Kyi Beom Lee

Melasma: histopathological characteristics in 56 Korean patients

Summary Background  Melasma is a common acquired symmetrical hypermelanosis characterized by irregular light to dark brown macules and patches on sun‐exposed areas of the skin. Its histopathological characteristics are not fully understood.

P-glycoprotein: The intermediate end point of drug response to induction chemotherapy in locally advanced breast cancer

Expression and clinical relevance of p-glycoprotein (p-gp) were evaluated in 31 cases of locally advanced breast cancer and 9 cases involving inflammatory breast cancer after induction chemotherapy. The de novo p-gp expression rate was 26% and increased up to 58% (p = 0.03) with the FAC (5-fluorouracil, adriamycin, cyclophosphamide) regimen. Although more clinically complete responders were found in the secondary p-gp negative group (p = 0.02), this difference was not found in pathological tumor response. Moreover, as the grade of the secondary p-gp expression increased, the chemotherapeutic effect decreased, suggesting an inverse relationship between p-gp expression and drug effect (p = 0.04). When we subgrouped the patients into 4 groups using these two parameters, p-gp negative patients presenting with a high drug effect showed a low recurrence rate (p = 0.05) and marginal survival benefits (p = 0.09) as opposed to patients with a low drug effect. But in p-gp positive groups, the recurrence rate was the same between the two groups regardless of the drug effect. Thus, in the p-gp negative patient with a high drug effect, adjuvant chemotherapy with the same regimen as induction chemotherapy may induce more prognostically favorable results. Therefore, clinical application of the secondary p-gp detection can be used as an intermediate endpoint in evaluating drug response for an induction regimen.

Clinical usefulness of the fluorodeoxyglucose (FDG)-PET maximal standardized uptake value (SUV) in combination with CT features for the differentiation of adenocarcinoma with a bronchioloalveolar carcinoma from other subtypes of non-small cell lung cancers

PURPOSE To evaluate the clinical usefulness of fluorodeoxyglucose (FDG)-PET maximal SUV in combination with CT features for differentiation of adenocarcinoma with bronchioloalveolar carcinoma (BAC) from other subtypes of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS This retrospective study included 125 patients (104 men and 21 women; mean age, 64 years) who underwent CT and subsequent FDG-PET examinations for preoperative evaluation and underwent curative intent operation with the final diagnoses of NSCLC made by surgical histopathology. We categorized NSCLC into adenocarcinoma with BAC feature and other subtypes. Finally, there were 16 cases of adenocarcinoma with BAC and 109 cases of other NSCLC subtypes included in the study. Several CT features of lung cancer were analyzed, including tumor size, presence of spiculation, margin (irregular or smooth), pattern of the mass (pure solid, pure ground glass opacity and mixed), associated pleural effusion and location (center, mid and periphery). Maximal SUV and visual scores of FDG uptakes of primary NSCLC were evaluated. The diagnostic performances of CT alone, PET alone, and combination of two modalities to predict adenocarcinoma with BAC from other subtypes of NSCLC were calculated. RESULTS A nodule with a mixed pattern with partly solid and ground glass opacity was significantly more frequent CT feature of an adenocarcinoma with BAC (8/16, 50%) as compared with the other subtypes (2/109, 1.8%) (p<0.0001). Maximal SUV of adenocarcinoma with BAC (mean=7.2) was significantly lower than that of other subtypes of NSCLC (mean=13.33) (p<0.0001). Sensitivity, specificity, PPV, and NPV of CT for differentiating adenocarcinoma with BAC from other subtypes was 50% (8/16), 98.2% (107/109), 80% (8/10), and 93% (107/115), respectively. Sensitivity, specificity, PPV, and NPV of FDG-PET was 68.8% (11/16), 86.2% (94/109), 42.3% (11/26), and 94.9% (94/99), respectively. Sensitivity, specificity, PPV, and NPV of combination of two modalities was 81.3% (13/16), 85.3% (93/109), 44.8% (13/29), 96.9% (93/96), respectively. CONCLUSION Careful combined assessment of the FDG-PET maximal SUV and CT findings have the potential to differentiate an adenocarcinoma with BAC from other NSCLC subtypes, such as a pure BAC. These findings might be useful for imaging interpretations and will help initial planning of NSCLC management.

