temporal lobe cystic tumor with a mural nodule enhanced by contrast medium. She underwent gross total resection of the tumor. The tumor was histologically marked by a mixture of glial and neural components. A pseudopapillary component was comprised of highly hyalinized vessels surrounded by a single layer of thin spindle cells stained for glial fibrillary acidic protein. Specific abortive glial cells stained for vimentin/S-100 protein accompanied pseudopapillary structure. Intervening neural areas were occupied by neural cells of varying size, including neurocyte-like cell and ganglionic cells. Ganglionic cells demonstrated abnormal cluster, lack of normal polarity and epiperikaryal immunoreactivity for synaptophysin staining suggesting neural neoplastic nature. No mitotic activity or necrosis was noted. A MIB-1 labeling index was 1.8%. Our patient remains free of disease 33 months after surgical treatment.     

Basal cell adenoma with myoepithelial cell-derived “stroma”: A new major salivary gland tumor entity

The light microscopic, immunohistochemical, and ultrastructural features of a unique variant of tubular-trabecular basal cell adenoma are described. The unusual feature of the six examples reported is the richly cellular “stroma” composed of spindle cells coursing between the anastomosing cords of epithelial tumor cells. Immunohistochemistry of all six cases and electron microscopy of two examples illustrated the biphasic differentiation of the epithelial portion of this form of basal cell adenoma, with a central core of duct luminal cells bordered on either side by one or more layers of modified myoepithelial cells. By light microscopy, the features and arrangement of cells in “stromal” regions of this tumor convey a fibroblastic derivation. However, this population of cells stains strongly for S-100 protein, ultrastructurally displays excessive external lamina production, intercellular junctions, and a growth pattern unlike fibroblasts, and is involved in the formation of extracellular mucinous materials. Such aspects indicate a second population of neoplastic myoepithelial cells in this tumor. Thus, this form of tubulartrabecular basal cell adenoma displays tricellular differentiation and, perhaps, may be considered either a hybrid basal cell adenoma and myoepithelioma or a cellular pleomorphic adenoma.     

Basal cell adenoma with myoepithelial cell-derived "stroma": a new major salivary gland tumor entity

The light microscopic, immunohistochemical, and ultrastructural features of a unique variant of tubular-trabecular basal cell adenoma are described. The unusual feature of the six examples reported is the richly cellular "stroma" composed of spindle cells coursing between the anastomosing cords of epithelial tumor cells. Immunohistochemistry of all six cases and electron microscopy of two examples illustrated the biphasic differentiation of the epithelial portion of this form of basal cell adenoma, with a central core of duct luminal cells bordered on either side by one or more layers of modified myoepithelial cells. By light microscopy, the features and arrangement of cells in "stromal" regions of this tumor convey a fibroblastic derivation. However, this population of cells stains strongly for S-100 protein, ultrastructurally displays excessive external lamina production, intercellular junctions, and a growth pattern unlike fibroblasts, and is involved in the formation of extracellular mucinous materials. Such aspects indicate a second population of neoplastic myoepithelial cells in this tumor. Thus, this form of tubular-trabecular basal cell adenoma displays tricellular differentiation and, perhaps, may be considered either a hybrid basal cell adenoma and myoepithelioma or a cellular pleomorphic adenoma.     

Lipoblastic nerve sheath tumors: report of a distinctive variant of neural soft tissue neoplasm with adipocytic differentiation

