Open Access
Case report Tuberous sclerosis complex presenting as pulmonary lymphangioleiomyomatosis - a clinicoradiological diagnosis Kamini Gupta1,&, Amit Goyal1, Kavita Saggar1, Avik Banerjee1 1
Department of Radiodiagnosis, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
&
Corresponding author: Kamini Gupta, Department of Radiodiagnosis, Dayanand Medical College and Hospital, Tagore Nagar, Ludhiana-141001,
Punjab, India Key words: Tuberous sclerosis, lymphangioleiomyomatosis, angiomyolipoma Received: 25/09/2014 - Accepted: 04/03/2015 - Published: 06/03/2015 Abstract Tuberous sclerosis complex (TSC) manifests predominantly as a neurocutaneous disorder. Lymphangioleiomyomatosis (LAM) is a rare pulmonary manifestation of TSC. Imaging evaluation plays an important role in the assessment of patients with tuberous sclerosis complex. In newly diagnosed patients, it helps not only to confirm the diagnosis of TSC, but also helps in identifying clinically significant complications.We describe the radiological findings in lungs and other organs in a middle aged female with TSC.
Pan African Medical Journal. 2015; 20:207 doi:10.11604/pamj.2015.20.207.5490 This article is available online at: http://www.panafrican-med-journal.com/content/article/20/207/full/ © Kamini Gupta et al. The Pan African Medical Journal - ISSN 1937-8688. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Pan African Medical Journal – ISSN: 1937- 8688 (www.panafrican-med-journal.com) Published in partnership with the African Field Epidemiology Network (AFENET). (www.afenet.net) Page number not for citation purposes
1
Introduction
Discussion
Tuberous sclerosis complex is an autosomal-dominant disorder
Tuberous sclerosis complex (TSC) is the second most common
characterized by the formation of hamartomatous lesions in multiple
phakomatosis after neurofibromatosis type 1 and is characterized by
organ systems. It is the second most common neurocutaneous
the formation of histologically benign hamartomas and low-grade
syndrome after neurofibromatosis type 1. Almost all patients with
neoplasms in multiple organ systems. It has a prevalence of about 1
TSC have numerous cutaneous stigmata like hypopigmented
in 6,000 newborns and affects approximately 1.5 million people
macules, adenoma sebaceum & periungual fibromas. In addition,
worldwide, occurring in all races and both genders equally [1]. The
TSC patients develop numerous brain lesions, AMLs, LAM in the
diagnostic criteria for TSC were revised at the TSC Consensus
lungs, cardiac rhabdomyomas, skeletal lesions, and vascular
Conference [2]. Definite TSC: Two major features or one major
anomalies. All these manifestations are well visualized using various
feature plus two minor features. Probable TSC: One major feature
imaging modalities.
plus one minor feature. Possible TSC: One major feature or two or more minor features. Major and minor features have been described in Table 1.
Patient and observation The index case had five major criterias (facial angiomas, periungual 42 year female presented with cough since 3 days, breathlessness since 2 days and chest pain since 1 day. She also had long standing history of seizures and low intelligence. On physical examination multiple adenoma sebaceum (Figure 1, left image) and periungual fibromas (Figure 1, right image) were observed on the face and feet respectively. Chest examination revealed decreased movements and reduced air entry on the left side for which CXR was done which showed pneumothorax on left side and bilateral reticulations. To characterize these lesions MDCT chest was done which revealed bilateral multiple thin walled cystic lesions of varying sizes causing partial replacement of the lung parenchyma in addition to left sided pneumothorax (Figure 2, left image). Chest tube was inserted and repeat MDCT after three days showed complete resolution of the pneumothorax. Later on patient developed bilateral pleural effusions (Figure 2, right image). Diagnostic pleural tap was done which came out to be chylous. On the basis of clinical history, physical examination and MDCT chest findings, a diagnosis of TSC was made. For the evaluation of the rest of the organs, ultrasound abdomen was done which showed few hyperechoic lesions in the liver (Figure 3,white arrows, left image) which had fat attenuation
fibromas, pulmonary lymphangioleiomyomatosis, angiomyolipomas and subependymal nodules) and one minor (renal cysts). Therefore, this constellation of pathognomonic clinical and imaging features was consistent with the diagnosis of TSC even in the absence of genotyping. LAM is the major lung disease associated with TSC. It was initially thought to be rare in TSC. Earlier studies estimated it to occur in 2-3% of TSC patients [3], however recently, Moss et al reported a high prevalence of 34 % [4] and Costello et al reported that LAM was found in 20 (26%) of the patients [5]. Pulmonary LAM is characterized by interstitial lung injury as a result of diffuse proliferation of abnormal smooth muscles [6,7]. Bronchovascular smooth muscle proliferation results in alveolar destruction and cystic parenchymal damage. Pulmonary lymphangioleiomyomatosis mainly affects
females
of
reproductive
age
with
dypsnoea
and
pneumthorax as the commonest clinical presentations. In a comprehensive evaluation of 35 patients with LAM, Chu et al noted dyspnoea
in
83%,
while
69%
presented
with
spontanous
pneumothorax. Other clinical manifestations of LAM include nonproductive cough, haemoptysis, chylous pleural effusion and chylous ascites [8].
