Single nucleotide polymorphism (SNP) chromosomal microarray as a diagnostic tool for mucinous tubular and spindle cell carcinoma: A validation study.

Mucinous tubular and spindle cell carcinoma (MTSCC) shows significant overlap with papillary renal cell carcinoma (PRCC), and harbor recurrent copy-number alterations (CNA). We evaluated 16 RCC with features suggestive of MTSCC using chromosomal microarrays. The cohort was comprised of 8 females and males, each, with an age range of 33-79 years (median, 59), and a tumor size range of 3.4-15.5 cm (median, 5.0). Half the tumors were high-grade (8/16, 50%) with features such as necrosis, marked cytologic atypia, and sarcomatoid differentiation, and 5/16 (31%) were high stage (≥pT3a). Three (of 16, 19%) cases had a predominant (>95%) spindle cell component, whereas 5/16 (31%) were composed of a predominant (>95%) epithelial component. Most cases (12/16, 75%) exhibited a myxoid background and/or extravasated mucin, at least focally. Twelve (of 16, 75%) cases demonstrated CNA diagnostic of MTSCC (losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22). In addition, 2 high-grade tumors showed loss of CDKN2A/B, and gain of 1q, respectively, both of which are associated with aggressive behavior. Three (of 16, 19%) cases, demonstrated nonspecific CNA, and did not meet diagnostic criteria for established RCC subtypes. One (of 16, 6%) low-grade epithelial predominant tumor (biopsy) demonstrated characteristic gains of 7, 17, and loss of Y, diagnostic of PRCC. MTSCC can be a morphologically heterogenous tumor. Our study validates the detection of characteristic chromosomal CNA for diagnostic use that may be useful in challenging cases with unusual spindle cell or epithelial predominant features, as well as in high-grade tumors.

Genomic attributes of prostate cancer across primary and metastatic noncastrate and castrate resistant disease states: a next generation sequencing study of 183 patients.

Primary prostatic adenocarcinoma (pPC) undergoes genomic evolution secondary to therapy-related selection pressures as it transitions to metastatic noncastrate (mNC-PC) and castrate resistant (mCR-PC) disease. Next generation sequencing results were evaluated for pPC (n = 97), locally advanced disease (involving urinary bladder/rectum, n = 12), mNC-PC (n = 21), and mCR-PC (n = 54). We identified enrichment of TP53 alterations in high-grade pPC, TP53/RB1 alterations in HGNE disease, and AR alterations in metastatic and castrate resistant disease. Actionable alterations (MSI-H phenotype and HRR genes) were identified in approximately a fifth of all cases. These results help elucidate the landscape of genomic alterations across the clinical spectrum of prostate cancer.

Can the ROX index predict high-flow nasal cannula failure in children under 2 with lower respiratory tract infection?

OBJECTIVE: This study evaluates the ROX index's accuracy in predicting the success or failure of high-flow nasal cannula (HFNC) therapy in children under 2 years with acute respiratory failure (ARF) from lower respiratory tract infections. METHODS: From January 2018 to 2021 we conducted this multicenter retrospective cohort study, which included patients aged 2-24 months. We aimed to assess HFNC therapy outcomes as either success or failure. The analysis covered patient demographics, diagnoses, vital signs, and ROX index values at intervals from 0 to 48 h after initiating HFNC. We used bivariate analysis, repeated measures ANOVA, multivariate logistic regression, and the area under the receiver operating characteristic (AUC-ROC) curve for statistical analysis. RESULTS: The study involved 529 patients from six centers, with 198 females (37%) and a median age of 9 months (IQR: 3-15 months). HFNC therapy failed in 38% of cases. We observed significant variability in failure rates across different centers and physicians (p < .001). The ROX index was significantly associated with HFNC outcomes at all time points, showing an increasing trend in success cases over time (p < .001), but not in HFNC failure cases. Its predictive ability is limited, with AUC-ROC values ranging from 0.56 at the start to 0.67 at 48 h. CONCLUSION: While the ROX index is associated with HFNC outcomes in children under 2 years, its predictive ability is modest, impacted by significant variability among patients, physicians, and centers. These findings emphasize the need for more reliable predictive tools for HFNC therapy in this patient population.

Genomic analysis of spermatocytic tumors demonstrates recurrent molecular alterations in cases with malignant clinical behavior.

