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PubMed1996

Malignant mesenchymoma.

BACKGROUND: Malignant mesenchymomas are rare soft tissue tumors that contain two or more distinct histologic subtypes of sarcoma within the same tumor (exclusive of a fibrosarcomatous or hemangiopericytomatous component). They are generally considered high grade neoplasms and are associated with a poor prognosis, although experience with these tumors is limited. METHODS: We report 8 patients seen at our center over the last 22 years and describe the clinical course of a patient with a malignant mesenchymoma arising in the retroperitoneum whose experience typifies the aggressive behavior of this tumor. RESULTS: All eight patients had large, high grade tumors located in the retroperitoneum or thigh. Six of the 8 died of disease and 2 were alive with disease at a median of 30 months from diagnosis. CONCLUSIONS: Malignant mesenchymoma represents a particularly aggressive form of soft tissue sarcoma. Our experience with this disease highlights the need for more effective treatment strategies for these patients.

Adult↗

PubMed1997

Usefulness of radiography in differentiating enchondroma from central grade 1 chondrosarcoma.

OBJECTIVE: The purpose of this study was to evaluate clinical symptoms and radiographic features that allow radiologists to differentiate between enchondroma and central grade 1 chondrosarcoma. Such differentiation is important because of differences in management. MATERIALS AND METHODS: Clinical symptoms and location and size of 35 enchondromas and 43 central grade 1 chondrosarcomas were analyzed. Radiographic features were assessed independently by three observers. The chi-square test and linear discriminant analysis were used to identify features with discriminating strength. Kappa values were calculated to validate the consistency of observations among observers. A consensus diagnosis made by histology and long-term follow-up was used as the standard. RESULTS: No statistically significant correlation was found between clinical symptoms and the benign or malignant nature of the neoplasms. Grade 1 chondrosarcomas were more likely to be found in the axial skeleton and in flat bones. Also, chondrosarcomas were significantly larger than enchondromas (p < .001). Ill-defined margins and lobulated contours were the only morphologic features seen on radiographs that allowed significant discrimination (p = .004 and .009, respectively). An optimal combination of four radiographic features still left 72 of the 78 lesions with a 10-90% probability of malignancy, indicative of poor discriminating power. Kappa values generally showed poor to fair agreement. CONCLUSION: Location in the axial skeleton and size greater than 5 cm are the most reliable predictors of central grade 1 chondrosarcoma. Morphologic features seen on radiographs and clinical symptoms do not improve the ability to differentiate between enchondromas and central grade 1 chondrosarcomas.

Adolescent↗

PubMed1991

Epithelioid angiosarcoma of deep soft tissue: a distinctive tumor readily mistaken for an epithelial neoplasm.

We report eight cases of epithelioid angiosarcoma arising in deep, usually intramuscular soft tissue. All the patients were men (mean age, 58). All the lesions arose in a limb or limb girdle. Cardinal morphologic features were the diffuse, sheetlike growth pattern, with only focally apparent vascular differentiation, and epithelioid tumor cells with a degree of intracytoplasmic vacuolation/lumen formation. Immunohistochemically, all eight cases coexpressed keratin as well as endothelial markers. In three cases, endothelial differentiation was confirmed ultrastructurally. Clinically, deep-seated epithelioid angiosarcomas are high-grade neoplasms that rapidly develop metastases. These findings expand the range of recognized epithelioid endothelial tumors and provide further evidence of keratin expression by such lesions. The presence of intracytoplasmic lumina/vacuoles (sometimes containing red blood cells) combined with the characteristic reticulin pattern and striking positivity for Factor VIII-RAg provide the clearest means of distinction from an epithelial metastasis.

Adult↗

PubMed2006

Spindle cell oncocytoma of the adenohypophysis: report of a case with a 16-year follow-up.

