Ezrin expression in stromal cells of capillary hemangioblastoma. An immunohistochemical survey of brain tumors.

Ezrin is a cytoskeleton-associated protein that appears to link actin filaments to the plasma membrane. Immunocytochemical studies suggest that ezrin is expressed in epithelial cells but not in mesenchymal cells. In addition, ezrin is expressed by certain epithelial tumors, such as renal cell adenocarcinomas. Ezrin serves as a tyrosine kinase substrate, and is phosphorylated in epidermal growth factor-stimulated cells. Ezrin may thus mediate regulatory signals in different cell functions. We studied the distribution of ezrin in 104 cases of primary tumors of the central nervous system (CNS) by immunocytochemistry. Special interest was focused on capillary hemangioblastoma, owing to its resemblance to renal cell adenocarcinoma, and on malignant gliomas, owing to their frequent epidermal growth factor receptor amplification. The stromal cells of hemangioblastomas were found to be strongly positive for ezrin. No expression was detected in gliomas and, except for hemangioblastomas, ezrin expression was restricted to those few CNS tumors that show epithelial differentiation, ie, choroid plexus papillomas, craniopharyngiomas, ependymomas, and cysts. The diffuse cytoplasmic expression of ezrin in the stromal cells of capillary hemangioblastoma may indicate that stromal cells overexpress ezrin or express ezrin with deficient binding properties.     

PAX8 expression in sporadic hemangioblastoma of the kidney supports a primary renal cell lineage: implications for differential diagnosis

Hemangioblastoma is a benign, morphologically distinctive neoplasm of disputed histogenesis that typically occurs in the central nervous system either in the setting of von Hippel-Lindau disease or more often sporadically. Extraneural hemangioblastoma is exceptional and raises a challenging differential diagnosis. Herein, we report a primary renal hemangioblastoma occurring in 51-year-old woman without stigmata of von Hippel-Lindau disease. Histologically, the tumor was composed of sheets of polygonal epithelioid stromal cells with ample pale or eosinophilic, vacuolated cytoplasm in an arborizing capillary network. Tumor cells showed variable nuclear pleomorphism, intranuclear cytoplasmic invaginations, scattered hyaline globules, and psammoma-like calcifications. Some areas showed branching hemangiopericytoma-like vessels with tumor cells radiating from the wall, while other areas were edematous and hyalinized with sparse stromal cells and abundant reticular vessels. Immunohistochemically, the tumor cells reacted strongly and diffusely with antibodies to PAX8, CD10, α-inhibin, S100 protein, neuron-specific enolase, and vimentin, and they showed focal positivity with antibodies to epithelial membrane antigen and AE1/AE3. Tumor cells were negative for CK7, CK8/18, RCC antigen, synaptophysin, chromogranin, c-kit, D2-40, HMB45, melan-A, cathepsin K, SMA, desmin, CD31, CD34, and estrogen and progesterone receptors. Positive immunoreactivity for PAX8 is unexpected and contrasts to central nervous system (CNS) hemangioblastomas, which are essentially always negative for PAX8. This novel finding adds support to the hypothesis that the immunoprofile of extraneural hemangioblastoma varies with site of origin, perhaps as a result of tumor cell lineage and retention of organ-specific markers or acquisition of site-specific antigens due to local factors.     

Retroperitoneal peripheral hemangioblastoma: a case report and review of the literature

Central nervous system hemangioblastomas are uncommon tumors of controversial etiology that are usually found in the posterior fossa of the cranial cavity, retina, and spinal cord. Peripheral involvement is rare; only isolated case reports have been identified. We report an unusual case of hemangioblastoma involving the retroperitoneum. A 47-year-old African-American man presented with polycythemia on routine laboratory testing. Computed tomography revealed a large retroperitoneal mass near the pancreas, in a left suprarenal location, without adrenal involvement and without attachment to a nerve. Although hemangioblastoma may be associated with the von Hippel-Lindau syndrome, this patient did not have any of the stigmata of this disease. The histologic features included a highly vascular tumor with cellular areas composed of plump, pleomorphic spindled and epithelioid (stromal) cells with variable cytoplasmic lipid vacuoles and hypocellular areas with inflammatory cells and collagenous fibrils. Immunohistochemical staining showed that the tumor (stromal) cells were positive for vimentin, calponin, S-100 protein, neuron-specific enolase, and CD57 and negative for glial fibrillary acidic protein, cytokeratins, epithelial membrane antigen, CD34, HMB-45, desmin, and the actins. These morphologic and immunohistochemical findings are consistent with hemangioblastoma. To our knowledge this is the first reported case of a hemangioblastoma in this location. Based on this case we conclude that hemangioblastoma may occur in the retroperitoneum and outside of the central nervous system in a patient without von Hippel-Lindau syndrome. The immunoprofile of this case suggests that hemangioblastomas are mesenchymal neoplasms exhibiting both neural and myofibroblastic differentiation.     

