Distribution of lymphomas in Poland according to World Health Organization classification: analysis of 11718 cases from National Histopathological Lymphoma Register project - the Polish Lymphoma Research Group study.

Most national lymphoma registers rely on broad classifications which include Hodgkin and non-Hodgkin lymphomas (NHL), multiple myeloma and leukaemia. In Poland the National Histopathological Lymphoma Register project (NHLR) was implemented by hematopathologists in accordance with the 2008 WHO classification into haematopoietic and lymphoid tissues. We present the NHLR data and compare lymphoma distribution in Poland, Europe, as well as in North Central and South America. Records of 11718 patients diagnosed in 24 pathology departments from all over the country were retrieved and reclassified into indolent and aggressive lymphomas according to the 2008 revised WHO classification system. DLBCL (32.9%; 2587), CLL/SLL (31.84%; 2504) and MCL (9.04%; 711) were the three most frequent NHL. The ratio of indolent to aggressive NHL was 1.72; 63.25% (4809) to 36.25% (2794) of cases respectively. Multiple myeloma was less frequent as compared to the data from population-based national cancer register (13.32% vs. 28.94%). Major differences between NHLR and European and American data on NHL subtypes concered: higher incidence of aggressive B-cell lymphomas including DLBCL, lower FL and MALT incidence rate. The percentage of unclassified lymphomas in the study was minimal due to participation of hematopathologists.

Primary angiosarcoma of the colon.

Angiosarcoma of gastrointestinal tract is extremely rare. Since 1948, we can find only six reported cases of primary colonic angiosarcoma. The review of the six reported cases and a report on the first colonic angiosarcoma to be seen in an adolescent male are presented. The treatment of the colon angiosarcoma is wide surgical excision. The prognosis is poor. Our case is the second one to be alive, more than 18 months after surgery, with no evidence of recurrent disease.

A ratio of apoptosis to mitosis, proliferation pattern and prediction of radiotherapy response in cervical carcinoma.

The prognostic significance of apoptotic (AI) and mitotic (MI) indices, and the ratio of these parameters (AI/MI), MIB-1 labeling index (MIB-1LI) and proliferation pattern was studied in 130 (FIGO stage IB-IIIB) squamous cervical cancer patients before radiotherapy. Also the influence of the patients age and tumors pathological features (stage, grade, degree of keratinization) and DNA ploidy on the biological parameters were analysed. AI and MI were assessed on histological sections stained with hematoxylin and eosin, and the MIB-1LI on specimens stained with rabbit anti-human Ki-67 antibody (DAKO Ltd). Sections stained with MIB-1 antibody were used for assessment of the tumor proliferation pattern. The median age of the patients was 55 years (29-80). The median values for MIB-1LI, AI, MI, AI/MI, were: 52.3%, 1.1%, 1.5, and 0.9, respectively. In the univariate analysis median values for cut-off points were used for MIB-1LI, and AI, however, for other parameters significant cut-off points have been chosen. For MI it was 2.6 and for the AI/MI ratio 0.7. The median time of follow-up was 29 months, with a range of 2-145 months. The univariate analysis showed that tumor stage (p=0.7009), grade (p=0.6660) and AI (p=0.9378) had negligible influence on patients survival. However, MI >2.6 (p=0.0442), AI/MI

Comparative analysis of DNA content estimated by flow and image cytometry in breast tumor samples.

The DNA ploidy status of 186 fresh primary breast tumors was analyzed in a comparative study of flow cytometric (FCM) and image (IA) analyses. Tumor size, histology and nodal status were also taken into account. The same piece of fresh tissue was used for touch imprints (IA) and for DNA analysis by FCM. Both methods provided concordant DI values in 158 (85%) tumors (r = 0.7490). The tumor grade and lymph node status significantly correlate with ploidy estimated by FCM and IA. We conclude that FCM and IA provide comparable results of DNA content although occasional discrepancies occur. IA seems to be a more sensitive method especially for diploid cases detected by FCM.

