Oncology 36 : 19-22 (1979)
C Cell Adenoma of the Human Thyroid Gland Miroslaw Beskid Laboratory of Histochemistry, Department of Pathophysiology, Centre of Postgraduate Medical Education, Warsaw
Key Words. Thyroid C cells • Thyroid C cell nodule • Thyroid C cell adenoma • C cell nodule
Introduction C cells are a normal component of the thyroid gland in man. Studies of their pathology have been almost exclusively restricted to C cell carcinoma and there are numerous papers describing its pathological and hor monal properties. Owing to the fact that, so far, few reports deal with C cell adenoma, the presentation of the clinical and pathological features of such a case seems relevant.
Case Report Female patient aged 47. In February 1970 the pa tient underwent a surgical intervention. The left lobe of the thyroid was excised as there was swelling and deformation of the upper pole of the lobe. The above pathological symptoms appeared when the patient was 13 and persisted for 34 years. The swelling and deforma tion were but slight at the beginning but progressed steadily. The progress was specially marked after a confinement (the patient had had three deliveries). For the last 2 years the patient suffered from diarrhea. The diarrhea occurred irregularly, irrespective of diet and most often after a stress. In the course of the examination a nodule was found within the site of swelling and deformation of the upper lobe of the thyroid, which was found to be ‘cold’ on
scintillography. Clinical observation reported the reces sion of diarrhea symptoms after surgical excision of the deformed lobe. Control examinations stated that in the course of 8 years after excision (February 1970 tc February 1977) no metastases or recurrence occurred. Macroscopic study revealed within the deformed thyroid pole a nodule of about 4 cm in diameter. It was surrounded by a thick hyaline capsule. The nodule tissue was solid, yellowish in color and sharply outlined against the surrounding thyroid tissue. The specimen tissue was examined both unfixed and fixed in Baker’s fluid at 4°C, and glutaraldehydepicric/acetic acid (GPA) after Solcia et al. [14], The unfixed sections were examined for a-glycerophosphate menadione reductase after Wattenberg and Leong [15], and for monoamine oxidase (MAO) according to Glenner et al. [8]. Sections fixed in GPA were stained by the method of Solcia et al. [14] using HC1metachromatic procedure with toluidine blue and lead hematoxylin; presence of amyloid was detected by Congo red staining of sections fixed in Baker’s fluid; the presence of fats was observed in sections, using oil red O. Standard sections were stained with hematoxylin and eosin. For electron microscopic studies, samples of the nodule tissue were placed in 2.5 % glutaraldehyde, minc ed into tiny pieces and fixed for 2 h in 2.5% glutaralde hyde at 4°C. The material was postosmicated in 1% 0 s 0 4. After the tissue had been washed in buffer, it
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Abstract. A case of C cell thyroid adenoma in a 47-year-old female patient is described. The nodule showed progression over 34 years. The adenoma cells showed histochemical and ultrastructural properties characteristic for C cells. Histologic examination revealed no atypical features of nodule cells nor infiltration of capsule by neo plastic cells. In the period of 8 years following the excision there was neither recurrence nor métastasés.
Beskid
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Fig. 5. C cell thyroid adenoma. Portion of C cells of the adenoma tissue. Pale cells with dark secretory granules. Zone of Golgi apparatus well developed, x 20.000. 4
Fig. I. C cell thyroid adenoma. Alveolar structures of the adenoma tissue. HE. x 120. Fig. 2. C cell thyroid adenoma. Alveolar structures and solid nests. HE. x 120. Fig. 3. C cell thyroid adenoma. Light form of C cell in part of the adenoma tissue. HE. x 120. F'ig. 4. C cell thyroid adenoma. Mctachromatie reaction after Solcia cl al. 114] with toluidine blue, x 120.
was processed through graded ethanol and propylene oxide and then embedded in Epon 812. Sections of 0.5 ,«m were stained with toluidine blue and examined under the light microscope. Ultrathin sections from the selected areas were cut off and stained with uranyl acetate and lead citrate. The sections were then studied in a JEM 7A microscope.
Histologically, the nodule proved to be encapsulated, composed of alveolar structures (fig. 1) and small solid nests (fig. 2) of cells separated by numerous broad collagenous, hyaline stromal tissue. The nodule cells were either spherical or cuboidal. The nulei were round located centrally and usually rich in chromatin. The cytoplasm of some cells was granular (fig. 2) of others light and foamy (fig. 3). In the light cell cytoplasm the presence of fats was detected. Histologically, no atypical signs and no infiltration of the capsule by the nodule cells were observed. Histochemically, the nodule cells were marked by a strong reaction of «-glycerophosphate menadione reductase and MAO activity. Marked metachromasia reaction was strong in some cells and hardly evident in others (fig. 4). Lead hematoxylin staining was weak. The staining for amyloid in tissue was nega tive.
