Chi-Yuan Tzen

Idiopathic Inflammatory Myopathy with Diffuse Alveolar Damage

Abstract: Interstitial lung disease (ILD) in patients with myositis is defined by the presence of interstitial changes on radiographic examination. The reported prevalence of ILD varies from 0% to nearly 50%. However, only rarely has the pathological pattern of diffuse alveolar damage (DAD) associated with idiopathic inflammatory myopathy (IIM) been reported. We report five patients with IIM (one with dermatomyositis, one with polymyositis, and three with amyopathic dermatomyositis) and respiratory failure. Four underwent open lung biopsy with pathological proof of diffuse alveolar damage (DAD). Despite intensive immunosuppressive therapy, all of them died. In addition to the case reports, we discuss DAD in patients with IIM.

Phyllodes Tumor of the Breast: The Challenge Persists

IntroductionPhyllodes tumors of the breast are uncommon, and it is difficult to predict biologic behavior based on clinicopathologic features. Despite the wealth of data on the factors to predict recurrence, little is known about the impact of treatment refinements. This study seeks to define changes in patient characteristics, histopathologic parameters, and outcome between the two periods before and after the care of patients with breast diseases was centralized to a breast specialty.MethodsThe records of 182 patients with phyllodes tumors managed surgically were reviewed. Patients treated from 1985 to 1996 (n = 81) were compared with those seen from 1997 to 2004 (n = 101).ResultsThe analysis of the two treatment periods revealed that there was a decrease in tumor size at diagnosis, from 7.7 cm during the earlier period to 4.6 cm during the recent period (P = 0.003). The patients undergoing breast-conserving surgery were significantly increased during the recent period. In contrast, pathologic features and local recurrence rates remained unchanged during the study period. Multivariate analysis revealed that positive surgical margin was the only independent predictor of recurrence, with an increased hazard of 8.0. Overall, upgrading to the next grade was observed in 16% of recurrences.ConclusionsBreast-conserving surgery with clear margins is the current treatment of choice for phyllodes tumors, but this strategy does not further reduce local recurrence effectively. Optimal management continues to be a challenge.

Clinicopathologic significance of leptin and leptin receptor expressions in papillary thyroid carcinoma

BACKGROUND Epidemiologic studies have shown that obesity is associated with an increased risk of thyroid cancer. Leptin, an adipocyte-derived cytokine, can act as a growth factor on certain normal and transformed cells. Aberrant expression of leptin or leptin receptor has been detected in some types of cancer. The aim of this study is to determine immunohistochemical expression of leptin and leptin receptor in papillary thyroid cancer to investigate the relationship between their expression and clinicopathologic features. METHODS The expression of leptin and leptin receptor was assessed in 49 primary neoplasms and 15 lymph node metastases using a semiquantitative immunohistochemical staining method. RESULTS Leptin and leptin receptor were expressed in 37% and 51% of papillary thyroid cancer, respectively. They were not expressed in normal follicles. In the primary neoplasms and the metastatic nodes, expression of leptin correlated closely with leptin receptor (P < .001 for the primary neoplasms and P = .017 for nodal metastases). Expression of either protein was associated with greater neoplasm size (leptin expression, 32.0 +/- 10.7 vs 20.5 +/- 8.4 mm; P = .001; leptin receptor expression, 27.9 +/- 11.5 vs 21.4 +/- 9.0 mm; P = .032). Coexpression of leptin and leptin receptor in primary neoplasms had greater incidence of lymph node metastasis (P = .038). CONCLUSION Expression of leptin and/or leptin receptor in papillary thyroid cancer is associated with neoplasm aggressiveness, including tumor size and lymph node metastasis.

Incidence of gastrointestinal stromal tumor: a retrospective study based on immunohistochemical and mutational analyses.

The aim of this study is to estimate the incidence of the gastrointestinal stromal tumor after the previous diagnoses were confirmed and/or revised by both immunohistochemical and mutational analyses. We reviewed 17,858 surgically excised gastrointestinal lesions in our hospital from 1998 to 2004. All mesenchymal tumors were examined for CD117 expression by immunohistochemistry, and every CD117-negative mesenchymal tumors were further subjected to mutational analysis for KIT and PDGFRA exons. The results showed that approximately 35% of gastrointestinal stromal tumors were misdiagnosed if immunohistochemical analysis of CD117 expression was not performed; and approximately 15% misdiagnosed if mutation analysis was not available. Because approximately 4.72% of patients with gastrointestinal malignancies in Taiwan were treated in our hospital and the average of newly diagnosed gastrointestinal stromal tumors in our hospital was 14.33 cases per year, the estimated annual incidents of gastrointestinal stromal tumor in Taiwan were 303.60. Therefore, the annual incidence of gastrointestinal stromal tumor is 13.74 per million Taiwanese.

