[Blast-like tumor tissue in cervical lymph node with expression of placental alkaline phosphatase]. / Blastäres Tumorgewebe in Halslymphknoten mit Expression plazentaalkalischer Phosphatase.

We report a case of ALK1-positive anaplastic large cell lymphoma with expression of placental alkaline phosphatase (PLAP) in many tumor cells. Initially, due to the positivity of tumor cells for CD30 and PLAP, lymph node metastasis of a germ cell neoplasm was discussed. Anaplastic large cell lymphomas of T­cell lineage form a group of rare non-Hodgkin lymphomas with heterogeneous morphological and immunohistochemical appearance. They may imitate other neoplasms, such as large cell B­cell lymphomas, metastasis of a carcinoma, melanoma, embryonal carcinoma or seminoma, rhabdomyosarcoma and inflammatory myofibroblastic tumor. Only an extended immunohistochemistry panel leads to an accurate diagnosis.

[Retroperitoneal bronchogenic cyst]. / Retroperitoneale bronchogene Zyste.

We describe a 35-year-old female patient who underwent surgery because of a coincidentally occurring cryptic tumour near the left adrenal gland and a right renal carcinoma (pT1, N0, G2, R0). The left-sided tumour was intraoperatively identified as a cystic structure filled with secretion. Histopathological analysis provided the diagnosis of a bronchogenic cyst.

PCR-based assays for the detection of monoclonality in non-Hodgkin's lymphoma: application to formalin-fixed, paraffin-embedded tissue and decalcified bone marrow samples.

In crucial cases the diagnosis of non-Hodgkin's lymphoma (NHL) still represents a challenge to the pathologist since morphological criteria do not always help to distinguish between reactive and malignant lymphoproliferations. Clonality assays are a useful supplement since monoclonal cell proliferation is strong evidence for malignancy. The polymerase chain reaction (PCR) can be utilized to establish the clonal origin of B- or T-cell lymphocyte populations by amplification of rearranged immunoglobulin and T-cell receptor (TCR) genes. In the present study DNA was isolated from a variety of neoplastic and nonneoplastic formalin-fixed, paraffin-embedded lymph nodes (n = 62), cutaneous tissue (n = 9), samples of miscellaneous origin (n = 11), and reported here for the first time, decalcified bone marrow samples (n = 35). These samples were submitted to PCR-based assays directed against the immunoglobulin heavy-chain (IgH), immunoglobulin kappa light-chain (IgL kappa), and TCR gamma chain genes. The impact of various decalcifying agents on the ability to amplify DNA was investigated by PCR-based amplification of a single copy gene. Buffered and nonbuffered EDTA was found not to impede amplification of DNA fragments up to 300 bp in length. In lymph node and cutaneous specimens monoclonality was detected in 83% of B-NHL cases using a seminested PCR approach for the amplification of IgH, whereas the same approach gave rise to monoclonal bands in 80% of bone marrow samples. The subsequent amplification of IgL kappa helped to raise the sensitivity of detection to 94%. Monoclonality was detected in seven of nine T-cell NHLs by amplification of TCR gamma.(ABSTRACT TRUNCATED AT 250 WORDS)

Differentiation of focal nodular hyperplasia and hepatocellular adenoma by contrast-enhanced ultrasound.

Non-invasive differentiation of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) is difficult. The aim of this study was to assess the accuracy of contrast-enhanced phase inversion ultrasound to differentiate between histologically proven FNH and HCA, analysing the arterial and (early) portal venous phase. 32 patients with histological proven FNH (n=24) or HCA (n=8) have been included in this prospective study. Examination technique: Siemens Elegra, phase inversion harmonic imaging (PIHI) with low mechanical index (MI)<0.2-0.3 using SonoVue (BR 1). The contrast enhancing tumour characteristics were evaluated during the hepatic arterial (starting 8-22 s) and early portal venous phase (starting 12-30 s). The image analysis was performed by three examiners. In 23 of 24 patients with FNH the contrast pattern revealed pronounced arterial and (early) portal venous enhancement. Homogeneous enhancement was detected during the hepatic arterial phase in all eight patients with HCA. In contrast to patients with FNH, no enhancement was seen during the portal venous phase. In conclusion, contrast-enhanced phase inversion ultrasound demonstrated pronounced arterial and portal venous enhancement in patients with focal nodular hyperplasia. In contrast, after homogeneous enhancement during hepatic arterial phase, no enhancement during hepatic portal venous phase was detected in patients with hepatocellular adenoma. Therefore, this technique might improve the functional characterization of benign hypervascular focal liver lesions.