A detailed immunohistochemical analysis of cerebellar hemangioblastoma: an undifferentiated mesenchymal tumor

We studied 23 cases of capillary hemangioblastoma (CHB) of the cerebellum with 17 immunohistochemical cell markers in an attempt to define the nature of the so-called "stromal" cells. These cases were compared to four cases of intracranial metastatic renal cell carcinoma (RCC), which may mimic CHB histologically. The 17 markers studied included vimentin (VIM), Factor VIII-related antigen (FVIIIR:Ag), blood group antigens A, B, and H, Ulex I lectin (Ulex), Alkaline Phosphatase (Alk P), neurofilament protein (NF), glial fibrillary acidic protein (GFAP), S-100 protein (S-100), nerve growth factor receptor (NGFR), muscle-specific actin (MSA), desmin (Des), monoclonal keratin (MKER, including Cam 5.2 and AE1/3), epithelial membrane antigen (EMA), and chromogranin (Chrom). No significant stromal cell staining was seen by markers for endothelial, epithelial, chromaffin, or smooth muscle origin. In some cases individual cells demonstrated positivity for GFAP (4/22) and S-100 protein (13/23); these cells were generally stellate and located near the periphery, and we conclude that these were the result of entrapment of surrounding cerebellum. No case demonstrated NF in stromal cells. However, nearly all cases of CHB showed stromal cell staining with VIM (19/22). In contrast, all of the cases of RCC showed significant staining for at least one marker of epithelial origin (3/4 for MKER and 4/4 for EMA). We conclude that the stromal cell of CHB is neither endothelial, neural, epithelial, pericytic, nor neuroendocrine in origin, and is instead of undifferentiated mesenchymal origin. The designation of this tumor as an "hemangioblastoma," although a misnomer, is firmly established in the literature and should probably be retained.     

Fibrohistiocytic differentiation in capillary hemangioblastoma.

Seven cases of capillary hemangioblastoma from the cerebellum and spinal cord were studied by immunohistochemical methods to determine the origin of the stromal cells. A subpopulation of factor XIIIa-positive tumor cells was a constant feature in hemangioblastomas. These stellate or spindle-shaped cells transformed into typical vacuolated stromal cells. Factor VIII-related antigen was limited to the vascular endothelium. Glial fibrillary acidic protein was present only in entrapped astrocytes. Staining for alpha-1-antitrypsin (alpha 1AT) and alpha-1-antichymotrypsin (alpha 1 ACT) was occasionally observed in stromal cells. It was concluded that the factor XIIIa-positive stromal cells in capillary hemangioblastoma indicate fibrohistiocytic differentiation, which is part of the differentiation spectrum of hemangiopericytomas.     

Transthyretin and transferrin in hemangioblastoma stromal cells

Hemangioblastoma, a rare benign tumor of the CNS, consists of two main components: capillaries and stromal cells. Despite many efforts, the histogenesis of stromal cells is still unknown. We took a new approach to clarify the origin of stromal cells using immunohistochemical methods. Paraffin-embedded tissue of 24 surgically removed hemangioblastomas of the CNS was examined with antibodies against transthyretin, transferrin, vimentin, NSE, protein S-100, CK 8, KL-1, EMA, CD34, factor VIII rAg, and collagen IV. Stromal cells showed a positive reaction with anti-transthyretin in 12 of 24 hemangioblastomas, a positive reaction with anti-transferrrin, to a different extent, in 13 of 24 cases, and many stromal cells expressed basal membrane collagen IV on the cell surface in 19 of 24 cases. The expression of transthyretin and transferrin in stromal cells of hemangioblastomas is reported for the first time, thus providing an antigenic profile of hemangioblastoma stromal cells that is very similar to that of immature choroid plexus epithelium. These findings support the notion that hemangioblastoma stromal cells may originate from the embryonal plexus epithelium. We discuss our results with special regard to stromal cell histogenesis, including a review of the literature.     

