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 3: Axial pelvic computed tomography, illustrating urinary bladder
with hematoma (white arrow) which was later evacuated with cystoscopy.
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).