[Imaging of primary muscular diseases : What do neurologists expect from radiologists?] / Bildgebung primärer Muskelerkrankungen : Was erwartet der Neurologe vom Radiologen?

Imaging, in particular magnetic resonance imaging (MRI), has in recent years increasingly become a crucial tool for the diagnostics of inherited and acquired muscular diseases. The aim of imaging in neuromuscular disorders goes beyond the detection and quantification of degenerative muscular changes, such as fatty degeneration and includes recognition of very early signs of muscular pathologies presenting as muscular edema. Therefore, imaging is a valuable diagnostic method to support the clinical diagnosis and to narrow down the differential diagnoses, leading to specific additional diagnostic tests in order to establish the correct diagnosis. Although advances in MRI hardware and technology have led to a faster, more accurate and advanced image acquisition allowing whole body examination in a feasible fashion, the standardization of image acquisition and interpretation remains a challenge. The aim of this review article is to address the important and clinically relevant issues concerning the role of imaging of neuromuscular diseases in order to facilitate a good interdisciplinary management for the diagnostics and monitoring of neuromuscular diseases.

Only a Touch of the Flu? The Simultaneous Manifestation of Acute Necrotizing Encephalopathy in Two Consanguineous Patients.

This case report describes the simultaneous manifestation of acute necrotizing encephalopathy in 2 consanguineous patients after infection with influenza B based on the autosomal dominant missense mutation of the RANBP2-gene. Differential diagnosis of acute encephalopathy, clinical and radiological clues, and treatment strategies are outlined.

[PSAP expression in a primary presacral neuroendocrine tumor. Potential for confusion with prostate cancer]. / PSAP-Expression in einem primären präsakralen neuroendokrinen Tumor. Verwechslungsmöglichkeit mit einem Prostatakarzinom.

Primary presacral neuroendocrine tumors are a rare entity with less than 30 cases described in the literature so far. Here we report of a primary presacral neuroendocrine tumor diagnosed at autopsy which was wrongly diagnosed as metastasized prostate cancer before. Misdiagnosis was due to the localization of the tumor, its morphology and its positivity for prostate-specific acid phosphatase (PSAP) when the patient was alive. This is the first report of PSAP and somatostatin receptor expression in this type of tumor.

Comparison of full-field digital mammography and film-screen mammography: image quality and lesion detection.

The objective of this study is to compare image quality and lesion detection for full field digital mammography (FFDM) and film-screen mammography (FSM). In 200 women we performed digital mammography of one breast and film-screen mammography of the other breast. Imaging parameters were set automatically. Image quality, visualization of calcifications and masses were rated by three readers independently. Mean glandular dose was calculated for both systems. We found no significant difference in mean glandular dose. Image quality was rated by reader A/B/C as excellent for FFDM in 153/155/167 cases and for FSM in 139/116/114 cases (p<0.03/0.001/0.001). Microcalcifications were detected by FFDM in 103/89/98 and by FSM in 76/76/76 cases (p<0.01/0.06/0.01). Detection of masses did not differ significantly. FFDM provided significantly better visibility of skin and nipple-areola region (p<0.01). FFDM demonstrated improved image quality compared with film-screen mammography. Microcalcification detection was also significantly better with the digital mammography system for two of the three readers.

Microcalcifications of the breast: how does radiologic classification correlate with histology?

PURPOSE: To assess the correlation between the pre-biopsy classification of microcalcifications and the underlying histology. MATERIAL AND METHODS: Using the morphology and distribution patterns according to the Breast Imaging-Reporting and Data System (BI-RADS) lexicon, the microcalcifications of 199 lesions in 163 consecutive patients scheduled to undergo 11 G vacuum core biopsy were classified within the BI-RADS categories. The correlation between BI-RADS assessment categories 3, 4, and 5 and the final histological results was statistically evaluated with the chi2 test. The diagnostic indices were calculated. RESULTS: The prospectively classified BI-RADS 3/4/5 findings revealed a malignant histology in 5.9%/17.6%/90.9% of all lesions, respectively. The relationship between BIRADS categories 3, 4, and 5 and histology was statistically highly significant (P<0.0001). The sensitivity, specificity, positive and negative predictive values were 95.7%/21.2%,/37.8%/94.3%, respectively. CONCLUSION: The BI-RADS lexicon describes microcalcifications of the breast and provides diagnostic categories that lead to standardized biopsy recommendations. Nevertheless, how to link description to classification of microcalcifications is still a difficult diagnostic task. The evaluation of microcalcifications as proposed in this article may help to set standards in the clinical routine and in the comparability of scientific data.

