[Treatability of sporadic late onset nemaline myopathy]. / Behandelbarkeit der "sporadic late onset nemaline myopathy".

Sporadic late onset nemaline myopathy (SLONM) is an extremely rare disorder which can be associated with monoclonal gammopathy of unclear significance (MGUS). Clinically SLONM appears mostly after the fourth decade of life as rapidly progressing tetraparesis, respiratory insufficiency and features, such as dropped head syndrome, facial and bulbar involvement. Diagnosis is confirmed by muscle biopsy with detection of nemaline bodies and also frequently lobulated fibres. Immunosuppressant and immunomodulating therapies have been shown to be ineffective but clinical improvement accompanied by disappearance of monoclonal gammopathy and even nemaline bodies was reported following autologous stem cell transplantation and chemotherapy with melphalan. This article presents the case of a 53-year-old man with a 4-year history of SLOMN with MGUS in which administration of intravenous immunoglobulin therapy (IVIG) was not successful in reversing gammopathy, histopathological changes or clinical symptoms.

Evaluation of Mucin-1 protein and mRNA expression as prognostic and predictive markers after neoadjuvant chemotherapy for breast cancer.

BACKGROUND: Mucin-1 (MUC1) is a promising antigen for the development of tumor vaccines. We evaluated the frequency of MUC1 expression and its impact on therapy response and survival after neoadjuvant chemotherapy for breast cancer. PATIENTS AND METHODS: Pre-treatment core biopsies of patients from the GeparTrio neoadjuvant trial (NCT 00544765) were evaluated for MUC1 by immunohistochemistry (IHC; N = 691) and quantitative RT-PCR (qRT-PCR; N = 286) from formalin-fixed paraffin-embedded (FFPE) samples. RESULTS: MUC1 protein and mRNA was detectable in the majority of cases and was associated with hormone-receptor-positive status (P < 0.001). High MUC1 protein and mRNA expression were associated with lower probability of pathologic complete response (P = 0.017 and P < 0.001) and with longer patient survival (P = 0.03 and P < 0.001). In multivariable analysis, MUC1 protein and mRNA expression were independently predictive (P = 0.001 and P < 0.001). MUC1 protein and mRNA expression were independently prognostic for overall survival (P = 0.029 and P = 0.015). CONCLUSIONS: MUC1 is frequently expressed in breast cancer and detectable on mRNA and protein level from FFPE tissue. It provides independent predictive information for therapy response and survival after neoadjuvant chemotherapy. In clinical immunotherapy trials, MUC1 expression may serve as a predictive marker.

Primary and secondary breast lymphoma: prevalence, clinical signs and radiological features.

OBJECTIVES: The purpose of this study was to determine the prevalence, clinical signs and radiological features of breast lymphoma. METHODS: This is a retrospective review of 36 patients with breast lymphoma (22 primary and 14 secondary). 35 patients were female and 1 was male; their median age was 65 years (range 24-88 years). In all patients, the diagnosis was confirmed histopathologically. RESULTS: The prevalence of breast lymphoma was 1.6% of all identified cases with non-Hodgkin lymphoma and 0.5% of cases with breast cancer. B-cell lymphoma was found in 94% and T-cell lymphoma in 6%. 96 lesions were identified (2.7 per patient). The mean size was 15.8 ± 8.3 mm. The number of intramammary lesions was higher in secondary than in primary lymphoma. The size of the identified intramammary lesions was larger in primary than in secondary lymphoma. Clinically, 86% of the patients presented with solitary or multiple breast lumps. In 14%, breast involvement was diagnosed incidentally during staging examinations. CONCLUSION: On mammography, intramammary masses were the most commonly seen (27 patients, 82%). Architectural distortion occurred in three patients (9%). In three patients (9%), no abnormalities were found on mammography. On ultrasound, the identified lesions were homogeneously hypoechoic or heterogeneously mixed hypo- to hyperechoic. On MRI, the morphology of the lesions was variable. After intravenous administration of contrast medium, a marked inhomogeneous contrast enhancement was seen in most cases. On CT, most lesions presented as circumscribed round or oval masses with moderate or high enhancement.

Expression of microRNA 210 associates with poor survival and age of tumor onset of soft-tissue sarcoma patients.

