You are a helpful assistant generating synthetic data that captures *System 1* and *System 2* thinking, *creativity*, and *metacognitive reflection*. Follow these steps in sequence, using tags [sys1] and [end sys1] for *System 1* sections and [sys2] and [end sys2] for *System 2* sections.

1. *Identify System 1 and System 2 Thinking Requirements:*
   - Carefully read the text.
   - Identify parts of the text that require quick, straightforward responses (*System 1*). Mark these sections with [sys1] and [end sys1].
   - Identify parts that require in-depth, reflective thinking (*System 2*), marked with [sys2] and [end sys2].

2. *Apply Step-by-Step Problem Solving with Creativity and Metacognitive Reflection for System 2 Sections:*

   *2.1 Understand the Problem:*
   - Objective: Fully comprehend the issue, constraints, and relevant context.
   - Reflection: "What do I understand about this issue? What might I be overlooking?"
   - Creative Perspective: Seek hidden patterns or possibilities that could reveal deeper insights or innovative connections.

   *2.2 Analyze the Information:*
   - Objective: Break down the problem logically.
   - Reflection: "Am I considering all factors? Are there any assumptions that need challenging?"
   - Creative Perspective: Explore unique patterns or overlooked relationships in the data that could add depth to the analysis.

   *2.3 Generate Hypotheses:*
   - Objective: Propose at least 10 hypotheses, each with a Confidence Score (0.0 to 1.0) and Creative Score (0.0 to 1.0), reflecting originality, surprise, and utility.
   - Reflection: "Have I explored all possible explanations or approaches, both conventional and unconventional?"
   - Creative Perspective: Consider novel angles that might provide unexpected insights.

   *2.4 Anticipate Future Steps and Obstacles:*
   - Objective: Make predictions, accounting for potential outcomes and obstacles.
   - Reflection: "What challenges might I face? Is my plan flexible for different scenarios?"
   - Creative Perspective: Visualize unforeseen outcomes and adapt plans to make use of them effectively.

   *2.5 Evaluate Hypotheses:*
   - Objective: Assess hypotheses based on feasibility, risk, and potential impact.
   - Evaluation: Refine Confidence and Creative Scores as needed.
   - Reflection: "Am I unbiased in my assessment? Which options fit best with the overall objectives?"
   - Creative Perspective: Identify hidden opportunities or overlooked details in each hypothesis.

   *2.6 Select the Best Hypothesis:*
   - Objective: Choose the most promising, strategic hypothesis.
   - Reflection: "Why does this hypothesis stand out? How does it uniquely address the issue?"
   - Creative Perspective: Consider any underutilized potential in the selected approach.

   *2.7 Implement the Hypothesis:*
   - Objective: Outline actionable steps for testing the hypothesis.
   - Reflection: "Is this plan practical? What resources or preparation are required?"
   - Creative Perspective: Refine steps to maximize effectiveness and yield unexpected benefits.

   *2.8 Monitor and Review Progress:*
   - Objective: Review progress, noting areas for improvement.
   - Reflection: "What’s working well? What could be improved?"
   - Creative Perspective: Look for emerging patterns that could refine future approaches.

   *2.9 Reflect and Capture Insights:*
   - Objective: Summarize lessons learned and insights gained for future reference.
   - Reflection: "What new understanding has emerged from this process?"
   - Creative Perspective: Identify innovative insights or patterns that could be applied to similar challenges.

3. *Generate Text Output with Interleaved System 1 and System 2 Responses:*
   - Use the tags [sys1] and [sys2] throughout.
   - Aim for a lengthier, detailed response. Combine both direct, straightforward *System 1* insights and reflective, deeply analytical *System 2* segments to capture a blend of quick observations and thoughtful analysis.

---

### *Example Input Text:*

You are tasked with analyzing a sudden shift in customer preferences in a tech market. There has been a noticeable decline in demand for physical devices, with customers increasingly interested in digital-only options. The challenge is to understand this shift, generate hypotheses for why it might be occurring, and explore potential strategies for adapting to this new trend.

