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Supplemental digital content is available in the text., Objectives The aim of this study was to identify differentially expressed proteins among various stages of pancreatic ductal adenocarcinoma (PDAC) by shotgun proteomics using nano-liquid chromatography coupled tandem mass spectrometry and stable isotope dimethyl labeling. Methods Differentially expressed proteins were identified and compared based on the mass spectral differences of their isotope-labeled peptide fragments generated from protease digestion. Results Our quantitative proteomic analysis of the differentially expressed proteins with stable isotope (deuterium/hydrogen ratio, ≥2) identified a total of 353 proteins, with at least 5 protein biomarker proteins that were significantly differentially expressed between cancer and normal mice by at least a 2-fold alteration. These 5 protein biomarker candidates include α-enolase, α-catenin, 14-3-3 β, VDAC1, and calmodulin with high confidence levels. The expression levels were also found to be in agreement with those examined by Western blot and histochemical staining. Conclusions The systematic decrease or increase of these identified marker proteins may potentially reflect the morphological aberrations and diseased stages of pancreas carcinoma throughout progressive developments leading to PDAC. The results would form a firm foundation for future work concerning validation and clinical translation of some identified biomarkers into targeted diagnosis and therapy for various stages of PDAC.

Although hypersensitivity reaction to insulin was supposed to be less-frequent with current insulin analogue, case reports with different types of allergic reactions to insulin analogue were still reported. The most common form is type I hypersensitivity reaction with IgE-mediated. Besides, type III (IgG and IgM-mediated) and type IV (T-cell mediated delayed reaction) hypersensitivity reactions were also reported. Here we presented a long-standing type 2 diabetes with insulin requirements with hypersensitivity reactions to insulin actrapid, insulin aspart, insulin glargine, insulin detemir, and biphasic insulin aspart 30. Insulin desensitization was performed as initial management but failed as skin biopsy with immunohistochemical staining proved type IV hypersensitivity reaction. We continued with the next treatment approach using subcutaneous injection with the mixture of biphasic insulin aspart 30 and dexamethasone to alleviate allergy, and the result was successful with steroid-free biphasic insulin aspart 30 injection eight months later. Besides, the treatment effect had lasted after ten years even with switched type of insulin analogue from biphasic insulin aspart 30 to insulin glargine and insulin aspart. The case report demonstrated a good example of how clinicians deal with the rare but important questions of hypersensitivity reactions to insulin analogue. Keywords: Insulin, Hypersensitivity, Glucocorticoids

Objective. Diagnosing melanocytic lesions is among the most challenging problems in the practice of pathology. The difficulty of physically masking melanin pigment and the similarity of its color to commonly used chromogens often complicate examination of the cytomorphology and immunohistochemical staining results for tumor cells. Melanin bleach can be very helpful for histopathological diagnosis of heavily pigmented melanocytic lesions. Although various depigmentation methods have been reported, no standardized methods have been developed. This study developed a fully automated platform that incorporates hydrogen peroxide–based melanin depigmentation in an automated immunohistochemical analysis. Methods and Materials. The utility of the method was tested in 1 cell block of malignant melanoma cells in pleural effusion, 10 ocular melanoma tissue samples, and 10 cutaneous melanoma tissue samples. Our results demonstrated that the proposed method, which can be performed in only 3 hours, effectively preserves cell cytomorphology and immunoreactivity. Results. The method is particularly effective for removing melanin pigment to facilitate histopathological examination of cytomorphology and for obtaining an unmasked tissue section for immunohistochemical analysis.

Introduction Pulmonary infiltration and pleural effusion caused by permeability syndrome are the hallmark of pulmonary manifestation of dengue cases. Objective and Methods We report a 95-year-old chronic obstructive pulmonary disease case having dengue shock syndrome. Chest X-ray examination revealed diffuse lung infiltration. However, bilateral pneumotoceles were unexpectedly found in computed tomography (CT) images. Dengue virus type 2 infection was confirmed by virus culture, serology and reverse transcriptase-polymerase chain reaction. Profound shock with bilateral lung infiltration developed rapidly in 2 days with supportive care and empirical ampicillin/ sulbactam. Bronchoscopy revealed a whitish plaque over bilateral upper bronchi. Biopsy via bronchoscopy revealed moulds with vascular invasion. Culture of bronchial alveolar lavage yielded Aspergillus flavus. The patient died despite amphotericin B treatment, which was started since finding the whitish plaque with bronchoscopy examination. Results and Conclusion Besides to considering capillary leakage syndrome, our case report and literature review alert clinicians that CT and bronchoscopy may help to identify the true pathogen though all cases with concurrent dengue and Aspergillus infections had fatal outcomes.

Diagnosing melanocytic lesions is among the most challenging problems in the practice of pathology. The difficulty of physically masking melanin pigment and the similarity of its color to commonly used chromogens often complicate examination of the cytomorphology and immunohistochemical staining results for tumor cells. Melanin bleach can be very helpful for histopathological diagnosis of heavily pigmented melanocytic lesions. Although various depigmentation methods have been reported, no standardized methods have been developed. This study developed a fully automated platform that incorporates hydrogen peroxide-based melanin depigmentation in an automated immunohistochemical analysis. The utility of the method was tested in one cell block of malignant melanoma cells in pleural effusion, ten ocular melanoma tissue samples, and ten cutaneous melanoma tissue samples. Our results demonstrated that the proposed method, which can be performed in only 3 hours, effectively preserves cell cytomorphology and immunoreactivity. The method is particularly effective for removing melanin pigment to facilitate histopathological examination of cytomorphology and for obtaining an unmasked tissue section for immunohistochemical analysis.

Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, is widely used to treat diabetes. However, its effect on pulmonary arterial hypertension (PAH) is unknown. In this study, we investigated its effects on rats with monocrotaline (MCT)-induced PAH and mechanisms on rat pulmonary artery smooth muscle cells (PASMCs). Liraglutide was investigated for both prevention and treatment of MCT-induced PAH. The hemodynamic and body weight changes, right heart hypertrophy, lung morphology, immune-reactivity of endothelial nitric oxide synthase (eNOS), endothelin-1 and cyclic guanosine monophosphate (cGMP) levels, protein expressions of eNOS, soluble guanylyl cyclase (sGCα), protein kinase G (PKG) and Rho kinase (ROCK) II pathway were measured in both in vivo and in vitro. Cell migration and cell cycle were also determined. Liraglutide both prevented and reversed MCT-induced PAH, right ventricle hypertrophy and pulmonary vascular wall remodeling. Protein expression of ROCK II was increased while eNOS, sGC and PKG were decreased. Pretreatment with liraglutide inhibited platelet-derived growth factor (PDGF)-BB stimulated PASMCs migration, which were associated with cell-cycle arrest at G0/G1 phase. Liraglutide may have both preventive and therapeutic effects on MCT-induced PAH, through the eNOS/sGC/PKG and Rho kinase pathways. Thus, liraglutide may have a therapeutic role in pulmonary vascular remodelling.

In vivo 1 H MRS is a noninvasive imaging technique for the identification of malignancy. Musculoskeletal lesions vary in their composition, causing field inhomogeneity and magnetic susceptibility effects which may be technical and diagnostic challenges for MRS. This study investigated the factors that affect diagnostic accuracy in the use of MRS for the characterization of musculoskeletal neoplasms. During a 7-year period, 210 consecutive patients with musculoskeletal lesions larger than 1.5cm in diameter were examined. MRS of a single-voxel point-resolved spectroscopy sequence with TE=135ms was undertaken using a 1.5-T scanner. Lesions with a choline signal-to-noise ratio larger than 3.0 were considered to be malignant tumors. The diagnostic accuracy was calculated for all lesions and for subgroups on the basis of lesion type (bone and soft tissue), lesion composition (mixed and solid nonsclerotic), lesion size (≤4, >4–10 and >10cm), MR scanner (MR scanner 1 and 2) and selected voxel size (≤3, >3– 8a nd>8cm 3 ). Multivariate logistic regressions were performed to estimate the associations between each factor and diagnostic accuracy. The diagnostic accuracy was 73.3% for all lesions. The accuracy was 54.4% for mixed lesions and 80.4% for solid nonsclerotic lesions (p 4–10cm (p=0.04) and 63.6% for lesions of >10cm (p=0.007)]. There was no difference in diagnostic accuracy for bone versus soft-tissue lesions or as a function of MR scanner or voxel size. By the use of multivariate logistic regression, a solid nonsclerotic lesion was 3.15 times (95% confidence interval, 1.59–6.27) more likely than a mixed lesion to have a diagnosis (p=0.001). MRS can be used to characterize musculoskeletal lesions, particularly solid nonsclerotic lesions. Copyright # 2011 John Wiley & Sons, Ltd.

Elective abortion complicated by bilateral renal cortical necrosis (BRCN) is not common in a developed country. We reported a patient having anuric acute renal failure after elective abortion. Initial laboratory studies implied thrombotic thrombocytopenic purpura/Hemolytic uremic syndrome, but plasma exchange was not prescribed since magnetic resonance imaging study suggested BRCN soon after. The patient was treated as septic abortion and reached partial renal recovery after antibiotic treatment and short-term hemodialysis. Early diagnosis of BRCN is essential not only for prognosis prediction but also for treatment decision. We suggest that any anuric patient in suspicion of BRCN should receive MRI study as soon as possible.

Squamous cell carcinoma (SCC) of the renal pelvis is a rare cancer with a extremely poor prognosis. Its incidence is only 0.5–1% of all urothelial cancers. In most patients’ cases, SCC of the renal pelvis is associated with long-term renal calculi. We report a case of renal pelvic SCC patient developing disseminated metastatic disease rapidly. There are still no standard treatments for SCC of the renal pelvis. Some literature suggests the primary treatment of renal pelvic SCC is nephrectomy. Adjuvant chemotherapy or radiotherapy, though presents no concrete evidence of survival benefits, may still play a role for the control of local symptoms. New treatment modalities of patients with renal pelvic SCC and efforts at improving the accuracy of diagnosis at presentation are warranted.

A diagnosis of sporadic medullary thyroid carcinoma (MTC) is complicated. On first diagnosis it may present with distant metastasis. There has been inconsistency regarding metastatic MTC tissue expression of calcitonin, its tumor marker. Adding to the difficulty is the fact that the radiographic pattern of pulmonary metastasis from MTC may vary substantially among patients. Herein is reported the case of a 73-year-old man who presented with two ill-defined pulmonary opacities, clinically resembling primary lung carcinoma. MTC was diagnosed on histopathology of tissue obtained from a total thyroidectomy. The pulmonary biopsy specimens were confirmed to be MTC metastasis on positive immunohistochemical staining of chromogranin-A and synaptophysin, even though only a few cells were stained for calcitonin. To the authors' knowledge this is the first reported case of MTC presenting initially as complex pulmonary metastasis with weakened expression of calcitonin in the metastatic lesion.