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C Cell Adenoma of the Human Thyroid Gland
a distinct cellular membrane which formed intercellular spaces, many of them showing microvillous projections between the neighboring cells (fig. 5, 6).
Fig. 6. C cell thyroid adenoma. Portion of C cells of the adenoma tissue. A number of microfilaments and singly situated dark secretory granules, x 16.000.
In the electron microscopic image the central part of the cell was occupied by an oval but more often irregularly shaped nucleus. The cytoplasm matrix was light in appearance. The rough endoplasmic reticulum was well developed. The smooth endoplasmic reticulum was as a rule poorly represented. Among the structures of the endoplasmic reticulum, agglomerations of ribo somes and polysomes could be observed. In some of the cells the Golgi zone was well developed. In various parts of the cytoplasm membrane-limited dark secretory granules appeared either singly or in small clusters. Occasionally, in some cells fine microfilaments could be observed. Small quantities of mitochondria were also present in some particular cells. They varied in size and shape as well as in electron density of the matrix. In various parts of the cytoplasm lipid droplets of different size were observed. All the cells possessed
Human pathology of C cells manifests itself by hyper plasia, presence of adenoma and carcinoma. Hyper plasia presents either a primary [2] or a secondary [4] form. The presence of the C cell adenoma in human thyroid gland was demonstrated on the basis of cytochemical methods [1] and an assay of calcitonin content [ 11]. The described findings have demonstrated that the thyroid nodule, development of which lasted for 34 years, is a C cell adenoma. The nodule was found to lie within a capsule, similarly to a true adenoma. The nodule pattern did not show malignancy, alveolar struc tures and solid nests were composed of cells which did not show any atypic signs, moreover there was no infiltration of the nodule capsule by neoplastic cells. Clinically in the course of 8 years after the excision of the nodule, during follow-up control examinations no metastases or recurrence were found. The presence of C cells in the nodule is evidenced by histochemical properties characteristic of C cells as well as by the electron microscopic image. The cells of the nodule were marked by the presence of histo chemical reactions, which are usually considered as characteristic of C cells, namely the metachromatic reaction [13, 14], a-glycerophosphate menadione re ductase [3, 13] and MAO activities [1, 3, 7, 10, 13]. Ultrastructurally, the cells of the nodule were similar to the C cells of a normal thyroid gland [5, 6], to that of C cell hyperplasia [2, 4], and to that of cells of some form of C cell carcinoma [3, 9, 12, 13]. On the other hand it has been demonstrated that C cells of thyroid gland have the ability to metabolize biogenic amines [3, 7, 10, 13] or their precursors [7, 10, 13]. These facts can be associated with the diarrhea mentioned in this case, and which receded after the excision of the nodule. Calcitonin was isolated according to a method pre viously described [11], Bioassay procedure established the calcitonin content in the case of C cell adenoma as 36 MRC per gram of wet tissue weight [11]. The calcitonin content was about 90 times higher than in the cases of simple goiter and about 600 times higher when compared with the case of thyrotoxicosis.
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Discussion
Bcskid
References 1 Bcskid. M.: I.orenc, R.. and Rosciszewska, A.: C cell thyroid adenoma in man. J. Path. Bact. 103: 1—4 (1971). 2 Beskid. M.: Primary C cell hyperplasia within a nodule of thyroid isthmus. Oncology 32: 11-20 (1975). 3 Beskid, M.; Dabska, M.; Kfos. H.. and Majdecki, T.: Histochemical features of C cell thyroid carcinoma. Acta histochcm. 58: 210-218 (1977). 4 Beskid. M.; Hartwig, W.; Nielubowicz, J., and Tolloczko, T.: Thyroid C cells in primary hyperparathyroidism. Acta histochcm. 59: 70-78 (1977). 5 Braunstcin, H. and Stephens, C.L.: Parafollicular cells of human thyroid. Archs Path. 86: 659-666 (1968). 6 Chan, A.S. and Conen, P. E.: Ultrastructural observations on cytodifferentiation of parafollicular cells in the human fetal thyroid. Lab. Invest. 25: 249-259 (1971). 7 Englund. N. E .; Nilsson, G.; Owman. C., and Sundlcr, F.: Human thyroid C cells: occurrence and amine formation studied by per fusion of surgically removed goitrous gland. J. clin. Endocr. Metab. 35: 90-96 (1972). 8 Glenner. G. G.; Burtncr, H. J.. and Brown. G. W.: The histochemi cal demonstration of monoamine oxidase activity by tetrazolium salts. J. Histochcm. Cytochem. 5: 591-600 (1957). 9 Horvath, E.; Kovacs, K.. and Ross, R.C.: Medullary cancer of the thyroid gland and its possible relations to carcinoids. Virchows Arch. path. Anat. Physiol., Scr. A 356: 281-292 (1972).