Cellular and reticular variants of hemangioblastoma differ in their cytogenetic profiles

Capillary hemangioblastomas of the central nervous system are benign tumors and occur either sporadically or as a manifestation of von Hippel-Lindau disease. A rarer cellular and a more common reticular variant can be distinguished on the basis of the abundance of the stromal cell component, with the cellular variant being significantly associated with a greater probability of recurrence. To investigate whether these subtypes differ in their cytogenetic profile, a comparative genomic hybridization analysis of 10 cellular and 10 reticular hemangioblastomas was undertaken. Comparative genomic hybridization revealed DNA copy number changes in 14 of 20 cases (8 of 10 cellular and 6 of 10 reticular hemangioblastomas). The most common changes overall were losses of chromosomes 19 (35%), 6 (30%), and 22q (15%), whereas loss of 3 and gain of 4 were encountered in one case each (5%). The cellular variant showed losses of chromosomes 6 (60%), 22q and 19 (20% each), as well as gain of 4 (10%), whereas the reticular variant presented with losses of chromosomes 19 (50%), 22q and 3 (10% each). Loss of chromosome 6 was significantly associated with the cellular subtype (P < .005), whereas loss of 19/19p was found more frequently in the reticular variant, albeit not significantly (P = .16). In conclusion, our data may point toward different genetic pathways in the pathogenesis of the 2 histologic subtypes of capillary hemangioblastoma.     

Inhibin and CD99 (MIC2) expression in uterine stromal neoplasms with sex-cord-like elements.

Uterine mesenchymal neoplasms with sex-cord-like elements are designated as endometrial stromal tumor with sex-cord-like elements (ESTSCLE) or uterine tumor resembling ovarian sex-cord tumor (UTROSCT), depending on the extent of sex-cord-like differentiation. Occasionally, sex-cord elements similar to those in ESTSCLE and UTROSCT occur in uterine adenosarcomas. To determine whether the sex-cord-like elements in these tumors show immunohistological evidence of sex-cord differentiation, we studied a series of uterine neoplasms for expression of inhibin, a peptide hormone expressed by normal ovarian granulosa cells and ovarian sex-cord neoplasms, and CD99, a protein also expressed by granulosa cells, Sertoli cells, and some ovarian sex-cord tumors. Thirty uterine mesenchymal neoplasms (five epithelioid or plexiform smooth muscle tumors, three endometrial stromal tumors, two mixed endometrial stromal and smooth muscle tumors, 10 ESTSCLE, five UTROSCT, and five miscellaneous stromal processes) and five epithelial neoplasms were evaluated for expression of CD99 (clone 12E7) and inhibin (clone R1) in formalin-fixed, paraffin-embedded tissue. Three of 10 (30%) ESTSCLE and five of five (100%) UTROSCT were inhibin and CD99 immunoreactive. Inhibin staining was confined to the areas with sex-cord-like differentiation, and staining was generally much stronger and more extensive in areas featuring prominent foam cells. There were no differences in the degree or intensity of staining for inhibin in premenopausal and postmenopausal women. CD99 expression tended to correlate with inhibin and was typically confined to similar cell types in the individual neoplasms. Weak CD99 immunoreactivity was seen in one additional epithelioid smooth muscle tumor, whereas all other mesenchymal and epithelial neoplasms studied for inhibin and CD99 were negative. These results provide further immunohistological support for true sex-cord differentiation within uterine mesenchymal proliferations and suggest that the degree of sex-cord differentiation may correlate with the expression of these markers.     

Vascular growth factors and receptors in capillary hemangioblastomas and hemangiopericytomas.

