Correlation of BAG-3 and heat shock protein 70 with CD30 expression in T-cell lymphomas.

T-cell lymphomas are aggressive lymphomas with decreased prognosis and resistance to therapy. BAG-3 and heat shock protein 70 (HSP70) function in chemotherapeutic resistance and cellular survival. Expression of BAG-3 has not been investigated in T cell lymphomas. We investigated fifty cases including benign, systemic and cutaneous T cell lymphomas. Benign T cells were negative for BAG-3 and HSP70 immunohistochemical staining. BAG-3 expression correlated with increased HSP70 expression in a subset of systemic T cell lymphoma cases co-expressing the CD30 antigen. Correlation between BAG-3, HSP70 and CD30 expression was not seen in cutaneous T cell lymphoma cases. However, these cases showed a significant increase in BAG-3 staining when compared to CD30 negative systemic T cell lymphoma cases. The differential protein expression profile of BAG-3 and HSP70 may indicate a specific role for these proteins and the ubiquitin-proteasome system/autophagy in T cell lymphomas which may help guide future targeted therapy.

Fluorescence enhancement from nano-gap embedded plasmonic gratings by a novel fabrication technique with HD-DVD.

We demonstrate strong electromagnetic field enhancement from nano-gaps embedded in silver gratings for visible wavelengths. These structures fabricated using a store-bought HD-DVD worth $10 and conventional micro-contact printing techniques have shown maximum fluorescence enhancement factors of up to 118 times when compared to a glass substrate under epi-fluorescent conditions. The novel fabrication procedure provides for the development of a cost-effective and facile plasmonic substrate for low-level chemical and biological detection. Electromagnetic field simulations were also performed that reveal the strong field confinement in the nano-gap region embedded in the silver grating, which is attributed to the combined effect of localized as well as propagating surface plasmons.

Plasmacytoma-like posttransplant lymphoproliferative disorder following orthotopic liver transplantation: a case report.

Posttransplant lymphoproliferative disorders (PTLDs) are among the most serious and potentially fatal complications of both stem-cell and solid-organ transplantation. Most monomorphic PTLDs are of B-cell origin and frequently associated with Epstein-Barr virus (EBV) infection in the setting of pharmacological immunosuppression posttransplantation. The majority of monomorphic PTLDs commonly resemble diffuse large B-cell or Burkitt's lymphoma; plasmacytoma-like PTLDs are very rare. We report a case of plasmacytoma-like PTLD arising in the allograft in a 66-year-old male diagnosed 2 months following an orthotopic liver transplant for alcohol-related end-stage liver disease. The liver biopsy revealed marked infiltration of atypical plasma cells with lambda light chain restriction and positivity for EBV by in situ hybridization confirming the diagnosis. Also noted was a remarkable increase of tissue eosinophils. Reduction of immunosuppression led to improvement in his clinical condition, and also resolution of the hepatic lesions and abdominal lymphadenopathy noted on imaging studies. While a few cases of plasmacytoma-like PTLDs have been described in literature, to our knowledge, this is the first reported case of early onset plasmacytoma-like PTLD in a liver transplant recipient occurring in the allograft with associated lymphadenopathy having distinct histopathologic features including tissue eosinophilia. Timely recognition of such an entity is critical in order to initiate early and appropriate intervention.

Reactive nodular hyperplasia mimicking malignant lymphoma in donor liver allograft.

The transmission of malignancy from donor to recipient can have devastating outcomes. Therefore, careful examination of the thoracic cavity, abdominal organs, and lymphoid tissue is important. In this report, we have described a case of a healthy 37-year-old donor with no significant past medical history who was found to have a nodule in the liver allograft during the examination at the back table. The frozen section revealed atypical lymphoid hyperplasia. Further workup revealed a rare benign lesion in the liver known as reactive lymphoid hyperplasia. Unfortunately, the liver allograft had to be discarded since low-grade lymphoma could not be excluded at the time of transplantation.