Eccrine porocarcinoma (EP) is a rare skin malignant lesion representing 0.005–0.01% of all cutaneous tumors. It is a tumor that most commonly present in elderly people aged over 60 years. Approximately 250 cases of EP have been reported since this disease was first described in 1963. However, only three cases occurring specifically on the ear (including the current case) have been documented in the literature to date. Based on the rarity of EP of the ear, we present this 78-year-old man with EP on the right ear lobule, which was diagnosed accidentally during the management of other unrelated problems. The etiology, diagnosis, treatment and prognosis of this disease are discussed, with a brief review of the literature in this report.

Objective: To describe a case of possible cocaine-related vasculitis resulting in gangrene of the scrotum and review the literature on cocaine-related vascular complications. Case Summary: A 22-year-old male presented with fever, painful swelling of the right scrotum, and a blackened ulcerated lesion on the right scrotum 3 hours after smoking crack cocaine. Blood and urine cultures and serologic tests were negative, and the D-dimer level was normal. Echocardiogram showed no evidence of vegetation and results of a chest X-ray were normal. Despite treatment for presumptive orchitis with intravenous levofloxacin 750 mg/day, the ulcerated lesion of the right scrotum progressed the next day. The patient received debridement of the necrotic tissue and pathology revealed some degenerated vessels with fibrinoid deposits and inflammatory infiltrates, suggestive of vasculitis. No further tenderness and swelling of the scrotum occurred and the patient was discharged after 10 days. When he returned for follow-up, the wound had healed completely. Discussions: Cocaine-related vascular complications, including ischemic stroke, myocardial infarction, and peripheral occlusive disease, all of which have various possible mechanisms, are of clinical importance. Vasculitis is one of the mechanisms of vascular complications associated with cocaine use. According to the Naranjo probability scale, cocaine was the possible causative agent of the patient's vasculitis, which led to scrotum gangrene. To our knowledge, this is the first report in the literature of scrotum gangrene developing after crack cocaine was smoked. Conclusions: This case report describes a rare occurrence of gangrene of the scrotum associated with cocaine smoking, which is consistent with cocaine's potent vasoconstrictive activity. Cocaine abuse has the potential to cause clinically significant ischemic events anywhere in the body, independent of the method of administration.

Pilomatricoma is an asymptomatic, slowly growing, benign skin tumor that is typically located in the regions of head and neck. We present 1 case of pilomatricoma studied with dynamic magnetic resonance imaging and bone scintigraphy. Our case revealed late enhancement in the dynamic magnetic resonance imaging study that is a common pattern more in a benign soft tissue tumor and caused dramatic uptake in the bone scintigraphy. These findings are not ever reported in published articles. Surgical excision of the lesions was performed, and the pathological evaluation revealed a pilomatricoma.

Hereditary hemochromatosis (HH) is very rare in Asia. Here, we describe a Taiwanese woman presenting with fully developed characteristics of HH including bronze skin, DM, decreased MRI T2 signal intensity over liver and pituitary gland. Biochemistry of iron profile indicated a severe status of iron overload by serum iron: 194 microg/dL, serum ferritin: 6640 microg/L, transferrin saturation: 92.8%. By measuring the hepatic iron index 8.48 (>1.9) of her liver biopsy tissue, the diagnosis of HH was established. Diagnosis of non-HFE HH was carried out since the whole HFE genome was sequenced but failed to localize any genetic alterations. The whole genome of transferrin receptor 2 (TfR2) was sequenced and a novel mutation of 13528 G-->A (Arg 481 His) in exon 11 was detected. Therefore, type 3 hemochromatosis was confirmed. The distinct clinical features, extremely high iron index and impressive iron staining in her liver biopsy tissue may represent an aggravated iron deposition in the liver caused by this novel mutation. Our finding implicates functional importance of histidine in exchange of arginine at amino acid 481 of transferrin receptor 2 in iron homeostasis. This case reminds physicians in Asia to keep in mind that hemochromatosis could be a rare cause of DM.

Because there are no standardized radiologic and histologic criteria, the differential diagnosis of malignant peripheral nerve sheath tumors (MPNSTs) from other spindle cell neoplasms poses great challenges for pathologists. Because early diagnosis of MPNSTs arising from benign peripheral nerve sheath tumors (BPNSTs) means a better prognosis, many immunohistochemical and molecular studies have recently emerged. Nevertheless, no gold standard diagnostic criterion is to be found in the literature. For example, S-100 protein is widely used in the diagnosis of MPNST. Other promising ancillary markers are p53 and Ki-67; however, the staining patterns and possible mechanisms of these markers are seldom mentioned in the literature. These evoke our interest. Only six cases diagnosed as MPNST were retrieved from the archives of the Department of Pathology, Kaohsiung Medical University Chung-Ho Memorial Hospital between 1988 and September 2005. Clinical files were available for three of them, and we found nuances in the immunohistochemistry from these previous reports. Here, we present these rare sarcomas and review the literature.

Primary mediastinal germ-cell tumors (GCTs) without gonadal involvement are rare and can be divided into benign mature teratoma and malignant seminoma or nonseminoma. We describe our experience of malignant mediastinal GCTs and compare the presentations and outcome with those of benign teratomas. Four malignant GCTs (1 seminoma, 1 choriocarcinoma, and 2 yolk-sac tumors) have been treated in our hospital. All patients were men with obvious symptoms before diagnosis. The patient with seminoma was treated with surgery and radiation, while those with nonseminoma tumors were treated with chemotherapy and/or surgery. Two patients died, one with extended pulmonary metastasis and the other with relapsed disease and high levels of tumor markers. Compared with the nine cases of benign teratomas, the four malignant GCTs showed overwhelming male dominance, advanced symptoms at presentation, and poor outcome. These cases highlight the important role of disease staging and tumor-marker levels in malignant GCTs, and suggest that new treatment strategies for malignant GCTs await further investigation.