Capillary hemangioblastomas and hemangiopericytomas are highly vascular central nervous system tumors of controversial origin. Of interest in their pathogenesis are mechanisms regulating endothelial cell growth. The endothelial cell mitogen vascular endothelial growth factor (VEGF) stimulates angiogenesis, and together with its two receptor tyrosine kinases VEGFR-1(FLT1) and VEGFR-2(KDR), is up-regulated during the malignant progression of gliomas. We have analyzed the expression of VEGF and its receptors, the related placental growth factor (PlGF) and the endothelial receptors FLT4 and Tie by in situ hybridization in capillary hemangioblastomas and hemangiopericytomas. VEGF mRNA was up-regulated in all of the hemangiopericytomas studied and highly expressed in the stromal cells of hemangioblastomas. In addition, some hemangioblastoma tumor cells expressed high levels of PlGF. Significantly elevated levels of Tie mRNA, Tie protein, VEGFR-1, and VEGFR-2 but not FLT4 mRNAs were observed in the endothelia of both tumor types. In hemangioblastomas, however, the receptors were also highly expressed by a subpopulation of stromal cells. Consistent results were obtained for a human hemangioblastoma cell line in culture. Up-regulation of the endothelial growth factors and receptors may result in autocrine or paracrine stimulation of endothelial cells and their precursors involved in the genesis of these two vascular tumors.     

Metastasis of renal cell carcinoma to central nervous system hemangioblastoma in two patients with von Hippel-Lindau disease

Here we report tumor-to-tumor metastases identified in two patients with von Hippel-Lindau (VHL) disease. The first patient had bilateral renal carcinomas and multiple cerebellar hemangioblastomas, and the second patient had a renal carcinoma and multiple hemangioblastomas in the retina, cerebellum and spinal cord. A cerebellar lesion from the first patient and a spinal lesion from the second patient contained two distinct components. The inner part of these tumors consisted of a nested mass of polygonal clear cells that expressed cytokeratin and epithelial membrane antigen, while the outer part of the tumors showed proliferation of capillaries and intervening foamy stromal cells that were negative for cytokeratin and epithelial membrane antigen. The tumors were thus considered to be hemangioblastomas complicated by metastatic lesions of renal cell carcinoma of clear cell type. These cases indicate that tumor-to-tumor metastasis should be considered when hemangioblastoma contains a clear cell carcinoma component in the setting of VHL disease, and that immunohistochemical staining for cytokeratin and epithelial membrane antigen is useful for the diagnosis.     

Angiogenic histogenesis of stromal cells in hemangioblastoma: ultrastructural and immunohistochemical study

Controversy regarding the origin of characteristic stromal cells (SC) is responsible for the placement of hemangioblastoma as a single entity in the category of "tumors of uncertain histogenesis" in the current WHO classification of brain tumors. This subclassification of hemangioblastoma is, to a large extent, a consequence of a remarkable antigenic heterogeneity of SC demonstrated in many, often contradictory immunohistochemical studies. In contrast, most of the electron microscopic studies demonstrated a number of features indicating angiogenic nature of SC and, therefore, hemangioblastoma. This study reevaluated the histogenesis of SC, applying immunohistochemistry as well as electron microscopy and immunoelectron microscopy. Immunohistochemical studies confirmed most of the previous results indicating a very frequent expression of vimentin, S-100 protein, neuron-specific enolase, and cytokeratins. SC were less commonly immunoreactive for desmin, factor XIIIa, and Ricinus communis lectin receptors, and only occasionally for factor VIII and Ulex europeus lectin. They were negative for other markers of endothelial, neuronal, glial, neuroendocrine, and smooth muscle differentiation. Approximately 1% of SC showed Ki67 immunoreactivity, indicating their slight proliferative activity, consistent with the benign nature of the tumor. In contrast to the inconclusive results of the immunohistochemistry, electron microscopy demonstrated a clear relationship of SC to endothelial cells, smooth muscle cells, and pericytes. Occasional SC were found within the vascular lumina. SC often showed intracellular caveolae consistent with the formation of early capillary lumina. Moreover, occasional SC contained small Weibel-Palade bodies positive for factor VIII in immunoelectron microscopy. SC represent a heterogenous population of abnormally differentiating mesenchymal cells of angiogenic lineage, with some morphological features of endothelium, pericytes, and smooth muscle cells. Occurrence of SC in hemangioblastoma could be related to a limited ability of angioformative stromal cells to develop an architecture of capillary lumina integrated with the vascular network of the tumor. Hemangioblastoma should be reclassified and included together with other vascular tumors of the central nervous system.     

