Machine learning-based immune phenotypes correlate with STK11/KEAP1 co-mutations and prognosis in resectable NSCLC: a sub-study of the TNM-I trial.

BACKGROUND: We aim to implement an immune cell score model in routine clinical practice for resected non-small-cell lung cancer (NSCLC) patients (NCT03299478). Molecular and genomic features associated with immune phenotypes in NSCLC have not been explored in detail. PATIENTS AND METHODS: We developed a machine learning (ML)-based model to classify tumors into one of three categories: inflamed, altered, and desert, based on the spatial distribution of CD8+ T cells in two prospective (n = 453; TNM-I trial) and retrospective (n = 481) stage I-IIIA NSCLC surgical cohorts. NanoString assays and targeted gene panel sequencing were used to evaluate the association of gene expression and mutations with immune phenotypes. RESULTS: Among the total of 934 patients, 24.4% of tumors were classified as inflamed, 51.3% as altered, and 24.3% as desert. There were significant associations between ML-derived immune phenotypes and adaptive immunity gene expression signatures. We identified a strong association of the nuclear factor-κB pathway and CD8+ T-cell exclusion through a positive enrichment in the desert phenotype. KEAP1 [odds ratio (OR) 0.27, Q = 0.02] and STK11 (OR 0.39, Q = 0.04) were significantly co-mutated in non-inflamed lung adenocarcinoma (LUAD) compared to the inflamed phenotype. In the retrospective cohort, the inflamed phenotype was an independent prognostic factor for prolonged disease-specific survival and time to recurrence (hazard ratio 0.61, P = 0.01 and 0.65, P = 0.02, respectively). CONCLUSIONS: ML-based immune phenotyping by spatial distribution of T cells in resected NSCLC is able to identify patients at greater risk of disease recurrence after surgical resection. LUADs with concurrent KEAP1 and STK11 mutations are enriched for altered and desert immune phenotypes.

Thorough design and pre-trial quality assurance (QA) decrease dosimetric impact of delineation and dose planning variability in the STRICTLUNG and STARLUNG trials for stereotactic body radiotherapy (SBRT) of central and ultra-central lung tumours.

INTRODUCTION: SBRT of central lung tumours implies significant risk of toxicity. We are initiating two phase II trials prescribing 56 Gy/eight fractions to PTV, allowing for dose escalation of GTV. We prioritize organs at risk (OAR) constraints over target coverage, making the treatment plans very sensitive to OAR delineation variations. The aim of this study is to quantify the dosimetric impact of contouring variations and to provide a thorough description of pre-trial quality assurance to be used in upcoming trials to provide consistent clinical care. MATERIALS AND METHODS: Delineation: Seven physicians delineated OAR in three rounds, with evaluations in-between. For each patient case, seven treatment plans, repeatedly using each of the OAR structure sets from the seven physicians, were made and compared to evaluate the dosimetric effect of delineation variability. Treatment planning: Treatment plans for seven cases were made at six departments in two rounds, with discussion in-between. RESULTS: OAR delineation variation between centres resulted in high variabilities in OAR dose for simulated plans and led to potential overdosage of the lobar bronchus (constraint: D0.03cc < 45 Gy), with maximum doses ranging between 58 Gy (first round), and 50 Gy (third round). For mediastinal tissue, the constraint (D0.03cc < 45 Gy) was violated for the majority of the delineations in all three rounds, with maximum doses of 84 Gy (first round), and 72 Gy (third round).For the treatment planning study, the range of the standard deviation for GTV mean dose was 12.8-18.5 Gy (first round) and 2.8-3.5 Gy (second round). CONCLUSIONS: Even small variations in OAR delineation led to high OAR overdosage. The study demonstrates the importance of having extensive QA procedures in place before initiating clinical trials on dose escalation in SBRT.

Surveillance imaging with FDG-PET/CT in the post-operative follow-up of stage 3 melanoma.

