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Necrosis as a prognostic factor in glioblastoma multiforme.

BACKGROUND: Many pathologists require the presence of tumor necrosis within an astrocytic neoplasm to establish the diagnosis of glioblastoma multiforme (GM). Two new grading systems for astrocytic neoplasms allow a tumor to be diagnosed at the highest level of anaplasia without requiring the presence of tumor necrosis. METHODS: To determine whether GMs without necrosis had biologic behavior most compatible with a diagnosis of GM or of anaplastic astrocytoma (AA), we examined the survival of 299 patients whose tumors were diagnosed as GM because they contained endothelial proliferation and who were treated according to prospective clinical protocols. Multivariate proportional-hazards survival analysis was used to assess the importance of tumor necrosis after adjustment for other prognostic factors. RESULTS: Of 275 patients with GMs containing endothelial proliferation, 88% had tumor necrosis. Absence of necrosis was associated with younger age and with less extensive surgical resection. The absence of necrosis predicted longer survival in univariate analysis (P = 0.02) and after adjustment for age, Karnofsky performance score, and extent of resection in a multivariate analysis (P = 0.04). However, the magnitude of the survival difference was not clinically important: patients without tumor necrosis had a median survival of 12.5 months, and those with tumor necrosis had a median survival of 10.9 months. Kaplan-Meier survival rates two years after diagnosis were 13.0% for patients with necrosis and 27.1% for patients without necrosis; the difference in 2-year survival was not statistically significant (difference in survival rates = 14.1%, 95% confidence interval -2.2% to 30.4%). CONCLUSIONS: The survival of patients with astrocytic neoplasms containing endothelial proliferation and no necrosis conforms best to the pattern expected for patients with GM rather than AA. This supports the classification of these tumors as GM in the revised World Health Organization grading system and as grade 4 astrocytomas in the St. Anne-Mayo grading system.

Adolescent↗

Flow cytometric DNA ploidy and S-phase fraction correlate with histopathologic indicators of tumor behavior in colorectal carcinoma.

BACKGROUND: The clinical behavior of colorectal carcinoma is highly variable without reliable predictive biomarkers. Previous reports have shown that flow cytometric DNA analysis may provide valuable prognostic information in these tumors. PURPOSE AND METHODS: This study evaluates the DNA ploidy and the S-phase fraction (SPF) on frozen samples obtained from 61 patients with colorectal carcinoma by using flow cytometry, and it correlates the data with histopathologic features known to affect disease prognosis. Tumors were classified using the World Health Organization's histologic criteria and were staged according the American Joint Committee on Cancer's classification system. Grade of the neoplasm, vascular invasion, and perineural tumor spread were evaluated in every case. RESULTS: Fifty-nine percent of tumors were aneuploid and showed statistically significant higher S-phase values than diploid tumors (22.5 vs. 11.2 percent; P < 0.00001). Mean SPF of the whole series was 17.9 (range, 4.2-44.2) percent. A statistically significant association was found between SPF values and histologic grade (P < 0.0016), nodal status (P < 0.0007), distant metastasis (P < 0.0001), tumor stage (P < 0.0001), venous invasion (P < 0.0002), and lymphatic permeation (P < 0.01) but not with perineural growth and infiltration of the neoplasm through the bowel wall (T). DNA ploidy correlated positively with tumor stage (P < 0.03), and the association between aneuploidy and advanced stages of the disease was statistically significant. CONCLUSIONS: These findings showed that flow cytometric DNA ploidy and SPF, evaluated in fresh samples, are potentially useful parameters to estimate colorectal carcinoma biopathology. Aneuploidy and high replicative neoplastic activity correlated with histopathologic features that are commonly associated with the prognosis of colorectal carcinoma, being SPF-related to disease dissemination and, therefore, an indicator of clinical relevance.

Adult↗

[Sarcoma of the endometrial stroma].

BACKGROUND: To evaluate the most important risk factors and the efficacy of endometrial stromal sarcoma therapy. METHODS: During a period of 9 years, 5 cases of ESS have been observed at the IInd Obstetrical and Gynecological Institute of the University of Bari. The patients were staged according to the FIGO classification of endometrial carcinoma and studied from an epidemiological, histopatological and clinical point of view. All patients firstly received uterine courettage and then total simple laparohysterectomy. In 4 cases bilateral salpingo-oophorectomy and then polychemotherapy. Only in 1 case total hysterectomy and monolateral salpingo-oophorectomy were performed. RESULTS: Two patients were affected by low grade ESS malignancy respectively at Ib and Ic stage and received only surgery. High grade ESS malignancy was diagnosed in 3 patients at stage IIIa and they received surgery followed by chemotherapy. These 3 patients survived for 14, 25 and 30 months. The other two are still alive, with no evidence of the disease at 25 and 36 months. CONCLUSION: ESS is a rare neoplasm; the low grade malignancy may survive from 80-100%, while the high ones can have a fatal prognosis with exitus in 12-30 months.

