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PubMed2004

Low-grade tubular-mucinous renal neoplasm with neuroendocrine differentiation: a histological, immunohistochemical and ultrastructural study.

Low-grade tubular-mucinous renal neoplasm (LGTMRN) was recently established as a distinct carcinoma classification. A 70-year-old, female traffic accident victim underwent a detailed examination that disclosed a huge mass in the lower pole of the left kidney. The patient underwent a nephrectomy based on a diagnosis of renal tumor. Macroscopically, the tumor was well demarcated and a whitish color with focal hemorrhage. Histological examination showed that tumor cells proliferated through tubular, trabecular, and solid growth patterns in the mucinous background. Focally, foci of clear cells or the proliferation of spindle cells was also observed. Nuclei were generally round and uniform in size. No abnormal mitotic figures were identified. Immunohistochemically, tumor cells were diffusely positive for AE1/AE3, vimentin and chromogranin A, and focally positive for cytokeratin (CK) 18, CK19, Ulex europaeus agglutinin-1, epithelial membrane antigen, neuron-specific enolase (NSE), CD9 and CD57. Ultrastructurally, tumor cells contained a moderate number of mitochondria, rough endoplasmic reticulum and dense-core granules. No renin granules or glycogen were observed. Microvilli were focally seen. Our results render further evidence that LGTMRN is a distinct entity from the hitherto established renal neoplasms. Foci of clear cells and neuroendocrine differentiation should be added to the histological spectrum of LGTMRN.

Adenocarcinoma, Mucinous↗
PubMed2000

The diagnosis of low-grade peripheral B-cell neoplasms in bone marrow trephines.

The aim of this study was to establish how effective is the use of immunohistochemistry on formalin-fixed bone marrow in diagnosing low-grade B-cell neoplasms. We investigated a series of 41 consecutive patients with bone marrow involvement for whom no other diagnostic tissues were available. The sections were stained with the following antibodies: CD3, CD20, CD79a, CD5, CD10, CD23, anti-cyclin D1 and kappa and lambda light chains. Antigen retrieval was performed using either a microwave oven or a pressure cooker. Labelling was performed with an avidin-biotin-peroxidase labelling system. A final diagnosis was reached in 37 out of 41 cases (90%): B-chronic lymphocytic leukaemia (15 cases), follicular lymphoma (10 cases), mantle-cell lymphoma (eight cases) and lymphoplasmacytoid lymphoma/immunocytoma (four cases). In the remaining four cases, a generic diagnosis of low-grade B-cell neoplasm was made. The immunophenotyping of formalin-fixed marrow is a useful technique for diagnosing most of the low-grade B-cell neoplasms.

Antigens, CD↗
PubMed2004

Neurofibromatous changes in dermatofibrosarcoma protuberans: a potential pitfall in the diagnosis of a serious cutaneous soft tissue neoplasm.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignant neoplasm that has the potential for aggressive local growth and destruction if not treated appropriately. Although the storiform arrangement of spindle cells in DFSP is relatively characteristic, histologic patterns simulating other benign as well as malignant neoplasms such as dermatofibroma, neurofibroma, malignant fibrous histiocytoma, and atypical fibroxanthoma have been described. METHODS: We collected and analyzed six cases of probable DFSP in which a specific diagnosis could not be rendered due to the predominant neurofibromatous changes in the histologic sections. In an attempt to reach a definitive diagnosis, the clinical history and physical characteristics of the lesions were taken into account, and all cases were further evaluated using immunostaining for CD34 and S-100 protein. RESULTS: The average age of the patient was 56 years (range 21-80), and the male to female ratio was 1 : 1. The location of lesions included the scalp, neck, back, and abdomen. All cases displayed two distinct histological patterns: (i) a proliferation of spindle cells with wavy nuclei in a loose mucinous stroma suggesting neural differentiation and (ii) a proliferation of spindle cells which interweaved and filled the reticular dermis extending into the subcutis. The wide variety of clinical impressions and descriptions indicated that the diagnoses were not always straightforward, and clinical information did not always assist in the clinicopathologic correlation. All lesions stained positively for CD34; however, three of six cases also stained positively for S-100. The three cases which were CD34 positive and S-100 negative were likely DFSP, and this was the final diagnosis given. The three cases that were CD34 and S-100 positive did not allow for a straightforward diagnosis. CONCLUSIONS: DFSP may demonstrate areas with features more characteristic of a benign neural lesion, such as a neurofibroma, which can lead to underdiagnosis and subsequent failure to treat. Clinicians and pathologists should recognize this potential diagnostic pitfall and understand that equivocal clinical information, combined with non-specific immunohistochemical staining patterns, can further complicate the dilemma. In these situations, where DFSP is the likely diagnosis but definitive evidence cannot be obtained, full excision of the lesion should be recommended to avoid mistreatment of a potentially malignant lesion.