on MDCT suggesting lipomas (Figure 3, right image). Multiple heterogenous and echogenic lesions were also seen in bilateral kidneys (Figure 4, white arrows). MRI brain revealed few calcified
Conclusion
subependymal nodules (Figure 5, black arrow).These features were consistent with a diagnosis of TSC with LAM.
LAM which occurs mainly in women of childbearing age is the major pulmonary disorder seen in TSC. History of shortness of breath or chest pain in a female particularly of child bearing age with skin
Page number not for citation purposes
2
lesion should alert physicians to the possibility of tuberous sclerosis. To conclude we want to highlight that MDCT findings of LAM are
References
very characteristic and can be considered diagnostic, particularly when typical abdominal lesions are also present.
1.
Baskin HJ Jr. The pathogenesis and imaging of the tuberous sclerosis
complex.
Pediatr
Radiol.
2008;
38(9):936-
952. PubMed | Google Scholar
Competing interests 2. The authors declare no competing interests.
Hyman MH, Whittemore VH. National Institutes of Health consensus conference: tuberous sclerosis complex. Arch Neurol. 2000;57(5):662-665. PubMed | Google Scholar
3.
Authors’ contributions
Glassberg MK. Lymphangioleiomyomatosis. Clinics in chest medicine. 2004;25(3): 573-82. PubMed | Google Scholar
All the authors have read and approuved the final version of the manuscript.
4.
Moss J, Avilla NA, Barnes PM, Litzenberger RA, Bechtle J, Brooks PG et al. Prevalence and clinical characteristics of lymphangioleiomyomatosis in patients with tuberous sclerosis complex. Am J Respir Crit Care Med. 2001;164(4): 669-
Table and figures
71.PubMed | Google Scholar
Table 1: revised diagnostic criteria for TSC at the TSC Consensus
5.
Costello LC, Hartman TE, Ryu JH. High frequency of pulmonary
Conference by National institutes of health
lymphangioleiomyomatosis in women with tuberous sclerosis.
Figure 1: multiple Facial Angiofibromas-Adenoma Sebaceum (left
Mayo Clin Proc. 2000;75(6): 591-594. PubMed | Google
image) and Periungual Fibromas (right image)
Scholar
Figure 2: left sided pneumothorax with multiple thin walled cystic lesions of varying sizes replacing lung parenchyma bilaterally (left
6.
Ramphal PS, Shah D, Mitchell DIG, Wynter-Daley J. A case of
image). Bilateral pleural effusion is seen (R>L) (right image)
pulmonary lymphangioleiomyomatosis. West Indian Med J.
Figure 3: ultrasound image shows hepatic lipomas appearing as
2003;52(3): 250-2. PubMed |Google Scholar
hyperechoic lesions (white arrows). Right pleural effusion is also noted (black arrow).Corresponding CT section show fat attenuation
7.
in hepatic lesions (white arrow, right image) Figure
4:
ultrasound
image
shows
Sullivan EJ. Lymphangioleiomyomatosis -a review. Chest. 1998;114(6):1689-1703.PubMed | Google Scholar
renal
cysts
and
angiomyolipomas seen as cystic and hyperechoic lesions in the
8.