Preclinical activity of taxotere (RP 56976, NSC 628503) against freshly explanted clonogenic human tumour cells: comparison with taxol and conventional antineoplastic agents.

Taxotere (TER) and taxol (TA) are new antitumour agents currently undergoing clinical evaluation. We studied the antineoplastic effects of these agents (final concentrations: 4.0, 0.4, 0.04 mumol/l) on the in vitro proliferation of clonogenic cells from freshly explanted human tumours using a capillary soft agar cloning system. We also compared the activity of these new compounds to conventional antineoplastic agents (bleomycin, cisplatin, dacarbazine, doxorubicin, etoposide, 5-fluorouracil, vinblastine, interferon-alpha 2). Using a 21-28-day continuous drug exposure, 54/81 specimens (67%) were evaluable for comparisons, and using a 1-h drug exposure followed by 21-28 days incubation, 50/80 specimens (63%) were similarly evaluable. With both schedules, TA and TER showed concentration-related antitumour activity. At 0.4 mumol/l, median colony survival was 0.61 x control (range 0.09-0.96) for TA and 0.51 x control (0.15-0.81) for TER in the 1-h incubation (P = 0.0002). Median colony formation was also reduced significantly more by TER as compared to TA in the long-term incubation schedule. Statistical analysis indicated that TER but not TA was significantly more active than cisplatin (P = 0.02), doxorubicin (P = 0.01), 5-fluorouracil (P = 0.01) and interferon-alpha 2 (P = 0.01). We conclude that TER and TA are more active against in vitro tumour colony formation from freshly explanted human tumours. TER appears to be slightly more active than taxol and promises to be active against tumours resistant to conventional antineoplastics.

Semantic networks of English.

Principles of lexical semantics developed in the course of building an on-line lexical database are discussed. The approach is relational rather than componential. The fundamental semantic relation is synonymy, which is required in order to define the lexicalized concepts that words can be used to express. Other semantic relations between these concepts are then described. No single set of semantic relations or organizational structure is adequate for the entire lexicon: nouns, adjectives, and verbs each have their own semantic relations and their own organization determined by the role they must play in the construction of linguistic messages.

Monoclonal antibodies Ki-B3 and Leu-M1 discriminate giant cells of infectious mononucleosis and of Hodgkin's disease.

In infectious mononucleosis (IM), the involved lymphatic tissue may contain large blasts which are generally referred to as Hodgkin cell-like cells when mononuclear and as Sternberg-Reed cell-like cells when multinuclear. The resemblance of these reactive cells to true Hodgkin and Sternberg-Reed cells constitutes a major differential diagnostic problem. In this paper, we report a study of 20 cases of Hodgkin's disease (HD); five of nodular sclerosis and 15 of mixed cellularity type) and of 20 clinically and serologically confirmed cases of IM with the aim of developing immunohistologic criteria for their reliable differentiation. Routinely processed paraffin sections were subjected to the immunoperoxidase reaction using the monoclonal antibodies Leu-M1 (anti-CD15) and Ki-B3. The subcellular distribution of the immunoreactivity to Ki-B3 was controlled at the electron microscopic level. In all cases of HD, many Hodgkin and Sternberg-Reed cells were found to be positive for Leu-M1, whereas the same cells were invariably negative for Ki-B3. By contrast, cells similar to Hodgkin and Sternberg-Reed cells in IM were consistently negative for Leu-M1. The majority of these cells reacted positively for Ki-B3. The results imply that immunohistochemical application of these two antibodies facilitates a clear-cut discrimination of true Hodgkin and Sternberg-Reed cells from similar cells of IM.