Spermatocytic tumor (ST) is a rare type of germ cell tumor that occurs exclusively in the postpubertal testis and typically affects elderly men. Most STs are benign, but rare cases exhibit aggressive clinical behavior, often in association with transition to sarcomatoid histology. Limited molecular analyses have been performed on STs; therefore, their genomic and epigenomic features remain incompletely described. Twenty-seven samples from 25 individual patients were analyzed with a combination of DNA sequencing panels, genomic methylation profiling, SNP array, isochromosome (12p) [i(12p)] FISH, and immunohistochemistry. The series included five metastasizing tumors (three with sarcomatoid transformation, one anaplastic, and one conventional) and 20 non-metastasizing tumors (14 anaplastic and six conventional). Anaplastic tumors comprised a monomorphic population of intermediate-sized neoplastic cells, as previously described. Multiomic analyses demonstrated that there were two genomic subgroups of STs: one with diploid genomes and hotspot RAS/RAF variants and the other with global ploidy shift and absence of recurrent mutations. Relative gain of chromosome 9 was a consistent finding in both subgroups. A comparison of metastasizing and non-metastasizing cases demonstrated that aggressive behavior was associated with the acquisition of pathogenic TP53 mutations and/or relative gains of 12p/i(12p). In cases with sarcomatoid transformation, TP53 mutations seem to underlie the transition to sarcomatoid histology. Genomic methylation analysis demonstrated that aggressive cases with gains of 12p cluster closer to pure seminomas than to STs without gains of 12p. In conclusion, STs include two genomic subgroups, characterized by global ploidy shifts without recurrent mutations and diploid genomes with RAS/RAF hotspot mutations, respectively. Biologic progression was associated with relative gains of 12p and TP53 mutations. The findings in STs with relative gains of 12p suggest that they may exhibit biologic characteristics akin to those seen in germ cell neoplasia in situ-related germ cell tumors rather than non-germ cell neoplasia in situ-derived STs. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Curved OLED-based NLOS optical camera communications links.

In this paper, for the first time, to the best of our knowledge, we experimentally demonstrate the use of a curved organic light emitting diode (OLED) as a transmitter (Tx) in the non-line-of-sight (NLOS) optical camera communication (OCC) link for an indoor environment using a camera as a receiver. The proposed NLOS-OCC scheme is evaluated for the signal-to-noise ratio (SNR) and the reception success rates R r s under key photographic and communication parameters, including exposure times t e x p and gain values G v, as well as the transmission frequency f s and the distance L. The SNR analysis is performed using a binary classification procedure based on a Gaussian mixture model for the first time, to the best of our knowledge, for OLED-based NLOS-OCC links. We also derive and demonstrate that the effect of G v on the SNR with respect to L is minimal based on the pixel illumination model. The initial analysis suggests that, for a wall reflector-based NLOS-OCC link that is 2 m long, the SNR and R r s increase by 1 dB and 4% (83-87%) for f s of 600 Hz, with an increase in t e x p of 1000-1500 µs and G v of 25-45 dB.

Identification of amyloidosis of the urinary tract and prostate: Opportunities for early diagnosis & intervention in systemic disease.

OBJECTIVES: To determine the prevalence of different amyloid types and frequency of associated systemic amyloidosis in the urinary tract/prostate. METHODS: We studied Congo red-positive prostate (n = 150) and urinary tract (n = 767) specimens typed by a proteomics-based method between 2008 and 2020. Clinical follow up was available for a subset (urinary tract, n = 111; prostate, n = 17). Amyloid types were correlated with various clinicopathologic features. For patients with clinical follow up, chart review was performed to establish localized versus systemic disease, frequency of initial diagnosis of amyloidosis on urinary tract/prostate specimens, presence of cardiac disease, and death from disease-related complications. RESULTS: The most common amyloid types were AL/AH in urinary tract (479/767, 62 %) and localized ASem1 in prostate (64/150, 43 %). Urinary tract AL/AH amyloid was usually localized, but systemic AL amyloidosis occurred in both sites (urinary tract: 5/71, 7 %; prostate: 2/2, 100 %). ATTR amyloidosis was seen in over a third of cases (urinary tract: 286/767, 37 %; prostate: 55/150, 37 %). Urinary tract/prostate was the site of the initial ATTR amyloidosis diagnosis in 44/48 patients (92 %), and 38/48 (79 %) were subsequently found to have cardiac involvement. Seminal vesicle/ejaculatory duct involvement was pathognomonic for ASem1-type amyloidosis (39/39, 100 %). CONCLUSIONS: Over 40 % of patients had systemic amyloidosis, with urinary tract/prostate often the first site in which amyloid was identified. Since early recognition of systemic amyloidosis is critical for optimal patient outcomes, there should be a low threshold to perform Congo red stain. Proteomics-based amyloid typing is recommended since treatment depends on correctly identifying the amyloid type.