Factor VIII related antigen and glial fibrillary acidic protein immunoreactivity in the differential diagnosis of central nervous system hemangioblastomas

Nineteen hemangioblastomas, nine angioblastic meningiomas, ten metastases to the brain (including five renal cell carcinomas), and five primary renal cell carcinomas were studied using the immunoperoxidase method for Factor VIII related antigen and glial fibrillary acidic protein (GFAP). All tumor types showed Factor VIII immunoreactivity confined to endothelial cells. Factor VIII immunostaining revealed a distinct, though probably nondiagnostic, vascular pattern for hemangioblastomas as compared with metastatic carcinomas and angioblastic meningiomas. Most of the hemangioblastomas and metastases showed numerous GFAP-reactive cells with unequivocal astrocytic morphology primarily at the interface with brain parenchyma but also occasionally deep within the tumor. Within metastases these cells often were associated with penetrating fibrovascular septa. In a minority of hemangioblastomas and metastatic carcinomas there were rare GFAP immunoreactive cells that were indistinguishable from stromal or metastatic tumor cells, respectively. Angioblastic meningiomas showed no GFAP reactivity. It is concluded that the presence of GFAP-reactive cells alone is not helpful in differentiating between hemangioblastomas and intra-axial lesions. The lack of stromal cell immunoreactivity in angioblastic meningiomas and the rare staining of stromal cells in hemangioblastomas, seen also in central nervous system (CNS) metastases, suggest that except for the endothelial cells lining vessels, these primary CNS lesions are not antigenically closely related to either endothelial cells or astroglia. Furthermore, in the evaluation of tumors within the CNS, the significance of rare GFAP-positive tumor cells must be interpreted with caution.     

Myxoid mesenchymal tumors of uterus: endometrial stromal and smooth muscle tumors, myxoid variant

Four myxoid variant of uterine mesenchymal tumors are reported. One was a low grade stromal sarcoma with infiltrative margins and the others were well circumscribed tumors corresponding to an endometrial stromal nodule and two leiomyomas. They were hypocellular neoplasms composed of stellated cells with an abundant Alcian Blue positive myxoid matrix. The myxoid nature of the neoplasms obscured their cellular nature and made the distinction between smooth muscle and endometrial stromal tumors difficult. Endometrial stromal tumors, showed very focal areas of small basophilic cells, characteristic of endometrial stroma. The diagnosis was based on the presence of a spiral arteriolar network, a CD10 positivity as well as the absence of h-caldesmon and desmin expression. The two myxoid leiomyomas showed more spindle cells and a desmin expression while h-caldesmon was negative and CD10 focally positive in both cases. Myxoid variant of endometrial stromal tumors does not necessarily exhibit the typical morphology of endometrial stroma. They may demonstrate morphological features of smooth muscle tumors in the uterus. Also, myxoid changes in uterin smooth muscle tumors may modify the classical immunoreactivity of smooth muscle markers in these tumors and make it difficult to distinguish between benign and malignant neoplasms. An immunohistochemical panel of antibodies including CD10, h-caldesmon and desmin may help in establishing the correct diagnosis.     

Thymoma with pseudosarcomatous stroma.

Thymoma with psuedosarcomatous stroma is a recently described, rare variant of thymomas that are characterized by having a biphasic histologic pattern which consists of both an epithelial and a spindle cell stromal component. So far only 11 cases having similar histologic findings have been reported worldwide. At this time we report a case of this rare variant of thymoma which occurred in a 53-year-old Korean man. This previously healthy patient presented with coughing and an anterior mediastinal mass was then detected radiographically. Mediastinal exploration revealed a 9 x 8 x 8 cm-sized well- encapsulated, ovoid, cystic mass. Histological examination showed a biphasic neoplasm composed of anastomosing nests of epithelial cells and somewhat cellular stromal spindle cells that had advanced degenerative changes. Immunohistochemical staining using the antibodies for cytokeratins, EMA, e-cadherin, and p75NGFR showed a strong expression of these markers in the epithelial component but no expression in the spindle stromal cells. The epithelial tumor cells showed no reactivity to CD5 and L26 and a high proportion of the infiltrated lymphocytes were the cortical type that expressed CD99 and terminal deoxynucleotidyl transferase. Ultrastructural examinations revealed tonofilaments in the spindle cells. Follow up has been done for 5 years after the surgical excision and the patient has been free of disease during that period. Similar to previous reports, this patient had a benign clinical course that was unassociated with myasthenia gravis which appears to be a characteristic of this histologic variant of thymoma. However, our case also showed advanced degenerative features and we could demonstrate ultrastructural evidence of epithelial differentiation in the stromal spindle cells that were not mentioned in the previously reported cases. Based on the results of our studies, we suggest this entity is a distinct type of organotypic thymoma that shows cortical differentiation and abundant cellular stroma.     

