Discrepancies between clinical and pathological findings seen at renal biopsy in rheumatological diseases.

OBJECTIVE: Renal biopsy contributes to the diagnosis, follow-up, and treatment of many rheumatic conditions. This study assessed the diagnostic role and safety of renal biopsies in a tertiary rheumatology clinic. METHODS: Renal biopsies performed between June 2020 and December 2022 were screened, and demographic, clinical, histopathological, and safety data were collected from patient records. RESULTS: In this study, 33 males and 38 females were included. Except for 1 patient who received acetylsalicylic acid, antiaggregant, and/or anticoagulant drugs were stopped before the biopsy. Complications included a decrease of hemoglobin in 8 patients (11.3%) and microscopic hematuria in 40 patients (56.3%). Control ultrasonography was performed in 16 patients (22.5%), and a self-limiting hematoma was found in 4 of them (5.6%) without additional complications. While less than 10 glomeruli were obtained in 9 patients (9.9%), diagnosis success was 94.4%. Histopathological data were consistent with one of the pre-biopsy diagnoses in 54 of 67 cases (80.6%) but showed discrepancies in 19.4% (n=13) of patients. A repeat biopsy was performed in 7 patients for re-staging or insufficient biopsy. CONCLUSIONS: Renal biopsy significantly contributes to rheumatology practice, especially in patients with complex clinical and laboratory findings or in whom different treatments can be given according to the presence, severity, and type of renal involvement. Although the possibility of obtaining insufficient tissue and the need for re-staging and repeat biopsy in the follow-up might be expected, complication risk does not seem to be a big concern. Renal biopsy often evidenced discrepancies between pre-biopsy diagnosis and histopathological findings.

Serum and urine TNF-like weak inducer of apoptosis, monocyte chemoattractant protein-1 and neutrophil gelatinase-associated lipocalin as biomarkers of disease activity in patients with systemic lupus erythematosus.

OBJECTIVES: TNF-like weak inducer of apoptosis (TWEAK), monocyte chemoattractant protein-1 (MCP-1) and neutrophil gelatinase-associated lipocalin (NGAL) are proinflammatory cytokines/chemokines that are considered as potential biomarkers reflecting disease activity in systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of serum (s) and urine (u) levels of TWEAK, MCP-1 and NGAL with disease activity in both renal and extra-renal SLE. METHODS: Thirty active patients with SLE (15 renal and 15 extra-renal) were recruited. Thirty-one inactive patients with SLE (16 renal and 15 extra-renal), 14 patients with ANCA-associated vasculitis (AAV) all of whom had active renal involvement and 20 healthy volunteers were selected as control groups. Serum and urine levels of TWEAK, MCP-1 and NGAL were tested using ELISA. RESULTS: Serum and urine levels of TWEAK and NGAL were significantly higher in the active SLE group compared to the inactive SLE group (sTWEAK p = 0.005; uTWEAK p = 0.026; sNGAL p < 0.001; uNGAL p = 0.002), whilst no significant differences regarding serum and urine MCP-1 levels were observed (p = 0.189 and p = 0.106, respectively). uTWEAK (p = 0.237), sMCP-1 (p = 0.141), uMCP-1 (p = 0.206), sNGAL (p = 0.419) and uNGAL (p = 0.443) levels did not differ between patients with active renal and extra-renal SLE. Serum TWEAK was higher in patients with active renal SLE (p = 0.006). There were no differences between active renal SLE and active renal AAV. Levels of all biomarkers were correlated with the SLE Disease Activity Index. CONCLUSION: sTWEAK, uTWEAK, sNGAL and uNGAL are biomarkers showing disease activity in SLE. However, our results implicate that these biomarkers may not be specific for SLE, and can be elevated in patients with active renal involvement of AAV.

DICER1 Hotspot Mutations in Pleuropulmonary Blastoma: A Case Series From a Tertiary Center.

