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PubMed1994

Unusual fibro-osseous lesion of the spinal cord with positive staining for glial fibrillary acidic protein and radiological progression: a case report.

A rare intradural lesion of the lumbar spine producing leg pain and minimal neurological deficits is described in a 48-year-old man. Previous reports of similar lesions have been described under the designation "fibro-osseous lesions" and "calcifying pseudoneoplasms." This is the first report of an unusual fibro-osseous lesion with an intradural spinal location as well as the first to show immunohistochemical positivity for glial fibrillary acidic protein (GFAP) within cellular components of this process and crystal formation suggestive of calcium pyrophosphate. This case also shows radiographic progression suggesting the possibility that this entity may be a form of low grade neoplasm.

Glial Fibrillary Acidic Protein↗

PubMed2004

Pituicytoma.

Pituicytoma is a rare, low-grade neoplasm that originates in the neurohypophysis of the pituitary gland. We report the clinicopathologic features of a pituicytoma arising in a 52-year-old man who presented with a mass and panhypopituitarism, clinically suggestive of a pituitary adenoma. The tumor was marked by a proliferation of elongated cells arranged in bundles and interlacing fascicles. The tumor demonstrated positive staining with S-100 protein and glial fibrillary acid protein antibodies. The tumor did not stain with antibodies to cytokeratin, synaptophysin, chromogranin, anterior pituitary hormones, or p53. An MIB-1 labeling index of 1.1% was observed. The tumor was subtotally resected and recurred 11 months after the initial surgery. The literature on this rare tumor will be reviewed and differential diagnosis discussed.

Biomarkers, Tumor↗

PubMedDate not supplied

Fever of unknown origin: chronic lymphatic leukemia versus lymphoma (Richter's transformation).

Currently, malignancies are more common than infections as a cause of fever of unknown origin (FUO) in adults. Many malignant disorders are associated with fever, which may either be of the hectic-septic variety resembling an infectious disease or prolonged and low-grade. Neoplasms with either kind of fever may present as an FUO. The malignancies usually associated with fever are lymphoreticular malignancies involving the blood, liver, spleen, or bone marrow. Most malignancies do not have fever, e.g., chronic lymphatic leukemia (CLL), as part of their clinical presentation. We present a case of long-standing CLL in an elderly woman who presented with an FUO. Initially, it was thought that her FUO was caused by CLL or a CLL-related opportunistic infection. The naprosyn test was used in this patient with CLL and FUO to differentiate a malignant from an infectious etiology. Her response to naprosyn indicated that the etiology of her FUO was neoplastic rather than infectious. The absence of tonsillar enlargement and peripheral adenopathy, as well as the presence of fever, argued against CLL as the cause of her fever. Computed axial tomography scans showed central adenopathy in addition to splenomegaly. The presence of fever, splenomegaly, and central adenopathy indicated that the cause of her FUO was a lymphoma (Richter's transformation) and not CLL.

Aged, 80 and over↗

PubMed2005

Novel estrogen receptor coactivator PELP1/MNAR gene and ERbeta expression in salivary duct adenocarcinoma: potential therapeutic targets.

Salivary duct carcinoma (SDC) is a high-grade neoplasm with marked morphological resemblance to mammary duct carcinoma. The novel estrogen receptor (ER)-interacting protein and the proline-, glutamic acid-, and leucine-rich protein 1 ( PELP1 ), also called the modulator of nongenomic activity of ER ( MNAR ), have been shown to activate steroid hormone receptors in mammary carcinomas by nongenomic and genomic mechanisms. The expression and the relationship of this gene to the ER status in SDCs are unknown. We investigated the differential expression of the PELP1 / MNAR and the ERs alpha and beta proteins in SDCs, using Western blotting and immunohistochemistry. Western blot analysis of 7 paired normal and tumor specimens showed increased expression of PELP1 / MNAR and ER beta in 3 and 4 of the SDCs, respectively. No detectable expression of ER alpha in any normal or SDC specimens was noted. Immunohistochemical staining performed on 70 SDCs revealed strong expression of PELP1 / MNAR in 51 (73%) and ER beta in 52 (74%) tumors. PELP1 / MNAR and ER beta were coexpressed in 35 (50%), individually in 17 (24.2%), and negative in 18 (25.7%) tumors. PELP1 / MNAR staining was predominantly cytoplasmic whereas ER beta staining was nuclear and occasionally cytoplasmic in tumor cells. Our results indicate that PELP1 / MNAR and ER beta are coexpressed in most SDCs and may play a role in the pathobiology of these tumors.