Nodular paragranuloma can transform into high-grade malignant lymphoma of B type.

A follow-up study of 537 cases of Hodgkin's disease, lymphocyte predominance type, nodular--designated as nodular paragranuloma (NP)--found simultaneous presence of (n = 11) or subsequent transition into (n = 3) a large cell lymphoma (LCL) in 14 cases. Morphologically, the LCLs were classified in ten cases as centroblastic lymphoma (malignant lymphoma, diffuse, large cell, non-cleaved cell), in three cases as immunoblastic lymphoma (malignant lymphoma, large cell, immunoblastic), and in one case as large cell anaplastic lymphoma. Eleven of the 14 LCLs were studied immunohistologically. Five cases showed a monotypic immunoglobulin (Ig) pattern, seven were positive to the monoclonal B-cell marker Ki-B3, and three showed both monotypic Ig and Ki-B3 positivity. With anti-Ig and Ki-B3, nine of the 11 LCLs could be classified as B-cell non-Hodgkin's lymphoma. Only one case of LCL exhibited the typical phenotype of Hodgkin cells, ie, positivity to anti-CD15 (3C4) and anti-CD30 (Ber-H2). A retrospective follow-up study of these secondary LCLs of B type revealed a longer survival time than that of primary B-type LCLs and other secondary LCLs. These findings indicate that B-type LCL is the most common outcome when NP progresses into a lesion of higher malignancy and provide further evidence of a close relationship of NP to the B-cell system. They also suggest that it would be clinically relevant to distinguish between cases of B-type LCLs secondary to NP and cases of LCLs without association with NP. This implies that signs of a preexisting NP should be looked for when a B-type LCL is diagnosed.

Molecular evidence of bone marrow involvement in advanced case ot Tgammadelta lymphoma with secondary myelofibrosis.

We describe the case of a middle-aged man with long indolent course of generalized Tgammadelta lymphoma. The onset of secondary myelofibrosis made cytological monitoring of the bone marrow infiltrates impossible. As during progression of the disease splenectomy revealed typical histological features of a high-grade hepatosplenic Tgammadelta lymphoma, the low-grade bone infiltrate was considered a secondary lymphoma. The use of the polymerase chain reaction helped to detect a constant and identical monoclonal rearrangement pattern of the T-cell receptor gamma-chain gene in both bone marrow and splenic T-cell infiltrates. The notion of a secondary spread of malignant T-cells to the bone marrow was thereby confirmed despite striking cytological differences between bone marrow and splenic infiltrates. This is the first report of a diagnostic DNA-based molecular approach using fixed decalcified bone marrow. This method may provide a major tool when dealing with myelofibrosis, which normally hampers sampling of cytological specimens.

Correlation of content of B cells and Leu7-positive cells with subtype and stage in lymphocyte predominance type Hodgkin's disease.

Cases of lymphocyte predominance type Hodgkin's disease were investigated using immunohistochemical methods and compared for morphological subtype and clinical stage. Cases of nodular paragranuloma showed a high, diffuse paragranuloma a moderate, and the mixed type a low, content of B cells. There was no significant correlation between B cell content and clinical stage. The number of Leu7+ cells was significantly increased in stage I of nodular paragranuloma. Hodgkin cells did not react with the CD15 antibody in most cases of paragranuloma but showed reactivity in the mixed type.

Progressive transformation of germinal centers with and without association to Hodgkin's disease.