Adult↗
PubMed2006

D2-40 functions as an effective chondroid marker distinguishing true chondroid tumors from chordoma.

Chordomas and low-grade chondrosarcomas of the central nervous system share many histological features, generating, at times, considerable diagnostic difficulty and, not infrequently, requiring immunohistochemical analysis for appropriate classification. While both chordomas and chondrosarcomas stain positively for S100, only chordomas typically express epithelial antigens like cytokeratins and epithelial membrane antigen. Positive or negative staining with these latter two markers currently represents the only immunohistochemical technique that effectively distinguishes chordomas from chondrosarcomas. A marker that is reliably positive in chondrosarcomas and negative in chordomas has, to date, not been reported. D2-40 is a monoclonal antibody initially developed against M2A, a fetal testis-related antigen now known as podoplanin (aggrus), which has been found to stain a diverse collection of both benign and malignant tissues. In this study, we systematically investigated D2-40 immunoreactivity in a series of 22 chordomas, 20 chondrosarcomas, and 12 enchondromas, in conjunction with cytokeratin and S100 immunostaining. We found that D2-40 robustly and reliably immunostains low-grade chondroid neoplasms (100% of enchondromas and 94% of grades I and II chondrosarcomas), but not chordomas. By contrast, we observed generally strong and diffuse cytokeratin positivity in all cases of chordoma, but not in cases of enchondroma or low-grade chondrosarcoma. Thus, we show that D2-40 behaves as a chondroid marker differentiating true chondroid neoplasms from chordoma. We also demonstrate D2-40 immunoreactivity in two cases of chordoid meningioma and, in doing so, tentatively provide a means to distinguish this tumor from chordoma.

Adult↗
PubMed1997

Morbidity, mortality, and survival after bronchoplastic procedures for lung cancer.

OBJECTIVE: Bronchoplastic procedures represent an effective surgical therapy for benign lesions, tumors of low-grade malignancy and also bronchogenic carcinoma in patients with a limited pulmonary function. We analyzed our experience in order to verify the mortality, morbidity, and long term survival in our patients. METHODS: From 1980 to 1994, 217 patients underwent bronchoplastic procedures. We performed 92 bronchoplasties, 94 bronchial sleeves, and 31 tracheo-bronchial sleeves. Histologic examination revealed 133 epidermoid carcinomas, 28 adenocarcinomas, 11 small cells lung cancers, 5 large cells carcinomas, 2 adenosquamous carcinomas, 29 bronchial carcinoids, 6 adenoidocistic carcinomas, and 3 mucoepidermoid tumors. Regarding nodal status, 99 patients had N0 disease, 64 patients had N1 disease, and 54 patients had N2 disease. Thirty-six patients had preoperative irradiation and 181 patients had no preoperative irradiation. In 63 patients we used a perianastomotic pedicled flap; in 154 we did not use it. We considered all the 217 patients for the analysis of 30-day mortality and morbidity; of the 217 patients we analyzed long-term survival only in 179 because we excluded 38 patients with low grade malignant neoplasm. RESULTS: Twenty-seven patients (12.5%) had postoperative complications. The 30-day mortality was 6.2% (14 patients). Survival at 5 and 10 years for all patients but those with low grade malignant neoplasm was 49 and 38%, respectively. For patients with N0 status 5- and 10-year survival was 72.4 and 59.4%; for patients with N1 status these rates were 35.7 and 26.8%; for patients with N2 status, 5- and 10-year survival was 22 and 14.4%. Postoperative complication rates for patients with or without pedicled flap are not significantly different; however, the rates for patients with or without preoperative irradiation are significantly different. CONCLUSIONS: Bronchoplastic procedures are a safe and effective therapy for selected patients with pulmonary malignancy. Tracheo-bronchial sleeves are associated with high postoperative mortality and complication rates and these procedures should be limited to patients without N2 disease. Preoperative irradiation increases significantly the mortality and morbidity. A multivariate analysis shows that only the nodal status affects long-term survival (P = 0.0002).