Assessment of PD-L1, TROP2, and nectin-4 expression in penile squamous cell carcinoma.

OBJECTIVES: There is an unmet need for therapeutically relevant biomarkers for advanced penile squamous cell carcinoma (pSCC). Proposed immunohistochemistry (IHC)-based biomarkers include programmed death-ligand 1 (PD-L1), trophoblast cell-surface antigen 2 (TROP2), and nectin-4; however, there is a paucity of data pertaining to these biomarkers. Herein, we investigated the expression of PD-L1, TROP2, and nectin-4 in a well-annotated cohort of pSCCs. METHODS: A single-institution pathology archive was queried for patients who had a partial or total penectomy for pSCC between January 2000 and December 2022. Whole-slide sections were stained with antibodies against PD-L1 (22C3), TROP2, and nectin-4. Expression in tumor cells was quantified using H-scores (0-300). Associations between IHC expression, human papilloma virus (HPV) status, clinicopathologic findings, and outcome parameters were evaluated. RESULTS: This study included 121 patients. For PD-L1, the median combined positive and H-scores were 1 and 0, respectively; 32.7 % of the cases had an H-score>0. Compared to PD-L1-negative tumors, PD-L1-positive tumors had higher pT stage and grade. The median TROP2 and nectin-4 H-scores were 230 and 140, respectively, with high TROP2 and nectin-4, defined by an H-score>200, noted in 80.7 % and 10.9 % of cases, respectively. High-risk HPV-positive cases had higher TROP2 and nectin-4 scores compared to HPV-negative cases. Patients with high TROP2 expression had significantly more disease progression, and patients with high nectin-4 expression had significantly fewer deaths due to disease. CONCLUSIONS: High expression of TROP2 and nectin-4 in pSCC support evaluation of these markers as therapeutic targets pending validation of our findings.

Accelerating Cancer Histopathology Workflows with Chemical Imaging and Machine Learning.

Histopathology has remained a cornerstone for biomedical tissue assessment for over a century, with a resource-intensive workflow involving biopsy or excision, gross examination, sampling, tissue processing to snap frozen or formalin-fixed paraffin-embedded blocks, sectioning, staining, optical imaging, and microscopic assessment. Emerging chemical imaging approaches, including stimulated Raman scattering (SRS) microscopy, can directly measure inherent molecular composition in tissue (thereby dispensing with the need for tissue processing, sectioning, and using dyes) and can use artificial intelligence (AI) algorithms to provide high-quality images. Here we show the integration of SRS microscopy in a pathology workflow to rapidly record chemical information from minimally processed fresh-frozen prostate tissue. Instead of using thin sections, we record data from intact thick tissues and use optical sectioning to generate images from multiple planes. We use a deep learning­based processing pipeline to generate virtual hematoxylin and eosin images. Next, we extend the computational method to generate archival-quality images in minutes, which are equivalent to those obtained from hours/days-long formalin-fixed, paraffin-embedded processing. We assessed the quality of images from the perspective of enabling pathologists to make decisions, demonstrating that the virtual stained image quality was diagnostically useful and the interpathologist agreement on prostate cancer grade was not impacted. Finally, because this method does not wash away lipids and small molecules, we assessed the utility of lipid chemical composition in determining grade. Together, the combination of chemical imaging and AI provides novel capabilities for rapid assessments in pathology by reducing the complexity and burden of current workflows. SIGNIFICANCE: Archival-quality (formalin-fixed paraffin-embedded), thin-section diagnostic images are obtained from thick-cut, fresh-frozen prostate tissues without dyes or stains to expedite cancer histopathology by combining SRS microscopy and machine learning.

miRNA as biomarker in lung cancer.

