Bronchial Angiofibromata in a Suspected Case of Tuberous
Seleresis" Allan P. Freedman, M.D.;o ° R. F. Radocha, B.S.;t and James P. Shinnick, D.O."
Widespread hamartomatous proliferatious are often seen
with tuberous sclerosis, yet pulmonary involvement Is rare. We describe a patient with a probable forme fruste of tuberous sclerosis in whom the diagnosis of bronchial angiofibromata was made broncboscopically. ThIs is the first description of this pulmonary manifestation.
T
h e association of cerebral tuberous sclerosis with extracerebral hamartomas was recognized by Bourneville in his description of this pathologic entity in 1880. The triad of dermal angiofibromata, mental retardation, and epilepsy in tuberous sclerosis represents the neurocutaneous syndrome recognized thereafter. 1 Tuberous sclerosis is now thought to represent a congenital defect of tissue differentiation resulting in multiple hamartomatous proliferations from all germ layers. Benign tumors of almost all organs have been reported including hamartomas of the kidney, phakomas of the retina and optic disc, and rhabdomyomas of the heart.2 , 3 Pulmonary involvement is rare and manifests as interstitial lung disease with occasional nodular hamartomas. 2 ,. This case report demonstrates the as yet unreported occurrence of bronchial angiofibromata in a patient with suspected tuberous sclerosis.
CASE
REPoRT
A 42-year-old white woman was admitted in August, 1976 for evaluation of a central, left mid-lung field nodule (Fig 1). Her medical history revealed development of grand mal epilepsy at age 18. She was under psychiatric treatment for a diagnosis of possible paranoid schizophrenia, but there was no mental retardation. The family history was non-contributory. In 1976, biopsy of leg and facial skin nodules showed benign follicular hyperkeratosis, not diagnostic of tuberous sclerosis. She had long used oral narcotic analgesics for relief of intractable stabbing pains in her extremities and lower back. No skeletal abnormalities or neurofibromata were ever found. A chronic cough productive of thick grey sputum, occasionally blood streaked, was present since 1971. Her smoking history included three to four packs of cigarettes daily for 18 years, and she complained of significant dyspnea on exertion after climbing five steps. Physical examination revealed multiple small, white, hard, confluent nodules on the nasolabial and malar regions of the °From the Division of Pulmonary Piseases, Hahnemann Medical College and Hospital, Philadelphia. 00 Assistant Professor of Medicine. tSenior Medical Student. Reprint requests: Dr. Freedman, Division of Pulmal16ry Disease, 230 North Broad Street, Philadelphia 19102.
CHEST, 76: 4, OCTOBER, 1979
FIGURE 1. Left mid-lung field nodule. face. There was no evidence of shagreen plaques, cafe-aulait spots, or periunga} and subungual fibromata. No optic phakomata were seen. Bilateral diffuse wheezing and a prolonged expiratory phase were present. Results of cardiac and abdominal examination showed normal findings. Shotty left axillary adenopathy and a discrete 1 centimeter (diameter) right axillary node were palpable. Clubbing was absent. The neurologic examination was completely normal. Routine admission blood studies and urinalysis gave normal results . Skull films showed no calcified gliomata. The intravenous pyelogram revealed no evidence
FIGURE 2. Raised whitish mucosal lesion on the anterior trachea.
BRONCHIAL ANGIOFIBROMATA •
connective tissue (Fig 4). This was felt to represent an angiofibroma. Since the axillary adenopathy resolved and a chest x-ray mm from 1974 was found to show the identical left upper lobe lesion, no further evaluation was considered necessary. DISCUSSION
FiGURE 3. Multiple raised mucosal lesions in the right lower lobe bronchus.
