Biomedical subjects

Eunhee S Yi

Publications and source records attributed to Eunhee S Yi.

14 recordsLinked to original sources

PubMed2006

Morphologic changes in explanted lungs after prostacyclin therapy for pulmonary hypertension.

Prostacyclin (PGI2) causes vasodilation and inhibition of platelet aggregation in vivo. PGI2 is also postulated to affect pulmonary vascular remodeling, at least partly through anti-proliferative effect via PGI2 receptor (PGIR). However, the mechanism(s) of action by which (PGI2) exerts its therapeutic effect is still not clear despite clear clinical benefit seen in severe pulmonary hypertension (PH) patients. We performed a histopathologic and morphometric study on the explanted lung tissues from PGI2-treated patients prior to lung transplantation (n = 9), in an attempt to elucidate morphologic changes associated with PGI2 treatment. Explanted lungs from PH patients without PGI2 treatment were examined as the control (n = 11). We also studied the possible differences in PGIR expression between the treated and untreated groups by immunohistochemical method. Seven out of 9 treated patients showed moderate to severe bronchial and perivascular inflammation, as opposed to only 1 such case in the control group. Five out of 9 treated cases showed moderate to severe alveolar edema with or without evidence of old hemorrhage, in contrast to only 1 case showing moderate alveolar edema in control patients. Morphometry did not reveal any significant difference between the two groups either in the % thickness of intima, media, or adventitia or in the density of plexiform lesions. Immunostain also failed to demonstrate any notable difference in PGIR expression. In conclusion, PGI2-treated cases revealed more pronounced pulmonary alveolar edema and inflammation, but no morphological evidence of altered vascular remodeling or PGIR expression after PGI2 therapy.

Adult↗

PubMed2006

Strong PDGFRA positivity is seen in GISTs but not in other intra-abdominal mesenchymal tumors: Immunohistochemical and mutational analyses.

Mutation of the platelet-derived growth factor receptor-alpha (PDGFRA) gene has been well documented as an alternative oncogenic mechanism in a subset of gastrointestinal stromal tumors (GISTs) lacking c-kit mutations. However, the role of PDGFRA immunohistochemistry in the diagnosis of GISTs has not been well studied. We investigated PDGFRA immunoreactivity in GISTs and in other intra-abdominal mesenchymal tumors, and correlated PDGFRA expression with CD117 positivity and with the mutational status of PDGFRA and c-kit genes. In addition, expression of phosphorylated AKT, an activated downstream molecule in the PDGFRA and c-kit signaling pathways, was correlated with PDGFRA and CD117 status. A total of 39 GISTs and 20 other mesenchymal tumors in the abdomen were included in this study. Thirty-five of 39 GIST cases (89.7%) were positive for PDGFRA and 19 of these 35 positive cases were strongly positive. Five of 20 non-GIST lesions (25%) were positive for PDGFRA, but none of these cases were strongly positive. With one exception, PDGFRA-positive cases were also positive for CD117. Phosphorylated AKT positivity was not associated with the immunoreactivity or mutation of PDGFRA and c-kit, suggesting that the activation of AKT is probably independent of the activation of PDGFRA and c-kit in GISTs. Of 14 GISTs assayed, 4 had mutations in c-kit at exons 11 or 17, and 4 had mutations in PDGFRA at exons 12 or 18. Three of 4 GIST cases with PDGFRA mutations show epithelioid morphology and strong PDGFRA immunoreactivity with prominent perinuclear dotlike accentuation (so-called Golgi pattern). In conclusion, strong PDGFRA positivity with Golgi pattern is a useful adjunct in the diagnosis of GISTs with PDGFRA mutation.

Abdominal Neoplasms↗

PubMed2006

Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder following lung transplantation is more commonly of host origin.

CONTEXT: Posttransplantation lymphoproliferative disorder (PTLD) in patients who have undergone solid organ transplantation is thought to be mostly of host (ie, transplant recipient) origin, as opposed to being predominantly of donor origin, which is observed in patients who have undergone bone marrow transplantation. Donor-origin PTLDs reportedly follow a more indolent course than host-origin PTLDs. OBJECTIVE: To determine the origin of PTLD and its clinical implications in patients who have undergone lung transplantation. DESIGN: Patients' medical records were reviewed for clinical data. We performed a molecular study to determine the origin of abnormal lymphoid cells in 4 PTLD cases identified from our autopsy files. Each case underwent restriction fragment length polymorphism analysis using polymerase chain reaction-based genotyping for CYP2D6. Epstein-Barr virus (latent membrane protein 1) immunostaining and polymerase chain reaction analysis were performed on PTLD-involved tissues. RESULTS: Three of 4 PTLD cases were of host origin, and the remaining case was of donor origin. Epstein-Barr virus was detected by immunohistochemical and polymerase chain reaction methods in all PTLD-involved tissues that were examined. There was no apparent difference in clinical manifestations between host-origin and donor-origin PTLD cases in our study. CONCLUSIONS: The PTLDs in our patients who had undergone lung transplantation were Epstein-Barr virus-positive and mostly of host origin, without any notable clinical difference from donor-origin PTLD.