Adenocarcinoma↗

PubMed1999

Prolactin receptor expression in the developing human prostate and in hyperplastic, dysplastic, and neoplastic lesions.

In situ hybridization and immunohistochemistry were used to localize and compare the expression of the long form of the human prolactin receptor in fetal, prepubertal, and adult prostate. Results were then compared with hyperplastic, dysplastic, and neoplastic lesions. Both receptor message and protein were predominately localized in epithelial cells of the fetal, neonatal, prepubertal, and normal adult prostate. In hyperplastic lesions the expression of the receptor was unchanged with respect to normal epithelial cells. Irrespective of grade, markedly enhanced expression of the receptor was evident in dysplastic lesions. In lower Gleason grade carcinomas the intensity of receptor signal at the message and protein levels approximated that found in normal prostatic epithelium. However, in foci within higher grade cancers, receptor expression appeared diminished. Results from our study suggest that prolactin action plays a role in the development and maintenance of the human prostate and may also participate in early neoplastic transformation of the gland. Diminution of receptor expression in high grade neoplasms could reflect the emergence of a population of cells that are no longer responsive to the peptide hormone.

Aged↗

PubMed1996

Differential expression of the bcl-2 oncogene in human basal cell carcinoma.

The bcl-2 protein increases cell longevity and reduces apoptosis. Expression of the bcl-2 oncogene is reported in certain low grade neoplasms including basal cell carcinomas (BCCs). The authors postulated that the indolent variants of BCC, namely, the superficial and circumscribed subtypes, might exhibit greater bcl-2 expression than their aggressive counterparts, and used a monoclonal antibody to identify its protein product in formalin-fixed tissue from 30 BCCs. Expression of bcl-2, observed in 28 to 30 BCCs, was greatest in indolent-growth BCCs and weakest in the aggressive-growth variants (P = .005). Variable bcl-2 expression is seen in BCC and may be integral to both its pathogenesis and its biological behavior.

Antibodies, Monoclonal↗

PubMed1998

Cyclin D1 and MIB-1 immunohistochemistry in pilocytic astrocytomas: a study of 48 cases.

Pilocytic astrocytoma is an infrequently encountered, generally low-grade neoplasm. No study has extensively looked at both cyclin D1 and MIB-1 labeling indices in pilocytic astrocytoma and their relation to clinical outcome. This study retrospectively examines the clinicopathologic features of 48 patients with pilocytic astrocytoma including MIB-1 (cell proliferation marker) and cyclin D1 (protein that regulates progression from G1 to S phase of the cell cycle) immunohistochemistry. Of 48 patients (27 females and 21 males; mean age, 12.7 years; age range, 2 to 57 years), 26 initially underwent gross total resection; 17, subtotal resection; four, biopsy alone; in one patient, the extent of tumor resection was unknown. Histological features observed included Rosenthal fibers (83.3%), granular bodies (75%), vascular sclerosis (56.2%), vascular proliferation (56.2%), prominent nuclear pleomorphism (14.6%), necrosis (10.4%), and identifiable mitotic figures (2.1%). MIB-1 labeling indices (n=45) (positive staining tumor nuclei per 1,000 nuclei evaluated) ranged from 0 to 3.5% (mean, 0.6%); seven tumors had a labeling index greater than 1.0%. Cyclin D1 labeling indices (n=45) ranged from 0 to 0.8% (mean, 0.1%). Most tumors (N=29, 66.7%) had no immunostaining. At last known follow-up, 27 patients were alive with no evidence of disease (mean, 49.2 months), 17 patients were alive with evidence of disease (mean, 36.8 months), three died with tumor at 2, 22, and 156 months, and one patient was lost to follow-up. Eight patients had at least one tumor recurrence requiring additional surgery; seven of these patients had an initial subtotal resection. In summary, MIB-1 labeling indices were generally low (mean, 0.6%) and are reflective of the slow growth of the tumors. Cyclin D1 immunostaining does not appear to be significantly increased in pilocytic astrocytoma. Adverse outcome in patients with pilocytic astrocytoma may be related to extent of surgical resection and does not seem to correlate with histology, MIB-1 labeling indices, or cyclin D1 immunoreactivity.

