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--a case report

Clear cell sarcoma of the kidney (CCSK) is a highly malignant childhood tumor, distinguished from classic Wilms' tumor by its propensity to metastasize to the skeletal system. Authors described a case of CCSK from a 3-year-old boy in the right kidney, showing various histologic features, such as classic, epithelioid, trabecular, neurilemmoma-like, cystic and entrapped collecting tubular pattern. Ultrastructurally epithelial differentiation was absent. Immunohistochemically, none of the intrinsic tumor cells showed positive staining with the antibodies against the keratin, S-100 protein, carcinoembryonic antigen, vimentin, desmin and myoglobin, suggesting primitive mesenchymal cell in origin.     

Intriguing Case: Primitive Pelvic Sarcoma Resembling Clear Cell Sarcoma of Kidney

Clear cell sarcoma of kidney (CCSK) is an aggressive childhood renal tumor of unknown histogenesis that has not been reported to occur outside the kidney. The article describes an extrarenal neoplasm arising in the pelvic soft tissues of a 13-year-old boy that was composed predominantly of uniform mesenchymal cells with optically clear cytoplasm supported by an arborizing network of small blood vessels, which was indistinguishable in appearance from CCSK. The electron microscopic findings, although nonspecific, were essentially identical to those of CCSK, with tumor cells displaying fine chromatin, electron-lucent cytoplasm, and intercellular collagen but no evidence of tissue-specific differentiation. Immunocytochemical studies showed positivity for vimentin but negative results for desmin, myoglobin, cytokeratin, epithelial membrane antigen, S-100 protein, neuron-specific enolase and factor VIII-related antigen. Tumor cells were also nonreactive with Ulex lectin. This unusual pelvic tumor and CCSK may both derive from primitive mesenchymal cells and may represent phenotypic but not necessarily histogenetic analogs.     

Intriguing Case: Primitive Pelvic Sarcoma Resembling Clear Cell Sarcoma of Kidney

Clear cell sarcoma of kidney (CCSK) is an aggressive childhood renal tumor of unknown histogenesis that has not been reported to occur outside the kidney. The article describes an extrarenal neoplasm arising in the pelvic soft tissues of a 13-year-old boy that was composed predominantly of uniform mesenchymal cells with optically clear cytoplasm supported by an arborizing network of small blood vessels, which was indistinguishable in appearance from CCSK. The electron microscopic findings, although nonspecific, were essentially identical to those of CCSK, with tumor cells displaying fine chromatin, electron-lucent cytoplasm, and intercellular collagen but no evidence of tissue-specific differentiation. Immunocytochemical studies showed positivity for vimentin but negative results for desmin, myoglobin, cytokeratin, epithelial membrane antigen, S-100 protein, neuron-specific enolase and factor VIII-related antigen. Tumor cells were also nonreactive with Ulex lectin. This unusual pelvic tumor and CCSK may both derive from primitive mesenchymal cells and may represent phenotypic but not necessarily histogenetic analogs.     

Primitive pelvic sarcoma resembling clear cell sarcoma of kidney.

Clear cell sarcoma of kidney (CCSK) is an aggressive childhood renal tumor of unknown histogenesis that has not been reported to occur outside the kidney. The article describes an extrarenal neoplasm arising in the pelvic soft tissues of a 13-year-old boy that was composed predominantly of uniform mesenchymal cells with optically clear cytoplasm supported by an arborizing network of small blood vessels, which was indistinguishable in appearance from CCSK. The electron microscopic findings, although nonspecific, were essentially identical to those of CCSK, with tumor cells displaying fine chromatin, electron-lucent cytoplasm, and intercellular collagen but no evidence of tissue-specific differentiation. Immunocytochemical studies showed positivity for vimentin but negative results for desmin, myoglobin, cytokeratin, epithelial membrane antigen, S-100 protein, neuron-specific enolase and factor VIII-related antigen. Tumor cells were also nonreactive with Ulex lectin. This unusual pelvic tumor and CCSK may both derive from primitive mesenchymal cells and may represent phenotypic but not necessarily histogenetic analogs.     