Progressively transformed germinal centers occurred in about 3.5% of cases of chronic nonspecific lymphadenitis. They are larger than germinal centers and are composed of follicular mantle lymphocytes, small clusters of proliferating mainly medium-sized B- and T-cells, as well as an extensive network of follicular dendritic cells. Sixty-six patients with lymph node enlargement containing progressively transformed germinal centers and staging and sequential biopsies of 213 patients with Hodgkin's disease (mixed and nodular sclerosis type) were investigated with special reference to the relationship of this lesion to Hodgkin's disease. In most cases, progressively transformed germinal centers developed without any obvious signs of illness and seemed to have no association with Hodgkin's disease. The patients could be differentiated into two groups. The larger group, Group 1 (n = 55 of 66) consisted of patients showing progressively transformed germinal centers without association to Hodgkin's disease. The smaller group, Group 2 (n = 11 of 66) showed progressively transformed germinal centers obviously with association to nodular paragranuloma (Hodgkin's disease lymphocytic predominance type). Progressively transformed germinal centers preceding (n = 3), simultaneously (n = 4), and after development of nodular paragranuloma (n = 4) were found. With regard to subtypes of Hodgkin's disease other than paragranuloma, progressively transformed germinal centers also could be found in sequential biopsies of Hodgkin's disease of mixed and nodular sclerosis type. In one case, progressively transformed germinal centers preceded, in another case they occurred simultaneously in mixed type of Hodgkin's disease, and in two cases of nodular sclerosis type progressively transformed germinal centers developed after the onset of Hodgkin's disease. These findings suggest that progressively transformed germinal centers may be a result of different processes that may be occasionally related not only to nodular paragranuloma, but also in rare cases to nodular sclerosis and mixed type of Hodgkin's disease.

Expression of the proliferating cell nuclear antigen in the different types of Hodgkin's disease.

Thirty-eight cases of Hodgkin's disease (HD, lymphocyte-predominant, n = 10; nodular sclerosis, n = 10; mixed cellularity, n = 10; lymphocyte depletion, n = 8) were investigated with the antibody PC10 directed against the proliferating cell nuclear antigen (PCNA) with B- and T-cell markers using a double-staining technique in paraffin-embedded material. It could be shown that nearly all (95-97%) Hodgkin's and Reed-Sternberg (HRS) cells and their variants were PCNA-positive regardless of the type of HD. There was only a low number of PCNA-positive lymphocytes (2.8-3.4%) in all types mostly consisting of MT1-positive T lymphocytes. In contrast to the other types, lymphocyte-predominant type showed a relatively high percentage (5%) of Leu-7-positive lymphocytes. The high percentage of PCNA-positive HRS cells correlates with their malignant nature, and might be another example of dysregulated expression of PCNA.

Follicular dendritic cells have prognostic relevance in Hodgkin's disease.

The authors' previous study showed the presence of follicular dendritic cell (FDC) networks--though altered--in neoplastic areas, not only in the nodular lymphocyte predominance type, but also in other types of Hodgkin's disease. The present retrospective study was performed on 102 patients to determine whether the presence or absence of FDC networks, or parts of them, in neoplastic areas has prognostic relevance in Hodgkin's disease. Follicular dendritic cells were visualized with the monoclonal antibody Ki-FDC1P, which selectively stains FDCs in paraffin-embedded tissues. Univariate statistical analysis, in which nodular sclerosis (NS) and mixed cellularity (MC) types were combined, showed three prognostically different groups: the best prognosis was associated with nodular lymphocyte predominance cases; the worst with FDC-negative NS or MC cases; and an intermediate prognosis with FDC-positive NS or MC cases. In the NS group, the prognosis of FDC-positive cases was better than that of FDC-negative cases. After multivariate analysis, stepwise modeling identified three prognostic factors at diagnosis: stage (P = .001), FDC status (P = .001), and age (P = .06). The authors conclude that in the most common types of Hodgkin's disease (nodular lymphocyte predominance, NS, and MC), FDC status in the neoplastic area(s) bears prognostic relevance, a positive FDC status predicting a favorable prognosis and a negative FDC status an unfavorable one.

Influence of Epstein-Barr virus genomes on patient survival in Hodgkin's disease.