10 Larson, B.; Owman, C„ and Sundler, F.: Monoamincrgic mecha nism in parafollicular cells of the mouse thyroid gland. Endo crinology 78: 1109-1114 (1966). 11 Lorenc. R. and Beskid, M.: Assay of C cell thyroid adenoma of man for calcitonin activity. Acta histochcm. 43: 1-7 (1972). 12 Meyer, J.S. and Abdcl-Bari, W.: Granules and thyrocalcitoninlike activity in medullary carcinoma of the thyroid gland. New Engl. J. Med. 278: 523-529 (1968). 13 Pearsc, A .G.E.: The cytochemistry and ultrastructure of poly peptide hormone producing cells of the APUD scries and the embryologie, physiologic and pathologic implications of the con cept. J. Histochem. Cytochem. 17: 303-313 (1969). 14 Solcia, E.; Vassallo, G., and Capclla, C.: Selective staining of endocrine cells by basic dyes after acid hydrolysis. Stain Technol. 43: 257-263 (1968). 15 Wattenberg, W. and Leong, J.L.: Effects of coenzyme Q 10 and menadione on succinic dehydrogenase activity as measured by tetrazolium salt reduction. J Histochem. Cytochem. 8: 288-292 (1965).
M. Beskid, Assistant Professor. Ml). DSc, Laboratory of Histochemistry. Center of Postgraduate Medical Education. Marmoncka 99, 01-813 Warsaw (Poland)
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C Cell Adenoma of the Human Thyroid Gland Miroslaw Beskid Laboratory of Histochemistry, Department of Pathophysiology, Centre of Postgraduate Medical Education, Warsaw
Key Words. Thyroid C cells • Thyroid C cell nodule • Thyroid C cell adenoma • C cell nodule
Introduction C cells are a normal component of the thyroid gland in man. Studies of their pathology have been almost exclusively restricted to C cell carcinoma and there are numerous papers describing its pathological and hor monal properties. Owing to the fact that, so far, few reports deal with C cell adenoma, the presentation of the clinical and pathological features of such a case seems relevant.
Case Report Female patient aged 47. In February 1970 the pa tient underwent a surgical intervention. The left lobe of the thyroid was excised as there was swelling and deformation of the upper pole of the lobe. The above pathological symptoms appeared when the patient was 13 and persisted for 34 years. The swelling and deforma tion were but slight at the beginning but progressed steadily. The progress was specially marked after a confinement (the patient had had three deliveries). For the last 2 years the patient suffered from diarrhea. The diarrhea occurred irregularly, irrespective of diet and most often after a stress. In the course of the examination a nodule was found within the site of swelling and deformation of the upper lobe of the thyroid, which was found to be ‘cold’ on
scintillography. Clinical observation reported the reces sion of diarrhea symptoms after surgical excision of the deformed lobe. Control examinations stated that in the course of 8 years after excision (February 1970 tc February 1977) no metastases or recurrence occurred. Macroscopic study revealed within the deformed thyroid pole a nodule of about 4 cm in diameter. It was surrounded by a thick hyaline capsule. The nodule tissue was solid, yellowish in color and sharply outlined against the surrounding thyroid tissue. The specimen tissue was examined both unfixed and fixed in Baker’s fluid at 4°C, and glutaraldehydepicric/acetic acid (GPA) after Solcia et al. [14], The unfixed sections were examined for a-glycerophosphate menadione reductase after Wattenberg and Leong [15], and for monoamine oxidase (MAO) according to Glenner et al. [8]. Sections fixed in GPA were stained by the method of Solcia et al. [14] using HC1metachromatic procedure with toluidine blue and lead hematoxylin; presence of amyloid was detected by Congo red staining of sections fixed in Baker’s fluid; the presence of fats was observed in sections, using oil red O. Standard sections were stained with hematoxylin and eosin. For electron microscopic studies, samples of the nodule tissue were placed in 2.5 % glutaraldehyde, minc ed into tiny pieces and fixed for 2 h in 2.5% glutaralde hyde at 4°C. The material was postosmicated in 1% 0 s 0 4. After the tissue had been washed in buffer, it
Downloaded by: Nagoya University 133.6.82.173 - 1/11/2019 3:17:53 PM
Abstract. A case of C cell thyroid adenoma in a 47-year-old female patient is described. The nodule showed progression over 34 years. The adenoma cells showed histochemical and ultrastructural properties characteristic for C cells. Histologic examination revealed no atypical features of nodule cells nor infiltration of capsule by neo plastic cells. In the period of 8 years following the excision there was neither recurrence nor métastasés.
