Germinal centers are associated with postthymectomy myasthenia gravis in patients with thymoma.

BACKGROUND AND PURPOSE: Germinal centers (GCs) can be observed in the thymic tissues of patients with thymoma-associated myasthenia gravis (MG). Although an association between thymic GCs and MG has been suggested, it is unknown whether the presence of GCs could predict the development of MG after the resection of thymoma, known as postthymectomy MG. METHODS: We conducted a retrospective analysis of previously nonmyasthenic patients who underwent surgical removal of the thymoma. All available thymic tissue slides were rereviewed by a pathologist to assess for GCs. Patients were classified into GC-positive and GC-negative groups based on the presence of GCs. The incidence of postthymectomy MG was compared between the two groups, and the risk factors for postthymectomy MG were assessed. RESULTS: Of the 196 previously nonmyasthenic patients who underwent thymoma resection, 21 were GC-positive, whereas 175 were GC-negative. Postthymectomy MG developed in 11 (5.6%) patients and showed a higher incidence in the GC-positive group than in the GC-negative group (33.3% vs. 2.3%, p < 0.001). No postoperative radiotherapy and the presence of GCs were risk factors for postthymectomy MG in the univariate analysis. In multivariate analysis, invasive thymoma (hazard ratio [HR] = 9.835, 95% confidence interval [CI] = 1.358-105.372), postoperative radiotherapy (HR = 0.160, 95% CI = 0.029-0.893), and presence of GCs (HR = 15.834, 95% CI = 3.742-67.000) were significantly associated with postthymectomy MG. CONCLUSIONS: Thymic GCs may be a significant risk factor for postthymectomy MG. Even in patients with thymoma who do not show clinical symptoms of MG, postthymectomy MG should be considered, especially if thymic GCs are observed.

Efficient diagnosis of IDH-mutant gliomas: 1p/19qNET assesses 1p/19q codeletion status using weakly-supervised learning.

Accurate identification of molecular alterations in gliomas is crucial for their diagnosis and treatment. Although, fluorescence in situ hybridization (FISH) allows for the observation of diverse and heterogeneous alterations, it is inherently time-consuming and challenging due to the limitations of the molecular method. Here, we report the development of 1p/19qNET, an advanced deep-learning network designed to predict fold change values of 1p and 19q chromosomes and classify isocitrate dehydrogenase (IDH)-mutant gliomas from whole-slide images. We trained 1p/19qNET on next-generation sequencing data from a discovery set (DS) of 288 patients and utilized a weakly-supervised approach with slide-level labels to reduce bias and workload. We then performed validation on an independent validation set (IVS) comprising 385 samples from The Cancer Genome Atlas, a comprehensive cancer genomics resource. 1p/19qNET outperformed traditional FISH, achieving R2 values of 0.589 and 0.547 for the 1p and 19q arms, respectively. As an IDH-mutant glioma classifier, 1p/19qNET attained AUCs of 0.930 and 0.837 in the DS and IVS, respectively. The weakly-supervised nature of 1p/19qNET provides explainable heatmaps for the results. This study demonstrates the successful use of deep learning for precise determination of 1p/19q codeletion status and classification of IDH-mutant gliomas as astrocytoma or oligodendroglioma. 1p/19qNET offers comparable results to FISH and provides informative spatial information. This approach has broader applications in tumor classification.

Genomic and transcriptomic profiling reveal molecular characteristics of parathyroid carcinoma.

Genomic and transcriptomic profiling has enhanced the diagnostic and treatment options for many cancers. However, the molecular characteristics of parathyroid cancer remain largely unexplored, thereby limiting the development of new therapeutic interventions. Herein, we conducted genomic and transcriptomic sequencing of 50 parathyroid tissues (12 carcinomas, 28 adenomas, and 10 normal tissues) to investigate the intrinsic and comparative molecular features of parathyroid carcinoma. We confirmed multiple two-hit mutation patterns in cell division cycle 73 (CDC73) that converged to biallelic inactivation, calling into question the presence of a second hit in other genes. In addition, allele-specific repression of CDC73 in copies with germline-truncating variants suggested selective pressure prior to tumorigenesis. Transcriptomic analysis identified upregulation of the expression of E2F targets, KRAS and TNF-alpha signaling, and epithelial-mesenchymal transition pathways in carcinomas compared to adenomas and normal tissues. A molecular classification model based on carcinoma-specific genes clearly separated carcinomas from adenomas and normal tissues, the clinical utility of which was demonstrated in two patients with uncertain malignant potential. A deeper analysis of gene expression and functional prediction suggested that Wilms tumor 1 (WT1) is a potential biomarker for CDC73-mutant parathyroid carcinoma, which was further validated through immunohistochemistry. Overall, our study revealed the genomic and transcriptomic profiles of parathyroid carcinoma and may help direct future precision diagnostic and therapeutic improvements.

