Distribution of glial fibrillary acidic protein in central nervous system lesions of tuberous sclerosis

The distribution of glial fibrillary acidic protein (GFAP) in the central nervous system (CNS) lesions of tuberous sclerosis (TS) was examined using antiserum against GFAP and the peroxidase antiperoxidase method of Sternberger. In cortical tubers there were islands of gemistocytic astrocytes staining intensely for GFAP and occasional giant cells having some cytoplasmic staining. The majority of the cortical giant cells had no GFAP. The islands were separated by areas devoid of astrocytes with perikaryal staining. A faintly staining fibrous network was found between these islands. The majority of cells in the subependymal nodules stained. The retinal phakoma stained but not as intensely as the subependymal nodules. There was no staining whatsoever in the giant cell subependymal tumors. Absence of GFAP staining in the subependymal giant cell tumors makes their classification as astrocytomas less certain.     

Correlation of very late activation integrin and CD44 expression with extrarenal invasion and metastasis of renal cell carcinomas

Cell adhesion molecules mediate cell-cell and cell-matrix interactions, and they are thought to play an important role in tumor invasion and metastasis. Altered expression of integrins and CD44 in renal cell carcinoma has been recently demonstrated, but an association with invasive or metastatic behavior has not been reported. We examined very late activation (VLA) integrin and CD44 expression in 37 renal cell carcinomas and correlated adhesion molecule expression with multiple histological and clinical parameters. Most tumors exhibited positive staining for VLA3 (81%). Approximately one third of the tumors stained positively for VLA6 and CD44, and fewer (27%) were positive for VLA2. Only a few tumors were positive for VLA4 (8%) and VLA5 (14%). Most of the tumors exhibiting positive staining showed a combination of membranous and cytoplasmic staining patterns. Low-grade tumors positive for VLA6 showed a tendency for basilar staining of the tumor cells, whereas high-grade tumors exhibited diffuse cytoplasmic staining. All tumors exhibiting weak or strong positive staining for VLA4 or VLA5 showed extrarenal invasion or were known to have developed metastases at the time of nephrectomy. All tumors strongly positive for VLA2 or CD44 showed invasion beyond the renal capsule or metastases. In contrast to a previous study, no association was observed between positive staining and tumor grade. Nor were tumor size, architectural pattern, cell type, or DNA ploidy found to be associated with particular staining patterns. Although many of the invasive tumors showed no difference in VLA integrin or CD44 expression compared with tumors confined to the kidney, increased expression in some of them suggests that these cell adhesion molecules may contribute to the invasive or metastatic phenotype.     

Prevalence of perioperative complications after anterior spinal fusion for patients with idiopathic scoliosis

BACKGROUND: The most common primary brain tumors in children and adults are of astrocytic origin. Classic histologic grading schemes for astrocytomas have included evaluating the presence or absence of nuclear abnormalities, mitoses, vascular endothelial proliferation, and tumor necrosis. MATERIALS AND METHODS: We evaluated the vascular pattern of 17 astrocytoma surgical specimens (seven from children and 10 from adults), and four normal brains obtained at autopsy, utilizing antibody to glial fibrillary acidic protein (GFAP) and von Willebrand factor (vWF) utilizing confocal microscopy. A modified WHO classification was used. RESULTS: All tumor cases showed cells positive for GFAP. Control tissues showed a few, widely separated vessels. Pilocytic astrocytomas (four cases) showed lacy clusters of small-to-medium sized vessels, with intact vessel wall integrity. Diffuse, low grade astrocytoma (three cases) showed a staining pattern similar to control tissue; intermediate grade (one case), anaplastic astrocytoma (three cases) and gliobastoma multiforme (six cases) showed an increased vessel density with multiple small vessels (glomeruloid clusters), some with prominent intimal hyperplasia, loss of vessel wall integrity, and with numerous vWF-positive single cells/microvessels within the tumor substance. CONCLUSIONS: Evaluation of astrocytomas utilizing antibody to vWF and confocal microscopy aids in the grading of these neoplasms.     

