Ill-defined germinal centers and severely reduced plasma cells are histological hallmarks of lymphadenopathy in patients with common variable immunodeficiency.

Given the severely reduced numbers of circulating class-switched memory B cells and plasmablasts in patients with common variable immunodeficiency (CVID) the germinal center (GC) reaction as the source of both populations is expected to be disturbed in many CVID patients. Therefore immunohistochemical studies were performed on lymph node (LN) biopsies from ten CVID patients with benign lymphoproliferation. According to the Sander classification the majority of patients presented with reactive lymphoid hyperplasia (7/10), 6/10 showed granulomatous inflammation. All cases showed some normal GCs but in 9/10 these concurred to a varying degree with hyperplastic, ill-defined GCs in the same LN. The percentage of ill-defined GCs correlated significantly with the percentage of circulating CD21(low) B cells suggesting a common origin of both immune reactions. In 9/10 CVID LNs significantly higher numbers of infiltrating CD8+ T cells were found in GCs of CVID patients compared to controls, but no HHV-8 and only in 2/10 LNs EBV infection was detected. Class switched plasma cells (PCs) were severely reduced in 8/10 LNs and if present, rarely found in the medulla of the LN. Based on the presence of large GCs in all examined patients, the reduction of circulating memory B cells and PCs points towards a failure of GC output rather than GC formation in CVID patients with lymphadenopathy.

[Paraganglioma of the urinary bladder-a rare, but relevant differential diagnosis]. / Das Paragangliom der Harnblase ­ eine seltene, aber relevante Differentialdiagnose.

A paranglioma is a rare, extra-adrenal neuroendocrine tumour. Paraganglioma of the urinary bladder is very rare, accounting for < 1% of all paranglioma and only 0.05% of all bladder tumours. Presentation varies greatly and its clinical significance is dependent on the tumour functionality. Since paranglioma may look histologically very similar to urothelial carcinomas, the risk of misdiagnosis is relatively high, with considerable therapeutic and medicolegal consequences. This case describes an incidental paraganglioma of the urinary bladder, diagnosed cystoscopically due to painless microhaematuria and confirmed histologically after performing several immunohistochemical examinations.

B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans.

B-cell survival depends on signals induced by B-cell activating factor (BAFF) binding to its receptor (BAFF-R). In mice, mutations in BAFF or BAFF-R cause B-cell lymphopenia and antibody deficiency. Analyzing BAFF-R expression and BAFF-binding to B cells in common variable immunodeficiency (CVID) patients, we identified two siblings carrying a homozygous deletion in the BAFF-R gene. Removing most of the BAFF-R transmembrane part, the deletion precludes BAFF-R expression. Without BAFF-R, B-cell development is arrested at the stage of transitional B cells and the numbers of all subsequent B-cell stages are severely reduced. Both siblings have lower IgG and IgM serum levels but, unlike most CVID patients, normal IgA concentrations. They also did not mount a T-independent immune response against pneumococcal cell wall polysaccharides but only one BAFF-R-deficient sibling developed recurrent infections. Therefore, deletion of the BAFF-R gene in humans causes a characteristic immunological phenotype but it does not necessarily lead to a clinically manifest immunodeficiency.

Immunohistochemical expression of fibronectin in the lungs of fire victims proves intravital reaction in fatal burns.

Immunohistochemical studies about the presence of fibronectin in the lungs were performed in a group of 73 fire victims (63 cases of intravital and 10 cases of postmortem burn) as well as in an unselected control group of 55 individuals not exposed to fire before death. The cases of intravital burn showed a significantly stronger fibronectin expression than the control cases and the cases of postmortem burn. Fibronectin was mainly present in macrophages of the peribronchial lung parenchyma and, not associated with cells, in the matrix of peribronchial tissue. Our findings suggest that higher levels of fibronectin expression in the lung tissue of burn victims compared to fire-unrelated deaths may serve as an indicator of an early intravital inflammatory response to fire damage.

MAGE qPCR improves the sensitivity and accuracy of EBUS-TBNA for the detection of lymphatic cancer spread.