[Tumors of borderline malignancy or atypical proliferative tumors of the ovary?]. / Guzy o granicznej zlosci czy atypowe proliferacyjne guzy jajnika?

Nearly sixty years have passed since Taylor first published the concept of ovarian epithelial semimalignant tumors. After confirmation of this suggestion by FIGO and WHO these tumors became the subject of analyses which helped to separate unfavourable prognostic cases in this group. We would like to present a description of basic and latest papers on borderline ovarian tumors.

Prognostic and predictive evaluation of DNA content, S-phase fraction and immunophenotyping in non-Hodgkin's lymphomas in adults. A prospective study.

In non-Hodgkin's lymphoma (NHL) patients, prognostic significance of S-phase fraction (SPF) is well known, however the significance of DNA ploidy status and antigen expressions is still unclear. The purpose of the present study is to evaluate the prognostic and predictive impact of SPF, immunophenotype and DNA ploidy in prospectively analysed NHL patients. The study was performed on lymph node biopsies of 117 nodal NHL patients. The median follow-up of patients was 25 months (range 1-64 months). All histologically verified lesions were considered according to the Working Formulation and Kiel classification. SPF, immunophenotype and ploidy were determined by flow cytometry. The rate of 2-year overall survival was 56%. SPF and DNA ploidy status were found to be independent prognostic factors in low and high grade lymphomas, respectively. Patients with near-tetraploid lymphomas were characterised by unfavourable clinical outcome, whereas hypertetraploidy was a favourable prognostic indicator. Among B-cell lymphomas CD5 expression seems to be of prognostic significance.

Prognostic factors in retroperitoneal sarcomas: ploidy of DNA as a predictor of clinical outcome.

BACKGROUND AND OBJECTIVES: Radical surgery is the best mode of treatment of retroperitoneal sarcomas (RS); however, common recurrences are unpredictable. METHODS: For the better understanding of outcomes and possibilities of treatment retrospective analysis of different factors, including DNA content, was performed based on 70 patients. RESULTS: Leiomyosarcoma and liposarcoma were most common histologic types of classified sarcomas. Different kinds of resection were successfully performed in 51 patients (73%) and 35 of their available DNA specimens were analyzed. The actuarial 5- and 10-year survival rates in the resection group were 53% and 40%, respectively, with the median survival of 57 months. Patients with diploid resected tumors had a better 10-year survival rate (58%), than those patients with aneuploid tumors (25%,)--P<0.005. Those patients with low-grade sarcomas had a significantly longer survival than those with high-grade sarcomas (10-year survival rate: 44% compared to 29%). In the univariate analysis, adjuvant therapy, type of histology, type of surgery, location of tumor, and S-phase fraction had no influence on survival. In the multivariate analysis (Cox), only ploidy was an independent prognostic variable. Relative risk of death was over three times higher for aneuploid than for diploid tumors. CONCLUSION: Tumor ploidy should be analyzed in every case of retroperitoneal sarcoma for better assessment of prognosis and possible indication for adjuvant therapy.

Prognostic evaluation of cutaneous malignant melanoma: a clinicopathologic and immunohistochemical study.

BACKGROUND AND OBJECTIVES: Depth of invasion and stage of the disease are established prognostic indicators in cutaneous malignant melanoma. The role of other parameters is still an open problem. METHODS: In 93 consecutive patients with cutaneous malignant melanoma, the level of invasion, tumor thickness, ulceration, vascular invasion, lymphoplasmocytic infiltrates, and mitotic index were evaluated by histology. Expression of Ki-67 and PCNA proliferative antigens together with vimentin, S100, and HMB 45 proteins were assessed by immunohistochemistry. RESULTS AND CONCLUSIONS: Disease-free and overall survival were correlated with tumor stage, tumor thickness, level of invasion, macroscopic pattern, ulceration, vascular invasion, expression of HMB 45, PCNA, and Ki-67/MIB1. Stage, HMB 45, and PCNA were independent prognostic factors for disease-free survival, whereas tumor stage, tumor thickness, and expression of both proliferative antigens influenced overall survival independently. The variables studied demonstrated reciprocal correlation; therefore, analysis of many prognostic parameters in malignant melanoma could be recommended.

