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Image cytometric measurement of nuclear proliferation markers (MIB-1, PCNA) in astrocytomas. Prognostic significance.

Proliferative activity in astrocytomas, measured by image cytometry, was related to prognosis. Fifty-eight astrocytic neoplasms (grade 1 or 2, 11; grade 3, 31; glioblastoma multiforme, 16) were immunostained for Ki-67 (MIB-1; 1:50) and proliferating cell nuclear antigen (PCNA; prediluted). Proliferative activity (nuclear immunostain) was measured as the percentage positive nuclear area by image cytometry. With a median of 12.0% and 24.0% for MIB-1 and PCNA, respectively, for all astrocytomas, the mean percentage positive nuclear area for MIB-1 and PCNA was, respectively, 3.06% and 13.11% in low-grade (1 or 2) astrocytomas, 14.34% and 29.68% in high-grade (3) astrocytomas, and 18.77% and 44.11% in glioblastoma multiforme (grade 4). One-way analysis of variance showed a significant correlation between the histologic grade and MIB-1 and between the histologic grade and PCNA. The Cox Proportional Hazards Regression Model showed a statistically significant correlation between survival and MIB-1 and between survival and PCNA. Increasing proliferation correlated with shortened survival. Proliferation in astrocytomas, measured as MIB-1 and PCNA by image cytometry, correlates significantly with histologic grade and patient survival, providing useful additional information for determining the diagnosis and prognosis.

Adolescent↗

Stereotactic brain biopsy in the diagnosis of malignant lymphoma.

Fifteen patients with cerebral involvement by malignant non-Hodgkin's lymphoma were identified, among more than 200 patients who underwent stereotactic biopsy at The Johns Hopkins Hospital. All but one of these cases were diagnosed accurately by the stereotactic biopsy procedure. In 12 of 14 patients, the material was adequate to classify the lymphoma according to the Working Formulation. Because all but one of the lesions were intermediate or high-grade neoplasms, a diagnosis of lymphoma was often possible by conventional light microscopic examination alone. Monotypic light chain expression was demonstrated by immunohistochemical techniques in six patients, and positivity for B-cell markers was observed in an additional case. In one instance, two stereotactic biopsy specimens were interpreted as being suggestive of lymphoma, but necrosis and inflammation prevented a definitive diagnosis. Nine patients had no known risk factors for cerebral lymphoma, and the diagnosis often was unsuspected clinically.

Adolescent↗

Mammary mucocele-like lesions. Benign and malignant.

In 1986 mucocele-like lesions (MLL) were described as benign tumors; subsequent reports identified MLL associated with ductal hyperplasia or carcinoma (CA). To characterize MLL further, we studied 53 lesions from 49 patients, in whom 25 MLL were benign and 28 were malignant (14 in situ, 14 invasive). Two had bilateral benign MLL, and two had bilateral MLL with CA. Patients ranged in age from 24 to 79 years (mean, 48 years). There were no appreciable differences in age, tumor size, or laterality between patients with benign or malignant MLL, although MLL with CA had coarse calcifications more often than benign MLL and were more likely to be detected mammographically. Intraductal carcinoma was micropapillary or cribriform, and invasive carcinoma was usually mucinous. Fewer of the benign lesions were estrogen and progesterone receptor positive. HER2/neu positivity was more common in MLL with CA. Known treatment was as follows: for benign MLL, excisional biopsy was done in 22 patients (one with axillary dissection) and total mastectomy in one patient; for MLL with CA, excisional biopsy was done in 17 patients, biopsy followed by wider excision in four patients (three of whom had axillary dissection), and mastectomy and axillary dissection in five patients (one also had radiotherapy). Follow-up ranged from less than a 1 year to 15 years (mean and median, 3.7 years). Two patients had recurrences in the breast (one benign MLL and one MLL with CA). At the time of this report, all were alive without evidence of disease. We conclude that MLL with CA is a low-grade neoplasm with few clinical differences from benign MLL except for more prominent calcifications, leading to mammographic detection. Excisional biopsy is recommended for benign MLL. Breast-conserving surgery is appropriate therapy for MLL with CA. Radiotherapy is indicated if CA involves margins or if extensive intraductal carcinoma is present.

