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Histopathology of different types of atrophy of the human tongue
Path. Res. Pract. 182, 87-97 (1987)
Histopathology of Different Types of Atrophy of the Human Tongue~-
R. Bassler Institute of Pathology, City and Academic Hospital, Fulda, F.R.G.
SUMMARY Numerous studies have been devoted to the various histopathologic changes of the surface of the tongue. The muscles of the tongue and their changes in the process of ageing as well as in neurogenic atrophies, however, have not been systematically examined so far. Enlarging upon previous studies, an autopsy material of 170 tongues from all age groups was histologically examined in order to identify the steps in the development of age-related atrophy. These are characterized by a histometrically documented atrophy of the musculature with progressive lipomatosis. Fatty infiltration starts in the 2nd/3rd decade at three sites of predilection: body, root and tip of the tongue in the region of the anteriof lingual gland (NUHN). The age-dependent atrophy and the known clinical behaviour of neurogenic atrophies of the tongue are correlated with the histopathology of three typical forms: a neurogenic myasthenic atrophy of the tongue with high-grade symmetrical fatty replacement as an expression of a progressive myasthenic denervationj a lipomatous atrophy of the tongue as a late stage of poliomyelitis and long-term treatment in the "Iron Lung", and a lipomatous hemiatrophy due to posttraumatic extracranial hypoglossus paresis. The paretic part of this tongue consists of 85-90% fatty tissue. The different degrees of muscular atrophy of the tongue are largely compensated by metaplasia of fatty tissue in the perimysium following muscular degeneration (in the sense of a fatty replacement). With the exception of general and severe myasthenic atrophy, size, form and function of the tongue fail to show any significant changes in age-related atrophy and hemiatrophy.
Introduction The mucous membrane of the tongue, a special subtype of the oral mucosa, may be affected by different forms of infections, and by a number of metabolic, precancerous and neoplastic diseases. Considering that the muscular body of the tongue in these manifestations mostly remains unchanged, the pathology of the tongue predominantly has to be regarded as a "surface-pathology". Exceptions from this rule are amyloidosis, which in about 50% of cases is connected with macroglossia, and also the rare benign and malignant mesenchymal tumors, as well as * Dedicated to Prof. Dr. H. BredtiMainz, in Honour of His 80th Birthday. © 1987 by Gustav Fischer Verlag, Stuttgart
invasive carcinomas and lymphomas of the musculature of the tongue?' 10, 12, 18, 21. As compared to the numerous investigations on the pathohistology of the oral mucosa, the morphology of age-related changes and neurogenic diseases of the human tongue has not been systematically examined so far. Therefore, this study will be concerned with the steps in the development of age-related atrophy, which will then be confronted with three characteristic types of neurogenic atrophy: - a muscular atrophy in myasthenia gravis involving the whole tongue; - a late stage of poliomyelitis, and - a hemiatrophy of the tongue in unilateral hypoglossus paresis. 0344-0338/87/0182-0087$3.50/0
88 . R. Bassler Material and Methods Considering the different tissues, the age-dependent morphological changes of the 170 tongues from our autopsy material were histologically described and morphometrically evaluated. Macroscopic and microscopic examinations were performed on three transverse sections through tip, body and root of the tongue, and on a median sagittal section. Of the transverse sections, microscopical gross sections were made to determine the topical relations of the fatty deposits. Our material comprised all age groups, from the embryonal stage to the 92nd year of life in the distribution depicted in Table I.
Table 1. Age-distribution of the material Years of life
No. of cases
15
0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 80-89 over 90
13
17 10
12 30 29 22 11 9
Quantitative Evaluation
The relative volume proportion of fatty tissue, determined with an integration ocular, was stratified into the fatty tissue content of the tip, the body and the root of the tongue in the respective age groups. Scatter diagrams were used for defining the relation between age and fat content, formulated as percentual integration value. A certain dependence of fat content on age was discovered, which, though, was not linear. Logarithmic transformation of the fat content failed to yield a satisfactory rectification. Logittransformation finally led to a satisfactory linearisation. The values for the tongues in neurogenic atrophy were similarly measured using the integration ocular. In myasthenia gravis evaluation was based on 10 visual fields, respectively, with 25 measuring points at the tip, body and root of the to'ngue. The middle parts with preserved musculature were compared with the lateral parts with predominantly fatty tissue. The tongue after hypoglossus paresis was examined in the left and right half at three points with ten visual fields, respectively. The results for the left half corresponded to the age-dependent mean value, the measurements for the right half were listed as mean value (Fig. 1).
Results Age-related Atrophy and Lipomatosis of the Tongue
Histopathologic and morphometric investigations reveal an age-related progressive increase of fatty tissue in the musculature of the tongue, in the ligual glands and in the aponeurosis (Fig. 4). Up the fifth year of life, the muscular fascicles are densely packed containing no fatty tissue. In the second, and even more so in the third decade of life, small, single groups of fat cells occur at three sites of predilection: 1) at the base of the tongue in the borderline area between the genioglossus m. and the inner musculature, in the region of a gliding layer; 2) at the root of the tongue; 3) in the region of the mucous glands of the root (Weber) and of the aponeurosis linguae of the back of the tongue, as well as in the regio-n of the anterior lingual gland (Nuhn).
% Fat tissue
90
I
} Lipomatous Hemiatrophy in Hypoglossal Paralysis
80
•
70
• • • • • •
60
lateral ports
50
Neurogenic Atrophy in Myasthenia gravis
medial : } ports
40
3
Age - related Atrophy
20 10 5 3~~~
1:L---
o
10 20 30 40 50 60 70 80 90 100 years
Fig. 1. Schematic representation of percentual content of fatty tissue of the tongue in age-related atrophy (regression values for the correlation between age and fat content) with the values obtained for neurogenic atrophies.
In the course of the first two decades, these areas become confluent, mostly by formations of small bridges of single or grouped fat cells, so that in the third and fourth decade a lowgrade lipomatosis of the base of the tongue arises at the lower margin of the longitudinal superior muscle, at the base of the tongue and in the basal gliding layers of the genioglossus muscle. An increase of
Atrophy of the Human Tongue· 89
a
c
Fig. 2. Comparison of macroscopic sections of the tongue: a) normal tongue of a 53-year-old woman b) myasthenic atrophy of the tongue with shrinking and flattening of the whole tongue; mainly fatty tissue in the lateral parts c) lipomatous atrophy of the right side due to hypoglossus paresis.
single foci in the fifth and sixth decade of life to an almost band-shaped lipomatosis in and under the aponeurosis linguae, in the lateral parts of the tongue, in the region of the septum linguae, and at the base of the tongue. At this age and later, there are striated vertical deposits of fatty tissue between the muscular fascicles at the root of the tongue, which have to be considered a typical macroscopical finding in high age. Only a small increase in fatty tissue occurs after the 80th year of life (Figs. 2 a, 4 and 10). Correlations between age-related lipomatosis of the tongue and body weight were not examined. In the younger age group there was no morphologically :remarkable lipomatosis of the musculature of the tongue in general adiposity. . Lipomatosis of the tongue is connected with an increasing atrophy of the musculature connected with a varying
narrowing of muscle fibres in the fascicles and with fibrosis of the perimysium (Fig. 3). The fascicular form of atrophy, especially in high age, corresponds to the bland neurogenic type of atrophy because we found a varying pattern of grouped fibre atrophies. With regard to the volume of the tongue, the loss of musculature is mainly compensated by fatty tissue, so that form and volume of the tongue are largely preserved in high age. Histology of the Lingual Glands The changes depicted in Table II show that metaplasias in a sense of atrophy of the glandular parenchyma with fatty and fibrous replacement of the posterior serous Ebner's glands and of the sero-mucous anterior lingual gland (Nuhn) are stronger and present earlier than those
90 . R. Bassler
o-
19 y.
20 - 39 y.
40 - 59 y.
60 - 90 y.
Fig. 3. Age-related lipomatous atrophy of the tongue (woman, aged 53). a) Septum linguae with symmetrical lipomatosis. b) Musculature of the tongue with lipomatosis and focal fibrosis. Muscular fascicles of different calibre; focal a lowgrade fascicular atrophy. Form., Paraffin, HE; Magn. 120 x
Fig. 4. Degree and localisation of age-dependent lipomatous atrophy of the tongue. Black hatching shows content of fatty tissue in sites of predilection and increase with age.