Chu SC, Horiba K, Usuki J, Avilla NA, Chen CC, Travis WD et al.
kidneys (arrows)
Comprehensive
Figure 5: axial section on T2W sequence shows hypointense
lymphangioleiomyomatosis.
subependymal nodules (black arrow) and hyperintense cortical
52. PubMed | Google
evaluation
of Chest.
35
patients
with
1999;115(4):1041Scholar
tubers (white arrows)
Page number not for citation purposes
3
Table 1: revised diagnostic criteria for TSC at the TSC Consensus Conference by National institutes of health Major Features
Minor Features
Facial angiofibromas or forehead plaque
Multiple randomly-distributed pits in dental enamel
Nontraumatic ungual or periungual fibromas
Hamartomatous rectal polyps
Hypomelanotic macules (three or more)
Bone cysts
Shagreen patch (connective tissue nevus)
Cerebral white matter radial migration lines
Multiple retinal nodular hamartomas
Gingival fibromas
Cortical tuber
Nonrenal hamartoma
Subependymal nodule
Retinal achromic patch
Subependymal giant cell astrocytoma
"Confetti" skin lesions
Cardiac rhabdomyoma, single or multiple
Multiple renal cysts
Lymphangioleiomyomatosis Renal angiomyolipoma
Figure 1: multiple Facial Angiofibromas-Adenoma Sebaceum (left image) and Periungual Fibromas (right image)
Figure 2: left sided pneumothorax with multiple thin walled cystic lesions of varying sizes replacing lung parenchyma bilaterally (left image). Bilateral pleural effusion is seen (R>L) (right image)
Page number not for citation purposes
4
Figure 3: ultrasound image shows hepatic lipomas appearing as hyperechoic lesions (white arrows). Right
pleural
effusion
arrow).Corresponding
is
CT
also section
noted show
(black fat
attenuation in hepatic lesions (white arrow, right image)
Figure 4: ultrasound image shows renal cysts and angiomyolipomas seen
as
cystic
and
hyperechoic
lesions in the kidneys (arrows)
Figure 5: axial section on T2W
sequence
hypointense nodules
subependymal
(black
hyperintense
shows
arrow)
cortical
and
tubers
(white arrows)
Page number not for citation purposes
5
Case report Tuberous sclerosis complex presenting as pulmonary lymphangioleiomyomatosis - a clinicoradiological diagnosis Kamini Gupta1,&, Amit Goyal1, Kavita Saggar1, Avik Banerjee1 1
Department of Radiodiagnosis, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
&
Corresponding author: Kamini Gupta, Department of Radiodiagnosis, Dayanand Medical College and Hospital, Tagore Nagar, Ludhiana-141001,
Punjab, India Key words: Tuberous sclerosis, lymphangioleiomyomatosis, angiomyolipoma Received: 25/09/2014 - Accepted: 04/03/2015 - Published: 06/03/2015 Abstract Tuberous sclerosis complex (TSC) manifests predominantly as a neurocutaneous disorder. Lymphangioleiomyomatosis (LAM) is a rare pulmonary manifestation of TSC. Imaging evaluation plays an important role in the assessment of patients with tuberous sclerosis complex. In newly diagnosed patients, it helps not only to confirm the diagnosis of TSC, but also helps in identifying clinically significant complications.We describe the radiological findings in lungs and other organs in a middle aged female with TSC.
Pan African Medical Journal. 2015; 20:207 doi:10.11604/pamj.2015.20.207.5490 This article is available online at: http://www.panafrican-med-journal.com/content/article/20/207/full/ © Kamini Gupta et al. The Pan African Medical Journal - ISSN 1937-8688. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Pan African Medical Journal – ISSN: 1937- 8688 (www.panafrican-med-journal.com) Published in partnership with the African Field Epidemiology Network (AFENET). (www.afenet.net) Page number not for citation purposes
1
Introduction
Discussion
Tuberous sclerosis complex is an autosomal-dominant disorder
Tuberous sclerosis complex (TSC) is the second most common
characterized by the formation of hamartomatous lesions in multiple
phakomatosis after neurofibromatosis type 1 and is characterized by
organ systems. It is the second most common neurocutaneous
the formation of histologically benign hamartomas and low-grade
syndrome after neurofibromatosis type 1. Almost all patients with
neoplasms in multiple organ systems. It has a prevalence of about 1
TSC have numerous cutaneous stigmata like hypopigmented
in 6,000 newborns and affects approximately 1.5 million people
macules, adenoma sebaceum & periungual fibromas. In addition,
worldwide, occurring in all races and both genders equally [1]. The
TSC patients develop numerous brain lesions, AMLs, LAM in the
diagnostic criteria for TSC were revised at the TSC Consensus
lungs, cardiac rhabdomyomas, skeletal lesions, and vascular
Conference [2]. Definite TSC: Two major features or one major
anomalies. All these manifestations are well visualized using various
feature plus two minor features. Probable TSC: One major feature
imaging modalities.