We present a case of polypoid sinusitis with maxillary sinus antrolith, which is composed of Aspergillus species. Unlike most muddy or necrotic fungal balls, this first reported fungal antrolith is solid and extremely hard. Aspergillus served as a central fungal nidus associated with long-standing sinusitis, and poor sinus drainage could be a possible pathophysiology for the formation of a sinus stone. Aspergillosis infection should be considered in the differential diagnosis of a radiopaque paranasal sinus lesion. The endoscopic sinus surgery can be a reliable and minimally invasive method not only for the removal of the stone, but also for the restoration of ventilation and drainage of the diseased sinus.

Heterotopic salivary gland tissue (HSGT) in the lower neck is an unusual developmental anomaly with characteristic clinical and microscopic findings. The exact embryogenesis remains unclear. This rare entity must be considered in the differential diagnosis of neck mass with fistula. We present a typical HSGT totally removed using the stepladder excision technique and showing an internal fistula. Interpretation of this case from the anatomical and pathological points of view, we support the argument that the embryogenesis of HSGT is more probably related to ectodermal heteroplasia of the precervical sinus of His and further conclude that an association with branchial cleft sinus may exist and cannot be seen as an exclusion criteria for diagnosis of HSGT. Due to possible but infrequent neoplastic transformation, it is important to check HSGT in every encountered cervical anomaly related to any branchial apparatus derived lesion.

Solitary fibrous tumors (SFTs) are uncommon, and most are found in the pleura. Extrapleural SFTs are rare and have been found in the lung, pericardium, mediastinum, soft tissue of any site, and upper respiratory tract. SFTs of the central nervous system (CNS) are very rare. The biologic features are unknown and remain poorly understood from a clinical standpoint. Most neurosurgeons do not believe that SFTs can present as primary CNS neoplasms. Most SFTs are clinically benign and indolent, and recurrences after surgical excision are scarce. Because malignant transformation or metastasis has been reported, all SFTs should be treated as having malignant potential. Long-term follow-up is recommended. We report two cases, so that surgeons may recognize that this is an entity different from other spindle-cell CNS tumors.

The case of an ectopic pancreatic mass at the umbilicus in an 8-day-old male neonate is reported, the youngest patient with this condition ever reported in an English-language journal. The patient was healthy except for a protruding mass with intermittent mucous discharge at the base of the umbilical stump. Surgical intervention was performed under the impression of the umbilical mass. Pathology diagnosed an ectopic pancreas with acute hemorrhage. To the best of our knowledge, only one case of ectopic pancreas presenting as an umbilical mass with intermittent mucous discharge has previously been reported.

An 81-year-old male with early-stage laryngeal carcinoma had been treated with 60 Gy curative radiotherapy. He complained of a sore throat, foul odor in the mouth, progressive dyspnea, and fever 2 months after the completion of radiotherapy. Direct laryngoscopy revealed narrowing of the glottis with diffuse ulcerative necrotic tissue. Biopsies at multiple sites and pathology revealed intense coagulation necrosis with complete denudation of covering epithelium without any malignancy. Since laryngeal radionecrosis was suspected, the patient received hyperbaric oxygen (HBO) therapy 40 times for 1 hour of 100% O 2 at 2 atm absolute pressure. His clinical symptoms gradually improved and repeated endolaryngeal biopsies were undertaken near the end of HBO therapy and again 6 months later. The patient's larynx healed completely with diffuse fibrosis and no malignant cells were found on pathology. Radionecrosis must be differentiated from cancer recurrence following curative radiotherapy for early laryngeal cancer. HBO therapy could be a useful treatment adjunct for laryngeal radionecrosis.

Gallbladder and bile duct carcinomas belong to the family of biliary tract tumors, but they demonstrate different clinical behavior. We evaluated a series of biliary tract carcinomas to determine whether they also had genotypic differences by analysis of the tumor suppressor genes DPC4 and p53. Twenty-one gallbladder cancers, 20 intrahepatic bile duct carcinomas, and 10 extrahepatic bile duct carcinomas were retrieved from the surgical pathology files of Kaohsiung Medical University Hospital. Sections were immunostained with monoclonal antibodies to the DPC4 and P53 proteins. Statistical differences between gallbladder cancer and bile duct carcinomas were determined using chi2 analysis or the Fisher's exact test, when appropriate. Two of the 21 gallbladder cancers (9.5%), 7 of the 20 intrahepatic bile duct carcinomas (35%), and five of the 10 extrahepatic bile duct carcinomas (50%) were negatively labeled for DPC4. The differences were significant between gallbladder carcinoma and both intrahepatic bile duct carcinomas (p = 0.023) and extrahepatic bile duct carcinomas (p = 0.012). A higher frequency of P53 overexpression was found in gallbladder cancers (61.9%) than in intrahepatic bile duct carcinomas (26.3%) (p = 0.024). This study suggests that the DPC4 gene may play a limited role in gallbladder carcinoma; however, p53 gene mutation is more frequently found in gallbladder cancers. In contrast, DPC4 deletion may be more common in bile duct carcinomas, especially in those arising from the extrahepatic bile duct. These findings support the concept that gallbladder and bile duct carcinomas are different tumors with differing etiologies and tumorigenesis.

