Testicular Stromal Tumor: Ultrastructural, Immunohistochemical, and Gel Electrophoretic Evidence of Epithelial Differentiation

A testicular tumor, removed from a 52-year-old man, was composed of uniform spindle cells and abundant interposed collagen, and was histologically diagnosed as a stromal tumor. Electron microscopy revealed cords of cells sometimes surrounded by a basal lamina. Desmosome-like junctions were found between some cells, and immunostaining for desmoplakins was positive. Immunofluorescence studies also showed cytokeratin-positivity in most and vimentin-positivity in some of the tumor cells. The presence of typical simple epithelial cytokeratins of M, 40000, 45000 and 52000 was revealed by the western blotting method.

Cytokeratin positivity in the tumor cells suggests the epithelial nature of this mesenchymal-looking tumor. The tumor might arise from cytokeratin-positive epithelial elements of the testis or its covering mesothelium, but the histogenesis remains unresolved. Our findings suggest that some of the so-called testicular stromal tumors may in fact be of epithelial nature by presenting features typical of epithelial differentiation.     

Metaplastic Breast Carcinoma Invading Chest Wall

Metaplastic breast carcinoma refers to a heterogeneous group of neoplasms in which the typical glandular growth pattern of the tumor undergoes metaplasia, either epithelial or stromal. A 59-year-old woman presented with a breast mass that recurred in 1 year and showed invasion of the chest wall. Histological sections of both the tumor and the recurrence showed a tumor composed predominantly of stromal spindle cells with neoplastic epithelial ducts. Squamous metaplasia was seen in some ducts. Immunohistochemical staining showed positive cytokeratin and epithelial membrane antigen staining of the epithelial cells. Smooth muscle actin, S100, and vimentin were diffusely positive in the stromal cells. Electron microscopy of the original lesion showed cells with squamous epithelial and smooth muscle characteristics, and other cells that formed lumens into which microvilli projected. Electron microscopy of the recurrent lesion showed primarily spindle-shaped cells with abundant tonofilaments in the perinuclear cytoplasm, desmosomes with associated tonofilaments, filaments with focal densities, often aligned parallel with the cell membranes, surface attachment plaques, and fragments of basement membrane. Pinocytotic vesicles were rare. These metaplastic cells are derived from myoepithelial cells which are multipotential and able to differentiate into epithelial or stromal cells.     

Malignant myoepithelioma of the breast (histological, immunomorphological and electron microscopic study)

A rare kind of a breast tumor was identified in a woman of 47. The disease ran a malignant course and presented difficulties for morphological verification. Histological appearance showed areas of spindle-shaped or lamellar cells occasionally encircled with homogeneous hyalin-like substance. Locally, there were structures of alveolar or glandular type with an irregular basal membrane and loose position of cells. The primary histological diagnosis suggested a tumor of mesenchymal origin. Followed by immunomorphologic (monoclonal antibody to KL 1) and electron-microscopic examinations, the diagnosis was verified providing evidence for epithelial nature of the tumor cells, loose, forming glandular-like structures and simulating stromal elements with ultrastructural features typical of myoepithelial differentiation. The evidence obtained justify the tumor definition as a rare neoplasm of the breast known in the literature as myoepithelioma.     

Epithelial to mesenchymal transition in human breast cancer can provide a nonmalignant stroma

A breast carcinoma biopsy showed cytochemical evidence of epithelial mesenchymal transition and an alpha-smooth muscle actin-positive stromal reaction. To study the lineage, and the nature of the cells in the stromal reaction, we derived a novel cell line, HBFL-1, from the explanted biopsy. HBFL-1 cells are immortal and exhibit a shared non-random X-chromosome inactivation pattern with the epithelial tumor of origin. Yet they closely resemble normal, finite-life-span fibroblasts by morphology, lack of tumor formation in nude mice, marker expression profile, protein pattern using two-dimensional gel electrophoresis and the ability to undergo myofibroblast conversion. HBFL-1 interacts reciprocally with tumor cells in collagen gel to induce activation of MMP2, leading to tumor-like behavior of epithelial colonies. In vivo, HBFL-1 cells resembled normal-derived myofibroblasts and conferred a significant 3.5- to 7-fold increase in MCF-7 tumor size in nude mice. However, that they were indeed not normal fibroblasts was revealed by residual keratin expression and formation of epithelial microfoci in a reconstituted basement membrane and in nude mice. We conclude that breast cancer can generate its own nonmalignant stroma and that one function for this is that of a reciprocal interaction with epithelial tumor cells to facilitate tumor growth.     