Evaluation of DNA content and proliferative activity in prediction of short-term relapses in mammary carcinoma: a prospective study.

DNA content according to six various ploidy classes was analysed by flow cytometry on fresh tumor tissue in 701 unselected, consecutive breast cancers. Age, menopausal status, tumor size, histology and in particular nodal status were also taken into consideration. Diploid and nondiploid mammary carcinomas differed significantly in values of proliferative indicators. In node positive patients nondiploid tumors were more frequent. In node negative and node positive breast cancer patients tumor grade strongly influenced disease free survival and in the last group hypertriploidy (1.6 < DI < or = 1.8) was also an independent prognostic factor. The combination of tumor grade and hypertriploidy permitted differentiation of three groups of node positive patients, differing in the risk of relapses.

Prognostic assessment of histologic parameters in breast carcinomas: a prospective study.

A group of 350 unselected breast cancer patients, treated at the Center of Oncology in Cracow, Poland, between January 1992 and December 1994, was analyzed. The following reciprocally interrelated histologic characteristics were evaluated: 1) histologic tumor type (considered in 3 categories of aggressivity), 2) tumor grade (according to Scarf-Bloom-Richardson), 3) constituent of in-situ carcinoma in invasive cancers and characterization of breast lobuli, 4) tumor growth pattern (microfocal, macrofocal or mixed), 5) invasion of nerves, 6) vascular invasion by cancer cells in tumor surroundings, 7) extensiveness of tumor necrosis, 8) involvement of the breast distant from the tumor mass by cancer cells, 9) status of axillary lymph nodes, 10) invasion of metastatic lymph node surroundings. Metastases in axillary lymph nodes were independently influenced by vascular invasion in tumor surroundings and tumor diameter. The disease-free survival was independently influenced by tumor diameter, necrosis and stage of the disease (pTNM), whereas total survival related to tumor diameter, nodal status, microfocal pattern of tumor growth, vascular invasion and involvement of breast by cancer distant from the tumor mass was independently influenced only by tumor stage (pTNM).

Assessment of proliferative activity, DNA values and some clinicopathologic parameters in mesenchymal tumors. Immunohistochemical and flow cytometric study.

Clinicopathologic parameters of 70 consecutive mesenchymal tumors from 63 patients were evaluated. In all these cases, the DNA content was analyzed by flow cytometry, and the expression of proliferative antigen MIB1 and p53 protein was assessed by immunohistochemistry. Our study verified the prognostic usefulness of proliferative indicators, above all MIB1-index, which strongly correlated with tumor grade and independently influenced overall survival.

Rhabdomyosarcoma. Morphologic, immunohistochemical, and DNA study.

In this study 80 cases of predominantly adult rhabdomyosarcoma are presented as follows: 20 cases of the embryonal type, 32 cases of the alveolar and 8 cases of the pleomorphic type. Additional histologic classification was performed in each type. In myotube stage the histologic picture of fetal muscles cannot be compared to the alveolar type of rhabdomyosarcoma. Desmin and sarcomeric actin are observed in 47.7% of all cases, and myoglobin and myosin in only 23.1%. The reactions were diffuse, disperse, or focal. Electron microscopic study subdivides desmin positive tumors into three groups of differentiation. DNA analysis shows that most desmin positive cells are diploid in comparison to all the tumor cells that are hyperdiploid and tetraploid.

[Prognostic factors in gastric lymphoma]. / Czynniki rokownicze w chloniaku zoladka.