Adenocarcinoma, Mucinous↗

Extraskeletal myxoid chondrosarcoma.

The medical records and histologic material of 16 patients with extraskeletal myxoid chondrosarcoma were reviewed. The mean age of the patients was 52 years. Thirteen tumors arose in the lower extremity. Thirteen patients presented with primary, localized disease, whereas three presented with pulmonary metastases. Treatment of the primary site included wide excision or amputation in 13 patients and marginal or intralesional resections with radiation in three patients. The mean followup was 7.4 years. Five patients were continuously disease free (5- and 10-year event free survival 43% and 14%, respectively). Local recurrence developed in four, and metastases developed in six of 13 patients presenting with localized disease. Of six patients who received chemotherapy for systemic disease, four had disease progression and died, and two had a response to chemotherapy (one partial, one complete). The mean survival after onset of metastases was 45 months. Overall 5- and 10-year survival was 87% and 63%, respectively. The current series suggests that extraskeletal myxoid chondrosarcoma is an intermediate-grade neoplasm with a tendency toward recurrence and metastasis. Survival after relapse may be prolonged. More effective therapy for systemic disease is needed.

Adult↗

Positron emission tomography with ([11C]methyl)-L-methionine, [11C]D-glucose, and [68Ga]EDTA in supratentorial tumors.

Sixteen patients with supratentorial tumors were examined with positron emission tomography (PET) using [( 11C]methyl)-L-methionine, [11C]D-glucose, and [68Ga]EDTA as well as CT. There were nine astrocytomas (grade II), three oligoastrocytomas (grade II), two anaplastic astrocytomas (grade III), and two meningiomas. Six patients with low-grade astrocytomas and all three patients with oligoastrocytomas had an accumulation of [11C]methionine varying from slightly to intensely increased as compared with normal brain tissue. There was a markedly increased uptake of methionine in the anaplastic astrocytomas. Three of the low-grade astrocytomas had a decreased uptake of [11C]methionine in at least part of the tumor as compared with normal brain tissue. Contrast enhancement on CT or uptake of [68Ga]EDTA was not a prerequisite for increased accumulation of methionine. Uptake of [11C]glucose was lower than or equal to that of normal brain tissue in the low-grade tumors and also in one of the two anaplastic astrocytomas and in the bulk of the other. In each individual case the methionine uptake tended to be higher--or less decreased--than the glucose uptake. In the low-grade tumors the uptake of methionine and that of glucose were often different, occasionally markedly different, as far as the tumoral-peritumoral areas involved. These differences were even more remarkable in the two anaplastic astrocytomas. An increased uptake of methionine was often seen in areas appearing normal on CT. It appears that PET with [11C]glucose has limitations with regard to delineation of the low-grade astrocytomas, whereas PET with [11C]methionine usually better reflects the extent of these tumors and, to a lesser degree, the extent of the high-grade neoplasms. The results of PET with [68Ga]EDTA were similar to those with postcontrast CT in most patients. The two meningiomas exhibited a high uptake of all tracers used for PET as well as a marked contrast enhancement on CT. The extent of the meningiomas judged by PET with the various tracers correlated well with the extent assessed by postcontrast CT.

Adult↗

Temporal lobe microdysgenesis in epilepsy versus control brains.