Spindle cell oncocytoma (SCO) is a recently described, rare neoplasm of the anterior pituitary. Clinically and radiologically simulating a non-functioning macroadenoma, its eponymous fusiform cells display a non-epithelial phenotype with conspicuous cytoplasmic accumulation of mitochondria. We report a case of SCO retrospectively identified in a biopsy specimen 16 years after transsphenoidal operation of a 48-year-old woman. Presenting symptoms were adynamia and transient decrease of visual acuity. Neuroimaging showed an isointense, enhancing, sellar-centered mass 1.8 cm in diameter without evidence of invasive growth. No postoperative adjuvant therapy was administered. The patient was left with panhypopituitarism, yet no recurrence was seen during follow-up. Initially diagnosed as a null cell adenoma of oncocytic type, repeat immunohistochemistry showed the characteristic coexpression of S100 protein, vimentin, and epithelial membrane antigen. Oncocytic granula stained intensely with antimitochondrial antibody 113-1, and were negative with the lysosomal marker CD68. Anterior pituitary hormones tested negative, and there was no evidence of neuroendocrine differentiation using antibodies to synaptophysin and chromogranin. Few cells stained for glial fibrillary acidic protein (GFAP). SCO has been proposed to represent a neoplasm of folliculo-stellate cells (FSCs). While the dynamic properties of the latter are incompletely characterized, and indeed no specific marker allows for their identification, overlapping features of SCO with look alikes, in particular pituicytoma, point to FSCs being a potential adult stem cell. The favorable outcome of the present case further argues for SCO to be considered a low-grade neoplasm. Moderate tumor size, lack of invasiveness, and low proliferation rate are likely predictors of benign behavior.

Adenoma, Oxyphilic↗

PubMed1993

Relationship between p53 expression and other prognostic factors in human breast carcinoma. An immunohistochemical study.

Among 843 cases of breast cancer, p53 oncoprotein was detected by the monoclonal antibody (MoAb) Pab-1801 in only 13%. Low-grade carcinomas (tubular, mucinous, papillary, and invasive cribriform types) did not express p53 protein, but it was observed in 4.2% of infiltrating lobular carcinomas (6 of 140 cases) and 50% of pure medullary carcinomas (5 of 10 cases). In intermediate-grade neoplasms, no correlation was seen between p53 status and other putative determinants of a poor prognosis. The latter included high tumor stage, lymph nodal involvement, high growth fraction (as determined by labeling with the MoAb Ki-67), negative results for estrogen receptor (ER) and progesterone receptor (PR) proteins, and amplification of the c-erbB-2 oncogene product in the neoplastic cells. Ninety-nine of 640 (15.5%) cases of high-grade, invasive, ductal breast carcinoma, however, showed an inverse relationship between expression of p53 protein and positive results for ER/PR proteins and a direct correlation with large tumor size, Ki-67-determined growth fraction, and amplification of c-erbB-2 oncopeptide. All of the latter associations were highly significant statistically. The authors conclude that mutant p53 protein may serve a prognostic role in a subset of cases of invasive ductal mammary carcinoma.

Breast Neoplasms↗

PubMed2006

Glioblastomatous recurrence of oligodendroglioma remote from the original site: a case report.

BACKGROUND: As in all diffuse gliomas, recurrence is an inherent feature of oligodendrogliomas, either as the same or higher grade neoplasm at the primary site. The rate of remote recurrence after surgery for the primary tumor cannot be estimated from the scarce literature, but delayed treatment of the primary tumor and genetic alterations may be associated with this phenomenon. CASE DESCRIPTION: A 40-year-old man presented with generalized seizures. A magnetic resonance imaging scan disclosed a right frontal mass lesion showing features of a low-grade glioma for which he refused any treatment. Seven months after diagnosis upon uncontrollable seizures, he underwent a stereotactic biopsy, which was followed by a right frontal craniotomy, both of which confirmed the lesion as a grade 2 oligodendroglioma. Six months after surgery, the patient presented with a left frontal lobe GBM without evidence of recurrence at the primary site. The genetic analysis of the primary and recurrent tumors showed trisomy 7, monosomy 10, but not 1p or 19q deletions, which have been proposed as markers for favorable prognosis. CONCLUSION: Recurrence of a frontal lobe oligodendroglioma remote from the primary site as a GBM is a rare occurrence. Single-cell invasion across the corpus callosum with subsequent or simultaneous malignant degeneration into a secondary GBM is the likely mechanism. As the genetic analysis suggests, conversion of oligodendroglioma to GBM may be associated with gain of chromosome 7, loss of chromosome 10, and other genetic markers that may represent late events in the oncogenesis of oligodendroglial tumors.