Adult↗
PubMedDate not supplied

Intravesical bacillus Calmette-Guérin versus epirubicin in the prophylaxis of recurrent and/or multiple superficial bladder tumours.

A prospective, randomized trial was conducted to evaluate and compare the effects of modified adjuvant intravesical bacillus Calmette-Guérin (BCG) and epirubicin regimens in patients with superficial bladder cancer. One hundred thirty-two individuals with recurrent and/or multiple neoplasms, i.e. at high risk for tumour recurrence and progression, were enrolled. After complete transurethral resection of their tumours, the patients received a 6-week course of BCG instillations or an early 4-week course of epirubicin instillations as their initial therapy. Those with stage Ta and grade 1 neoplasms who remained free of recurrences received maintenance therapy consisting of single quarterly instillations. However, for those with stage T1 cancer of any grade or stage Ta of grade 2 or 3 neoplasms who also remained free of recurrences, the treatment schedules were modified: they received, instead of single maintenance doses, 3 weekly instillations of epirubicin at months 3 and 6 of follow-up, or a 3-week course of BCG at month 6 of follow-up. The recurrence-free rates did not differ significantly between the two study groups (44% for epirubicin versus 55% for BCG), for an identical median follow-up of 43 months. However, in terms of relative risk of recurrences, disease-free intervals and recurrence rate per 100 patient-months, a significant benefit in favour of BCG when compared with epirubicin was demonstrated in patients who had stage T1 or grade 3 neoplasms.

Administration, Intravesical↗
PubMed1980

Estimating rate of growth in bone lesions: observer performance and error.

In an experimental study of reader experience in identifying the variables essential to grading bone neoplasms, reader error is measured against book grade, a human consensus of the presence or absence of key variables. The average accuracy for classifying focal lesions into slow or fast categories is 83.4% for 890 readings as compared with average diagnostic accuracy of 53.7%. Analyses of human error have provided insight into how to improve the grading algorithm without significant loss of its ability to separate lesions into meaningful categories.

Bone Neoplasms↗
PubMed1982

Cytophotometric characterization of the WHO grades of transitional cell neoplasms.

The WHO classification of urothelial bladder tumours is widely used, but does not seem to be entirely satisfactory. The main problem is the unhomogeneous WHO II group, and borderline cases in particular are difficult to evaluate histopathologically. Objective assessment of atypia would allow more reliable correlation between morphology and biological behaviour of the tumours to be made. We describe measurements of atypia in 3 characteristic cases of papillary bladder tumour of each WHO grade I, II, and III using Feulgen-DNA-cytophotometry. The mean optical density and nuclear area is determined in 5 micron thick tissue sections. The optical density and nuclear area for each specimen are plotted in a scatter diagram, and the position and variability of the cluster are evaluated. Cytophotometric characterization resulted in defined groups of WHO-graded tumours, and due to this encouraging result the method will be applied in a more comprehensive study of WHO II carcinomas.

Biopsy↗
PubMed1992

[Histologic grading of malignancy and prognosis in laryngeal neoplasms].

The semi-quantitative grading system for squamous cell carcinoma based on estimation of multiple histologic variables according to Jakobsson is presented. Selected histologic parameters have been also evaluated regarding their importance in predicting patient outcome. Features such as differentiation of the tumor cells, their nuclear polymorphism, number of mitoses and vascular invasion significantly correlated with clinical outcome. The structure of the tumor and cellular host response had no influence on survival. There was statistically significant relationship between the patient outcome and histologic grade of malignancy expressed by total point value. The incidence of cervical node and distant metastases was three times more frequent in the group of poorly differentiated tumors than in others. There was no correlation found between the localization of the tumor and the degree of cancer differentiation, but the supraglottic tumors poorly and moderately differentiated infiltrated towards the glottis more often then highly differentiated.

Adult↗
PubMed1997

Immunophenotypic analysis of non-Hodgkin's lymphoma.