Background: As early detection of recurrent melanoma maximizes treatment options, patients usually undergo post-operative imaging surveillance, increasingly with FDG-PET/CT (PET). To assess this, we evaluated stage 3 melanoma patients who underwent prospectively applied and sub-stage-specific schedules of PET surveillance. Patients and methods: From 2009, patients with stage 3 melanoma routinely underwent PET +/- MRI brain scans via defined schedules based on sub-stage-specific relapse probabilities. Data were collected regarding patient characteristics and outcomes. Contingency analyses were carried out of imaging outcomes. Results: One hundred and seventy patients (stage 3A: 34; 3B: 93; 3C: 43) underwent radiological surveillance. Relapses were identified in 65 (38%) patients, of which 45 (69%) were asymptomatic. False-positive imaging findings occurred in 7%, and 6% had treatable second (non-melanoma) malignancies. Positive predictive values (PPV) of individual scans were 56%-83%. Negative scans had predictive values of 89%-96% for true non-recurrence [negative predictive values (NPV)] until the next scan. A negative PET at 18 months had NPVs of 80%-84% for true non-recurrence at any time in the 47-month (median) follow-up period. Sensitivity and specificity of the overall approach of sub-stage-specific PET surveillance were 70% and 87%, respectively. Of relapsed patients, 33 (52%) underwent potentially curative resection and 10 (16%) remained disease-free after 24 months (median). Conclusions: Application of sub-stage-specific PET in stage 3 melanoma enables asymptomatic detection of most recurrences, has high NPVs that may provide patient reassurance, and is associated with a high rate of detection of resectable and potentially curable disease at relapse.

Localized melanoma in older patients, the impact of increasing age and comorbid medical conditions.

BACKGROUND: Elderly patients experience a different spectrum of disease and poorer outcomes than younger patients. This study investigated the impact of age and medical comorbidities on the management and outcome of patients ≥65 years. METHODS: A retrospective review of all patients ≥65 years (481 patients with 525 primary melanomas) presenting with AJCC clinical stage I-II melanoma to an Australian cancer centre between 2000 and 2008. RESULT: The median age was 74 years (65-94) with a male predominance (313 males, 65.0%) and median tumour thickness of 1.90 mm (IQR = 0.40-2.90, T1 = 33%, T2 = 20%, T3 = 24%, T4 = 23%). Inadequate surgical margins of excision (<10 mm) were common in older patients independent of site, thickness and ulceration (OR = 1.04, 95%CI = 1.00-1.07, p = 0.038). Inadequate excision margins were strongly associated with time to local recurrence, independent of age, thickness, ulceration and mitotic rate (HR = 3.00, 95%CI = 1.49-6.03, p = 0.0021), but not time to progression (p = 0.10) or disease specific survival (DSS, p = 0.27). Overall survival (OS) was strongly related to increasing age (HR = 1.04, 95%CI = 1.01-1.07, p = 0.015) and comorbid medical conditions (HR = 1.26, 95%CI = 1.12-1.42, p < 0.001), as assessed by the Charlson comorbidity index (CCI). DSS was significantly related to CCI (HR = 1.20, 95%CI = 1.01-1.42, p = 0.041) and not age (p = 0.46), when adjusting for thickness, ulceration and mitotic rate on multivariate analysis. CONCLUSION: Older patients present with poor prognosis melanomas yet are less likely to receive adequate surgical excision margins resulting in higher rates of local recurrence. In melanoma patients ≥65 years, the increasing number of medical comorbidities explains much of the age related variations in OS and DSS and should be considered when planning treatment.

Strategies for clinical implementation of TNM-Immunoscore in resected nonsmall-cell lung cancer.

Immunoscore is a prognostic tool defined to quantify in situ immune cell infiltrates and appears highly promising as a supplement to the tumor-node-metastasis (TNM) classification of various tumors. In colorectal cancer, an international task force has initiated prospective multicenter studies aiming to implement TNM-Immunoscore (TNM-I) in a routine clinical setting. In breast cancer, recommendations for the evaluation of tumor-infiltrating lymphocytes (TILs) have been proposed by an international working group. Regardless of promising results, there are potential obstacles related to implementing TNM-I into the clinic. Diverse methods may be needed for different malignancies and even within each cancer entity. Nevertheless, a uniform approach across malignancies would be advantageous. In nonsmall-cell lung cancer (NSCLC), there are several previous reports indicating an apparent prognostic importance of TILs, but studies on TILs in a TNM-I setting are sparse and no general recommendations are made. However, recently published data is promising, evoking a realistic hope of a clinical useful NSCLC TNM-I. This review will focus on the TNM-I potential in NSCLC and propose strategies for clinical implementation of a TNM-I in resected NSCLC.