Table 2. Qualitative histological changes of the lingual glands in age-related atrophy and types of neurogenic atrophy
1.-30. yrs ,~
...U
....:
..I:l
ti::l
0 u I':
....: til
S 0
,&
1. Posterior lingual gland (Ebner) 2. Anterior lingual gland (Nuhn) 3. Mucous glands of the root (Weber)
31.-60. yrs
... en 0
OJ
~
....: til
S 0
0-
61.-90. yrs
....: u
....:
...
....: u
~
Ci
0 u I':
0
-
+
(+) ++
,~
en 0
..I:l
(l)
::l
~
....: u
....:
...
....: u
~
Ci
0 u I':
++
++
....: til
S 0
J
,~
en 0
..I:l
OJ
::l
.....l
~
Ci
0
;J
-
-
-
-
(+)
-
-
-
-
++ +
+
(+) +++ +++ ++
-
-
-
-
+
(+) (+)
"'
-
-
i>U
0
Myasthenia gravis (62 yrs) ....: ....: u til i>,~ OJ U S 0en 0
...
0 0-
;J
... ..I:l ~
+++ ++ ++ ++
+++ (+)
ti::l
(+)
(l)
Ci
0
J
-
-
++ ++ + -
u I':
Hypoglossus Paresis (63 yrs) ....: ....: ....: U til i>,~ U en S 0 ...0 ....:u u0
-
..I:l
::l
I':
Ci
0
+++ (+)
-
-
+
++
+
++ ++
-
++
+
++
~
-
Atrophy of the Human Tongue· 91
of the mucous glands and of the root of the tongue. Surrounded by focal duct ectasias, they remain largely unchanged up to the 7th/8th decade of life. The focal and low-grade lipomatosis of the younger age group increases in the 5th and 6th decade and is connected with an increasing atrophy of the serous acini. In neurogenic muscular atrophies the anterior lingual gland (Nuhn) and the posterior Ebner's glands show the most significant changes of atrophy, lipomatosis and fibrosis; in the case of myasthenia gravis in a age-related level but in the case of hypoglossus paresis in a high grade of lipomatosis and atrophy (Fig. 9). Neurogenic Muscular Atrophy of the Tongue in Myasthenia Gravis Case Report (short Version)
We report on a 62-year-old woman who for some years had been suffering from increasing tiring, dysphasia and disturbances of speech. In 1984 and 1985 she received repeated stationary treatment for bulbar symptoms, dysarthria and disturbed innervation of the soft palate, and atrophy of the tongue. Weak proximal pareses occurred in the upper and lower extremities. Liquor: IgG 1,580 mg%. EMG: significant 30% decrease of amplitude: Tensilon test positive. CT of the mediastinum: no tumor, but signs of thymus hyperplasia. Neurologic diagnosis: myasthenia gravis. Therapy led to improvements as far as tiring and dysarthria were concerned. November 1985: aspiration pneumonia. Exitus.
Tongue
Macroscopically, the tongue is reduced in size, measuring 9 X 5 X 2 cm, its consistency being flabby and soft, its color grey-yellow, especially in both margins. The surface is laterally flattened and smooth, in the middle there is an elongated area with preserved, partly coarsened papillae. There is a trough-shaped, flat depression. Fronto-dorsal sections reveal high-grade atrophy of the musculature on both sides and large deposits of fatty tissue, predominantly in marginal parts (Fig. 2 b). Under the median sulcus and in the area of the septum linguae the musculature is preserved rather well (vertical, transverse, and partly the longitudinal superior muscles). Thin fascicles of the genioglossus muscle can be observed in the basal part. As the hypoglossus and the styloglossus muscle, this muscle is atrophic and contains a great amount of interstitial fatty tissue. At the surface, this fatty tissue permeates the aponeurosis linguae, and has proceeded laterally and on the base of the tongue below the epithelial membrane (Fig. 10).
Autopsy (no. 42185)
Myasthenia gravis with neurogenic lipoIl}atous atrophy of the tongue and inferior constrictor muscle of the pharynx. Segmental fibrous atrophy and focal lymphorrhagia of the pectoralis major, sartorius and iliopsoates muscles. Lymphofollicular hyperplasia of the thymus with infiltration of plasma cells and mast cells (autoimmune thymitis) *. Performed tracheotomy with long-term ventilation. Aspiration pneumonia. Cardiac muscle of both ventricles without pathological changes. Neuropathologic Findings
No significant changes in cerebrum and cerebellum, i.e. no signs of meningitis or encephalitis, no necroses, no hemorrhages. Serial sections through medulla oblongata and medulla spinalis cervicalis yielded minimal lacks of single ganglion cells, but neither necroses nor cysts. Nucleus of n. hypoglossus with many well-preserved ganglion cells in symmetrical arrangement, without myelomalacia or inflammatory changes. Segments of the median and lower cervical part of the medulla without pathologic changes * * . ~
* * * Special thanks to Prof. Dr. OttolHeidelberg and Prof. Dr.
Schroder/Aachen for their kind support and expert advice.
Fig. 5. Myasthenic atrophy of the tongue with severe lipomatosis. Few large muscular fascicles preserved; next to them grouped fibre atrophies with focal and septal fibroses (no. 241/ 84). Form., Paraffin, HE; Magn. 120 X
92 . R. Bassler
Histopathology
Comparison of the different regions of the tongue reveals extent and progression of the muscular atrophy and lipomatosis. Only few, mainly central regions of the inner musculature show regular fascicles. Their texture appears looser at the margin due to lower fibre calibres, increase in reticular and collagenous connective tissue and a strong increase in fatty tissue. The intensity of fibromatosis and lipomatosis correlates with the degree of muscular atrophy: the more pronounced the muscular atrophy, the more intense are fibromatosis as well as lipomatosis. The fatty tissue contains numerous well-preserved peripheral nerves. Inflammatory reactions are missing (Fig. 5 and lOb). The musculature of the meso- and hypopharynx shows strong and progressive muscular atrophy with fibrosis and lipomatosis (Fig. 6), fully corresponding to the transformations of the muscles of the tongue itself. Epicrisis
In the course of the next years, the 62-year-old woman had developed an initially unclear clinical picture with
symptoms of bulbar paralysis, which proved to be a manifestation of myasthenia gravis. The autopsy findings with lymphofollicular thymus hyperplasia and lymphorrhagias in the skeletal musculature confirmed this diagnosis. In different skeletal muscles, myasthenia gravis led to focal, mainly low-grade neurogenic atrophies and to an unusually strong muscular atrophy of the tongue and of the pharynx. Neurogenic Atrophy of the Tongue Following Poliomyelitis Case Report (short version)
17-year-old girl, ill with poliomyelitis since the age of five. Since that time, i.e. for twelve years, she had been living in the so-called "iron lung". She died in 1964 from respiratory insufficiency. Autopsy (no. 890164 MZ)
Late stage of a poliomyelitis with extended loss of motor neurons in the cervical, thoracic and lumbal regions of the spinal cord, partly in the medulla oblongata. Highgrade atrophy of the total skeletal musculature. Disuse atrophy of the complete bone system with paper-thin compacta of the long bones. Infantile genitals. Tongue: Size and form corresponding to the age of the patient. Transverse sections revealed a marked content of fatty tissue. Histologically, atrophy of the musculature with formation of small groups of fibres, with fibrosis of the perimysium and lipomatosis. Epicrisis
The girl who died at the age of 17 was suffering from the sequels to a severe poliomyelitis with paralysis of the respiratory musculature. She had been living in the "iron lung" for 12 years. Skeletal musculature and tongue showed a high-grade muscular atrophy and an extended fatty replacement. Hemiatrophy of the Tongue Following Traumatic Hypoglossus Paresis Case Report (shc/rt version):
Fig. 6. Musculature of the hypopharynx in myasthenic atrophy with signs of progressive transformation of the muscles with fibrosis and focal lipomatosis. Focally preserved muscular fascicles. (no. 241/84)." Form., Paraffin, HE; Magn. 120 x
63-year-old woman. For several years suffering from chronic renal insufficiency, hypertension and cardiac insufficiency. In 1955 head traume with loss of the right eye in a domestic quarrel. In 1969 strumectomy. For a number of years swelling of the soft parts of the right part of the neck, the cause of which could not be clarified. Paresthesias occurred in the perioral region and in the region of the fingers. No signs of tongue paresis, no hemiatrophy of the face. Autopsy (no. 302184)
Chronic glomerulonephritis with performed hemodialysis. Sepsis. Bacterial endocarditis.