One hundred and three cases of Non-Hodgkin's lymphoma were evaluated immunohistochemically using a panel of monoclonal antibodies which includes leucocyte common antigen (LCA), CD45R (Pan-B marker), L-26 (CD 20-Pan-B marker) and UCHL-1 (Pan-T marker). Of the total 63 cases (61.17%) showed a B-cell phenotype while 40 (38.83%) were of T-cell origin. Most B-cell neoplasms belonged to intermediate (79.36%) or high grade (15.87%) according to the International Working Formulation (WF). Most T-cell lymphomas were of either intermediate (52.5%) or high grade (32.5%) neoplasms. Some T-cell neoplasms presented as specific clinicopathological entities like lymphomatoid granulomatosis (2 cases), mycosis fungoides (1 case) and AILD type NHL (1 case). In 27 cases the immunostaining pattern of two. Pan-B markers i.e., L26 and CD45R was compared. L26 staining was expressed in all 27 cases (100% sensitivity) while CD45R showed positive reaction in 22 cases (82% sensitivity). UCHL-1 is proved to be a sensitive and lineage specific T-cell marker and in 67% cases the staining pattern was moderate (+2) to intense (+3). The mean age for the B-cell lymphomas was 49 years and 36 years in T-cell neoplasm. Male to female ratio in both types of lymphomas was 2:1. The study indicates a high prevalence of T-cell when comparing the data from western countries and lower to those from Japan and Caribbean countries.

Adult↗
PubMed1998

Primary liposarcoma of the skin: a rare neoplasm with unusual high grade features.

Liposarcoma is the most common soft tissue sarcoma in adults. It presents in three main forms: well-differentiated liposarcoma (which includes adipocytic, sclerosing, inflammatory, spindle cell, and dedifferentiated subtypes), myxoid/round cell liposarcoma, and pleomorphic liposarcoma. Anatomic distribution depends largely on histologic subtype, but the deep soft tissue of the extremities and the retroperitoneum are most frequently affected. Whereas it is accepted that liposarcoma rarely occurs in the subcutaneous soft tissue, the dermis seems to represent an exceedingly rare site of occurrence. The clinicopathologic features of a series of seven primary cutaneous liposarcomas (two atypical lipomatous tumors/well-differentiated liposarcomas, one myxoid/round cell liposarcoma, and four pleomorphic liposarcomas) are analyzed here. Clinically, all of the patients were adults (four men, three women) with a median age of 72 years, and four of seven cases arose on the scalp. Local recurrences occurred in two patients, but no distant metastases or disease-related deaths have been observed. Although follow-up is relatively short, it appears that, exceptionally, liposarcoma occurs primarily in the skin and, despite an apparent tendency to show high-grade morphologic features, it seems to exhibit relatively indolent clinical behavior in this location.

Adipose Tissue↗
PubMed2006

Intraductal papillary mucinous neoplasm of the pancreas: cytologic features predict histologic grade.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is an increasingly recognized cystic neoplasm of the pancreas, histologically classified by the degree of epithelial atypia and by the presence or absence of invasion of the cyst wall. To the authors' knowledge, the cytologic features of this neoplasm are poorly characterized, especially with respect to tumor grade. METHODS: Thirty-three endoscopic ultrasound (EUS)-guided pancreatic fine-needle aspiration biopsy (FNAB) samples and 1 pancreatic duct brush specimen from 25 patients with a histologically confirmed IPMN were retrospectively reviewed. Blinded to tumor grade, background mucin, inflammation, necrosis, overall cellularity, the presence of gastrointestinal-contaminating epithelium, architecture of cell clusters, and nuclear and cellular morphology were evaluated. In cases in which special stains for mucin were performed, the diagnostic utility of these stains was assessed. These cytologic features were subsequently correlated with the histologic diagnosis. RESULTS: The 34 cytology samples represented 4 adenomas, 15 IPMN-moderate dysplasias, 7 intraductal carcinomas, and 8 IPMNs with invasive carcinoma. Extracellular mucin was present in 97% of all cases; 53% had thick, viscous, "colloid-like" mucin. Special stains for mucin were positive in 6 of 11 cases (54%), helping to identify thin mucin in only 2 cases. Gastrointestinal contamination did not appear to create diagnostic difficulty due to an apparent dual (dysplastic-nondysplastic) epithelial population, but only 4 adenomas were evaluated in this study. Necrosis distinguished IPMN with carcinoma from IPMN-adenomas and IPMN with moderate dysplasia (P < .00001), and was more often observed with invasion than IPMN-carcinoma in situ (P < .05). Tight epithelial cell clusters with hyperchromatic nuclei and a high nuclear to cytoplasmic ratio was more significant in IPMN of at least moderate dysplasia (P = .03). Pale nuclei with parachromatin clearing was found to be a nuclear feature that was suspicious for at least carcinoma in situ (P < .001). In addition, significant background inflammation (neutrophils and histiocytes) was found to be more characteristic of IPMN with at least carcinoma in situ (P = .002). CONCLUSIONS: The presence of thick, "colloid-like" mucin is noted in half of the IPMN cases, but was not found to be specific to grade. The absence of such mucin does not exclude an IPMN. The presence of tight epithelial cell clusters is consistent with a neoplasm of at least moderate dysplasia, and abundant background inflammation and parachromatin clearing correlated with the presence of at least carcinoma in situ. Necrosis was the only feature found to be strongly suggestive of invasion.