Histopathologic evaluation of brain tissue derived from surgically treated patients with medically refractory temporal lobe epilepsy (TLE) frequently reveals structural brain lesions in the surgical specimen. While several of the most commonly encountered lesions such as low-grade neoplasms or vascular malformations are well established as structural substrates of epilepsy, the significance of subtle microscopic characteristics has remained controversial. Within the spectrum a broad range of microscopic features has previously been reported as "mild cortical dysplasia," "focal cortical dysplasia," or "microdysgenesis," including cortical laminar disorganization, columnar arrangement of cortical neurons, marked clustering of neurons throughout cortical layers II-VI, increased numbers of molecular layer neurons, marked perivascular clustering of oligodendroglia in the white matter, single heterotopic neurons in the deep white matter, glioneuronal hamartia, giant neurons, and balloon cell change. In this paper we report the frequency of these features in temporal lobe tissue of 47 surgically treated TLE-patients vs 29 normal autopsy controls. While most of them were found in both cases and controls, clustering of neurons throughout cortical layers II-VI, perivascular clustering of oligodendroglia in the white matter, increased single heterotopic white matter neurons, and glioneuronal hamartias predominated in tissue from patients with epilepsy (p < 0.05). A count of more than 10 white matter neurons/HPF was associated with a worse postoperative outcome (p < 0.05). These data suggest that certain microscopic characteristics are associated with the epileptic process, while others appear as normal variants.

Case-Control Studies↗

Colon signet ring cell adenocarcinoma: immunohistochemical characterization and comparison with gastric and typical colon adenocarcinomas.

Colon signet ring cell adenocarcinomas are uncommon, high-grade neoplasms. Given their rarity, the question of primary colon or metastatic gastric adenocarcinoma frequently arises when signet ring cell carcinoma is seen in a colonoscopic biopsy or in biopsies procured from other regions of the body. A second related question regarding colon and gastric signet ring cell carcinomas is their immunophenotypic similarities with the glandular form of adenocarcinoma in each site. We studied the immunohistochemical phenotype of 14 colonic signet ring cell adenocarcinomas and compared them with immunophenotype of 27 gastric signet ring cell adenocarcinomas. We also compared the immunophenotype of the 27 gastric signet ring cell with the immunophenotype of 19 gastric gland-forming adenocarcinomas, and the immunophenotype of the 14 colonic signet ring cell adenocarcinomas to the immunophenotype of 20 colonic gland-forming adenocarcinomas to identify staining differences in the neoplastic cells of the two architectures. Antibodies studied were cytokeratins 7, 17, 19, and 20, CA 19-9, CA-125. estrogen receptor, and gross cystic disease fluid protein 15. Sixty-four percent of colon signet ring cell adenocarcinomas had either no staining or focal staining with cytokeratin 7 compared with diffuse staining in 63% of gastric signet ring cell adenocarcinomas (P = 0.016). Seventy-two percent of colon signet ring cell adenocarcinomas had diffuse staining with cytokeratin 20 compared with no or focal staining in 50% of gastric signet ring cell adenocarcinomas (P = 0.019). Fifty-seven percent of the colon signet ring cell adenocarcinomas had a cytokeratin 7 (-)/cytokeratin 20 (+) staining pattern compared with 11% of gastric signet ring cell adenocarcinomas (P = 0.004). Forty-four percent of gastric signet ring cell adenocarcinomas had a cytokeratin 7 (+)/cytokeratin 20 (-) pattern, compared with none of the colon signet ring cell adenocarcinomas (P = 0.004). The staining distribution of the antibody battery was similar in colon signet ring cell and colon glandular adenocarcinoma and gastric signet ring cell and gastric glandular adenocarcinomas. When signet ring cell adenocarcinoma is encountered in a colon biopsy, a colon primary is supported if the neoplastic cells have a cytokeratin 7 (-)/cytokeratin 20 (+) staining pattern, and a gastric primary is supported if they have a cytokeratin 7 (+)/cytokeratin 20 (-) staining pattern. The signet ring morphology at each site had an identical immunophenotype as the cells forming their glandular counterpart.

Adenocarcinoma↗

Cytokeratin 20 and Ki-67 to distinguish carcinoma in situ from flat non-neoplastic urothelium.