[Oncologic screening with whole-body MRI: possibilities and limitations]. / Onkologische Früherkennung mit der Ganzkörper-MRT: Möglichkeiten und Grenzen.

In the last decade the interest in radiological screening examination increased among informed laymen enormously. Independent from the evidence of whole-body examinations for cancer prevention the discussion about screening must again be considered again due to the newest technical developments, since MRI of the whole-body with high spatial resolution is feasible now within one single examination. The newest system permits simultaneous connection of up to 76 coil elements and signal reception from 32 independent receiving channels. Whole-body MRI including magnetic resonance colonography (MRC) is feasible within 60 min. In this review potential investigation protocols will be presented. Potentials, challenges and limitations of whole-body MRI in the prevention of the malignancies most frequently leading to death are discussed on the basis own experiences examples and the literature.

[Radiologic-histopathologic correlation of microcalcifications from 11g vacuum biopsy: analysis of 3196 core biopsies]. / Radiologisch-histopathologische Korrelation von Mikrokalzifikationen in 11-G-Vakuumbiopsaten - eine Analyse von insgesamt 3196 Proben.

PURPOSE: To perform a statistical evaluation of microcalcifications (MC) from suspicious breast lesions detected by radiography and histopathology. MATERIALS AND METHODS: Histological and radiological detection of calcifications were compared from 116 biopsies in 96 women. Lesions with identical description of calcifications detected in histopathology and radiography were considered concordant, patients with obvious discrepancies discordant. If histological and radiological groups of calcifications were identical in number but differed in location, the case was considered pseudo-concordant. RESULTS: Histopathology classified 24 of 116 lesions as malignant and 92 as benign. A total of 3196 core biopsies were examined, 851 of these contained groups of calcifications or single calcifications. Both modalities detected 579 calcifications, with 169 exclusively detected by radiography and 103 exclusively by histopathology. In 35 cases (30 %) radiologic and pathologic results were concordant, in 6 cases pseudo-concordant (4 %) and in 75 cases (65 %) discordant. The case-based Kappa coefficient was - 0.09 (- 0.24 to 0.07). The 122 calcifications not detected by histopathology were few or single calcifications at the edge of the core that were probably lost during processing, 18 were possible artefacts. Six cores contained calcium oxalate, 3 contained milk of calcium. In 6 cases malignant disease was found after the first examination, hence the cores were not searched thoroughly for the missing calcifications. In the remaining 14 cases, no calcifications were found despite complete processing of the tissue. In 49 of 103 cases of radiologically undetected microcalcifications, the retrospect analysis showed dense tissue areas that probably contained the calcification. The remaining 54 cases contained calcifications, which were too small to be detected radiologically. SUMMARY: Discordant results from pathological and radiological examinations of biopsies can mainly be explained by calcifications at the edge of the specimen lost during processing, which are therefore not detected in histopathology, and calcifications too small to be visualized radiologically.

[Stereotactic vacuum-assisted breast biopsy--success, histologic accuracy, patient acceptance and optimizing the BI-RADSTM-correlated indication]. / Stereotaktische Vakuumbiopsie mammographisch detektierter Läsionen - Erfolg, histologische Sicherheit, Patientenakzeptanz und BI-RADS trade mark -korrelierte Indikationsoptimierung.

PURPOSE: To evaluate success, histologic accuracy, patient acceptance and BI-RADS TM-correlated malignancy rate of stereotactic vacuum-assisted breast biopsies in order to optimize the indication. MATERIALS AND METHODS: In 132 patients with mammographically detected breast lesions 166 stereotactic vacuum- assisted 11 gauge core biopsies were performed. All lesions were classified according to the BI-RADS TM categories of the ACR. Removal of the lesion was radiographically assessed as complete, representative or not representative. Patient acceptance was evaluated. RESULTS: Of the 166 lesions, 54 (32.5 %) lesions were judged completely removed, 110 (66.3 %) representatively removed and 2 (1.2 %) not representatively removed. Malignancy was found in 38 (22.9 %) lesions. The rate of malignancy increased from 6.3 % (2/32) for BI-RADS TM category 3 to 16.7 % (19/114) for BI-RADS TM category 4 and increased further to 85 % (17/20) for BI-RADS TM category 5 (p < 0.001). The histology of a sufficient vacuum-assisted biopsy was underestimated in 6 (15 %) of the 40 lesions that were subsequently excised surgically. Most patients (98.5 %; 130/132) stated they would undergo a vacuum-assisted biopsy again. CONCLUSION: Vacuum-assisted breast biopsy is accurate, has a justifiable rate of histologic underestimation and is well accepted by patients. Patients with BI-RADS TM category 4 microcalcification benefit the most. Lesions of BI-RADS TM category 3 and BI-RADS TM category 5 should be biopsied only under special circumstances (family risk of breast cancer; assessment of lesions extension).

