Diagnostic Radiology
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lipoid Proteinosls A Case Report 1 Robert S. Francis, M.D.
Lipoid proteinosis caused specific changes in the brain , larynx , and cervical esophagus of a young adult man. laryngography clearly depicts the distribut ion and degree of pharyngeal and laryngeal pathology. Florid calcification. conforming to the classical temporal lobe distribution. is documented by plain IIIms and tomography. The clinical picture and the pert inent literature are reviewed. INDEX TERMS: Brain, calcification. Esophagus. abnormalities. larynx, abnormalities' Lipoid proteinosls •
Radiology 117:301-302. November 1975
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was originally described as a ... dermatologic condition by Urbach and Wiethe in 1929 (8). They established that the nodular dermatosis which results from this disease is secondary to a lipid-glycoprotein complex infiltration (5, 6). Hoarseness, secondary to vocal cord infiltration, was also noted as a common symptom. Subsequent studies have established a widespread multisystem involvement, including the central nervous system. the respiratory system. the gastrointestinal system, the genitourinary tract, the lymph nodes, and striated muscle (1-4). Characteristic bilateral "bean-shaped" calcification within the region of the hippocampus was first described by Ramos e Silva (7) in 1949, and in the case presented here is particularly extensive . Tomography reveals areas of lucency within the calcification which are suggestive of the hippocampal gyri (Fig. 7). Extensive nodular infiltration of the pharynx and larynx, demonstrated by laryngography, highlights this case. liPOID
Fig. 4 Lateral skull film shows a triangular. well circumscribed calcific density superimposed over the sella turcica. Fig. 5 Caldwell projection shows that the triangular calcified densities (arrows) are paired and lateral to the sella turcica.
PROTEINOSIS
laryngoscopy was interpreted as normal. The skin of his face and pretibial areas gradually became atrophic and friable, with warty growths appearing at the medial lid margins and on the elbows and knees. At age 24, episodes of seizures began which were characterized by an absence of memory and complex motor activity. In spite of relatively high doses of Dilantin, phenobarbital and Valium, the frequency and duration of the seizures increased, and the patient was referred to the National Institutes of Health. Physical examination revealed the skin involvement characteristic of lipoid proteinosis, and raised " lipid-like " lesions were seen on the soft palate and tongue. Laryngoscopy showed a thickening and nodularity of the base of the tongue, valecullae, epiglottis and aryepiglottic folds . Biopsy also showed the characteristic histological changes of lipoid prote inosis. The vocal cords could not be visualized. so laryngeal tomography and positive contrast laryngography were obta ined, showing a diffuse vocal cord thickening , thickened aryepiglottic folds, and a markedly thickened epiglottis (Fig . 1). Laryngography clearly delineated diffuse coarse and fine nodularity of the pharynx and larynx and the marked thicken-
CASE REPORT L. W . S. is a 25 year old white man who was entirely well until the age of four, when he became hoarse and plaque-like skin lesions on his hands and feet were noted. At age six a
Fig. 1 Anteroposterior tomogram of the larynx shows diHuse thickening of the true and false cords (arrow) with obliteration of the laryngeal ventricles. Both aryepiglottic folds, especially the left, are nodular (arrowheads). Fig. 2 Anteroposterior film of larynx during laryngography corroborates the marked vocal cord thickening (arrowheads) and the nodularity of the aryepiglottic folds. The med ial walls of the pyriform sinuses are also nodular. Fig.3 Laterallaryngogram shows thickening of the epiglottis (arrowheads) and diffuse "cobblestone " appearance of the pharynx. 1 From the Diagnostic Radiology Department. The Clinical Center. National Institutes of Health. Bethesda, Md. Accepted for publication in June 1975. ss