Sinonasal Teratocarcinosarcoma: Ultrastructural and Immunohistochemical Evidence of Neuroectodermal Origin

The authors report a case of sinonasal teratocarcinosarcoma in a 37-year-old man, which was located in the anterior skull base and extended to the right nasal cavity and paranasal sinuses. The tumor was surgically resected twice, but it could not be removed completely. Microscopically, it was mainly composed of primitive cell nests within a moderately cellular stroma. The components of squamous cell epithelia with focal teratoid appearance and adenocarcinomatous differentiation were observed. There were many rhabdomyoblasts scattered in the nests and stroma. Ultrastructurally, the primitive cells had many neural processes with parallel microtubules, resembling olfactory neuroblastoma. Rhabdomyoblasts showed various degrees of skeletal muscle differentiation. Some of the stromal spindle cells had actin filaments with dense patches and dense core granules. Immunohistochemically, the primitive cells were positive for epithelial markers, neuron-specific enolase, synaptophysin, and myogenic regulatory proteins. The rhabdomyoblasts showed immunoreactivity for myoid markers, cytokeratin, epithelial membrane antigen, and synaptophysin. Most of the stromal spindle cells were positive for smooth muscle actin, neuron-specific enolase and synaptophysin. The immunohistochemical and ultrastructural findings suggest that primitive cells had the most primitive phenotype of placodes, and support the possibility that sinonasal teratocarcinosarcoma is essentially a neuroectodermal tumor with divergent differentiation.     

Sinonasal teratocarcinosarcoma: ultrastructural and immunohistochemical evidence of neuroectodermal origin

The authors report a case of sinonasal teratocarcinosarcoma in a 37-year-old man, which was located in the anterior skull base and extended to the right nasal cavity and paranasal sinuses. The tumor was surgically resected twice, but it could not be removed completely. Microscopically, it was mainly composed of primitive cell nests within a moderately cellular stroma. The components of squamous cell epithelia with focal teratoid appearance and adenocarcinomatous differentiation were observed. There were many rhabdomyoblasts scattered in the nests and stroma. Ultrastructurally, the primitive cells had many neural processes with parallel microtubules, resembling olfactory neuroblastoma. Rhabdomyoblasts showed various degrees of skeletal muscle differentiation. Some of the stromal spindle cells had actin filaments with dense patches and dense core granules. Immunohistochemically, the primitive cells were positive for epithelial markers, neuron-specific enolase, synaptophysin, and myogenic regulatory proteins. The rhabdomyoblasts showed immunoreactivity for myoid markers, cytokeratin, epithelial membrane antigen, and synaptophysin. Most of the stromal spindle cells were positive for smooth muscle actin, neuron-specific enolase and synaptophysin. The immunohistochemical and ultrastructural findings suggest that primitive cells had the most primitive phenotype of placodes, and support the possibility that sinonasal teratocarcinosarcoma is essentially a neuroectodermal tumor with divergent differentiation.     

Mixed tumors of the vagina: an immunohistochemical study of 13 cases with emphasis on the cell of origin and potential aid in differential diagnosis.