Prenatal diagnosis of otocephaly with microphthalmia/anophthalmia using ultrasound and magnetic resonance imaging

A 30-year-old primigravid woman was referred to hospital at 29 weeks’ gestation because of polyhydramnios and regular uterine contractions. She and her husband were non-consanguineous and healthy. There was no family history of congenital malformations, nor any history of teratogenic medication, recent infection, diabetes mellitus, or hypertension during this pregnancy. A level II, twodimensional (2D) ultrasound examination revealed a single live fetus with a biparietal diameter of 7.99 cm (appropriate for 29 weeks’ gestation), a femur length of 5.4 cm (29 weeks), an abdominal circumference of 24 cm (29 weeks), polyhydramnios with an amniotic fluid index of 45 cm, absence of the mandible, hypotelorism, lowset ventromedially displaced ears, left microphthalmia with an ocular diameter of 1.29 cm (< 5th centile), and right anophthalmia with absence of the right lens (Figure 1). A tentative diagnosis of otocephaly was made. Magnetic resonance imaging (MRI) demonstrated agnathia and right anophthalmia (Figure 2). The other internal organs were unremarkable. A 1404-g female baby (Figure 3) was delivered 1 day later because of premature rupture of the membranes and preterm labor. The proband died shortly after birth. Autopsy confirmed the diagnosis of otocephaly, which was characterized by the isolated agnathia, aglossia, microstomia, and synotia without central nervous system and other organ defects except for the ocular abnormalities of left microphthalmia and absence of the right lens. The karyotype of the proband was 46,XX. Computed tomography (CT) scans following three-dimensional (3D) reconstruction showed a characteristic otocephalic skull (Figure 4). Prenatal diagnosis of otocephaly using 2D and 3D ultrasound has been well described in the literature1–5. To the best of our knowledge, this

Pseudomembranous tracheobronchitis caused by Aspergillus in immunocompromised patients

We report 2 cases of Aspergillus pseudomembranous tracheobronchitis in patients with diabetes. The first patient succumbed to progressive obstructive respiratory failure despite mechanical ventilation and antifungal therapy. However, the second patient survived. Aspergillus tracheobronchitis should be considered in immunocompromized patients presenting with cough, chest pain, fever, dyspnea and upper airway obstruction. Early bronchoscopy and histologic examination should be performed. Early, appropriate treatment may be life saving.

Prognostic factors in desmoid-type fibromatosis: a clinicopathological and immunohistochemical analysis of 46 cases

Aims: To determine risk factors for recurrence of desmoid‐type fibromatosis (aggressive fibromatosis). Methods: Forty‐six cases of desmoid‐type fibromatosis in Taiwanese patients were analysed for an association between tumour recurrence and clinical features, pathology, and the presence of p53 protein and β‐catenin on immunohistochemical staining. Results: Six (13%) of 46 patients developed recurrence after surgical resection. The only factor significantly associated with tumour recurrence was positive surgical margin (p = 0.035). Conclusions: A positive surgical margin is a risk factor for recurrence of desmoid‐type fibromatosis.

Detection of mycobacteria in Crohn's disease by a broad spectrum polymerase chain reaction.

BACKGROUND The role of mycobacterial infection, particularly related to Mycobacterium avium subsp paratuberculosis (Map), in Crohns disease has long been debated. We developed primer pairs capable of detecting a broad spectrum of mycobacterium and employed them to investigate surgical specimens from patients with Crohns disease. METHODS Pan mycobacterium primers of the 65-kDa heat shock protein gene (Hsp65) were used in a polymerase chain reaction (PCR) to examine 12 surgically-resected, formalin-fixed, paraffin-embedded specimens from 11 patients with Crohns disease. The DNA sequences of amplicons were aligned with those in GenBank. RESULTS Mycobacterial DNA was found in specimens from three of 11 patients. M. mucogenicum was identified in a specimen from one patient and M. tuberculosis in two, but Map was not identified in any. CONCLUSION Hsp65-based PCR can be employed to search for occult mycobacterial infection of the gastrointestinal tract in patients with a diagnosis or suspicion of Crohns disease. This approach may have a therapeutic implication.