[Diagnostic and interventional endoscopy in gastroenterology : from high-resolution chips and procedures for endoscopic resection to NOTES]. / Diagnostische und interventionelle Endoskopie in der Gastroenterologie : Von "High-resolution-Chips" über endoskopische Resektionsverfahren zu NOTES.

In the past 10 years endoscopic diagnostics has benefited from technologies such as big chips, high-definition television (HDTV) and narrow band imaging (NBI). Video capsule endoscopy and double balloon enteroscopy have facilitated visualization of the entire small bowel. A number of studies on mucosal Barrett's and gastric cancers could prove that endoscopic mucosal resection (EMR) is oncologically equivalent to surgical resection when certain criteria are respected. However, EMR is less invasive and carries a substantially lower complication risk and mortality compared to surgery. Endoscopic submucosal dissection (ESD) facilitates en bloc resection with thorough histopathologic evaluation of the specimen, e.g. for mucosal lesions in the stomach and rectum. Endosonography (EUS) guided transgastric necrosectomy using a flexible gastroscope has set a milestone in the treatment of infected pancreatic necroses and has replaced open surgery in many centers. Natural orifice transluminal endoscopic surgery (NOTES) uses natural body openings as minimally invasive access to the abdomen and mediastinum. Interventional GI endoscopists and minimally invasive surgeons have profited from these innovations in micromechanics and microelectronics.

Reduction of miss rates of colonic adenomas by zoom chromoendoscopy.

BACKGROUND AND AIMS: The aim of this study was to determine the detection rate of polyps using zoom chromoendoscopy (ZE) compared with standard video colonoscopy. PATIENTS AND METHODS: End-to-end colonoscopies were performed in 50 patients by two different endoscopists blinded for each other's results. Lesions detected during initial standard colonoscopy (C1) were biopsied or removed by snare resection. The second colonoscopy (C2) was done with a zoom colonoscope spraying the whole colon with indigocarmine (0.4%). In addition, detected mucosal lesions were documented prior to ZE and then classified according to the pit pattern classification before biopsy or removal. The retrieval time for each procedure was determined. RESULTS: The average retrieval time for C1 was 13+/-9 min (9-24) and 28+/-11 min (16-38, p<0.05) for ZE. During C1, 56 lesions were detected in 26 of 50 patients (34 hyperplastic and 22 adenomatous). During C2, 19 additional polyps were documented prior to ZE (15% tandem miss rate), and 20 further lesions were detected with ZE (21% additional polyp detection rate compared to C1 and C2 without ZE). Of the 39 additional lesions removed during C2 after ZE, 29 were hyperplastic and 10 were adenomatous. Most adenomas detected during the second investigation were found in patients in whom adenomatous polyps had already been removed during the initial colonoscopy (9 of 26 patients vs 1 of 24 patients, p<0.02). No carcinoma was detected. The pit pattern classification allowed a correct differentiation between hyperplastic and adenomatous polyps (accuracy 93%, sensitivity 90%, specificity 97%). CONCLUSION: Using zoom chromoendoscopy, the rate of detecting colonic polyps can be increased at the cost of a longer retrieval time.

Myofibrosarcoma of the adrenal gland.

Adrenal masses have varying presentations. Most commonly, adrenal masses are discovered incidentally on CT or MRI during an evaluation for an unrelated complaint. Although the majority of these are nonfunctional cortical adenomas, hormonally active tumors and adrenocortical carcinoma must also be considered in the differential diagnosis. Rarely, retroperitoneal tumors may mimic an adrenal mass. We report a case of a 49-year-old man with anemia and weight loss who was found to have a large retroperitoneal mass arising from the adrenal gland. Surgical treatment involved en bloc resection of the right kidney, adrenal gland, segments 7 and 8 of the liver, and a portion of the right hemidiaphragm. Final pathology revealed a low-grade myofibrosarcoma. We believe that this is the first case report of a myofibrosarcoma of the adrenal gland. Myofibrosarcomas are rare malignant tumors composed of myofibroblasts that arise from the deep soft tissues. These tumors have a predilection for the head and neck, trunk, or extremities. Myofibrosarcomas can be differentiated from other sarcomas by immunohistochemical staining and pathologic features. We will briefly discuss the workup of an adrenal mass and focus on the diagnosis of myofibrosarcoma.