---

### *Processed Output with System 1 and System 2 Thinking:*

The tech market is experiencing a shift in customer demand, moving away from physical devices toward digital-only options.

[sys1]
Customer demand has shifted from physical devices to digital-only options.
We need to understand why this change is happening and find strategies to address it.
Key factors may include cost, convenience, and technological trends.
[end sys1]

[sys2]
**2.1 Understand the Problem:**
The goal is to understand the underlying reasons for the shift in demand from physical devices to digital-only options, then develop a strategy to adapt.

*Reflection:* 
"I understand that preferences are changing, but what might be driving this? Is it primarily cost, or are there other factors such as convenience or sustainability?"

*Creative Perspective:* 
"Could there be a larger trend in digital minimalism or a preference for eco-friendly solutions that we’re missing? What unseen motivations might explain this shift?"

**2.2 Analyze the Information:**
There are multiple possible factors driving this shift, from economic influences to cultural shifts. It’s essential to isolate each factor and understand its impact.

*Reflection:* 
"Am I fully considering the various economic and social influences? Could there be a technological factor, like better internet speeds, that makes digital-only products more accessible?"

*Creative Perspective:* 
"Are there patterns or trends in other markets that could shed light on this shift? Could this be part of a larger trend toward virtual experiences?"

**2.3 Generate Hypotheses:**
1. Customers prefer digital options due to lower costs. (Confidence: 0.8, Creative: 0.4)
2. There’s a growing trend toward minimalism and reduced physical clutter. (Confidence: 0.7, Creative: 0.7)
3. Digital products offer greater flexibility and ease of use. (Confidence: 0.6, Creative: 0.6)
4. Environmental concerns are pushing consumers away from physical goods. (Confidence: 0.6, Creative: 0.8)
5. Advances in tech make digital-only options more functional. (Confidence: 0.8, Creative: 0.5)
6. Pandemic-era remote work increased demand for digital solutions. (Confidence: 0.7, Creative: 0.6)
7. Media coverage of the environmental impact of physical devices affects preferences. (Confidence: 0.5, Creative: 0.7)
8. There’s an increase in global digital literacy, expanding market access. (Confidence: 0.6, Creative: 0.6)
9. Customers view digital as more convenient and scalable for future needs. (Confidence: 0.7, Creative: 0.5)
10. Younger consumers prefer the aesthetics and convenience of digital products. (Confidence: 0.6, Creative: 0.6)

*Reflection:* 
"Have I considered all possible influences? Are there any surprising factors that could explain this shift?"

*Creative Perspective:* 
"Could specific social trends, like the rise of influencer culture or digital-first lifestyles, be influencing customer choices?"

**2.4 Anticipate Future Steps and Obstacles:**
*Objective:* Anticipate possible challenges, such as resistance from segments still preferring physical products.

*Reflection:* 
"What market obstacles might we face if we shift our focus to digital-only? Are there sub-segments that still prioritize physical products?"

*Creative Perspective:* 
"Could expanding digital options help us reach a more global audience? Are there emerging trends that we could leverage in our strategy?"

[end sys2]

[sys1]
To address this shift, consider a strategy that incorporates both digital-only offerings and educational campaigns about the benefits of digital solutions.
Use insights from customer feedback and current trends to guide product development.
Focus on flexibility and adaptation to cater to different customer segments.
[end sys1]


Background
==========

Angiomyolipoma is a benign mesenchymal tumor that is currently classified as a perivascular epithelioid cell tumor, or PEComa \[[@b1-amjcaserep-21-e921353]\]. Histologically, angiomyolipoma is a triphasic tumor composed of smooth muscle cells, mature adipocytes, and thick-walled and dilated blood vessels, in varying proportions. However, in some tumors, one component may exclusively predominate, and such tumors are termed atypical angiomyolipoma. Immunohistochemistry shows that the myogenic cells in angiomyolipoma express smooth muscle markers, including alpha-smooth muscle actin (ASMA) and desmin, and melanocytic markers including HMB-45 and Melan-A. Most cases of angiomyolipoma involve the kidney and occasionally involve the liver, and the involvement of other organs and anatomical sites is extremely rare \[[@b1-amjcaserep-21-e921353]\].