Alveolar soft part sarcoma, granular cell tumor, and paraganglioma. An immunohistochemical comparative study

Five cases of alveolar soft part sarcoma, 5 cases of granular cell tumor, and 6 cases of paraganglioma were investigated immunohistochemically to examine the expression of tissue-specific intermediate filaments (cytokeratin, vimentin, desmin, and glial fibrillary acidic protein (GFAP], actin, myoglobin, and nervous tissue markers (S-100 protein, neuron-specific enolase, and Leu-7). In alveolar soft part sarcomas, some of the tumor cells were positive for desmin, but negative for nervous tissue markers. The tumor cells of granular cell tumors were stained with anti-S-100 protein antibody, but not with anti-neuron-specific enolase antibody. In contrast, the tumor cells of paragangliomas were positive for neuron-specific enolase, but not for S-100 protein except for stellate cells surrounding the tumor cell nests. This immunohistochemical approach was valuable for the differential diagnosis of these three tumors. Furthermore, the complete absence of cytokeratin in all of the tumor cells may be helpful in distinguishing these three tumors from metastatic carcinoma in soft tissue. The histogenesis of alveolar soft part sarcoma is a matter of controversy. The result that besides desmin actin was also demonstrated in some of the tumor cells may support the myogenic origin of this tumor.     

ALVEOLAR SOFT PART SARCOMA, GRANULAR CELL TUMOR, AND PARAGANGLIOMA: An Immunohistochemical Comparative Study

Five cases of alveolar soft part sarcoma, 5 cases of granular cell tumor, and 6 cases of paraganglioma were Investigated immunohistochemically to examine the expression of tissue-specific intermediate filaments (cytokeratin, vimentin, desmin, and glial flbrillary acidic protein (GFAP)), actin, myoglobin, and nervous tissue markers (S-100 protein, neuron-specific enolase, and Leu-7). In alveolar soft part sarcomas, some of the tumor cells were positive for desmin, but negative for nervous tissue markers. The tumor cells of granular cell tumors were stained with anti-S-100 protein antibody, but not with antineuron-specific enolase antibody. In contrast, the tumor cells of paragang-liomas were positive for neuron-specific enolase, but not for S-100 protein except for stellate cells surrounding the tumor cell nests. This immunohisto-chemical approach was valuable for the differential diagnosis of these three tumors. Furthermore, the complete absence of cytokeratin in all of the tumor cells may be helpful in distinguishing these three tumors from metastatic carcinoma in soft tissue. The histogenesis of alveolar soft part sarcoma is a matter of controversy. The result that besides desmin actin was also demonstrated in some of the tumor cells may support the myogenic origin of this tumor. ACTA     

The in vitro growth, heterotransplantation, and immunohistochemical characterization of the blastemal component of Wilms' tumor

Wilms' tumor has been proposed to originate from a developmental abnormality of the metanephric blastema. This undifferentiated component of Wilms' tumors has previously eluded efforts for in vitro growth. Blastema from a "classical" Wilms' tumor was transplanted into nude mice and passaged through 12 generations of heterotransplantation. Tumors from heterotransplants were grown for 12 serial passages in a serum-free growth medium supplemented with hormones and conditioned media from human kidney proximal tubule cells. The blastema initially grew on a collagen-fetal calf serum matrix as multicellular spheroids, and the cells proliferating from the rim of the spheroids had a flattened shape. Pulse-labeling with bromodeoxyuridine (BrdU) identified the proliferating cell population as blastemal in origin. Except for a loss of extracellular matrix, ultrastructural studies demonstrated morphologic similarities in the cultured cells, compared with the primary tumor and heterotransplants. Lectin histochemical stains for the peanut lectin (PNA) and immunohistochemical stains for cytokeratin (CYTO), vimentin (VIM), and epithelial membrane antigen (EMA) were performed on the original tumor, successive heterotransplants, and cells grown in vitro. The PNA stained the surface of the blastemal cells after sialidase digestion in the original tumor, heterotransplants, and cultured cells. The blastema of the original tumors was negative for CYTO and EMA but reactive for vimentin. This lack of differentiation was maintained in heterotransplants through 12 passages. However, blastemal cells demonstrated coexpression of CYTO and VIM intermediate filaments when grown in a serum-free medium on a matrix material. These studies demonstrate that the blastemal component of Wilms' tumor can be successfully grown in culture, passaged in nude mouse heterotransplants, and shown to undergo early stages of blastemal differentiation in vitro by growth in serum-free medium. This in vitro system provides a model for testing the factors that influence the growth and differentiation of the blastemal component of Wilms' tumors.     