Central neurocytoma

INTRODUCTION: A central neurocytoma (CN) is a rare tumor, of neuronal origin, well-differentiated and found intraventricularly. It mainly affects young adults. Firm diagnosis is made on immunohistochemical (IHQ) and ultrastructural studies, since on optic microscopy it is similar in appearance to an oligodendroglioma or to an ependymoma. PATIENTS AND METHODS: We studied 4 cases, three after surgical resection and one on autopsy. The average age was 29, ranging from 3 to 63. Both sexes were equally affected. In all cases IHQ techniques were used (GFAP, neurofilament, synaptophysin and specific neuronal enolase) and they were studied by electron microscopy. RESULTS: IHQ was negative for GFAP and neurofilament, but intensely positive for synaptophysin and specific neuronal enolase. On ultrastructural study there were few neurofilaments, microtubules and dense central granules typical of neural differentiation. CONCLUSIONS: The findings in our cases lead to diagnosis of NC and confirm that this tumor is a distinct clinicopathological entity.     

Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses

Small cell neuroendocrine carcinomas (SNECs) of the sinonasal tract are extremely uncommon tumors. We reviewed the clinicopathologic features of six cases of this neoplasm. There was no sex preponderance with three females and three males and a mean age at presentation of 51 years (range, 38 to 68). Two patients had disease limited to the nasal cavity, and in four the tumor involved the nasal cavity and maxillary or ethmoid sinuses. Involvement of the orbit was present in two patients. Surgery was the primary treatment. After a mean follow-up of 37 months, one patient died of local disease and liver metastases, four were alive with recurrent or metastatic disease, and one died of unrelated causes. The tumors were composed of sheets, nests, and trabeculae with extensive areas of necrosis and hemorrhage. The individual cells were small to intermediate in size and had scanty cytoplasm. The nuclei were oval or round and hyperchromatic with absent or inconspicuous nucleoli. Nuclear molding and crush artefact were present in five cases. All tumors had a high mitotic rate with frequent abnormal mitotic figures. All cases stained for Cam 5.2, neuron-specific enolase, and chromogranin. Five cases were positive for AE1:AE3, and four for synaptophysin. No case stained for S-100 protein, or neurofilaments. O-13 stained one case. No case contained EBV-RNA. SNECs of the nasal cavity and paranasal sinuses are aggressive tumors with pathological features similar to those of anaplastic small cell carcinomas of the lung. They exhibit morphological and immunophenotypic features different from olfactory neuroblastoma and should be distinguished from this tumor.     

Detection of terminal deoxynucleotidyl transferase (TdT) in nonhematopoietic small round cell tumors of children

In the differential diagnosis of small round cell tumors (SRCTs), terminal deoxynucleotidyl transferase (TdT) is often used as a marker for lymphoblastic lymphomas and leukemias. However, the specificity of TdT using the avidin-biotin-immunoperoxidase (ABC) method is not well documented. To address this issue, we stained paraffin-embedded biopsy specimens of 64 cases of childhood SRCTs using the ABC method with anti-TdT. For any TdT-positive tumors, an additional antibody panel for lymphoid markers was applied. Two patterns of TdT positivity were observed: (1) tumor specific, consisting of strong to moderate nuclear staining, and (2) scattered positive lymphoid cells, usually in a perivascular location and expressing T-cell markers. Analysis showed that 7 of 10 medulloblastomas stained with TdT in a tumor-specific pattern (4 cases moderately to strongly positive in 75-100% of tumor cells, 3 cases weakly to moderately positive in 25-50% of cells). Also, 1 of 19 rhabdomyosarcomas and 1 of 8 Ewing's sarcomas showed moderate to strong tumor-specific TdT staining in 100 and 10% of cells, respectively. Scattered TdT-positive lymphoid cells were observed in 27% of these 64 SRCTs. These findings emphasize that TdT positivity should not be relied upon exclusively for making a diagnosis of lymphoblastic leukemia or lymphoma or ruling out other SRCTs.     

Atypical angiomyolipoma of the kidney: a distinct morphologic variant that is easily confused with a variety of malignant neoplasms