Adolescent↗

PubMed1999

Chordoid glioma of the third ventricle: confirmatory report of a new entity.

The term "chordoid glioma" was recently introduced to denote a circumscribed, apparently low-grade neoplasm arising in or preferentially involving the third ventricle of middle-aged women. We report biopsy and postmortem findings in a 60-year-old woman with symptoms of forgetfulness, headache, and lethargy. Neuroimaging showed a contrast-enhancing third ventricular mass with obstructive hydrocephalus. The tumor was subtotally resected. Microscopically, it consisted of clusters and strands of epithelioid cells in a mucoid matrix. Its margins were remarkably discrete and showed little tendency to infiltrate surrounding brain parenchyma. The majority of neoplastic cells were glial fibrillary acidic protein (GFAP) and vimentin positive, whereas S100 protein labeled only individual cells. Stains for epithelial membrane antigen (EMA) and cytokeratin were nonreactive. There was no evidence of neuroendocrine differentiation or expression of estrogen and progesteron receptors. Lymphoplasmacellular infiltrates were noted throughout the lesion and at the tumor-brain interface. The MIB-1 labeling index averaged 1.5%. At present, chordoid glioma is considered a glial neoplasm of uncertain histogenesis with distinct clinicopathologic features.

Biomarkers, Tumor↗

PubMed2003

Analysis of epithelial-myoepithelial carcinoma based on the establishment of a novel cell line.

Epithelial-myoepithelial carcinoma of the salivary gland is a rare, low-grade, neoplasm, composed of ductal and myoepithelial cells. We present two novel cell lines, which have been characterised by immunofluorescence, derived from an epithelial-myoepithelial carcinoma of the parotid gland. A resected mass of the parotid gland was diagnosed as an epithelial-myoepithelial carcinoma by routine histological examination. Part of the specimen was labelled with a panel of antibodies confirming the tumour type. The other part was finely minced and the explants were incubated in DMEM supplemented with penicillin and streptomycin, at 37 degrees C in a humidified 5% CO(2) atmosphere. Two cell types were identified by immunofluorescence-a small cobblestone cell, positive for AE1/AE3 and p53, and a polyhedral cell, positive for vimentin, smooth muscle markers and S-100. Herein two cell lines are presented in order to open up possibilities of new studies and a discussion of the events that culminate in this bimodal neoplasm is also performed.

Adult↗

PubMed2003

Human chorionic gonadotropin in sarcomatoid carcinoma of the bladder: a case report.

Sarcomatoid carcinoma is a high-grade neoplasm of the bladder which has a transitional, squamous or undifferentiated malign epitelial component and having areas with a sarcoma-like appearence. Most patients with sarcomatoid carcinoma are elderly males. The death rate is about 50% in these cases. Urethelial and renal pelvis involvement may occur. Metastases develop in regional lymph nodes and distant organs. In this case report, a patient who is diagnosed to have sarcomatoid carcinoma of bladder with human chorionic gonadotropin positivity, is presented and the literature is reviewed.

Aged↗

PubMed2004

Anaplastic lymphoma kinase (ALK 1) staining and molecular analysis in inflammatory myofibroblastic tumours of the bladder: a preliminary clinicopathological study of nine cases and review of the literature.