Expression of microRNAs can affect age of tumor onset and prognosis of cancer patients. However, nothing is known about the effects of microRNAs on altered age of cancer onset and disease-specific survival of soft-tissue sarcoma (STS) patients. The levels of miR-210, also known as hypoxia-regulated microRNA, were analyzed by quantitative real-time (RT)-PCR in the tumors of 78 STS patients. The patients were stratified according to their microRNA levels with low, intermediate and high expression levels and the association of microRNA expression and patients' survival was analyzed using multivariate Cox's regression hazard analyses. A significant correlation between an intermediate miR-210 expression and disease-specific death of STS patients [relative risk (RR) = 3.19; p = 0.018] was observed compared with patients with high expression levels in their tumors. Interestingly, the association between an intermediate expression of miR-210 and a poor prognosis was only significant in female STS patients (RR = 11.28; p = 0.010), but not observed in male individuals. Furthermore, the expression of miR-210 showed a significant association with the age of tumor onset in a gender-specific manner. Specifically, male patients with an intermediate expression of miR-210 associated with a 9.6-year later age of tumor onset (p = 0.017) compared with males with a low expression of miR-210 in their tumors. However, no significant differences in the female patients were observed. This study provides the first evidence of a correlation of expression levels of a single microRNA (miR-210) with the prognosis and age of tumor onset in a gender-specific manner in STS patients.

[Unexplained fever and B-symptoms in a young male Black African]. / Unklares Fieber und B-Symptome bei einem jungen Schwarzafrikaner.

An immunocompetent Nigerian developed a fulminant hemophagocytic lymphohistiocytosis due to Epstein-Barr virus reactivation. The patient initially presented with fever, hepatosplenomegaly and pancytopenia. The clinical status of our patient deteriorated quickly despite treatment with corticoids. Escalation of immunosuppressive treatment was not possible. He died of lung, liver and circulatory failure in our intensive care unit.Hemophagocytic lymphohistiocytosis is a rare disease characterized by inflammation due to prolonged and excessive activation of antigen-presenting cells. High plasma ferritin levels and phagocytosis of hematopoetic cells in bone marrow, spleen and liver lead to the diagnosis. Hemophagocytic lymphohistiocytosis should therefore be included in the differential diagnosis in patients with persistent fever, hepatosplenomegaly and cytopenia.

Expression and distribution of tenascin in rat submandibular glands following irradiation.

UNLABELLED: The aim of this study was to investigate the late changes in the expression of tenascin-C (TN-C) in salivary glands (SG) following irradiation (IRR). MATERIALS AND METHODS: In 124 submandibular SG from 62 Wistar rats, the effect of IRR dose (fractionated IRR, 2 Gy per day, total dose of 20, 40, or 60 Gy), time since IRR (6 months vs. 12 months), and animal age (1 year vs. 1.5 years) on TN-C expression profile and its distribution pattern was investigated. RESULTS: Expression of TN-C showed slight to moderate alterations in the irradiated specimens. The expression differed in frequency and degree among various tissue structures. The most striking finding was pronounced dose-dependent heterogeneity, with increases, decreases and fluctuations in staining. CONCLUSION: The staining of TN-C predominantly showed notable dose-dependent heterogeneity, persisting for up to 1 year after completion of IRR. Thus, these findings can be attributed to late radiation effects. The altered expression of tenascin-C may play at least a partial role in late radiogenic dysfunction of the submandibular SG.

[Mucosal remodeling in chronic rhinosinusitis without nasal polyposis - an ultrastructural evaluation]. / Ultrastrukturelle Untersuchungen bei chronischer Rhinosinusitis ohne Polypen.

OBJECTIVE: Because of recurrent scarring of the ostiomeatal complex after paranasal sinus surgery the therapy of chronic rhinosinusitis without nasal polyps (CRSsNP) seems to be difficult. The aim of this study was to evaluate ultrastructural changes of nasal mucosa in patients with CRSsNP. MATERIAL AND METHODS: In case of revision sinus surgery we took specimens of altered mucosa from 21 patients. All subjects suffered from recurrent CRSsNP. Twelve patients without signs of chronic rhinosinusitis dealed as control group. To prepare for electron microscopy the samples were immersed in 3% phosphate-buffered glutaraldehyde and refixed in 1% osmium acid. After dehydration and heat polymerization ultrathin cuts were prepared. After double-contrasting ultrastructures were evaluated by transmission electron microscopy. RESULTS: Typical changes evaluated by electron microscopy were loss of cilia, an increase of microvilli, collagen fibres, fibrocytes, fibroblasts and myofibroblasts as well as perivascular alterations and endothelial changes. CONCLUSION: The study revealed the presence of evident ultrastructural changes in the mucosa of patients with chronic rhinosinusitis without nasal polyps. Mucosal remodeling seems to be not reversible by conservative treatment.