Urothelial carcinoma in situ (CIS) is a high-grade neoplasm and an indicator of recurrence and progression that requires specific treatment. The distinction of CIS from flat non-neoplastic urothelium, in particular dysplasia, on the basis of histologic features is often difficult, and this study aims to validate cytokeratin 20 (CK20) and Ki-67 as discriminatory markers for this purpose. Immunostaining of these markers was applied to 26 cases of CIS, 14 atypia of unknown significance, 4 dysplasia, 6 normal, and 9 hyperplastic urothelium. CIS showed CK20 staining of deep urothelial cells in 23/26 CIS compared with restricted staining in surface cells in all non-neoplastic lesions. CIS had significantly increased Ki-67 index with a mean of 53.37% compared with that of non-neoplastic urothelium, which was <10% (P<0.0001). The proliferating cells were distributed randomly in CIS, whereas in non-neoplastic urothelium, staining was confined to the basal layer. Among the cases of atypia, 3/14 displayed deep staining for CK20 and 6/14 had elevated Ki-67 counts. In dysplasia similar findings were present in 1/4 and 2/4 cases, respectively. These findings suggest that CK20 and Ki-67 are objective markers to distinguish CIS from non-neoplastic urothelium. In cases of "atypia of unknown significance" and "dysplasia," positivity for both markers should raise the possibility of CIS or preneoplastic change and identify those cases for follow-up.

Biomarkers, Tumor↗

Pleomorphic hyalinizing angiectatic tumor: analysis of 41 cases supporting evolution from a distinctive precursor lesion.

The pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare, low-grade neoplasm that features atypical stromal cells containing hemosiderin, partially thrombosed ectatic vessels with circumferential hyalinization, and a variable inflammatory infiltrate. Over the years, we have occasionally observed a monomorphic partially myxoid spindle cell component (provisionally termed "early PHAT") co-existing with classic PHAT. In some instances, this monomorphic lesion occurs by itself, suggesting an early stage in the evolution of PHAT. To explore this hypothesis and to better define the long-term behavior of PHAT, we have reviewed our experience with these lesions. Forty-one cases were identified from consultation files. They occurred chiefly in adults (median 51 years, range 10-79 years) of either sex (23 female, 18 male), ranged from 0.3 to 19.7 cm (median 5.6 cm), and involved the subcutis of the ankle/foot (N = 15), leg (N = 10), thigh (N = 6), and other sites. Thirteen tumors had been present for more than 1 year prior to biopsy. Fifteen tumors consisted entirely of typical PHAT. Twelve cases conformed to "early PHAT," lacked fully developed features of PHAT, and showed instead short fascicles of hemosiderin-stippled spindled cells that infiltrated fat and surrounded congeries of small, damaged vessels. With close scrutiny, all contained rare pleomorphic cells with intranuclear pseudo-inclusions, as seen in typical PHAT. Fourteen cases contained both classic and early PHAT, in variable proportions. Follow-up was available in 18 patients (mean 84 months, median 52 months; range 13-420 months). Six of 18 patients developed recurrences, 1 with classic PHAT, 1 with mixed early-classic PHAT, and 4 with early PHAT. Following resection, 16 are disease free and 2 have persistent disease. None has developed metastasis. Based on the histologic overlap between early and classic PHAT, the presence of early PHAT at the periphery of classic PHAT, and the admixture of both patterns within the same tumor, we conclude that early PHAT represents a precursor lesion for PHAT. It appears essentially identical to the lesion termed "hemosiderotic fibrohistiocytic lipomatous lesion," supporting the notion that the latter is a neoplastic rather than a reactive lesion. PHAT should be considered mesenchymal tumors of intermediate malignancy, given their high rate of (sometimes aggressive) local recurrence.

Adolescent↗

The MAPK-AP-1/-Runx2 signalling axes are implicated in chondrosarcoma pathobiology either independently or via up-regulation of VEGF.