Hepatitis C-related posttransplant plasma cell proliferative disorder with hepatitis C virus in neoplastic plasma cells: a new posttransplant disease entity?

Plasma cell proliferative disorder (PCPD) developed in two patients with actively replicating hepatitis C virus (HCV) in neoplastic plasma cells after orthotopic liver transplantation for HCV-related end-stage liver disease. PCPD was confined to the transplanted liver and was associated with monoclonal proteins in blood. Bone marrow biopsy did not show any evidence of PCPD. Epstein-Barr virus was not detected by in situ hybridization in either case. In situ hybridization for HCV RNA with sense and antisense probes in liver biopsy specimens showed signals in neoplastic plasma cells as well as in hepatocytes. We suggest that our patients had posttransplant PCPD resulting from HCV. It may represent a new posttransplant disease entity different from previously described posttransplant lymphoproliferative disorder. The findings raise intriguing questions about the role of HCV in PCPDs in patients with chronic HCV infection.

Massive amniotic fluid embolism: diagnosis aided by emergency transesophageal echocardiography.

A 36-year-old woman was hospitalized at term and in labor at 3-cm cervical dilatation. The early labor course was remarkable only for oxytocin augmentation and combined spinal-epidural analgesia. Eight hours after admission, tetanic uterine contractions ensued, followed by persistent fetal bradycardia. An emergency cesarean section was performed and a viable male infant was delivered. Intraoperatively, a placental abruption was identified, and disseminated intravascular coagulation and persistent hypotension developed despite resuscitative efforts. Transesophageal echocardiography revealed normal left ventricular contractility and gross enlargement of the right ventricle and main pulmonary trunk, consistent with acute right ventricular pressure overload and underloading of the left ventricle. Despite resuscitative efforts, the patient died three hours postoperatively. Autopsy showed extensive microvascular plugging of the pulmonary capillaries by fetal cells in all lung fields. This is a rare case of amniotic fluid embolism diagnosed in part and managed pre-mortem with transesophageal echocardiography and confirmed by autopsy findings.

Staging of colonic neoplasms by colonoscopic miniprobe ultrasonography.

BACKGROUND AND AIMS: In contrast to the situation in the upper gastrointestinal tract staging of colonic neoplasm by endoscopic ultrasonography (EUS) has not gained importance because until yet preoperative staging is without any clinical consequences. This may change with the introduction of minimally invasive surgical procedures and endoscopic resection techniques as an alternative to conventional (open) surgery. PATIENTS AND METHODS: We performed EUS with a miniprobe in 54 consecutive patients with colonic tumors who had been referred to our hospital for endoscopic resection or for laparoscopic resection of their lesions. Therefore patients with locally advanced tumors or systemic tumor spread were not included. After detection of the lesion during colonoscopy miniprobe EUS was performed with water-filling of the colonic lumen. The depth of invasion (T classification) and the local lymph node status (positive or negative) was ascertained. Lymph node-negative lesions staged as T1 underwent endoscopic resection whenever this was technically possible. In lymph node-negative T2-3 tumors laparoscopic resection was planned if they were localized at least 10 cm apart from the flexuras. All other lesions were resected by open surgery. The EUS findings were later compared with the final pathological results (pTN classification) of the resected specimen. RESULTS: In 50 patients (93%) a sufficient EUS evaluation of the colonic tumor was possible. In one patient with a tumor at the left flexura the lesion could not be completely visualized, and in three patients a sufficient water filling of the colon was impossible. The infiltration depth was correctly classified in 17 adenomas, 16 T1, 8 T2, 5 T3, and one T4-carcinoma (EUS accuracy for T staging: 94%). Two T2 and one T3 carcinoma were overstaged by EUS while no understaging was recorded. The lymph node status was correctly classified in 42/50 patients (84%), and a false-negative lymph node status was found in only 4/50 cases (8%). The overall accuracy of EUS was 80%. CONCLUSION: Miniprobe EUS is suitable and has a sufficient but not optimal accuracy for staging of colonic neoplasm. Its employment makes sense if minimally invasive resection techniques in patients with high-risk for open surgery are planned.