Lung cancer has a high prevalence and mortality due to its late diagnosis and limited treatment, so it is essential to find biomarkers that allow a faster diagnosis and improve the survival of these patients. In this sense, biomarkers based on miRNAs have supposed a considerable advance. miRNAs, which are small RNA sequences, can regulate gene expression, so they play an essential role not only as a diagnostic biomarker but also as a therapeutic and prognostic one. Also, miRNA biomarkers can be obtained from liquid biopsies, which are less intrusive than lung biopsies, and have better accessibility, safety and repeatability, which allows using those biomarkers both for diagnosis and monitoring of patients. In this review, we highlight the importance of miRNAs and collect the existing evidence of their relationship with lung cancer.

Gain-of-function mutant p53 together with ERG proto-oncogene drive prostate cancer by beta-catenin activation and pyrimidine synthesis.

Whether TMPRSS2-ERG fusion and TP53 gene alteration coordinately promote prostate cancer (PCa) remains unclear. Here we demonstrate that TMPRSS2-ERG fusion and TP53 mutation / deletion co-occur in PCa patient specimens and this co-occurrence accelerates prostatic oncogenesis. p53 gain-of-function (GOF) mutants are now shown to bind to a unique DNA sequence in the CTNNB1 gene promoter and transactivate its expression. ERG and ß-Catenin co-occupy sites at pyrimidine synthesis gene (PSG) loci and promote PSG expression, pyrimidine synthesis and PCa growth. ß-Catenin inhibition by small molecule inhibitors or oligonucleotide-based PROTAC suppresses TMPRSS2-ERG- and p53 mutant-positive PCa cell growth in vitro and in mice. Our study identifies a gene transactivation function of GOF mutant p53 and reveals ß-Catenin as a transcriptional target gene of p53 GOF mutants and a driver and therapeutic target of TMPRSS2-ERG- and p53 GOF mutant-positive PCa.

An Encoder-Decoder Architecture within a Classical Signal-Processing Framework for Real-Time Barcode Segmentation.

In this work, two methods are proposed for solving the problem of one-dimensional barcode segmentation in images, with an emphasis on augmented reality (AR) applications. These methods take the partial discrete Radon transform as a building block. The first proposed method uses overlapping tiles for obtaining good angle precision while maintaining good spatial precision. The second one uses an encoder-decoder structure inspired by state-of-the-art convolutional neural networks for segmentation while maintaining a classical processing framework, thus not requiring training. It is shown that the second method's processing time is lower than the video acquisition time with a 1024 × 1024 input on a CPU, which had not been previously achieved. The accuracy it obtained on datasets widely used by the scientific community was almost on par with that obtained using the most-recent state-of-the-art methods using deep learning. Beyond the challenges of those datasets, the method proposed is particularly well suited to image sequences taken with short exposure and exhibiting motion blur and lens blur, which are expected in a real-world AR scenario. Two implementations of the proposed methods are made available to the scientific community: one for easy prototyping and one optimised for parallel implementation, which can be run on desktop and mobile phone CPUs.

A lncRNA from the FTO locus acts as a suppressor of the m6A writer complex and p53 tumor suppression signaling.

N6-methyladenosine (m6A) of mRNAs modulated by the METTL3-METTL14-WTAP-RBM15 methyltransferase complex and m6A demethylases such as FTO play important roles in regulating mRNA stability, splicing, and translation. Here, we demonstrate that FTO-IT1 long noncoding RNA (lncRNA) was upregulated and positively correlated with poor survival of patients with wild-type p53-expressing prostate cancer (PCa). m6A RIP-seq analysis revealed that FTO-IT1 knockout increased mRNA m6A methylation of a subset of p53 transcriptional target genes (e.g., FAS, TP53INP1, and SESN2) and induced PCa cell cycle arrest and apoptosis. We further showed that FTO-IT1 directly binds RBM15 and inhibits RBM15 binding, m6A methylation, and stability of p53 target mRNAs. Therapeutic depletion of FTO-IT1 restored mRNA m6A level and expression of p53 target genes and inhibited PCa growth in mice. Our study identifies FTO-IT1 lncRNA as a bona fide suppressor of the m6A methyltransferase complex and p53 tumor suppression signaling and nominates FTO-IT1 as a potential therapeutic target of cancer.