Intermediate filament proteins in human testis and testicular germ-cell tumors

Normal testicular tissue and 76 testicular germ-cell tumors of various types were immunohistochemically evaluated for the expression of intermediate filament proteins of different types. In normal testes, the rete testis epithelium was positive to cytokeratin, and the Sertoli cells, stromal cells, and Leydig cells were positive for vimentin. Cytokeratin-positive cells were also found lining atrophic seminiferous tubules and were occasionally seen within nonatrophic seminiferous tubules. The classical seminomas showed vimentin positivity, but this was usually observed in a small number of tumor cells. In addition, nearly half the seminomas contained single cytokeratin-positive cells, some of which were multinucleated and appeared to represent syncytiotrophoblastic giant cells. The tumor cells in embryonal carcinomas, endodermal sinus tumors, and choriocarcinomas displayed cytokeratin positivity. In some embryonal carcinomas vimentin-positive tumor cells were also found, probably representing attempts at further differentiation of the tumor cells. In immature teratomas, both the immature and the mature epithelial structures showed cytokeratin positivity. The stromal components, including cartilage, contained vimentin, and the smooth-muscle elements, desmin. Neural tissue positive for neurofilaments and glial tissue positive for glial fibrillary acidic protein, were observed in 5 and 3 of 15 cases, respectively. It is considered that antibodies to intermediate filaments are suitable tools to characterize the differentiation patterns of testicular germ-cell tumors and have the potential to aid in the differential diagnosis especially between seminoma and embryonal carcinoma.     

Immunohistochemical examination of mucinous cystadenoma of the testis

A case of mucinous cystadenoma of the testis in a 55-year-old man is reported. The tumor was confined to the testis and was clearly separated from the epididymis. There was no connection between the tumor cyst and the rete testis. The lumen of the cyst was lined with a single-layer of columnar cells interspersed with goblet cells. There was neither stromal invasion nor metastasis to other organs and there were no ovarian or germ cell neoplastic elements in the tumor. Immunohistochemical analysis revealed that MUC2, MUC5AC, carcinoembryonic antigen, CA19-9, CK7 and CK20 proteins were expressed on the tumor epithelial cells, whereas expression of MUC6, alpha-fetoprotein, CA125, human chorionic gonadotrophin, estrogen receptor, progesterone receptor, calretinin, chromogranin A, p53, cyclin D1 and bcl-2 proteins was absent. Ki-67 protein was weakly and sparsely expressed in the nuclei of epithelial cells. The mucinous cystadenoma in the present case, which was devoid of a connection to testicular appendices and had the immunohistochemical characteristics of gastrointestinal mucosa, might have originated from one-sided differentiation of teratoma cells.     

Giant cell tumour (osteoclastoma) of the pancreas--an epithelial tumour probably of pancreatic acinar origin

A case of giant cell tumour of the pancreas has been studied. The light microscopical appearance of the tumour is indistinguishable from osteoclastoma of bone. Electron microscopy of the tumour shows many typical desmosomes between stromal cells. This is strong evidence of its epithelial nature. The cytoplasm of both the osteoclast-like giant cells and stromal cells contain abundant rough endoplasmic reticulum, many with dilated cisternae containing prominent dense granules. There are also some larger homogeneous granules, some of them electron-dense, in the cytoplasm of the cells. These findings when compared with the features of other cases of giant cell tumour of the pancreas studied by electron microscopy support the view that this epithelial tumour is of acinar origin.     

Myofibroblastoma of the tunica testis: evolving phase of so-called fibrous pseudotumor?

A collagen-rich stromal tumor attached to the testicular tunica albuginea of a 22-year-old male is reported. Immunocytochemical and ultrastructural characterization revealed a predominant population of myofibroblasts, an as yet unrecognized observation in tumors arising from testicular tunics. The possible relationship with so-called fibrous pseudotumor (nodular fibrous proliferation) is discussed. The myofibroblastic nature of the cell population would support the hypothesis of a reactive contractile process if one accepts this tumor as an evolving phase of fibrous pseudotumor.     

CLEAR CELL SARCOMA OF THE KIDNEY An Immunohistochemical Study

Three cases of clear cell sarcoma of the kidney (CCSK) and 5 cases of Wilms' tumor were investigated immunohistochemically to examine the expression of tissue-specific intermediate filaments (cytokeratin, vimentin, and desmin) and myoglobin. In CCSK, tumor cells were negative for cytokeratin, except for occasional tubular structures, and vimentin was demonstrated in only one case. In Wilms' tumor, epithelial components were positive for cytokeratin and stromal cells were positive for vimentin, while no staining was found in blastemal cells for either. Both desmin and myoglobin were negative in all tumor cells except for skeletal muscle cells in Wilms' tumor. In the current study, some neoplastic cells in CCSK were revealed to be of mesenchymal nature, but blastemal cells in Wilms' tumor were not.     