Mixed tumors of the vagina (MTsV) are rare benign neoplasms characterized by an admixture of well-differentiated epithelial cells and stromal-type cells in various proportions. In contrast to mixed tumors in other anatomic sites, the histogenesis of the vaginal tumors is unclear. We studied the immunohistochemical profile of 13 examples to explore their histogenesis and determine whether their immunohistochemical profile might be useful in the differential diagnosis. The panel of antibodies used and the number of cases studied were: AE1/3 (12), cytokeratin 7 (CK7) (13), cytokeratin 20 (CK20) (13), epithelial membrane antigen (EMA) (13), muscle actin (MA) (12), desmin (11), h-Caldesmon (13), CD10 (13), CD34 (11), CD99 (8), and S-100 (7). Eight out of 12 tumors were positive for AE1/3, 7/13 for CK7, 2/13 for CK20, and 6/13 for EMA. MA was positive in 11/12 mixed tumors, desmin in 10/11 tumors and h-Caldesmon in 5/13. All tumors were extensively positive for CD10; CD34 was positive in 7/11; and none out of eight tumors showed membranous CD99 staining. Focal S-100 immunoreactivity was seen in 1/7 tumors. These results show that MTsV coexpress epithelial and mesenchymal markers. The expression of muscle actin (usually extensive), and focal desmin and h-Caldesmon positivity suggests the presence of a smooth muscle or myoepithelial component; however, the S-100 negativity and diffuse CD10 expression argue against it. Positivity for muscle markers does not help distinguish MTsV from smooth muscle or skeletal muscle tumors. The frequent expression of CD10 negates its use in the differential diagnosis with endometrial stromal tumors, and the CD10 and CD34 expression suggests that mixed tumors may arise from a primitive pluripotential cell. MTsV are positive for h-Caldesmon and CD10, two markers that have been used in gynecologic pathology primarily to aid in establishing the smooth muscle or endometrial stromal phenotype of a neoplasm.     

Epithelioid gastrointestinal stromal tumor with PDGFRA activating mutation and immunoreactivity.

The authors report a unique case of an intra-abdominal, epithelioid mesenchymal tumor that had an activating mutation of PDGFRA and a strong PDGFRA immunoreactivity but lacked both c-kit mutation and c-kit protein (CD117) expression. IHC study showed that the tumor cells were diffusely and strongly positive for PDGFRA, vimentin, CD34, and Bcl-2 but completely negative for CD117 as well as for muscle, epithelial, endothelial, endocrine, mesothelial, neural, and melanocytic cell markers. Molecular study revealed a mutation at the juxtamembrane domain of exon 12 in PDGFRA gene with GTC to GAC transition at codon 561 (V561D), as shown in the previous mutational studies on gastrointestinal stromal tumor (GIST). This case likely represents an example of GIST with PDGFRA activating mutation and PDGFRA immunoreactivity without CD117 positivity, which has not been documented in the literature. STI 571 (imatinib mesylate [Gleevec]) might be an effective therapy in this case, since Gleevec targets both PDGFRA and c-kit oncoproteins.     

Immunophenotypic features of uterine stromal cells

CD34 is a myeloid progenitor cell antigen present in endothelial cells and some other mesenchymal cells, including perivascular and periadnexal dermal fibroblasts. It was evaluated immunohistochemically in uterine stromal tissue and in 4 aggressive angiomyxomas and 6 endometrial stromal sarcomas with potentially related and similar stromal tissues. The stromal cells in normal endocervix and endocervical polyps were strongly CD34 positive irrespective of the cycle phase, and negative for muscle actins. Ectocervical stroma was variably but generally less CD34 reactive. In the endometrium, the CD34 reactivity was limited to the stromal cells of the basal endometrium and was found only in 4 of 20 from proliferative endometria and 1 of 8 from secretory endometria. The uterine cervical and myometrial smooth muscle tissues showed CD34 positive cells only between the muscle bundles and around the vessels. In pelvic aggressive angiomyxomas and endometrial stromal sarcomas the tumour cells were CD34 negative and only the vascular endothelial cells were positive. Endothelial cell-specific antigen, CD31, was identified only in endothelial cells and was not present in the endocervical stroma. These results illustrate the particular immunohistochemical profile of endocervical stromal tissue, namely the strong CD34 expression. The CD34 reactivity of the endocervical tissues should be noted and not confused with neoplasms known to be strongly CD34 positive, such as angiosarcomas, Kaposi's sarcomas and some other spindle cell sarcomas.     

九例小脑血管母细胞瘤的超微结构观察

Ultrastructural study of 9 cases of cerebellar hemangioblastoma demonstrated the presence of three major component cells: endothelial cells, pericytes, and stromal cells. These three kinds of cells share the following similar fine features: presence of micropinocytic vesicles, lots of microfilaments, hemidesmosomes, and basement membranes. Weibel-palade bodies were found not only in the endothelial and stromal cells but also in the pericytes. We support the idea that these three kinds of cells belong to a common lineage. Ultrastructurally, pericytes show less differentiation than endothelial and stromal cells. Some transitional forms between pericytes and endothelial cells, or between pericytes and stromal cells were obtained. We suggest that pericytes probably have the capacity of being transformed to endothelial and stromal cells.