[Unusual masquerade of an ocular carcinoma metastasis]. / Untypische Masquerade einer okulären Karzinommetastase.

BACKGROUND: Idiopathic and therapy resistant uveitis especially of unclear origin, is a diagnostic challenge for ophthalmologists. Metastases to the anterior chamber or vitreous body can occasionally mimic the clinical picture of uveitis, a variant on the usual lymphomatous masquerade syndrome. The underlying pathological pathways leading to the metastatic spread of tumor cells within the fluid compartments of the eye remain unclear. CASE REPORT: We present an unusual case of vitreous metastases to the right eye of a patient in whom an underlying primary malignancy was unknown. After recurrent episodes of cortisone-refractive panuveitis with pseudohypopyon, a diagnostic vitreous biopsy was performed. Cytopathological examination of the vitreous sample revealed carcinoma cells with an immune profile suggestive of lung cancer metastasis. Subsequent staging investigations revealed a primary lung adenocarcinoma as well as cerebral, adrenal and osseous metastases. THERAPY: Due to the extent of dissemination of this non-small cell lung cancer (NSCLC), only palliative treatment including external beam irradiation and systemic chemotherapy was possible to reduce pain and to maintain vision as well as an attempt at systemic control of the disease.

[Urethral meatus deformities and urethra hypospadias in women: prevalence, problems and definitions. Study of 12,739 patients]. / Méat urétral enfoui et urètre hypospade chez la femme : prévalence, problématiques et définitions. Étude sur 12 739 patientes.

UNLABELLED: The difficulty to access to the urethral meatus is found in women in relation to morphological abnormalities of urogenital or ectopic locations meatus, whether acquired (urethral meatus buried [UMB]) or congenital reality (urethra hypospadias [UH]). The pathophysiology is not unequivocal with lack of clear and specific studies. PURPOSE: Verify the existence of specific functional problems, assess the prevalence and identify the anatomical features of UMB and UH. MATERIALS: UMB and UH were sought in a computerized database listing the patients attending a neurourology department between 2000 and 2014 for a pelvic-perineal disease. Each case was analysed for specific reached leaks, urinary tract infections and difficulties catheterization. RESULTS: Of the 12,739, 131 patients (1%) met the inclusion criteria, including 18 UH and 113 UMB. Ninety-one patients consulted for urinary disorders of neurological origin. The circumstances of UMB and UH discovery were: perineal systematic review in 63 cases (48%); difficulties of urethral catheterization in 65 cases (49%); urinary incontinence for 3 patients (3%). Urinary tract infections have not led to the discovery of UMB or UH. Difficulties locating the urethral meatus were congenital (UH) in 18 cases (13%). In 113 cases (87%), it was an acquired abnormality (UMB) overweight for 16 patients (12%), troublesome spasticity of the adductor muscles in 18 cases (14%), vulvovaginal atrophy in 5 cases (4%) and a patient (1%) with a pelvic organ prolapse. No details were given for the remaining 72 patients (54%). CONCLUSION: The urethral meatus difficult access due to MUE or UH can be met in a specialized service but the exact concept of MUE be defined. It can be considered as urethral meatus difficult to access and the cause is acquired. Functional impairment may be particularly important in patients requiring catheterization for bladder emptying. LEVEL OF EVIDENCE: 4.

SSX2-4 expression in early-stage non-small cell lung cancer.

The expression of cancer/testis antigens SSX2, SSX3, and SSX4 in non-small cell lung cancers (NSCLC) was examined, since they are considered promising targets for cancer immunotherapy due to their immunogenicity and testis-restricted normal tissue expression. We characterized three SSX antibodies and performed immunohistochemical staining of 25 different normal tissues and 143 NSCLCs. The antibodies differed in binding to two distinctive splice variants of SSX2 that exhibited different subcellular staining patterns, suggesting that the two splice variants display different functions. SSX2-4 expression was only detected in 5 of 143 early-stage NSCLCs, which is rare compared to other cancer/testis antigens (e.g. MAGE-A and GAGE). However, further studies are needed to determine whether SSX can be used as a prognostic or predictive biomarker in NSCLC.

[Intensive care unit acquired weakness. Pathogenesis, treatment, rehabilitation and outcome]. / Erworbene Muskelschwäche des kritisch Kranken. Pathogenese, Behandlung, Rehabilitation, Outcome.