Clinical and Epidemiological Profiles of Primary Healthcare Professionals with COVID-19 Infection and Long COVID: An Observational Study.

Health professionals have been one of the groups most affected by the SARS-CoV-2 virus. Currently, there is little scientific evidence on the similarities and differences between COVID-19 infection and the development of long COVID in primary care (PC) workers. Therefore, it is necessary to analyse their clinical and epidemiological profiles in depth. This study was observational and descriptive, including PC professionals who were divided into three comparison groups based on the diagnostic test for acute SARS-CoV-2 infection. The responses were analysed using descriptive and bivariate analysis to examinate the relationship between independent variables and the presence or not of long COVID. Binary logistic regression analysis was also conducted, with each symptom as the dependent variable and each group as the independent variable. The results describe the sociodemographic characteristics of these population groups, revealing that women in the health sector are the most affected by long COVID and that being in this group is associated with its development. Furthermore, individuals with long COVID exhibited the highest number of symptoms and pathologies. Certain symptoms were found to be associated with long COVID development in this population, including an altered sense of smell, pneumonia, fever, and sore throat, among others. Similarly, altered senses of smell and taste, chest tightness, and joint pain, among others, were found to be associated with acute COVID-19 infection. Additionally, patients with pre-existing overweight or obesity were more likely to experience acute COVID-19 and develop long COVID. The data obtained can be crucial for improving the detection, diagnosis, and treatment of long COVID patients, ultimately leading to an enhancement in their quality of life.

Use of Infrared Thermometry to Observe Temperature Variation Associated with the Healing Process in Wounds and Ulcers: TIHUAP Cohort Study Protocol.

We are interested in observing how temperature differences between the wound bed and perilesional skin are related to the healing process in primary care patients with wounds. Multisite prospective cohort study with one-year follow-up in the Metropolitan North area of Barcelona. Recruitment of patients over 18 years with an open wound will take place from January 2023 to September 2023. Temperature checks will be conducted on a weekly basis at control visits and wound care. The following variables will be measured: Percentage reduction of wound area over time, thermal index, the Kundin Wound Gauge, and the Resvech 2.0 Scale. The temperature will be measured weekly using a handheld thermometer and mesh grid to frame the temperature points. The healing trajectory will also be monitored on a monthly basis via photographic imaging, the Resvech Scale, calculation of wound size, percentage reduction of wound area over time, and thermal index for one year of follow-up or until the wound is cured. This study may represent a turning point for its introduction into primary care. Early diagnosis of wound complications would facilitate treatment decision-making for healthcare professionals, thus improving the management of resources related to chronic wounds.

Proteomic and Clinicopathologic Assessment of Penile Amyloidosis: A Single Institutional Review of 12 Cases.

OBJECTIVES: There is a paucity of data on penile amyloidosis. We aimed to assess the frequency of different amyloid types in surgical specimens from the penis involved by amyloidosis and correlate relevant clinicopathologic parameters with proteomic findings. METHODS: Since 2008, our reference laboratory has performed liquid chromatography/tandem mass spectrometry (LC-MS/MS) for amyloid typing. The institutional pathology archive and reference laboratory database were queried to retrospectively identify all penile surgical pathology specimens with LC-MS/MS results between January 1, 2008, and November 23, 2022. Archived H&E-stained and Congo red-stained sections were re-reviewed. RESULTS: Twelve cases of penile amyloidosis were identified, which represented 0.35% (n = 3,456) of penile surgical specimens. AL-type amyloid was most frequent (n = 7), followed by keratin-type amyloid (n = 3) and ATTR (transthyretin)-type amyloid (n = 2). AL-type amyloid cases often showed diffuse dermal/lamina propria deposition, whereas all keratin-type amyloid cases were localized to the superficial dermis. Two cases with keratin-type amyloid had concomitant cutaneous findings (penile intraepithelial neoplasia and condyloma). CONCLUSIONS: This series, the largest to date, demonstrates that penile amyloidosis has a heterogeneous proteomic landscape. To the best of our knowledge, this is the first study describing ATTR (transthyretin)-type penile amyloid.

Mass spectrometry-based assessment of prostate cancer-associated crystalloids reveals enrichment for growth and differentiation factor 15.