BACKGROUND: The purpose of this study was to fully characterize and emphasize the salient features of an unusual variant of angiomyolipoma that the authors believe has been underrecognized. METHODS: Five cases of atypical angiomyolipoma (AAML) of the kidney, two of which were reported previously, were retrieved from the consultation files of one of the authors. In one patient a small extrarenal tumor was examined in addition to the primary renal tumor. The histopathologic features of all six tumors, the immunohistochemical findings of five tumors (including the extrarenal tumor), and the ultrastructure of three tumors were analyzed. Clinical follow-up was obtained for all patients. RESULTS: Two tumors occurred in children and presented as large masses (> or = 15 cm), and 2 tumors were small (< 5 cm) and affected middle-aged adults; the remaining tumor, of intermediate size (6 cm), occurred in an adolescent. One child with tuberous sclerosis also had a small (2 cm) extrarenal lesion. All tumors were circumscribed and had a red-brown cut surface. The largest tumors showed areas of hemorrhage and necrosis. The tumors were highly cellular and composed of various types of multinucleated and mononuclear cells. The most distinguishing of these, and virtually pathognomonic of this entity, were huge cells with abnormal strap-like and ameboid configurations having copious eosinophilic hyaline cytoplasm and myriad nuclei disposed peripherally in a ring-like fashion. Ganglion-like cells, polygonal cells, and spindle cells also were observed. For the most part, all cell types shared the same nuclear features, and except for one tumor, mitoses were negligible. The cells displayed a perivascular arrangement, and grew as loosely organized sheets oriented around abnormally dilated vascular channels or in a hemangiopericytic pattern; glomeruloid vessels were variably present. Notably, adipose tissue was inconspicuous. The tumors stained positive for HMB-45 protein, smooth muscle specific actin, and muscle specific actin antibodies, with a tendency for immunoreactivity to segregate along with individual cell phenotypes. Immunoperoxidase stains also disclosed a prominent and consistent intratumoral histiocytic component and a T-cell lymphoid infiltrate. Ultrastructurally, the tumor cells were replete with organelles showing highly electron-dense granules. All patients underwent radical nephrectomy; three patients with significant follow-up remain free of disease. CONCLUSIONS: AAML exhibits unusual but distinctive "pseudomalignant" histomorphologic features that facilitate its recognition, and a singular immunohistochemical profile that allows diagnostic confirmation. It occurs both sporadically and in association with tuberous sclerosis, affects both the adult and pediatric populations, and has shown an indolent behavior. AAML attests to the biologic and morphologic diversity that characterizes tuberous sclerosis hamartomata in general, and to the plasticity of the yet unclarified precursor of angiomyolipoma in particular.     

Extrarenal rhabdoid tumors of soft tissue: a clinicopathologic and immunohistochemical study of 18 cases

Rhabdoid tumor is a well-accepted clincopathologic entity among childhood renal neoplasms; similar tumors have been described in extrarenal locations. We present the clinicopathologic profile and the immunohistochemical features of a series of soft tissue rhabdoid tumors. Twenty-eight cases coded as extrarenal rhabdoid tumor (ERRT), RT, possible ERRT, and "large cell sarcoma" were retrieved from the Armed Forces Institute of Pathology soft tissue registry. The tumors were reclassified according to strict criteria by light microscopy, clinical information, immunohistochemistry, and, in some cases, electron microscopy. Soft tissue rhabdoid tumor (STRT) was defined as (1) a tumor composed of noncohesive single cells, clusters, or sheets of large tumor cells with abundant glassy eosinophilic cytoplasm, an eccentric vesicular nucleus, and an extremely large nucleolus; (2) positivity for vimentin and/or cytokeratin or other epithelial markers by immunostaining; and (3) exclusion of other tumor types with rhabdoid inclusions (melanoma, other sarcomas, carcinoma). Eighteen cases met our criteria for soft tissue rhabdoid tumors. The median patient age was 13 years (range, 6 months to 56 years). Ninety-four percent of STRT cases were positive for vimentin and 59% for pan-cytokeratin. Sixty-three percent and 60% were positive for CAM 5.2 and EMA, respectively. Seventy-nine percent stained for at least one epithelial marker; 76% stained for both vimentin and epithelial markers simultaneously. Forty-two percent stained for MSA, and 14% for CEA and SMA. CD99, synaptophysin, CD57 (Leu-7), NSE, and focal S100 protein were identified in 75%, 66%, 56%, 54%, and 31% of the STRT cases, respectively. All STRT cases examined were negative for HMB-45, chromogranin, BER-EP4, desmin, myoglobin, CD34, and GFAP. Follow-up examination in 61% of the STRT patients revealed that 64% of patients died of disease within a median follow-up interval of 19 months (range, 4 months to 5 years); 82% had metastases to lung, lymph nodes, or liver; 22% had local recurrences before metastasis; and 18% were alive without known disease status (median, 5.5 years). Soft tissue rhabdoid tumor is a highly aggressive sarcoma, predominantly of childhood. Besides having nearly consistent coexpression of vimentin and epithelial markers, STRTs show positivity for multiple neural/neuroectodermal markers that overlap with those of primitive neuroectodermal tumor.     

