Tuberous Sclerosis with Angiomyolipoma and Renal Cell Carcinoma

Ambikavathy Mohan,a S Kumar,b Krishna Shettyc

Departments of aSurgery, bMedicine and cUrology, Sri Devaraj Urs Medical College, Kolar, Karnataka

Abstract

Angiomyolipomas and renal cysts are the common renal lesions associated with Tuberous Sclerosis.  Reported incidence of Renal Cell Carcinoma (RCC) in Tuberous Sclerosis is only 2%.  We report a case of Tuberous Sclerosis with bilateral angiomyolipomas and left Renal Cell Carcinoma. A 30-yr-old female presented with history of pain and mass in the left lumbar region of 3 months duration.  She had undergone laparotomy and left partial nephrectomy at a local hospital.  Histopathology showed sarcomatoid variant of RCC.  On examination, she had features of Tuberous Sclerosis such as Adenoma Sebaceum over the face, Subungual Fibroma and white leaf shaped macules over the thigh.

Keywords: , , ,

Introduction

The renal lesion usually associated with Tuberous Sclerosis is Angiomyolipoma.  Renal cyst is the next most commonly found renal lesion. The reported incidence of Renal Cell Carcinoma in Tuberous Sclerosis is 2-4%.2  We report a case of Tuberous Sclerosis with bilateral renal Angiomyolipomas and left Renal Cell Carcinoma.

The Case

Figure 1. Adenoma Sebaceum over the face

Figure 1. Adenoma Sebaceum over the face

A 30- year- old female presented with the history of pain and mass in the left lumbar region of 3 months duration.  She had undergone exploratory laparotomy one year back for a mass in the left iliac and lumbar regions with a provisional diagnosis of ovarian cyst at a local hospital.  Discharge summary revealed histopathology report showing sarcomatoid variant of Renal Cell Carcinoma.  She gave history of epileptic attacks during childhood.

Figure 2. Subungual Fibroma over right index finger (Koenen Tumor)

Figure 2. Subungual Fibroma over right index finger (Koenen Tumor)

On examination, the patient had all the classical features of Tuberous Sclerosis: Adenoma Sebaceum on the face, Subungual Fibroma over right index finger (Koenen tumor), Semi lunar hypo pigmented patches over back and Ash-Leaf macules over the left thigh (Figures 1-3). Per-abdominal examination showed a right paramedian scar and bilateral large ballotable flank masses. Higher mental functions were normal.

Investigations

Figure 3. Shagreen patches (Ash leaf macules) over the  left thigh

Figure 3. Shagreen patches (Ash leaf macules) over the left thigh

Urine examination showed 1 to 2 RBC’s/hpf.  Haemoglobin was down to 9.0g/dl and ESR was 40 mm in the first hour.   Chest X-ray was normal. Abdominopelvic Ultrasound showed that Left kidney was enlarged with a large (7x6cm) hypoechoic lesion in the upper pole.  Right Kidney was also enlarged and outline deformed with multiple hyper echoic regions all over the parenchyma. C T Abdomen showed a large (9x6x7cm) necrotic mass in left lumbar region infiltrating and encasing splenic flexure and upper descending colon.  Multiple enlarged lymph nodes were seen in left renal fossa, para-aortic region and retro-crural region.  Multiple fat density lesions were seen in both kidneys suggestive of angiomyolipomas (Figures 5 & 6).

Figures 5,6. CT abdomen showing large 9x6x7cm necrotic mass in left lumbar region and multiple fat density lesions in both kidneys

Figures 5,6. CT abdomen showing large 9x6x7cm necrotic mass in left lumbar region and multiple fat density lesions in both kidneys

C T Brain showed calcified subependymal hamartomas in the lateral ventricular surface and right temporal horn (Figures 7 & 8).  Echocardiography showed mild Left Ventricular Hypertrophy, and no evidence of Rhabdomyoma (Figure 4). Histopathology showed cystic and necrotic areas with sarcomatoid elements made up of spindle cells admixed with epithelial component.  Cells had irregular nuclei with nucleoli. Also observed were clear cell areas admixed with stromal components.

Figures 7,8. CT brain showing calcified subependymal hamartomas in the lateral ventricular surface and right temporal horn

Figures 7,8. CT brain showing calcified subependymal hamartomas in the lateral ventricular surface and right temporal horn

Treatment

In view of the extensive disease, when the patient and their attendants were explained the risks of attempting nephron sparing surgery and probable need for renal replacement therapy later, they were not willing for any surgical intervention.  So, palliative chemotherapy with vinblastine was started.

