The nexin-dynein regulatory complex subunit DRC1 is essential for motile cilia function in algae and humans.

Primary ciliary dyskinesia (PCD) is characterized by dysfunction of respiratory cilia and sperm flagella and random determination of visceral asymmetry. Here, we identify the DRC1 subunit of the nexin-dynein regulatory complex (N-DRC), an axonemal structure critical for the regulation of dynein motors, and show that mutations in the gene encoding DRC1, CCDC164, are involved in PCD pathogenesis. Loss-of-function mutations disrupting DRC1 result in severe defects in assembly of the N-DRC structure and defective ciliary movement in Chlamydomonas reinhardtii and humans. Our results highlight a role for N-DRC integrity in regulating ciliary beating and provide the first direct evidence that mutations in DRC genes cause human disease.

Malacoplakia and spermatic granuloma complicating vasectomy.

Malacoplakia is a granulomatous disease with a histiocytic infiltrate containing calcified structures called Michaelis-Gutmann bodies. These structures are considered to represent an abnormal response to infection involving defective lysosomes and abnormal microbubular assembly. The disease most frequently involves urinary and genital tracts, but has also been described from most other organs. Here we present the first case of malacoplakia only involving the vas deferens.

Primary ciliary dyskinesia: a review.

The entity sinusitis, bronchiectasis, and situs inversus is since long named Kartagener syndrome. Nowadays the designation used is primary ciliary dyskinesia (PCD), which implies cilia with decreased or total absence of motility, which may result in sinusitis, chronic bronchitis, bronchiectasis, and male infertility. A large number of deficiencies detectable on the ultrastructural level give rise to PCD. There may also be aberrations not detected up to the present. The normal left-right asymmetry of the body is thought to be due to the beating of the cilia in the embryonic (Hensen's) node. Total immotility of the cilia should therefore result in random asymmetry of the body that is situs inversus in 50% of the cases. It has also been claimed that 50% of cases with PCD have situs inversus. However, several deficiencies apparently do not cause total immotility, and all ultrastructural variants are not associated with situs inversus in 50% of the cases. Several of the deficiencies are difficult to detect. Optimal fixation and handling are therefore obligatory. The genetic changes behind the variants are now being studied in several laboratories. Patients with PCD have very low levels of nasal nitric oxide, which is of increasing diagnostic importance. Other established diagnostic methods are the saccharine test and determination of ciliary beat frequency.

Core-needle biopsy performed by the cytopathologist: a technique to complement fine-needle aspiration of soft tissue and bone lesions.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is gaining increased popularity in the diagnosis of musculoskeletal lesions; and, in many patients, a definitive diagnosis can be rendered from aspiration smears alone. The main limitation of FNAC of soft tissue and bone neoplasms is in the evaluation of tissue architecture. In addition cytologic specimens are not always adequate for ancillary studies. METHODS: A consecutive series of 130 patients with soft tissue and bone lesions was examined by core-needle biopsy (CNB) performed by a cytopathologist in conjunction with FNAC. The findings of this combined diagnostic approach were compared with histologic diagnoses made on surgical biopsies and resected specimens from 86 patients. Adequate follow-up was available in all patients. RESULTS: FNAC combined with CNB correctly could identify 77 of 78 malignant lesions and 50 of 52 benign lesions. Only seven patients underwent incisional biopsy. The tumor subtype was determined correctly in 30 of 39 patients (77%) and the malignancy grade was determined in 35 of 39 patients (90%) with primary soft tissue and bone sarcomas compared with the biopsy or operative specimens. CONCLUSIONS: FNAC of musculoskeletal tumors/lesions complemented with CNB combined cytomorphology with tissue architecture and ancillary procedures. In the current study, obtaining FNAC as well as CNB at the same clinic visit and by the cytopathologist made preliminary diagnosis on the day of referral possible. This speeded diagnosis increased the number of correct diagnoses and usually enabled correct subtyping and malignancy grading of sarcomas.

Elastofibroma dorsi has distinct cytomorphologic features, making diagnostic surgical biopsy unnecessary: cytomorphologic study with clinical, radiologic, and electron microscopic correlations.