Eutocic delivery

BACKGROUND AND METHODS: Because the use of immunohistochemistry in the diagnosis of granulosa cell tumor (GCT) has not been fully explored, routinely processed (formalin-fixed, paraffin-embedded) tissue from 11 GCT, adult type, was investigated immunohistochemically (ABC method) with a broad spectrum of antibodies against various markers, including p53 and Ki-67. All of the tumors exhibited typical morphology, were limited to the ovary (stage I), and 7 cases followed a benign clinical course. RESULTS: All the tumors exhibited strong expression of vimentin, but most other antigens (including smooth muscle actin) were expressed infrequently by a minority of tumor cells or not at all. Tumor cells in 9 GCT expressed inhibin A. All the tumors exhibited very low proliferative activity, fewer than 10% of the tumor cell nuclei being stained by the antibody MIB-1 (Ki-67 antigen). The antibody D07 revealed marked overexpression of p53 protein in only one tumor. Clinical outcome was not found to be related to immunophenotypic differences. CONCLUSIONS: The diagnosis of GCT should be based primarily on the typical morphology revealed by conventional stains, but additional immunohistochemical staining with a small panel of selected antibodies (for example, against keratin, vimentin, and inhibin A) may be helpful in a few cases. The very low proliferative activity and the lack of overexpression of p53 protein are consistent with the benign clinical behavior of the majority of GCT.     

The mechanism of positive scintigraphy with 99mTc-pertechnetate in adenolymphomas of the parotid grand

Inhibin is a peptide hormone produced by ovarian granulosa cells and testicular Sertoli cells. Ovarian granulosa cell and other sex cord-stromal tumors usually exhibit positive immunohistochemical staining with antiinhibin antibodies, and this may be valuable in differentiating these neoplasms from histologic mimics. In the present study, we investigated the immunohistochemical staining of testicular sex cord-stromal tumors using antiinhibin. Immunostaining with CAM5.2, vimentin, S-100 protein, desmin, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), and placental alkaline phosphatase (PLAP) also was performed because few studies have investigated in detail the immunophenotype of testicular sex cord-stromal tumors. Fifteen of 16 Leydig cell tumors exhibited strong positive staining with antiinhibin. A proportion of Leydig cell tumors also stained positively with CAM5.2 (7 of 16), vimentin (14 of 16), S-100 protein (10 of 16), desmin (2 of 16) and epithelial membrane antigen (4 of 16). Four of six testicular sex cord-stromal tumors with varying degrees of Sertoli or granulosa cell differentiation were positive with antiinhibin, as were two of three sex cord-stromal tumors that were unclassified. Some of these tumors were positive with CAM 5.2, vimentin, S-100 protein, desmin, and epithelial membrane antigen. All tumors were negative with carcinoembryonic antigen and placental alkaline phosphatase. The immunohistochemical findings show that, analogous to their ovarian counterparts, most testicular sex cord-stromal tumors are immunoreactive with antiinhibin. Immunohistochemistry using this antibody as part of a panel may be valuable in confirming a diagnosis of testicular sex cord-stromal tumor and in differentiating these neoplasms from others that may mimic them.     

Oncogene expression in carotid body tumors

BACKGROUND: The genetic etiology of carotid body tumors is suggested by the familial occurrence of the neoplasm. Environmental influences are also implied by the fact that the tumor is more common in those living at high altitudes. However, the development of sporadic tumors occurring at sea level, which account for the majority of cases, remains unknown. METHODS: The clinical and pathologic features of 13 carotid body tumors excised in 13 patients were reviewed. Two patients had bilateral tumors, one with a strong family history, and two patients had recurrent carotid body tumors. All tumors were benign except for one that had local lymph gland metastases. All patients were followed up for a period ranging from 1 to 17 years. Each tumor was examined for the oncoproteins c-myc, bcl-2 c-erbB-2, c-erbB-3 and c-jun and for the proliferating cell nuclear antigen (PCNA) by immunohistochemistry. RESULTS: c-myc immunoreactivity was observed in all tumors and, in 12 of 13 cases, was present in more than 10% of tumor cells, bcl-2 immunoreactivity was found in 11 cases with 6 tumors exhibiting more than 10% immunopositive cells, c-jun expression was found in 5 cases with 3 tumors containing more than 10% immunopositive cells. Only two tumors were positive for c-erb-B2 immunoreactivity with a cytoplasmic staining pattern. One tumor was positive for c-erb-B3. CONCLUSIONS: The oncogenes c-myc, bcl-2 and c-jun, are abnormally expressed in some carotid body tumors. Their expression may contribute to the genesis of carotid body tumors.     