Pathologic Diagnosis of Recurrent Glioblastoma: Morphologic, Immunohistochemical, and Molecular Analysis of 20 Paired Cases

To evaluate the prognostic value of the volume of residual viable tumor versus therapy-induced necrosis in resection material and the diagnostic value of ancillary tests in recurrent glioblastoma (GBM), we conducted a retrospective review of 20 patients whose initial and recurrent specimens were available. Recurrent GBMs were graded according to the extent of histopathologic parameters: recurrent tumor with high-grade, non–high-grade, and pure high-grade tumor components and therapy-related necrosis. We also examined MIB-1 labeling, isocitrate dehydrogenase 1R132H mutation, and epidermal growth factor receptor amplification in primary and recurrent GBMs. To evaluate patient outcomes according to clinical and pathologic parameters, a survival analysis was performed, and correlations between histopathologic parameters and each ancillary test were assessed. Among clinical parameters, age above 60 years was associated with decreased survival (P=0.022), but other clinical parameters showed no significant association with overall survival. Among the 3 histopathologic parameters, the extent of recurrent tumor, including high-grade and non–high-grade components, revealed a significant association with overall survival (P=0.042), but neither the extent of pure high-grade components nor therapy-related necrosis showed any prognostic value. MIB-1 labeling, isocitrate dehydrogenase 1R132H mutation, and epidermal growth factor receptor amplification were useful for the diagnosis of recurrent GBMs but showed no prognostic value. Our data suggest that histopathologic evaluation on the basis of tumor extent in resected recurrent GBM specimens may provide additional prognostic information on the survival of patients with recurrent GBM.

Cyclooxygenase-2 and p53 expression as prognostic indicators in conventional renal cell carcinoma.

The aim of this study was to investigate the relationship of cyclooxygenase (COX)-2 and p53 expression with prognosis in patients with conventional renal cell carcinoma (RCC). Formalin-fixed, paraffin-embedded tissue sections of conventional RCC from 92 patients, who had undergone radical nephrectomy, were examined for COX-2 and p53 expression by immunohistochemistry and compared with clinicopathological variables. The COX-2 expression significantly correlated only with tumor size (p=0.049), whereas the p53 expression profoundly correlated with the TNM stage (p=0.024), M stage (p=0.001), and metastasis (synchronous or metachronous; p=0.004). The COX-2 overexpression did not significantly associate with p53 positivity (p=0.821). The survival rate of patients correlated with the p53 expression (p<0.0001) but not with the COX-2 expression (p=0.7506). Multivariate analyses indicated that tumor size, M stage, and p53 expression were independent prognostic factors for cancer-specific survival. The COX-2 expression was not an independent factor. These results show that the increased expression of p53 was associated with metastasis and a worse prognosis in conventional RCC, which suggests that p53 might have played an important role in the progression of conventional RCC. The increased expression of COX-2 was associated only with tumor size, but may not be an important prognostic factor in conventional RCC. No association was observed between COX-2 overexpression and p53 positivity in conventional RCC.

A probable case of oral bisphosphonate-associated osteonecrosis of the jaw and recovery with parathyroid hormone treatment.

INTRODUCTION Bisphosphonates are effective for treating osteoporosis, Pagets disease of bone, and malignancy-associated bone diseases. Bisphosphonate-associated osteonecrosis of the jaw (ONJ) is a rare but serious adverse effect of bisphosphonate therapy. Due to inhibitory actions on bone turnover, bisphosphonate therapy may result in the accumulation of microdamage. CASE SUMMARY A 74-year-old Korean woman (height, 150 cm; weight, 51 kg) was referred to the Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, South Korea, for evaluation of pain and persistent abnormal exposure of jaw bone after extraction of teeth. She had been receiving weekly oral alendronate treatment for osteoporosis for ~5 years. The patient had the clinical features of bisphosphonate-associated osteonecrosis of the mandible, which was precipitated by teeth extraction ~14 months prior to the outpatient referral visit. At her clinical baseline visit, serum hormone concentrations and bone turnover markers were as follows: thyroid-stimulating hormone, 0.88 μIU/mL (reference range, 0.25-5.00 μIU/mL); 25-hydroxyvitamin D3, 20.9 (9.0-37.6) ng/mL; parathyroid hormone (PTH), 57 (11-62) pg/mL; serum osteocalcin, 8.7 (12.9-55.9) ng/mL; and urine N-telopeptide 21 (26-124) nM/mM creatinine. She had multiple systemic risk factors for ONJ, including older age, type 2 diabetes mellitus, and long duration of bisphosphonate therapy. There was no mandibular lesion improvement despite repeated surgical procedures performed within a 14-month period. Bisphosphonate therapy was discontinued and PTH therapy was started. After 2 months, exposed oral mucosa had healed. After 4 months of treatment, the pain had completely subsided, and after 6 months the patients eating and drinking habits returned. The serum concentration of osteocalcin, a bone formation marker, which was initially suppressed (8.7 ng/mL), increased 174% (15.1 ng/mL) from baseline after 6 months of treatment with PTH. CONCLUSIONS Here we report a probable case of oral bisphosphonate-associated ONJ featuring suppressed bone turnover. Treatment with the bone formation-stimulating agent PTH was beneficial.