Adenocarcinoma, Mucinous↗
PubMed2001

Low-grade myxoid renal epithelial neoplasms with distal nephron differentiation.

We report 4 distinctive renal epithelial neoplasms that are essentially identical at the morphologic and immunohistochemical levels and do not fit an accepted category in the existing classification of these lesions. The patients were all females, with ages ranging from 32 to 79 years (mean, 50 years). The tumors were well circumscribed and were composed of uniform, predominantly low cuboidal cells with eosinophilic, focally vacuolated cytoplasm. Tumor cells generally formed interconnecting tubules, with smaller areas of cordlike growth and spindling in a bubbly, myxoid stroma. All tumors were confined to the kidney, and all were immunoreactive for high-molecular-weight cytokeratin 34betaE12, cytokeratin 7, epithelial membrane antigen, and cytokeratin cocktail AE1/3. Only 1 tumor was focally immunoreactive for Ulex europaeus agglutinin. Ultrastructural study showed tumor cells forming tubular structures reminiscent of the loop of Henle or distal convoluted tubule. Follow-up in all 4 cases was benign. These distinctive tumors may be confused with aggressive sarcomatoid renal cell carcinomas because of their spindled morphology. The morphologic, immunohistochemical, and ultrastructural features of these lesions indicate differentiation toward distal nephron segments. Similar tumors probably have been reported among low-grade collecting duct carcinomas or tumors "possibly related to the loop of Henle."

Adult↗
PubMedDate not supplied

Fine needle aspiration biopsy of renal cell carcinoma. Cytologic parameters and their concordance with histology and flow cytometric data.

Fine needle aspiration biopsy (FNAB) is increasingly utilized in the initial diagnosis of renal neoplasms. Nuclear grading assessment, however, has not been applied routinely to these neoplasms, and data on its validity are lacking. To determine the reproducibility and clinicopathologic significance of Fuhrman's nuclear grading (FNG) on FNAB specimens, we retrospectively analyzed cytologic and histologic tissues from 49 cases of renal cell carcinomas (RCC). Our data indicate a high concordance between nuclear grading in FNA material and histologic specimens (80-92%). Moreover, interobserver and intraobserver reproducibility was high (89-92% and 86-96%, respectively). The flow cytometric DNA content of 13 specimens (65%) yielded DNA diploidy in five cases (38%) and DNA aneuploid in eight cases (62%). All eight DNA aneuploid neoplasms were FNG 3 (7 cases) and 4 (1 case), while two of the four DNA diploid neoplasms manifested FNG 3. We conclude that cytologic nuclear grading of RCC correlates with corresponding grading of histologic specimens and could be performed reproducibility for clinical use.

Aneuploidy↗
PubMed1983

Role of "third-look" laparotomy in the guidance of ovarian cancer treatment.