Adult↗

Steroid hormone receptors in astrocytic neoplasms.

The presence of specific steroid hormone-binding receptors has been correlated with the clinical response to hormonal therapy in a number of different neoplasias, including breast and prostate cancer. In this article, we investigated the expression of the androgen, estrogen, glucocorticoid, and progesterone receptor messenger ribonucleic acid (mRNA) and protein in a number of astrocytic neoplasms of various histological grades. Androgen and glucocorticoid receptor mRNA were detected in all astrocytic neoplasms examined, regardless of histological subtype. In contrast, progesterone receptor mRNA was observed more frequently in high-grade tumors than in low-grade tumors. Estrogen receptor mRNA was undetectable in all astrocytic tumors examined. These studies suggest a possible adjunct clinical use of hormonal therapy for the treatment of astrocytomas. Specific antagonists and agonists may allow the modulation of the growth of these tumors. Development of this body of knowledge may lead to the development of better treatment for these aggressive tumors.

Adolescent↗

Pediatric intramedullary spinal cord tumors: special considerations.

Intramedullary spinal cord tumors (IMSCTs) of the pediatric population are rare and comprise thirty-five percent of intraspinal neoplasms. Low-grade astrocytomas predominate; ependymomas increase in frequency with ascending age and become the most frequent IMSCT in adults. Gangliogliomas are very rare in adults but comprise nearly thirty percent of tumors in children under three years of age. The cervical spine is the region of the spine most affected. Pain is the most common presenting symptom with weakness, gait deterioration, torticollis also frequently reported. Hydrocephalus occurs with greater frequency than in adult patients and often requires a shunt. Motor and sensory evoked potential monitoring is routinely utilized. Osteoplastic laminotomy is performed to forestall the development of progressive spinal deformity. Gross total resection is feasible in most ependymomas and results in surgical cure. Astrocytomas are infiltrating neoplasms and gross total resection is occasionally possible only in the pediatric population. However, the role of radical resection of low-grade fibrillary astrocytomas of the spinal cord in children has not been definitively demonstrated in the literature. Outcome for low-grade astrocytomas is better in children than adults, but not as favorable as that for ependymomas. Malignant tumors have dismal outcomes and surgery in these patients serves only to provide a diagnosis.

Adult↗

[Retroperitoneal sarcoma: therapeutic and prognostic characteristics, report of 6 cases].

Retroperitoneal sarcoma is a rare solid tumor that accounts for less than 15% of soft tissue sarcoma. The authors conducted a retrospective study about 6 cases to evaluate the natural history of the tumors and the causes of treatment failure in an attempt to develop a rational approach to the management of the neoplasm. The histological grade and complete resection are the most important prognosis factors.

Adult↗

Impact of second opinion pathology in the definitive management of patients with bladder carcinoma.