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ing of the epiglottis and aryepiglottic folds (Figs. 2 and 3). An oral barium study showed nodules at the immediate post-cricoid cervical esophagus in the anterolateral position . Unfortunately, this was seen only on a video-tape recording. Skull films displayed prominent bean-shaped calcifications in the region of the temporal horns, documented both on plain film and tomography (Figs . 4-7). An adjustment of the drug therapy controlled his seizures, and local cortisone preparations reduced some of the pruritis. On follow-up admission one year later there had been no progression in hoarseness, seizures or skin involvement; skull films were unchanged. DISCUSSION Weidner et at. described laryngeal and lower respiratory tract changes in one case of lipoid proteinosis (9), when laryngeal laminography showed true and false vocal cord thickening and subglottic effacement. In this case, laminography showed a similar thickening, with obliteration of the laryngeal ventricles and distortion and thickening of the aryepiglottic folds confirmed by positive contrast laryngography. In both cases, laryngoscopy revealed diffuse and slightly raised yellowish-white plaques, which histologically consisted of a Iipidglycoprotein complex (5, 6). These histological changes have prompted McCusker and Caplan to suggest that the disorder be relabeled Iipoglycoproteinosis (6). The intracranial calcifications typical of lipoid proteinosis are located symmetrically within the anterior and medial aspects of the temporal horns. Histological studies by Holtz show the calcifications to be within the pericapillary regions of the hippocampal gyri (2). These bean-shaped calcifications are considered pathognomonic for lipoid proteinosis. At least one-third of the reported cases include this finding, and it is present in most patients with an associated epilepsy. Pathologists have described sclerosis and gliosis within the hippocampus in 50 % of the cases of idiopathic epilepsy and in 65 % of those with temporal lobe epilepsy. Similar lesions are seen as a result of hypoxia and after transtentorial uncal herniation (10), but in neither of these conditions is calcification noted. It would seem, however, that these areas of sclerosis are likely sites for dystrophic calcification . Microscopic involvement of other body tissues, including the gastrointestinal and genitourinary tracts, has been reported, but no gross radiographic changes have been documented. The upper esophagus is a site of involvement only slightly less often than is the larynx (1). In this case, nodules were demonstrated in the upper anterolateral area of the cervical esophagus, and confirmed by endoscopy. No pulmonary changes of any type were seen, and in view of the minimal perivascular deposits described histologically it is doubtful that specific radiographic Changes would be seen. The interstitial infiltrates described by Weidner (9) are most likely secondary to the patient's repeated upper and lower respiratory tract infections.
S.
November 1975
FRANCIS
Fig. 6 Lateral tomographic cut within the middle fossa defines the character of the calcific deposit (arrowheads) and shows it to be within the temporal lobe tip in the middle fossa. (The patient is fac ing right.) Fig. 7 Anteroposterior tomogram at the level of the dorsum sella shows lucent areas within the calcifications. Their configuration suggests the hippocampal gyrus.
Recognition of the relationship between the characteristic intracranial calcifications and the laryngeal involvement is important because the lipid complex infiltration of the larynx is progressive and may uncommonly result in a significant airway compromise. No good time-course studies have been done on the relative appearance of temporal lobe calcification with laryngeal changes. The skin changes in lipoid proteinosls usually appear by age twelve (3). One may surmise that the mucosal laryngeal changes parallel the skin involvement, and therefore usually precede the intracranial manifestations, especially in the absence of se izures. REFERENCES 1. Caplan RM: Lipoid proteinosis: A rev iew including some new observations. Univ Michigan M Bull 28:365-377, Mar 1962 2. Caplan RM: Visceral involvement in lipoid protelnosls, Arch Derm 95:149-155, Feb 1967 3. Cowan MA, Alexander S, Vickers HR, et al: Case of lipoid proteinosis. Brit Med J 52:557-560,26 Aug 1961 4. Heyl T: Lipoid protelnosls. I. The clinical picture. Brit J Derm 75:465-472,"Dec 1963 5. Heyl T, De Kock DH: A chromatographic study of skin lipoids in lipoid proteinosis. J Invest Derm 42:333-336, Apr 1964 6. McCusker JJ, Caplan RM: Lipoid proteinosis (Iipoglycoproteinosis): A histological study of two cases. Amer J Path 40:599613, May 1962 7. Ramos e Silva J: Lipo id proteinosis: (Urbach-Wiethe). Arch Derm 47:301-326, Apr 1974 8. Urbach E, Wiethe, C: Lipoidosis cutis et mucosae. Arch f Path Anat 273:285~319, Jun 1929 9. Weidner WA, Wenzi JE, Swischuk LE: Roentgenographic findings in lipoid proteinosis: a case report. Am J Roentgenol 110: 457 -461, Nov 1970 10. Williams JP, Slimach NM , FowlerFW: Radiographic hippocampal calcifications. Neuroradiology 4:159-161, Jan 1972 Diagnostic Radiology Department The Clinical Center Building 10, Room 6S-21 1 National Institutes of Health Bethesda, Maryland 20014
•
lipoid Proteinosls A Case Report 1 Robert S. Francis, M.D.