Clear cell sarcoma of the kidney. An immunohistochemical study

Three cases of clear cell sarcoma of the kidney (CCSK) and 5 cases of Wilms' tumor were investigated immunohistochemically to examine the expression of tissue-specific intermediate filaments (cytokeratin, vimentin, and desmin) and myoglobin. In CCSK, tumor cells were negative for cytokeratin, except for occasional tubular structures, and vimentin was demonstrated in only one case. In Wilms' tumor, epithelial components were positive for cytokeratin and stromal cells were positive for vimentin, while no staining was found in blastemal cells for either. Both desmin and myoglobin were negative in all tumor cells except for skeletal muscle cells in Wilms' tumor. In the current study, some neoplastic cells in CCSK were revealed to be of mesenchymal nature, but blastemal cells in Wilms' tumor were not.     

肾脏混合性上皮间质肿瘤

目的探讨肾脏混合性上皮间质肿瘤的临床病理特征。方法观察4例肾脏混合性上皮间质肿瘤的临床资料、镜下及免疫组织化学特点。结果患者3例女性,1例男性。临床表现主要为腰部不适和血尿,影像学检查示肾脏囊实性占位性病变。病理检查：肉眼肿瘤呈囊实性结构,镜下肿瘤由上皮和间质成分共同构成。上皮细胞可呈立方状、柱状、鞋钉样;其中1例上皮成分呈苗勒管上皮分化和肠上皮分化。间质成分为梭形细胞,并可见特征性呈束状分布的平滑肌组织和厚壁血管。免疫组织化学：上皮细胞AE1／AE3阳性,间质细胞雌激素受体（ER）、孕激素受体（PR）、平滑肌肌动蛋白（SMA）阳性。患者行肾切除术,术后随访未见复发。结论肾脏混合性上皮间质肿瘤为具有独特组织病理学特点的良性肿瘤,需要和肾脏其他良恶性肿瘤鉴别。     

Intra-abdominal desmoplastic small cell tumor in an adolescent suggesting a neurogenic origin

A case of a desmoplastic small cell tumor of the large omentum associated with gross ascites that occurred in a male adolescent is reported. Light microscopic studies revealed that the tumor cells were small and epithelioid in nature with eosinophilic hyaline material located in the perinuclear area. They were surrounded by rich desmoplastic and myxoidal stromal bands. Immunohistochemical staining revealed globoid perinuclear positivity for desmin. Vimentin, cytokeratin (AE3, CaM 5.2), epithelial membrane antigen, tissue polypeptide antigen, neuron-specific enolase, chromogranin A, endocrine granule constituent and synaptophysin were also positive in the cytoplasm. Electron microscopy revealed whorled intermediate filaments and some dense core granules in the cytoplasm. Bundles of microtubules in the cytoplasmic process and occasional cell junctions of zonulae adherentes in the tumor cells were also observed. DNA analysis of the tumor cells showed the three-fold amplification of the N-myc gene. Although desmoplastic small cell tumors showed a heterogeneous pattern with immunohistochemical studies, it is suggested that the tumor may originate from neurogenic cells.     

Ultrastructure of gonadoblastoma.

We examined, ultrastructurally, gonadoblastomas from two phenotypic females with a 46,XY and 46,XY/45, XO genotype, respectively. Ultrastructurally, germ cells of gonadoblastoma resembled immature gonocytes; it was not possible to classify them into exact developmental stages given for normal fetal testes or ovaries. In the dysgerminomatous part of the first tumor, germ cells showed ultrastructural signs of differentiation comparable to abortive spermatogenesis as seen in testicular but not ovarian dysgerminosa. The sex cord cells resembled either Sertoli, granulosa, or ovarian stromal cells. The stroma surrounding the epithelial nests resembled the ovarian stroma and contained interstitial cells like Leydig or ovarian hilar cells or both. The epithelial nests of gonadoblastoma were surrounded by laminar multilayered basement membranes. The hyaline masses inside the tumor nests were composed of the same material.     