Co-detection of members of the urokinase plasminogen activator system in tumour tissue and serum correlates with a poor prognosis for soft-tissue sarcoma patients.

BACKGROUND: The urokinase plasminogen activator (uPA) system is one of the best-investigated protease systems, both under physiological and pathological conditions, including various types of cancer. However, effects of co-expression of members of the uPA system in soft-tissue sarcoma (STS) patients at the protein level in both tumour tissue and serum have not been investigated yet. METHODS: We examined 82 STS patients for protein levels of uPA, PAI-1and uPAR in tumour tissue and serum by ELISA. RESULTS: A significant correlation between high antigen levels of uPA, PAI-1 or uPAR in tumour tissue, and of uPAR in serum, with poor outcome of STS patients was found for the first time. Most strikingly, we observed an additive effect of combined uPA, PAI-1 or uPAR levels in tumour tissue extracts with uPAR levels in serum on patients' prognosis. High uPA/uPAR, PAI-1/uPAR and uPAR/uPAR antigen levels in tumour tissue/serum were associated with a 5.9-fold, 5.8-fold and 6.2-fold increased risk of tumour-related death (P=0.003, 0.001 and 0.002, respectively) compared with those patients who displayed low levels of the respective marker combination. CONCLUSION: As expression of members of the uPA system in tumour tissue and serum is additively correlated with prognosis of STS patients, our results suggest that combinations of these biomarkers can identify STS patients with a higher risk of tumour-related death.

Sinonasal hemangiopericytoma.

UNLABELLED: Hemangiopericytoma (HPC) is a rare entity that is found in only 1% of vascular tumours. Only 5% of HPC are localized in the nasal cavity or paranasal sinuses. The exact incidence is not stated in the literature. CASE REPORT: A case of a 76-year-old female patient is presented. As she suffered from stroke a cranial CT was performed and the tumour of the paranasal sinuses was diagnosed incidentally. The patient had a history of paranasal sinus surgery under local anaesthesia twenty years ago. The former histological diagnosis was stated as "angiofibroma with signs of proliferation ". The histopathologic diagnosis after endonasal sinus surgery was primarily a neoplasia with spindle-shaped cell formation. Just additional immunocytochemistry revealed the finding of primitive mesenchymal cells. This confirmed the diagnosis of a hemangiopericytoma. The two years follow-up showed no signs and symptoms of recurrent tumour on endoscopic examination and CT scans. CONCLUSION: Hemangiopericytoma is a rare endonasal or sinonasal tumour. Occasionally histological diagnosis is difficult. Its characteristics are marked cellularity, vascularity and a dense net of reticular fibres. The entity shows a considerable tendency to recurrence, malignant transformation and metastasizing. After complete sinonasal surgery a regular short term follow up is advisable.

Case report: ectopic pancreas with pseudocyst and pseudoaneurysm formation.

Ectopic pancreas is a rare congenital anomaly. It is usually asymptomatic, or presents with non specific gastrointestinal symptoms. We describe here a case of ectopic pancreas in the gastric antrum, with pseudocyst and pseudoaneurysm formation. This entity has not been reported previously in the literature.

[Symptomatic cardiac metastasis. Isolated visceral manifestation of a cutaneous malignant melanoma]. / Symptomatische Herzmetastase. Solitäre viszerale Manifestation eines kutanen malignen Melanoms.

Symptomatic cardiac melanoma metastases are very rare. A 76-year-old woman was admitted because of dyspnea and intrathoracic pain 8 years after surgery of a superficial spreading melanoma and 4 years after resection of in-transit metastases. MRI and echocardiography disclosed an intracavitary right atrial mass. Histologically a cardiac melanoma metastasis was found. Unspecific cardiac symptoms in a patient with elevated risk for distant metastases of melanoma should be further investigated to discover cardiac metastasis early.

Allergic and idiopathic rhinitis: an ultrastructural study.

Nasal hyperreactivity is one of the most important underlying mechanisms in both allergic (AR) and idiopathic rhinitis (IR). In order to study the pathomorphological changes in this entity, tissue samples from patients with AR, IR, and from patients without chronic inflammation were taken during nasal surgery. Primary antibodies against Substance P (SP), calcitonin gene-related peptide (CGRP), and endothelial nitric oxide synthases (NOS III) were applied and the immunocomplexes were visualized by immunocytochemistry. The nasal mucosa of patients with AR and IR showed similarities on the ultrastructural level. Neurogenic inflammation was indicated by a strong innervation pattern with sensory nerve fibers containing SP and CGRP. We could show that extensive edema and cellular infiltration might be characteristic for AR. On other hand there was no evidence of eosinophilic or NO involvement in IR. Finally, on the ultrastructural level, AR and IR showed many similarities. Based on these findings anti-inflammatory therapy modalities could be recommended for both types of rhinitis.