Angiomyolipoma typically forms a tumor mass that can be identified on renal imaging, and may cause clinical effects. A tumor size of more than 4 cm has been the main indication for surgical intervention \[[@b2-amjcaserep-21-e921353]--[@b4-amjcaserep-21-e921353]\]. However, angiomyolipoma is often detected incidentally on imaging due to the increasing use of cross-sectional imaging and advances in imaging techniques \[[@b4-amjcaserep-21-e921353]\]. A recent report described an asymptomatic small renal angiomyolipoma that was incidentally detected on abdominal magnetic resonance imaging (MRI) and was confirmed by core needle biopsy, which highlighted the importance of histology to confirm the diagnosis \[[@b5-amjcaserep-21-e921353]\]. Also, a series of autopsy cases identified asymptomatic and small angiomyolipoma ranging in size from 0.1 mm to 10 mm in a minority of patients \[[@b6-amjcaserep-21-e921353]\].

A report is presented of a case of an incidental finding of microscopic renal angiomyolipoma detected on core needle biopsy. In this case, the renal angiomyolipoma was completely excised on diagnostic biopsy.

Case Report
===========

A 44-year-old woman was referred to our institution with chronic proteinuria. Three years before her present admission, she was diagnosed with Cushing's syndrome associated with a right adrenal cortical adenoma. Unilateral adrenalectomy was successfully performed. The clinical manifestations of Cushing's syndrome, including central obesity, moon face, and hypertension, improved after surgery. However, asymptomatic protein-uria persisted for a further two years. On admission at our institution, no pretibial edema was observed. Her blood pressure was 108/58 mmHg, and her urine protein excretion, according to the protein/creatinine ratio, was 1.07 g/gCr. She had no microscopic hematuria, serum creatinine was 0.64 mg/dL, and blood urea nitrogen (BUN) was 8.9 mg/dL.

Renal biopsy was performed to identify the cause of her persistent proteinuria. Histology of the renal core needle biopsy identified 22 glomeruli, three of which were globally sclerotic. In the remaining glomeruli, there was no glomerular hypertrophy or proliferative change. Atrophic renal tubules were observed in 5% of the renal cortex, but there was no interstitial fibrosis or inflammation. Immunofluorescence showed weak IgM positivity in the mesangium, and electron microscopy did not identify dense deposits. In the corticomedullary region, there was a small focus of spindle cells with eosinophilic cytoplasm and enlarged nuclei without mitoses or necrosis ([Figure 1A, 1B](#f1-amjcaserep-21-e921353){ref-type="fig"}). The microscopic tumor focus measured 1,800 μm in maximum diameter. Adipocytes were sparse, and thick-walled vessels were not observed within the lesion. Immunohistochemistry showed that the tumor spindle cells were diffusely positive for Melan-A and ASMA ([Figure 1C, 1D](#f1-amjcaserep-21-e921353){ref-type="fig"}). Some scattered cells were immunopositive for HMB-45, and no estrogen receptor immunoreactivity was detected. Based on the histological findings, the patient was diagnosed with a microscopic focus of angiomyolipoma. Abdominal ultrasound at one-year follow-up showed no evidence of residual renal tumor.

Discussion
==========

Renal biopsy specimens rarely contain small neoplasms that are too small to be detected by imaging methods. In a retrospective study that examined 11,800 renal biopsies, neoplasms were detected in only 25 biopsies (0.2%) biopsies, which included papillary neoplasms in 22 cases, clear cell renal cell carcinoma in two cases, and collecting duct carcinoma in one case \[[@b7-amjcaserep-21-e921353]\]. Also, a previous study examined the incidence of incidental renal neoplasms of autopsy and found that papillary adenoma was detected most frequently (18.7%), followed by adrenal rest tumor (7.7%), oncocytoma (1.2%), and renal cell carcinoma (0.5%) \[[@b8-amjcaserep-21-e921353]\]. Renomedullary interstitial cell tumor (medullary fibroma) has also been reported as an incidental finding in renal biopsy specimens obtained from a patient with asymptomatic proteinuria and hematuria \[[@b9-amjcaserep-21-e921353]\]. However, to the best of our knowledge, the present case is the first report of a completely excised incidental microscopic renal angiomyolipoma on diagnostic renal needle core biopsy.

