Investigation of MTAP and BAP1 staining loss and P16/CDKN2A deletion in pleural cytology specimens and its role in the diagnosis of mesothelioma.

BACKGROUND: Mesothelioma is a malignant neoplasm with a poor survival rate. We aimed to investigate the importance of BAP1, MTAP (IHC), and p16/CDKN2A homozygous deletion (FISH) in cytologic material obtained from pleural effusion sampling, which is a less invasive procedure in the diagnosis of mesothelioma. METHODS: Our study discussed pleural cytology samples of cases with histopathologically proven mesothelioma diagnoses between 2017 and 2022. As the control group, materials that had pleural effusion sampling for other reasons and reactive mesothelial hyperplasia were included in the study. Cell blocks prepared from these materials were subjected to fluorescent in situ hybridization for p16/CDKN2A homozygous deletion and immunohistochemistry for BAP1 and MTAP. RESULTS: The specificity of the P16/CDKN2A homozygous deletion in diagnosing mesothelioma is 100%. Its sensitivity is 68.75%. The specificity of BAP1 immunohistochemical nuclear expression loss is 95%, while the sensitivity is 60%. Loss of nuclear expression of MTAP alone has the lowest specificity and sensitivity, with a specificity of 86% and a sensitivity of 43%. The highest sensitivity is reached when BAP1 loss and p16/CDKN2A homozygous deletion are evaluated together, increasing to 81%. The specificity is 95%. CONCLUSION: It has been determined that any marker alone cannot be used for a definitive mesothelioma diagnosis in pleural effusion cytological specimens; however, sensitivity increases in some combinations. The combination of BAP1 immunohistochemistry and p16/CDKN2A homozygous deletion detected by FISH, which has a higher specificity and sensitivity, can be routinely used in the diagnosis of mesothelioma under the guidance of clinical and radiologic information.

Adult-onset carnitine palmitoyl transferase II (CPT II) deficiency presenting with rhabdomyolysis and acute kidney injury.

Metabolic myopathies are among the treatable causes of rhabdomyolysis and myoglobinuria. Carnitine palmitoyl transferase 2 (CPT II) deficiency is one of the most common causes of recurrent myoglobinuria in adults. It is an inherited disorder of fatty acid oxidation pathway, commonly associated with elevated acylcarnitine levels. In this case report, we present a 49-year-old male patient who developed acute kidney injury after rhabdomyolysis and was thus diagnosed with CPT2 deficiency after his first episode of rhabdomyolysis. Inborn errors of metabolism should be kept in mind in patients with rhabdomyolysis. Acylcarnitine profile may be normal in CPT II deficiency, even during an acute attack, and molecular genetic diagnostics should be applied if there is high index of clinical suspicion.

Peritubular Capillaritis in Native Kidney Biopsies.

OBJECTIVES: To determine the frequency and predictors of peritubular capillaritis (PTCitis) among native kidney biopsies. METHODS: Consecutive native kidney biopsies of 169 patients were reexamined for capturing possible PTCitis according to the Banff Classification. The relation of PTCitis with demographic and clinicopathologic findings was evaluated. Logistic regression analysis was performed to determine predictors of PTCitis. RESULTS: Peritubular capillaritis was captured in 90 (53.3%) patients, with scores of 1, 2, and 3 in 57 (33.7%), 31 (18.3%), and 2 (1.2%) patients, respectively. The highest frequency of PTCitis was observed in pauci-immune glomerulonephritis. In univariate analysis, male sex, the presence of interstitial inflammation, pauci-immune glomerulonephritis, and a higher serum creatinine level were associated with a higher risk of PTCitis, while severe interstitial fibrosis/tubular atrophy was associated with a lower risk. The presence of interstitial inflammation (odds ratio [OR], 5.94 [95% confidence interval (CI), 1.41-25.03]; P = .015), pauci-immune glomerulonephritis (OR, 3.08 [95% CI, 1.01-9.36]; P = .048), and a higher serum creatinine level (per 1 mg/dL) (OR, 1.56 [95% CI, 1.14-2.11]; P = .005) were independent predictors of PTCitis development in a multivariate regression model. CONCLUSIONS: Peritubular capillaritis is common in native biopsies and more likely to be observed in the presence of interstitial inflammation, pauci-immune glomerulonephritis, and a higher serum creatinine level.

Hypercalcemia in IgG4-related disease: coincidental or associated? Case based review.