Benign nerve sheath tumors of soft tissue can occasionally adopt unusual or unfamiliar morphologic appearances that may introduce difficulties for diagnosis, such as multinucleation, bizarre nuclei, intranuclear vacuoles, and other degenerative changes. Tumor cells adopting a signet-ring or lipoblast-like configuration, however, are mostly associated with epithelial malignancies, liposarcoma and melanoma, and have been only rarely observed in spindle cell tumors of soft tissue. We report 5 cases of benign nerve sheath neoplasms that displayed prominent signet-ring cells with lipoblast-like features. The cases presented as solitary soft tissue masses in the groin, thigh, retroperitoneum, and shoulder in 4 men and 1 woman between the ages of 31 to 57 years. Four tumors predominantly showed features of schwannoma and one of neurofibroma; however, intimately admixed with the spindle cell population, there were also numerous scattered mature adipocytes as well as lipoblast-like cells displaying a signet-ring cell appearance. Immunohistochemical studies showed strong S-100 protein positivity in the spindle cells as well as in the signet-ring lipoblast-like cells and the mature adipocytes. The signet-ring cells were negative for mucin stains, cytokeratin, EMA, CEA, and several other differentiation markers. Ultrastructural examination was performed in 2 cases. The signet-ring cells contained large cytoplasmic lipid droplets that displaced the nuclei to the periphery, consistent with lipoblastic differentiation, whereas complex, interdigitating cytoplasmic processes covered by basal lamina material characteristic of nerve sheath differentiation could be identified in the spindle cells. Four patients for whom follow-up was available were alive and well with no evidence of recurrence over a period of 28 to 116 months (median follow-up, 50 months). The presence of mature fat and signet-ring lipoblast-like cells within a nerve sheath neoplasm is quite rare and may signify a process of aberrant differentiation. Neurogenic tumors should be added in the differential diagnosis of spindle cell tumors capable of displaying prominent signet-ring cell features.     

Benign fibroblastic polyps of the colon: a histologic, immunohistochemical, and ultrastructural study

Mesenchymal proliferations presenting as mucosal polyps are relatively uncommon and are represented by gastrointestinal stromal tumors, smooth muscle and neural tumors, and inflammatory fibroid polyps. In this report, we describe the clinicopathologic features of a distinctive type of mucosal polyp composed of cytologically bland spindled cells with fibroblastic features. Fourteen cases with histologic features of"fibroblastic polyps" were identified from our case files from January 2000 to December 2003. The clinical and endoscopic findings were reviewed. Immunohistochemistry using a panel of antibodies (vimentin, smooth muscle actin, desmin, CD31, CD34, Bcl-2, c-Kit, S-100, and epithelial membrane antigen) was performed in all cases, and electron microscopy was performed in two cases. The lesions were solitary in all cases and not associated with an identifiable polyposis syndrome. Associated adenomata and/or hyperplastic polyps at different sites were present in 10 cases and hyperplastic polyps were seen in close association in 3 cases. These polyps were characterized by a monomorphic spindle cell proliferation in the lamina propria, without necrosis or mitotic activity. The lesions were intimately associated with the muscularis mucosae and resulted in wide separation and disorganization of the colonic crypts. Immunohistochemical analysis revealed strong and diffuse positivity for vimentin only. Weak and focal reactivity was noted in 2 cases for CD34 and smooth muscle actin, while staining for other antibodies was negative. Electron microscopy revealed sparse cytoplasmic organelles and many intermediate filaments. The histology and ultrastructural and immunohistochemical findings are suggestive of fibroblastic differentiation of these spindle cells. In summary, these lesions represent a distinctive type of colonic mucosal polyp that should be distinguished from other stromal polyps of the gastrointestinal tract.     

睾丸富于细胞纤维瘤临床病理观察

目的:探讨睾丸富于细胞纤维瘤的临床病理特征、鉴别诊断和预后。方法:对1例睾丸富于细胞纤维瘤的临床表现、组织形态和免疫组化进行综合分析,并结合文献讨论其病理特点及鉴别诊断。结果:30岁男性患者,右侧睾丸不适并无痛性肿大为主诉。睾丸纤维瘤实性边界清楚,包膜亦厚亦薄,切面灰白色,镜下梭型瘤细胞排列成席纹状、鱼骨状或束状,细胞丰富,细胞核无多形性,核分裂像为0～1个/10HP。免疫组化显示肿瘤细胞波形蛋白(+)、S-100局灶(+)、平滑肌蛋白局灶(+)、肌纤维蛋白(-)、α-抑制素(-)、CD34(-)、CD99(-)、Ki-67阳性率不足1%。结论:睾丸富于细胞纤维瘤是一种罕见的睾丸性索间质肿瘤,与卵巢同源性肿瘤病理特征相同;容易与睾丸的其它梭型细胞肿瘤混淆,形态学结合免疫组化可资鉴别;手术切除预后良好。     