of hamartoma. The ECG was normal. Computerized transaxial tomography showed a small area of high density in the right frontal area, possibly a meningioma. Arterial blood gas levels on room air at rest revealed a pH of 7.40, Pco, 31 mm Hg, and P0 2 57 mm Hg prior to therapy. A PPD-5 TU test was negative . Pulmonary function tests after administration of oral theophylline was started showed normal lung volumes, flow rates and single breath diffusing capacity for CO. Whole lung tomograms revealed the nodular density in the anterior segment of the left upper lobe to be sharply circumscribed and spherical, with a diameter of 1.5 X 2.0 X 1.5 em. The lung fields were otherwise normal. Bronchoscopic examination was performed transnasally under local anesthesia with the Olympus BF B2 flberoptic bronchoscope. The nasal passageway demonstrated turbinate hyperemia but the oropharynx and hypopharynx were normal. There were multiple white mucosal nodules on the right arytenoid, the right false cord, and the interarytenoid commissure. Numerous, scattered, whitish mucosal lesions were present in the trachea (Fig 2), and there were several lesions in the right lower lobe bronchus anteriorly (Fig 3) along with changes consistent with chronic bronchitis. The left bronchial tree was normal except fOf: chronic bronchitis. The left upper lobe lesion could not be reached endobronchially under fluoroscopic guidance. Cytologic examination of the left upper lobe washings was negative . Sections of the right lower lobe bronchial biopsy specimen revealed a broad based polypoid structure covered with flattened respiratory epithelium. It contained multiple, scattered, dilated blood vessels surrounded by loose fibrous
FIGURE 4. Forceps biopsy showing multiple scattered dilated blood vessels surrounded by loose fibrous connective tissue
(X 100).
470 FREEDMAN, MDOCHA, SHINNICK
It is now accepted that tuberous sclerosis can be manifested by only one aspect of the classic triad, this being called a fonne fruste or incomplete form.! In view of the history of seizure disorder, the presence of striking facial skin lesions, and a benign-appearing lung mass consistent with hamartoma, the diagnosis of forme fruste of tuberous sclerosis was strongly suspected. Despite the nonspecific nature of the skin le- : sions on biopsy, the only mildly abnormal EMI, and the absence of mental retardation, we feel the diagnosis of tuberous sclerosis is probable. Pulmonary involvement in tuberous sclerosis is rare and occurs in less than 1 percent of cases.2 ,. It is a cystic interstitial process caused by hamartomatous proliferation of fibrous tissue, smooth muscle, and vascular elements," The affected lungs have multiple air-filled pea-sized cysts, although larger, solid hamartomas have been descrfbed.v" Pulmonary tuberous sclerosis classically presents with progressive dyspnea or recurrent spontaneous pneumothoraces. Hemoptysis and a nonproductive cough may be present. The roentgenographic appearance varies from a fine reticular pattern to a coarse honeycomb appearance. A frequently described characteristic of pulmonary tuberous sclerosis is the progressive appearance of signs and symptoms as the patient, usually a female, grows older.2-4 The pulmonary lesions are more common in the incomplete forms of tuberous sclerosis, where cerebral involvement is less marked.s Less than 50 percent of the patients have epilepsy or mental retardation compared with the usual clinical picture of the disease. However, the cutaneous and hamartomatous manifestations of tuberous sclerosis are present in the usual inoidence.s-' Angiofibromata of the skin are part of the classic triad in tuberous sclerosis. This lesion has never been reported to occur in tracheobronchial mucosa . Its presence in this woman leads us to conclude that tracheobronchial angiofibromata are another hamartomatous manifestation of tuberous sclerosis.
1 Lagos JC, Gomez MR: Tuberous sclerosis. Reappraisal of a clinical entity. Mayo Clin Proc 42 :20-49, 1967 2 Dawson J : Pulmonary tuberous sclerosis and its relationship to other forms of the disease. Quart J Med 23:113145,1954 3 Marshall D, Saul GB, Sachs E Jr: Tuberous sclerosis. A report of 16 cases in two family trees revealing genetic dominance . N Engl J Med 261:1102-1105, 1959 4 Dwyer JM, Hickie JB, Garwan J : Pulmonary tuberous sclerosis. Quart J Med 40 :115-125, 1971 5 Spencer A: Pathology of the Lung. Oxford, Pergamon Press, 1977 p 985
CHEST, 76: 4, OCTOBER, 1979
Seleresis" Allan P. Freedman, M.D.;o ° R. F. Radocha, B.S.;t and James P. Shinnick, D.O."