[Clinical value of intraductal ultrasonography for clarification of confusing ERCP results]. / Klinischer Stellenwert desintraduktalen Ultraschalls zur Klärung unklarer ERCP-Befunde.

OBJECTIVE: This study assesses the value of intraductal ultrasound (IDUS) when the findings of endoscopic retrograde cholangio-pancreatography (ERCP) are unclear. PATIENTS AND METHODS: IDUS was performed over a two-year period in cases of bile duct or pancreatic duct stenosis of unknown origin found during ERCP or if cholelithiasis was suspected but ERC was seemingly normal. Duct stenoses were classified,before and after IDUS, as benign or malignant ductal or malignant extraductal, the findings then being checked by clinical follow-up,histology or, if bile duct stones had been suspected, by instrumental bile duct exploration. RESULTS: Among 1303 ERCP investigations IDUS was attempted in 125 patients (9.6%; average age 60+/-14 years; 62 females). IDUS failed in seven patients for technical reasons (failure rate 6%). IDUS took an average time of 9+/-3 min. ERCP plus IDUS provided correct classification in 52 of 60 patients with bile duct stenosis (87%), and in 14 of 16 (88%) patients with pancreatic duct stenosis.ERCP alone correctly classified duct stenosis in 54 of 76 patients(87%), but in 66 of 76 (87%) with additional IDUS. The correct demonstration or exclusion of choledocholithiasis was obtained by IDUS in 40 of 42 patients (95%). Thus IDUS changed the diagnosis made by ERCP in 28 of 118 patients (24%). CONCLUSION: With minor expenditure of time and an acceptable failure rate, additional IDUS after ERCP increases the diagnostic accuracy in cases where ductal stenosis or bile duct stones have not been clearly demonstrated.

Chymase expressing bone marrow mast cells in mastocytosis and myelodysplastic syndromes: an immunohistochemical and morphometric study.

BACKGROUND: Two cell specific neutral proteases, tryptase and chymase, are produced by human mast cells (MC). Tryptase is constitutively expressed by all MC, whereas chymase is found only in an MC subset. Very little is known about chymase expression in MC proliferative disorders (mastocytosis). AIMS AND METHODS: Routinely processed, formalin fixed, and paraffin wax embedded bone marrow trephine biopsy specimens obtained from patients with various subtypes of mastocytosis (n = 47) and myelodysplastic syndromes (MDS; n = 28) were immunostained with antibodies against chymase and tryptase. Normal/reactive bone marrow specimens with intact haemopoiesis (n = 31) served as controls. The numbers of chymase expressing (C+) and of tryptase expressing (T+) MC were assessed morphometrically using a computer assisted video camera system. RESULTS: In normal/reactive bone marrow, the numbers of C+ MC (median, 8/mm(2); maximum, 159/mm(2)) were in the same range as those of T+ MC (median, 4/mm(2); maximum, 167/mm(2)). Because normal MC express both chymase and tryptase, these findings indicate that the common phenotype of bone marrow MC in normal/reactive states is MC(TC) (MC expressing both tryptase and chymase). In contrast, in MDS and mastocytosis, the bone marrow exhibited far more T+ MC than C+ MC in almost all cases. CONCLUSIONS: According to these findings, the predominant MC type in the bone marrow in neoplastic states such as MDS and mastocytosis is MC(T) (MC expressing only tryptase). Although the pathophysiological basis of this apparent lack of chymase expression in most neoplastic MC in mastocytosis and MC involved in MDS remains unknown, this study has produced further evidence of the superior value of antitryptase antibodies in the diagnosis of mastocytosis.