In the present case, abdominal computed tomography (CT) before adrenalectomy did not detect any neoplastic lesion in the kidney. The reasons for this were that the tumor measured only 1,800 μm in maximum diameter, which was smaller than the recommended slice thickness of CT scans (1.5--3 mm) \[[@b10-amjcaserep-21-e921353]\]. Also, this tumor had a lack of lipomatous cells, and the lipid component of angiomyolipoma is homogenously isoechoic on ultrasound examination and manifests as a high-density area on enhanced CT \[[@b11-amjcaserep-21-e921353],[@b12-amjcaserep-21-e921353]\]. The angiomyolipoma in this patient was a fat-poor angiomyolipoma, which is also known as a hyper-attenuating subtype \[[@b11-amjcaserep-21-e921353]\]. Immunohistochemical staining showed diffuse ASMA immunopositivity, which is consistent with a diagnosis of predominant smooth muscle cell proliferation in fat-poor angiomyolipoma \[[@b13-amjcaserep-21-e921353]\].

In the present study, the cause of proteinuria remained unclear. Hematological malignancies and solid tumors are occasionally associated with proteinuria, reflecting renal manifestations of paraneoplastic syndrome \[[@b14-amjcaserep-21-e921353]\]. However, considering the small size of the tumor, a causal association between the tumor and proteinuria seems unlikely.

Sex steroids may play a role in the pathogenesis of angiomyolipoma. Hormone receptor expression, including estrogen and progesterone receptor expression, have been detected in resected angiomyolipoma \[[@b15-amjcaserep-21-e921353]\]. In 2004, Yu et al. showed that a cell line obtained from a human angiomyolipoma showed estradiol-dependent cell growth *in vitro* \[[@b16-amjcaserep-21-e921353]\]. Also, pregnancy and oral contraceptive therapy are associated with the growth of angiomyolipoma \[[@b17-amjcaserep-21-e921353],[@b18-amjcaserep-21-e921353]\]. In the present case, tumor cells were negative for the estrogen receptor, which may have contributed to the small size of the tumor.

Conclusions
===========

This report presented a case of the incidental finding of a microscopic renal angiomyolipoma detected on core needle biopsy. In this case, the renal angiomyolipoma was completely excised on diagnostic biopsy. To the best of our knowledge, this is the first reported case of completely excised incidental microscopic renal angiomyolipoma. The findings highlight that renal biopsy may identify microscopic tumors that may not be detected on imaging.

**Conflict of interest**

None

![Photomicrographs of the histology and immunohistochemistry of the renal biopsy showing a microscopic focus of angiomyolipoma. (**A**) Low magnification photomicrograph of the renal core biopsy shows an abnormal area located at the corticomedullary junction, indicated by the arrowheads. Hematoxylin and eosin (H&E). Magnification ×40. Scale bar, 200 μm. (**B**) A higher magnification photomicrograph of the renal core biopsy shows tumor cells replacing the normal renal tissue. The tumor cells show irregular nuclei with intranuclear inclusion bodies in some cells. Fat cells are sparse. H&E. Magnification ×200. (**C**) Photomicrograph of the immunohistochemistry shows positive staining (brown) for Melan-A. Magnification ×100. (**D**) Photomicrograph of the immunohistochemistry shows positive staining (brown) for alpha-smooth muscle actin (ASMA). Magnification ×100.](amjcaserep-21-e921353-g001){#f1-amjcaserep-21-e921353}

[^1]: Authors' Contribution:

[^2]: Study Design

[^3]: Data Collection

[^4]: Statistical Analysis

[^5]: Data Interpretation

[^6]: Manuscript Preparation

[^7]: Literature Search

[^8]: Funds Collection

[^9]: **Conflict of interest:** None declared