BACKGROUND: The accurate diagnosis, staging, and grading of bladder neoplasms depend heavily on the interpretation of biopsies and transurethral resection (TUR) specimens. Although many centers require review of outside pathologic material before definitive treatment such as radical cystectomy, the authors are unaware of data supporting the utility of this approach in urothelial (transitional cell) carcinoma. The authors therefore examined the clinical and cost impact of pathologic review on patients referred to an academic urology department for treatment of bladder neoplasia. METHODS: The pathologic material from 97 patients referred to an academic center for evaluation of urothelial carcinoma of the bladder from July 1996 to July 1999 was reviewed. This material was received from 30 community hospitals and 4 academic centers. The 97 patients had undergone 131 (mean, 1.35; range, 1-10) biopsies or TUR procedures before referral. Surgical pathologists at the authors' institution reviewed all outside patient material, and discordant cases were rereviewed by one of the authors (S.E.M), an experienced genitourinary pathologist. Follow-up chart review was performed in discordant cases to determine clinical and pathologic outcomes. RESULTS: Upon review at the authors' institution, 24 of 131 (18%) specimens with a referring diagnosis of urothelial carcinoma exhibited significant discrepancies with regard to the diagnosis, stage, grade, or tumor histologic type made at the outside institution. Four tumors (3%) were found to be nonurothelial neoplasms. Five specimens (4%) were judged inadequate for staging because they contained no muscularis propria. Three patients were upstaged, including two patients shown to have muscle invasive disease. Eight patients were downstaged, including two patients referred with purported muscle invasive disease who were determined to have only superficial disease on pathology review. Two patients initially thought to have carcinoma in situ (tumor in situ [Tis]) showed no evidence of Tis on pathology review. One patient with purported muscle invasive disease was shown to have only metaplasia, and one patient had a highly significant change in tumor grade. As a result of the pathology review, five radical cystectomies were avoided, whereas five repeat TUR procedures were recommended for inadequate staging. One patient shown to have muscle invasion on pathology review proceeded directly to cystectomy, avoiding a planned repeat TUR. A cystectomy also was recommended to a second patient who was shown to have invasive disease by the pathology review. Pathology review of 131 specimens resulted in net savings of $86,176 or $658 per TUR reviewed. CONCLUSIONS: The review of bladder pathologic materials before definitive therapy can impact clinical decisions significantly and can reduce overall expenditures for the management of this cohort of bladder carcinoma patients.

Biopsy↗

Expression of growth factor/receptor genes in postthymic T cell malignancies.

This study was undertaken to explain the molecular basis for the diverse pathology and clinical behavior of postthymic T cell malignancies. Total cellular RNAs were extracted from four HTLV-1 positive and ten HTLV-1-negative T cell lymphomas and cell lines, and investigated for homology with cloned DNA probes specific for interleukin-2 (IL-2), IL-2 receptor (IL-2R), transforming growth factor beta (TGF-beta), platelet-derived growth factor (PDGF), and epidermal growth factor receptor (EGF-R). Tumor cells associated with clinically high grade HTLV-1-positive adult T cell leukemia (ATL) and large cell morphology (T immunoblastic lymphomas) were found to have higher levels of expression of IL-2 and TGF-beta genes than low grade T cell neoplasms (mycosis fungoides and Sezary's syndrome). High expression of IL-2R gene was restricted to Ki-1-positive lymphomas and to one ATL. Cell lines corresponding to the advanced stage of a cutaneous T cell lymphoma (CTCL) showed enhanced expression of PDGF. Therefore, high grade T cell malignancies had consistently elevated expression of growth factor/receptor (GF/R) genes. Expression of EGF-R was negligible in all T cell malignancies. An inverse relationship was found between the expression of T cell antigen receptor (differentiation antigen) and GF/R (activation antigen) genes, accounting for the frequent aberrant expression of T cell antigens in high grade T cell lymphomas. The results suggest that post-thymic T cell malignancies derived from activated T cells produce and secrete GF, conferring a growth advantage on neoplastic T cells, and correlating well with their histologic subtype and clinical behavior.

Blotting, Northern↗

Monocytoid B-cell lymphoma. The biologic and clinical implications of peripheral blood involvement.

Monocytoid B-cell lymphoma (MBCL) is a newly recognized malignant lymphoma that shares clinical and pathologic features with other low-grade B-cell neoplasms, especially small lymphocytic lymphoma and hairy cell leukemia. However, although circulating malignant cells and bone marrow involvement are relatively common in small lymphocytic lymphoma and are characteristic features of hairy cell leukemia, MBCL in the peripheral blood and bone marrow rarely have been described. From 124 patients entered in the MBCL registry, three cases with peripheral blood involvement are described and the clinical and pathologic features in these patients are compared with those of other low-grade B-cell neoplasms. Monocytoid B-cell lymphoma was confirmed by lymph node biopsy in each case. Two patients had lymphocytosis at the time of presentation; the remaining patient presented with pancytopenia. For each patient, phenotypic studies of lymph node and peripheral blood revealed identical monoclonal surface immunoglobulin expression. The morphologic appearance of the circulating MBCL cells was different in each case, varying from a relatively homogeneous population of small lymphocytes to a heterogeneous collection of large and small lymphoid cells. The two patients with lymphocytosis also had extensive replacement of the bone marrow by MBCL; the third patient had diffuse infiltration by MBCL in a normocellular marrow. All three patients had advanced-stage (Stages III or IV) disease, and all required systemic chemotherapy for disease control. The two patients with lymphocytosis had relentless, progressive infirmity despite relatively aggressive treatment regimens. These patients ultimately died of lymphoma 13 and 18 months after initial diagnosis. The third patient is alive and well with stable disease 30 months after coming to the authors' institution. The clinical and pathologic features of the patients reported here reaffirms the placement of MBCL in the spectrum of low-grade B-cell neoplasms. However, unlike small lymphocytic lymphoma and hairy cell leukemia, MBCL only rarely undergoes leukemic conversion. Furthermore, it appears that peripheralization of MBCL occurs primarily in patients with advanced-stage disease and may be indicative of a relentless course and progressive disease despite aggressive chemotherapeutic intervention.