Beskid
20
Fig. 5. C cell thyroid adenoma. Portion of C cells of the adenoma tissue. Pale cells with dark secretory granules. Zone of Golgi apparatus well developed, x 20.000. 4
Fig. I. C cell thyroid adenoma. Alveolar structures of the adenoma tissue. HE. x 120. Fig. 2. C cell thyroid adenoma. Alveolar structures and solid nests. HE. x 120. Fig. 3. C cell thyroid adenoma. Light form of C cell in part of the adenoma tissue. HE. x 120. F'ig. 4. C cell thyroid adenoma. Mctachromatie reaction after Solcia cl al. 114] with toluidine blue, x 120.
was processed through graded ethanol and propylene oxide and then embedded in Epon 812. Sections of 0.5 ,«m were stained with toluidine blue and examined under the light microscope. Ultrathin sections from the selected areas were cut off and stained with uranyl acetate and lead citrate. The sections were then studied in a JEM 7A microscope.
Histologically, the nodule proved to be encapsulated, composed of alveolar structures (fig. 1) and small solid nests (fig. 2) of cells separated by numerous broad collagenous, hyaline stromal tissue. The nodule cells were either spherical or cuboidal. The nulei were round located centrally and usually rich in chromatin. The cytoplasm of some cells was granular (fig. 2) of others light and foamy (fig. 3). In the light cell cytoplasm the presence of fats was detected. Histologically, no atypical signs and no infiltration of the capsule by the nodule cells were observed. Histochemically, the nodule cells were marked by a strong reaction of «-glycerophosphate menadione reductase and MAO activity. Marked metachromasia reaction was strong in some cells and hardly evident in others (fig. 4). Lead hematoxylin staining was weak. The staining for amyloid in tissue was nega tive.
Downloaded by: Nagoya University 133.6.82.173 - 1/11/2019 3:17:53 PM
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C Cell Adenoma of the Human Thyroid Gland
a distinct cellular membrane which formed intercellular spaces, many of them showing microvillous projections between the neighboring cells (fig. 5, 6).
Fig. 6. C cell thyroid adenoma. Portion of C cells of the adenoma tissue. A number of microfilaments and singly situated dark secretory granules, x 16.000.
In the electron microscopic image the central part of the cell was occupied by an oval but more often irregularly shaped nucleus. The cytoplasm matrix was light in appearance. The rough endoplasmic reticulum was well developed. The smooth endoplasmic reticulum was as a rule poorly represented. Among the structures of the endoplasmic reticulum, agglomerations of ribo somes and polysomes could be observed. In some of the cells the Golgi zone was well developed. In various parts of the cytoplasm membrane-limited dark secretory granules appeared either singly or in small clusters. Occasionally, in some cells fine microfilaments could be observed. Small quantities of mitochondria were also present in some particular cells. They varied in size and shape as well as in electron density of the matrix. In various parts of the cytoplasm lipid droplets of different size were observed. All the cells possessed
Human pathology of C cells manifests itself by hyper plasia, presence of adenoma and carcinoma. Hyper plasia presents either a primary [2] or a secondary [4] form. The presence of the C cell adenoma in human thyroid gland was demonstrated on the basis of cytochemical methods [1] and an assay of calcitonin content [ 11]. The described findings have demonstrated that the thyroid nodule, development of which lasted for 34 years, is a C cell adenoma. The nodule was found to lie within a capsule, similarly to a true adenoma. The nodule pattern did not show malignancy, alveolar struc tures and solid nests were composed of cells which did not show any atypic signs, moreover there was no infiltration of the nodule capsule by neoplastic cells. Clinically in the course of 8 years after the excision of the nodule, during follow-up control examinations no metastases or recurrence were found. The presence of C cells in the nodule is evidenced by histochemical properties characteristic of C cells as well as by the electron microscopic image. The cells of the nodule were marked by the presence of histo chemical reactions, which are usually considered as characteristic of C cells, namely the metachromatic reaction [13, 14], a-glycerophosphate menadione re ductase [3, 13] and MAO activities [1, 3, 7, 10, 13]. Ultrastructurally, the cells of the nodule were similar to the C cells of a normal thyroid gland [5, 6], to that of C cell hyperplasia [2, 4], and to that of cells of some form of C cell carcinoma [3, 9, 12, 13]. On the other hand it has been demonstrated that C cells of thyroid gland have the ability to metabolize biogenic amines [3, 7, 10, 13] or their precursors [7, 10, 13]. These facts can be associated with the diarrhea mentioned in this case, and which receded after the excision of the nodule. Calcitonin was isolated according to a method pre viously described [11], Bioassay procedure established the calcitonin content in the case of C cell adenoma as 36 MRC per gram of wet tissue weight [11]. The calcitonin content was about 90 times higher than in the cases of simple goiter and about 600 times higher when compared with the case of thyrotoxicosis.