Twenty-seven patients with Stage III epithelial ovarian carcinoma received a "third-look" celiotomy. Each patient received a minimum of an additional 12 courses of chemotherapy after persistent tumor had been documented at a "second-look" procedure. Twelve of the twenty-seven patients have died. No tumor-associated deaths occurred in patients with grade 1 neoplasms. Of the patients with microscopic disease at the second-look procedure who came to third-look laparotomy, none had died secondary to tumor growth. The survival time of patients with microscopic disease at third-look is greater than that of patients with macroscopic disease (P = 0.0009). In patients who had effective tumor reductive surgery performed at second-look, the third-look findings were highly predictive as to survival. Long-term chemotherapy had a significant incidence of related mortality. Four of the twenty-seven patients died as a direct result of the chemotherapeutic toxicity. The patients receiving melphalan for at least 24 courses appeared to be at greatest risk, with 23% dying from either aplastic bone marrow changes or leukemia. The morbidity associated with third-look laparotomy was not excessive. Many factors need careful review prior to planning a third-look laparotomy. This retrospective study demonstrates that patients with either a grade 1 neoplasm or only microscopic disease at the second-look procedure do well regardless of the third-look findings.

Antineoplastic Agents↗
PubMed1997

Chromosomal and DNA ploidy characterization of salivary gland neoplasms by combined FISH and flow cytometry.

Concurrent DNA ploidy by flow cytometry and interphase FISH analysis of chromosomes 6 through 12, 17, 18, X, and Y were prospectively performed on 22 salivary gland neoplasms (four benign and 18 malignant) to investigate the diagnostic and biological implications of their alterations in these neoplasms. Our results show that benign neoplasms lack DNA aneuploidy and numerical chromosomal abnormalities. Low-grade malignant neoplasms, except for two lesions, manifested small chromosomal gains and losses and were generally DNA diploid or near-diploid aneuploid, whereas all high-grade tumors showed marked polysomy and were DNA aneuploid. Marked intratumoral and intertumoral chromosomal heterogeneity also were noted in and between individual tumors. Although polysomy was the main finding in DNA aneuploid lesions, monosomy was more noted in DNA diploid neoplasms and was restricted to chromosomes 8, 11, and 17. Significant correlation between the DNA index, chromosomal aneusomy, histological grade, and tumor stage was noted. Our study indicates that (1) benign salivary gland neoplasms lack gross DNA content and numerical chromosomal abnormalities, (2) clonal chromosomal alterations are manifested in most DNA diploid and all DNA aneuploid malignant tumors, (3) chromosomal gain is the most common alteration; chromosomal loss is less frequent and restricted to certain chromosomes, and (4) DNA aneuploidy and chromosomal aneusomy characterize tumors with aggressive features.

Adult↗
PubMed1990

Prognostic factors in patients with primary transitional cell carcinoma of the upper urinary tract.

A total of 50 patients with primary transitional cell carcinoma of the upper urinary tract underwent deoxyribonucleic acid ploidy characterization by flow cytometric analysis of paraffin embedded specimens. The primary tumor was diploid in 29 patients (58%) and aneuploid in 21 (42%). Aneuploidy was identified more frequently in grade 3 than in grades 1 and 2 neoplasms (p = 0.001). Additionally, grade 3 neoplasms occurred more often with invasive (stages T2 to T3) compared to superficial (stages TA, TIS and T1) tumors (p = 0.002). However, deoxyribonucleic acid ploidy was not significantly associated with tumor stage. Among the 49 patients treated by a definitive operation the median survival free of disease and median over-all survival were 33.7 and more than 120 months, respectively. Variables examined included deoxyribonucleic acid ploidy, tumor grade, tumor stage, primary tumor site and type of operation. In the univariate analysis deoxyribonucleic acid ploidy was the only significant predictor of survival free of disease (p = 0.04). Aneuploid tumors had a median survival free of disease of 19 versus 59 months for diploid tumors. However, in the multivariate analysis of factors affecting survival free of disease, the type of operation performed was the only significant variable. Patients undergoing nephroureterectomy with en bloc bladder cuff excision had a favorable survival free of disease (p = 0.04). Tumor stage was the only significant factor associated with over-all survival in univariate and multivariate analyses (p = 0.02 and 0.005, respectively). Patients with superficial tumors had a median survival of more than 120 versus 72 months for patients with invasive tumors. The data suggest that deoxyribonucleic acid ploidy may be a useful parameter to identify risk groups and plan the management of patients with primary transitional cell carcinoma of the upper urinary tract.

Carcinoma, Transitional Cell↗