Stomach is the most common site of extranodal lymphoma, but lymphoma's biology differs from other types of gastric cancer. From 1982 to 1994, 80 cases of primary gastric lymphoma were treated in Cancer Center in Kraków. In order to assess the best mode of treatment the retrospective analysis of disease related parameters was performed. Sixty four patients were primary treated with surgery, and 11 with radiotherapy. After surgery 21 patients received adjuvant chemo or radiotherapy. Radical resection of tumor was done in 37 cases, in next 25 only palliative surgery was possible. There was 28 cases of lymph node metastases in resected specimens. At 5 years, the overall survival was 64.4% with the median survival of 43 months. Patients primarily treated with surgery had better 5--years survival rates compared with others (72.1% and 36.8%, respectively-p < 0.05). The chance of survival was related with the tumor grading and 5 years survived 86.5% patients with well differentiated lymphomas, and 52.6% patients with nondifferentiated tumors. There was no influence on survivals other variables as duration of symptoms, type of surgery, histological margins or adjuvant therapy. The Cox multivariate analysis showed the grading, type of first treatment and lymph node status as the only three significant factors related to survivals. The relative risk of death for nondifferentiated lymphomas was 7 times higher, than for well differentiated tumors. The primary surgery (even nonradical) of gastric lymphoma is the best mode of treatment and the grading is the most important prognostic factor influencing the survivals.

Flow cytometric DNA-analysis of cells obtained with fine needle aspiration biopsy of the breast.

In 221 consecutive, unselected palpable breast lesions, evaluated by aspiration biopsy, flow cytometric DNA analysis was performed on cell material remaining in needle and syringe after smears had been prepared. DNA histograms were obtained in 186 cases, whereas in 44 samples the cell number was too low for detailed estimation of cell kinetics. Aneuploidy was observed in 71 of 90 samples where cancer cells were detected by cytology, in four of 20 samples where breast cancer could only be suspected and in 12 of those 76 where no cancer cells occurred in cytologic specimens. The average S-phase and S+G2M values were higher in aneuploid than in diploid cell samples. In the group of 40 cases (34 breast cancers, 6 benign lesions) comparative analysis of DNA histograms obtained on aspirates and tissue fragments revealed a concordance in 88.9%. Modified radical mastectomy was performed in 41 breast cancers and in 33 cases ductal infiltrating carcinomas were recognized by histology and scored according to Bloom-Richardson score. Cell features assessed by cytology in these cases did not correlate with histology. In most cases, however, nuclear polymorphism and numerous naked nuclei were present in cytologic specimens. These alterations, characterized as score 3, reflect values of DNA-index in compartment of 1.4-1.8.

Reverse transcriptase-polymerase chain reaction amplification of MDR1 gene expression in adult soft tissue sarcomas.

Expression of the multidrug resistance gene MDR1 is reported to be an important determinant of the response to chemotherapy and survival in some cancers. We compared three methods for determining the intrinsic MDR1 expression in soft tissue sarcomas. We studied MDR1 gene expression in 39 samples from 33 cases of soft tissue sarcomas comprising 11 liposarcomas, nine malignant fibrous histiocytomas, six leiomyosarcomas, four malignant schwannomas, three fibrosarcomas, three synovial sarcomas, and three epithelioid sarcomas, and seven cases of benign soft tissue tumors in adult patients. To detect MDR1 mRNA, reverse transcriptase-polymerase chain reaction (RT-PCR) was performed in all samples. Furthermore, RNA dot-blot analysis with digoxigenin-labeled RNA probe and immunohistochemistry with JSB-1 and C-219 antibodies for P-glycoprotein were employed in 34 and 37 samples in soft tissue sarcomas, respectively. We compared these three detection techniques. Of the 39 specimens, 18 (46%) showed MDR1 PCR products. Liposarcomas (six of 11), malignant fibrous histiocytomas (six of nine), leiomyosarcomas (four of six), fibrosarcomas (two of three) revealed high or intermediate MDR1 expression at high frequency. No MDR1 expression was detectable in malignant schwannomas, synovial sarcomas, or epithelioid sarcomas. Of seven benign soft tissue tumors, one ganglioneuroma and one lipomatosis showed low levels of MDR1 expression. By RNA dot-blot analysis, MDR1 transcripts were detectable in 12 of 34 specimens (35%). Four samples were negative by dot blot despite positivity with RT-PCR. Concordance between MDR1 expression by RNA level with RT-PCR and dot blot and at the protein level with immunohistochemistry using C-219 was found in 16 (47%) of the 34 comparable specimens. Eight samples showed positive immunoreactivity for C-219 despite negative results in RT-PCR and dot-blot analysis. The intrinsic MDR1 expression in soft tissue sarcoma seemed to depend on certain tumor types, such as liposarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and fibrosarcoma. For the evaluation of MDR1 expression, RT-PCR is useful because of its relative simplicity and sensitivity. However, the clinical significance of such low levels of MDR1 expression detected only by RT-PCR must be discussed within systematically treated patient groups.

