Biologic differences between noninvasive papillary urothelial neoplasms of low malignant potential and low-grade (grade 1) papillary carcinomas of the bladder.
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Carcinomas of the bladder cause important problems of mortality and morbidity despite diagnostic and therapeutic improvements. A variety of grading systems has been developed to reflect the different biologic behavior and malignant potential of this heterogeneous neoplasm. However, these histologic grading systems are subjective and reproducibility is low. In this study, the nuclear morphometric features and DNA ploidy status of 86 cases of transitional cell bladder carcinomas have been studied using image analysis methods with different data selection methods in nucleus suspension to evaluate the relationship of these parameters with the conventional prognostic factors. The relationship between these parameters and likelihood of relapse has also been investigated. In conclusion, the mean nuclear area of the 10 largest nuclei and DNA ploidy status have been shown to be significantly correlated with conventional prognostic factors. Cytomorphometrically, a binary grading system seems more suitable for transitional cell carcinoma of the bladder. For superficial carcinomas, morphometric parameters and DNA ploidy analysis can be helpful in the separation of the patients into prognostically different groups.
The monoclonal antibody Ki-67, which reacts with cells in the active part of the cell cycle, was used to evaluate immunocytochemically the growth fraction in 22 primary brain neoplasms. The percentage of labelled cells reflected the histological grade of malignancy of each neoplasms. High percentage of Ki-67-positive cells were observed in one choroid plexus carcinoma (60%), one primary melanoma of meninges (40%), three medulloblastomas (40%-50%), one anaplastic astrocytoma and six glioblastomas (10%-40%). One ependymoma had 7% positive cells. Rare positive cells (1%) were present in one pilocytic astrocytoma and one ganglioglioma. Except one negative case, the meningiomas (five cases) had values of positivity ranging from 1% to 6%. Two acoustic schwannomas were negative. These results suggest that immunocytochemical staining with the Ki-67 may be a useful method for measuring the growth fraction in brain neoplasms.
In a prospective study on the grading of superficial papillary neoplasms of the bladder a distinction was made between tumours showing only increased cellularity without appreciable cellular and nuclear deviation (grade 1), tumours showing slight cellular variation (grade 2a), and tumours showing clear cytological deviation and a tendency to lose normal polarity (grade 2b). Ninety-one patients with a superficial tumour were followed up for a mean of 24 months. Grade 2a tumours recurred later and in fewer patients than grade 2b tumours. Progression was seen in 4% of grade 2a tumours and in 33% of grade 2b carcinomas. Adapting our results to the WHO grading system, we suggest that all tumours in this study defined as grades 1 and 2a should be classified as low grade and tumours defined as grade 2b should be classified as intermediate grade.
We report clinical and pathological data of 419 image-guided stereotactic biopsies. In the present series the diagnostic yield, estimated by comparing the original histological diagnoses with follow-up data, was found to be approximately 94% in gliomas. As it has been suggested that malignancy of astrocytic gliomas may be considerably underestimated in the small tissue samples obtained by stereotactic biopsy, we have reviewed 160 adult, diffuse supratentorial astrocytic tumours, correlating the original Kernohan tumour grades with survival. In this grading system, although there was generally a good correlation between histological grade and survival probability (P < 0.0001), no distinction could be made between the grade 3 (anaplastic astrocytoma) and grade 4 (glioblastoma) groups. Tumour grades obtained by applying the criteria of the more recent Daumas-Duport grading system were also determined and correlated with survival. These latter tumour grades not only correlated well with survival (P < 0.0001), but also enabled us to identify a group of patients with intermediate grade malignancy (grade 3, anaplastic astrocytoma), surviving longer than those with grade 4 tumours. Image-guided stereotactic biopsy is a useful means of providing tissue samples for histological diagnosis of brain neoplasms, including gliomas. Histological grading of adult, diffuse supratentorial astrocytic gliomas diagnosed by this technique is possible and should be carried out using an appropriate grading system.