plus one minor feature. Possible TSC: One major feature or two or more minor features. Major and minor features have been described in Table 1.
Patient and observation The index case had five major criterias (facial angiomas, periungual 42 year female presented with cough since 3 days, breathlessness since 2 days and chest pain since 1 day. She also had long standing history of seizures and low intelligence. On physical examination multiple adenoma sebaceum (Figure 1, left image) and periungual fibromas (Figure 1, right image) were observed on the face and feet respectively. Chest examination revealed decreased movements and reduced air entry on the left side for which CXR was done which showed pneumothorax on left side and bilateral reticulations. To characterize these lesions MDCT chest was done which revealed bilateral multiple thin walled cystic lesions of varying sizes causing partial replacement of the lung parenchyma in addition to left sided pneumothorax (Figure 2, left image). Chest tube was inserted and repeat MDCT after three days showed complete resolution of the pneumothorax. Later on patient developed bilateral pleural effusions (Figure 2, right image). Diagnostic pleural tap was done which came out to be chylous. On the basis of clinical history, physical examination and MDCT chest findings, a diagnosis of TSC was made. For the evaluation of the rest of the organs, ultrasound abdomen was done which showed few hyperechoic lesions in the liver (Figure 3,white arrows, left image) which had fat attenuation
fibromas, pulmonary lymphangioleiomyomatosis, angiomyolipomas and subependymal nodules) and one minor (renal cysts). Therefore, this constellation of pathognomonic clinical and imaging features was consistent with the diagnosis of TSC even in the absence of genotyping. LAM is the major lung disease associated with TSC. It was initially thought to be rare in TSC. Earlier studies estimated it to occur in 2-3% of TSC patients [3], however recently, Moss et al reported a high prevalence of 34 % [4] and Costello et al reported that LAM was found in 20 (26%) of the patients [5]. Pulmonary LAM is characterized by interstitial lung injury as a result of diffuse proliferation of abnormal smooth muscles [6,7]. Bronchovascular smooth muscle proliferation results in alveolar destruction and cystic parenchymal damage. Pulmonary lymphangioleiomyomatosis mainly affects
females
of
reproductive
age
with
dypsnoea
and
pneumthorax as the commonest clinical presentations. In a comprehensive evaluation of 35 patients with LAM, Chu et al noted dyspnoea
in
83%,
while
69%
presented
with
spontanous
pneumothorax. Other clinical manifestations of LAM include nonproductive cough, haemoptysis, chylous pleural effusion and chylous ascites [8].
on MDCT suggesting lipomas (Figure 3, right image). Multiple heterogenous and echogenic lesions were also seen in bilateral kidneys (Figure 4, white arrows). MRI brain revealed few calcified
Conclusion
subependymal nodules (Figure 5, black arrow).These features were consistent with a diagnosis of TSC with LAM.
LAM which occurs mainly in women of childbearing age is the major pulmonary disorder seen in TSC. History of shortness of breath or chest pain in a female particularly of child bearing age with skin
Page number not for citation purposes
2
lesion should alert physicians to the possibility of tuberous sclerosis. To conclude we want to highlight that MDCT findings of LAM are
References
very characteristic and can be considered diagnostic, particularly when typical abdominal lesions are also present.
1.
Baskin HJ Jr. The pathogenesis and imaging of the tuberous sclerosis
complex.
Pediatr
Radiol.
2008;
38(9):936-
952. PubMed | Google Scholar
Competing interests 2. The authors declare no competing interests.
Hyman MH, Whittemore VH. National Institutes of Health consensus conference: tuberous sclerosis complex. Arch Neurol. 2000;57(5):662-665. PubMed | Google Scholar
3.