The diagnosis of intensive care unit acquired weakness (ICUAW) in the setting of neurological rehabilitation is steadily increasing. This is due to the fact that the intensive care of patients with sepsis or after cardiac or abdominal surgery is improving. A longer duration of respiratory weaning and comorbidities frequently complicate rehabilitation. Clinically, patients present with a flaccid (tetra) paresis and electrophysiological studies have shown axonal damage. Besides involvement of peripheral nerves, muscle can also be affected (critical illness myopathy) leading to ICUAW with inconstant myopathic damage patterns found by electrophysiological testing. Mixed forms can also be found. A specific therapy for ICUAW is not available. Early mobilization to be initiated on the intensive care unit and commencing neurological rehabilitation improve the outcome of ICUAW. This review highlights the current literature regarding the etiology and diagnosis of ICUAW. Furthermore, studies about rehabilitation and outcome of ICUAW are discussed.

[Colorectal cancer - personalized, stage-adjusted tumour therapy]. / Kolorektale Karzinome - personalisierte, stadienadaptierte Tumortherapie.

Colorectal cancer (CRC) is the second leading cause of cancer death in the western world. Every second patient dies of the disease. The introduction of new and effective chemotherapeutic substances and biologics during the past decade has significantly improved the systemic treatment of patients with CRC. In stage III colon cancer combination chemotherapy with oxaliplatin is the standard of care. Primary resection of metastases or resection after combination therapy and downsizing of lesions offers a chance for cure for some patients. In the treatment of rectal carcinoma, multimodality and neoadjuvant treatment concepts have replaced adjuvant chemoradio-therapy for locally advanced rectal cancer. In the palliative setting intensive combination treatment is indicated in colorectal cancer if tumor related symptoms or a rapid progress of the disease occur. The aim of palliative therapy is the prolongation of survival and the improvement of quality of life. The introduction of the mutational status of the KRAS oncogene as the first predictive marker into clinical care is an important step towards the personalization of treatment in CRC.

Capecitabine/irinotecan or capecitabine/oxaliplatin in combination with bevacizumab is effective and safe as first-line therapy for metastatic colorectal cancer: a randomized phase II study of the AIO colorectal study group.

BACKGROUND: This randomized phase II trial investigated the efficacy and safety of capecitabine/oxaliplatin (CapOx) plus bevacizumab and dose-modified capecitabine/irinotecan (mCapIri) plus bevacizumab as first-line therapy in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients received bevacizumab 7.5 mg/kg with oxaliplatin 130 mg/m(2)/day 1 plus capecitabine 1000 mg/m(2) bid/days 1-14 or with irinotecan 200 mg/m(2)/day 1 plus capecitabine 800 mg/m(2) bid/days 1-14 both every 21 days. The primary end point was 6 months progression-free survival (PFS). RESULTS: A total of 255 patients were enrolled. The intent-to-treat population comprised 247 patients (CapOx-bevacizumab: n = 127; mCapIri-bevacizumab: n = 120). The six-month PFS rates were 76% (95% CI, 69%-84%) and 84% (95% CI, 77%-90%). Median PFS and OS were 10.4 months (95% CI, 9.0-12.0) and 24.4 months (95% CI, 19.3-30.7) with CapOx-bevacizumab, and 12.1 months (95% CI, 10.8-13.2) and 25.5 months (95% CI, 21.0-31.0) with mCapIri-bevacizumab. Grade 3/4 diarrhea as predominant toxic effect occurred in 22% of patients with CapOx-bevacizumab and in 16% with mCapIri-bevacizumab. CONCLUSIONS: Both, CapOx-bevacizumab and mCapIri-bevacizumab, show promising activity and an excellent toxic effect profile. Efficacy is in the range of other bevacizumab-containing combination regimen although lower doses of irinotecan and capecitabine were selected for mCapIri.

Biomarkers of anti-angiogenic therapy in metastatic colorectal cancer (mCRC): original data and review of the literature.