Pleuropulmonary blastoma (PPB) is a potentially aggressive, rare childhood neoplasia. We investigated histopathological features, survival, and DICER1 hotspot mutations among PPB patients. Archive records at our institution were reviewed, covering a 20-year period. Thirteen children (6 males and 7 females) with a mean age of 30.5 (range 6-83) months were included. The tumor subtypes were type I in 6 (46%), type II in 4 (31%), and type III in 3 (23%). Only tumors with type II and type III histology showed anaplasia (4/7, 57%). Median follow-up was 28 (range 9-216) months. Three-year overall survival rate was 83.3% and 3-year progression-free survival rate was 25%. Progression was seen in 60% (3/5) of type I and 66.7% (4/6) of type II and type III cases. Two patients died of disseminated disease at 9 and 44 months. Hotspot missense mutations on DICER1 gene were detected in all 11 patients with available tumor tissue. We found an additional novel germline loss-of-function mutation (c.5436dupT; p.E1813*) in 1 case. To the best of our knowledge, this is the first study to investigate hotspot missense mutations on DICER1 gene among the largest series of Turkish children with PPB.

Urinary CXCL9 and CXCL10 Levels and Acute Renal Graft Rejection.

BACKGROUND: Monitoring of chemokines, CXCL9 and CXCL10, in serum may present a non-invasive detection method for rejection. OBJECTIVE: To investigate the relationship between urinary levels of CXCL9 and CXCL10 and graft function following renal transplantation. METHODS: 75 living-related donor renal transplant recipients were studied. Urinary levels of chemokines were collected pre-operatively, on post-operative 1st day, 7th day, 1st month, 3rd month, and at the time of rejection. Chemokines levels were assayed using and enzyme-linked immunosorbent assay. RESULTS: Clinical variables were monitored. 10 (15%) patients had biopsy-proven rejection during the follow-up period. The urinary CXCL9 level in those with rejection was significantly higher than that in those with non-rejection group at the 1st day (p<0.001), 7th day (p<0.001), and at the time of rejection (p=0.002). The urinary CXCL10 level was also significantly higher in those with rejection compared with non-rejection group at 1st day (p<0.001), 7th day (p<0.001), and at the time of rejection (p=0.001). Serum creatinine level was strongly correlated with the urinary CXCL9 and CXCL10 levels at the time of rejection (r=0.615, p=0.002; and r=0.519, p=0.022, respectively). Among those with T cell-mediated rejections the mean urinary CXCL10 level increased to as high as 258.12 ng/mL. CONCLUSION: Urinary CXCL9 and CXCL10 levels might have a predictive value for T cell-mediated rejection in early post-transplantation period. Measurement of urinary CXCL9 and CXCL10 levels could provide an additional tool for the diagnosis of rejection.

THE ROLE OF THYROID FINE-NEEDLE ASPIRATION CYTOLOGY IN THE TREATMENT AND FOLLOW-UP OF THYROID NODULES IN THE PEDIATRIC POPULATION.

OBJECTIVE: Thyroid fine-needle aspiration (FNA) and cytology is a reliable diagnostic method used in the assessment of malignancy when evaluating thyroid nodules, in conjunction with clinical and ultrasonographic findings. The aim of this study is to compare clinical, ultrasonographic, cytological and histopathological findings in children who underwent thyroid FNA. METHODS: Subjects comprised 80 patients (52 female) aged 13.7±2.8 years at the time of FNA who where evaluated for thyroid nodules. Clinical, ultrasonographic and cytological findings of patients were evaluated retrospectively. RESULTS: Autoimmune thyroiditis was present in 30% and history of radiotherapy to the head or neck in 10%. The cytological diagnosis of patients included: inadequate or hemorrhagic sample in 10%; benign in 42.5%; atypia or follicular lesion of undetermined significance (AUS/FLUS) in 15%; suspicion of follicular neoplasia (SFN) in 7.5%; suspicion of malignancy (SM) in 8.8%; and malignant in 16.3%. Thirty-seven patients underwent thyroidectomy. Malignancy rates for histopathologic follow-up were 75%, 85.7% and 100% for SFN, SM and malignant categories, respectively. Only one benign and two AUS/FLUS FNAs were found to be malignant on histopathological examination. Among patients who had received radioiodinetherapy, 87.5% had malignancy. In this study, the sensitivity of FNA was 96%, specificity 50%, positive predictive value 90.9%, negative predictive value 75%, and diagnostic value of FNA was 89.2%. CONCLUSION: Thyroid FNA results were highly compatible with histopathological examination. Sensitivity, positive predictive value and diagnostic value of FNA were high.