Adult↗

[Indications for elective neck dissection in malignant epithelial parotid tumors].

The purpose of the present study was to define the indications and extension for the treatment of lymph nodes in clinically NO patients with primary malignant epithelial parotid tumors. A retrospective analysis was performed on 46 cases with such tumor out of 307 parotid neoplasms (246 benign, 61 malignant) consecutively treated from 1985 to 1994. Lymph node metastases were present only in the histotypes with a high degree of malignancy (overall incidence, 24%). Two patients (5%) showed occult metastases. No correlation was found between the size of the neoplasm and the incidence of lymph node metastases. However, the latter were significantly more common in locally highly aggressive neoplasms (class "a"), 8%; class "b" 43%; P = 0.006). Due to the small number of cases, it was not possible to correlate the incidence of occult metastases with neoplasm size or local extension. As regards topographic distribution of lymph node metastases, level II was always involved, level V was never involved, and level i.v was involved only when metastases were found in the upper levels. Occult metastases were found only at level II. Over a follow-up period of 2 to 10 years, no cases were seen with cervical recurrences. Although drawn from a limited series, the results are similar to the data generally reported in the literature, showing that lymph node metastases are rare in neoplasms with a low grade of malignancy whereas there is a significant increase in the incidence of metastatic lymph nodes and occult metastases when the grade of malignancy is high. In conclusion, in clinically NO patients, a suprahomohyoid neck dissection (levels I-II-III) is indicated only when the neoplasm shows a high grade of malignancy or when it is a class "b" malignancy. In the other cases, neck dissection is determined by the clinical evidence of metastasis and can be extended to the lower levels. Neck dissection can be avoided in NO patients whenever ultrasound and fine needle biopsy are both routinely used in the preoperative evaluation of the cervical lymph nodes.

Epithelial Cells↗

c-erbB-2 in astrocytomas: infrequent overexpression by immunohistochemistry and absence of gene amplification by fluorescence in situ hybridization.

Recent studies suggest that aberrations of c-erbB-2 may be involved in astrocytic brain tumours. We screened immunohistochemically c-erbB2 protein (p185) expression in 94 astrocytic grade 1-4 neoplasms of the brain. The amplification of the c-erbB-2 oncogene was investigated in protein overexpression cases by dual colour fluorescence in situ hybridisation (FISH). p185 overexpression was correlated with p53 and epidermal growth factor receptor (EGFR) expression, as well as with clinicopathological features. Only two anaplastic (grade 3) astrocytomas and one glioblastoma (grade 4) showed overexpression of p185 protein by immunohistochemistry (monoclonal MAb1 antibody TA250), whereas none of the grade 1-2 astrocytomas was positive. Interestingly, the expression of p185 was confined solely to the cytoplasm of neoplastic astrocytic cells and not to the cell membranes as found in malignancies with amplification of the c-erbB-2 oncogene. Two of the three overexpression cases were also positive by EGFR. No amplification of the c-erbB-2 gene was observed by FISH in the three tumours with immunohistochemical p185 overexpression or seven weakly positive/negative tumours. In conclusion, our results suggest that p185 overexpression is infrequent in astrocytomas, that it is of no important diagnostic or prognostic value and that c-erbB-2 oncogene amplification is not seen in the few cases in which there is overexpression.

Adolescent↗

Bone grafting in the surgical management of osseous neoplasms.

The diagnosis and treatment of osseous neoplasms are challenges for the foot and ankle surgeon. Osseous neoplasms are potentially debilitating, thus appropriate diagnosis and management are critical to success. Resection of these lesions can result in large osseous deficits, requiring bone grafting for replacement. The graft may provide osteogenesis, structural support, or both. This article presents possible surgical therapeutic alternatives in management of benign and low-grade malignant osseous neoplasms in the foot and ankle.