Inflammatory myofibroblastic tumours (IMFT) may arise at any anatomical site, including lung, soft tissues, retroperitoneum and bladder. Although morphologically similar, these lesions encompass a spectrum of entities with differing aetiology, ranging from reactive/regenerative proliferations to low-grade neoplasms with a risk of local recurrence, but no significant metastatic potential. Vesical IMFT usually presents as a polypoid mass with a pale firm cut surface and can be of considerable size, mimicking a malignant tumour clinically and radiologically. Its good outcome, however, warrants conservative surgical excision, emphasising the importance of identification and distinction from malignant tumours of the bladder that may require more radical surgery and/or adjuvant therapy. We conducted a preliminary retrospective, comparative immunocytochemical study of 20 bladder tumours, including nine IMFTs, five spindle cell (sarcomatoid) carcinomas, two rhabdomyosarcomas, two leiomyosarcomas and two neurofibromas. The results confirmed IMFT positivity for smooth muscle actin, desmin and cytokeratin in 78-89% cases, resulting in potential confusion with sarcomatoid carcinoma or leiomyosarcoma. In contrast, cytoplasmic anaplastic lymphoma kinase (ALK 1) staining was present in eight IMFT (89%), but was not seen in any other lesion examined. The ALK 1 staining was confirmed by fluorescence in situ hybridisation, with translocation of the ALK gene present in 15-60% tumour cells in four of six IMFT examined, but not in four cases of sarcomatoid carcinoma or three of leiomyosarcoma. In conclusion, ALK 1 staining may be of value in the distinction of vesical IMFT from morphologically similar entities, and often reflects ALK gene translocations in these lesions.

Actins↗

PubMed2001

Hamartin and tuberin expression in human tissues.

Tuberous sclerosis (TSC) is a bigenic autosomal dominant disease caused by mutations in one of two tumor-suppressor genes, TSC1 and TSC2, resulting in benign hamartomas and low grade neoplasms in multiple organs including brain, heart, kidney, and skin. We report the results of an immunohistochemical study of the expression of the TSC gene products, tuberin and hamartin, in multiple tissues obtained at autopsy from 12 non-TSC affected patients ranging in age from 20 weeks gestation to 8 years, and surgical specimens from some organs. Tuberin and hamartin are expressed and are colocalized in most tissues. Contrary to a previous report, immunostaining with our antisera detected hamartin in liver, small and large intestine, prostate, and testes. We did not detect significant developmental differences in tuberin or hamartin expression in comparable tissues from patients of different ages. Although tuberin and hamartin colocalize in most tissues and cell types, we provide data that hamartin is more abundantly expressed than tuberin in cells within some tissues including the distal nephron and a population of cells of the endocrine pancreas. These data support the hypothesis that hamartin and tuberin interact and may function together in many tissues where they are co-expressed, but also suggest that hamartin has a discrete and specialized function in certain cell types.

Blotting, Western↗

PubMed1997

High-grade papillary cystadenocarcinoma of the tongue.

AIMS: Salivary gland tumours of the tongue are rare. The most common type is low-grade mucoepidermoid carcinoma followed by adenoid cystic carcinoma. Papillary cystadenocarcinoma of salivary glands are uncommon lesions with low-grade mucoepidermoid carcinoma followed by adenoid cystic carcinoma. Papillary cystadenocarcinoma of salivary glands are uncommon lesions with low-grade histological and clinical features. We report a high-grade papillary cystadenocarcinoma in an 80-year-old man who presented with a tongue mass and metastatic disease in the neck. METHODS AND RESULTS: He was treated with partial glossectomy and bilateral neck dissection but developed local and regional recurrences 6 months later. The tumour had a prominent cystic appearance and had areas of necrosis. The cyst lumen was occupied by numerous papillae lined by pseudostratified columnar cells with a high nuclear-cytoplasmic ratio. The cytoplasm was eosinophilic, the nuclei were pleomorphic and exhibited irregular nuclear membranes, vesicular chromatin and prominent eosinophilic nucleoli. The mitotic activity was high and there were occasional abnormal mitotic figures. Metastatic carcinoma was present in four lymph nodes. The differential diagnosis of this unusual lesion includes cystadenoma, salivary duct carcinoma and metastases. CONCLUSIONS: This case and a review of the literature indicates that papillary cystadenocarcinomas of salivary gland origin exhibit a wider morphologic spectrum than described in the latest World Health Organization (WHO) classification which defines these lesions as low-grade neoplasms.