Juvenile systemic lupus erythematosus in Turkey: demographic, clinical and laboratory features with disease activity and outcome.

Objectives This paper aims to assess in a retrospective fashion the clinical and laboratory features, severity and outcome of juvenile systemic lupus erythematosus (jSLE) from a referral center in Turkey. Methods We have included all jSLE patients ( n = 92) diagnosed according to the revised American College of Rheumatology 1997 criteria between January 2004 and January 2017. Results The most prevalent clinical feature in our cohort was mucocutaneous manifestations (97.8%), followed by constitutional (81.5%), hematological (59.8%) and musculoskeletal manifestations (56.5%). Renal involvement was observed in 38% ( n = 35) of the patients, whereas biopsy-proven lupus nephritis was detected in 29.3% ( n = 27) of the cohort. Neurologic involvement was seen in 15 (16.3%) individuals. Among the patients positive for anticardiolipin IgM and/or IgG ( n = 11, 12%), only three developed antiphospholipid antibody syndrome. The mean SLEDAI-2K scores at disease onset (10.5 ± 4.8) showed a substantial decrease at last visit (4.3 ± 4.6). One-quarter of the patients (26.1%, n = 24) had damage according to the PedSDI criteria with a mean score of 0.45 ± 1.0 (range 0-7). When the PedSDI damage items were evaluated individually, growth failure was the most frequent damage criterion ( n = 6), followed by seizure ( n = 5). Two patients died during the designated study period of end-stage renal disease. The five-year and 10-year survival rate of our cohort was 100% and 94.4%, respectively. Conclusions Given the lower frequency of nephritis and central nervous system disease and lower basal disease activity and damage scores, we could conclude that children with jSLE in Turkey have a more favorable course compared to Asian and African American children, as expected from Caucasian ethnicity.

EGFR mutation testing using archival-stained smears in non-small cell lung carcinoma.

OBJECTIVE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown benefits regarding progression-free and overall survival in patients whose tumours show EGFR mutations. Most patients' lung cancer is metastatic when detected. Small tissue samples and cytological materials are widely used in diagnosis. The aim of the present study was to compare the EGFR mutation analysis results between cytology, small biopsies and resections. METHODS: Archival material for EGFR testing was reviewed. Cell blocks and/or stained smears and tissue blocks were used where appropriate. The tumour cell count and percentage were recorded as well as the DNA content. The influence of TTF-1 immunoreactivity on EGFR testing was also investigated. RESULTS: The study cohort included 300 unpaired specimens of 84 resections, 83 small biopsies and 133 cytological materials. EGFR mutation rates did not differ significantly for cytology, small biopsy and resections (P > 0.05). The higher tumour cell percentage in FNAs than in exfoliative cytology did not affect the EGFR mutation status. EGFR mutation rates were similar when either slides or cell blocks were used. Cytology slides revealed a higher tumour cell content and DNA concentration than the cell blocks. May-Grünwald-Giemsa (MGG)-stained smears had higher rates of the EGFR mutation than the Papanicolaou (Pap)-stained slides (P < 0.05). Tumours with negative immunoreactivity for TTF-1 are less likely to have an EGFR mutation (P < 0.05). CONCLUSIONS: Cytological materials can be used successfully for mutation analysis in lung cancer.