Bone Neoplasms↗

Molecular analysis of astrocytoma associated with Turcot syndrome type 1--case report.

A 49-year-old man presented with a brain tumor and colon carcinoma. The patient had been treated under diagnoses of hereditary non-polyposis colorectal cancer syndrome and Muir-Torre syndrome. Magnetic resonance imaging revealed a mass lesion in the right frontal lobe with diffuse high intensity on T2-weighted and fluid-attenuated inversion recovery images. A few small lesions were enhanced by gadolinium on the T1-weighted images. Histological examination revealed the brain neoplasm was astrocytoma grade III according to the World Health Organization classification. Molecular genetic analysis detected microsatellite instability and p53 mutation only in the tumor tissue, indicating a failure of the deoxyribonucleic acid mismatch repair system. These results suggest that inactivation of mismatch repair system and p53 is closely associated with the tumorigenesis of this neoplasm. The final diagnosis was Turcot syndrome type 1.

Astrocytoma↗

Proton magnetic resonance spectroscopy and intracranial tumours: clinical perspectives.

Proton magnetic resonance spectroscopy (1H-MRS) was applied to characterize intracranial tumours of different hystological types. Seventy patients with intracranial neoplasms were studied before receiving surgery, radiotherapy or chemotherapy. All tumours were characterized by reduced or absent N-acetylasparate and increased signal from choline-containing compounds. Distinctive patterns were observed only for primitive brain neoplasms; high-grade gliomas were differentiated from low-grade ones by higher levels of choline-containing compounds. The metabolic aspects of metastatic lesions were similar to high-grade gliomas. These results, together with the limitations of 1H-MRS and future applications are reviewed.

Adenoma↗

The prognostic significance of vascular invasion in stage T1 bladder cancer.

Transurethral resection specimens from 170 T1 bladder carcinomas were reviewed for the presence of vascular (blood vessel and/or lymphatic) invasion by tumour cells. Such a finding was noted in 17 cases (10%), and occurred most frequently in high grade tumours. Tumour recurrence was documented in 11 of these cases (65%), including seven patients who showed progression to more invasive disease (T2-T4) and six patients (55%) who died of disease. Five-year survival for cases without vascular invasion was 81% versus 44% for those with. This was a statistically significant difference (log-rank, P = 0.004). Neoplasms of high grade (grades 2 to 3), without a papillary configuration, and exceeding 5 cm were associated with vascular invasion (chi-squared; P < 0.001, P = 0.043, and P = 0.061 respectively). In multivariate analysis vascular invasion proved to be an independent prognostic factor (Cox's regression, P = 0.015). We therefore stress the clinical relevance of a thorough evaluation of the state of vascular invasion in stage T1 bladder cancer.

Aged↗

[Bladder inverted papilloma. Can it be considered as a neoplasm with low degree of malignancy?].

We report a case of inverted papilloma of the bladder. The clinical features, diagnosis and treatment of this tumor type are discussed. We underscore the histology and histogenesis of the two types: trabecular inverted papilloma and glandular inverted papilloma. A review of the literature has shown that inverted papillomas do not show clinical or histological features of malignancy most of the time. The cases with synchronous or metachronous association with transitional cell carcinoma, recurrence or histologic signs of malignant transformation of a lesion may be considered to have a neoplasm of low grade malignancy and these patients must be followed closely.

Humans↗

Fine-needle aspiration cytology of a primary ectopic meningioma.

Meningiomas are benign tumors derived from arachnoid cells. Most commonly an intracranial lesion, meningiomas may be found extracranially in various anatomic sites. A 23-yr-old white female presented with left-sided palpable mass located submucosally in the floor of the mouth. CT scan revealed no evidence of mass elsewhere in the head and neck region. Fine-needle aspiration cytology (FNAC) showed loose and cohesive cellular fragments with lobular growth pattern and uniform round or ovoid cells. The diagnosis of low-grade salivary gland neoplasm, not further classified, was made. The tumor was locally excised. The differential diagnoses of an extracranial meningioma and pleomorphic adenoma were discussed at the frozen section. Based on light microscopic, immunohistochemical, and electron microscopic (EM) findings, the final diagnosis of an ectopic meningioma was rendered. Ectopic meningiomas may pose a diagnostic challenge to clinicians and cytopathologists. It is easily forgotten in the list of differential diagnosis at an ectopic site. Primary ectopic meningioma in a region containing salivary gland(s) may mimic benign and low-grade malignant salivary gland tumors in FNAC.

Adenoma↗