Low-grade myofibroblastic sarcoma: analysis of 18 cases in the spectrum of myofibroblastic tumors

The clinicopathologic, immunohistochemical, and ultrastructural features of a seemingly distinctive low-grade spindle cell sarcoma showing myofibroblastic differentiation have been analyzed in a series of 18 patients. The age range of the patients (7 women and 11 men) was 19-72 years (median: 42 years). A painless, enlarging mass was the most common clinical presentation. Five tumors arose in the oral cavity (including four lesions in the tongue), four in the lower extremities and three in the upper extremities, four cases in the abdominal/pelvic cavity, and two on the trunk. Eight soft-tissue cases involved skeletal muscle, three cases were located in perifascial tissues, and two arose in subcutaneous tissue. Tumor size ranged from 1.4 to 17 cm (median: 4 cm); in six cases (of which four were abdominal/pelvic) the lesion was larger than 5 cm. All patients were treated surgically, and four received additional adjunctive therapy. Histologically, most cases were cellular lesions showing a diffusely infiltrative pattern, and were composed of spindle-shaped tumor cells arranged mainly in fascicles. Tumor cells had poorly defined, palely eosinophilic cytoplasm and fusiform nuclei, which were either tapering and wavy or plumper and vesicular with indentations and small inconspicuous nucleoli. Tumor cells were set in a collagenous matrix often with prominent hyalinization. Mild nuclear atypia was noted in 16 cases; in the other 2 cases, and in the metastases of one other lesion, a greater degree of nuclear atypia was seen. In all but one case, the mitotic rate ranged from 1 to 6 mitoses in 10 HPFs (mean: 2/10 HPFs); in a single case, there were more than 20 mitoses in 10 HPFs. Immunohistochemically, all cases stained positively for at least one myogenic marker; 12 cases were positive for desmin, 11 for alpha-smooth muscle actin, and 6 for muscle actin (HHF35). Seven neoplasms were desmin positive/ alpha-smooth-muscle actin negative, and five cases were desmin negative/alpha-smooth-muscle actin positive emphasizing the variable immunophenotype of myofibroblastic lesions. In addition, 7 of 10 tumors stained at least focally positive for fibronectin. Ultrastructural examination in five cases showed characteristic features of myofibroblasts. Follow-up in 11 patients (median: 29 months) revealed local recurrence in 2 cases, and multiple distant soft-tissue, intraosseous, and pulmonary metastases in one other patient. Low-grade myofibroblastic sarcoma seems to represent a distinct entity in the spectrum of low-grade myofibroblastic neoplasms and is distinguishable from fibromatosis, myofibromatosis, solitary fibrous tumor, fibrosarcoma, and leiomyosarcoma.     

A brain-tumor model utilizing stereotactic implantation of a permanent cannula

A tumor model involving stereotactically implanted culture-reared tumor cells is presented. Stainless steel cannulas were stereotactically and permanently implanted into the caudate nucleus of 30 rats. The animals were separated into two groups. In Group I, 15 animals received a 10-microliters injection containing 10(6) C6 glioblastoma cells (five rats), 10(6) Walker 256 breast carcinoma cells (five rats), or cell medium (five rats). The coordinates were A(+1.5), L(+3.0), and DV(-5.0). In Group II, the coordinates were changed to A(+1.0), L(+3.0), and DV(-5.0) and the same number of rats received a 1-microliter injection containing 10(5) cells of each tumor in an attempt to produce more focal tumors. Two weeks after implantation, brain sections were stained with cresyl violet and a subset was stained for glial fibrillary acid protein (GFAP). A computerized morphometric analysis system was used to quantify tumor size. In Group I, the mean C6 tumor areas (+/- standard error of the mean) at specific coordinates were (in sq mm): A(+4.7) 0.4 +/- 0.2; A(+3.7) 3.5 +/- 1.1; A(+2.7) 5.7 +/- 1.7; A(+1.7) 9.5 +/- 2.3; A(+0.7) 7.5 +/- 3.2; A(-0.3) 3.7 +/- 2.9; and A(-1.3) 0.3 +/- 0.3. A nearly identical tumor mass and extension into the brain was produced in rats injected with Walker 256 cells. Similar C6 tumor areas were indicated in adjacent sections stained with cresyl violet and GFAP. Tumor was found in the caudate nucleus in all 10 rats, but not in the nucleus accumbens, fornix, or hippocampus. In Group II animals, tumor magnitude and extension into the brain were greatly reduced. The 10(6) cells in the 10-microliters volume was the most reliable tumor load for obtaining uniform tumors in different animals. The similarity of tumor distribution across different animals was indicated by the low variance of tumor area at specific anteroposterior coordinates. Reproducible and well-circumscribed caudate nucleus tumors were produced using this stereotactic procedure.     