Lipoid proteinosis caused specific changes in the brain , larynx , and cervical esophagus of a young adult man. laryngography clearly depicts the distribut ion and degree of pharyngeal and laryngeal pathology. Florid calcification. conforming to the classical temporal lobe distribution. is documented by plain IIIms and tomography. The clinical picture and the pert inent literature are reviewed. INDEX TERMS: Brain, calcification. Esophagus. abnormalities. larynx, abnormalities' Lipoid proteinosls •
Radiology 117:301-302. November 1975
•
•
was originally described as a ... dermatologic condition by Urbach and Wiethe in 1929 (8). They established that the nodular dermatosis which results from this disease is secondary to a lipid-glycoprotein complex infiltration (5, 6). Hoarseness, secondary to vocal cord infiltration, was also noted as a common symptom. Subsequent studies have established a widespread multisystem involvement, including the central nervous system. the respiratory system. the gastrointestinal system, the genitourinary tract, the lymph nodes, and striated muscle (1-4). Characteristic bilateral "bean-shaped" calcification within the region of the hippocampus was first described by Ramos e Silva (7) in 1949, and in the case presented here is particularly extensive . Tomography reveals areas of lucency within the calcification which are suggestive of the hippocampal gyri (Fig. 7). Extensive nodular infiltration of the pharynx and larynx, demonstrated by laryngography, highlights this case. liPOID
Fig. 4 Lateral skull film shows a triangular. well circumscribed calcific density superimposed over the sella turcica. Fig. 5 Caldwell projection shows that the triangular calcified densities (arrows) are paired and lateral to the sella turcica.
PROTEINOSIS
laryngoscopy was interpreted as normal. The skin of his face and pretibial areas gradually became atrophic and friable, with warty growths appearing at the medial lid margins and on the elbows and knees. At age 24, episodes of seizures began which were characterized by an absence of memory and complex motor activity. In spite of relatively high doses of Dilantin, phenobarbital and Valium, the frequency and duration of the seizures increased, and the patient was referred to the National Institutes of Health. Physical examination revealed the skin involvement characteristic of lipoid proteinosis, and raised " lipid-like " lesions were seen on the soft palate and tongue. Laryngoscopy showed a thickening and nodularity of the base of the tongue, valecullae, epiglottis and aryepiglottic folds . Biopsy also showed the characteristic histological changes of lipoid prote inosis. The vocal cords could not be visualized. so laryngeal tomography and positive contrast laryngography were obta ined, showing a diffuse vocal cord thickening , thickened aryepiglottic folds, and a markedly thickened epiglottis (Fig . 1). Laryngography clearly delineated diffuse coarse and fine nodularity of the pharynx and larynx and the marked thicken-
CASE REPORT L. W . S. is a 25 year old white man who was entirely well until the age of four, when he became hoarse and plaque-like skin lesions on his hands and feet were noted. At age six a
Fig. 1 Anteroposterior tomogram of the larynx shows diHuse thickening of the true and false cords (arrow) with obliteration of the laryngeal ventricles. Both aryepiglottic folds, especially the left, are nodular (arrowheads). Fig. 2 Anteroposterior film of larynx during laryngography corroborates the marked vocal cord thickening (arrowheads) and the nodularity of the aryepiglottic folds. The med ial walls of the pyriform sinuses are also nodular. Fig.3 Laterallaryngogram shows thickening of the epiglottis (arrowheads) and diffuse "cobblestone " appearance of the pharynx. 1 From the Diagnostic Radiology Department. The Clinical Center. National Institutes of Health. Bethesda, Md. Accepted for publication in June 1975. ss
301
302
ROBERT