In previous studies, Epstein-Barr virus was considered a possible etiologic factor in Hodgkin's disease. Two hundred twenty-nine cases of Hodgkin's disease were investigated for the presence of Epstein-Barr virus DNA using the polymerase chain reaction technique on formalin-fixed, paraffin-embedded lymph node tissue to clarify the clinical importance of the incidence of this genome. In 42 cases (18.3%), genomic DNA was not amplifiable. The remaining 187 cases included the following subtypes: lymphocyte-predominant type (n = 13), nodular sclerosis type (n = 98), mixed cellularity type (n = 68), and lymphocyte-depleted type (n = 8). Sixty-six cases (35.2%) were positive for Epstein-Barr virus DNA. In the statistical analysis of available follow-up data from 130 patients, no influence of a positive Epstein-Barr virus DNA finding on length of survival time was revealed. This was true within the cohort of all patients and within the histologically defined subtypes of Hodgkin's disease. In this investigation, detection of Epstein-Barr virus DNA by polymerase chain reaction showed no prognostic relevance for patients with Hodgkin's disease.

Pulmonary nodule caused by an alveolar adenoma of the lung.

Alveolar adenomas of the lung may be a rare cause of solitary coin lesions on chest radiographs. We report a case of this neoplasm, describe its morphological and immunohistochemical characteristics and give further evidence that alveolar adenomas of the lung represent a benign proliferation of both the alveolar epithelium and the septal mesenchyme.

p53 alterations in thymic epithelial tumours.

The prognosis of thymic epithelial tumours depends on malignant behaviour that cannot always be predicted on histological grounds. This study aimed at identifying a molecular marker that would be useful in overcoming the drawbacks of histopathology. Forty-four thymic epithelial tumours were analysed for alterations of the tumour suppressor gene p53 using immunohistochemistry (antibodies D0-1 and CM-1) and PCR-based single-strand conformation polymorphism and DNA sequencing. Histological and clinical evaluation and also p53 analysis revealed three major tumour groups: non-organotypic thymic carcinomas with frequent p53 alterations (7/9) and occurrence of p53 gene mutations (2/9); malignant thymomas with frequent p53 alterations but without p53 gene mutations (11/18); and benign thymomas with rare p53 alterations and without p53 gene mutations (2/17). In non-organotypic thymic carcinomas p53 was detected with both antibodies. In contrast, thymomas lacked immunoreaction with D0-1 suggesting alteration of the antibody-binding site. Overall immunohistochemical results correlated with clinical stages (P < 0.01), pathohistology (P < 0.01), and survival times (P < 0.05). We consider immunohistochemical p53 detection to be a useful new prognostic factor for the evaluation of thymic epithelial tumours.

Right hemihepatectomy for bile duct injury following laparoscopic cholecystectomy.

Laparoscopic cholecystectomy (LC) has become the treatment of choice for patients with symptomatic cholecystolithiasis. But with the introduction of this technique, the incidence of bile duct injuries has increased. We report the case of a 33-year-old man who was transferred from an affiliated hospital to our department for the treatment of a bile duct injury 2 weeks after LC. Prior to transfer, a laparotomy had been performed, with insertion of a T-tube and a Robinson drain on day 5 after LC. Endoscopic retrograde cholangiography (ERC) on admission day revealed an extensive defect of the right biliary system, which could not be treated endoscopically. An emergency laparotomy had to be performed at night for acute bleeding from the portal vein. Due to massive inflammation in the porta hepatis and intraparenchymal destruction of the right bile duct, liver resection was performed 2 days later, after the patient had stabilized in the intensive care unit (ICU). The patient had a prolonged postoperative course, but he finally recovered well from these operations. In conclusion, the management of bile duct injuries should include ultrasound to detect and drain fluid collections and ERC to classify the injury. Emergency laparotomy should never be performed without these examinations, since the majority of bile duct injuries can be treated endoscopically. Surgery for this serious complication should always be performed at specialized centers for hepatobiliary surgery.

Pitfalls in intraoperative frozen section histology of mediastinal neoplasms.