Sarcomatoid carcinoma of the small intestine: histologic, immunohistochemical and ultrastructural features of three cases and its differential diagnosis

Three cases of sarcomatoid carcinoma of the small intestine are presented. One of them was found accidentally in the duodenum of a patient with a well differentiated adenocarcinoma and a malignant lymphoma that were limited to the stomach. The other two cases arose from the ileum. All of the tumors were whitish, soft and ulcerated with focal hemorrhage and necrosis and showed expansive growth. Each tumor consisted of a mixture of polygonal and spindle shaped anaplastic neoplastic cells arranged in sheet, short fascicular or haphazard fashion, with no finding suggesting epithelial differentiation. Special stains demonstrated intracellular mucin in only a small number of tumor cells in two cases, but not in the other case. Immunohistochemically, the tumor cells of two cases at both primary and metastatic sites showed a positive immunoreaction for cytokeratin and epithelial membrane antigen. In the other case, only a few tumor cells at the metastatic site, but not at the primary site, showed cytokeratin positivity. Various numbers of tumor cells positive for vimentin, alpha-1-antitrypsin (AAT), alpha-1-antichymotrypsin (ACT) and KP-1 were detected in each case. Ultrastructurally, some populations of tumor cells possessed various amounts of tonofilaments with a few intercellular connections between adjacent tumor cells. These cases should be classified as sarcomatoid carcinoma of the small intestine, despite partial or complete loss of epithelial features, and distinguished from the various sarcomas.     

Thyroidal oxyphilic tumors

Treatment of thyroidal oxyphilic (Hurthle cell) tumors is controversial due to difficulties in grading tumor malignancy. We classify these tumors into 3 histological subtypes: adenomas, atypical adenomas, and carcinomas. The purpose of this study was to find out whether this classification is a useful criterion for determination of the extent of surgery. Our retrospective study included 5 cases of adenoma, 2 of atypical adenoma and 13 of carcinoma. All histological specimens were revised and were stained immunohistochemically for thyroglobulin. All specimens were positive for thyroglobulin; staining for factor VIII was performed in cases in which the tumor had penetrated into blood vessels. Hemithyroidectomy was used for typical adenomas, while atypical adenomas were treated as carcinomas and total thyroidectomy was performed. 5 patients were treated with radioactive iodine. Taking into account the clinical results, we conclude that histological subtype is a useful guide for proper surgical management. Hemithyroidectomy is proper therapy for adenomas. The management of atypical adenomas was not determined as all were treated as carcinomas.     