AIMS: Pleomorphic carcinoma is a poorly described entity whose phenotype is not well recognized as within the morphological spectrum of breast carcinoma. The purpose of this report is to describe the clinicopathological features of this tumour, and to promote its recognition as an unusual high-grade morphological variant of mammary ductal carcinoma. METHODS AND RESULTS: Histological slides of breast carcinomas (N = 64) coded between 1978 and 1995 as having pleomorphic or anaplastic features were reviewed. Pleomorphic carcinoma (N = 26) was diagnosed when > or = 50% of the tumour manifested a pleomorphic cell population (> sixfold variation in nuclear size). Tumours of lobular origin were excluded. All neoplasms occurred in women with a mean age of 53 years. Patients underwent biopsy and/or mastectomy (n = 24) or lumpectomy (n = 2). The tumours' mean size was 54 mm. All were high-grade neoplasms. The pleomorphic cell population comprised 50-100% of the tumour; 31% had a prominent spindled morphology. Fifty-eight per cent of the tumours were initially misclassified by referring pathologists as sarcomas or carcinomas, possibly metastatic. Adjacent DCIS or a transition to classic ductal carcinoma was present in 73%. Five (19%) patients were stage I and three (12%) had stage IV disease. Axillary dissections yielded > or = 3 (mean 7.2) positive lymph nodes in 52%. Most (68%) tumours were aneuploid; a high S-phase (> 10%) was present in 63%. All neoplasms were ER negative and all but one were PR negative. p53 expression was present in 71%; none expressed bcl-2. c-erbB-2 was detected in four (19%) node-positive and in 0 (0%) node-negative cases (P = 0.01). Of 16 patients with follow-up, 6 (38%) were disease-free (mean, 74 months), four (25%) alive with disease (mean, 33 months) and six (38%) dead of disease at a mean of 22 months. CONCLUSIONS: Pleomorphic carcinoma is a prognostically unfavourable lesion and represents the extreme end of the morphological spectrum of grade III infiltrating ductal carcinoma.
Weiss proposed 9 histologic criteria to evaluate the malignancy of adrenal cortical tumors. Each tumor is graded from 0 to 9 according to how many of the criteria are present. Eight of the 17 neoplasms from the present study were graded from 0 to 2; none of these 8 tumors metastasized or recurred. The grade of the nine other neoplasms ranged from 3 to 8; seven lesions metastasized (grade 4 to 8), one recurred (grade 5), and the last one neither metastasized nor recurred (grade 3) although this tumor was considered malignant according to Weiss' system. Even thought the results obtained using Weiss' system are similar to the results that were put forwards initially, and despite prognostic uncertainty with grade 3 tumors, we think that the later system provides a more objective evaluation of the prognosis of adrenal cortical tumors, compared with usual morphologic methods.
PURPOSE OF REVIEW: Fine needle aspiration is a safe diagnostic technique that is widely employed for lesions of the head and neck. Among head and neck sites, the parotid gland stands apart for the number, diversity and peculiarity of pathologic processes to target this structure. This matchless complexity has prompted a thoughtful discussion regarding the application of the fine needle aspiration to parotid masses--a discussion that has primarily focused on the reliability of the fine needle aspiration as a diagnostic tool, and on its utility in guiding patient management. RECENT FINDINGS: Recent studies have confirmed a high overall accuracy rate for fine needle aspiration evaluation of parotid masses, ranging from 90 to 95%. At the same time, these soaring accuracy rates cannot be uniformly anticipated across all diagnostic scenarios. Fine needle aspiration is notoriously unreliable in recognizing the malignant nature of the parotid carcinoma, providing its precise classification, and establishing its grade. A few malignant neoplasms are particularly prone to diagnostic error. Acinic cell carcinoma is frequently interpreted as benign or even nonneoplastic; and low-grade lymphomas are often discounted as inflammatory processes. SUMMARY: Parotid gland masses are not particularly conducive to diagnostic accuracy and precision by fine needle aspiration. Accordingly, indiscriminant reliance on the fine needle aspiration findings at the expense of the clinical, radiographic, and intraoperative findings is unwarranted. Whether one uses the fine needle aspiration routinely or selectively in patients with parotid masses, the fine needle aspiration findings should contribute to, not displace, the overall diagnostic impression.
Papillary renal cell carcinoma is considered a less-aggressive histomorphologic variant of renal cell carcinoma. We investigated the clinicopathologic features and the DNA ploidy pattern in 22 papillary renal cell carcinoma cases and correlated the findings to the patients' length of survival. In this study the demographic data were similar to those of previously published series. Histologically, two neoplasms were Fuhrman's nuclear grade 1, eight were nuclear grade 2, 11 were nuclear grade 3, and one was nuclear grade 4. Six tumors were stage I, three were stage II, five were stage III, and eight were stage IV. With a mean follow-up period of 42 months, eight patients died of disease and 14 were alive and well. DNA aneuploidy was found in 50% of the neoplasms and was frequently associated with high tumor nuclear grade, high tumor stage, and poor prognosis. Conversely, DNA diploidy was preponderantly noted in neoplasms with low tumor nuclear grade and stage, and none of the patients died of their disease. A statistically significant difference between DNA ploidy/tumor stage and patient outcome was obtained. No significant correlation between DNA ploidy and nuclear grade was observed. Our results suggest that DNA content measurements may assist in evaluating the clinical outcome of this neoplasm. Moreover, they indicate that papillary renal cell carcinomas manifest clinicopathologic, DNA content, and biologic characteristics akin to those of nonpapillary variants.