Immunoglobulin (Ig) G4-related disease (IgG4RD) is a chronic autoimmune disorder characterized by dense lymphoplasmacytic infiltrations and fibrosis of storiform pattern. The most typical manifestations include major salivary or lacrimal gland involvement, autoimmune pancreatitis, and retroperitoneal fibrosis. While the increase in IgG4 is the typical feature of the disease, hypercalcemia has been rarely reported in IgG4RD so far, only one of these cases has been shown parathyroid gland involvement (isolated involvement). In this study, we present a 43-year-old female patient with weight loss, pancreatic mass, lymphadenopathy, nodular lesion in the lung, hypercalcemia, and also increased level of serum IgG4. Histopathological investigation following parathyroidectomy revealed a dense lymphoplasmacytic infiltrate with an IgG4 to IgG ratio of > 50% in the fat tissue surrounding the parathyroid gland, particularly at the perivascular areas. This is the first systemic IgG4RD case in combination with hypercalcemia in the literature who was detected to have parathyroid adenoma. Our aim in this review is to emphasize that, although rarely, IgG4RD may be accompanied by hypercalcemia and parathyroid gland may be one of its target sites.

Prognostic significance of tumor budding in muscle invasive urothelial carcinomas of the urinary bladder.

OBJECTIVE: The aim of the present study was to analyze the prognostic significance of tumor budding in muscle-invasive urothelial carcinomas of the urinary bladder, and also to determine an optimal threshold value in evaluation. PATIENTS AND METHODS: The study included 108 patients diagnosed with muscleinvasive conventional urothelial carcinoma between 2010 and 2020. Tumor budding was evaluated on H&E-stained slides. The critical tumor budding number was determined with the "receiver operating characteristics (ROC)" curve. Cases with a tumor budding number of ≤6 were categorized as low, and cases with >6 as high tumor budding. RESULTS: The univariate Cox proportional hazards regression model for recurrence-free survival showed that lymphovascular invasion (P = 0.001), tumor budding (P = 0.012), pT stage (T4 vs. T2) (P = 0.005), and lymph node metastasis (P = 0.009) were significantly associated with recurrence-free survival. The multivariate Cox proportional hazards regression model utilizing backward stepwise (wald) method revealed that only LVI (P = 0.001) was independent risk factor for recurrence-free survival. The univariate Cox analysis showed that lymphovascular invasion (P = 0.001), tumor budding (P = 0.004), pT stage (T4 vs. T2) (P = 0.003), and lymph node metastasis (P = 0.001) were significantly associated with overall survival. The multivariate Cox analysis (backward stepwise (wald) method) revealed that tumor focality (P = 0.018), pT stage (T4 vs. T2) (P = 0.015), and lymphovascular invasion (P = 0.002) were independent factors for overall survival. CONCLUSIONS: Our findings suggested that the evaluation of tumor budding may be a useful parameter for predicting outcome in patients with muscle-invasive bladder cancer.

The coexistence of IgA vasculitis and tuberculosis: a case-based review.

Immunoglobulin (Ig) A vasculitis (IgAV), formerly known as Henoch-Schonlein purpura (HSP), is a relatively uncommon form of vasculitis primarily targeting the skin, gastrointestinal system, and the kidneys. Although the pathogenesis has not yet been well identified, several triggering factors, such as infections, drugs, have been implicated in the development of IgAV. Tuberculosis (TB), albeit rare, may precipitate IgAV. Herein, we have presented a case manifested by purpuric skin rash and proteinuria 6 weeks following diagnosis of pulmonary tuberculosis while receiving anti-TB drugs. The case was diagnosed as having active tuberculosis and TB-related IgA vasculitis with multi-organ involvement. In this case-based review, we recruited cases with TB-related Ig A vasculitis from the literature and discussed the features of tuberculosis that mimic vasculitides and vice versa. We also discussed the difficulties in diagnosis and the therapeutic approach in the light of the literature.

Glomerulonephritis and Coombs-positive hemolytic anemia mimicking scleroderma renal crisis in an overlap of systemic lupus erythematosus and diffuse systemic sclerosis.

Systemic sclerosis (SSc) may overlap frequently with other rheumatic diseases, including systemic lupus erythematosus (SLE), which can require high-dose steroids depending on the clinical presentation. We present a case involving this overlap in which the patient concomitantly developed lupus nephritis and Coombs (+) hemolytic anemia, which was confused with scleroderma renal crisis. In this condition, assessing for lupus nephritis with timely renal biopsy and lupus serology can aid in guiding the appropriate treatment. We discuss the clinical features and challenging management of this case with a review of the English-language literature for SSc and SLE overlap with glomerulonephritis.