Peripheral T-cell lymphoma that developed during the follow-up of IgG4-related disease

IgG4-related disease is a recently recognized fibroinflammatory disorder characterized by extensive IgG4-positive plasma cell and lymphocyte infiltration of various organs. The pancreatic manifestation of IgG4-related disease is called autoimmune pancreatitis (AIP), in which autoimmune mechanisms are likely involved. On the other hand, some autoimmune and chronic inflammatory disorders, such as Sj?gren's syndrome and rheumatoid arthritis, are associated with increased risks of non-Hodgkin lymphoma (NHL). There have been a few reports of cases with IgG4-related disease that had subsequently developed NHL, however, all of them suffered from B-cell lymphoma. We describe the first case of NHL, compatible with a subtype of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), which arose in IgG4-related sclerosing cholangitis. As patients with IgG4-related disease may be at an increased risk of developing NHL, such presentation during the follow-up of IgG4-related disease should be carefully scrutinized to exclude NHL.     

High-resolution computed tomography features of pulmonary chronic graft-versus-host disease following hematopoietic stem cell transplantation: histopathological correlation

Purpose  

The purposes of this study were to evaluate the development pattern in patients with multiple episodes of chronic graft-versus-host disease (cGVHD) and to analyze the computed tomography (CT) appearances of the pulmonary parenchymal injury and its relation to treatment response.     

Palisade vessels as a new histologic marker of esophageal origin in ER specimens from columnar-lined esophagus

It is difficult for surgical pathologists to determine the origin of tissues in samples taken from the columnar-lined esophagus (CLE) or stomach by biopsy or endoscopic resection (ER) on the basis of histologic examination alone. We examined histopathologically a single section (5 to 22 mm in size; mean, 12 mm) from each of 66 cases of CLE (36 short segments, 30 long segments) from German patients with reference to 3 histologic markers of esophageal origin: esophageal glands proper and/or ducts, squamous islands, and double muscularis mucosae, all of which had been reported previously, and palisade vessels as a new histologic parameter as well. Palisade vessels were defined histologically as veins >100 μm in size in and above the original muscularis mucosae. Esophageal glands proper and/or ducts, squamous islands, and double muscularis mucosae were seen in 33%, 18%, and 71% of the specimens, respectively. Palisade longitudinal vessels were observed in 78% and 63% of specimens of short-segment and long-segment CLE, respectively. Palisade vessels were never seen in ER specimens from the stomach or in the middle esophagus and stomach among control autopsy specimens. At least 1 of these 4 markers was seen in 88% of the sections. Therefore, ER specimens were confirmed to originate from CLE in 88% of single histologic sections of CLE on the basis of histologic examination alone.     

A practical approach estimating etiologic agents using real-time PCR in pediatric inpatients with community-acquired pneumonia

To evaluate pathogens in pediatric inpatients with community-acquired pneumonia (CAP), an Acute Respiratory Diseases Study Group organized by ten Japanese medical institutions devised a rapid, reliable process based on real-time PCR results in nasopharyngeal swab samples plus admission blood test results. From April 2008 to April 2009, we enrolled 903 children with CAP based on chest radiographs and clinical findings who were hospitalized within 5 days of onset. Comprehensive real-time PCR was used to detect 6 bacteria and 11 respiratory viruses. The swab specimens also were used for bacterial cultures. After initial determination of presence or absence of viral and mycoplasmal infections, significant bacterial contributions were defined by bacterial identification, clinical efficacy of antimicrobial agent, and reference to blood test results. Children were stratified by age: below 1 year, 1 year, 2–5 years, or at least 6 years old. Among patients studied, 34.4 % were diagnosed with viral infection; 21.8 %, bacterial infection; 17.5 %, viral/bacterial co-infection; 5.9 %, mycoplasmal infection; 0.3 %, mycoplasmal/bacterial co-infection; and 1.7 %, viral/mycoplasmal co-infection. The remaining 18.4 % had unknown pathogens. Purely viral infection was suggested mainly in infants younger than 1 year; mycoplasmal infection typically occurred in children at least 6 years old. Our results suggest usefulness of real-time PCR for nasopharyngeal samples together with blood tests in estimating etiologic agents in clinical settings.     

Close correlation between chronic sclerosing sialadenitis and immunoglobulin G4

In four patients with chronic sclerosing sialadenitis, serum immunoglobulin G4 concentration was markedly increased and abundant infiltration of immunoglobulin G4-positive plasma cells was observed in the salivary glands. Autoimmune pancreatitis occurred in the two patients during follow up. Chronic sclerosing sialadenitis and autoimmune pancreatitis would appear to show essentially the same pathophysiological mechanism. Measurement of serum immunoglobulin G4 concentration is useful in differentiating chronic sclerosing sialadenitis from neoplasia.     