肾透明细胞肉瘤的临床病理及免疫表型特征

目的 探讨肾透明细胞肉瘤（clear cell sarcoma of the kidney,CCSK）的临床病理特点、免疫表型特征及鉴别诊断。方法 应用HE和免疫组化vimentin、bcl-2、desmin、S-100蛋白、CD99、CD34、CDll7、CK、EMA染色,观察2例CCSK的病理组织学形态,并复习文献。结果 镜下见瘤细胞为上皮样或短梭形,被分枝状纤维血管间质分隔成巢团状,部分区域见黏液样变性微囊肿和细胞外胶原玻璃样变类似骨样组织的硬化型等形态变异。免疫组化示：瘤细胞vimentin和bcl-2弥漫阳性,余为阴性。结论 CCSK是一种罕见的儿童期恶性肾肿瘤,诊断主要依靠组织病理学和免疫组化,熟悉其形态学变异有利于与其它类似病变如肾母细胞瘤、先天性中胚叶肾瘤、肾恶性横纹肌样瘤、原始神经外胚叶肿瘤等鉴别。     

Extrarenal Wilms' tumor: an analysis of four cases

During a review of Wilms' tumor, four located external to the kidney were identified. Patient age ranged from 7 months to 4 years; three were female. One neoplasm was located in the parametrial connective tissue to the left of the uterus; both kidneys were radiographically normal. Three neoplasms were located in the right retroperitoneum adherent to the surface of the ipsilateral kidney, but separated from the parenchyma by a thick fibrous capsule. Two were attached to the upper pole, while the third was attached to the midportion of the kidney. Radiologic studies showed displacement of all three kidneys, but intravenous pyelogram (IVP) revealed no calyceal distortion. All four neoplasms were favorable histology Wilms' tumor: one was monophasic epithelial type, one was monophasic blastemal type, and two had a mixture of stromal, epithelial, and blastemal tissue. No teratomatous elements were present. Immunoperoxidase staining for cytokeratin (AE-1, AE-3, CAM 5.2), vimentin, and epithelial membrane antigen (EMA) showed the strongest focal positive staining of tubular structures with CAM 5.2, and slight staining with EMA. Staining reaction to vimentin was variable, but negative in most areas. Three tumors extracted from paraffin were diploid by quantitative flow cytometric DNA analysis; in one case, flow cytometry could not be performed. Clinical follow-up from 2 years to 6 years showed all children to be alive without evidence of disease. Based on the similarity to conventional renal Wilms' tumor, these findings support the hypothesis of displaced mesonephric/metanephric rests for the origin of extrarenal Wilms' tumor.     

Immunohistochemical study of rhabdomyosarcoma. Unexpected staining with S100 protein and cytokeratin

The immunohistochemical study of 60 cases of rhabdomyosarcomas made it possible to test eight different antibodies currently used in tumour pathology: i.e., antisera to vimentin, desmin, myoglobin, cytokeratin, epithelial membrane antigen, S100 protein, neurofilaments, and leukocyte common antigen. Vimentin was found in 58 cases (97 per cent), desmin in 49 cases (82 per cent), myoglobin in 23 cases (38 per cent), S100 protein in 7 cases (12 per cent), and cytokeratin in 3 cases (5 per cent). Other markers were negative. S100 protein was present in large round tumour cells with abundant eosinophilic cytoplasm (round rhabdomyoblasts), whereas cytokeratin was present in small tumour cells similar to those observed in rhabdoid sarcoma. This unexpected staining should become common knowledge for the correct interpretation of the immunohistochemical study of small cell tumours in the young.     