Endoscopic snare resection of large colonic polyps: how far can we go?

BACKGROUND AND AIMS: Colonoscopic polypectomy is preventing colorectal cancer. Videoendoscopy and new perendoscopic hemostasis techniques make endoscopic polypectomy of large colonic polyps an alternative to the surgical approach. This study examined whether complete snare resection of giant colonic polyps is feasible and safe and for determining how often surgery is necessary due to invasive cancer detected histologically after polypectomy. PATIENTS AND METHODS: The study included 59 consecutive patients with 68 colonic polyps larger 30 mm in diameter. Snare polypectomy was performed after an endoscopic ultrasound with a miniprobe found no sign of invasive, or, depending on the appearance of the polyp, a bleeding prophylaxis had been carried out. Acute procedural or delayed bleeding was treated endoscopically. RESULTS: Of the 68 polyps 26, mostly pedunculated were resected en bloc (38%) and histologically ensured as completely resected; 42 polyps had to be resected by piecemeal technique (62%). Piecemeal resection was performed significantly more often in sessile polyps (38/41, 93%) than in pedunculated polyps (4/27, 15%, P<0.01). Follow-up colonoscopy after 3 months showed remaining adenomatous tissue of piecemeal-resected polyps in 12 cases (28%), which were 12 resected sessile polyps (29%) and no case of resected pedunculated polyp. To achieve complete resection of sessile polyps a second procedure was necessary significantly more often than for resection of pedunculated polyps (12 cases in sessile polyps, 18% vs. no case in pedunculated polyps). Remaining adenomatous tissue was removed in all 12 cases during the first follow-up colonoscopy after 3 months, confirmed by a biopsy 6 months after the initial procedure. Overall coexisting malignancy was found in only 7 polyps (12%). Due to high-risk factors only one of them underwent secondary surgical procedure. CONCLUSION: The present study shows that endoscopic snare resection of giant colonic polyps is a safe procedure, and that secondary operative measures for managing coexisting malignancy are rarely necessary.

Agnogenic myeloid metaplasia associated with Klinefelter syndrome: a case report.

Klinefelter syndrome is the most commonly diagnosed sex chromosome disorder among males. It is usually associated with 47 chromosomes, including two Xs and one Y. The formal cytogenetic designation for Klinefelter syndrome is 47, XXY; the extra sex chromosome is due to meiotic chromosomal nondisjunction. Increased risk of various malignant diseases has been recognized among patients with different congenital chromosomal abnormalities. Since the early 1960s, numerous reports have appeared of an increased risk of malignant neoplasms among patients with Klinefelter syndrome. Evidence suggests a correlation with increased incidences of germ cell tumors and breast cancers. Whether these patients are at an increased risk of hematologic malignant disease, especially acute leukemia, is still uncertain. This report describes a patient with agnogenic myeloid metaplasia and Klinefelter syndrome, an association not previously reported.

Lack of cytogenetic abnormalities in Castleman's disease.