MEN1 gene mutations in sporadic neuroendocrine tumors of foregut derivation

Foregut-derived neuroendocrine (NE) tumors occur sporadically or in association with multiple endocrine neoplasia type 1 (MEN1) syndrome. Thirty-nine sporadic NE tumors of foregut derivation (six thymic, 21 bronchial, three gastric, and nine pancreatic tumors) as well as two hindgut-derived rectal carcinoids for somatic MEN1 gene mutation were analyzed by direct sequencing analysis. Five tumors showed mutations: nonsense mutations (Q393X and R98X) in thymic and pancreatic NE tumors, respectively, a 4 b.p. deletion (357del4) in a gastric NE carcinoma, and missense mutations (D172Y and S178Y) in pancreatic NE tumors. No mutation was identified in pulmonary or rectal NE tumors. In a patient with a pancreatic NE tumor (D172Y), the corresponding germline DNA showed the same mutation, suggesting that sporadic MEN1 syndrome was masked in this case. Somatic MEN1 gene mutations and deletions may play a crucial role in the tumorigenesis of a subset of foregut-derived NE tumors. Sporadic MEN1 syndrome may occur as a sporadic NE tumor of the pancreas.     

Intracranial meningioma masquerading as a primary pleuropulmonary tumor

Extracranial metastasis was found in an intracranial meningioma with low proliferative potential before the detection of the primary tumor. Pleuropulmonary tumors were incidentally detected on chest X-ray in an asymptomatic 25 year old female. Excised tumors of the right pleura and lung showed histological features similar to meningotheliomatous meningioma, which led to the discovery and excision of the intracranial tumor. Both tumors showed the same histologic pattern: meningotheliomatous meningioma with low mitotic activity. The proliferative component, determined by the monoclonal antibody Ki-67, was further evaluated in the primary tumor and the metastases of the present case, as well as in 12 other intracranial menin-giomas. Ki-67 positive ratios at the primary and metastatic sites of the present case were 1.2 and 1.1%, respectively, which is as low as other benign meningiomas, and this suggests that factors other than the proliferative potential is responsible for extracranial metastasis of meningioma.     

Gastrointestinal stromal tumors and KIT-positive mesenchymal cells in the omentum

Gastrointestinal stromal tumor (GIST) is currently considered to be derived from the interstitial cells of Cajal (ICC). To test the hypothesis that omental mesenchymal tumor is also a type of GIST, we evaluated the expression of specific molecules in GIST, and c-kit gene mutation in omental mesenchymal tumors, and we identified a possible counterpart of ICC in the omentum. Immunohistochemically, all of the omental mesenchymal tumors (n = 5) were positive for both KIT and CD34, and three of the five tumors were also positive for an embryonic form of smooth-muscle myosin heavy chain (SMemb). Polymerase chain reaction-single-strand conformational polymorphism analysis (PCR-SSCP) and direct sequencing revealed mutations in c-kit gene exon 11 in all five tumors. As for the ICC counterparts in the omentum, there were some KIT-positive mesenchymal cells resembling ICC at the surface of the omentum. Double fluorescence immunostaining, using anti-KIT polyclonal antibodies and monoclonal antibodies against other molecules, demonstrated that KIT-, CD34- and SMemb-positive cells were present just beneath the mesothelial cells of the omentum. These results show that omental mesenchymal tumor corresponds to GIST of the omentum, and that KIT-positive bipolar mesenchymal cells may be a counterpart of ICC in the gastrointestinal tract. Identification of a new type of KIT-positive mesenchymal cell in the omentum may lead to the discovery of a new physiological role for this organ.     

Molecular analysis of the alpha-N-acetylglucosaminidase gene in seven Japanese patients from six unrelated families with mucopolysaccharidosis IIIB (Sanfilippo type B), including two novel mutations

 Molecular analysis of the α-N-acetylglucosaminidase gene in seven Japanese patients with Sanfilippo syndrome type B from six unrelated families was carried out, and six disease-causing mutations were found. The parents of Patient 2 had a consanguinous marriage, but other families did not have any record of consanguinity. Two families were from Okinawa Island, where more patients with Sanfilippo syndrome were found than in other areas in Japan. Patients 1 and 6 showed the most severe phenotype with rapid progression. Patients 2, 5, and 7 were moderate. Patients 3 and 4 (sib cases) showed an attenuated form compared with other patients. Patients 1, 2, and 6 were homozygous for R482W, R565W, and R565P, respectively. Patients 3 and 4 were compound heterozygous for F314L and R565P. Patient 5 had delTG2171–2172 in exon 6 in one allele, and the other allele was unknown. Patient 7 was compound heterozygous for V241M and R482W. The family of Patients 3 and 4 and that of Patient 6 are unrelated, although both families are from Okinawa Island, and the patients have the same mutation, R565P; thus, R565P might be a common mutation in the Okinawa district. F314L and V241M are novel mutations. Received: March 27, 2002 / Accepted: June 9, 2002