AIMS: To investigate whether and how the JNK/ERK-AP-1/-Runx2 signalling pathways and vascular endothelial growth factor (VEGF) are engaged in the pathogenesis of cartilaginous tumours. Chondrosarcoma is the third most common primary skeletal malignancy. Nevertheless, the molecular events underlying its pathogenesis remain elusive. JNK/ERK MAPKs and their downstream effectors, c-Jun and c-Fos (AP-1), are involved in chondroblastic differention/proliferation. These proteins interact with the Runx2 transcription factor, which is also implicated in chondroblast biology. VEGF, a key angiogenic factor, is up-regulated in human chondrosarcomas. METHODS AND RESULTS: Normal cartilage and neoplastic cells from 45 chondrosarcomas and 21 enchondromas were investigated immunohistochemically. We evaluated the cellular levels of JNK2, p-JNK2 (phosphorylated/activated JNK2), its main substrate, c-Jun, pc-Jun (phosphorylated/activated c-Jun) and c-Fos. Moreover, the levels of p-ERK (phosphorylated/activated ERK), Runx2 and VEGF were assessed. Positive immunostaining for all proteins was observed in the majority of the examined chondrosarcomas and in a small fraction of enchondromas. The expression levels of all proteins were positively and significantly correlated with each other. These levels were substantially augmented in high-grade compared with low-grade chondrosarcomas and in low-grade tumours compared with benign enchondromas, implying a potential use as molecular markers for prediction of high-grade neoplasms. CONCLUSIONS: The JNK/ERK-AP-1/-Runx2 signal transduction 'network' is associated with chondroblastic malignant transformation and chondrosarcoma development, either separately or through coordinated induction of VEGF.

Adult↗

Desmoplastic infantile ganglioglioma: a questionably benign tumour.

Desmoplastic infantile ganglioglioma is a rare intracranial tumour of childhood that involves the cerebral cortex and the leptomeninges. We report two patients with desmoplastic infantile gangliogliomas and multiple cerebrospinal metastases. To our knowledge, only two similar cases have been reported in the published literature. Pathologically, this rare intracranial tumour shows glial and ganglionic differentiation, accompanied by an extreme desmoplastic reaction. These are low-grade neoplasms that are questionably benign.

Brain Neoplasms↗

Locally-confined signet-ring cell carcinoma of the prostate: a case report of a long-term survivor.

It is generally believed that signet-ring cell carcinoma (SRCC) of the prostate is a high-grade neoplasm with a poor prognosis. We report a case of a long-term survivor diagnosed with localized prostatic SRCC (T3N0M0), who has been alive without any clinical evidence of disease for 100 months after combination therapy which consisted of local irradiation and hormone administration. A posttreatment needle biopsy confirmed the pathological complete response.

Administration, Oral↗

Stereotactic interstitial brachytherapy--current concepts and concerns in twenty patients.

Recent advances in imaging and stereotactic techniques have resulted in wider application of interstitial brachytherapy (IBT) for brain tumors. The advantages of brachytherapy alone or in combination with teletherapy have been detailed, and may be responsible for increasing survival time. We report the preliminary results of 20 patients who underwent CT stereotactic IBT for malignant brain tumors. Despite both old and recent evidence about the efficacy of IBT, concerns remain about the proper grade neoplasm, the target, the dose, and the timing for treatment. Current usage of IBT should be limited to centers with both stereotactic and radiotherapeutic expertise, and where the risks and benefits are being investigated.

Adult↗

Tissue polypeptide antigen (TPA) in urinary bladder cancer cytology: a follow-up study.

Tissue polypeptide antigen (TPA) has been detected by immunocytochemical assay on urine cytological samples from 28 asymptomatic patients, who previously had a histological diagnosis of papillary transitional cell carcinoma (PTCT) of the urinary bladder (UB), in order to evaluate its role in follow-up controls. TPA staining intensity (SI) in urothelial cells was evaluated to improve the diagnostic accuracy of cytology. Differentiated tumor cells were strongly stained for TPA, heavier than normal urothelial cells. Undifferentiated neoplastic cells were less stained for TPA with a wide range of SI. TPA detection revealed positive cytology in 21 (75%) of the considered cases. The accuracy of our cytological findings compared with both routine examinations and subsequent histopathological diagnosis was of 95.2%. Follow-up urinary cytology limits could be reduced by TPA searching in differentiated tumor cells, deriving from low-grade neoplasms.

Aged↗

Chordoid glioma of the third ventricle: Report of a case with cytologic features and utility during intraoperative consultation.