Widespread hamartomatous proliferatious are often seen
with tuberous sclerosis, yet pulmonary involvement Is rare. We describe a patient with a probable forme fruste of tuberous sclerosis in whom the diagnosis of bronchial angiofibromata was made broncboscopically. ThIs is the first description of this pulmonary manifestation.
T
h e association of cerebral tuberous sclerosis with extracerebral hamartomas was recognized by Bourneville in his description of this pathologic entity in 1880. The triad of dermal angiofibromata, mental retardation, and epilepsy in tuberous sclerosis represents the neurocutaneous syndrome recognized thereafter. 1 Tuberous sclerosis is now thought to represent a congenital defect of tissue differentiation resulting in multiple hamartomatous proliferations from all germ layers. Benign tumors of almost all organs have been reported including hamartomas of the kidney, phakomas of the retina and optic disc, and rhabdomyomas of the heart.2 , 3 Pulmonary involvement is rare and manifests as interstitial lung disease with occasional nodular hamartomas. 2 ,. This case report demonstrates the as yet unreported occurrence of bronchial angiofibromata in a patient with suspected tuberous sclerosis.
CASE
REPoRT
A 42-year-old white woman was admitted in August, 1976 for evaluation of a central, left mid-lung field nodule (Fig 1). Her medical history revealed development of grand mal epilepsy at age 18. She was under psychiatric treatment for a diagnosis of possible paranoid schizophrenia, but there was no mental retardation. The family history was non-contributory. In 1976, biopsy of leg and facial skin nodules showed benign follicular hyperkeratosis, not diagnostic of tuberous sclerosis. She had long used oral narcotic analgesics for relief of intractable stabbing pains in her extremities and lower back. No skeletal abnormalities or neurofibromata were ever found. A chronic cough productive of thick grey sputum, occasionally blood streaked, was present since 1971. Her smoking history included three to four packs of cigarettes daily for 18 years, and she complained of significant dyspnea on exertion after climbing five steps. Physical examination revealed multiple small, white, hard, confluent nodules on the nasolabial and malar regions of the °From the Division of Pulmonary Piseases, Hahnemann Medical College and Hospital, Philadelphia. 00 Assistant Professor of Medicine. tSenior Medical Student. Reprint requests: Dr. Freedman, Division of Pulmal16ry Disease, 230 North Broad Street, Philadelphia 19102.
CHEST, 76: 4, OCTOBER, 1979
FIGURE 1. Left mid-lung field nodule. face. There was no evidence of shagreen plaques, cafe-aulait spots, or periunga} and subungual fibromata. No optic phakomata were seen. Bilateral diffuse wheezing and a prolonged expiratory phase were present. Results of cardiac and abdominal examination showed normal findings. Shotty left axillary adenopathy and a discrete 1 centimeter (diameter) right axillary node were palpable. Clubbing was absent. The neurologic examination was completely normal. Routine admission blood studies and urinalysis gave normal results . Skull films showed no calcified gliomata. The intravenous pyelogram revealed no evidence
FIGURE 2. Raised whitish mucosal lesion on the anterior trachea.
BRONCHIAL ANGIOFIBROMATA •
connective tissue (Fig 4). This was felt to represent an angiofibroma. Since the axillary adenopathy resolved and a chest x-ray mm from 1974 was found to show the identical left upper lobe lesion, no further evaluation was considered necessary. DISCUSSION
FiGURE 3. Multiple raised mucosal lesions in the right lower lobe bronchus.