Intravesical bacillus Calmette-Guérin-induced myopathy presenting as rhabdomyolysis: a case report.

Intravesical bacillus Calmette-Guérin (BCG) instillation is an adjuvant treatment for non-muscle-invasive urinary bladder cancer. Although most complications associated with BCG immunotherapy are mild and self-limiting, rare albeit serious complications have been reported. Only a few cases of BCG-related rhabdomyolysis have been reported. In this study, we present the case of a 72-year-old woman who developed severe weakness and hyperCKemia following intravesical BCG instillation. A muscle biopsy was performed, and a diagnosis of drug-induced myopathy was made.

TERT Promoter and BRAF V600E Mutations in Papillary Thyroid Cancer: A Single-Institution Experience in Korea.

Telomerase reverse transcriptase (TERT) promoter mutation has been investigated for its clinical and prognostic significance in aggressive papillary thyroid cancer (PTC). In this study, we aimed to assess the prevalence, clinicopathologic features, and treatment outcomes of TERT mutation-positive PTCs along with the common BRAF V600E mutation. We performed mutational analyses for BRAF and the TERT promoter in thyroid cancer patients who had undergone surgery at our institution since 2019. We reviewed and analyzed 7797 patients with PTC in this study. The prevalence of BRAF V600E and TERT promoter mutations was 84.0% and 1.1%, respectively. Multifocal gene mutations in bilateral PTCs were identified. TERT promoter mutations were associated with older age, larger tumor size, tumor multifocality, tumor variants, advanced stages, more adjuvant radioactive iodine treatment (RAI), higher stimulated serum thyroglobulin level before RAI, and more uptakes in the regions outside the surgical field on a post-RAI whole-body scan. The coexistence of BRAF V600E and TERT promoter mutations exacerbated all clinicopathologic characteristics. The frequency of TERT promoter mutations was the lowest in this study, compared to previous studies. TERT promoter mutations consistently correlated with aggressive PTCs, and the synergistic effect of both mutations was evident. Specific clinical settings in our institution and in Korea may have led to these distinctive results. Prospective multicenter studies with longer follow-up periods are required to establish valuable oncologic outcomes.

Preoperative Thoracic Muscle Mass Predicts Bone Density Change After Parathyroidectomy in Primary Hyperparathyroidism.

CONTEXT: Predicting bone mineral density (BMD) gain after parathyroidectomy may influence individualized therapeutic approaches for treating patients with primary hyperparathyroidism (PHPT). OBJECTIVE: This study aimed to assess whether skeletal muscle mass data could predict BMD change after parathyroidectomy in patients with PHPT. METHODS: This retrospective study collected data from 2012 to 2021 at Severance Hospital, Seoul, Korea. A total of 130 patients (mean age, 64.7 years; 81.5% women) with PHPT who underwent parathyroidectomy were analyzed. Thoracic muscle volume (T6-T7 level) was estimated using noncontrast parathyroid single photon emission computed tomography/computed tomography (SPECT/CT) scans and an automated deep-learning-based software. The primary outcome assessed was the change in femoral neck BMD (FNBMD, %) 1 year after parathyroidectomy. RESULTS: The median degree of FNBMD change after parathyroidectomy was + 2.7% (interquartile range: -0.9 to + 7.6%). Elevated preoperative PTH level was associated with lower thoracic muscle mass (adjusted ß: -8.51 cm3 per one log-unit PTH increment, P = .045) after adjusting for age, sex, body mass index (BMI), and baseline FNBMD. One SD decrement in thoracic muscle mass was associated with lesser FNBMD (adjusted ß: -2.35%, P = .034) gain and lumbar spine BMD gain (adjusted ß: -2.51%, P = .044) post surgery after adjusting for covariates. CONCLUSION: Lower thoracic skeletal muscle mass was associated with elevated preoperative PTH levels in patients with PHPT. Lower skeletal muscle mass was associated with lesser BMD gain after parathyroidectomy, independent of age, sex, BMI, preoperative BMD, and PTH level.