Expression of multidrug-resistance-associated protein gene in human soft-tissue sarcomas.

We examined the mRNA expression of the multidrug- resistance-associated protein gene (MRP) in soft-tissue sarcomas and compared it with the expression of the multidrug resistance gene (MDR1), using the reverse transcriptase/polymerase chain reaction. We investigate 39 samples from 33 cases of soft-tissue sarcomas (11 liposarcomas, 9 malignant fibrous histiocytomas, 6 leiomyosarcomas, 4 malignant schwannomas, 3 fibrosarcomas, 3 synovial sarcomas, and 3 epithelioid sarcomas) and 7 benign soft-tissue tumors. All samples were obtained prior to chemotherapy. An expression of MRP mRNA was noted in 56% of soft-tissue sarcoma specimens. The co-expression of MRP and MDR1 was recognized in 15 samples (38%) (5/11 liposarcomas, 5/9 malignant fibrous histiocytomas, 3/6 leiomyosarcomas, 2/3 fibrosarcomas) and significantly correlated with histological grade (P=0.0165). A positive and significant correlation was found between MRP and MDR1 expression in soft-tissue sarcomas(P=0.0013). In benign soft-tissue tumors, 1 chemodectoma and 1 neurothekeoma showed low MRP expression; however, no case showed co-expression of MRP and MDR1.

Relationship of histology, DNA-values and proliferative activity in unselected breast cancer patients (a preliminary study).

Based upon a group of 108 consecutive mammary carcinomas a comparative analysis of morphological parameters, DNA-ploidy and indicators of proliferation activity was made. A correlation between Bloom-Richardson scale, mitotic index, PCNA-labeling index and DNA-index was shown. The ploidy of mammary carcinomas was significantly related to the values of proliferative fraction, as well as to PCNA-labeling index. Among patients with axillary metastases the tumor size and the value of PCNA-labeling index were significantly higher than those in patients with negative lymph nodes.

Flow cytometric evaluation of Ki67 proliferative antigen in primary breast cancer.

In the group of forty five primary mammary carcinomas Ki67 reactivity was evaluated with flow cytometry and immunohistochemistry. The expression of proliferative antigen, evaluated with both methods did not correlate with other indicators of proliferative activity. This result is probably associated with the physicochemical properties of breast cancer cells.

Flow cytometric analysis of high grade B-cell non-Hodgkin's lymphoma: correlation between histology, immunophenotyping and cell cycle analysis.

The immunophenotype and the DNA parameters of 21 high grade B-cell non-Hodgkin's lymphomas considered in terms of the Kiel Classification were studied by flow cytometry. The centroblastic and immunoblastic lymphomas differed in the expression of lymphocyte markers, however no characteristic immunophenotype for each lymphoma type could be distinguished. Assessment of the FSC/SSC dot plots with histology enables to distinguish subpopulations of the lymphoma cells. The immunoblastic and centroblastic lymphomas were characterized by high proliferative activity although no significant differences in S-phase values between both groups could be found.