MAPK overexpression is associated with anthracycline resistance and increased risk for recurrence in patients with triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer is estimated to account for 15%-20% of all patients with breast cancer and is considered as a prognostically unfavorable subset. The aim of this study is to evaluate the prognostic impact of various molecular factors in patients with triple-negative breast cancer. PATIENTS AND METHODS: Tumor specimens from 109 patients with receptor-negative (estrogen receptor and progesterone receptor) breast cancer were analyzed for mitogen-activated protein kinase (MAPK), epidermal growth factor receptor (EGFR) and phosphoinositol-3-kinase (PI3K) expression by immunohistochemistry. The prognostic significance of these molecular factors, in addition to various prognostic variables, was investigated. RESULTS: Fifteen (13.8%), 38 (34.9%) and 33 patients (30.3%) had positive staining for EGFR, MAPK and PI3K, respectively. MAPK was associated with anthracycline resistance (P = 0.008) and lower MAPK score was significantly associated with shorter disease-free survival (P = 0.029). Survival following relapse was significantly worse for those with a higher MAPK score (P = 0.03). CONCLUSION: MAPK is a significant prognostic and predictive factor in patients with triple-negative breast cancer. Furthermore, the level of staining among those with a positive MAPK expression may play a prognostic role at different stages of relapse. Further translational research is required to elucidate molecular mechanisms of tumor proliferation in this subset of patients.

Laparoscopic treatment of splenic lymphangiomas: report of three cases.

BACKGROUND AND AIM: Since 1991, laparoscopic splenectomy has been performed in many different pathologies of the spleen. Although it is a rare lesion, splenic lymphangiomas are cystic lesions of the spleen requiring splenectomy. Herein, we present three females who have undergone laparoscopic splenectomy with the diagnosis of cystic splenic lymphangioma. PATIENTS AND METHODS: In the last four years, in Istanbul Medical School, Department of General Surgery (Turkey) and in University of Catania Medical School, Department of Surgery (Italy), we performed laparoscopic splenectomy in three cases of splenic lymphangioma. RESULTS: These three female patients, with the age of 26, 30 and 40, had nonspecific abdominal pain requiring abdominal CT scan and magnetic resonance imaging, which showed incidental cystic lesions in the spleen, associated with cholelithiasis in one case. Preoperative laboratory tests and physical examinations were normal. Laparoscopic splenectomy was performed successfully with three 10 mm trocars in two patients in less than 1 hour, and with an Hasson trocar, two 5 mm trocars and one 10-12 mm trocar in the last case, who required simultaneous cholecystectomy. No peroperative and postoperative complications has occurred. Histopathological examinations confirmed the preoperative diagnosis. CONCLUSION: Laparoscopic splenectomy is the best treatment for patients with suspected cystic lymphangioma. It permits a total pathological examination of the spleen, and it should be preferred to partial splenectomy because of possible multiple lesions. In conclusion, minimal invasive treatment of this rare pathology is an effective and safe procedure.

Radiation-induced benign glandular cells in posthysterectomy smears: a cytomorphologic and clinical analysis.

In this retrospective study, we aimed to investigate the frequency and cytomorphologic characteristics of benign glandular cells (BGCs) in hysterectomized individuals. We also discussed the possible effect of radiation therapy on these cells. We reviewed our cytopathology archive material through a 5.5-year period and found 1460 posthysterectomy vaginal smears. Of these, 508 smears were from patients who had undergone hysterectomy for a gynecological malignancy. Review of this vaginal cytology material revealed 17 posthysterectomy patients whose smears contained BGCs. We obtained detailed clinical information in 16 of these. In addition to routine Papanicolaou staining, mucicarmine stain was also used to demonstrate cytoplasmic mucin in some cases. All the patients had a history of gynecological malignancy and had radiation therapy. Glandular cells appeared singly or in rows and honeycomb groups and did not show cytologic atypia. We concluded that radiation might give rise to a metaplastic process in which basal cells of squamous epithelium of the vagina transform into glandular cells. Most probably this process is independent of radiation dosage and period and is irreversible. We also propose that the possibility of encountering glandular cells in posthysterectomy smears is higher than expected, if the mucin stains have been used for the microscopic examination.