胃肠道间质细胞瘤临床病理与免疫组化研究

目的　探讨胃肠间质瘤 (GISTs)的临床病理和免疫组化特征 ,为其诊断提供参考指标。方法　对 3 5例GISTs进行病理形态学观察 ,并采用免疫组化染色检测其CD1 1 7、CD3 4、vimentin、SMA和S-1 0 0蛋白表达检测。结果　 3 5例GISTs中 ,良性 1 6例 ,恶性 1 7例 ,潜在恶性 2例 ,主要由梭形细胞和上皮样细胞构成。免疫组化vimentin、CD3 4、CD1 1 7肿瘤细胞显示明显阳性 ,阳性率分别为 1 0 0 %、88 6%、60 0 % ,SMA和S -1 0 0蛋白呈散在细胞阳性 ,阳性率分别为 3 4 3 %和 6 1 %。结论　GISTs是胃肠道最常见的间质肿瘤 ,HE染色下形态与平滑肌肿瘤和神经源性肿瘤较相似 ,免疫组化染色对其诊断和鉴别诊断具有重要作用 ,CD1 1 7特异性较高 ,CD3 4敏感性较高     

Expression of melanocyte differentiation antigens and ki-67 in nodal nevi and comparison of ki-67 expression with metastatic melanoma

Nodal nevi represent a potential diagnostic pitfall in the analysis of lymph nodes. They may be confused with metastatic melanoma or carcinoma. Although several morphologic guidelines exist for the recognition of nodal nevi, on occasion immunohistochemical studies may be helpful for diagnosis, especially when melanocytes extend into the lymph node parenchyma. To learn more about the immunohistochemical profile of nodal nevi we examined 15 nodal nevi for the expression of S-100 protein, gp100 (HMB-45), Melan-A/MART-1 (A103), and tyrosinase (T311), and we studied the expression of Ki-67 (MIB-1) in nodal nevi and 40 melanoma metastases (35 lymph node and five cutaneous metastases). All nodal nevi were homogeneously immunoreactive for S-100 protein, tyrosinase, and Melan-A/MART-1. Two nodal nevi were focally positive for gp100. Fourteen of 15 nodal nevi were completely negative for Ki-67. One large cellular nodal nevus showed nuclear labeling in <0.2% of melanocytes. All metastases showed MIB-1 labeling. However, the percentage of labeled tumor cells varied widely, ranging from 2% to 80%. These results demonstrate that MIB-1 and HMB-45 are helpful reagents for the distinction of nodal nevi from melanoma. Immunohistochemistry for S-100 protein, Melan-A/MART-1, or tyrosinase facilitates the recognition of melanocytes but does not distinguish between nodal nevus and metastatic melanoma.     

S-100 protein immunostaining identifies cells expressing a chondrocytic phenotype during articular cartilage repair.

The healing of articular surface defects has been studied with conventional histology, which relies on the staining of the extracellular matrix to identify the phenotype of the cells present. A chondrospecific cellular marker would be useful. S-100 protein has been found in all chondroid tissues studied, and we evaluated its usefulness in the study of articular cartilage repair. Full-thickness rabbit femoral condylar defects were made, and the specimens were studied at serial time intervals. S-100 protein staining positively showed chondroid cells in the 7- and 14-day specimens, which were not identifiable by conventional techniques. At 30 and 60 days, an S-100 positive band of cells separated a deep safranin-O positive hypertrophic layer from a fibrocellular surface layer. At 120 days, the presence of S-100 protein identified cells with chondrogenic potential, and the lack of S-100 protein in other cells embedded in conventionally stained matrix suggested that these cells were no longer of a chondroid phenotype. The presence of S-100 protein-identified chondroid cells early in the repair process when the cells had not begun to synthesize conventionally stainable matrix and the lack of S-100 protein in cells late in the repair positively identified a phenotypic change earlier than conventional histology.     

Tissue engineering of human fat for soft tissue augmentation: in vitro results

. In our study we investigated whether human preadipocytes from human fat derived from routine abdominoplasty were suitable for the in vitro cultivation of fat. We could isolate and culture preadipocytes from patients of different ages and stimulate the cultured cells to differentiate into adipocytes and accumulate fat. We noticed age-related differences in the growth rate and differentiation capability into mature adipocytes. We believe that in the future a cell suspension of preadipocytes from a patient amplified in tissue culture might provide a relatively unlimited amount of injectable autologous transplant to fill soft tissue defects.     