Adult↗

PubMed1996

Primary malignant lymphoma of the bladder. Report of three cases.

Primary malignant lymphoma of the bladder is a rare tumour. In a recent literature search only 70 cases have been found since 1885. Most of these tumours were low grade B-cell non Hodgkin's lymphomas and only 20% were high grade neoplasms. This tumour usually appears in women between 20 and 85 years (median 64 yr.) of age. 20% of them have antecedents of chronic cystitic. Some authors have considered that some of the primary malignant lymphomas of the bladder arise from the mucosa-associated lymphoid tissue (MALT), therefore acting like MALT lymphomas which affect the gastrointestinal tract, the salivary glands or the thyroid. We report three additional cases of primary malignant lymphoma of the bladder, two of high grade, and discuss the histological criteria that support their MALT nature.

Aged↗

PubMed2001

Sinonasal undifferentiated carcinoma: immunohistochemical profile and lack of EBV association.

The role of Epstein-Barr virus (EBV) in the development of sinonasal undifferentiated carcinoma (SNUC) remains unresolved. Reports of EBV-positivity in SNUC may reflect inclusion of lymphoepithelioma-like carcinomas within this group. In addition, SNUC have been incompletely characterized immunohistochemically, and their undifferentiated appearance often requires such ancillary studies to aid in their distinction from other high-grade neoplasms. To address these two issues, 25 cases of SNUC diagnosed between the years 1983 and 1999 were selected from our files. EBER in situ hybridization (ISH) was performed on the paraffin-embedded tissue by using 3H-labeled EBER-1 RNA probes. Neoplasms with sufficient tissue (22 of 25) were evaluated immunohistochemically for Ki-67, p53, chromogranin, synaptophysin, placental alkaline phosphatase (PLAP), CD99, carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), neuron-specific enolase (NSE), and latent membrane protein-1 (LMP-1). The median patient age was 58 years (range, 20-81 years), with a male-to-female ratio of approximately 3:1. The most common tumor location was the nasal cavity (18 cases), followed by the ethmoid and maxillary sinuses. Median survival was 18 months. All 25 tumors were negative for EBER-I by ISH. Ki-67 was negative in one case, 1+ in nine, 2+ in six, 3+ in five, and 4+ in one. P53 was negative in nine, 1+ in five, 2+ in two, 3+ in none, and 4+ in six. CD99 expression was strongly positive in 3 of 22 (14%) and completely negative in the remainder. Variably intense focal staining for EMA was present in 4 of 22 (18%). NSE faintly stained 4 of 22 (18%). Chromogranin, synaptophysin, PLAP, CEA, and LMP-1 were negative (0 of 22). Our results suggest that EBV does not play a role in the development of SNUC. Strict histologic criteria are necessary to avoid confusion with lymphoepithelioma-like carcinoma or other high-grade malignancies in this region. The finding of occasional CD99-positive cases adds SNUC to the growing list of CD99-positive neoplasms.

Adenocarcinoma↗

PubMed2002

Intraepithelial high-grade neoplasia and early adenocarcinoma in short-segment Barrett's esophagus (SSBE): curative treatment using local endoscopic treatment techniques.