Atrophy of the Human Tongue . 93 Neuropathologic Examination Cerebrum and cerebellum without pathologic changes. Medulla oblongata and nuclei of hypoglossus nerve were not systematically examined, because the true extent of the changes of the tongue was only discovered later. During preparation of the n. hypoglossus of the tongue, a regular nerve was detected on the left side, on the right side the n. hypoglossus could not be assessed. There were only thin filaments at the dorso-Iateral margin of the tongue, which were surrounded by connective tissue. Tongue: Macroscopically of normal size (9,5 X 6 X 2,5 cm). Asymmetrical form because of low-grade flattening of the right margin with grey-yellow coloring. Regular structure of the surface with small deep longitudinal furrows. Papillae in regular arrangement. Fronto-dorsal transverse sections in the right half reveal a replacement of muscles by yellow fatty tissue reaching up to the tip of the tongue. The septum provides a sharp s-like limitation to the left side (Fig. 2 c). At the tip the fatty tissue is 2 cm of breadth, in the middle 2,5 -3 cm, reaching from the surface to the lower side (Fig. 10 c). Histopathology The left half of the tongue shows a regular musculature with minor age-related lipomatosis. Instead of musculature the right half contains homogeneous univacuolar fatty tissue from the aponeurosis up to the lateral margin and the lower side (Fig. 7). The border between both halfs of the tongue is formed by the septum linguae. Fascicles of the verticalis and transverse muscle under the aponeurosis are partly
"r'--> "~+r--"t
IfJ::- "
t ,,',
.">l ,;
'-~.4..4SJ~
,
-----
Fig. 8. Lipomatous hemiatrophy in hypoglossus paresis with few preserved isomorphous groups of muscular fascicles, surrounded by connective tissue. Form., Paraffin, HE; Magn. 120 x preserved in the right half, too. The residual musculature with preserved transverse striation forms small groups of fibres between the fat cells. These fibres are surrounded by connective tissue (Fig. 8). In the new-formed fatty tissue reticular fibroses can be seen laterally and above all caudally. There are also rich deposits of peripheral nerve trunks and blood vessels. The aponeurosis in the right half is full of fat cells and reduced in breadth. For the behaviour of the lingual glands d. Tab. II and Fig. 9. Epicrisis
Fig. 7. Lipomatous hemiatrophy in hypoglossus paresis. Severe lipomatosis of the aponeurosis linguae. Preserved scattered muscular fascicles with high-grade atrophy. Form., Paraffin, HE; Magn. 120 x
The 63-year-old woman died from sepsis and chronic renal and cardiac insufficiency. Underlying sepsis was chronic glomerulonephritis and hemodialysis. The lipomatous hemiatrophy on the right side of the tongue, detected at autopsy, was a sequel to a peripheral extracranial and traumatic hypoglossus paresis. After a cranial trauma the patient had lost her right eye in 1955. This cranial trauma had been connected with damage of the n. hypoglossus. At autopsy no residues of a fracture of the base of the skull were found.
94 . R. Bassler
a
Fig. 9. Qualitative changes of the lingual glands in hemiatrophy due to hypoglossus paresis. a) Root of the tongue with the well preserved mucous gland and the marked atrophy and lipomatosis of the posterior serous glands (Ebner). b) Anterior lingual gland (Nuhn) with atrophy, fibrosis and a marked lipomatosis of the stroma. Duct ectasias in a field on the upper margin. Form., Paraffin, HE; Magn. 60 x, 120 x
Discussion The transverse section through the root of the tongue, demanded at each autopsy, primarily aims at detecting developmental disturbances of the thyroid gland in the region of the foramen caecum 1, 13. In general, no attention is paid to the behaviour of the tissue of the muscular body of the tongue, often affected by atrophy or lipomatosis related either with age or with neurogenic diseases. In addition to previous investigations on age-related changes of the musculature of the tongue!, three typical forms of atrophy of the tongue are here described. The clinical aspects of this kind of atrophy have already been discussed in some detail elsewhere3, 14, 19, whereas histopathologic investigations concerned with this organ with the exception of two specimens of partial amputations in myasthenia gravis S - have not been presented so far.
Age-related Atrophy of the Tongue
The morphometric studies and the statistical data published in 1971 1 reveal a definitely linear relation between age and degree of lipomatosis. From this follows a slow increase in fatty tissue up to the 3 rd/4th decade, later followed by a more marked increase up to the 80th year of life. As far as the course of the curves is concerned, the examined regions of the tongue are very similar. Therefore, these general rules can be used for a forensic determination of age. Lipomatosis of the tongue in neurogenic atrophies exceeds the age-related measurements by two to three times higher values (Fig. 1). With regard to its texture and the manifold coordinated movements in speaking, eating, drinking and swallowing, the tongue has a special place among the skeletal muscles. This can be seen from the fact that even in age-related
Atrophy of the Human Tongue· 95
atrophy and lipomatosis there are only low-grade disturbances of function, although a loss of energetic output attributable to a loss of muscular mass can be expected. According to Patel et al. 17 it is remarkable that there is no disuse atrophy even after months of coma during which the tongue had been largely immobilised. Neurogenic Myasthenic Atrophy of the Tongue
Clinical examination in our first case indicated myasthenia gravis type II according to Osserman 16. A progressive bulbar-paralytic complex of symptoms with minor pareses of the proximal musculature of the extremities was prominent. Histopathologic investigations following autopsy revealed a high-grade atrophy of the tongue and of the musculature of the pharynx correlative to the bulbar paralysis; in addition, there were fascicular neurogenic atrophies in some skeletal muscles. These atrophies were connected with lymphorrhagia as well as with lymphofollicular thymus hyperplasia. Neuropathologic examinations especially of the medulla oblongata and of the spinal cord, however, did not · indicate any changes which might explain these atrophies. In the nucleus n. hypoglossi there were no necroses, the ganglion cells were of regular structure. Therefore, diagnosis of myasthenia gravis with exceptional neurogenic muscle atrophies was confirmed. The muscular atrophies interpreted in the literature as myasthenic myopathy or as neuro-muscular diseases can be observed in 6-10% of cases according to Oosterhuis and Bethlem l5 and Oosterhuisl 4. According to Schimrick and Samland20 the frequency of latent muscular atrophies is significantly higher. The proximal musculature - as in the case described - is preferentially affected. Atrophies of the tongue in myasthenia, which were first pointed to by Buzzard6 in 1905, occur isolated or in combination with atrophies of the musculature of the pharyrtx and of the face in 4% of cases l4 . In this, the tongue is reduced in size, flattened and flabby showing an asymmetrical surface. The histopathology of this especially marked atrophy of the tongue and lipomatosis has only been described for two specimens of the tongue following amputation by Brownell and coworkers in 19725. These preparations, examined in transverse sections, correspond to our own investigations. The latero-basal regions show the strongest degree of atrophy and lipomatosis, the central parts contain fascicles of the inner muscles (Fig. 10 b). Numerous large peripheral nerves without pathologic changes can be found in the fatty tissue. The different degrees of muscular atrophy depicted in Figs. 5 and 6 point to the progression of the disease. The constrictor pharyngis muscle, too, is involved in this atrophy. As compared to the tongue, the atrophy is not so strong, but progressive, and it shows focal lipomatous metaplasias. Following own investigations Tyle~4 in 1982 raised the question whether this might not merely be a myasthenic symptom in a Illotor neuron disease which in its early stages usually afb.:ts the tongue and the pharynx. As the case described shows no evident loss of the ganglion cells in medulla oblongata and spinalis, and as the histopathologic changes clearly point