Downloaded by: Nagoya University 133.6.82.173 - 1/11/2019 3:17:53 PM
Discussion
Bcskid
References 1 Bcskid. M.: I.orenc, R.. and Rosciszewska, A.: C cell thyroid adenoma in man. J. Path. Bact. 103: 1—4 (1971). 2 Beskid. M.: Primary C cell hyperplasia within a nodule of thyroid isthmus. Oncology 32: 11-20 (1975). 3 Beskid, M.; Dabska, M.; Kfos. H.. and Majdecki, T.: Histochemical features of C cell thyroid carcinoma. Acta histochcm. 58: 210-218 (1977). 4 Beskid. M.; Hartwig, W.; Nielubowicz, J., and Tolloczko, T.: Thyroid C cells in primary hyperparathyroidism. Acta histochcm. 59: 70-78 (1977). 5 Braunstcin, H. and Stephens, C.L.: Parafollicular cells of human thyroid. Archs Path. 86: 659-666 (1968). 6 Chan, A.S. and Conen, P. E.: Ultrastructural observations on cytodifferentiation of parafollicular cells in the human fetal thyroid. Lab. Invest. 25: 249-259 (1971). 7 Englund. N. E .; Nilsson, G.; Owman. C., and Sundlcr, F.: Human thyroid C cells: occurrence and amine formation studied by per fusion of surgically removed goitrous gland. J. clin. Endocr. Metab. 35: 90-96 (1972). 8 Glenner. G. G.; Burtncr, H. J.. and Brown. G. W.: The histochemi cal demonstration of monoamine oxidase activity by tetrazolium salts. J. Histochcm. Cytochem. 5: 591-600 (1957). 9 Horvath, E.; Kovacs, K.. and Ross, R.C.: Medullary cancer of the thyroid gland and its possible relations to carcinoids. Virchows Arch. path. Anat. Physiol., Scr. A 356: 281-292 (1972).
10 Larson, B.; Owman, C„ and Sundler, F.: Monoamincrgic mecha nism in parafollicular cells of the mouse thyroid gland. Endo crinology 78: 1109-1114 (1966). 11 Lorenc. R. and Beskid, M.: Assay of C cell thyroid adenoma of man for calcitonin activity. Acta histochcm. 43: 1-7 (1972). 12 Meyer, J.S. and Abdcl-Bari, W.: Granules and thyrocalcitoninlike activity in medullary carcinoma of the thyroid gland. New Engl. J. Med. 278: 523-529 (1968). 13 Pearsc, A .G.E.: The cytochemistry and ultrastructure of poly peptide hormone producing cells of the APUD scries and the embryologie, physiologic and pathologic implications of the con cept. J. Histochem. Cytochem. 17: 303-313 (1969). 14 Solcia, E.; Vassallo, G., and Capclla, C.: Selective staining of endocrine cells by basic dyes after acid hydrolysis. Stain Technol. 43: 257-263 (1968). 15 Wattenberg, W. and Leong, J.L.: Effects of coenzyme Q 10 and menadione on succinic dehydrogenase activity as measured by tetrazolium salt reduction. J Histochem. Cytochem. 8: 288-292 (1965).
M. Beskid, Assistant Professor. Ml). DSc, Laboratory of Histochemistry. Center of Postgraduate Medical Education. Marmoncka 99, 01-813 Warsaw (Poland)
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