BACKGROUND AND STUDY AIMS: In recent years, short-segment Barrett's esophagus (SSBE) has attracted increasing attention in the context of reflux disease. However, there is continuing controversy regarding its potential for malignant transformation. PATIENTS AND METHODS: Between October 1996 and September 1999, 50/115 patients (43 %) with intraepithelial high-grade neoplasia or early Barrett's adenocarcinoma, who underwent local endoscopic treatment, had developed a malignant lesion in an (SSBE). In the framework of a prospective observational study, 28 patients were treated with endoscopic mucosal resection (EMR), 13 with photodynamic therapy, and three with argon plasma coagulation; six patients received combinations of these treatments. RESULTS: Complete local remission was achieved in 48/49 patients (98 %). One patient switched to surgery after the first EMR, because there was submucosal tumor infiltration, and in one patient out of 50 local endoscopic treatment failed. A mean of 1.7 +/- 1.4 treatment sessions was required for local endoscopic treatment. The method-associated mortality was 0 %. The rate of relevant complications (stenosis, bleeding) was 6 % (3/50 patients). No cases of severe hemorrhage (Hb fall >2 g/dl) or perforation occurred. During a mean follow-up period of 34 +/- 10 months, metachronous intraepithelial high-grade neoplasms or early adenocarcinomas were seen in 11/48 patients (23 %), who received further successful endoscopic treatment. Four patients died during the follow-up period, but in only one patient was this due to his Barrett's adenocarcinoma (this was the patient who underwent esophageal resection). CONCLUSIONS: The malignant potential of short-segment Barrett's esophagus must not be underestimated. Organ-preserving local endoscopic treatment shows good acute-phase and long-term results. Local endoscopic treatment represents an alternative to esophageal resection in the case of intraepithelial high-grade neoplasia and selected early adenocarcinomas in Barrett's esophagus.

Adenocarcinoma↗

PubMed1991

Early brain metastases in endometrial carcinoma.

Endometrial carcinoma is the most common invasive neoplasm of the female genital tract. Yet, intracranial metastases are rare and usually associated with widespread disease. We report three patients with endometrial carcinoma and early brain metastases, two with unsuspected endometrial carcinoma presenting with neurologic symptoms and one who developed neurologic symptoms on the day of hysterectomy. Histologically, one tumor was a clear cell carcinoma and two were endometrial adenocarcinoma. In tumors with a mixture of nuclear grades, the most undifferentiated portion metastasized. Two tumors displayed vascular invasion and deep myometrial invasion. Only one had positive estrogen receptors. Intracranial metastases can occur early in the course of endometrial carcinoma. They are associated with aggressive high-grade neoplasms with deep myometrial and vascular invasion.

Adenocarcinoma, Papillary↗

PubMed2003

Low-grade malignant Triton tumor of the oral cavity: a case report.

Malignant Triton tumor (MTT) is a malignant peripheral nerve sheath tumor showing rhabdomyoblastic differentiation. It is considered a high-grade neoplasm with poor outcome. This report describes an MTT appearing in the oral cavity. On histologic examination the encapsulated lesion was composed of interlacing fascicles of spindle cells and scattered, large, strap-like pleomorphic cells with abundant eosinophilic cytoplasm. No cross striations were seen. Examination of levels through the tissue showed a total of only 4 normal mitoses and no necrosis. Immunohistochemistry demonstrated diffuse S100 positivity in the spindle cells. The large pleomorphic cells were weakly positive for alpha-sarcomeric actin and myoglobin, although variably but strongly positive for desmin. Management involved a small en bloc resection of the maxilla. After 33 months there was no sign of recurrence or distant metastasis. It was concluded that low-grade variants of MTT occur that do not have an aggressive clinical course.

Actins↗

PubMed1996

Characterizations of the extracellular matrix and proteinase inhibitor content of human myoepithelial tumors.

Myoepithelial tumors are intriguing low-grade neoplasms that exhibit the property of accumulating an abundant extracellular matrix. Because accumulation of an extracellular matrix represents an important exception to the rule of matrix degradation otherwise exhibited by the vast majority of human epithelial neoplasms, this study investigated the composition of this matrix to gain insight into the biological behavior of this class of neoplasms. Several different human myoepithelial tumors and their derived cell lines and xenografts were thus examined by ultrastructural, immunohistochemical, molecular, and biochemical methods. Results indicated that although the extracellular matrix of these tumors contains some basement membrane components such as laminin, nidogen, and heparan sulfate proteoglycan (8%), it is also largely cartilagenous in nature, containing large amounts of chondroitin sulfate proteoglycan (78%). In addition to extracellular matrix structural proteins, myoepithelial cells secreted relatively large amounts of proteinase inhibitors including maspin, protease nexin II, alpha1-antitrypsin, a 31-kd serine proteinase inhibitor, and TIMP-1. Immunolocalization and extraction studies further demonstrated that protease nexin II and alpha1-antitrypsin especially accumulated within the myoepithelial extracellular matrix. In addition, protease nexin II likely underwent extracellular in vivo processing to a 95-kd product retaining full proteinase inhibitor activity. These specific biochemical observations unite the classes of myoepithelial tumors, confer an anti-invasive property to their extracellular matrix, and likely contribute to their low-grade biological behavior.