We evaluated the reliability of intraoperative frozen section histology in 149 mediastinal tumours of which 106 lesions were localized in the anterior, 18 in the central and 25 in the posterior mediastinum. Gross non-resectability was ruled out by preoperative imaging. No preoperative cytological or histological diagnosis was obtained in any case. At thoracotomy, 3 biopsies from 3 different sites of the tumour were processed for frozen section as well as for paraffin histology and immunohistochemistry. In 67 of 73 benign lesions (91%), the intraoperative diagnosis was correct, 5 cases could not be classified by frozen section and 1 case had to be revised. Only 28 of 76 malignant lesions (36.8%) were diagnosed correctly by intraoperative frozen section. In 27 cases (35.5%), no intraoperative classification was possible and in 21 patients (27.6%), the diagnosis was wrong with the consequence of surgical overtreatment for lymphoma misinterpreted as thymic cancer in 3 cases. In patients in whom preoperative investigations suggest borderline resectability, a staged procedure to obtain histology prior to definitive surgery could prevent overtreatment.

An unusual cutaneous T cell lymphoma presenting as leonine facies.

We report an unusual case of a cutaneous T cell lymphoma with the clinical picture of leonine facies as the only skin symptom appearing during the first years of the disease. Small atypical lymphocytes with partly pleomorphic, partly indented cerebriform nuclei are present in the facial skin as well as in the peripheral blood and in the bone marrow. The lymphoma shows an indolent clinical behaviour without rapid progression of the disease. It shares features with both pleomorphic small/medium-sized T cell lymphoma and mycosis fungoides, but cannot be classified according to the criteria of the European Organization for Research and Treatment of Cancer (EORTC) Classification for Primary Cutaneous Lymphomas. At present the lymphoma has to be ranged among the group of so-called unspecified peripheral T cell lymphomas according to the proposal of the International Lymphoma Study Group.

[MRI staging of prostate cancer with the combined endorectal body phased-array coil and histologic correlation]. / Kernspintomographisches Staging des Prostatakarzinoms mittels kombinierter Endorektal-Body-Phased-Array-Spule und histopathologische Korrelation.

PURPOSE: Evaluation of the diagnostic value of the combined endorectal body-phased array technique regarding the staging of prostate cancers, especially in the differentiation between stages T2 and T3. MATERIALS AND METHODS: Forty-two patients with biopsy-proven or clinically suspected prostate cancer were examined on a 1.5 T scanner (Siemens, Symphony) prior to radical prostatectomy. T (2)-weighted TSE (axial, coronal) and T (2)-weighted FSE (axial) sequences were obtained with and without fat suppression. After application of 0.2 mmol/kg body-weight Gd-DTPA, T (1)-weighted GRE sequences were obtained using dynamic MRI. All images were prospectively interpreted by two observers. The MR images were correlated with the histopathological findings of wide-area sections of prostatectomy specimens. RESULTS: For the detection of extracapsular growth and seminal vesicle infiltration (T2 versus T3) the accuracy was between 94 % and 97 % (sensitivity 100 %, specificity between 87 % and 93 %, observer 1 and 2). In two cases with a histologically proven stadium pT2b, observer 1 had diagnosed stadium pT3a. The results of observer 2 were marginally better in only one case, which was histologically proven to be pT2b and overstaged as pT3a. MRI did not lead to under-staging of a single tumor with regard to the differentiation between T2 and T3. Overall, the staging of the tumor stages (T1 - T4) was correct in 25 of 33 cases (75 %). The dynamic MRI showed no improvement regarding sensitivity (100 %) and specificity (62 %) and achieved a staging accuracy of only 75 %. CONCLUSION: MRI performed with a combination of a pelvic phased-array coil (PPA) and integrated endorectal coil plays a significant role in the preoperative staging of prostate cancer. However, differentiation between capsular infiltration (T2) and penetration (T3) as well as evaluation of the seminal bladder (T3b) seem to be difficult.