Aged↗

PubMed2002

Salivary duct carcinoma: cytokeratin 14 as a marker of in-situ intraductal growth.

AIMS: The aim of this study was to determine the immunoprofile of salivary duct carcinoma and to differentiate intraductal growth from invasive growth. METHODS AND RESULTS: We applied a panel of antibodies (cytokeratins 7, 8, 13, 14, 19, vimentin and alpha-smooth muscle actin) in five cases of salivary duct carcinoma. This panel is currently used for identification of different components of salivary gland tumours in our laboratory. All tumour cells were positive for cytokeratins 7 and 8. Few neoplastic structures expressed cytokeratin 14 in cells surrounding tumour islands. CONCLUSION: The finding of cytokeratin 14 was important to confirm the in-situ intraductal growth, which probably characterizes this low-grade neoplasm.

Adenocarcinoma↗

PubMed2001

Tau-associated neuropathology in ganglion cell tumours increases with patient age but appears unrelated to ApoE genotype.

Ganglion cell tumours, including gangliogliomas and gangliocytomas, are low grade neoplasms with a mature neuronal component. Ganglion cells within these lesions occasionally exhibit neurodegenerative changes including neurofibrillary tangles (NFT) similar to those in Alzheimer's disease. The frequency and spectrum of degenerative pathology in these lesions have not been defined, nor has their relation to patient age or factors such as apolipoprotein E (ApoE) genotype that predispose to Alzheimer's disease. We studied 72 ganglion cell tumours (61 gangliogliomas, 11 gangliocytomas) from patients 7 months to 72-years-old. Haematoxylin and eosin (H&E), silver stains (Hirano method) and immunohistochemistry for tau, alpha-synuclein and beta-amyloid were performed on formalin-fixed, paraffin-embedded tissue from surgical specimens. Tau-and silver-positive NFT and neuropil threads (NPT) were present in four of 26 ganglion cell tumours from patients over 30-years-old (ages 31, 38, 50, and 58 years). Neuronal granulovacuolar degeneration (GVD) was noted in five of 26 tumours from patients over 30-years-old (mean, 48 years). NFT, NPT, and GVD were not seen in ganglion cell tumours from patients under 30-years-old[0/46]. Cytoplasmic argentophilic bodies distinct from NFT were present in five of 26 tumours from patients over 30-years-old and in two of 46 under 30 years. Neither alpha-synuclein positive neuronal inclusions nor beta-amyloid immunoreactivity was noted in ganglion cell tumours from any age group. The distribution of ApoE genotypes was similar among those tumours that contained tau-associated neuropathology and those that did not. Neurodegenerative changes are uncommon in ganglion cell tumours, but increase in frequency with patient age. GVD, tau-positive NFT and NPT, and argentophilic bodies occur more often in ganglion cell tumours from patients over 30-yrs-old, but do not appear to be associated with a specific ApoE genotype.

Adolescent↗

PubMed2000

Use of markers in defining urothelial premalignant and malignant conditions.