To determine if in vivo detection of choline by using hydrogen 1 (1H) magnetic resonance (MR) spectroscopy with dynamic contrast material-enhanced MR imaging can help differentiate between benign and malignant musculoskeletal tumors.MR imaging was performed in 36 consecutive patients with bone and soft-tissue tumors larger than 1.5 cm in diameter. Examinations were performed at 1.5 T with a surface coil appropriate for the location of the lesions. Single-voxel 1H MR spectroscopy was performed by using a point-resolved spectroscopic sequence with echo times of 40, 135, and 270 msec. The volume of interest within lesions was positioned on the areas of early enhancement (8 seconds after arterial enhancement) according to the findings of dynamic contrast-enhanced MR imaging with subtraction. The criterion for determining whether choline was present in a lesion was a clearly identifiable peak at 3.2 ppm in at least two of the three spectra acquired at echo times. MR spectroscopic results and histopathologic findings were determined in blinded fashion and compared with kappa statistics. P.001 was considered to indicate a significant difference.Choline was detected in 18 of 19 patients with malignant tumors and in three of 17 patients with benign lesions. The three benign lesions included one perineurioma, one giant cell tumor, and one abscess. Choline was not detected in 14 patients with benign lesions nor in one patient with a densely ossifying low-grade parosteal osteosarcoma. In vivo 1H MR spectroscopy characterized bone and soft-tissue tumors, resulting in a sensitivity of 95%, specificity of 82%, and accuracy of 89% (P.001).Choline can be reliably detected in large malignant bone and soft-tissue tumors by using a multiecho point-resolved spectroscopic protocol. 1H MR spectroscopy can help differentiate malignant from benign musculoskeletal tumors by revealing the presence or absence of water-soluble choline metabolites.

PURPOSE: Acute hemorrhagic rectal ulcer syndrome is characterized by sudden onset, painless, and massive hemorrhage from rectal ulcer(s) in patients with serious underlying illnesses. It is a matter of controversy whether acute hemorrhagic rectal ulcer syndrome is a distinct clinical entity. This is the first Asian report on acute hemorrhagic rectal ulcer syndrome to be made outside Japan. METHODS: From January 1989 to December 1999, 8,085 patients underwent total colonoscopy at our institution. We retrospectively analyzed the medical records and colonoscopic files. The diagnosis of acute hemorrhagic rectal ulcer syndrome was made by means of the clinical, histologic, and colonoscopic findings. RESULTS: Among the 8,085 patients, 19 patients (11 males; mean age, 71.2 ± 10.1 years) were diagnosed with acute hemorrhagic rectal ulcer syndrome, which accounted for 2.8 percent of the patients with massive lower gastrointestinal bleeding. The duration from hospitalization to the onset of massive bleeding ranged from 3 to 14 (mean, 9 ± 3.3) days. Characteristics of colonoscopic appearance were solitary or multiple rectal ulcer(s), with round, circumferential, geographical, or Dieulafoy-like lesions located within a mean of 4.7 cm ± 1.5 cm from the dentate line. Histopathologically, the lesions appeared as necrosis with denudation of covering epithelium, hemorrhage, and multiple thrombi in the vessels of the mucosa and underlying stroma, which is considered to be similar to stress-related mucosa injury. Successful hemostasis was obtained in 74 percent (14/19) of patients with direct therapeutic maneuvers. Prognosis was largely dependent on accurate diagnosis and management of the underlying disorders. CONCLUSIONS: We assert that acute hemorrhagic rectal ulcer syndrome is a rare but important entity and stress that awareness of this clinical entity should lead to a high index of suspicion resulting in early detection, diagnosis, and appropriate therapy.

Multiple symmetric lipomatosis (Madelung's disease) is a rare disease characterized by non-encapsulated adipose deposits in the neck, the superior part of the trunk and, very rarely, in the limbs. It is common in middle-aged Caucasian Mediterranean males but very rare in Chinese people. We describe two cases of Madelung's disease: both patients presented complaining of a development of a painless neck mass that was increasing in size. Panendoscopy was normal. Both underwent incisional biopsies that revealed benign adipose tissue characterizing Madelung's disease. We discuss the clinical presentation, associated morbidity, and treatments for Madelung's disease.

Objective . Leptin and its receptor are the key players in the regulation of energy balance and body weight control. However, their roles in gynecological malignancies are mostly unclear. In this study, we analyzed the expression and possible involvement of leptin and the leptin receptor in the pathogenesis of endometrial cancer. Methods . Radioimmunoassay was performed to analyze the serum leptin levels in the endometrial cancer patients, while RT-PCR, immunoblotting, and immunohistochemistry techniques were applied to study the expression of leptin receptor in the endometrioid-type endometrial cancer tissues. Furthermore, BrdU labeling followed by immunofluorescent analysis was used to analyze the effect of leptin receptor overexpression on endometrial cancer cell proliferation. Results . Serum leptin levels are elevated in endometrial cancer patients, but show no significant difference to those of normal controls when normalized by body mass index. On the other hand, lower expression levels of leptin receptor short form (Ob-Ra) were observed in most endometrial cancer tissues, especially in the poorly differentiated ones, and the forced expression of Ob-Ra in RL95-2 endometrial cancer cells prevented them from entering the S-phase. Conclusion . In summary, our data demonstrates for the first time that the leptin receptor is aberrantly expressed in endometrial cancer tissues and is possibly involved in the pathogenesis of endometrial cancer.