Rhabdomyosarcoma in childhood. An immunohistological analysis with myoglobin, desmin and vimentin

A retrospective immunohistological analysis of 64 rhabdomyosarcomas in children was performed using antibodies against desmin and in 35 cases against myoglobin. In addition a group of 12 undifferentiated tumours in which the differential diagnosis included rhabdomyosarcomas was studied. Rhabdomyosarcomas were desmin positive in 57 cases (89%), 28 cases of which showed positivity of undifferentiated small cells (44%). Myoglobin was positive in 23 cases (66%), but only one case showed positivity of undifferentiated small cells. The results show the limited use of myoglobin in the diagnosis of rhabdomyosarcoma, especially of cases with a low degree of differentiation. Three out of 12 undifferentiated tumours were desmin positive and were reclassified as rhabdomyosarcomas. In 49 rhabdomyosarcomas the investigation was complemented by the demonstration of vimentin. Vimentin was shown to be present in 27 cases in tumour cells (55%). Undifferentiated cells were positive in 26 tumours (53%) and rhabdomyoblasts reacted in 9 cases (18%). Coexpression of vimentin and desmin in some cases reflects a situation in rhabdomyosarcomas that aberrantly mimics skeletal muscle embryogenesis. In three cases desmin and vimentin positive globular inclusions were observed. It is suggested that their formation is related to dystrophic changes of contractile and cytoskeletal filaments. From the diagnostic point of view a high percentage of desmin positive cases makes desmin a successful marker for rhabdomyoblastic tumours. It is pointed out, however, that even immunohistochemistry may not contribute to solving the problem of undifferentiated tumours and that each case must be evaluated comprehensively.     

Clear cell sarcoma of the kidney--a study of seven cases over a period of three years

Clear cell sarcoma of the kidney (CCSK) can display diverse morphological patterns and mimic various other pediatric renal tumors. An accurate diagnosis of this tumour is important considering the therapeutic and prognostic implications. AIM: The present study was undertaken to describe the various histological patterns of CCSK. The histology of 7 cases and the available case files of CCSK accrued over a period of3 years were reviewed. Immunohistochemical (IHC) stains were performed in 3 cases. The histological patterns observed in this study were classical (observed in 4 cases), epithelioid trabecular, myxoid, palisading and hyaline sclerosis types. IHC revealed reactivity to vimentin and non-reactivity to cytokeratin, desmin, smooth muscle actin, neuron specific enolase (NSE) and S-100 protein. Since CCSK is essentially a histological diagnosis, the importance of an accurate diagnosis of CCSK by a pathologist cannot be overemphasized. This study describes the various histological patterns that can be observed in CCSK.     

Sarcomatoid carcinoma of the pancreas: A case report with immunohistochemical study

Sarcomatoid carcinoma of the pancreas is an uncommon neoplasm. The immunohistochemical characteristics of this unique type of pancreatic tumor were studied. Histologically, there was diffuse proliferation of atypical spindle cells that had hyperchromatic, short, spindle-shaped nuclei and pale cytoplasm. A few tiny foci of small tubular structures were seen in connection with the atypical spindle-shaped cells. Immunohistochemical examination showed that the spindle cells were positive for epithelial cell markers (cytokeratin AE3, cytokeratin AE1, epithelial membrane antigen) and DF3 (MUC1 apomucin-related antigen (ARA)), and were negative for markers such as vimentin, desmin, neuron-specific enolase, and myoglobin. DF3 antigen is known to be expressed in invasive ductal carcinoma of the pancreas and liver, as well as of the breast. Other MUC1-ARA (MY.1E12, MUC1 glycoprotein, HMFG-1, HMFG-2) and anti-CA19-9 were also detected in the present case. Thus, this tumor was diagnosed as anaplastic carcinoma (sarcomatoid carcinoma).     

EXPRESSION OF VARIOUS ANTIGENS BY DIFFERENT COMPONENTS OF UTERINE MIXED MÜLLERIAN TUMORS: An Immunohistochemical Study

An immunohistochemical study of keratin, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), vimentin, desmin, myoglobin and S-100 protein in 15 cases of uterine mixed Müllerian tumor was performed in order to analyze the expression of various antigens in different elements of this tumor. In general, the epithelial and mesenchymal components were separated easily by the presence of keratin/EMA or vimentin, respectively. However, in eight cases vimentin was expressed by epithelial cells and in four cases keratin by solid "sarcomatous" element. EMA was also identified in the "sarcomatous" areas of two cases. Specific differentiation was much easier to identify by immunohistochemical staining than by routine histologic examination. Areas with muscle differentiation were positive for desmin; myoglobin was identified in rhabdomyoblasts. 5–100 protein was present in chondrosarcomatous and liposarcomatous areas. S-100 protein was also widely distributed in other elements. Quite diverse expression of various antigens revealed by immunohistochemistry reflects the histologic multiplicity of this tumor.     