to myasthenia gravis, such a primary motor neuron disease is not probable. The depicted atrophies of skeletal muscles are localized in the preferential regions of myasthenic disturbances of function. They explain the bulbar-paralytic symptoms as well as the pareses of the proximal musculature of the extremities. The pattern of distribution of fascicular atrophy is considered as the result of a denervation of the skeletal muscles ll , 15,22. Underlying this denervation are degenerative changes of the motor end-plates, mainly in the region of the postsynaptic membranes. This has been confirmed by enzymehistochemical investigations by EngelS and Brody and Engel4 , according to whom advanced denervations occur only in the late stages of myasthenia gravis. Silver stainings yielded irregular proliferations of terminal nerve fibres in the atrophic skeletal musculature, which by Brownell et aU are considerd as an expression of the nerve's compensation behaviour aiming at repair of the neuromuscular transmitter function. Therefore, muscular atrophies in myasthenia gravis are neither a disuse atrophy nor a myopathy in the strict sense, but an expression of a peripheral neurogenic manifestation of this denervating disease. Atrophy of the Tongue Following Poliomyelitis
Following poliomyelitis with paralysis of the diaphragm which the patient had been ill with at child's age, she had been treated for 12 years in the so-called "iron lung". As a consequence, high-grade disuse atrophy of the skeletal musculature and of the bone system had developed. The tongue showed marked muscular atrophy and lipomatosis, which has to be interpreted as an expression of a combined neurogenic and disuse atrophy. This can be explained by the fact that the patient had been living in isolation for years, during which she had lost contact and motility. These observations mal be in contrast to the opinion of Patel and coworkers I , they can be explained, however, by the extreme situation of a late stage of poliomyelitis. Lipomatous Hemiatrophy of the Tongue in Hypoglossus Paresis
As compared to the numerous studies on causes, forms and symptoms of glossoplegia, the pathomorphology of a hemiatrophy of the human tongue with an extended fatty replacement has not been dealt with in the available literature starting from 1899 23 • This applies especially to the clinically known forms of hypoglossus paresis and to the rare cases of facial hemiatrophy, which can be connected with a unilateral atrophy of the tongue9 • In our third case, a unilateral lipomatosis of the root of the tongue was detected at autopsy. Form and volume of the tongue did not seem conspicuous. Further preparation, however, revealed a homogeneous, extended unilateral lipomatosis with septal fibrosis (Fig. 2 c and 10 c) and inclusion of small single groups of bundles of muscle fibres (Fig. 8); this lipomatosis reached from the tip to the root of the tongue and includes the stroma of the lingual glands
96 . R. Bassler
(Fig. 2 c). Diameters of the single muscle fibres differed only slightly. The lipomatosis involved the complete aponeurosis, so that the fatty tissue there extended to the epithelial membrane, which explaines the yellow coloring of the surface on the right half of the tongue. According to the histopathologic results there was a long-term, almost total hemiatrophy of the musculature of
the tongue in the innervation area of the n. hypoglossus dexter. The sharp limitations of the fatty tissue and the few included isomorphic bundles of muscle fibres indicate that atrophy and metaplasia have to be considered as a finished and resting process (Fig. 10 c). As compared to the left side, the n. hypoglossus dexter could not be detected in the specimen. Instead, there was a
b
Fig. 10. Gross sections through median part of the tongue depicting the physiological, age-dependent lipomatosis and the neurogenic atrophies: a) Normal degree of lipomatosis (no. 15/86; 53-year-old woman. b) Myasthenic atrophy with large fatty deposits in the lateral and basal parts with preserved inner musculature in the middle (no. 241/84; 62-year-old woman. c) Hemiatrophy of the right side with low-grade deformation of the tongue and severe pseudo-hypertrophy of fatty tissue to the lower side of the epithelial layer. Physiological lipomatosis of the musculature of the left half (no. 302/84; 63year-old woman). Magn.2 X
Atrophy of the Human Tongue· 97
connective tissue with few, thin fibres between the hypoglossus muscle and the root of the tongue, the fibres corresponding to markedly atrophic nerves. Accordingly, these must be the result of an extracranial peripheral damage of the n. hypoglossus. As the patient had suffeteda cranial trauma with loss of the right eye some 29 years ago, it can be concluded that the hemiatrophy of the tongue is the sequel of a peripheral traumatic hypoglossus paresis. The depicted patterns and grades of atrophy and lipomatosis point to the enormous ability of functional compensation of this organ, even if large parts of specific texture are lost. References 1 Bassler R, Bilden J, Lange JH (1971) Alternsveranderungen der menschlichen Zunge. Act Gerontol 1: 29-44 2 Baker RD (1967) Postmortem Examination: Specific Methods and Procedures. WB Saunders Cp, London - Philadelphia - Toronto 3 Bodechtel H (Ed) (1963) Differentialdiagnose neurologischer Krankheitsbilder. 2. Auf!. Georg Thieme, Stuttgart 4 Brody WA, Engel WK (1964) Denervation of muscle in myasthenia gravis. Arch Neurolll: 350-354 5 Brownell B, Oppenheimer DR, Spalding JMK (1972) Neurogenic muscle atrophy in myasthenia gravis. J Neurol Neurosurg Psychiatr 35: 311-322 6 Buzzard EF (1905) The clinical history and post-mortem examination of five cases af myasthenia gravis. Brain 28: 538-583 7 Dockerty MB, Parkhill EM, Dahlin DC, Woolner LB, Soule EH, Harrison EG (1968) Tumors of the oralcavity and pharynx. Atlas of Tumor Pathology, Sect IV, Fasc 10 b. Armed Forces Institute of Pathology, WashingtonlDC 8 Engel WK (1962) Essentiality of histo- and cytochemical studies of skeletal muscle in investigation of neuromuscular diseases. Neurology 12: 778-794
9 Gagel 0 (1953) Die Erkrankungen des vegetativen Systems. In: Bergmann G v, Frey W, Schwiegk H (Eds) Handbuch der Inneren Medizin. Bd. Y, 2. Teil (Neurologie), pp. 877-880. Springer, Berlin - Gottingen - Heidelberg 10 Lucas RB (1984) Pathology of Tumors of the Oral Tissue. Churchill Livingstone, Edinburgh - London - New York 11 McDermot C (1960) The changes in the motor end plate in myasthenia gravis. Brain 83: 24-36 12 Morgenroth K (1984) Mundhohle, Zahne, Kiefer, Waldeyer-Rachenring, Oro- und Hypopharynx. In: Remmele R Pathologie II, pp. 3-84. Springer, Berlin - Heidelber - New York - Tokyo f 1 Nauwerk C (1921) Sektionstechnik fur Studierende und Arzte. 6. Auf!. G. Fischer, Jena 14 Oosterhuis HS (1984) Myasthenia gravis. Churchill Livingstone, Edinburgh - London - Melbourne - New York 15 Oosterhuis HS, Bethelm J (1973) Neurogenic Muscle Involvement in myasthenia gravis. A clinical and histopathological study. J Neurol Neurosurg Psychiatr 36: 244-254 16 Ossermann KE (1958 ) Myasthenia gravis. Grune & Stratton New York 11 Patel AN, Razzak ZA, Dastur DK (1969) Disuse atrophy of human skeletal muscles. Arch Neurol 20: 413-421 18 Pindborg JJ (1969) Atlas der Erkrankungen der Mundschleimhaut. C. Hanser, Miinchen 19 Scheid W (1980) Lehrbuch der Neurologie. 4. Auf!., Georg Thieme, Stuttgart 20 Schimrigk K, Samland 0 (1977) Muskelatrophien bei Mrasthenia gravis. Nervenarzt 48: 65-68 1 Seifert G (1966) Mundhohle, Mundspeicheldriisen, Tonsillen und Rachen. In: Spezielle pathologische Anatomie. Bd. l. Springer, Berlin - Heidelberg - New York 22 Steidl RM, Oswald AJ, Kottke FJ (1962) Myasthenia syndrome with associated neuropathy. Arch Neurol 6: 451-461 23 Tyler HR (1982) Nonfamilial amyotrophy with dementia or multisystem degeneration and other neurological disorders. In: Rowland LP (Ed) Human Motor Neuron Diseases. Raven Pr., New York 24 Wiersman E (1899) faile von Hemiatrophia linguae. Neurol Zb118: 818- 829
Received July 9, 1986 . Accepted in revised form September 9, 1986
Key works: Tongue - Age-related atrophy - Neurogenic atrophy in myasthenia gravis - Poliomyelitis - Hemiatrophy due to hypoglossus paresis Prof. Dr. R. Bassler, Pathologisches Institut, Stadtische Kliniken, Pacelliallee 4, D-6400 Fulda, FRG