Purpose To evaluate the potential of a new lipophilic paramagnetic complex [Gd(Bz-TTDA)]2– [(4s)-4-benzyl-3,6,10-tri(carboxymethyl)-3,6,10-triazadodecandioic acid]2– designed for use as a hepatobiliary MR contrast agent. Materials and Methods MR imaging studies for normal and hepatocellular carcinoma (HCC) rat models were performed using a 1.5-T scanner. Sequential multislice T1-weighted turbo field echo (TFE) (TR/TE/flip angle: 15 msec/6.1 msec/25°) coronal images of normal rats were obtained before and after intravenous injections of 0.1 mmol/kg [Gd(Bz-TTDA)]2– in study groups (N = 12) or 0.1 mmol/kg gadopentate dimeglumine (Gd-DTPA)2– in control groups (N = 12). Similar protocols of MR imaging with additional T2-weighted images were used for the rats with implanted HCC in both study and control groups (N = 12, in each group). MR images were analyzed to evaluate the time-enhancement change (% increase of signal-to-noise ratio [SI/N]) in normal liver, renal cortex, renal medulla, and tumors. The liver-lesion contrast-to-noise ratios (CNR) were also evaluated in study and control groups. The rats were killed immediately after the last MR scan to undergo autopsy and histopathologic observation. The acute toxicity test (medial lethal dose, LD50) in mice was also done. Results The liver enhancement in normal rats reached a plateau 5–50 minutes after injection of [Gd(Bz-TTDA)]2–, maintained for three hours, then gradually declined. Intensity of enhancement in liver, renal cortex, and medulla after injection of [Gd(Bz-TTDA)]2– was significantly higher than with Gd-DTPA. The efficacy of tumor characterization with injection of [Gd(Bz-TTDA)]2– was similar to that of Gd-DTPA at the early dynamic phase of the contrast study. However, the liver-lesion CNRs were significantly higher in the study group in the later phase, when tumor enhancement decreased and liver enhancement persisted. The dose of LD50 in acute toxicity test of [Gd(Bz-TTDA)]2– in mice was 7.5 mmol/kg. Conclusion The preliminary results in this animal study indicated that [Gd(Bz-TTDA)]2– has the potential of becoming a reliable liver MR contrast agent. J. Magn. Reson. Imaging 2004;20:632–639. © 2004 Wiley-Liss, Inc.

This study investigated the role of nuclear factor-kappa B (NF-kappaB) activity in human breast cancer with overexpression of HER-2/neu oncoprotein, as well as its role on expression of different histological grades of cancer cells taken from Taiwanese breast cancer patients.Specimens were collected from 82 female breast cancer patients. The HER-2/neu oncoprotein was measured by immunohistochemistry. NF-kappaB activity expression was assessed by the electrophoretic mobility shift assay, and confirmed by the supershift technique using anti-P65 antibody in both breast cancer tissue and the adjacent normal tissue. The histological grades were measured by Modified Bloom-Richardson Grading Scheme.Of the 82 cancer specimens, 81 (98.7%) showed higher or equal expressions of NF-kappaB activity when compared to the adjacent normal tissue. Fifty-five cases (67.1%) had higher levels of NF-kappaB activity in the cancerous tissue than in the adjacent normal tissue (p0.005). With regard to tumor size, steroid receptors, stages, histological types, and node status, there were no statistically significant differences in NF-kappaB activity between cancerous tissues and adjacent normal tissues. However, significantly higher expressions of NF-kappaB activity were seen in those cases with positive HER2/neu oncoprotein, poorly differentiated histological grades, high nuclear pleomorphisms, and high mitotic counts (p0.05). Positive HER-2/neu overexpression of oncoprotein had higher NF-kappaB activity (86%) than negative overexpression (60%) (p0.05). It has been shown that the NF-kappaB activity increases in the HER-2/neu oncoprotein overexpression in human breast cancer.Overexpression of HER-2/neu gene could induce NF-kappaB activity in human breast cancer cells, as has been confirmed in other research on cell lines.

Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma in adults. However, primary MFH of the lung is rare, with only a few cases reported in the literature. Here, we report the case of an 86-year-old male who was admitted to our hospital with the chief complaint of exertional dyspnea and poor appetite. Chest roentgenography revealed a 9 x 15 cm, pleural-based opacity in the left lower lobe. Chest computerized tomography disclosed a well-defined mass with heterogeneous density in the left lower lung field. The diagnosis of MFH was confirmed by thoracoscopic lung biopsy and pathologic examination. Supportive care was given because of extreme old age and poor performance status (the patient's Karnofsky performance status was 30). The patient died from respiratory failure 2 months later.

Cutaneous squamous cell carcinoma (SCC) is a common cancer. Although most patients with primary cutaneous SCC have an excellent prognosis, for those with metastatic disease, the long-term prognosis is poor. The most common sites of metastasis are regional lymph nodes, lung, liver, brain, skin, and bone. However, metastatic soft tissue SCC from cutaneous lesions is extremely rare, with only two reported cases. We report a case in which the patient had a primary SCC lesion on his left palm in 1986. A second primary SCC on his left forearm was confirmed in 2001, with subsequent metastasis to the proximal muscles and bone invasion in spite of the initial wide excision.

Although spontaneous nipple discharge without mass is a common complaint, only about 5–15% of patients with nipple discharge have cancer. The standard preoperative evaluations, including mammography, physical examination, ultrasonography and squeezing cytology, do not provide enough definite data to make a decision for surgery. We have investigated whether preoperative intraductal aspiration cytology and galactography supply sufficient information about the location and nature of the lesion, and have carried out a one-step operative procedure by adding frozen section diagnosis during surgery. A retrospective review of Kaohsiung Medical University Hospital patients presenting symptoms of nonpalpable mass was conducted from January 1989 to June 2000. The medical charts, pathology and cytology reports, and imaging studies were reviewed. Of 487 patients with spontaneous nipple discharge, 190 with pathologic discharge had complete preoperative galactography and intraductal aspiration cytology, and 176 received surgery. Fourteen cases with negative cytology and normal galactography, who had not had an operation, did not develop cancer during an average 7 years follow-up. The diagnostic accuracy rates of 35 cancer patients using galactography and cytology were 91.4% and 88.6%, respectively, and 97.1% in combination, which is better than those of 141 patients with benign lesions (77.3% and 84.4%, and 90.0% in combination, P

