Among the cutaneous lesion in TS hypomelanotic macule occurs in about 90%, angiofibroma in 75%, shagreen patch is seen in about 50%, %, ungual fibroma in 20% and confetti skin lesion in 3% to 58%. Forehead plaque is seen in 25% of TSC patient and is paired with angiofibroma in diagnostic criteria.This patient had both multiple facial angiofibroma and multiple forehead plaque.

Approximately half of the patient with TS have normal intelligence, seizure accounts in about 63% to 78% of infants with TSC and facial angiofibroma occur in about 75% of patients with onset typically occurring between ages 2 to 5 years. In a study on epilepsy in adult patient with TSC, authors found 71.2% of the patient had epilepsy. The classic triad of mental retardation, epilepsy, and facial angiofibroma, also known as Vogt triad occurs only in 29% of the cases with 6% lacking all three of them. Hence, it can be corelated to our patient who has no history of epilepsy and has normal intelligence.

Brain findings in TSC comprises of multiple cortical tubers observed in 90% which is commonly seen together with radial migration lines, subependymal nodules (SEN) and subependymal giant cell astrocytoma (SEGA) which are observed in 80% and 5% to 15% respectively. SEN is often detected prenatally or at birth and SEGA are likely to arise during childhood or adolescence but unlikely after 20 years of age. Calcified multiple subcortical tubers with radial migration lines and subependymal nodules were seen in our patient as well.

In regards to renal findings, three major renal manifestations of TSC are: angiomyolipoma, cysts and renal cell carcinoma. Out of these three, only angiomyolipoma has been considered a part of major diagnostic criteria. Angiomyolipomas are benign tumors composed of varying proportion of vascular, smooth muscle and adipose tissue. It is to be noted that a patient who has lymphangiomatosis (LAM) and renal angiomyolipoma but no other features of TSC, does not meet criteria for a definite diagnosis.

Angiomyolipomas are relatively specific for TSC with incidence of 50 to 75% however it does occur in general population as well with an incidence of 1-2% and a female predominance of 6:1. Classic angiomyolipoma occurs mostly in female in fifth decade sporadically while angiomyolipoma in TSC presents earlier in third decade with no sex predominance. Angiomyolipoma in TSC is more likely to be multiple (97% vs. 13%), bilateral (80% vs 12%), grows with time (67% vs 21%) and bleeding tendency (44 vs 14%). Number and size of angiomyolipoma are known to increase with age which has been corelated with the second-hit hypothesis, marked more in adolescence with a higher frequency in girls. Since, patient in this report had her first presentation at the age of 27 years, increase in size and number could not be estimated. However, she had multiple such lesions of variable size which could have been increasing since long.

Symptoms of angiomyolipoma are absent or minimal with most complains being painless hematuria as in our patient, flank pain or a gross retroperitoneal bleed. There are some other complications that have been reported which include Wunderlich syndrome and end stage renal disease (ESRD). Wunderlich syndrome is a spontaneous bleeding that is confined to the subcapsular and perirenal space which can arise when enlarging vessel becomes aneurysmal and ruptures within angiomyolipoma. Our patient did not have classical Lenk’s triad of the syndrome which consists of acute flank pain, palpable flank mass, and hypovolemic shock. However, the imaging findings does demonstrate aneurysmal vessel and hematoma. The incidence of ESRD in TSC is low and that can be ascertained in our patient with no signs of renal failure despite the presence of multiple angiolipoma in bilateral kidney.

In relation to the imaging finding for diagnosis presence of focal or diffuse fat containing masses is the characteristics feature of an angiomyolipoma which can be visualized with all ultrasonography, CT and MRI with latter being the best alternative in case of limitations or equivocal findings with other modality. It is needless to say biopsy should not be the mode of diagnosis due to the vascularity of the tumor and increased morbidity. In our case, CT was done and it was able to delineate the lesion accurately for us to be able to diagnose the condition.

Regarding treatment of renal angiomyolipoma, recommendations are to use both tumor size and symptomatology to assess the course of tumor progression and intervention to be used. One study found that lesion less than 4 cm were less likely to be symptomatic than lesions that are ≥4 cm (24% vs 52%) and is also less likely to grow (27% vs 46%). Surgical interventions in angiomyolipoma are reserved for patients with symptomatic lesions or lesions with rapid growth. Our patient had symptom of hematuria for which she underwent cystoscopy with the evacuation of hematoma from the bladder, however surgical management of the condition was declined.

Renal manifestations of TSC were the second leading cause of premature death after severe intellectual disability thus it is recommended to have a closer observation and prompt treatment as needed.

Angiomyolipoma has been found not only in kidney but also in other organs including liver as seen in this patient.. Incidence of hepatic angiolipoma is increasing in part due to routine monitoring of patients of TS with renal angiomyolipoma. Hepatic angiomyolipoma are usually asymptomatic though one study mentioned about spontaneous hemorrhage of hepatic angiolipoma in a patient with TS. The clinical significance of recognition of hepatic angiomyolipoma lies in the fact, that misdiagnosis of these usually benign lesion may result in unnecessary and invasive diagnostic procedure.

Other findings associated with TS such as LAM, cardiac rhabdomyoma, dental and ophthalmologic findings, other skin findings along with associated clinical manifestations were not evident in our patient. However, counselling regarding the conditions, possible manifestations in future and treatment was given to the patient.

Conclusions

TS is a rare neurocutaneous disorder. Sometimes a patient may appear with life-threatening symptoms or may not have any symptoms at all for an extended period of time. It is advised that any patient who is suspected to have the condition should undergo further assessment. Additionally, as it can be passed down the generation, information dissemination in the family with this condition needs to be done accordingly.

In conclusion, even though studies have pointed to different aspects and manifestations of the illness, further research and reporting has to be continued to fully comprehend its varied expressions.

References

Figure 1: Facial angiofibromas.

Figure 2: Multiple fibrous plaque on forehead.

Figure 4: Axial abdominal computed tomography, illustrating multiple bilateral renal angiomyolipoma. White arrow shows darker fat attenuation seen in the lesion.

Figure 5: Axial abdominal computed tomography, illustrating aneurysm (black arrow) with adjacent hematoma (white arrow) in the left kidney.

Figure 6: Axial abdominal computed tomography, illustrating fat attenuating lesion (white arrow) with enhancing solid component (black arrow) in the liver

Figure 7: Axial computed tomography of the brain, calcified subependymal nodules along the margin of the ventricles (black arrows).

Figure 8: Axial computed tomography of the brain, illustrating calcified cortical dysplasia (black arrows) in the left frontal region (A), right frontal region (B) and right occipital region (C).

Figure 9: Axial computed tomography of the brain, illustrating cerebral white matter radial migration lines (black arrow).