High-sensitivity C-reactive Protein and Regression of Low-grade Squamous Intraepithelial Lesion: The Role of Low-grade Inflammation in Cervical Carcinogenesis.

BACKGROUND: Inflammation is emerging as a potential mechanism of cervical carcinogenesis. However, few studies have investigated the association between host inflammatory status and the natural course of cervical precursor lesion. The aim of this study was to assess the probability of LSIL regression, associated with an inflammatory biomarker, high-sensitivity C-reactive protein (hs-CRP). METHODS: In a longitudinal cohort study, female participants were examined annually or biannually using cervical cytology between 2006 and 2015. Incident LSIL cases were included in the analysis, with regression defined as at least one consecutive normal cytologic result. A total of 520 women aged 22-64 years were followed up for LSIL regression. The multivariable-adjusted hazard ratios (HRs) for LSIL regression were estimated using a parametric proportional hazards model. RESULTS: During 827.5 person-years of follow-up, 486 out of 520 subjects (93.5%) showed LSIL regression. After adjusting several important potential confounders, a higher quartile of hs-CRP levels was significantly associated with a lower rate of regression (for quartile 4 vs quartile 1, inverse HR 1.33; 95% CI, 1.04-1.69; P for trend = 0.028). CONCLUSIONS: The low rate of spontaneous regression recorded in women with higher hs-CRP lends support to the role of the perturbated host inflammatory status in cervical carcinogenesis, and suggests that hs-CRP level could help monitor LSIL.

Expression of UTX Indicates Poor Prognosis in Patients With Luminal Breast Cancer and is Associated With MMP-11 Expression.

Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX) is involved in the epigenetic regulation. A previous mouse xenograft study revealed that UTX knockdown is associated with downregulated expression of matrix metalloproteinase-11 (MMP-11). The authors investigated 224 cases of breast cancer from Kangbuk Samsung Medical Center between 2000 and 2005. Nuclear UTX and cytoplasmic MMP-11 expressions were assessed using immunohistochemistry of tumor tissue microarray specimens. The relationships between the expression of UTX, MMP-11, and patients' outcomes were analyzed. UTX expression was significantly associated with high histologic grade, lymphatic invasion, vascular invasion, and tumoral expression of MMP-11. Survival analysis revealed that patients with UTX expression had a poorer overall survival rate (P=0.010) as well as diminished disease-free survival rate (P=0.001). The prognostic power of UTX expression was significant in patients with luminal-type breast cancer (P=0.027, overall survival; P=0.008, disease-free survival). Validation of UTX can provide further prognostic information beyond traditional indicators and represents a potential therapeutic target for breast cancer.

Prognostic impact of high p16/cyclin D1 index in breast cancer.

Proteins p16 and cyclin D1 (CCND1) are known to tightly regulate the G1/S transition during the cell cycle, but their role in breast cancer development and progression is not clear. We investigated 224 cases of breast cancer from the Kangbuk Samsung Medical Center between 2000-2005. Expression levels of p16 and CCND1 were assessed by tissue microarray-based immunohistochemistry. A p16/CCND1 index was divided into low- and high-expression groups using receiver operating characteristic curves. The p16/CCND1 index was significantly different across molecular subtypes and a high p16/CCND1 index was statistically correlated with survival rates. This p16/CCND1 index may be an indicator of poor patient outcome and thus, represents a potential therapeutic target.

Loss of p27kip1 expression is associated with poor prognosis in patients with taxane-treated breast cancer.

PURPOSE: Decreased expression of p27kip1 and p57kip2 is considered as a prognostic indicator in patients with breast cancer receiving adjuvant chemotherapy. Previous in vitro studies have reported that reduced expression of p27kip1 and p57kip2 is associated with resistance to taxane, which is one of the most effective chemotherapeutic agents. In this study, we investigated the association of low p27kip1 and p57kip2 expression with outcomes in patients with breast cancer. METHODS: We investigated 226 cases of breast cancer from Kangbuk SMC between 2000 and 2005. Levels of p27kip1 and p57kip2 expression were evaluated using immunohistochemical staining of tumor tissue microarray specimens. The relationships between the expression levels of the markers and patients' outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazard model. RESULTS: Low p57kip2 expression was only associated with negative progesterone receptor status (p = 0.034), whereas p27kip1 expression was associated with poor prognosis of patients receiving adjuvant chemotherapy (p = 0.005). More detailed analysis revealed that low p27kip1 expression affects the overall survival rate of patients receiving adjuvant chemotherapy including taxane (p = 0.026), but not that of patients receiving chemotherapy without taxane. CONCLUSIONS: Low p27kip1 expression may be useful to predict overall survival in patients with breast cancer who are treated with taxane. Evaluation of p27kip1 expression may provide further prognostic information beyond traditional prognostic biomarkers and an understanding of the mechanisms that impart resistance against chemotherapy.