Figure 4. Echocardiography showing mild Left Ventricular Hypertrophy. No evidence of Rhabdomyoma

Figure 4. Echocardiography showing mild Left Ventricular Hypertrophy. No evidence of Rhabdomyoma

Discussion

Tuberous Sclerosis is an inherited, autosomal dominant neurocutaneous disorder characterized by seizures, mental retardation, cutaneous lesions and visceral hamartomas described by Bourneville in 1880.4,5 Incidence is 10.6 cases /1,00,000 persons.1 Lesions associated with tuberous sclerosis are as follows: Brain: Cortical tuber Retina : Phakomas Skin   : Angiofibroma Heart : Rhabdomyoma Bone : Sclerotic lesions Lung : Lymphangioma Kidney: Angiomyolipoma and renal cysts2,6 Renal angiomyolipomas occur in 50 – 80% of patients and are usually small, multiple and bilateral.3 Large angiomyolipomas are more likely to bleed and prophylactic embolisation or surgical excision is recommended if size is > 4cm.1,7,8  Renal cysts develop in about 20% of patients. The cystic disease can lead to renal failure, probably because of compression of the parenchyma by the expanding cysts, which is uncommon before 4th decade. Biopsy of renal cysts in Tuberous Sclerosis is pathognomonic, showing eosinophilic epithelial hyperplasia lining the cysts.4  The incidence of Renal Cell Carcinoma in Tuberous Sclerosis complex has been reported to be 2-4 %, which is higher than that of the general population. These occur at a younger age (mean 28 yrs), 80% occur in women and 43% are bilateral. 50% of lesions show high-grade sarcomatoid features. Renal cell carcinoma evolves from the cystic epithelium.2,8

Conclusion

Tuberous sclerosis is a lifelong disease and patients are at risk of developing malignancies and hence patients need to be regularly followed up.  Other members of the family also need to be screened for the disease.

References

  1. Stillwell TJ, Gomez MR, Kelalis PP. Renal lesions in tuberous sclerosis. J Urol. 1987 Sep;138(3):477–81.
  2. Lendvay TS, Marshall FF. The tuberous sclerosis complex and its highly variable manifestations. J Urol. 2003 May;169(5):1635–42.
  3. Chonko AM ,Weiss JM ,Stein JH ,et al : Renal involvement in tuberous sclerosis .Am J Med 1974;56:124-132.
  4. Stapleton FB, Johnson D, Kaplan GW, Griswold W. The cystic renal lesion in tuberous sclerosis. J Pediatr. 1980 Oct;97(4):574–9
  5. Taylor RS, Joseph DB, Kohaut EC, Wilson ER, Bueschen AJ. Renal angiomyolipoma associated with lymph node involvement and renal cell carcinoma in patients with tuberous sclerosis. J Urol. 1989 Apr;141(4):930–2.
  6. Tongaonkar HB, Sampat MB, Dalal AV, Dandekar NP, Kulkarni JN, Kamat MR. Bilateral renal angiomyolipoma. J Surg Oncol. 1994 Sep;57(1):65–70.
  7. Graves N, Barnes WF. Renal cell carcinoma and angiomyolipoma in tuberous sclerosis: case report. J Urol. 1986 Jan;135(1):122–3.
  8. Roach ES, Sparagana SP. Diagnosis of tuberous sclerosis complex. J Child Neurol. 2004 Sep;19(9):643–9.
  9. Williams JM, Racadio JM, Johnson ND, Donnelly LF, Bissler JJ. Embolization of renal angiomyolipomata in patients with tuberous sclerosis complex. Am J Kidney Dis. 2006 Jan;47(1):95–102.

Author Information

  1. Ambikavathy Mohan, Associate Professor, Department of Surgery, Sri Devaraj Urs Medical College, Kolar, Karnataka
  2. Kumar Srinivasan, Associate Professor, Department of Medicine, Sri Devaraj Urs Medical College, Kolar, Karnataka
  3. Krishna Shetty, Professor, Department of Urology, Sri Devaraj Urs Medical College, Kolar, Karnataka

Conflict of Interest – None Declared

Leave Your Comment

*