Summary Strongyloidiasis is endemic in tropic and subtropic areas, but is currently seldom encountered in developed area like Taiwan. We present an elder man with acute respiratory distress syndrome complicating Strongyloides stercoralis hyperinfection. There was no significant clue initially for diagnosing this patient as having S. stercoralis hyperinfection. Neither peripheral eosinophilia nor significant hemoptysis was noted. Bronchoscopy played a critical role to define the unexpected cause of his progressive pulmonary infiltrates. The correct diagnosis was soon made by recognition of the worm in bronchioloalveolar lavage cytology, and specific treatment was initiated promptly. For a septic patient with progressive pulmonary infiltrates, bronchoscopic studies including cytology may be necessary for defining the cause. Hyperinfection strongyloidiasis should be considered as a cause of acute respiratory distress syndrome in immunocompromised patient, especially with the presence of chronic gastrointestinal symptoms.

A 26-year-old woman presented with symptoms of bowel obstruction. An emergent computed tomography (CT) scan was performed which showed ileoileal intussusceptions due to a fatty nodule. Exploratory laparotomy and removal of the involved small bowel was performed. The pathology showed the leading point of the intussusception to be ectopic pancreas with abundant fatty infiltration.

OBJECTIVE To increase cytodiagnostic accuracy for women with spontaneous nipple discharge using a simple intraductal aspiration method. STUDY DESIGN We compared the cytodiagnostic accuracy of the conventional squeezing collection method and intraductal aspiration by intravenous catheter in a total of 146 women with spontaneous nipple discharge in a single duct without a mass; they had been pathologically identified at Kaohsiung Medical University Hospital. RESULTS Adequate specimens were collected in 96.6% (141/146 cases) of the sample by the intraductal aspiration method as compared to 76.0% collected by the conventional squeezing method (P < .05). An adequate specimen should consist, at a minimum, of six cohesive clusters of well-preserved epithelial cells, with each cluster composed of at least five cells other than foam cells. The cytologic diagnosis was divided into five categories: positive in 9 cases, suspicious in 10, negative with atypical findings in 59, negative in 33 and inadequate specimens in 35 cases that employed the squeezing method. These results were less satisfactory than with the intraductal aspiration method: the smears were positive in 17 cases, suspicious in 14, negative with atypical findings in 78, negative in 32 and inadequate specimens in 5. Our results showed a sensitivity of 92.3% and specificity of 93.9% for the intraductal aspiration method as compared to a sensitivity of 52.9% and specificity of 89.3% for the squeezing method. Among the 27 cancers in this series, correct cytodiagnosis, including suspicious cases, was made in 24 cases by intraductal aspiration, with an accuracy of 88.9%, as compared to the 33.3% (9/27) accuracy of the squeezing method (P < 0.5). CONCLUSION For patients with spontaneous nipple discharge, the intraductal aspiration method provides much more accurate cytodiagnosis than does the conventional squeezing method.

Background Intraductal papillary-mucinous carcinoma (IPMC) of the pancreas is a newly identified clinicopathologic entity of the exocrine pancreas. It has been considered a slowly growing and less-aggressive carcinoma with a favorable prognosis. There have been only a few documents reporting its distant metastasis and cytologic features, with no report of thyroid metastasis until the present. Case A case of IPMC occurred in a 45-year-old male, who was admitted with rapid growth and tenderness of the thyroid. Abdominal computed tomography showed the typical cystic dilatation of IPMC with adjacent organ metastasis. Fine needle aspiration of the thyroid yielded papillary fronds of carcinoma cells with nuclear pleomorphism, abundant cytoplasm and prominent nucleoli in a mucinous background. Immunohistochemical findings from the skin and thyroid characterized the papillary-mucinous carcinoma as having originated in the pancreas. Conclusion This case suggests that papillary carcinoma fronds aspirated from the thyroid should be further differentiated from the primary site and that a pleomorphic nucleus in a mucinous background is a useful feature to exclude a thyroid origin. Before this, distant metastasis of IPMC to the skin and thyroid has not been reported. The prognosis of IPMC with wide, distant metastasis at an advanced stage is poor.

Spontaneous pneumothorax is a rare manifestation of primary lung cancer or metastasis. We report a 39-year- old man with well-differentiated squamous cell carcinoma of the tongue and cervical lymph node metastases. He developed lung metastases and spontaneous pneumothorax 22 months later after intra-arterial infusion chemotherapy. The patient was managed with partial lung resection under thoracotomy. The pneumothorax resolved completely after the operation. Histological examination demonstrated metastatic squamous cell carcinoma, which had led to a bronchopleural fistula with subsequent induction of pneumothorax. The patient recovered uneventfully and continued to receive adjuvant chemotherapy in the oncology surgery outpatient department. Unfortunately, the tumors of the tongue and cervical lymph nodes progressively enlarged despite treatment. Eventually, the patient died of respiratory failure 5 months later. In most of the previously reported cases, pulmonary metastases associated with spontaneous pneumothorax usually originate from osteogenic or soft-tissue sarcomas. Although rare, pulmonary metastasis should be considered in the etiology of spontaneous pneumothorax. Despite advanced disease, surgical treatment may be feasible.

The aim of this study is to evaluate the effect of ultraviolet B (UVB) on arsenic-induced Bowen's disease. Four patients were irradiated with 750 mJ/cm2 of UVB and biopsies were performed before treatment and 2 weeks later. Immunohistochemical stains of p53 and Ki-67 were compared by the labelled-streptavidin method before and after the UVB treatment. We found that the number of p53 and Ki-67 positive cells after the UVB treatment were significantly fewer than those of non-UVB-treated specimens. These results suggest that the UVB inhibitory effect in Bowen's disease needs further studies to clarify its value in potentially retarding the progression of the hyperproliferative status in overt skin cancer on a molecular basis.