[Papillary thyroid carcinoma in a thyroglossal duct cyst: primary tumor or metastasis?]. / Papilläres Schilddrüsenkarzinom in einer medianen Halszyste : Primärtumor oder Metastase?

Thyroglossal duct cysts are the most common anomaly in thyroid development. The occurrence of carcinoma in a cyst is reported to be about 1% of cases. Histopathological examinations reveal a papillary thyroid carcinoma in about 94% of these. We report the case of 38-year-old female having a massive, cervical cystic mass over a period of 18 months. An ectopic papillary thyroid carcinoma was diagnosed. A total thyoidectomy and bilateral neck dissection were performed. This revealed a small thyroid carcinoma and three positive lymphatic nodes. Whether the cystic carcinoma is the primary or a metastasis of the thyroid carcinomais discussed.

Cutaneous dissemination of nasal NK/T-cell lymphoma in a young girl.

In Europe and the USA, the incidence of primary nasal natural killer (NK)/T-cell lymphoma is rare. The skin is one of the predilection sites for dissemination. Cutaneous dissemination is a poor prognostic sign and is consistently fatal. We describe the case of a 17-year-old white German girl with a primary nasal NK/T-cell lymphoma and cutaneous dissemination. She presented with multiple maculopapular patches involving the trunk and thighs, and a 4-week history of headache, fever and fatigue. Biopsies of the skin and the nasal mucosa were taken. Pathological examination of both specimens revealed a NK/T-cell lymphoma. Epstein-Barr virus RNA was detected in the lymphoma cells by in situ hybridization. Unfortunately, the patient died of disease within 1 week.

[Ultrastructural changes in allergic rhinitis vs. idiopathic rhinitis]. / Pathomorphologische Veränderungen bei der allergischen und idiopathischen Rhinitis.

BACKGROUND: Nasal hyperreactivity is one of the most important underlying mechanisms in allergic rhinitis (AR) as well as idiopathic rhinitis (IR). The aim of the present study was to examine pathomorphological changes in nasal mucosa in these subgroups of rhinitis. PATIENTS AND METHODS: Tissue samples of human inferior turbinates from 20 patients with AR and 16 patients with IR were taken during nasal surgery and preserved in glutaraldehyde or paraformaldehyde. Ultrathin sections of specimens from 15 patients without chronic inflammation of nasal mucosa were used as controls. Primary antibodies against substance P (SP), calcitonin-gene-related peptide (CGRP), and endothelial nitric oxide synthase (NOS III) were applied, and the immunocomplexes were visualized by an immunocytochemical staining technique using gold-labeled antibodies. Immunostained structures were photodocumented using light and transmission electron microscopy. RESULTS: The nasal mucosa of patients with AR and IR showed similarities on the ultrastructural level. A strong innervation pattern with sensory nerve fibers containing SP and CGRP demonstrated neurogenic inflammation. Extensive edema and cellular infiltrations were found in AR. A decreased presence of eosinophils and nitric oxide was observed in IR. CONCLUSIONS: On the ultrastructural level, AR and IR showed many similarities but also some differences. Based on these findings, anti-inflammatory therapy could be recommended for both types of rhinitis.

[Primary cutaneous manifestation of Wegener's granulomatosis]. / Primär kutane Manifestation einer Wegener-Granulomatose.

HISTORY: A 57-year-old man was admitted with hemorrhagic papules and necrotising nodules on both elbows and upper legs. Recurrent arthralgia occurred. INVESTIGATIONS: The skin biopsy showed a cutaneous necrotising vasculitis. Positive test results for c-ANCA and proteinase 3 antibodies and a slightly increased WBC and a mild proteinuria were noticeable. DIAGNOSIS, TREATMENT AND COURSE: The diagnosis of an early systemic Wegener's granulomatosis was based on elevated proteinase 3-titres and cutaneous histologic findings as necrotising vasculitis and granulomatous inflammation. Treatment with prednisolone followed by methotrexate resolved the cutaneous symptoms and the arthralgia completely. Three months later the patient developed a progredient methotrexate toxicity caused by a glomerulonephritis. CONCLUSION: Wegener's granulomatosis should be considered if a cutaneous necrotising vasculitis is diagnosed. A cutaneous manifestation could be an early symptom. Methotrexate could be used for treatment of mild courses of Wegener's disease without renal involvement.