Primary pulmonary malignant fibrous histiocytoma mimics pulmonary artery aneurysm with partial thrombosis: various radiologic evaluations

Primary pulmonary malignant fibrous histiocytoma (MFH) is very rare, so only a few imaging features have been reported. We report one case of rapidly growing primary pulmonary MFH mimicking a partially thrombosed pulmonary artery aneurysm and its radiologic findings, including multidetector row computed tomography (MDCT), conventional angiography, and fluorodeoxyglucose-positron emission tomography CT ([18F] FDG-PET/CT). On multi-phasic MDCT, this mass mimicked a pulmonary artery aneurysm with partial thrombosis. However, pulmonary artery aneurysm was excluded and suggested as a hypervascular parenchymal mass by subsequent conventional angiography. On [18F] FDG-PET/CT, it was a highly metabolic mass, showing a maximal standard uptake value (SUV) 12.1. Although primary pulmonary MFH is very rare and has no specific imaging findings, our experience might be helpful to differentiate a hypervascular pulmonary mass.

Silencing of homeobox B9 is associated with down-regulation of CD56 and extrathyroidal extension of tumor in papillary thyroid carcinoma

Papillary thyroid carcinoma is the most common type of thyroid malignancy, and CD56, a neural cell adhesion molecule, is typically down-regulated in almost all cases of papillary thyroid carcinoma. Homeobox B9 is a transcription factor, belongs to the products of the homeobox transcription factor gene family, and has been known to regulate transcription of CD56 and to promote tumorigenicity and metastasis in some malignancies. In this study, we investigated the expression and relation of homeobox B9 to reduced expression of CD56 in papillary thyroid carcinomas and also a relationship between their expression and clinicopathologic parameters. Therefore, we performed CD56 and homeobox B9 immunohistochemical staining on 72 papillary thyroid carcinomas and Western blotting on 31 papillary thyroid carcinomas. CD56 protein staining revealed that it was reduced or absent in 65 papillary thyroid carcinomas (90.3%) and was related to silencing of homeobox B9 (77.8%) (P = .003). The loss of homeobox B9 expression was associated with extrathyroidal extension (P = .002), pathologic stage of tumor (P = .01), and age older than 45 years (P = .032). However, the CD56 staining did not reveal any significant relationship with clinicopathologic features (P > .05). In conclusion, reduced expression of CD56 is associated with homeobox B9 in papillary thyroid carcinomas. Furthermore, silencing of homeobox B9 is more common in older age and is linked to extrathyroidal extension and advanced pathologic stage of papillary thyroid carcinoma.

VE1 Antibody Is Not Highly Specific for the BRAF V600E Mutation in Thyroid Cytology Categories With the Exception of Malignant Cases

OBJECTIVES We evaluated the utility of the VE1 antibody that can detect a mutant protein resulting from the BRAF V600E mutation as a diagnostic tool for thyroid fine-needle aspiration cytology (FNAC). METHODS We performed VE1 immunocytochemistry on 202 FNAC specimens from surgically confirmed thyroid nodules. The results were compared with the molecular analyses of the BRAF mutation in these specimens matched with their corresponding histology. RESULTS Diagnoses of FNAC specimens included benign (9.4%), atypia of undetermined significance/follicular lesion of undetermined significance (11.4%), follicular neoplasm/suspicious for follicular neoplasm (2.0%), suspicious for malignancy (9.4%), and malignancy (65.8%). VE1 immunostaining was positive in 71.3% of FNAC specimens. The overall sensitivity of the VE1 antibody was 88.8%, specificity was 71.2%, positive predictive value was 88.2%, negative predictive value was 72.4%, and diagnostic accuracy was 83.7%. CONCLUSIONS VE1 immunocytochemistry in thyroid FNAC as a screening test for BRAF mutations is highly specific for malignant category cases but can be suboptimal due to its high false-positive rate for the nonmalignant cases.

Focal hematopoietic hyperplasia of the rib

We report a case of focal hematopoietic hyperplasia in the rib of a 24-year-old woman. This is only the fourth case to be reported in the English literature, all of which have involved the rib. Radiologically they all manifested as an expansive and radiolucent lesion and contained ill-defined areas of increased density or calcification. Histologically, all have been characterized by mixed areas of hypercellular marrow and fatty marrow. The lesion is considered a form of pseudotumor. Treatment in our case was by wide marginal excision of the rib.