Two- and three-dimensional ultrasound demonstration of a giant epignathus

A 41-year-old woman, gravida 6 para 3, was referred to hospital in the second trimester for genetic amniocentesis. She and her husband were non-consanguineous and healthy. There was no family history of congenital malformations. She did not have teratogenic medication, recent infection, diabetes mellitus, or hypertension during this pregnancy. Her previous pregnancies resulted in two miscarriages and uneventful deliveries of three healthy children. Amniocentesis revealed a 46,XY karyotype in this pregnancy. A detailed two-dimensional (2D) ultrasound examination at 17 weeks’ gestation revealed a single live fetus with a biparietal diameter of 3.4 cm (equivalent to 16 weeks’ gestation), an abdominal circumference of 13.1 cm (equivalent to 18 weeks’ gestation), a femur length of 2.1 cm (equivalent to 16 weeks’ gestation), a normal amniotic fluid index of 16.8 cm, and a giant mixed echogenic mass measuring 8.1 × 4.8 × 7.1 cm in the left face in continuation with the skull. The intracranial structures were intact. Doppler flow study showed a high-volume and high-velocity flow within the tumor. Echocardiography was normal. The left orbit was absent. The nose and mouth were difficult to identify. There was no fetal head movement. Three-dimensional (3D) ultrasound displayed a giant left facial mass (Figure 1a). 3D color power angiography showed that the large facial tumor parasitized blood supply from the fetal circulation. A tentative diagnosis of epignathus was made. The woman opted for termination of the pregnancy. A 372-g male fetus with epignathus was delivered (Figures 1b and 2a). Autopsy revealed a teratoma arising from the palate without involving the skull and brain. Cytogenetic analysis of the teratoma revealed a 46,XY karyotype. Multiple transectional skull computed tomography scans showed intralesional calcification and an intact skull. Magnetic resonance imaging scans showed a giant facial mass distorting the skull and brain structures (Figure 2b). An epignathus is a rare teratoma of the oropharynx with an incidence between 1 in 35 000 and 1 in 200 000 live births1. The majority of epignathi originate from the base of the skull in the posterior nasopharynx and usually involve the hard palate or sphenoid bone2. Cleft palate and bifid tongue or nose may be present3. A few epignathus teratomas have been associated with chromosome aberrations, such as 45,X/46,X,r(X) mosaicism3, trisomy 134, duplication of 1q and 19p5, and inverted proximal 1q duplication3. Prenatal diagnosis of epignathi by 2D ultrasound has been well documented1–16. However, to our knowledge, 3D ultrasound demonstration of an epignathus has not yet been described. The 2D ultrasound features of epignathi include a mass projecting from the oral cavity, a mass adjacent to the face with or without intracranial extension, polyhydramnios, and hydrops fetalis. Fetal prognosis depends on the extent of the neighboring tissue involvement and the size of the tumor. Fetuses with a bidirectional epignathus invading the intracranial structures usually have a poor outcome. We have presented the 2D and 3D ultrasound findings of a second-trimester fetus with a giant epignathus distorting the face and skull but without an intracranial extension. 2D ultrasound demonstrated a large complex facial mass and intact intracranial structures. 3D ultrasound displayed comprehensive images and the vasculature of the tumor. The effect of the craniofacial teratoma on the fetal circulation can be documented by Doppler flow study and echocardiography. Doppler flow study may demonstrate high-volume and high-velocity flow of the tumor and echocardiography may reveal dilated ventricles in association with high-output cardiac failure due to massive tumor arteriovenous shunting17. 3D color power angiography further provides a perfusion display of the vasculature, thus allowing visualization of the blood flow between the tumor and fetal circulation and an understanding of the hemodynamic pathophysiology. We believe that both 2D and 3D ultrasound scans are very useful in the prenatal investigation of fetal epignathi for which detailed assessments of the craniofacial structural abnormalities of the fetus and the vasculature of the tumor are required.

Upregulated hPuf-A promotes breast cancer tumorigenesis

AbstracthPuf-A is a member of RNA-binding PUF family that regulates mRNA translation. Redistribution of hPuf-A from the nucleolus to the nucleoplasm upon genotoxic stress modulates the poly(ADP-ribosyl)ation activity of PARP-1. Here, we report a novel function of hPuf-A involved in promoting breast cancer progression. Immunohistochemical studies showed higher expression levels of hPuf-A in stage I, II, III, and IV breast cancer specimens in contrast with those of hPuf-A in ductal carcinoma in situ. The presence of hPuf-A is highly associated with colony formation capacities in breast cancer T47D and MDA-MB-231 cells. Xenograft growth of hPuf-A-silenced and hPuf-A overexpressing MDA-MB-231 cells in nude mice was substantially in concert with colony formation capacities. This promoting effect of hPuf-A in tumorigenesis might be correlated with the regulation of its associated mRNAs, such as RbAp48 and DDX3. Collectively, hPuf-A may have diagnostic values in breast cancer progression.