Claudin-1 and claudin-5 expression and tight junction morphology are altered in blood vessels of human glioblastoma multiforme.

The aim of the study was to characterize the interendothelial junctions in tumor microvessels of five cases of human glioblastoma multiforme. In addition to morphological analysis, tumors were screened for the expression of junctional proteins, such as occludin, claudin-1, ZO-1 and catenins. The expression of the tight junction protein claudin-1 was lost in the majority of tumor microvessels, whereas claudin-5 and occludin were significantly down-regulated only in hyperplastic vessels. As shown by freeze-fracture analysis, under the conditions of tumor growth tight junction particles of endothelial cells were almost exclusively associated with the exocytoplasmic fracture face, providing evidence for a switch of the particles from the protoplasmic to the external leaflet of the endothelial membrane. These results suggest a relationship between claudin-1 suppression and the alteration of tight junction morphology, which is likely to correlate with the increase of endothelial permeability. Underlining the undifferentiated state of tumor microvessels, plakoglobin, a crucial protein for mature endothelial junctions, was not detectable in most microvessels, whereas beta-catenin was abundantly labeled. In this context, it is of particular interest that the majority of microvascular pericytes were negative for alpha-smooth muscle actin, which is a marker of differentiated pericytes, although pericytes were frequently found in electron micrographs. In conclusion, the data suggest that the increase in microvascular permeability in human gliomas, contributing to the clinically severe symptoms of brain edema, is a result of a dysregulation of junctional proteins.

Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome.

PURPOSE: This phase II study was undertaken to assess the efficacy and toxicity of the addition of continuous low-dose interferon alfa-2a (IFN) to fludarabine in patients with advanced or refractory mycosis fungoides (MF) or the Sézary syndrome (SS). PATIENTS AND METHODS: Thirty-five patients were treated with fludarabine 25 mg/m2 intravenously (IV) on days 1 to 5 every 28 days along with IFN 5 x 10(6) U/m2 subcutaneously three times per week continuously for up to eight cycles. IFN doses were escalated to 7.5 x 10(6)/m2 at day 29 if constitutional toxicities were less than grade 3. Twenty-one patients had not responded to prior chemotherapy or total-skin electron-beam irradiation (TSEB), and 10 of these had received prior deoxycoformycin (pentostatin; DCF) and intermittent high-dose IFN; seven had received only topical therapies, and seven were untreated. RESULTS: Four patients achieved a complete response (CR) and 14 achieved a partial response (PR) for an overall response rate of 51% (95% confidence interval, 35% to 70%). Four of 11 patients with visceral involvement responded. The median progression-free survival duration of the patients who responded was 5.9 months, and three of the complete responders are in unmaintained response after 18 to 35 months. Grade 3 or 4 hematologic toxicity occurred in 21 patients, including two who developed persistent bone marrow aplasia. Eighteen patients developed infections during therapy, including five with herpes zoster, one with Pneumocystis carinii, one with extrapulmonary tuberculosis, and two with disseminated toxoplasmosis. CONCLUSION: The combination of fludarabine with continuous low-dose IFN is an active regimen in patients with advanced MF/SS, including patients with visceral involvement and patients who progressed after prior therapy with DCF and IFN. This regimen has induced unmaintained remissions in a small subset of patients.

Phase II study of pentostatin and intermittent high-dose recombinant interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome.

PURPOSE: This phase II study was undertaken to assess the efficacy and toxicity of alternating administration of pentostatin (deoxycoformycin [DCF]) and interferon alfa-2a (IFN) in patients with advanced or refractory mycosis fungoides (MF) or the Sézary syndrome (SS). PATIENTS AND METHODS: Forty-one patients underwent therapy with alternating cycles of DCF 4 mg/m2 intravenously (IV) days 1 through 3 and IFN 10 million U/m2 intramuscularly (IM) day 22, and 50 million U/m2 intramuscularly (IM) days 23 through 26. Twenty-nine patients had not responded to prior chemotherapy or total-skin electron-beam irradiation (TSEB), six had not responded to topical therapies, and six had no previous treatment. RESULTS: Two patients achieved a complete response (CR) and 15 achieved a partial response (PR), for an overall response rate of 41% (95% confidence interval, 26% to 58%). No responses were observed in the seven patients with visceral involvement. The median progression-free survival of patients who responded was 13.1 months. IFN-related constitutional symptoms were reported in 39% of patients; severe toxicities included cardiomyopathy in one patient, acute and chronic pulmonary dysfunction in four, and reversible mental status changes in two. Seven patients developed herpes zoster during therapy and six had staphylococcal bacteremia. CONCLUSION: These results suggest that the combination of DCF and IFN is an active regimen in MF patients without visceral involvement.