of hamartoma. The ECG was normal. Computerized transaxial tomography showed a small area of high density in the right frontal area, possibly a meningioma. Arterial blood gas levels on room air at rest revealed a pH of 7.40, Pco, 31 mm Hg, and P0 2 57 mm Hg prior to therapy. A PPD-5 TU test was negative . Pulmonary function tests after administration of oral theophylline was started showed normal lung volumes, flow rates and single breath diffusing capacity for CO. Whole lung tomograms revealed the nodular density in the anterior segment of the left upper lobe to be sharply circumscribed and spherical, with a diameter of 1.5 X 2.0 X 1.5 em. The lung fields were otherwise normal. Bronchoscopic examination was performed transnasally under local anesthesia with the Olympus BF B2 flberoptic bronchoscope. The nasal passageway demonstrated turbinate hyperemia but the oropharynx and hypopharynx were normal. There were multiple white mucosal nodules on the right arytenoid, the right false cord, and the interarytenoid commissure. Numerous, scattered, whitish mucosal lesions were present in the trachea (Fig 2), and there were several lesions in the right lower lobe bronchus anteriorly (Fig 3) along with changes consistent with chronic bronchitis. The left bronchial tree was normal except fOf: chronic bronchitis. The left upper lobe lesion could not be reached endobronchially under fluoroscopic guidance. Cytologic examination of the left upper lobe washings was negative . Sections of the right lower lobe bronchial biopsy specimen revealed a broad based polypoid structure covered with flattened respiratory epithelium. It contained multiple, scattered, dilated blood vessels surrounded by loose fibrous
FIGURE 4. Forceps biopsy showing multiple scattered dilated blood vessels surrounded by loose fibrous connective tissue
(X 100).
470 FREEDMAN, MDOCHA, SHINNICK
It is now accepted that tuberous sclerosis can be manifested by only one aspect of the classic triad, this being called a fonne fruste or incomplete form.! In view of the history of seizure disorder, the presence of striking facial skin lesions, and a benign-appearing lung mass consistent with hamartoma, the diagnosis of forme fruste of tuberous sclerosis was strongly suspected. Despite the nonspecific nature of the skin le- : sions on biopsy, the only mildly abnormal EMI, and the absence of mental retardation, we feel the diagnosis of tuberous sclerosis is probable. Pulmonary involvement in tuberous sclerosis is rare and occurs in less than 1 percent of cases.2 ,. It is a cystic interstitial process caused by hamartomatous proliferation of fibrous tissue, smooth muscle, and vascular elements," The affected lungs have multiple air-filled pea-sized cysts, although larger, solid hamartomas have been descrfbed.v" Pulmonary tuberous sclerosis classically presents with progressive dyspnea or recurrent spontaneous pneumothoraces. Hemoptysis and a nonproductive cough may be present. The roentgenographic appearance varies from a fine reticular pattern to a coarse honeycomb appearance. A frequently described characteristic of pulmonary tuberous sclerosis is the progressive appearance of signs and symptoms as the patient, usually a female, grows older.2-4 The pulmonary lesions are more common in the incomplete forms of tuberous sclerosis, where cerebral involvement is less marked.s Less than 50 percent of the patients have epilepsy or mental retardation compared with the usual clinical picture of the disease. However, the cutaneous and hamartomatous manifestations of tuberous sclerosis are present in the usual inoidence.s-' Angiofibromata of the skin are part of the classic triad in tuberous sclerosis. This lesion has never been reported to occur in tracheobronchial mucosa . Its presence in this woman leads us to conclude that tracheobronchial angiofibromata are another hamartomatous manifestation of tuberous sclerosis.
1 Lagos JC, Gomez MR: Tuberous sclerosis. Reappraisal of a clinical entity. Mayo Clin Proc 42 :20-49, 1967 2 Dawson J : Pulmonary tuberous sclerosis and its relationship to other forms of the disease. Quart J Med 23:113145,1954 3 Marshall D, Saul GB, Sachs E Jr: Tuberous sclerosis. A report of 16 cases in two family trees revealing genetic dominance . N Engl J Med 261:1102-1105, 1959 4 Dwyer JM, Hickie JB, Garwan J : Pulmonary tuberous sclerosis. Quart J Med 40 :115-125, 1971 5 Spencer A: Pathology of the Lung. Oxford, Pergamon Press, 1977 p 985
CHEST, 76: 4, OCTOBER, 1979