INTRODUCTION: Microscopic examination of histologic slides or cytologic specimens of mediastinal lymph node samples obtained by diagnostic mediastinoscopy or endobronchial ultrasound-guided fine-needle aspiration (EBUS-TBNA) is routinely used for the staging of lung cancer patients. Therefore, we explored whether the detection of tumor-associated mRNA in lymph node samples from patients with suspected lung cancer adds diagnostic accuracy to conventional histopathological staging. METHODS: We examined 202 lymph nodes obtained by EBUS-TBNA or mediastinoscopy from 89 patients with lung cancer. Lymph node samples from patients with nonmalignant disease were available as controls (60 samples from 31 patients). Real-time quantitative mRNA analysis was performed for melanoma antigen-A genes (MAGE-A 1-6, MAGE-A 12) using a LightCycler 480 instrument. RESULTS: MAGE transcript levels in control and cancer patients differed widely, and the 95% confidence interval served to define the threshold between negative and positive samples. MAGE 1 to 6 transcripts were detected in 35 of 122 (28.7%) lymph nodes obtained by EBUS-TBNA and 16 of 80 (20.0%) lymph nodes obtained by mediastinoscopy. MAGE 12 transcripts were detected in 10 of 122 (8.2%) lymph nodes obtained by EBUS-TBNA and 9 of 80 (11.3%) lymph nodes obtained by mediastinoscopy. Although the accuracy of histopathological diagnosis after EBUS-TBNA and mediastinoscopy was 69.6% and 84.1%, respectively, it increased to 81.2% and 86.4%, respectively, when combined with MAGE-quantitative polymerase chain reaction. CONCLUSIONS: The combination of EBUS-TBNA and MAGE-quantitative polymerase chain reaction increases the accuracy of tumor cell detection to the level seen with mediastinoscopy.

Advanced imaging findings and computer-assisted surgery of suspected synovial chondromatosis in the temporomandibular joint.

Synovial chondromatosis of the joint occurs mainly in teenagers and young adults. Only 3% of these neoplasms are located in the head and neck region. Synovial chondromatosis of the temporomandibular joint is therefore a very rare disorder. Therefore, developing a working, histological confirmation is required for differential diagnosis. In this case series, the outcome of histological investigation and imaging techniques are compared. Based on clinical symptoms, five cases of suspected synovial chondromatosis of the temporomandibular joint are presented. In each of the subjects, the diagnosis was confirmed by histology. Specific imaging features for each case are described. The tomography images were compared with the histological findings. All patients demonstrated preauricular swelling, dental midline deviation, and limited mouth opening. Computer-assisted surgery was performed. Histology disclosed synovial chondromatosis of the temporomandibular joint in four cases. The other case was found to be a developmental disorder of the tympanic bone. The diagnosis of synovial chondromatosis of the temporomandibular joint can only be based on histology. Clinical symptoms are too general and the available imaging techniques only show nonspecific tumorous destruction, infiltration, and/or residual calcified bodies, they are only for advanced cases. A rare developmental disorder of the tympanic bone--persistence of foramen of Huschke--has to be differentiated.

Primary (AL) amyloidosis in plasma cell disorders.

Primary (AL) amyloidosis is the most common form of systemic amyloidosis. The morbidity arises from extracellular deposition of immunoglobulin light chain (LC) fibrils in major organs, such as the kidneys, heart, and bowel. Organ dysfunction contributes to a high mortality and poor prognosis, with a median survival time of 1-2 years from diagnosis. Here, we present a 46-year-old man with an exceptional clinical course of an LC multiple myeloma with generalized amyloidosis, causing renal insufficiency, congestive heart failure, and complete intestinal necrosis. We have summarized recent knowledge on AL amyloidosis, its association with monoclonal gammopathies, clinical presentations, diagnostic tools, and treatment strategies. Our comprehensive overview of this rare and often fatal disease aims to increase the awareness of AL amyloidosis. This may facilitate earlier diagnosis, and thus allow initiation of prompt and specific therapies, which are indispensable in order to improve disease prognosis.

Lung cancer and Rosai-Dorfman's disease. A clinicopathological study.

CASE REPORT: A 60-year-old female patient underwent craniotomy for a cerebral lesion in the frontoparietal lobe. Histologically, it turned out to be a metastasis from an adenocarcinoma. The primary tumor was found in the upper lobe of the left lung. The patient had whole brain radiation therapy only, the lung tumor was not treated. 4 years later, she presented with enlarged cervical lymph nodes. A biopsy showed dilated sinuses filled with histiocytes, but no tumor cells. The diagnosis of sinus histiocytosis with massive lymphadenopathy was made (Rosai-Dorfman's disease). Without any treatment, the swelling resolved completely a few weeks later. Similar episodes were observed several times in the following years. The patient died more than 7 years after the diagnosis of a metastasizing lung cancer due to pneumonia. CONCLUSION: In a patient with a pulmonary neoplasm and suspected supraclavicular lymph node spread, Rosai-Dorfman's syndrome should be considered as a rare differential diagnosis.