Orbital and extraorbital giant cell angiofibroma: a giant cell-rich variant of solitary fibrous tumor? Clinicopathologic and immunohistochemical analysis of a series in favor of a unifying concept

The clinicopathologic and immunohistochemical features of one orbital and nine extraorbital soft tissue lesions, the morphology of which overlaps with giant cell angiofibroma and solitary fibrous tumor, are presented. There were 3 male and 7 female patients. Age at diagnosis ranged from 18 to 81 years (median: 45 yrs). Development of a mass was the main presenting symptom. For two patients, the lesion had been evident for several years before excision. Extraorbital tumors were located in the head and neck area (3), back (3), retroperitoneum (1), hip (1), and vulva (1). Tumor size ranged from 1.3 cm to 11 cm (median: 4.5 cm). The lesions presented grossly as well-demarcated, unencapsulated soft tissue masses. Histologically, they were characterized by the presence of alternating cellular and sclerosing areas, keloidal collagen deposition, round- to staghorn-shaped, thick-walled vessels and multinucleated giant stromal cells often lining pseudovascular spaces. Cellular areas were composed of non-atypical spindle to round cells set in a variably collagenous background. Mitotic activity ranged from 1 to 3 mitoses/10 high-power fields. Immunohistochemical studies showed positive staining of the spindle/round cells and multinucleated stromal cells invariably for vimentin, CD34, CD99, and mostly for bcl-2 but negative for muscle specific actin, desmin, CD31, CD117 (c-kit), and inhibin. Occasionally, focal reactivity was observed for smooth muscle actin, S-100 protein, epithelial membrane antigen, and keratin. Treatment consisted of simple tumorectomy in eight patients and wide excision in two. Follow-up information for eight patients (range: 7-32 mos; median: 14 mos), including four with microscopically positive surgical margins, showed no recurrence. These lesions share the clinical, pathologic, and immunohistochemical features of giant cell angiofibroma and solitary fibrous tumor, supporting the view that these tumors are closely related. In addition, it shows that giant cell angiofibroma occurs equally in both sexes and has a wider distribution than initially thought, developing even more often in extraorbital locations than in the orbit.     

Proliferative activity and branching morphogenesis in the human prostate: a closer look at pre- and postnatal prostate growth

BACKGROUND: To gain further insight into the molecular cell biologic features of prostate development, we investigated the proliferative activity of prostate epithelial and stromal cells and their topographic relationship with neuroendocrine (NE) cell distribution and regional heterogeneity. METHODS: Consecutive sections from 43 prostates taken during autopsy representing fetuses (12-38 weeks of gestation), infants, prepubertal males and adults were double stained for chromogranin A and MIB-1. MIB-1 labeling index (LI) was calculated in the budding tips, forming acini, major collecting ducts, adjacent and non-adjacent stromal compartments. Furthermore, the topographic relationship between proliferating cells and NE cells was evaluated. RESULTS: In the first half of gestation, cell proliferation as revealed by MIB-1 LI was significantly higher in epithelial structures and stroma than in older fetuses and other age groups. MIB-1 LI was higher in budding tips than in other epithelial regions. MIB-1 LI in stroma adjacent to budding tips was not higher than that adjacent to other epithelial branching segments. Co-expression of chromogranin A and MIB-1 staining was not observed. MIB-1 LI was lower in cells in the direct vicinity of chromogranin A positive NE cells than at a distance from NE cells. CONCLUSIONS: Prostate development in the first half of gestation is explosive. Thereafter, the prostate basically is a slow-growing organ. Budding tips are the major growth foci during early prostate development, while stromal growth is evenly distributed throughout the prostate, probably indicating that stromal-epithelial interactions do not manifest in enhanced proliferation at their interface. NE cells may have an inhibitory effect on proliferation of exocrine epithelial cells and are probably only associated with differentiation of prostate exocrine cells in the prostate.