BACKGROUND: Urothelial carcinoma of the bladder often contains areas with different histologic grades. The influence of cancer heterogeneity on grading and its relation to patient outcome is uncertain. METHODS: The study group consisted of 164 patients with Ta urothelial carcinoma diagnosed at the Mayo Clinic between 1985 and 1986. None had previous or coexistent urothelial carcinoma in situ or invasive carcinoma. The primary (most common) and secondary (second most common if at least 5% of the cancer) patterns of cancer growth were graded by the newly proposed World Health Organization and International Society of Urological Pathology (WHO/ISUP) grading system. Scores of 1, 2, and 3 were assigned to urothelial neoplasms of low malignant potential (LMP), low grade urothelial carcinoma, and high grade urothelial carcinoma, respectively. The mean follow-up was 7.7 years (range, 0-13.3 years; median, 9.2 years). Progression was defined as the development of invasive carcinoma, distant metastasis, or death due to bladder carcinoma. RESULTS: Patient ages ranged from 36 to 96 years (mean, 69 years), and the male-to-female ratio was 4:1. Disease progression developed in 32 patients during a mean follow-up of 7.7 years. The mean interval from diagnosis to progression was 3.1 years (range, 0.01-8.7 years). Progression free survival was 82%, 77%, and 76% at 5, 7, and 10 years, respectively. Primary and secondary grades were different for 52 patients (32%). Based on the worst grade, 19 patients (12%) had urothelial neoplasms of low malignant potential (LMP), 92 (56%) had low grade carcinoma, and 53 (32%) had high grade carcinoma. Histologic grades based on worst, primary, secondary, and combined primary and secondary grades were all significant for predicting progression (P = 0.0009, 0.0004, 0.001, and 0.0001, respectively). Seven-year progression free survival rates for patients with LMP, low grade, and high grade carcinoma (based on worst grade) were 93%, 82%, and 61%, respectively; for patients with combined scores of 2, 3, 4, 5, and 6, survival rates were 93%, 80%, 82%, 68%, and 40%, respectively. The difference between patients with combined scores of 5 or 6 was statistically significant (P = 0.02). CONCLUSIONS: Histologic grade of urothelial carcinoma based on the newly proposed WHO/ISUP grading system stratifies patients into prognostically significant groups. Grading should also take cancer heterogeneity into consideration, and prognostic accuracy appears to be increased when the combined primary and secondary grades are applied. [See editorial counterpoint on pages 1509-12 and reply to counterpoint on pages 1513-6, this issue.]
BACKGROUND AND AIMS: Aberrant crypt foci (ACF) are thought to be preneoplastic lesions and are assessed by magnifying chromoscopy with methylene blue staining. The aim of this study was to evaluate the predictive value of rectal ACF recognized by conventional chromoscopy for colonic advanced neoplasms. METHODS: Total colonoscopy, involving rectal chromoscopy using indigo carmine with standard colonoscopies, was performed on 386 patients. Patients who showed no ACF were classified as Grade 0, and those who had 1-4, 5-9, and 10+ ACF were classified as Grades 1, 2, or 3, respectively. The correlation between ACF grading and the prevalence of colonic advanced neoplasm, any adenoma>or=1 cm in size and/or with villous or tubulovillous morphology, and/or with high-grade dysplasia or invasive cancer, was assessed. RESULTS: Sixty-three patients were classified as ACF Grade 0, 119 as Grade 1, 116 as Grade 2, and 88 as Grade 3. Colonic advanced neoplasm was observed in 4 patients (6.3%) for Grade 0, 43 (36.1%) for Grade 1, 61 (52.6%) for Grade 2, and 57 (64.8%) for Grade 3. As the ACF grade increased, the chance of a patient having a colonic advanced neoplasm increased. For multivariate analyses, compared with patients with Grade 0, those with Grades 1, 2, or 3 had a greater risk of colonic advanced neoplasm (odds ratio [OR] 9.18, 95% CI 3.08-27.33, OR 20.44, 95% CI 6.81-61.42, and OR 32.94, 95% CI 10.49-103.41, respectively). CONCLUSIONS: Chromoscopic assessment of rectal ACF by conventional techniques is useful for predicting colonic advanced neoplasms.