Aged↗

PubMed2005

Epithelioid gastrointestinal stromal tumor with PDGFRA activating mutation and immunoreactivity.

The authors report a unique case of an intra-abdominal, epithelioid mesenchymal tumor that had an activating mutation of PDGFRA and a strong PDGFRA immunoreactivity but lacked both c-kit mutation and c-kit protein (CD117) expression. IHC study showed that the tumor cells were diffusely and strongly positive for PDGFRA, vimentin, CD34, and Bcl-2 but completely negative for CD117 as well as for muscle, epithelial, endothelial, endocrine, mesothelial, neural, and melanocytic cell markers. Molecular study revealed a mutation at the juxtamembrane domain of exon 12 in PDGFRA gene with GTC to GAC transition at codon 561 (V561D), as shown in the previous mutational studies on gastrointestinal stromal tumor (GIST). This case likely represents an example of GIST with PDGFRA activating mutation and PDGFRA immunoreactivity without CD117 positivity, which has not been documented in the literature. STI 571 (imatinib mesylate [Gleevec]) might be an effective therapy in this case, since Gleevec targets both PDGFRA and c-kit oncoproteins.

Adult↗

PubMed2004

Congenital pulmonary airway malformation (congenital cystic adenomatoid malformation) with multiple extrapulmonary anomalies: autopsy report of a fetus at 19 weeks of gestation.

Congenital pulmonary airway malformation, or congenital cystic adenomatoid malformation, is postulated to be a disorder of pulmonary airway morphogenesis and encompasses 5 different types with distinct levels or stages of tracheobronchial development. We present a unique case of type 2 congenital pulmonary airway malformation with a previously undocumented combination of multiple extrapulmonary anomalies, featuring ipsilateral multicystic renal dysgenesis, contralateral renal agenesis, and ovarian germ cell hypoplasia, diagnosed in a 19-week gestational age fetus by autopsy. Epithelial cells comprising the pulmonary lesions were positive for thyroid transcription factor-1, surfactant protein-B, and cytokeratin-7 but negative for cytokeratin-20 immunostainings, with the pattern seen in normal terminal bronchioles. Chromosomal analysis showed a normal female karyotype, despite a high estimated risk for Down syndrome suggested by the low maternal serum alpha-fetoprotein level.

Abortion, Eugenic↗

PubMed2004

Tumors of the pulmonary vasculature.

Most primary tumors of the pulmonary vasculature are sarcomas arising in the main pulmonary arteries and veins with high mortality rates. Pulmonary artery sarcoma is far more prevalent than its venous counterpart, though both are rare. Pulmonary capillary hemangiomatosis is a rare low-grade tumor or tumor-like lesion of the pulmonary capillaries that causes severe pulmonary hypertension. Secondary involvement of pulmonary vasculature by malignant tumors may rarely mimic a primary vascular tumor or clinically present as unexplained pulmonary hypertension associated with thrombotic microangiopathy.

Diagnosis, Differential↗

PubMed2004

TTF-1 expression is specific for lung primary in typical and atypical carcinoids: TTF-1-positive carcinoids are predominantly in peripheral location.

Thyroid transcription factor (TTF)-1 expression in neuroendocrine tumors (NETs) has not been studied as widely as that in non-NETs, with the exception of small cell carcinomas, in which TTF-1 is highly sensitive but not specific for a primary lung tumor. The reported incidence of TTF-1 expression in pulmonary carcinoids has also been highly variable in the literature. To evaluate the expression of TTF-1 in NETs and potential value of TTF-1 in distinguishing pulmonary NETs from those of extrapulmonary origin, we performed an immunohistochemical study by using semiquantitative analysis on formalin-fixed, paraffin-embedded sections from 111 NETs, including 80 pulmonary (11 carcinoid tumorlets [TLs] or foci of neuroendocrine cell hyperplasia [NEH], 36 typical carcinoids [TCs], 17 atypical carcinoids [ACs], 16 large cell neuroendocrine carcinomas [LCNECs]), 13 thymic (3 TCs, 8 ACs, 2 LCNECs), 17 gastrointestinal or pancreatic (13 TCs, 4 ACs), and 1 ovarian (LCNEC). Pulmonary carcinoids were subdivided into those with central and those with peripheral location. TTF-1 positivity was seen exclusively in pulmonary NETs and was significantly higher in NEH or TLs (72.7%) than in TCs (27.8%), ACs (29.4%), and LCNECs (37.5%; P = 0.03). All extrapulmonary NETs were uniformly negative for TTF-1 staining. Interestingly, 12 of 14 TTF-1-positive pulmonary TCs and ACs had a peripheral location with spindle cell morphology, as did all cases of TL, a purported precursor of peripheral carcinoids. In conclusion, TTF-1 expression was 100% specific, though not so sensitive, for the lung primary in TCs and ACs and possibly also in LCNECs. Prevalent TTF-1 positivity in TLs and peripheral carcinoids suggest that they may be histogenetically distinct from the central carcinoids, which are typically composed of TTF-1-negative, more rounded cells.