Expression of various antigens by different components of uterine mixed müllerian tumors. An immunohistochemical study

An immunohistochemical study of keratin, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), vimentin, desmin, myoglobin and S-100 protein in 15 cases of uterine mixed Müllerian tumor was performed in order to analyze the expression of various antigens in different elements of this tumor. In general, the epithelial and mesenchymal components were separated easily by the presence of keratin/EMA or vimentin, respectively. However, in eight cases vimentin was expressed by epithelial cells and in four cases keratin by solid "sarcomatous" element. EMA was also identified in the "sarcomatous" areas of two cases. Specific differentiation was much easier to identify by immunohistochemical staining than by routine histologic examination. Areas with muscle differentiation were positive for desmin; myoglobin was identified in rhabdomyoblasts. S-100 protein was present in chondrosarcomatous and liposarcomatous areas. S-100 protein was also widely distributed in other elements. Quite diverse expression of various antigens revealed by immunohistochemistry reflects the histologic multiplicity of this tumor.     

Immunohistochemistry on needle biopsies of childhood malignancies.

Ultrasound-guided percutaneous needle biopsy proved to be a reliable and safe method to obtain material for histopathological and immunohistochemical diagnosis prior to treatment in childhood malignancies. A principal tumour identification could be obtained by a combined morphological and phenotypic examination of 38 small-sized tumour biopsy specimens using a fairly limited panel of immunological reagents, including antibodies to leucocyte common antigen (CD 45), certain B- and T-cell markers, various intermediate filaments (cytokeratin, desmin and vimentin), and neuroblastoma cells (UJ 167.11, A2B5, and UJ 13A; the latter recognizes NCAM). Five undifferentiated neuroblastomas were all positive with the neuroblastoma antibodies but negative for the other markers, including vimentin. The negative reactivity for desmin and vimentin was the major immunohistochemical distinction between neuroblastomas and rhabdomyosarcomas. In addition, limited reactivity with the neuroblastoma antibodies was seen in blastematous parts of Wilms' tumour, duct-like structures in a hepatoblastoma, and in tumour cells in a few undifferentiated myelo- and lympho-proliferative lesions. This study shows the importance of a combined evaluation of morphology and the pattern of immunoreactivity employing multiple markers.     

Sarcomas of the uterus: immunohistochemical characterization and diagnosis]

Pathologic findings and immunohistochemical characterizations of 18 cases of uterine sarcomas were studied. In endometrial stromal sarcoma (ESS), 5 out of 10 cases had ovarian sex cord-like pattern and 4 out of 10 cases had smooth muscle differentiation. Immunohistochemical findings showed vimentin, desmin and cytokeratin positive in 9/10, 6/10, 2/10 cases respectively which reflects that ESS may differentiate into both epithelium and muscle components morphologically. In malignant mixed Mullerian tumors (MMT), its carcinomatous structure may be positive about vimentin, and its sarcomatous structure may be positive to the epithelium markers, which indicates that both the sarcoma and carcinoma structures have possibly a common origin. It is considered to be of value for the diagnosis of MMT, if the tumor has differentiated both epithelium and mesoderm components or to be positive to myoglobin, NSE* in immunoreaction, accompanying with the morphologic characterizations of the tumor.     

Pulmonary blastomas. Immunohistochemical investigations of three cases

Three cases of pulmonary blastoma (PB) were investigated microscopically with conventional stainings and immunohistochemically with monoclonal antibodies to cytokeratin, vimentin, desmin and neurofilament protein. The tumors differed in terms of morphology as well as of immunohistochemistry. Two were epithelial and mesenchymal mixed tumors, and the remaining one was a monophasic tumor of a typical blastemic character. The two mixed tumors also differed from each other. In one of them, the epithelial and mesenchymal component expressed cytokeratin and vimentin in a clear-cut manner without any transition. The other mixed tumor displayed a gradual epithelial-to-mesenchymal transition accompanied by a switch in the expression of cytokeratin and vimentin. The third tumor was of pure mesenchymal origin, expressing vimentin in the majority of cells and desmin in few cells. It is concluded that the PB is a morphologically and histogenetically heterogeneous tumor. Metaplastic changes may take place within a PB and make the recognition of embryogenesis more difficult.