A study was carried out to determine the apoptotic index (AI) in cases of endometrial adenocarcinoma that are usually associated with a poor prognosis, and to identify in the AI in these cases differs from the AI's in grade I and II endometrial adenocarcinoma. The apoptotic index (defined as the percentage of morphologically identified apoptotic cells and apoptotic bodies in counting 3000 tumor cells) was calculated for five grade III endometrial adenocarcinomas of no specific type (NST), five clear cell adenocarcinomas (CCC), three high grade uterine papillary serous carcinomas (UPSC) and one undifferentiated carcinoma of the endometrium. Overall a higher mean AI (6.3%) was identified in these poor prognosis neoplasms than in 13 grade I and II endometrial adenocarcinomas (mean AI 2.7% p < 0.0001). The apoptotic index was highest in the undifferentiated carcinoma (AI = 9.7%). The mean AI for the cases of UPSC, CCC and grade III endometrioid (NST) adenocarcinomas were 7.4%, 5.9% and 5.2% respectively. There was no evidence of a statistically significant difference in the AI in these poor prognosis groups (Kruskall Wallis test p = 0.45). Although the results show that a high AI is a feature of poor prognosis endometrial carcinoma, no distinction in AI was demonstrated in the subtypes examined.
Neoplasms constitute the major complication of coeliac disease, and high-grade T-cell lymphoma of the small intestine (enteropathy-associated T-cell lymphoma) is the most common neoplasm in this category. HLA genotyping indicates that in patients with enteropathy-associated T-cell lymphoma have the coeliac disease associated DQA1*0501, DQB1*0201 phenotype, although additional HLA-DR/DQ alleles may represent risk factors for lymphoma development. Molecular biological and immunohistochemical studies have shown that the intestinal mucosa distant from the tumour contains clonal populations of small T cells, often of the same clone as the high-grade T-cell lymphoma. These findings suggest that enteropathy-associated T-cell lymphoma arises in the setting of coeliac disease and evolves from reactive intraepithelial lymphocytes through a low-grade lymphocytic neoplasm to a high-grade tumour, which is usually the cause of the presenting symptoms. Most cases of chronic ulcerative enteropathy (ulcerative jejunitis) are probably part of the same disease process. If the ulceration occurs at a time when the neoplastic T-cells are of a low grade, morphological recognition of tumour cells in the ulcers may be impossible. Carcinoma of the pharynx and oesophagus, and adenocarcinoma of the small intestine, are increased in frequency in patients with coeliac disease. The increased risk of carcinoma of the oesophagus may be related to vitamin A deficiency. A number of reports have indicated an increased prevalence of various types of chronic hepatitis in patients with coeliac disease, but no coherent view of the cause of this association has emerged. Similarly, patients with coeliac disease have been reported to have various forms of fibrosing lung disease of uncertain causation. In recent years, there have been several reports, mainly from Italy, of a syndrome of epilepsy and bilateral brain calcification occurring in coeliac patients. The pathogenesis of this condition is not known and its prevalence in other communities is uncertain. Splenic atrophy occurs frequently in patients with coeliac disease and is related to the severity of the disease and degree of dietary control. Splenic atrophy predisposes to infection with capsulated bacteria, although mortality studies indicate that infection with these organisms is not a major cause of death in patients with coeliac disease.
This is a case report on a 70-year old male patient with a huge ulcerative squamous cell carcinoma of the scalp as well as numerous palpable lymph nodes in the neck. Tumour extirpation and bilateral conservative neck dissection were performed. Histological examination of the excised lymph nodes did not reveal a metastatic infiltration but an additional neoplasm -- a low-grade malignant lymphoma (lymphoplasmocytic immunocytoma).
Benign lymphangioendothelioma (BL) is a rare vascular neoplasm that can histopathologically mimic a low-grade angiosarcoma or the patch stage of Kaposi sarcoma. We report on the case of a 49-year-old man with a benign lymphangioendothelioma on the right thigh that evolved on a vascular birthmark after a trauma. Because of constant pain and the slow but progressive growth of the lesion, we decided to excise the tumor. Three stages of surgery were needed to obtain negative margins. We review the reports of BL to date, with special attention to those that developed after trauma and those that had a preexistent vascular lesion, and expound on the histopathologic differential diagnosis with low-grade angiosarcoma.
Elevated amylase activity was noted in the pleural effusion of a patient who was later found to have a stage I low-grade serous papillary ovarian neoplasm. The effusion resolved spontaneously after resection of the ovarian tumor, which contained large amounts of amylase activity. The ultrastructure of the tumor epithelium resembled that of normal salpinx. Secretory-type cells were present with apical, variably electron-dense secretory granules and cytoplasmic glycogen deposits. Amylase activity in the ovarian neoplasm probably resulted from the presence of functioning endosalpingeal-type epithelium in the tumor. In cases of effusion with unexplained amylase elevations, the possibility of serous ovarian neoplasia should be considered, even in the absence of demonstrable extra-ovarian dissemination.