Histopathology of Different Types of Atrophy of the Human Tongue~-
R. Bassler Institute of Pathology, City and Academic Hospital, Fulda, F.R.G.
SUMMARY Numerous studies have been devoted to the various histopathologic changes of the surface of the tongue. The muscles of the tongue and their changes in the process of ageing as well as in neurogenic atrophies, however, have not been systematically examined so far. Enlarging upon previous studies, an autopsy material of 170 tongues from all age groups was histologically examined in order to identify the steps in the development of age-related atrophy. These are characterized by a histometrically documented atrophy of the musculature with progressive lipomatosis. Fatty infiltration starts in the 2nd/3rd decade at three sites of predilection: body, root and tip of the tongue in the region of the anteriof lingual gland (NUHN). The age-dependent atrophy and the known clinical behaviour of neurogenic atrophies of the tongue are correlated with the histopathology of three typical forms: a neurogenic myasthenic atrophy of the tongue with high-grade symmetrical fatty replacement as an expression of a progressive myasthenic denervationj a lipomatous atrophy of the tongue as a late stage of poliomyelitis and long-term treatment in the "Iron Lung", and a lipomatous hemiatrophy due to posttraumatic extracranial hypoglossus paresis. The paretic part of this tongue consists of 85-90% fatty tissue. The different degrees of muscular atrophy of the tongue are largely compensated by metaplasia of fatty tissue in the perimysium following muscular degeneration (in the sense of a fatty replacement). With the exception of general and severe myasthenic atrophy, size, form and function of the tongue fail to show any significant changes in age-related atrophy and hemiatrophy.
Introduction The mucous membrane of the tongue, a special subtype of the oral mucosa, may be affected by different forms of infections, and by a number of metabolic, precancerous and neoplastic diseases. Considering that the muscular body of the tongue in these manifestations mostly remains unchanged, the pathology of the tongue predominantly has to be regarded as a "surface-pathology". Exceptions from this rule are amyloidosis, which in about 50% of cases is connected with macroglossia, and also the rare benign and malignant mesenchymal tumors, as well as * Dedicated to Prof. Dr. H. BredtiMainz, in Honour of His 80th Birthday. © 1987 by Gustav Fischer Verlag, Stuttgart
invasive carcinomas and lymphomas of the musculature of the tongue?' 10, 12, 18, 21. As compared to the numerous investigations on the pathohistology of the oral mucosa, the morphology of age-related changes and neurogenic diseases of the human tongue has not been systematically examined so far. Therefore, this study will be concerned with the steps in the development of age-related atrophy, which will then be confronted with three characteristic types of neurogenic atrophy: - a muscular atrophy in myasthenia gravis involving the whole tongue; - a late stage of poliomyelitis, and - a hemiatrophy of the tongue in unilateral hypoglossus paresis. 0344-0338/87/0182-0087$3.50/0
88 . R. Bassler Material and Methods Considering the different tissues, the age-dependent morphological changes of the 170 tongues from our autopsy material were histologically described and morphometrically evaluated. Macroscopic and microscopic examinations were performed on three transverse sections through tip, body and root of the tongue, and on a median sagittal section. Of the transverse sections, microscopical gross sections were made to determine the topical relations of the fatty deposits. Our material comprised all age groups, from the embryonal stage to the 92nd year of life in the distribution depicted in Table I.
Table 1. Age-distribution of the material Years of life
No. of cases
15
0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 80-89 over 90
13
17 10
12 30 29 22 11 9
Quantitative Evaluation
The relative volume proportion of fatty tissue, determined with an integration ocular, was stratified into the fatty tissue content of the tip, the body and the root of the tongue in the respective age groups. Scatter diagrams were used for defining the relation between age and fat content, formulated as percentual integration value. A certain dependence of fat content on age was discovered, which, though, was not linear. Logarithmic transformation of the fat content failed to yield a satisfactory rectification. Logittransformation finally led to a satisfactory linearisation. The values for the tongues in neurogenic atrophy were similarly measured using the integration ocular. In myasthenia gravis evaluation was based on 10 visual fields, respectively, with 25 measuring points at the tip, body and root of the to'ngue. The middle parts with preserved musculature were compared with the lateral parts with predominantly fatty tissue. The tongue after hypoglossus paresis was examined in the left and right half at three points with ten visual fields, respectively. The results for the left half corresponded to the age-dependent mean value, the measurements for the right half were listed as mean value (Fig. 1).
Results Age-related Atrophy and Lipomatosis of the Tongue
Histopathologic and morphometric investigations reveal an age-related progressive increase of fatty tissue in the musculature of the tongue, in the ligual glands and in the aponeurosis (Fig. 4). Up the fifth year of life, the muscular fascicles are densely packed containing no fatty tissue. In the second, and even more so in the third decade of life, small, single groups of fat cells occur at three sites of predilection: 1) at the base of the tongue in the borderline area between the genioglossus m. and the inner musculature, in the region of a gliding layer; 2) at the root of the tongue; 3) in the region of the mucous glands of the root (Weber) and of the aponeurosis linguae of the back of the tongue, as well as in the regio-n of the anterior lingual gland (Nuhn).
% Fat tissue
90
I
} Lipomatous Hemiatrophy in Hypoglossal Paralysis
80
•
70
• • • • • •
60
lateral ports
50
Neurogenic Atrophy in Myasthenia gravis
medial : } ports
40
3
Age - related Atrophy
20 10 5 3~~~
1:L---
o
10 20 30 40 50 60 70 80 90 100 years
Fig. 1. Schematic representation of percentual content of fatty tissue of the tongue in age-related atrophy (regression values for the correlation between age and fat content) with the values obtained for neurogenic atrophies.
In the course of the first two decades, these areas become confluent, mostly by formations of small bridges of single or grouped fat cells, so that in the third and fourth decade a lowgrade lipomatosis of the base of the tongue arises at the lower margin of the longitudinal superior muscle, at the base of the tongue and in the basal gliding layers of the genioglossus muscle. An increase of
Atrophy of the Human Tongue· 89
a
c
Fig. 2. Comparison of macroscopic sections of the tongue: a) normal tongue of a 53-year-old woman b) myasthenic atrophy of the tongue with shrinking and flattening of the whole tongue; mainly fatty tissue in the lateral parts c) lipomatous atrophy of the right side due to hypoglossus paresis.
single foci in the fifth and sixth decade of life to an almost band-shaped lipomatosis in and under the aponeurosis linguae, in the lateral parts of the tongue, in the region of the septum linguae, and at the base of the tongue. At this age and later, there are striated vertical deposits of fatty tissue between the muscular fascicles at the root of the tongue, which have to be considered a typical macroscopical finding in high age. Only a small increase in fatty tissue occurs after the 80th year of life (Figs. 2 a, 4 and 10). Correlations between age-related lipomatosis of the tongue and body weight were not examined. In the younger age group there was no morphologically :remarkable lipomatosis of the musculature of the tongue in general adiposity. . Lipomatosis of the tongue is connected with an increasing atrophy of the musculature connected with a varying
narrowing of muscle fibres in the fascicles and with fibrosis of the perimysium (Fig. 3). The fascicular form of atrophy, especially in high age, corresponds to the bland neurogenic type of atrophy because we found a varying pattern of grouped fibre atrophies. With regard to the volume of the tongue, the loss of musculature is mainly compensated by fatty tissue, so that form and volume of the tongue are largely preserved in high age. Histology of the Lingual Glands The changes depicted in Table II show that metaplasias in a sense of atrophy of the glandular parenchyma with fatty and fibrous replacement of the posterior serous Ebner's glands and of the sero-mucous anterior lingual gland (Nuhn) are stronger and present earlier than those
90 . R. Bassler
o-
19 y.
20 - 39 y.
40 - 59 y.
60 - 90 y.
Fig. 3. Age-related lipomatous atrophy of the tongue (woman, aged 53). a) Septum linguae with symmetrical lipomatosis. b) Musculature of the tongue with lipomatosis and focal fibrosis. Muscular fascicles of different calibre; focal a lowgrade fascicular atrophy. Form., Paraffin, HE; Magn. 120 x
Fig. 4. Degree and localisation of age-dependent lipomatous atrophy of the tongue. Black hatching shows content of fatty tissue in sites of predilection and increase with age.