INTRODUCTION: Tumour angiogenesis via vascular endothelial growth factor (VEGF) is essential for promoting tumour progression and is overexpressed in colorectal cancer. The humanised monoclonal anti-VEGF antibody bevacizumab (Avastin®, Genentech Inc., South San Francisco, CA) has shown activity in metastatic colorectal cancer (mCRC) combined with conventional chemotherapy. The search for biomarkers to predict response to anti-angiogenic therapy in mCRC is of great interest. We investigated several potential predictive anti-angiogenic markers including circulating endothelial progenitor cells (EPC) in patients with mCRC receiving bevacizumab containing treatment within a randomised multicenter phase 2 study of the German AIO GI tumour study group. METHODS: We collected sequential blood samples and tumour tissues from patients participating in a clinical trial for patients with mCRC. We performed flow cytometry of mononuclear cells isolated from peripheral blood to assess CD 133 + or CD 34 + /KDR + EPC before the first bevacizumab containing chemotherapy and after 21 days. Circulating VEGF blood levels before a bevacizumab containing chemotherapy regimen and after 21 days and VEGF expression in tumour tissue were examined. RESULTS: Patients with mCRC and a partial remission after six months of immuno-chemotherapy containing bevacizumab showed a reduction of CD 34 negative KDR positive cells as early as 3 weeks after start of therapy. In contrast, no remarkable change in the number of CD 34 /KDR positive or CD 34 /CD133 positive cells was seen. Furthermore, there was no correlation between treatment response and VEGF expression within the tumour tissue. The mAb bevacizumab reduced serum-VEGF levels in patients independent of their treatment response to bevacizumab. DISCUSSION: We examined circulating endothelial progenitor cells (EPC), serum-VEGF levels and the tumour tissue VEGF expression of patients with mCRC under a bevacizumab containing chemotherapy. The patients with a partial remission after six months of immuno-chemotherapy showed a reduction of CD 34 negative KDR positive cells as early as 3 weeks after start of therapy. Neither serum nor tissue markers were of significant predictive value in our pilot study. Furthermore, we review the current data on biomarkers for anti-angiogenic therapy of mCRC.

Analysis of the Wilms' tumor suppressor gene (WT1) in patients 46,XY disorders of sex development.

CONTEXT: The Wilms' tumor suppressor gene (WT1) is one of the major regulators of early gonadal and kidney development. WT1 mutations have been identified in 46,XY disorders of sex development (DSD) with associated kidney disease and in few isolated forms of 46,XY DSD. OBJECTIVE: The objective of the study was the evaluation of WT1 mutations in different phenotypes of isolated 46,XY DSD and clinical consequences. DESIGN: The design of the study was: 1) sequencing of the WT1 gene in 210 patients with 46,XY DSD from the German DSD network, consisting of 150 males with severe hypospadias (70 without cryptorchidism, 80 with at least one cryptorchid testis), 10 males with vanishing testes syndrome, and 50 raised females with partial to complete 46,XY gonadal dysgenesis; and 2) genotype-phenotype correlation of our and all published patients with 46,XY DSD and WT1 mutations. RESULTS: We have detected WT1 mutations in six of 80 patients with severe hypospadias (7.5%) and at least one cryptorchid testis and in one of 10 patients with vanishing testes syndrome (10%). All patients except one developed Wilms' tumor and/or nephropathy in childhood or adolescence. CONCLUSION: WT1 analysis should be performed in newborns with complex hypospadias with at least one cryptorchid testis and in isolated 46,XY partial to complete gonadal dysgenesis. Kidney disease might not develop until later life in these cases. WT1 analysis is mandatory in all 46,XY DSD with associated kidney disease. WT1 analysis is not indicated in newborns with isolated hypospadias without cryptorchidism. Patients with WT1 mutations should be followed up closely because the risk of developing a Wilms' tumor, nephropathy, and/or gonadal tumor is very high.

Can human mesenchymal stem cells survive on a NiTi implant material subjected to cyclic loading?