Prognostic implications of evaluation for lymph node involvement by T-cell antigen receptor gene rearrangement in mycosis fungoides.

We investigated the correlation between the detection of clonal rearrangement of the T-cell antigen receptor gene (TCRR) in lymph node tissue with histopathologic lymph node classification in 33 patients with mycosis fungoides with and without the Sezary Syndrome. We analyzed DNA extracted from lymph nodes that were histologically uninvolved (LN1-2), dermatopathic nodes with clusters of atypical cells (LN3), and nodes effaced with lymphoma (LN4) and found TCRR in none of five LN1-2 nodes, 8 of 17 LN3 nodes, and 10 of 11 LN4 nodes. Further, the detection of TCRR correlated with presence of palpable adenopathy (P2 less than .0001) and was associated with a worse survival (P2 = .0024). Within the subgroup of patients with LN3 nodes, there was a trend (P2 = .14) toward inferior survival if nodes were involved by TCRR, irrespective of extent of skin disease. We conclude that detection of TCRR in nodes from mycosis fungoides patients is an objective and reliable means of assessing tumor infiltration of lymph node and is associated with an inferior survival.

A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides.

Mycosis fungoides is a T-cell lymphoma that arises in the skin and progresses at highly variable rates. Nonradomized studies have suggested that early aggressive therapy may improve the prognosis in this usually fatal disease. We studied 103 patients with mycosis fungoides, who, after complete staging, were randomly assigned to receive either combination therapy, consisting of 3000 cGy of electron-beam radiation to the skin combined with parenteral chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine (n = 52) or sequential topical treatment (n = 51). The prognostic factors were well balanced in the two groups. Combined therapy produced considerable toxicity: 12 patients required hospitalization for fever and transient neutropenia, 5 had congestive heart failure, and 2 were later found to have acute nonlymphocytic leukemia. Patients receiving combined therapy had a significantly higher rate of complete response, documented by biopsy, than patients receiving conservative therapy (38 percent vs. 18 percent; P = 0.032). After a median follow-up of 75 months, however, there was no significant difference between the treatment groups in disease-free or overall survival. We conclude that early aggressive therapy with radiation and chemotherapy does not improve the prognosis for patients with mycosis fungoides as compared with conservative treatment beginning with sequential topical therapies.

Histopathologic staging at initial diagnosis of mycosis fungoides and the Sézary syndrome. Definition of three distinctive prognostic groups.

STUDY OBJECTIVE: To determine the optimal staging evaluation at the time of initial diagnosis of mycosis fungoides or the Sézary syndrome. DESIGN: Retrospective review of a uniformly staged inception cohort. SETTING: Single-institution tertiary care center. PATIENTS: 152 consecutive patients who had mycosis fungoides with or without the Sézary syndrome within 6 months of the initial definitive diagnosis. INTERVENTION: A detailed staging evaluation including physical examination, routine laboratory studies, chest roentgenogram, lymphangiogram, peripheral blood smear, lymph node biopsy, bone marrow aspirate or biopsy, and liver biopsy in selected patients. MEASUREMENTS AND MAIN RESULTS: Univariate adverse prognostic features at initial diagnosis in patients with mycosis fungoides included (P less than 0.01) one or more cutaneous tumors or generalized erythroderma, adenopathy, blood smear involvement with Sézary cells, lymph node effacement, eosinophilia, and visceral involvement. Important, independent prognostic factors in a multivariate analysis are the presence of visceral disease and type of skin involvement. CONCLUSIONS: A staging system based on histopathologic evaluation of skin, lymph nodes, blood, and visceral sites provides more comprehensive prognostic information than clinical evaluation of skin disease and adenopathy. Patients may be divided at initial presentation into three prognostic groups: good-risk patients, who have plaque-only skin disease without lymph node, blood, or visceral involvement (median survival, greater than 12 years); intermediate-risk patients, who have cutaneous tumors, erythroderma, or plaque disease with node or blood involvement but no visceral disease or node effacement (median survival, 5 years); and poor-risk patients, who have visceral involvement or node effacement (median survival, 2.5 years).

Evaluation of circulating malignant cells provides prognostic information in cutaneous T cell lymphoma.