Table 2. Qualitative histological changes of the lingual glands in age-related atrophy and types of neurogenic atrophy
1.-30. yrs ,~
...U
....:
..I:l
ti::l
0 u I':
....: til
S 0
,&
1. Posterior lingual gland (Ebner) 2. Anterior lingual gland (Nuhn) 3. Mucous glands of the root (Weber)
31.-60. yrs
... en 0
OJ
~
....: til
S 0
0-
61.-90. yrs
....: u
....:
...
....: u
~
Ci
0 u I':
0
-
+
(+) ++
,~
en 0
..I:l
(l)
::l
~
....: u
....:
...
....: u
~
Ci
0 u I':
++
++
....: til
S 0
J
,~
en 0
..I:l
OJ
::l
.....l
~
Ci
0
;J
-
-
-
-
(+)
-
-
-
-
++ +
+
(+) +++ +++ ++
-
-
-
-
+
(+) (+)
"'
-
-
i>U
0
Myasthenia gravis (62 yrs) ....: ....: u til i>,~ OJ U S 0en 0
...
0 0-
;J
... ..I:l ~
+++ ++ ++ ++
+++ (+)
ti::l
(+)
(l)
Ci
0
J
-
-
++ ++ + -
u I':
Hypoglossus Paresis (63 yrs) ....: ....: ....: U til i>,~ U en S 0 ...0 ....:u u0
-
..I:l
::l
I':
Ci
0
+++ (+)
-
-
+
++
+
++ ++
-
++
+
++
~
-
Atrophy of the Human Tongue· 91
of the mucous glands and of the root of the tongue. Surrounded by focal duct ectasias, they remain largely unchanged up to the 7th/8th decade of life. The focal and low-grade lipomatosis of the younger age group increases in the 5th and 6th decade and is connected with an increasing atrophy of the serous acini. In neurogenic muscular atrophies the anterior lingual gland (Nuhn) and the posterior Ebner's glands show the most significant changes of atrophy, lipomatosis and fibrosis; in the case of myasthenia gravis in a age-related level but in the case of hypoglossus paresis in a high grade of lipomatosis and atrophy (Fig. 9). Neurogenic Muscular Atrophy of the Tongue in Myasthenia Gravis Case Report (short Version)
We report on a 62-year-old woman who for some years had been suffering from increasing tiring, dysphasia and disturbances of speech. In 1984 and 1985 she received repeated stationary treatment for bulbar symptoms, dysarthria and disturbed innervation of the soft palate, and atrophy of the tongue. Weak proximal pareses occurred in the upper and lower extremities. Liquor: IgG 1,580 mg%. EMG: significant 30% decrease of amplitude: Tensilon test positive. CT of the mediastinum: no tumor, but signs of thymus hyperplasia. Neurologic diagnosis: myasthenia gravis. Therapy led to improvements as far as tiring and dysarthria were concerned. November 1985: aspiration pneumonia. Exitus.
Tongue
Macroscopically, the tongue is reduced in size, measuring 9 X 5 X 2 cm, its consistency being flabby and soft, its color grey-yellow, especially in both margins. The surface is laterally flattened and smooth, in the middle there is an elongated area with preserved, partly coarsened papillae. There is a trough-shaped, flat depression. Fronto-dorsal sections reveal high-grade atrophy of the musculature on both sides and large deposits of fatty tissue, predominantly in marginal parts (Fig. 2 b). Under the median sulcus and in the area of the septum linguae the musculature is preserved rather well (vertical, transverse, and partly the longitudinal superior muscles). Thin fascicles of the genioglossus muscle can be observed in the basal part. As the hypoglossus and the styloglossus muscle, this muscle is atrophic and contains a great amount of interstitial fatty tissue. At the surface, this fatty tissue permeates the aponeurosis linguae, and has proceeded laterally and on the base of the tongue below the epithelial membrane (Fig. 10).
Autopsy (no. 42185)
Myasthenia gravis with neurogenic lipoIl}atous atrophy of the tongue and inferior constrictor muscle of the pharynx. Segmental fibrous atrophy and focal lymphorrhagia of the pectoralis major, sartorius and iliopsoates muscles. Lymphofollicular hyperplasia of the thymus with infiltration of plasma cells and mast cells (autoimmune thymitis) *. Performed tracheotomy with long-term ventilation. Aspiration pneumonia. Cardiac muscle of both ventricles without pathological changes. Neuropathologic Findings
No significant changes in cerebrum and cerebellum, i.e. no signs of meningitis or encephalitis, no necroses, no hemorrhages. Serial sections through medulla oblongata and medulla spinalis cervicalis yielded minimal lacks of single ganglion cells, but neither necroses nor cysts. Nucleus of n. hypoglossus with many well-preserved ganglion cells in symmetrical arrangement, without myelomalacia or inflammatory changes. Segments of the median and lower cervical part of the medulla without pathologic changes * * . ~
* * * Special thanks to Prof. Dr. OttolHeidelberg and Prof. Dr.
Schroder/Aachen for their kind support and expert advice.
Fig. 5. Myasthenic atrophy of the tongue with severe lipomatosis. Few large muscular fascicles preserved; next to them grouped fibre atrophies with focal and septal fibroses (no. 241/ 84). Form., Paraffin, HE; Magn. 120 X
92 . R. Bassler
Histopathology
Comparison of the different regions of the tongue reveals extent and progression of the muscular atrophy and lipomatosis. Only few, mainly central regions of the inner musculature show regular fascicles. Their texture appears looser at the margin due to lower fibre calibres, increase in reticular and collagenous connective tissue and a strong increase in fatty tissue. The intensity of fibromatosis and lipomatosis correlates with the degree of muscular atrophy: the more pronounced the muscular atrophy, the more intense are fibromatosis as well as lipomatosis. The fatty tissue contains numerous well-preserved peripheral nerves. Inflammatory reactions are missing (Fig. 5 and lOb). The musculature of the meso- and hypopharynx shows strong and progressive muscular atrophy with fibrosis and lipomatosis (Fig. 6), fully corresponding to the transformations of the muscles of the tongue itself. Epicrisis
In the course of the next years, the 62-year-old woman had developed an initially unclear clinical picture with
symptoms of bulbar paralysis, which proved to be a manifestation of myasthenia gravis. The autopsy findings with lymphofollicular thymus hyperplasia and lymphorrhagias in the skeletal musculature confirmed this diagnosis. In different skeletal muscles, myasthenia gravis led to focal, mainly low-grade neurogenic atrophies and to an unusually strong muscular atrophy of the tongue and of the pharynx. Neurogenic Atrophy of the Tongue Following Poliomyelitis Case Report (short version)
17-year-old girl, ill with poliomyelitis since the age of five. Since that time, i.e. for twelve years, she had been living in the so-called "iron lung". She died in 1964 from respiratory insufficiency. Autopsy (no. 890164 MZ)
Late stage of a poliomyelitis with extended loss of motor neurons in the cervical, thoracic and lumbal regions of the spinal cord, partly in the medulla oblongata. Highgrade atrophy of the total skeletal musculature. Disuse atrophy of the complete bone system with paper-thin compacta of the long bones. Infantile genitals. Tongue: Size and form corresponding to the age of the patient. Transverse sections revealed a marked content of fatty tissue. Histologically, atrophy of the musculature with formation of small groups of fibres, with fibrosis of the perimysium and lipomatosis. Epicrisis
The girl who died at the age of 17 was suffering from the sequels to a severe poliomyelitis with paralysis of the respiratory musculature. She had been living in the "iron lung" for 12 years. Skeletal musculature and tongue showed a high-grade muscular atrophy and an extended fatty replacement. Hemiatrophy of the Tongue Following Traumatic Hypoglossus Paresis Case Report (shc/rt version):
Fig. 6. Musculature of the hypopharynx in myasthenic atrophy with signs of progressive transformation of the muscles with fibrosis and focal lipomatosis. Focally preserved muscular fascicles. (no. 241/84)." Form., Paraffin, HE; Magn. 120 x
63-year-old woman. For several years suffering from chronic renal insufficiency, hypertension and cardiac insufficiency. In 1955 head traume with loss of the right eye in a domestic quarrel. In 1969 strumectomy. For a number of years swelling of the soft parts of the right part of the neck, the cause of which could not be clarified. Paresthesias occurred in the perioral region and in the region of the fingers. No signs of tongue paresis, no hemiatrophy of the face. Autopsy (no. 302184)
Chronic glomerulonephritis with performed hemodialysis. Sepsis. Bacterial endocarditis.