Adenocarcinoma↗

PubMed2002

Salivary gland tumours.

Salivary gland tumours are a relatively rare and morphologically diverse group of lesions. Although most clinicians and pathologists will have encountered the more common benign neoplasms, few have experience of the full range of salivary cancers, which are best managed in specialist centres. This review considers some current areas of difficulty and controversy in the diagnosis and management of these neoplasms. The classification of these lesions is complex, encompassing nearly 40 different entities, but precise classification and terminology is essential for an accurate diagnosis and for the allocation of tumours to prognostic groups. For many salivary tumours diagnosis is straightforward but the wide range of morphological diversity between and within tumour types means that a diagnosis may not be possible on small incisional biopsies and careful consideration of the clinical and pathological features together is essential. Although tumour grading is important and helpful, it is not an independent prognostic indicator and must be considered in the context of stage. Large malignancies tend to have a poor prognosis regardless of grade and even high-grade neoplasms may do well when they are small. A helpful guide to management of salivary cancers is the '4 cm rule'.

Adenocarcinoma↗

PubMed2004

Gliosarcoma: cytopathologic characteristics on fine-needle aspiration (FNA) and intraoperative touch imprint.

Gliosarcoma (GS) is a rare subtype of glioblastoma multiforme (GBM), which shows a dimorphic population of glial and mesenchymal elements. The cytopathology of GS to our knowledge has not been previously described. Although prognostically insignificant within the group of GBM, an accurate recognition of this subtype may help to rule out other morphologically similar primary and metastatic central nervous system (CNS) neoplasms. Thirteen cases of histologically confirmed GS with concomitant touch imprints (TI) or prior fine-needle aspiration (FNA) were retrieved from the files of The Johns Hopkins Hospital (1985-2002). A comprehensive review of the clinico-radiologic, cytologic, and histologic material was undertaken to define the morphologic characteristics of GS. Material was obtained via computerized tomography (CT)-guided needle biopsy. Slides were stained with DiffQuik and/or hematoxylin and eosin (H and E) stains. Smears were highly cellular and showed a high-grade neoplasm with glial and mesenchymal elements. The latter component, however, predominated and showed a variety of phenotypic patterns, which included fibrosarcoma-like, rhabdoid type, osteoclastic giant cell type, undifferentiated type, and tumor with heterologous components (such as chondroid or osteoid tissue). A rich arborizing capillary network was evident, as were a high mitosis/karyorrhexis index and foci of necrosis. The glial component consisted of pleomorphic round to oval nuclei and numerous gemistocytes embedded in a fibrillary stroma.

Adult↗

PubMed1984

Bladder cancer induced by noncarcinogenic substances.

Chemical carcinogenesis is currently regarded as a complicated series of events requiring initiation and promotion in specific sequences. Carcinogens are thought to be chemicals which can induce both initiation and promotion so that few if any additional host or environmental factors are required in the production of neoplasms. Most experimental studies to date have investigated bladder cancer using these highly active agents and the role of other substances in urothelial neoplasia has not been emphasized. We have examined the role of a variety of solutions, including water and saline, in pilot studies of urothelial carcinogenesis using the ALZA mini-pump for continuous infusion. Bladder tumors indistinguishable morphologically from papillary transitional cell carcinomas were induced. Although experimental induction of bladder cancer with powerful carcinogens may completely overwhelm host defenses and result in more and higher grade neoplasms, similar tumors may occur after exposure to substances not generally considered to be carcinogenic. This process, which probably requires cofactors and host-chemical interaction, may be more representative of environmental carcinogenesis than systems using powerful carcinogens and should be further investigated.