Aged↗

PubMed2004

Tracheobronchial adenoid cystic carcinoma: a clinicopathologic study of 14 cases.

STUDY OBJECTIVES: To investigate the clinicopathologic features of primary tracheobronchial adenoid cystic carcinoma (ACC), and to examine kit protein (CD117) expression, and a possible correlation between the histologic grade and Ki-67 positivity. DESIGN: Retrospective 10-year study (from 1992 to 2001). SETTING: Referral center for interventional pulmonology. PATIENTS: Fourteen patients referred to our institution for laser resection of tracheal or endobronchial tumors. INTERVENTIONS: Twelve patients were treated primarily by laser resection via bronchoscopy with subsequent radiation therapy. The remaining two patients had tracheal resection with postoperative radiation and radiation therapy alone. RESULTS: Fourteen patients (5 men and 9 women) had an average age of 44 years at diagnosis (age range, 29 to 57 years). Five of 14 patients were smokers (average smoking history, 28.5 pack-years), 8 were nonsmokers, and the smoking history was unknown in 1 patient. Major symptoms at presentation included cough (57.1%), dyspnea (71.4%), and hoarseness (14.3%). Two patients (14.3%) presented with respiratory failure. Eleven patients (78.6%) had one or more recurrences, and 4 patients (28.6%) had metastases, primarily to the lungs. The average time to either recurrence or metastasis was 4.6 years after the initial diagnosis. Five patients (35.7%), all of whom had recurrences and/or metastasis during the course of their disease, died of their disease (average time, 8.2 years). Thirteen of 13 cases stained for CD117 were positive in the tumor cell cytoplasm with membranous accentuation. Our cases included 8 grade I tumors, 4 grade II tumors, and 2 grade III tumors, which did not correlate with the degree of Ki-67 positivity. CONCLUSIONS: Tracheobronchial ACCs in our study were more common in women and nonsmokers who presented with nonspecific respiratory symptoms and followed a clinical course generally comparable to that of tumors in the salivary glands. CD117 expression was present in all cases tested, and Ki-67 stain results did not correlate with the tumor grade.

Adult↗

PubMed2004

Simultaneous serous cystadenoma of the pancreas and mucinous cystadenoma of the appendix.

CONTEXT: Serous cystadenoma of the pancreas and mucinous tumors of the vermiform appendix are rare. To our knowledge, the simultaneous occurrence of these two tumors has not been reported. CASE REPORT: Here, we report an adult female who presented with signs and symptoms of appendicitis. A preoperative CT scan confirmed the findings of appendicitis and also showed an incidental large mass in the head of the pancreas. The patient underwent uneventful appendectomy. Her pathology revealed an acutely inflamed appendix with a benign mucinous cystadenoma at the tip. Several months after her recovery, a Whipple procedure was performed. Pathologic examination showed a 5x5 cm serous cystadenoma of the head of the pancreas without evidence of malignancy. Two years later, the patient is alive and well without evidence of tumor recurrence. CONCLUSIONS: Cystadenomas of the pancreas and appendix are unusual and their simultaneous occurrence is a rare event.

Appendiceal Neoplasms↗

PubMed2003

Bone morphogenetic proteins induce apoptosis in human pulmonary vascular smooth muscle cells.

Pulmonary vascular medial hypertrophy in primary pulmonary hypertension (PPH) is mainly caused by increased proliferation and decreased apoptosis in pulmonary artery smooth muscle cells (PASMCs). Mutations of the bone morphogenetic protein (BMP) receptor type II (BMP-RII) gene have been implicated in patients with familial and sporadic PPH. The objective of this study was to elucidate the apoptotic effects of BMPs on normal human PASMCs and to examine whether BMP-induced effects are altered in PASMCs from PPH patients. Using RT-PCR, we detected six isoforms of BMPs (BMP-1 through -6) and three subunits of BMP receptors (BMP-RIa, -RIb, and -RII) in PASMCs. Treatment of normal PASMCs with BMP-2 or -7 (100-200 nM, 24-48 h) markedly increased the percentage of cells undergoing apoptosis. The BMP-2-mediated apoptosis in normal PASMCs was associated with a transient activation or phosphorylation of Smad1 and a marked downregulation of the antiapoptotic protein Bcl-2. In PASMCs from PPH patients, the BMP-2- or BMP-7-induced apoptosis was significantly inhibited compared with PASMCs from patients with secondary pulmonary hypertension. These results suggest that the antiproliferative effect of BMPs is partially due to induction of PASMC apoptosis, which serves as a critical mechanism to maintain normal cell number in the pulmonary vasculature. Inhibition of BMP-induced PASMC apoptosis in PPH patients may play an important role in the development of pulmonary vascular medial hypertrophy in these patients.