BACKGROUND: Chordoid glioma is a rare, low grade neoplasm with a unique chordoid appearance as well as distinct clinicopathologic and immunohistochemical features. Its cytologic features have not been described. CASE: A 42-year-old woman with recent-onset amnesia and confusion underwent magnetic resonance imaging, which revealed a 5-cm mass lesion arising in the third ventricle. Intraoperative squash smears showed cellular sheets as well as nests and strands of epithelioid tumor cells with bland nuclei and polygonal to elongated cytoplasm in a mucinous background. Binucleation was commonly seen. The tumor was intimately admixed with a benign lymphoplasmacytic infiltrate and scattered Russell bodies. Histologically, the tumor cells were arranged in a syncytium with prominent lymphoplasmacytic infiltrates and scattered small foci of necrosis in a mucinous matrix. The foremost differential diagnosis was chordoid meningioma. Immunohistochemically, the tumor cells were positive for glial fibrillary acid protein (GFAP), vimentin, epithelial membrane antigen, CD34, neuron-specific enolase and CK-7 and negative for synaptophysin, S-100 protein, neurofilament, and estrogen and progesterone receptors. CONCLUSION: Intraoperative smear cytology in this case of chordoid glioma revealed distinctive cytologic features, reflecting the unique histologic pattern. Cytologic features, such as binucleation, absence of intranuclear pseudoinclusions and GFAP immunoreactivity, are particularly helpful in differentiating chordoid glioma from chordoid meningioma.

Adult↗

Salivary duct carcinoma of the parotid gland. Report of a case with cytologic and immunocytochemical findings on fine needle aspiration biopsy.

BACKGROUND: Salivary duct carcinoma (SDC) is a rare high grade neoplasm arising from the larger ducts of the major salivary glands, most frequently in the parotid glands in the elderly. It is important to identify some characteristics that allow differentiating SDC from the other salivary gland adenocarcinomas, which have different prognoses. CASE: A 63-year-old, white male presented with an indolent swelling in the left parotid gland, the retromandibular angle. Fine needle aspiration biopsy (FNAB) showed polygonal or cuboidal, medium-sized, moderately pleomorphic cells with round to oval nuclei in cytocentrifuge preparations. Small tissue fragments with a prominent cribriform pattern and an area of comedocarcinoma were observed in the cytocentrifuged material. Tumor cells were diffusely immunoreactive for low- and high-molecular-weight cytokeratins, and strong positivity was observed with 115D8 and Ber-EP4 antibodies. Overexpression of c-ERB B-2 was absent, and < 5% of the nuclei were immunoreactive for p53. CONCLUSION: The cytologic and immunocytochemical appearance of SDC are characteristic, and FNAB results provide the surgeon with useful information for planning surgical therapy.

Biopsy, Needle↗

Low-grade and high-grade adenocarcinomas of the salivary duct system.

Adenocarcinomas of salivary glands are encountered less frequently than adenoid cystic or mucoepidermoid carcinomas. They fall into two well-defined clinicopathologic groups: 1) those arising from intercalated ducts and 2) those from the excretory and interlobular ducts. The former, designated terminal duct adenocarcinomas, are low-grade malignancies found preponderantly in the oral cavity, especially the palate. The latter, designated salivary duct carcinomas, are high-grade neoplasms and arise almost exclusively in major salivary glands, especially the parotid gland.

Adenocarcinoma↗

Synovial sarcomas of the head and neck.

Springing from mesenchyme rather than mature synovial tissues, synovial sarcomas are high-grade neoplasms that express epithelial as well as supporting tissue features. Accordingly, their histologic phenotypes can be epithelial, stromal, or mixed. Between 3% and 10% of all synovial sarcomas originate in the head and neck, particularly from parapharyngeal sites. These is no appreciable difference in biologic activity between synovial sarcomas of the head and neck and those arising from other anatomic sites. Five-year survivals are misleadingly optimistic and do not adequately reflect the natural history of the sarcoma. Synovial sarcoma is known to metastasize late, and few patients survive that event.

Head and Neck Neoplasms↗