Tumour epithelial and stromal characteristics of hepatocellular carcinomas with abundant fibrous stroma: fibrolamellar versus scirrhous hepatocellular carcinoma.

AIMS: The scirrhous variant of hepatocellular carcinoma (S-HCC) and fibrolamellar HCC (FL-HCC) are less common subtypes of HCC that are characterized by abundant fibrous stroma. Here, we aimed to investigate differences in the tumour microenvironment and the tumour epithelial cell characteristics of S-HCC and FL-HCC. METHODS AND RESULTS: Whole tissue sections of 17 S-HCCs and 9 FL-HCCs were subjected to immunohistochemical stains for keratin 7 (K7), K19, EpCAM, CD56/NCAM, CD163, CD68, pSTAT3, FAP, CCN2 and Ki-67. FL-HCC patients were younger than S-HCC patients (P < 0.001), and chronic liver disease was seen in the background of 88.2% of S-HCC and in none of the FL-HCC. CD68 and CD163-positive tumour-infiltrating macrophages, and FAP-positive cancer-associated fibroblasts (CAFs) were more abundant in the stroma of S-HCCs compared to FL-HCCs (all P < 0.05). Tumour epithelial K19 expression was more frequent in S-HCCs compared to FL-HCCs (P = 0.023). Significant positive correlations were seen between pSTAT3 expression status in tumour epithelial cells and CAFs, the extent of stromal CAF and macrophage infiltration and K19 expression status. No significant differences were seen for K7, EpCAM, CD56/NCAM, CCN2 expression and Ki-67 labelling index between S-HCCs and FL-HCCs. CONCLUSION: S-HCC and FL-HCC are subtypes of HCC with extensive fibrosis, and the nature of the fibrous stroma differs between them. While the stroma of FL-HCC is composed of dense lamellated collagenous bands with sparse cellular components, S-HCC demonstrates more abundant CAF and tumour-infiltrating macrophages and stemness-related marker expression, suggesting the presence of a complex tumour microenvironment that may influence the aggressive behaviour of S-HCCs.

Increased expression of CCN2, epithelial membrane antigen, and fibroblast activation protein in hepatocellular carcinoma with fibrous stroma showing aggressive behavior.

Tumor behavior is affected by the tumor microenvironment, composed of cancer-associated fibroblasts (CAFs). Meanwhile, hepatocellular carcinomas (HCC) with fibrous stroma reportedly exhibit aggressive behavior suggestive of tumor-stroma interaction. However, evidence of the crosstalk remains unclear. In this study, CCN2, epithelial membrane antigen (EMA), fibroblast activation protein (FAP), and keratin 19 (K19) expression was studied in 314 HCCs (cohort 1), 42 scirrhous HCCs (cohort 2), and 36 chronic hepatitis/cirrhosis specimens by immunohistochemistry. Clinicopathological parameters were analyzed according to the expressions of these markers. In tumor epithelial cells from cohort 1, CCN2 and EMA were expressed in 15.3% and 17.2%, respectively, and their expressions were more frequent in HCCs with fibrous stroma (≥5% of tumor area) than those without (P<0.05 for all); CCN2 expression was well correlated with K19 and EMA expression. In tumor stromal cells, FAP expression was found in 6.7%. In cohort 2, CCN2, EMA, and FAP expression was noted in 40.5%, 40.5%, and 66.7%, respectively, which was more frequent than that in cohort 1 (P<0.05 for all). Additionally, EMA expression was associated with the expression of K19, CCN2, and FAP (P<0.05 for all); EMA expressing tumor epithelial cells showed a topographic closeness to FAP-expressing CAFs. Analysis of disease-free survival revealed CCN2 expression to be a worse prognostic factor in both cohort 1 (P = 0.005) and cohort 2 (P = 0.023), as well as EMA as a worse prognostic factor in cohort 2 (P = 0.048). In conclusion, expression of CCN2, EMA, and FAP may be involved in the activation of CAFs in HCC, giving rise to aggressive behavior. Significant correlation between EMA-expressing tumor cells and FAP-expressing CAFs and their topographic closeness suggests possible cross-talk between tumor epithelial cells and stromal cells in the tumor microenvironment of HCC.