BACKGROUND: Castleman's disease (CD) is a distinctive type of atypical lymph node hyperplasia that is often clonal. In a previously reported series of CD, clonal populations of plasma cells were detected by immunohistology in 4 of 39 cases (10%, lambda restricted), and immunoglobulin gene rearrangements were detected by paraffin polymerase chain reaction (PCR) analysis in 10 of 37 cases (27%). Cytogenetic analysis has been used to detect clonal proliferations of plasma cells in myeloma and clonal proliferations of lymphocytes in lymphomas and has identified critical gene loci that are important in the histopathogenesis of these disorders. Cytogenetic studies have not been done on a large series of patients with CD. Thus, we reviewed the archives of our institution for cases of CD and lymphoma that had had cytogenetic analysis. METHODS: The cytogenetic and lymphoma archives of our institution (a tertiary care center) from 1985 to 1998 were reviewed for the diagnoses of CD and lymphoma. There were 21,006 lymphomas, 701 of which had cytogenetic analysis (400 abnormal). There were 162 cases of CD, 7 of which had cytogenetic analysis. The frequency of cytogenetic abnormalities in CD was compared with that in lymphoma. The sensitivity of cytogenetics for defining clonality in CD was compared with immunohistology and paraffin PCR-amplified immunoglobulin heavy-chain gene rearrangement. RESULTS: From 1985 to 1998, 162 cases of CD and 21,006 cases of lymphoma were diagnosed. Cytogenetic analysis yielded adequate numbers of metaphases for analysis of 4 cases of CD and 701 lymphomas. Cytogenetic abnormalities were not identified in CD but were identified in 400 lymphomas (57%). Although 1 of 4 cases of CD was clonal by immunohistology (lambda restricted), no immunoglobulin gene rearrangements were detected by paraffin PCR analysis. CONCLUSIONS: The frequency of cytogenetic abnormalities in lymphomas and the lack of cytogenetic abnormalities in CD suggest that cytogenetic abnormalities, as detected by conventional cytogenetic analysis, are important in the pathogenesis of lymphoma but not CD. The lack of cytogenetic abnormalities in CD supports the hypothesis that CD is an interleukin-6-driven lymphoproliferative disorder.

Prostate cancer metastasizing to the small bowel.

Although prostate cancer is one of the most commonly encountered malignancies in clinical practice, it is very unusual for prostate cancer to metastasize to the small bowel. Our search of the literature found no such cases published from 1966 to the present. We report the case of a 69-year-old man who presented for evaluation of anasarca and anorexia. He had a history of prostate cancer diagnosed 9 years before and had undergone a radical prostatectomy with subsequent radiotherapy for positive tumor margins. He developed anasarca 2 years before presentation to us. His serum albumin ranged between 1.5 and 2.5 g/dL. Upper endoscopy was performed for possible protein-losing enteropathy and the appearance of gastric and duodenal mucosa was found to be normal. Random small bowel biopsies revealed submucosal infiltrating adenocarcinoma with positive prostate-specific antigen stains consistent with the diagnosis of prostate cancer metastatic to the small bowel. This is a rare presentation of metastatic prostate cancer. Even though prostate cancer is the most commonly diagnosed cancer in American men, antemortem diagnosis of small bowel metastasis has not been reported. In patients with unexplained anasarca, especially with a history of malignancy, an upper endoscopy with small bowel biopsy may be useful in establishing the diagnosis.

Primary lymph node plasmacytomas (plasmacytic lymphomas).

To determine whether primary lymph node plasmacytoma (PLNP) is a distinct entity among other types of plasma cell neoplasia, we analyzed a large series of PLNPs from 2 large lymphoma registries to compare histologic, immunophenotypic, and clinical features of PLNPs, nonnodal extramedullary plasmacytomas, and multiple myeloma. Twenty-five PLNPs (clinical data on 15 cases) were compared with 10 non-lymph node plasmacytomas and 51 cases of multiple myeloma; 36 cases of reactive plasmacytoses were used as controls. The histologic features of PLNP and other extramedullary plasmacytomas were similar. The histologic features of PLNPs were more immature than those of reactive plasmacytoses and less immature than in multiple myeloma. The immunophenotype of PLNPs significantly differed from that of reactive plasmacytoses, other extramedullary plasmacytomas, and multiple myeloma. PLNPs did not progress to multiple myeloma, unlike other extramedullary plasmacytomas, even though survival in PLNPs and other extramedullary plasmacytomas was similar. Our findings suggest that PLNPs may be distinct from other plasma cell dyscrasias.

Solitary pelvic nodule: diagnosis of metastatic prostate cancer by endoscopic ultrasound-guided, fine-needle aspiration.

Prostate cancer manifesting as an isolated perirectal mass is a rare occurrence. The following is a report of a single pelvic nodule that was determined to be metastatic prostate cancer by endoscopic ultrasound-guided, fine-needle aspiration.