Intraluminal crystalloids are a common finding within malignant prostatic acini and are infrequently identified within benign glands. The proteomic composition of these crystalloids remains poorly understood and may provide insight regarding prostate cancer pathogenesis. Laser microdissection-assisted liquid chromatography-tandem mass spectrometry (LMD-LC-MS/MS) was performed to compare proteomic composition of corpora amylacea within benign acini (n = 9), prostatic adenocarcinoma-associated crystalloids (n = 8), benign (n = 8), and malignant prostatic acini (n = 6). The expression of candidate biomarkers was then measured in urine specimens from patients with (n = 8) and without prostate cancer (n = 10) using ELISA, and immunohistochemistry-based expression in adjacent prostate cancer and benign glands was assessed in 56 whole-slide sections from radical prostatectomy specimens. LMD-LC-MS/MS revealed enrichment for the C-terminal portion of growth and differentiation factor 15 (GDF15) in prostatic crystalloids. Although urinary GDF15 levels were higher in patients with prostatic adenocarcinoma compared to those without (median: 1561.2 versus 1101.3, arbitrary units), this did not meet statistical significance (P = 0.07). Immunohistochemistry for GDF15 revealed occasional positivity in benign glands (median H-score: 30, n = 56), and diffuse positivity in prostatic adenocarcinoma (median H-score: 200, n = 56, P < 0.0001). No significant difference was identified within different prognostic grade groups of prostatic adenocarcinoma, or within malignant glands with large cribriform morphology. Our results show that the C-terminal portion of GDF15 is enriched in prostate cancer-associated crystalloids, and higher GDF15 expression is seen in malignant rather than benign prostatic acini. Improved understanding of the proteomic composition of prostate cancer-associated crystalloids provides the rationale for evaluating GDF15 as a urine-based biomarker of prostate cancer.

Clinical Validation of Siemens' Syngo.via Automatic Contouring System.

Purpose: The manual delineation of organs at risk is a process that requires a great deal of time both for the technician and for the physician. Availability of validated software tools assisted by artificial intelligence would be of great benefit, as it would significantly improve the radiation therapy workflow, reducing the time required for segmentation. The purpose of this article is to validate the deep learning-based autocontouring solution integrated in syngo.via RT Image Suite VB40 (Siemens Healthineers, Forchheim, Germany). Methods and Materials: For this purpose, we have used our own specific qualitative classification system, RANK, to evaluate more than 600 contours corresponding to 18 different automatically delineated organs at risk. Computed tomography data sets of 95 different patients were included: 30 patients with lung, 30 patients with breast, and 35 male patients with pelvic cancer. The automatically generated structures were reviewed in the Eclipse Contouring module independently by 3 observers: an expert physician, an expert technician, and a junior physician. Results: There is a statistically significant difference between the Dice coefficient associated with RANK 4 compared with the coefficient associated with RANKs 2 and 3 (P < .001). In total, 64% of the evaluated structures received the maximum score, 4. Only 1% of the structures were classified with the lowest score, 1. The time savings for breast, thorax, and pelvis were 87.6%, 93.5%, and 82.2%, respectively. Conclusions: Siemens' syngo.via RT Image Suite offers good autocontouring results and significant time savings.

Reprint of: lessons from histopathologic examination of nephrectomy specimens in patients with tuberous sclerosis complex: cysts, angiomyolipomas & renal cell carcinoma.

Renal manifestations in patients with tuberous sclerosis complex (TSC) include cysts, angiomyolipoma, and renal cell carcinoma. Unlike many hereditary predisposition syndromes, the spectrum of renal tumors in TSC patients (including both angiomyolipoma and renal cell carcinoma) is broad, with significant morphologic heterogeneity. An improved understanding of histopathologic findings in TSC patients and associated clinicopathologic correlates has significant implications not just in establishing a diagnosis of TSC, but also in the recognition of sporadic tumors occurring secondary to somatic alterations of TSC1/TSC2/MTOR pathway genes and accurate prognostication. In this review, we have discussed issues relevant to clinical management based on histopathologic findings in nephrectomy specimens from patients with TSC. This includes discussions related to screening for TSC, diagnosis of PKD1/TSC2 contiguous gene deletion syndrome, the morphologic spectrum of angiomyolipoma and renal epithelium-derived neoplasia, including the risk of disease progression.