Peripheral blood lymphocyte morphology was evaluated prospectively by light microscopy of blood smears and E rosette preparations in 160 patients with cutaneous T cell lymphoma (CTCL). Blood involvement was related to the type of cutaneous T-stage, being present in 90% of patients with erythroderma (T4), 27% of those with cutaneous tumors (T3), 9% of those with generalized (T2), and 0% of those with limited skin plaques (T1). Untreated patients with blood involvement (38 of 105) had a higher frequency of CTCL in lymph nodes and viscera and survival inferior to that of patients with normal or nondiagnostic lymphocyte morphology (P less than .001). Multivariate analysis showed skin stage and age to be the most important pretreatment risk factors for survival. Although blood involvement was not an independent risk factor for the entire group, it appeared to have some adverse influence in the T2/T3 subsets (P = .051). Both lymphocytosis and size distribution of the circulating CTCL cells at initial diagnosis influenced survival. Patients with "mixed cell" cytology (greater than 20% large [greater than 11 microns] CTCL cells), had a worse survival than those with predominantly small circulating CTCL cells (P = .009). The former were more likely to have aggressive features, including lymph node effacement by tumor (P less than .001) and visceral disease (P = .074), than were "small cell" patients. Our data indicate that detailed review of the blood lymphocyte morphology in patients with diagnosed or suspected CTCL is helpful in predicting extent of disease and prognosis.

Combined modality treatment of cutaneous T cell lymphoma: results of a 6-year follow-up.

Thirty-nine patients with cutaneous T cell lymphoma (CTCL; including mycosis fungoides or the Sezary syndrome) with no previous treatment other than topical therapy or oral corticosteroids, received total skin electron beam irradiation (TSEB) and either sequential or simultaneous systemic chemotherapy. Median follow-up, measured from the time of initiation of therapy to the time of analysis, is in excess of 6 years and extends to 100+ months. Thirteen patients with stage I disease (limited to skin with no adenopathy) received 3,000 rad total skin electron beam irradiation followed by three 2-week courses of daily intravenous (IV) mechlorethamine. Twenty-six patients with advanced disease (stage II-IV) received 2,400 rad of TSEB and simultaneous chemotherapy with two alternating three-drug regimens: vinblastine, doxorubicin, and bleomycin (VAB) alternating with cyclophosphamide, methotrexate, and prednisone (CMP) administered over 54 weeks. The overall response rate was 92% with 16 of 39 patients (41%) achieving a histologically documented complete response (CR). Stage I patients had a significantly increased CR rate (77%) compared with stage II-IV (P less than .01). The overall 6-year survival was 92% for stage I patients and 26% for stage II-IV patients (23%) (P less than .001). Among ten completely responding stage I patients, six remain alive and disease-free in excess of 72 months. The median disease-free survival is 26 months for completely responding stage II-IV patients (P = .04), but none are continuous disease-free survivors after protocol treatment. We conclude that combined modality treatment can be safely administered and produces prolonged disease-free survival in some stage I patients, but not in more advanced stage patients.

Histologic assessment of lymph nodes in mycosis fungoides/Sézary syndrome (cutaneous T-cell lymphoma): clinical correlations and prognostic import of a new classification system.

Mycosis fungoides and the Sézary syndrome share common cutaneous histopathologic features, and this spectrum of malignant disease is referred to here as cutaneous T-cell lymphoma (CTCL). A method (LN classification) for describing the histopathologic features of lymph nodes in CTCL is presented. In this system, lymph node biopsy specimens are scored according to the number of atypical lymphoid cells in T-cell-dependent paracortical zones and the preservation or distortion of the lymph node architecture. Lymph node architecture is preserved in lymph nodes scored LN1 to LN3, and these nodes may have coexistent dermatopathic change. LN1 nodes have single infrequent atypical lymphocytes in paracortical T-cell regions. LN2 nodes have small clusters of paracortical atypical cells. LN3 nodes have large clusters of atypical cells. LN4 nodes are partially or totally effaced by atypical cells. This system was used to classify 96 lymph node biopsy specimens obtained within six months of the initial diagnosis of CTCL; no LN1 nodes, 37 LN2, 44 LN3, and 15 LN4 nodes were found. The LN class was significantly correlated with the extent of skin, blood, and visceral involvement, as well as with survival. Patients with LN2 lymph nodes have an estimated five-year survival of 70 per cent, while patients with LN3 and LN4 nodes have estimated five-year survivals of 30 and 15 per cent, respectively. The survival differences between the LN subgroups were all significant (P less than 0.05). The LN classification system was clearly shown to be reproducible among experienced pathologists. The LN system for the histopathologic classification of lymph nodes in CTCL is of prognostic value and should be used to assess lymph node biopsies in patients with CTCL.