[Tuberculosis of the parotid gland]. / Tuberkulose in der Glandula parotidea.

The different tumours of the parotid gland can be divided in benign or malignant tumours, regional inflammations and enlarged lymph nodes. We report on a 26-year-old male from Uganda with a slowly growing tumour of the right parotid gland for several months. The CT scan showed a poorly defined intraparotideal tumour. Ultrasonography revealed multiple enlarged cervical lymph nodes. Suspecting a neoplasm of the parotid gland we decided to perform a superficial parotidectomy for histological examination. The pathological analysis revealed a caseous necrosis and epitheloid granulomata containing Langhans giant cells. The polymerase chain reaction could not confirm our suspicion of tuberculosis. The Ziehl-Neelsen staining did not show any acid-proof rods. Only the breeding of the suspicious probes generated Mycobacterium tuberculosis. Initially denying any infections the patient admitted to having had tuberculosis that had been treated with antibiotics 2 years previously. Tuberculosis is a rare finding in parotid tumours. It must be considered as a differential diagnosis of parotid enlargements.

Expression and distribution of cytokeratins and vimentin in rat larynx and trachea following irradiation.

BACKGROUND: External irradiation (IRR) of advanced head and neck tumors often includes tissues of the larynx and trachea unaffected by cancer. In these normal tissues, both single-cell damage (necrosis, apoptosis, functional cell death) and interstitial damage (edema, fibrosis, vascular alterations, cellular infiltrations) resulting in tissue remodeling can occur, depending on various IRR parameters. However, reports on radiogenic intermediate filament protein alterations in laryngeal-tracheal tissues are very rare. In this study, we investigated the phenotypic characterization of the normal integrity-supporting cytokeratins (CK) and vimentin following a clinically relevant IRR protocol in laryngeal-tracheal tissues. MATERIALS AND METHODS: In 61 laryngo-tracheal specimens from Wistar rats the expression profile and distribution pattern of CK (CK13, CK17/19, CK18) and vimentin were investigated according to IRR dose (fractionated IRR, 2 Gy per day, total dose of 20, 40 or 60 Gy), time from IRR (6 months vs. 12 months) and animal age (1 year vs. 1.5 years) using immunohistochemical methods, semiquantitative assessment and multivariate analysis. RESULTS: In irradiated specimens, expression of both CK and vimentin showed slight to moderate dose-dependent alterations. The expression differed in frequency and level among the various tissue structures and showed remarkable heterogeneity, with increases, decreases and fluctuations in staining. In the glottic mucosal layer (non-keratinizing squamous epithelium), CK13 expression decreased with increasing dose. The CK17/19 expression of supra- and subglottic respiratory epithelia following 20 and 60 Gy exposure was significantly lower than in controls. The respiratory epithelia and, in part, the cuboidal epithelia of the indifferent type at the inner side of the aryepiglottic fold revealed increasing CK17/19 immunoreactions up to 40 Gy IRR, but a distinct decrease in expression at 60 Gy. In subglottic gland structures, CK18 was detected at significantly higher levels than in controls. There was increasing expression with increasing dose. CK18 reactions of supra- and subglottic respiratory mucosal layer, supraglottic gland structures and thyrocytes tended towards increasing expression with increasing dose and in older animals. Tracheal mucosal epithelia, tracheal glands, and respiratory epithelia of the inner side of the aryepiglottic fold tended towards decreasing expression of CK18 with increasing dose and in older animals. In part, these tissues showed dose-dependent fluctuations. Furthermore, the vimentin reactions showed dose-dependent, heterogeneous patterns, with increases, decreases, and fluctuations in staining. Moreover, there were differences in frequency and intensity of expression among the various tissue structures. Age and time from IRR had no significant effect on immunoreaction. CONCLUSION: The staining of CK and vimentin predominantly showed a notable dose-dependent heterogeneity, with increases, decreases and fluctuations in expression. The expression pattern persisted for up to 1 year after the completion of irradiation. Thus, these findings must reflect late radiation effects. The altered expression of CK and vimentin may play at least a partial role in structural (e.g. edema) and functional (e.g. voice disorders) changes associated with irradiation of the head and neck.