Elastofibroma dorsi (EFD) is a relatively rare soft tissue mass, probably of reactive nature. The lesion is typically located near the inferior margin of the scapula or between the inferior part of scapula and the chest wall in elderly women. Although location of the tumor together with the age/sex of the patients and radiologic findings is often suggestive of the diagnosis, tissue examination has been considered necessary to confirm the diagnosis. Although the histologic features of EFD are well known, there are only four single case reports of the cytologic findings in the English language literature. We describe the cytologic features of EFD in five patients with correlations to clinical, radiologic, histologic, and electron microscopic findings. The current study suggests that the fine-needle aspiration (FNA) features are highly diagnostic, permitting a firm diagnosis of EFD in a typical clinical setting and eliminating the need for preoperative histologic examination.

Absence of nexin links as a possible cause of primary ciliary dyskinesia.

Transmission electron microscopy of nasal cilia was performed in three patients, two of them siblings, with repeated respiratory infections. Number of microtubuli and dynein arms were within normal limits and they had an ordered arrangement except for a disarray of the microtubuli in some areas of the biopsies from two of the patients. In the normal areas radial spokes and sheaths were easily found but nexin links could not be discerned in any of the patients. The orientation of the cilia was partly random. As all patients repeatedly and constantly had very low nasal NO (range 9-15 ppb; normal findings for persons <10 years old are > 50 ppb), the diagnoses were very likely primary ciliary dyskinesia (PCD). Absence of nexin links may be an ultrastructural variant of PCD. Deficiency of these structures might be the cause of the microtubular disarray observed in some areas of the biopsies.

Extraskeletal myxoid chondrosarcoma with neuroendocrine differentiation: a case report with fine-needle aspiration biopsy, histopathology, electron microscopy, and cytogenetics.

Although extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma, its morphological, ultrastructural, and cytogenetical features have been well investigated. The authors describe a very rare variant of EMC with neuroendocrine differentiation. A 49-year-old woman presented with an 11-cm, deep-seated, lobulated soft tissue mass in the left thigh and a lymph node metastasis in the left groin. Analysis of fine-needle aspiration biopsy (FNAB) smears and a cellblock prepared from FNAB material, as well as histological sections of the excised tumor, showed a neoplasm composed of rounded and elongated cells arranged in strands and cords in a myxoid background matrix. The nuclei were rounded and often eccentric. The immunohistochemical phenotype was S-100 protein -, neuron specific enolase +, and chromogranin A+. Electron microscopy showed tumor cells harboring numerous mitochondria, partial basal lamina, and unequivocal neuroendocrine granules. Molecular genetic analysis revealed a TAF15/NR4A3 fusion, a characteristic rearrangement occurring in about 25% of cytogenetically investigated EMC. A few cases of EMC with neuroendocrine differentiation have been reported. However, the only previously described case with genetic information also displayed the t(9;17) instead of the more common t(9;22), suggesting an association between type of primary chromosome abnormality and neuroendocrine differentiation.

Intestinal spirochetosis in eight pediatric patients from Southern Sweden.

Intestinal spirochetes in humans have been recognized for more than a century, but it is still a matter of debate whether they are just commensal organisms or whether they cause colorectal disease. Most descriptions to date are of adult patients, while reports in the pediatric literature have been scarce. In a retrospective study we found eight children with intestinal spirochetosis. The findings, clinical as well as pathological, with light- and electron microscopy, are presented. In all patients, a 3 microm-thick layer of spirochetes was visualised on the luminal aspect of the epithelial cells covering the enterocytes and part of the gland openings. In five of the eight cases an inflammatory cell reaction was seen by light microscopy and in one patient a picture suggesting intracytoplasmatically located spirochetes was seen by electron microscopy. Despite partial or complete destruction of microvilli, spirochetes were still able to adhere to the enterocyte membranes. In three children there was a clear correlation between treatment and relief of symptoms. In four there was partial improvement and in one child no change in bowel-related symptoms. We believe that intestinal spirochetes may cause colorectal disease in children. Possible pathogenic mechanisms are discussed.