Atrophy of the Human Tongue . 93 Neuropathologic Examination Cerebrum and cerebellum without pathologic changes. Medulla oblongata and nuclei of hypoglossus nerve were not systematically examined, because the true extent of the changes of the tongue was only discovered later. During preparation of the n. hypoglossus of the tongue, a regular nerve was detected on the left side, on the right side the n. hypoglossus could not be assessed. There were only thin filaments at the dorso-Iateral margin of the tongue, which were surrounded by connective tissue. Tongue: Macroscopically of normal size (9,5 X 6 X 2,5 cm). Asymmetrical form because of low-grade flattening of the right margin with grey-yellow coloring. Regular structure of the surface with small deep longitudinal furrows. Papillae in regular arrangement. Fronto-dorsal transverse sections in the right half reveal a replacement of muscles by yellow fatty tissue reaching up to the tip of the tongue. The septum provides a sharp s-like limitation to the left side (Fig. 2 c). At the tip the fatty tissue is 2 cm of breadth, in the middle 2,5 -3 cm, reaching from the surface to the lower side (Fig. 10 c). Histopathology The left half of the tongue shows a regular musculature with minor age-related lipomatosis. Instead of musculature the right half contains homogeneous univacuolar fatty tissue from the aponeurosis up to the lateral margin and the lower side (Fig. 7). The border between both halfs of the tongue is formed by the septum linguae. Fascicles of the verticalis and transverse muscle under the aponeurosis are partly
"r'--> "~+r--"t
IfJ::- "
t ,,',
.">l ,;
'-~.4..4SJ~
,
-----
Fig. 8. Lipomatous hemiatrophy in hypoglossus paresis with few preserved isomorphous groups of muscular fascicles, surrounded by connective tissue. Form., Paraffin, HE; Magn. 120 x preserved in the right half, too. The residual musculature with preserved transverse striation forms small groups of fibres between the fat cells. These fibres are surrounded by connective tissue (Fig. 8). In the new-formed fatty tissue reticular fibroses can be seen laterally and above all caudally. There are also rich deposits of peripheral nerve trunks and blood vessels. The aponeurosis in the right half is full of fat cells and reduced in breadth. For the behaviour of the lingual glands d. Tab. II and Fig. 9. Epicrisis
Fig. 7. Lipomatous hemiatrophy in hypoglossus paresis. Severe lipomatosis of the aponeurosis linguae. Preserved scattered muscular fascicles with high-grade atrophy. Form., Paraffin, HE; Magn. 120 x
The 63-year-old woman died from sepsis and chronic renal and cardiac insufficiency. Underlying sepsis was chronic glomerulonephritis and hemodialysis. The lipomatous hemiatrophy on the right side of the tongue, detected at autopsy, was a sequel to a peripheral extracranial and traumatic hypoglossus paresis. After a cranial trauma the patient had lost her right eye in 1955. This cranial trauma had been connected with damage of the n. hypoglossus. At autopsy no residues of a fracture of the base of the skull were found.
94 . R. Bassler
a
Fig. 9. Qualitative changes of the lingual glands in hemiatrophy due to hypoglossus paresis. a) Root of the tongue with the well preserved mucous gland and the marked atrophy and lipomatosis of the posterior serous glands (Ebner). b) Anterior lingual gland (Nuhn) with atrophy, fibrosis and a marked lipomatosis of the stroma. Duct ectasias in a field on the upper margin. Form., Paraffin, HE; Magn. 60 x, 120 x
Discussion The transverse section through the root of the tongue, demanded at each autopsy, primarily aims at detecting developmental disturbances of the thyroid gland in the region of the foramen caecum 1, 13. In general, no attention is paid to the behaviour of the tissue of the muscular body of the tongue, often affected by atrophy or lipomatosis related either with age or with neurogenic diseases. In addition to previous investigations on age-related changes of the musculature of the tongue!, three typical forms of atrophy of the tongue are here described. The clinical aspects of this kind of atrophy have already been discussed in some detail elsewhere3, 14, 19, whereas histopathologic investigations concerned with this organ with the exception of two specimens of partial amputations in myasthenia gravis S - have not been presented so far.
Age-related Atrophy of the Tongue
The morphometric studies and the statistical data published in 1971 1 reveal a definitely linear relation between age and degree of lipomatosis. From this follows a slow increase in fatty tissue up to the 3 rd/4th decade, later followed by a more marked increase up to the 80th year of life. As far as the course of the curves is concerned, the examined regions of the tongue are very similar. Therefore, these general rules can be used for a forensic determination of age. Lipomatosis of the tongue in neurogenic atrophies exceeds the age-related measurements by two to three times higher values (Fig. 1). With regard to its texture and the manifold coordinated movements in speaking, eating, drinking and swallowing, the tongue has a special place among the skeletal muscles. This can be seen from the fact that even in age-related
Atrophy of the Human Tongue· 95
atrophy and lipomatosis there are only low-grade disturbances of function, although a loss of energetic output attributable to a loss of muscular mass can be expected. According to Patel et al. 17 it is remarkable that there is no disuse atrophy even after months of coma during which the tongue had been largely immobilised. Neurogenic Myasthenic Atrophy of the Tongue
Clinical examination in our first case indicated myasthenia gravis type II according to Osserman 16. A progressive bulbar-paralytic complex of symptoms with minor pareses of the proximal musculature of the extremities was prominent. Histopathologic investigations following autopsy revealed a high-grade atrophy of the tongue and of the musculature of the pharynx correlative to the bulbar paralysis; in addition, there were fascicular neurogenic atrophies in some skeletal muscles. These atrophies were connected with lymphorrhagia as well as with lymphofollicular thymus hyperplasia. Neuropathologic examinations especially of the medulla oblongata and of the spinal cord, however, did not · indicate any changes which might explain these atrophies. In the nucleus n. hypoglossi there were no necroses, the ganglion cells were of regular structure. Therefore, diagnosis of myasthenia gravis with exceptional neurogenic muscle atrophies was confirmed. The muscular atrophies interpreted in the literature as myasthenic myopathy or as neuro-muscular diseases can be observed in 6-10% of cases according to Oosterhuis and Bethlem l5 and Oosterhuisl 4. According to Schimrick and Samland20 the frequency of latent muscular atrophies is significantly higher. The proximal musculature - as in the case described - is preferentially affected. Atrophies of the tongue in myasthenia, which were first pointed to by Buzzard6 in 1905, occur isolated or in combination with atrophies of the musculature of the pharyrtx and of the face in 4% of cases l4 . In this, the tongue is reduced in size, flattened and flabby showing an asymmetrical surface. The histopathology of this especially marked atrophy of the tongue and lipomatosis has only been described for two specimens of the tongue following amputation by Brownell and coworkers in 19725. These preparations, examined in transverse sections, correspond to our own investigations. The latero-basal regions show the strongest degree of atrophy and lipomatosis, the central parts contain fascicles of the inner muscles (Fig. 10 b). Numerous large peripheral nerves without pathologic changes can be found in the fatty tissue. The different degrees of muscular atrophy depicted in Figs. 5 and 6 point to the progression of the disease. The constrictor pharyngis muscle, too, is involved in this atrophy. As compared to the tongue, the atrophy is not so strong, but progressive, and it shows focal lipomatous metaplasias. Following own investigations Tyle~4 in 1982 raised the question whether this might not merely be a myasthenic symptom in a Illotor neuron disease which in its early stages usually afb.:ts the tongue and the pharynx. As the case described shows no evident loss of the ganglion cells in medulla oblongata and spinalis, and as the histopathologic changes clearly point