Here is a rare case of lingual leiomyomatous hamartoma (LLH) with bifid tongue tip and tongue-tie in a patient with non-oral-facial-digital syndrome (OFDS). A 29-year-old male consulted for a painless tumor over the midline of the tongue dorsum measuring 2 × 1.5 cm. The tumor was excised and the tongue-tie was corrected. Diagnosis of LLH was based on histo-pathologic and immuno-histochemical studies. The epidemiologic data and differential diagnosis of LLH, as well as related literature, are discussed. To date, only 14 cases of LLH have been reported in English literature. This may be the first reported case of LLH with bifid tip and ankyloglossia in a non-OFDS patient.

Spontaneous and complete regression of malignant neoplasms is extremely unusual. To our knowledge, this case report is the first description of spontaneous regression of an extranodal malignant lymphoma occurring in the conjunctiva and orbit. A 40-year-old woman noticed a pink conjunctival mass at the medial aspect of her left eye that had been present for 3 weeks. She presented on May 5, 2003. Ophthalmologic examination showed a salmon-colored mass along the lateral side of the caruncle. CT revealed a mass in the medial orbit. Surgical biopsy exhibited a malignant lymphoma, diffuse large B-cell type. After biopsy, the tumor spontaneously decreased in size and completely disappeared in 5 weeks. At 6 months' follow-up, the tumor had not recurred.

Primary pulmonary choriocarcinoma is an extremely rare tumor in men, with 13 cases reported in the literature. Due to its rarity, primary choriocarcinoma of the lung in men is often incorrectly diagnosed as more common diseases, such as primary or metastatic lung cancer, and therefore potentially curative chemotherapy or surgery may be withheld from the patient. In this report, we present the case of a 23-year-old man with hemoptysis and progressive dyspnea. Airspace consolidation with multiple nodules of varying sizes was found on a chest radiograph. The results of a urine pregnancy test were positive, and the beta-human chorionic gonadotropin level was markedly elevated both in the serum and the urine. Subsequently, testing of a bronchoscopic biopsy specimen proved these tumors to be choriocarcinoma. We conclude that the urine pregnancy test, a simple and convenient method, would be very useful in the rapid diagnosis of primary pulmonary choriocarcinoma in men.

Mucormycosis is an invasive fungal infection associated with a high mortality rate, especially in immunocompromised hosts. Mucormycosis rarely occurs in cirrhotic patients. Here, we report a case of mucormycosis with underlying liver cirrhosis and diabetes mellitus. The patient suffered from maxillary sinusitis and osteomyelitis, and the infection was successfully treated with antifungal agents, surgical debridement, and hyperbaric oxygen therapy. The antifungal treatments used were liposomal amphotericin B, itraconazole, and posaconazole. Although our patient had liver cirrhosis (Child-Pugh classification B), no hepatic decompensation was developed during the treatment course of posaconazole. This is the first report of the safe and effective use of posaconazole for the treatment of mucormycosis in a cirrhotic patient.

BUBR1 is one of the key components of the spindle assembly checkpoint (SAC) machinery and is activated in response to kinetochore tension. Defects in the SAC contribute to an increased rate of aneuploidization during tumorigenesis. The aim of the present study was to examine the immunohistochemical expression of BUBR1 protein for human oral squamous cell carcinogenesis.A total of 120 samples of squamous cell carcinoma (SCC, n = 43) and 5 types of potentially malignant disorders (PMDs: oral epithelial dysplasia, n = 11; hyperkeratosis/epithelial hyperplasia, n = 20; lichen planus, n = 16; submucous fibrosis, n = 19; and verrucous hyperplasia, n = 11) of human oral mucosa (1991-2001) from our institution were retrieved and immunohistochemical staining were performed. Normal oral mucosa (n = 9) and fibrous hyperplasia (n = 9) from patients without the aforementioned oral habits were also included in the study.BUBR1 staining was detected at the basal and suprabasal layers in 75 (97.4%) of 77 samples of PMD and 43 (100%) of 43 samples of SCC of oral mucosa but was absent in all samples of normal oral mucosa (n = 9) and fibrous hyperplasia (n = 9). BUBR1 expression of various types of PMD and SCC of oral mucosa was significantly overexpressed as compared respectively with normal mucosa (P.001) and fibrous hyperplasia (P.001). Moreover, the expression of oral SCC was significantly higher as compared respectively with the 5 types of oral PMD; on the other hand, BUBR1 expression of verrucous hyperplasia was significantly higher than that of the other 4 types of PMD of oral mucosa (P.001).Our results may interpret that BUBR1 protein is suggested to be one of the contributing factors involved in the pathogenesis of oral SCC. These also hypothesize that BUBR1 protein is a putative biomarker for human oral squamous cell carcinogenesis.

CD4+/CD56+ hematodermic neoplasm (formerly known as blastic natural killer (NK) cell lymphoma) is a rare and aggressive neoplasm with a poor prognosis. It is a recently described entity with a predilection for skin involvement.[1][1] Previously, the disease was thought to originate from NK cells

Malignant lymphoma involving the genital tract is rare, and primary lymphoma of the uterus is even rarer. Immunohistochemically, most of the reported cases have been diffuse large cell lymphomas with a B-cell nature. Herein, we report an unusual case of uterine T-cell lymphoma in a 68-year-old woman. She suffered from fever, vaginal bleeding, and a huge mass in the lower abdomen. The initial clinical and histologic studies failed to indicate a cell type. We provide the clinical details of the case and discuss the diagnostic pitfalls.