Bone matrix proteins

Seminomas account for 50% of testicular germ-cell tumors, and more than 90% of these are classic seminomas. When patients with a histologically pure testicular seminoma show an elevated level of serum á-fetoprotein (AFP), it is generally assumed that an undetected focus of yolk sac tumor (YST) is present and the patient is managed with a treatment regimen for non-seminomatous tumor. We studied 10 cases of histologically pure seminoma with elevated levels of serum AFP in an attempt to identify any distinctive clinical, histopathologic, or immunohistochemical features. The patients ranged in age from 27 to 48 years (mean, 31 years). Eight patients had primary tumors of the testis, and two presented with supraclavicular and ileal tumors. The clinical stage at presentation varied: four tumors were stage I, four were stage II, and two were stage III. Serum levels of AFP were elevated in all patients at ranges of 10.4 to 16 ng/ml (mean, 12.0 ng/ml). In all patients, the primary tumors and metastases when present exhibited classic seminoma histology without other germ-cell components. The tumor cells expressed keratin in seven cases. The pattern of keratin immunoreactivity ranged from focal staining in five cases to moderate staining in two cases. All cases were negative for AFP, and the nine cases in which staining for CD30 (Ki-1) was performed were also negative. All four patients with stage I tumors underwent the conventional therapy for pure seminoma, i.e., orchiectomy and subsequent radiation therapy. Five patients received treatment for non-seminomatous tumors, i.e., chemotherapy after orchiectomy. Extensive work-up failed to detect the primary tumor in one patient, and he was treated for a non-seminomatous tumor, undergoing chemotherapy and irradiation. All patients are alive and well, and none has developed evidence of YST at a mean follow-up of 6 years (range, 6 months to 10 years). However, one patient who presented with an ileal metastasis recently developed a second primary extragonadal mediastinal mixed germ-cell tumor with YST and embryonal carcinoma components and an elevated serum level of AFP (27,000 ng/ml) after a 10-year disease-free follow-up. This study strongly suggests that minor elevations (相似文献   

Metastatic intestinal carcinomas simulating primary ovarian clear cell carcinoma and secretory endometrioid carcinoma: a clinicopathologic and immunohistochemical study of five cases

Five cases of ovarian metastases of intestinal adenocarcinomas that suggested the diagnosis of clear cell adenocarcinoma or the secretory variant of endometrioid carcinoma of the ovary are reported. Patient age ranged from 27 to 71 years at the time of diagnosis of the ovarian neoplasms. In four, the ovarian and intestinal tumors were discovered synchronously, and, in the fifth, the ovarian metastasis occurred 1 year after the intestinal primary was diagnosed. The ovarian tumors were unilateral in three patients and bilateral in two. They were up to 18 cm (mean, 12 cm) in maximum dimension and were characterized on microscopic evaluation by glands and cysts lined by cells whose most striking feature was abundant clear cytoplasm. In two cases, striking subnuclear or supranuclear vacuoles were present. An important clue to the diagnosis of metastatic intestinal adenocarcinoma was the presence in all cases of "dirty necrosis." The metastatic nature of the ovarian tumors was supported by the immunohistochemical findings. All tumors stained were strongly positive for carcinoembryonic antigen and cytokeratin 20 and failed to stain for CA125, whereas staining for HAM56 and cytokeratin 7 was absent or only focally positive in one case each. Three intestinal primary tumors involved the small bowel. Microscopic evaluation of the intestinal tumors in three cases and metastases in a fourth, in which the intestinal primary was not resected, showed the features of the uncommon clear cell variant of intestinal adenocarcinoma; the fifth was predominantly a conventional intestinal adenocarcinoma with only a focal clear cell component. Although intestinal adenocarcinomas metastatic in the ovary typically simulate endometrioid adenocarcinoma of the usual type or mucinous adenocarcinoma, they may mimic either primary clear cell adenocarcinoma or the secretory variant of endometrioid adenocarcinoma, particularly when the primary tumor is, even focally, the clear cell variant of intestinal adenocarcinoma.     

Exposure to high ambient temperature increases absorption and plasma concentrations of transdermal nicotine

Granulosa cell tumors with bizarre nuclei (GCT-BN) are rare lesions with a prognosis apparently similar to that of conventional granulosa cell tumors (GCT-NOS). The immunohistochemical features of GCT-BN have not been described, and the exact nature of the bizarre nuclei (BN) is unclear. Thirteen GCT-BN were studied with antibodies to cytokeratin, vimentin, epithelial membrane antigen, muscle-specific actin, alpha smooth muscle actin, desmin, and S-100 protein. Six cases were also examined by fluorescence in situ hybridization for trisomy 12, a nonrandom chromosomal aberration found in a proportion of ovarian sex-cord stromal tumors. Histologically, 12 tumors (86%) contained BN areas interspersed with large areas of GCT-NOS. The remaining tumor contained only microscopic foci of GCT-NOS. Immunohistochemically, the tumors stained for vimentin (13 tumors), S-100 protein (11 tumors), muscle-specific actin (10 tumors), cytokeratin (eight tumors), alpha smooth muscle actin (eight tumors), and desmin (one tumor), but none stained for epithelial membrane antigen. Immunostaining results for the BN and GCT-NOS areas were concordant in eight (73%) of the 11 tumors in which both areas could be independently assessed. The remaining three tumors (27%) showed discordant results for only one of the eight markers used. In five patients, trisomy 12 was detected by fluorescence in situ hybridization in areas of BN but not in areas of GCT-NOS present in the same tumor. Trisomy 12 was also present in another BN tumor in which the foci of GCT-NOS were too small to be evaluated. We conclude that within GCT-BN, areas with BN are immunohistochemically similar to areas of GCT-NOS present in the same tumor. The finding of trisomy 12 in areas with BN but not GCT-NOS in the same tumor, however, suggests that cells with BN represent a genetically distinct clone of tumor cells arising within GCT-NOS.     