Apoptosis↗

PubMed2002

Metastatic melanoma in a patient with Clouston syndrome successfully treated with isolated hyperthermic limb perfusion.

BACKGROUND: Clouston syndrome is an autosomal dominant disorder characterized by nail dystrophy, partial or total alopecia, and hyperkeratosis of the palms and soles. OBJECTIVE: Although a variety of unusual cutaneous manifestations have been described, the incidence of melanoma in this population is unknown. METHODS: This article reports a case of in-transit metastatic subungual melanoma in a patient with Clouston syndrome successfully treated with hyperthermic limb perfusion with melphalan. RESULTS: Six months postperfusion, the patient is doing well, with resolution of the extremity erythema and edema. Followup ultrasonography revealed reduction in size of the eight subcutaneous nodules, with the largest measuring 3.3 cm in maximum diameter, representing nearly a 50% reduction in tumor volume postperfusion. CONCLUSION: Although melanoma has also been associated with some forms of ectodermal dysplasia, such as ectrodactyly--ectodermal dysplasia--clefting (EEC) syndrome, the incidence of melanoma in patients with Clouston syndrome is unknown. Thus far, to our knowledge, this is the first case report of melanoma arising in a patient with Clouston syndrome.

Adult↗

PubMed2002

Beyond peripheral arteries in Buerger's disease: angiographic considerations in thromboangiitis obliterans.

Thromboangiitis obliterans is an inflammatory peripheral vascular disease that is strongly associated with smoking. It predominantly affects distal small- and medium-sized blood vessels of both the upper and lower extremities. We present histological evidence of this disease process affecting the internal mammary arteries. This can be of paramount clinical significance for patients with Buerger's disease who present with obstructive coronary artery disease and require coronary artery bypass grafting surgery (CABG). Internal mammary arteries involved with thromboangiitis obliterans cannot be utilized as arterial conduits during CABG and other alternatives have to be used. Therefore, we recommend preoperative angiography of both internal mammary arteries in patients with Buerger's disease requiring CABG to prevent extensive intraoperative dissection of diseased internal mammary arteries.

Adult↗

PubMed2002

Hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is a group of immunologically mediated lung diseases caused by the inhalation of environmental agents in susceptible individuals. Most HP patients are non-smokers and have been exposed to organic dusts from vegetable or animal products. Some HP cases are associated with exposures to relatively simple chemical compounds. HP may present as an acute, subacute, or chronic disease and may follow various clinical courses. The type of exposure is thought to be more important in the clinical outcome than the nature of the antigen. A diagnosis of HP is often considered on the basis of clinical history of exposure with resulting respiratory symptoms, but the definitive diagnosis requires a constellation of clinical, radiologic, laboratory, and pathologic findings. The characteristic histologic triad in HP includes bronchiolitis, interstitial lymphocytic infiltration, and granulomas; however, biopsy in HP cases may lack the diagnostic triad and manifest as nonspecific interstitial pneumonia (NSIP). Avoiding exposure to the offending antigen(s) is usually sufficient to resolve symptoms and physiological abnormalities. Pulmonary fibrosis and physiological abnormalities occurring in chronic HP may be irreversible. Steroid therapy is helpful for symptomatic relief, but probably does not affect the long-term prognosis. Type III and type IV hypersensitivity reactions are involved in the pathogenesis; alveolar macrophages and T cells (Th-1 type) play a central role in the immune responses after antigen exposure via their increased interaction and secretion of regulatory mediators.

Allergens↗

PubMedDate not supplied

Granulocytic sarcoma of the tracheobronchial tree: bronchoscopic and pathologic correlation.

Granulocytic sarcoma (GS) is an extramedullary, solid tumor composed of immature granulocytic cells, which occurs in association with myeloproliferative or leukemic disorders. GS can precede, accompany, or complicate the presence of hematologic malignancy in the blood or bone marrow. The anatomic distribution commonly includes bone, nerve, lymph node, and skin, but may involve a variety of soft tissues. Pulmonary involvement is uncommon but may invade the parenchyma, pleura, mediastinum, and airways. We report a rare case of endobronchial granulocytic sarcoma with bronchoscopic and pathologic correlation.

Acute Disease↗