ß-Catenin activated hepatocellular adenoma: a report of three cases in Korea.

Hepatocellular adenoma (HCA) is an uncommon benign hepatic tumor, and the use of oral contraceptives is known to contribute to the development of HCA. Recently, a genotype and phenotype classification system for HCA was suggested, and malignant transformation to hepatocellular carcinoma (HCC) was shown to be strongly associated with activating mutations in ß-catenin. Here, we report three cases of HCA in Korean patients: 7-cm, inflammatory and ß-catenin-activated HCA with HCC transformation in a 46-year-old man; 13-cm, ß-catenin-activated HCA with cytological atypia in a 23-year-old woman; and 10-cm, pigmented, inflammatory and ß-catenin-activated HCA in a 36-year-old man. All cases exhibited the nuclear expression of ß-catenin and diffuse cytoplasmic expression of glutamine synthetase upon immunohistochemical staining. All tumors were completely resected, and the patients were followed for 3 to 6 years with no evidence of local recurrence or metastasis.

Low-grade adenosquamous carcinoma of the breast with diverse expression patterns of myoepithelial cell markers on immunohistochemistry: a case study.

This paper reports a case of low-grade adenosquamous carcinoma (LGASC) arising in a 69-year-old woman, who presented with a 1-cm palpable mass on her right breast. Core needle biopsy diagnosed the mass as a fibroadenoma. After six months, the mass increased in size, and the patient received subsequent mammotome excision. On microscopic examination, bland-looking small glands were infiltrating into the fibrotic stroma with lymphocytic infiltrates at the periphery. Hematoxylin and eosin staining revealed relatively easily detectable myoepithelial cells along the outside in each of the glandular structures with variable degrees of squamous metaplasia. Based on histologic features, the patient was diagnosed with LGASC. LGASC is a rare variant of metaplastic carcinoma, which is characterized by a favorable prognosis. Due to the bland cytology and presence of myoepithelial cells, LGASC can be misdiagnosed as benign lesion. Additionally, inconsistent expression of myoepithelial markers could aid the diagnosis of LGASC.

Usefulness of FDG PET/CT in the diagnosis of eosinophilic fasciitis.

Eosinophilic fasciitis is a rare disorder with similar characteristics of scleroderma-like illness. We report a case of eosinophilic fasciitis in a 37-year-old woman with a 3-month history of progressive stiffness involving her forearms and lower legs. Laboratory test disclosed elevated erythrocyte sedimentation ratio and hypereosinophilia. On PET/CT images, FDG uptake was increased along the fasciae of bilateral upper and lower extremities while sparing muscles and subcutaneous fat. Biopsy was performed and histologic examination confirmed diagnosis of eosinophilic fasciitis. FDG PET/CT may be helpful in the diagnosis of eosinophilic fasciitis as it could clearly illustrate anatomical involvement of the disease.

Increased expression of Yes-associated protein 1 in hepatocellular carcinoma with stemness and combined hepatocellular-cholangiocarcinoma.