to myasthenia gravis, such a primary motor neuron disease is not probable. The depicted atrophies of skeletal muscles are localized in the preferential regions of myasthenic disturbances of function. They explain the bulbar-paralytic symptoms as well as the pareses of the proximal musculature of the extremities. The pattern of distribution of fascicular atrophy is considered as the result of a denervation of the skeletal muscles ll , 15,22. Underlying this denervation are degenerative changes of the motor end-plates, mainly in the region of the postsynaptic membranes. This has been confirmed by enzymehistochemical investigations by EngelS and Brody and Engel4 , according to whom advanced denervations occur only in the late stages of myasthenia gravis. Silver stainings yielded irregular proliferations of terminal nerve fibres in the atrophic skeletal musculature, which by Brownell et aU are considerd as an expression of the nerve's compensation behaviour aiming at repair of the neuromuscular transmitter function. Therefore, muscular atrophies in myasthenia gravis are neither a disuse atrophy nor a myopathy in the strict sense, but an expression of a peripheral neurogenic manifestation of this denervating disease. Atrophy of the Tongue Following Poliomyelitis
Following poliomyelitis with paralysis of the diaphragm which the patient had been ill with at child's age, she had been treated for 12 years in the so-called "iron lung". As a consequence, high-grade disuse atrophy of the skeletal musculature and of the bone system had developed. The tongue showed marked muscular atrophy and lipomatosis, which has to be interpreted as an expression of a combined neurogenic and disuse atrophy. This can be explained by the fact that the patient had been living in isolation for years, during which she had lost contact and motility. These observations mal be in contrast to the opinion of Patel and coworkers I , they can be explained, however, by the extreme situation of a late stage of poliomyelitis. Lipomatous Hemiatrophy of the Tongue in Hypoglossus Paresis
As compared to the numerous studies on causes, forms and symptoms of glossoplegia, the pathomorphology of a hemiatrophy of the human tongue with an extended fatty replacement has not been dealt with in the available literature starting from 1899 23 • This applies especially to the clinically known forms of hypoglossus paresis and to the rare cases of facial hemiatrophy, which can be connected with a unilateral atrophy of the tongue9 • In our third case, a unilateral lipomatosis of the root of the tongue was detected at autopsy. Form and volume of the tongue did not seem conspicuous. Further preparation, however, revealed a homogeneous, extended unilateral lipomatosis with septal fibrosis (Fig. 2 c and 10 c) and inclusion of small single groups of bundles of muscle fibres (Fig. 8); this lipomatosis reached from the tip to the root of the tongue and includes the stroma of the lingual glands
96 . R. Bassler
(Fig. 2 c). Diameters of the single muscle fibres differed only slightly. The lipomatosis involved the complete aponeurosis, so that the fatty tissue there extended to the epithelial membrane, which explaines the yellow coloring of the surface on the right half of the tongue. According to the histopathologic results there was a long-term, almost total hemiatrophy of the musculature of
the tongue in the innervation area of the n. hypoglossus dexter. The sharp limitations of the fatty tissue and the few included isomorphic bundles of muscle fibres indicate that atrophy and metaplasia have to be considered as a finished and resting process (Fig. 10 c). As compared to the left side, the n. hypoglossus dexter could not be detected in the specimen. Instead, there was a
b
Fig. 10. Gross sections through median part of the tongue depicting the physiological, age-dependent lipomatosis and the neurogenic atrophies: a) Normal degree of lipomatosis (no. 15/86; 53-year-old woman. b) Myasthenic atrophy with large fatty deposits in the lateral and basal parts with preserved inner musculature in the middle (no. 241/84; 62-year-old woman. c) Hemiatrophy of the right side with low-grade deformation of the tongue and severe pseudo-hypertrophy of fatty tissue to the lower side of the epithelial layer. Physiological lipomatosis of the musculature of the left half (no. 302/84; 63year-old woman). Magn.2 X
Atrophy of the Human Tongue· 97
connective tissue with few, thin fibres between the hypoglossus muscle and the root of the tongue, the fibres corresponding to markedly atrophic nerves. Accordingly, these must be the result of an extracranial peripheral damage of the n. hypoglossus. As the patient had suffeteda cranial trauma with loss of the right eye some 29 years ago, it can be concluded that the hemiatrophy of the tongue is the sequel of a peripheral traumatic hypoglossus paresis. The depicted patterns and grades of atrophy and lipomatosis point to the enormous ability of functional compensation of this organ, even if large parts of specific texture are lost. References 1 Bassler R, Bilden J, Lange JH (1971) Alternsveranderungen der menschlichen Zunge. Act Gerontol 1: 29-44 2 Baker RD (1967) Postmortem Examination: Specific Methods and Procedures. WB Saunders Cp, London - Philadelphia - Toronto 3 Bodechtel H (Ed) (1963) Differentialdiagnose neurologischer Krankheitsbilder. 2. Auf!. Georg Thieme, Stuttgart 4 Brody WA, Engel WK (1964) Denervation of muscle in myasthenia gravis. Arch Neurolll: 350-354 5 Brownell B, Oppenheimer DR, Spalding JMK (1972) Neurogenic muscle atrophy in myasthenia gravis. J Neurol Neurosurg Psychiatr 35: 311-322 6 Buzzard EF (1905) The clinical history and post-mortem examination of five cases af myasthenia gravis. Brain 28: 538-583 7 Dockerty MB, Parkhill EM, Dahlin DC, Woolner LB, Soule EH, Harrison EG (1968) Tumors of the oralcavity and pharynx. Atlas of Tumor Pathology, Sect IV, Fasc 10 b. Armed Forces Institute of Pathology, WashingtonlDC 8 Engel WK (1962) Essentiality of histo- and cytochemical studies of skeletal muscle in investigation of neuromuscular diseases. Neurology 12: 778-794
9 Gagel 0 (1953) Die Erkrankungen des vegetativen Systems. In: Bergmann G v, Frey W, Schwiegk H (Eds) Handbuch der Inneren Medizin. Bd. Y, 2. Teil (Neurologie), pp. 877-880. Springer, Berlin - Gottingen - Heidelberg 10 Lucas RB (1984) Pathology of Tumors of the Oral Tissue. Churchill Livingstone, Edinburgh - London - New York 11 McDermot C (1960) The changes in the motor end plate in myasthenia gravis. Brain 83: 24-36 12 Morgenroth K (1984) Mundhohle, Zahne, Kiefer, Waldeyer-Rachenring, Oro- und Hypopharynx. In: Remmele R Pathologie II, pp. 3-84. Springer, Berlin - Heidelber - New York - Tokyo f 1 Nauwerk C (1921) Sektionstechnik fur Studierende und Arzte. 6. Auf!. G. Fischer, Jena 14 Oosterhuis HS (1984) Myasthenia gravis. Churchill Livingstone, Edinburgh - London - Melbourne - New York 15 Oosterhuis HS, Bethelm J (1973) Neurogenic Muscle Involvement in myasthenia gravis. A clinical and histopathological study. J Neurol Neurosurg Psychiatr 36: 244-254 16 Ossermann KE (1958 ) Myasthenia gravis. Grune & Stratton New York 11 Patel AN, Razzak ZA, Dastur DK (1969) Disuse atrophy of human skeletal muscles. Arch Neurol 20: 413-421 18 Pindborg JJ (1969) Atlas der Erkrankungen der Mundschleimhaut. C. Hanser, Miinchen 19 Scheid W (1980) Lehrbuch der Neurologie. 4. Auf!., Georg Thieme, Stuttgart 20 Schimrigk K, Samland 0 (1977) Muskelatrophien bei Mrasthenia gravis. Nervenarzt 48: 65-68 1 Seifert G (1966) Mundhohle, Mundspeicheldriisen, Tonsillen und Rachen. In: Spezielle pathologische Anatomie. Bd. l. Springer, Berlin - Heidelberg - New York 22 Steidl RM, Oswald AJ, Kottke FJ (1962) Myasthenia syndrome with associated neuropathy. Arch Neurol 6: 451-461 23 Tyler HR (1982) Nonfamilial amyotrophy with dementia or multisystem degeneration and other neurological disorders. In: Rowland LP (Ed) Human Motor Neuron Diseases. Raven Pr., New York 24 Wiersman E (1899) faile von Hemiatrophia linguae. Neurol Zb118: 818- 829
Received July 9, 1986 . Accepted in revised form September 9, 1986
Key works: Tongue - Age-related atrophy - Neurogenic atrophy in myasthenia gravis - Poliomyelitis - Hemiatrophy due to hypoglossus paresis Prof. Dr. R. Bassler, Pathologisches Institut, Stadtische Kliniken, Pacelliallee 4, D-6400 Fulda, FRG