ing of the epiglottis and aryepiglottic folds (Figs. 2 and 3). An oral barium study showed nodules at the immediate post-cricoid cervical esophagus in the anterolateral position . Unfortunately, this was seen only on a video-tape recording. Skull films displayed prominent bean-shaped calcifications in the region of the temporal horns, documented both on plain film and tomography (Figs . 4-7). An adjustment of the drug therapy controlled his seizures, and local cortisone preparations reduced some of the pruritis. On follow-up admission one year later there had been no progression in hoarseness, seizures or skin involvement; skull films were unchanged. DISCUSSION Weidner et at. described laryngeal and lower respiratory tract changes in one case of lipoid proteinosis (9), when laryngeal laminography showed true and false vocal cord thickening and subglottic effacement. In this case, laminography showed a similar thickening, with obliteration of the laryngeal ventricles and distortion and thickening of the aryepiglottic folds confirmed by positive contrast laryngography. In both cases, laryngoscopy revealed diffuse and slightly raised yellowish-white plaques, which histologically consisted of a Iipidglycoprotein complex (5, 6). These histological changes have prompted McCusker and Caplan to suggest that the disorder be relabeled Iipoglycoproteinosis (6). The intracranial calcifications typical of lipoid proteinosis are located symmetrically within the anterior and medial aspects of the temporal horns. Histological studies by Holtz show the calcifications to be within the pericapillary regions of the hippocampal gyri (2). These bean-shaped calcifications are considered pathognomonic for lipoid proteinosis. At least one-third of the reported cases include this finding, and it is present in most patients with an associated epilepsy. Pathologists have described sclerosis and gliosis within the hippocampus in 50 % of the cases of idiopathic epilepsy and in 65 % of those with temporal lobe epilepsy. Similar lesions are seen as a result of hypoxia and after transtentorial uncal herniation (10), but in neither of these conditions is calcification noted. It would seem, however, that these areas of sclerosis are likely sites for dystrophic calcification . Microscopic involvement of other body tissues, including the gastrointestinal and genitourinary tracts, has been reported, but no gross radiographic changes have been documented. The upper esophagus is a site of involvement only slightly less often than is the larynx (1). In this case, nodules were demonstrated in the upper anterolateral area of the cervical esophagus, and confirmed by endoscopy. No pulmonary changes of any type were seen, and in view of the minimal perivascular deposits described histologically it is doubtful that specific radiographic Changes would be seen. The interstitial infiltrates described by Weidner (9) are most likely secondary to the patient's repeated upper and lower respiratory tract infections.
S.
November 1975
FRANCIS
Fig. 6 Lateral tomographic cut within the middle fossa defines the character of the calcific deposit (arrowheads) and shows it to be within the temporal lobe tip in the middle fossa. (The patient is fac ing right.) Fig. 7 Anteroposterior tomogram at the level of the dorsum sella shows lucent areas within the calcifications. Their configuration suggests the hippocampal gyrus.
Recognition of the relationship between the characteristic intracranial calcifications and the laryngeal involvement is important because the lipid complex infiltration of the larynx is progressive and may uncommonly result in a significant airway compromise. No good time-course studies have been done on the relative appearance of temporal lobe calcification with laryngeal changes. The skin changes in lipoid proteinosls usually appear by age twelve (3). One may surmise that the mucosal laryngeal changes parallel the skin involvement, and therefore usually precede the intracranial manifestations, especially in the absence of se izures. REFERENCES 1. Caplan RM: Lipoid proteinosis: A rev iew including some new observations. Univ Michigan M Bull 28:365-377, Mar 1962 2. Caplan RM: Visceral involvement in lipoid protelnosls, Arch Derm 95:149-155, Feb 1967 3. Cowan MA, Alexander S, Vickers HR, et al: Case of lipoid proteinosis. Brit Med J 52:557-560,26 Aug 1961 4. Heyl T: Lipoid protelnosls. I. The clinical picture. Brit J Derm 75:465-472,"Dec 1963 5. Heyl T, De Kock DH: A chromatographic study of skin lipoids in lipoid proteinosis. J Invest Derm 42:333-336, Apr 1964 6. McCusker JJ, Caplan RM: Lipoid proteinosis (Iipoglycoproteinosis): A histological study of two cases. Amer J Path 40:599613, May 1962 7. Ramos e Silva J: Lipo id proteinosis: (Urbach-Wiethe). Arch Derm 47:301-326, Apr 1974 8. Urbach E, Wiethe, C: Lipoidosis cutis et mucosae. Arch f Path Anat 273:285~319, Jun 1929 9. Weidner WA, Wenzi JE, Swischuk LE: Roentgenographic findings in lipoid proteinosis: a case report. Am J Roentgenol 110: 457 -461, Nov 1970 10. Williams JP, Slimach NM , FowlerFW: Radiographic hippocampal calcifications. Neuroradiology 4:159-161, Jan 1972 Diagnostic Radiology Department The Clinical Center Building 10, Room 6S-21 1 National Institutes of Health Bethesda, Maryland 20014