Combined hepatocellular-cholangiocarcinoma (cHC-CC) and some hepatocellular carcinomas (HCCs) express stemness-related markers, such as epithelial adhesion molecule (EpCAM) and keratin 19 (K19), the expression of which has been reported to be associated with more aggressive behavior therein than in HCCs without. Yes-associated protein 1 (YAP1), a potential oncogene, is known to promote stem cell proliferation. In the present study, YAP1 expression and clinicopathological features were evaluated and compared among three groups comprising 36 HCCs that expressed both EpCAM and K19, 64 HCCs that did not express EpCAM and K19, and 58 cHC-CCs, which consisted of 38 cases of the classical type and 20 cases of the intermediate-cell subtype. YAP1 expression was more frequently noted in EpCAM(+)/K19(+) HCCs (55.6%) and in cHC-CCs (67.2%) than in EpCAM(-)/K19(-) HCCs (17.2%) (P<0.001 for both). In cHC-CCs, YAP1 expression was observed in 63% of classical type cHC-CCs and in 75% of the intermediate subtype; moreover, such expression was correlated with poorer histological differentiation (P = 0.017) and was more frequently noted in transition zones than in HCC areas (P = 0.060). Disease-free and overall survival showed a statistically significant difference among the three groups: disease-free survival was highest for EpCAM(-)/K19(-) HCCs and lowest for cHC-CCs, with EpCAM(+)/K19(+) HCCs falling in between (P<0.05). Overall survival rate was lower in HCCs and cHC-CCs with YAP1 expression compared to those without (P = 0.05), whereas disease-free survival showed no significant difference according to YAP1 expression. Increased YAP1 expression was more frequently found in cHC-CCs and HCCs with stemness than in HCCs without, and a YAP1 pathway is suggested to be involved in the obtainment stemness characteristics in HCCs and cHC-CCs.

Minute pulmonary meningothelial-like nodules simulating hematogenous lung metastasis: a case report.

A 52-year-old man was referred to our clinic for an 11.3 mm nodule in the left lower lobe that was discovered on a chest computed tomography (CT) scan. Eleven small nodules were subsequently found in both lungs. Initially, we performed a transthoracic needle aspiration using CT scan guidance. The pathologic report showed a few clusters of atypical cells that were suspicious for malignancy. The positron emission tomography images revealed multiple lung nodules scattered throughout both lungs. The largest nodule (11.3 mm) in the left lower lobe did not have any discernible fludeoxyglucose uptake. For pathologic confirmation, we consulted a thoracic surgeon to perform the video-assisted thoracoscopic surgery. The final diagnosis was minute pulmonary meningothelial-like nodules (MPMNs). MPMNs are benign in nature, and only a few cases require treatment. However, when clinicians are suspicious of potential malignancy, a pathological correlation is essential, even if the final diagnosis is MPMNs.

RASSF1A-mediated regulation of AREG via the Hippo pathway in hepatocellular carcinoma.

Ras association domain family 1 isoform A (RASSF1A) is a tumor suppressor that is methylated in many human cancers, including hepatocellular carcinoma (HCC). RASSF1A has been shown to suppress tumors via activation of the Hippo tumor suppressor pathway, including mammalian STE20-like kinase (MST). Amphiregulin (AREG), a target gene for Yes-associated protein (YAP), is a known oncogenic component of the Hippo pathway; however, the tumor-suppressive effect of RASSF1A on AREG in regard to regulation of the Hippo pathway remains unclear in HCC. Overexpression of RASSF1A in HCC cells, which lack functional RASSF1A, significantly inhibited cell proliferation and induced apoptosis by activating the Hippo pathway. Consequently, overexpression of RASSF1A inhibited the oncogenic functions of YAP, leading to a significant reduction in AREG secretion via regulation of the Hippo pathway. In human specimens, greater expression of RASSF1A was observed in chronic hepatitis/cirrhosis than in HCC, whereas expression of YAP and AREG was higher in 81% and 86% of HCC than in corresponding chronic hepatitis/cirrhosis, respectively. Furthermore, RASSF1A protein gradually decreased as multistep hepatocarcinogenesis progressed from chronic hepatitis/cirrhosis dysplastic nodules toward HCC, whereas the protein expression of YAP and AREG gradually increased. These findings provide mechanistic insight into the regulation of YAP and AREG by RASSF1A in human multistep hepatocarcinogenesis.

A case of membranous nephropathy as a manifestation of graft-versus-host disease.

Nephrotic syndrome (NS) rarely occurs after hematopoietic stem cell transplantation (HSCT) as a late manifestation of graft-versus-host disease (GVHD). Herein, we report a case of HSCT-associated membranous nephropathy in a female patient with aplastic anemia. The patient received an allogeneic HSCT from her human leukocyte antigen-identical brother following myeloablative conditioning chemotherapy. NS occurred 21 months after HSCT without any concurrent features of chronic GVHD. The patient was treated with prednisolone and cyclosporine after renal biopsy confirmed membranous nephropathy, and achieved complete remission. Our report contradicts previous assumptions that concomitant chronic GVHD is responsible for the development of NS, suggesting that NS can develop as a new, independent manifestation of GVHD.