Markers have revealed the presence of phenotypically abnormal areas in histologically benign urothelium in bladders containing transitional cell carcinomas. This finding strongly suggests that at least some bladder cancers are associated with changes in the field and that markers can detect these lesions before they reach a grossly malignant stage. Markers have been used clinically for the detection of cancer in patients who are under regular surveillance for recurrence of bladder cancer. Much less information is available regarding the use of markers to detect bladder cancer without a prior history of the disease and for the prediction of which tumors are biologically more aggressive. However, ongoing clinical trials are addressing the latter issue. The type of specimen and its preparation will determine what type of markers can be analyzed. Although marker performance is based upon sensitivity and specificity, the prevalence of bladder cancer in the population being tested will dramatically affect the positive predictive value of an assay. Markers with high positive predictive value are indicators for interventions, such as biopsy, while markers with high negative specific values are useful for avoiding interventions. Cytology is used to detect occult high-grade neoplasms such as carcinoma in situ. While not yet clinically validated, tests with high negative predictive value could be used to decrease the frequency of cystoscopic evaluation. Markers must be validated by testing them prospectively using previously defined cut-off values. Furthermore, markers that will be used to alter treatment should be tested prospectively to determine the safety and cost-effectiveness of this strategy. Recommendations for future work include: (1) evaluation of markers in patients with dysplasia defined by the current pathologic classification; (2) evaluation of markers as indicators of tumor recurrence; (3) evaluation of markers as indicators of tumor progression; and (4) evaluation of markers in chemoprevention studies.

Biomarkers, Tumor↗

PubMedDate not supplied

Inflammatory myofibroblastic tumor of the gastroesophageal junction in childhood.

We report a unusual case of an inflammatory myofibroblastic tumor arising at the gastroesophageal junction in a 14-year-old girl. The bland histologic appearance with concurrent infiltration into adjacent structures made diagnostic interpretation difficult, but suggested a neoplastic process. A literature review was undertaken to address diagnostic and management issues raised in this case. Although the anatomic location was unusual, clinical, grass, histopathologic, and immunohistochemical data substantiated the diagnosis of inflammatory myofibroblastic tumor. The bland histologic appearance was consistent with the most widely accepted view of inflammatory myofibroblastic tumor as a low-grade neoplasm. Wide surgical excision was performed. This is considered the preferred treatment given the potential risk of recurrence and aggressive behavior, most frequently noted with extrapulmonary disease. Although inflammatory myofibroblastic tumor represents an heterologous spectrum of benign to malignant neoplastic proliferations, the prognosis is good in casts with benign histologic features.

Adolescent↗

PubMed1994

Cell kinetic analysis of interleukin-2 receptor-tested chronic lymphocytic leukemia using the AgNOR silver stain.

B-cell chronic lymphocytic leukemia (B-CLL) is typically a low-grade neoplasm with a diploid DNA index and low proliferative activity. Interleukin-2 receptor (IL-2R/CD25) positivity often indicates increased proliferative activity and activation in both T and B lymphocytes. The argyrophilic nucleolar organizer regions (AgNORs) are loops of DNA identified by a silver staining technique and have been correlated with ploidy and proliferative activity. Two distinct AgNOR counting methods have been previously shown to correlate with DNA ploidy and proliferative activity, respectively: the mean AgNOR count (mAgNOR) correlates more with ploidy, and the percentage of nuclei with > or = 5 AgNORs/nucleus (pAgNOR) reflects proliferative activity. We studied bone marrow specimens from 32 patients with B-CLL using both anti-IL-2R on the marrow aspirates and the AgNOR silver stain on marrow biopsy specimens, applying both AgNOR counts. All tumors were CD5+, CD19+, and CD19/CD20+. Sixteen tumors were IL-2R- (< 20% IL-2+ B cells), and 16 were IL-2R+ (> or = 20% IL-2R+ B-cells). No significant difference in morphology of bone marrow involvement was noted in the two groups. A male predominance was noted in the IL-2R+ group of patients (3:1). There was also a preponderance of lambda light chain expression in the IL-2R+ tumors (11/16) compared with the IL-2R- cases (5/16). Except for two cases, all tumors had mAgNOR counts within the diploid range (< 2.4). The 16 IL-2R- tumors had pAgNOR in the range of 0% to 7% (mean, 2.31 +/- 2.18 standard deviation), whereas the IL-2R+ tumors had pAgNOR ranging from 6% to 15% (mean, 10.20 +/- 2.70 standard deviation; P < .0001). This finding suggests that IL-2R+ B-CLL might represent a subgroup of tumors with higher proliferative activity.

Adult↗