Administration, Topical↗

PubMed1989

Flow cytometric analysis of granulosa tumors.

Paraffin blocks from 17 granulosa tumors, nonmetastatic (n = 10) and metastatic (n = 7), were analyzed by flow cytometry. Three neoplasms, one with and two without metastases, were found to have cells with an abnormal DNA (DNA aneuploid) content. The occurrence or absence of DNA aneuploid cells did not predict behavior. In addition, there was no correlation of tumor DNA content with tumor size or patient age at the time of surgery. There was no significant difference in cell proliferation (%S + %G2/M) between metastatic and nonmetastatic DNA diploid tumors, however, there was an increase in cell proliferation in tumors with a DNA aneuploid stemline. Granulosa tumors are low-grade neoplasms. At least 90% are seen in Stage I, and metastasis occurs subsequently in 5% to 15% of these cases. Features of Stage I neoplasms associated with subsequent metastasis in some reports, but not all, are involvement of the capsule (Stage IC), large size, and high mitotic rate, 1-5 Providing definitive statements about the behavior of granulosa tumors is hampered by their rarity, the subjectivity of the diagnosis, and their sluggish behavior. We attempted to determine if flow cytometric analysis of DNA could identify granulosa tumors with metastatic potential. We compared DNA histograms from ten Stage IA granulosa tumors that did not metastasize during 22 to 47 years of follow-up with seven granulosa tumors that showed malignant behavior.

Adult↗

PubMed1993

Extra-nodal monocytoid B-cell lymphoma of the urinary bladder.

Monocytoid B-cell lymphoma (MBCL) is a low-grade neoplasm considered to be the neoplastic counterpart to monocytoid B-lymphocytes, derived from marginal zone lymphocytes. Recently, a 72-yr-old woman presented with urinary symptoms of burning, urgency, and hematuria. Examination of the urinary bladder revealed the presence of an exophytic mass at the bladder base. This lesion was grossly suspected of being a transitional cell carcinoma, but on initial histologic examination it was found to be lymphoma composed of cells with moderately abundant cytoplasm and an overall size reminiscent of a large cell type. Detailed histologic examination led to a diagnosis of MBCL in this submucosal site. Clinical staging showed no evidence of lymphoma in other organs and the patient responded to therapy for non-Hodgkin lymphoma (NHL). This case represents an unusual presentation of low-grade NHL and may be consistent with previous suggestions of a relationship between MBCL and lymphomas of mucosa-associated lymphoid tissue.

Aged↗

PubMed2005

Identification of histological markers for malignant glioma by genome-wide expression analysis: dynein, alpha-PIX and sorcin.

Glioblastoma multiforme (GBM), the most malignant class of glial neoplasm (grade IV in WHO criteria), carries the worst clinical prognosis among primary brain tumors in adults. To identify a set of genes involved in the tumorigenesis of GBM, we evaluated expression profiles of GBM tissues from 11 patients using a cDNA microarray representing 25,344 human genes. By comparing the profiles with those of normal brain tissue, we identified a number of differentially expressed genes: 54 with increased expression and 45 with reduced expression in GBMs. Semi-quantitative RT-PCR experiments with 6 of those genes confirmed higher expression of DNCH2, ARHGEF6, NPM1 and SRI and lower expression of NRGN and TM4SF2 in GBM tumors. Immunohistochemical staining for 3 of the respective gene products, dynein (product of DNCH2), alpha-PIX (product of ARHGEF6), and sorcin (product of SRI) indicated that this technique might be useful for histological grading of glial tumors. To establish criteria for this diagnostic approach, we scored glial tumor tissues of different histological grades according to the staining results; the scores were significantly higher in anaplastic astrocytomas and GBMs than in diffuse astrocytomas or normal brain tissues. These findings indicated that levels of these three proteins might serve as histological markers for malignant glioma classification.

Biomarkers, Tumor↗