Authors’ contributions
Glassberg MK. Lymphangioleiomyomatosis. Clinics in chest medicine. 2004;25(3): 573-82. PubMed | Google Scholar
All the authors have read and approuved the final version of the manuscript.
4.
Moss J, Avilla NA, Barnes PM, Litzenberger RA, Bechtle J, Brooks PG et al. Prevalence and clinical characteristics of lymphangioleiomyomatosis in patients with tuberous sclerosis complex. Am J Respir Crit Care Med. 2001;164(4): 669-
Table and figures
71.PubMed | Google Scholar
Table 1: revised diagnostic criteria for TSC at the TSC Consensus
5.
Costello LC, Hartman TE, Ryu JH. High frequency of pulmonary
Conference by National institutes of health
lymphangioleiomyomatosis in women with tuberous sclerosis.
Figure 1: multiple Facial Angiofibromas-Adenoma Sebaceum (left
Mayo Clin Proc. 2000;75(6): 591-594. PubMed | Google
image) and Periungual Fibromas (right image)
Scholar
Figure 2: left sided pneumothorax with multiple thin walled cystic lesions of varying sizes replacing lung parenchyma bilaterally (left
6.
Ramphal PS, Shah D, Mitchell DIG, Wynter-Daley J. A case of
image). Bilateral pleural effusion is seen (R>L) (right image)
pulmonary lymphangioleiomyomatosis. West Indian Med J.
Figure 3: ultrasound image shows hepatic lipomas appearing as
2003;52(3): 250-2. PubMed |Google Scholar
hyperechoic lesions (white arrows). Right pleural effusion is also noted (black arrow).Corresponding CT section show fat attenuation
7.
in hepatic lesions (white arrow, right image) Figure
4:
ultrasound
image
shows
Sullivan EJ. Lymphangioleiomyomatosis -a review. Chest. 1998;114(6):1689-1703.PubMed | Google Scholar
renal
cysts
and
angiomyolipomas seen as cystic and hyperechoic lesions in the
8.
Chu SC, Horiba K, Usuki J, Avilla NA, Chen CC, Travis WD et al.
kidneys (arrows)
Comprehensive
Figure 5: axial section on T2W sequence shows hypointense
lymphangioleiomyomatosis.
subependymal nodules (black arrow) and hyperintense cortical
52. PubMed | Google
evaluation
of Chest.
35
patients
with
1999;115(4):1041Scholar
tubers (white arrows)
Page number not for citation purposes
3
Table 1: revised diagnostic criteria for TSC at the TSC Consensus Conference by National institutes of health Major Features
Minor Features
Facial angiofibromas or forehead plaque
Multiple randomly-distributed pits in dental enamel
Nontraumatic ungual or periungual fibromas
Hamartomatous rectal polyps
Hypomelanotic macules (three or more)
Bone cysts
Shagreen patch (connective tissue nevus)
Cerebral white matter radial migration lines
Multiple retinal nodular hamartomas
Gingival fibromas
Cortical tuber
Nonrenal hamartoma
Subependymal nodule
Retinal achromic patch
Subependymal giant cell astrocytoma
"Confetti" skin lesions
Cardiac rhabdomyoma, single or multiple
Multiple renal cysts
Lymphangioleiomyomatosis Renal angiomyolipoma
Figure 1: multiple Facial Angiofibromas-Adenoma Sebaceum (left image) and Periungual Fibromas (right image)
Figure 2: left sided pneumothorax with multiple thin walled cystic lesions of varying sizes replacing lung parenchyma bilaterally (left image). Bilateral pleural effusion is seen (R>L) (right image)
Page number not for citation purposes
4
Figure 3: ultrasound image shows hepatic lipomas appearing as hyperechoic lesions (white arrows). Right
pleural
effusion
arrow).Corresponding
is
CT
also section
noted show
(black fat
attenuation in hepatic lesions (white arrow, right image)
Figure 4: ultrasound image shows renal cysts and angiomyolipomas seen
as
cystic
and
hyperechoic
lesions in the kidneys (arrows)
Figure 5: axial section on T2W
sequence
hypointense nodules
subependymal
(black
hyperintense
shows
arrow)
cortical
and
tubers
(white arrows)
Page number not for citation purposes
5