Mixed Epithelial and Stromal Tumor of the Kidney: Preliminary Immunohistochemical and Electron Microscopic Studies of the Epithelial Component

Mixed epithelial and stromal tumor of the kidney is a rare biphasic tumor composed of cysts and tubules embedded in the spindle cell stroma. Although the histogenesis of this tumor is unknown, it has been proposed that both components of the tumor, i.e., stromal and epithelial, are neoplastic. The authors report preliminary immunohistochemical and electron microscopic studies of the epithelial component from one case of a typical, benign, mixed epithelial, and stromal tumor of the kidney. In this study, some tubules showed positivity for proximal, while others showed positivity for distal, nephron immunomarkers. By electron microscopy, some tubules had features of proximal tubular epithelium, while other tubules had features of the loop of Henle (thin segments). The authors believe that in a benign tumor such morphologic heterogeneity is inconsistent with neoplastic proliferation. Therefore, they postulate that in mixed epithelial and stromal tumor of the kidney the tubules are entrapped rather than neoplastic. Additional studies are needed to address this issue and electron microscopy should play a significant role in this process.     

Mixed Epithelial and Stromal Tumor of the Kidney: Preliminary Immunohistochemical and Electron Microscopic Studies of the Epithelial Component

Mixed epithelial and stromal tumor of the kidney is a rare biphasic tumor composed of cysts and tubules embedded in the spindle cell stroma. Although the histogenesis of this tumor is unknown, it has been proposed that both components of the tumor, i.e., stromal and epithelial, are neoplastic. The authors report preliminary immunohistochemical and electron microscopic studies of the epithelial component from one case of a typical, benign, mixed epithelial, and stromal tumor of the kidney. In this study, some tubules showed positivity for proximal, while others showed positivity for distal, nephron immunomarkers. By electron microscopy, some tubules had features of proximal tubular epithelium, while other tubules had features of the loop of Henle (thin segments). The authors believe that in a benign tumor such morphologic heterogeneity is inconsistent with neoplastic proliferation. Therefore, they postulate that in mixed epithelial and stromal tumor of the kidney the tubules are entrapped rather than neoplastic. Additional studies are needed to address this issue and electron microscopy should play a significant role in this process.     

Mixed epithelial and stromal tumor of the kidney: preliminary immunohistochemical and electron microscopic studies of the epithelial component

Mixed epithelial and stromal tumor of the kidney is a rare biphasic tumor composed of cysts and tubules embedded in the spindle cell stroma. Although the histogenesis of this tumor is unknown, it has been proposed that both components of the tumor, i.e., stromal and epithelial, are neoplastic. The authors report preliminary immunohistochemical and electron microscopic studies of the epithelial component from one case of a typical, benign, mixed epithelial, and stromal tumor of the kidney. In this study, some tubules showed positivity for proximal, while others showed positivity for distal, nephron immunomarkers. By electron microscopy, some tubules had features of proximal tubular epithelium, while other tubules had features of the loop of Henle (thin segments). The authors believe that in a benign tumor such morphologic heterogeneity is inconsistent with neoplastic proliferation. Therefore, they postulate that in mixed epithelial and stromal tumor of the kidney the tubules are entrapped rather than neoplastic. Additional studies are needed to address this issue and electron microscopy should play a significant role in this process.     

人子宫内膜基质细胞和腺体细胞的分离培养及鉴定

目的：人子宫内膜分离培工得到纯度较高的内膜基质细胞和腺体细胞。方法：采用二次滤网过滤法进行分离并通过光镜观察和免疫细胞化学染色对其进行鉴别。结果：基质细胞在接种后0．5h开始贴壁,可见梭形和多角形两种形态的细胞。免疫细胞化学染色显示这两种细胞均具有波形蛋白免疫反应,反应率可达95％以上,而细胞角蛋白无免疫反应性,提示它们为来源于内膜基质的基质细胞,大部分腺体细胞在接种24h后贴壁,培养后4d左右腺体细胞呈旋涡状排列,单个细胞为多角形,核大而圆,腺细胞呈细胞角蛋白反应性,反应率在90％以上,结论：采用二次滤网过滤法可成功地分离入人子宫内膜基质细胞和腺体细胞。     

Adenomyoepithelioma of the breast: Fine-needle sampling with histologic,immunohistologic, and electron microscopic analysis

Fine-needle sampling was performed in a woman with a subareolar breast mass. The cytologic diagnosis was consistent with a benign sweat gland-type tumor. Cytologic features included epithelial cells and spindle-shaped cells lying free or in fibrillary myxoid ground substance. Histologic study revealed the biphasic appearance of this tumor composed of proliferating myoepithelial cells and glandular epithelial cells as supported by immunohistologic and electron microscopic analyses. Epithelial cells were strongly positive for cytokeratins, and spindle cells were positive for actin, S-100 protein, and keratin and showed ultrastructurally typical features of myoepithelial cells.