Pain in the family

A case is reported of atypical glomus tumor occurring in the posterior inferior mediastinum of a 26-year-old woman complaining of severe back pain. The tumor was composed of atypical small, round tumor cells with scattered mitotic figures. In addition to sheet-like, diffuse proliferation of the tumor cells, some areas of the tumor contained small "glomoid" cells arranged in organoid and hemangiopericytomalike patterns. Immunohistochemically, many tumor cells were positive for muscle-type actins and a few cells were focally positive for desmin. Ultrastructural studies revealed smooth muscle features of tumor cells, that is, pinocytotic vesicles, external laminas, dense plaques, and occasional thin filaments with dense bodies. The patient remained well for 5 years and 4 months after the operation without additional radiation and chemotherapy. The tumor was diagnosed as an atypical, or low-grade malignant, glomus tumor morphologically. It seems important to recognize the presence of this type of tumor in sites other than extremities and to differentiate it from other malignant small, round cell tumors.     

Ancrod: understanding the agent

Five primary ovarian carcinomas composed of a high-grade neuroendocrine tumor of non-small-cell type and a surface-epithelial-stromal tumor are reported. The five tumors presented in women aged 36 to 77 (mean, 57) years with abdominal distension or a palpable mass in three cases, right lower quadrant pain with tenderness and fever in one case, and a cervicovaginal smear showing a high estrogen effect in one postmenopausal patient. The tumors were unilateral, 9 to 30 (mean, 16) cm in greatest dimension, and had solid and cystic components. Three tumors were stage I; one, stage II; and one, stage III. Two patients who received chemotherapy died of tumor 8 and 36 months postoperatively, another who refused chemotherapy but later received radiation died of tumor after 19 months, a fourth was lost to follow-up, and a fifth was treated recently. Microscopically, the neuroendocrine components of all the tumors were composed predominantly of sheets, closely packed islands, cords, and trabeculae of epithelial cells with little intervening stroma. The tumor cells in the neuroendocrine areas were medium-sized to large compared with the cells of small cell carcinoma, and they contained scanty to moderate amounts of cytoplasm and hyperchromatic nuclei with coarse chromatin clumping in three cases and abundant cytoplasm and vesicular nuclei with single, large eosinophilic nucleoli in the other two. In all the cases, areas of necrosis and single-cell necrosis were extensive, and mitotic figures were abundant. Positive argyrophil and argentaffin reactions were observed in occasional to many cells in all cases. The glandular components of the tumors were grade 1/3 endometrioid adenocarcinoma (one case), grade 2/3 mucinous adenocarcinoma (2 cases), and mucinous borderline tumor with small foci of mucinous adenocarcinoma (two cases). Numerous enterochromaffin cells were identified in hematoxylin and eosin sections of the borderline mucinous components of two tumors; occasional nonargentaffin argyrophilic cells were present in the endometrioid and mucinous carcinoma components. Luteinized stromal cells were present focally in two cases, including the case in which there was evidence of a high estrogen level. Immunohistochemical studies in five cases showed staining of most cells in the solid components for cytokeratin and chromogranin A and some to most cells for serotonin and neuron-specific enolase. Neuropeptides that were detected in the solid component of one or more of the cases included vasoactive intestinal peptide, somatostatin, gastrin, and glucagon; negative results were obtained for pancreatic polypeptide and insulin. Flow cytometry in four tumors revealed that the neuroendocrine component was aneuploid in two, suspicious for aneuploidy in one, and diploid in one. Tumors of the type described are distinct pathologically from primary ovarian carcinoid tumors and small cell carcinoma of pulmonary type. Although experience with this type of tumor is limited, the prognosis appears to be poor.