Nickel-titanium shape memory alloys (NiTi-SMAs) exhibit mechanical and chemical properties which make them attractive candidate materials for various types of biomedical applications. However, the high nickel content of NiTi-SMAs may result in adverse tissue reactions, especially when they are considered for load-bearing implants. It is generally assumed that a protective titanium oxide layer separates the metallic alloy from its environment and that this explains the good biocompatibility of NiTi. Cyclic loading may result in failure of the protective oxide layer. The scientific objective of this work was to find out whether cyclic dynamic strain, in a range relevant for orthopedic implants, diminishes the biocompatibility of NiTi-SMAs. In order to analyze the biocompatibility of NiTi-SMA surfaces subjected to cyclic loading, NiTi-SMA tensile specimens were preloaded with mesenchymal stem cells, transferred to a sterile cell culture system and fixed to the pull rods of a tensile testing machine. Eighty-six thousand and four hundred strain cycles at 2% pseudoelastic strain were performed for a period of 24 h or 7 days. Cytokines (IL-6, IL-8 and VEGF) and nickel ion release were determined within the cell culture medium. Adherent cells on the tensile specimens were stained with calcein-AM and propidium iodide to determine cell viability. Dynamic loading of the tensile specimens did not influence the viability of adherent human mesenchymal stem cells (hMSCs) after 24 h or 7 days compared with the non-strained control. Dynamic cycles of loading and unloading did not affect nickel ion release from the tensile specimens. The release of IL-6 from hMSCs cultured under dynamic conditions was significantly higher after mechanical load (873 pg ml(-1)) compared with static conditions (323 pg ml(-1)). The present work demonstrates that a new type of mechanical in vitro cell culture experiment can provide information which previously could only be obtained in large animal experiments.

[Chemotherapy of colorectal cancer]. / Die medikamentöse Therapie des kolorektalen Karzinoms.

Colorectal cancer (CRC) is the second leading cause of cancer death in the western world. Almost every second patient dies of the disease. The introduction of new and effective chemotherapeutic substances and biologics in the past decade has significantly improved the systemic treatment of patients with CRC. In stage III colon cancer combination chemotherapy with oxaliplatin is the standard of care. In stage IV cancer the choice of therapy is dependent on the clinical status of the patient. For some patients primary resection of metastases or resection after combination therapy and downsizing of lesions offers a chance for cure. In the palliative setting intensive combination treatment is indicated if the patient suffers from tumor related symptoms or a rapid progress of the disease. The aim of palliative therapy is the prolongation of survival and the improvement of quality of life. Combination with monoclonal antibodies leads to further improvement of survival. Furthermore, the introduction of the mutational status of the KRAS oncogene as the first predictive marker into clinical care is an important step towards the individualization of treatment in CRC.

Sonographic long-term study: paediatric growth charts for single kidneys.

AIMS: To explore the clinical course of children with "single kidney" (defined as either a solitary or single functioning kidney) with reference to renal function (glomerular filtration rate (GFR) and proteinuria), body height and particularly sonomorphological features. PATIENTS AND METHODS: This retrospective monocentric study evaluated 119 children with a solitary or single functioning kidney (>90% unilateral function on isotope scan) between 1997 and 2007. Patients were followed for 6.3 years (median, range 1-17) and had at least three renal ultrasound examinations (median 8). During recruitment six children were identified with chronic kidney disease (CKD) stage III or worse. These patients were analysed separately. RESULTS: The aetiology of "single kidney" was attributed to contralateral multicystic dysplastic kidney (26%), tumournephrectomy (24%), renal agenesis (18%), hypo/dysplasia (11%) and obstructive or refluxive uropathy (18%). Irrespective of aetiology, the sonographic dimensions of "single kidneys" were in the upper range of normal paired kidneys and showed adequate growth. Compensatory renal hypertrophy (defined as >95% CI on two or more recent measurements) occurred in a third of patients. All six patients with CKD and GFR less than 60 ml/minute per 1.73 m(2) had pathological sonomorphology of their "single kidney" with inadequate renal growth (6/6), abnormal echogenicity (5/6), hypo/dysplasia (5/6). In addition, proteinuria (5/6) and short stature (3/6) were found. CONCLUSIONS: New reference centiles were generated to assess renal size of "single kidneys" in paediatric patients. These charts will facilitate counselling of patients and parents. Further evidence for a benign clinical course of children with "single kidney" and absent additional pathology of the remnant kidney is presented.

Acute renal failure associated with bilateral enlargement of the kidneys: a rare manifestation of acute lymphoblastic leukemia (ALL).

We report a 6-year-old patient who presented with acute renal failure resolving after vigorous intravenous hydration. Renal biopsy was taken because of unexplained enlargement of both kidneys. Histological workup showed infiltration by lymphoblasts while blood counts showed a normal differential. Subsequent bone marrow aspiration revealed 34% lymphoblasts of T-lineage origin, leading to the diagnosis of T-ALL. This case underlines that malignant hematologic infiltration should be considered in patients presenting with unexplained renal failure and enlarged kidneys.