C Y T O P L A S M I C F I L A M E N T O U S MASSES I N C H R O M O PHOBE ADENOMA OF T H E H U M A N PITUITARY GLAND

s. ROY Department of Patizology, All India Institute of lvfedical Sciences, New Dellti-1 10016, India

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THEoccurrence of intracytoplasmic " fibrous bodies " composed of fine fdaments in pituitary adenoma was first reported by Racadot, Olivier and Porcile (1964) and since then a few more cases of pituitary adenoma with similar bodies have been recorded (Cardell and Knighton, 1966; Schochet, McCormick and Halmi, 1972; Kovacs et al., 1974; Horvath and Kovacs, 1976). Although they are seen generally in the adenomas associated with acromegaly, the nature and mechanism of their formation are not known. In the course of a study on the ultrastructure of chromophobe adenoma, three cases with the presence of intracytoplasmic aamentous masses were observed. In the present communication detailed ultrastructure of these masses is described along with a comment on the possible mode of their formation. MATERIALS AND

METHODS

This study is based on ultrastructural examination of three biopsy specimens obtained from three patients with acromegaly (two females aged 27 and 30 years respectively and one male aged 23 years). These three cases were found among the 18 cases of pituitary adenomas studied by electron microscopy, of which 13 were " non-functioning " adenomas and five were adenomas with acromegaly. Light microscopically all the 18 cases were chromophobe adenoma with no stainable granules, using the PAS-orange G stain (Pearse, 1960).

Small blocks (1 mm) were cut from the specimens and fixed in 4 per cent. glutaraldehyde solution in phosphate buffer. They were post-fixed in 1 per cent. cold osmium tetroxide and after dehydration in ascending grades of alcohol, they were embedded in epoxy resin. Thin sections were stained with uraiiyl acetate and lead citrate and examined with a Philips300 eIectron microscope.

RESULTS Ultrastructurally the neoplastic cells had the morphological appearance characteristic of secretorily active cells (Roy, 1977). They were sparsely granular and were generally rich in rough endoplasmic reticulum (RER). They exhibited many free ribosomes and often had a prominent Golgi apparatus. The other striking feature was the presence of intracytoplasmic masses generally composed of fine filaments. These masses were spherical with no Received 22 Oct. 1911; accepted 18 Nov. 1977 J. PATH.-VOL.

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limiting membrane around them (fig. 1). Secretory granules, endoplasmic reticulum, mitochondria or lipid vacuoles were found embedded in some of the filamentous masses (figs. 2 and 3). They were commonly located near the nuclei but were also found at the peripheral part of the cells. The filaments constituting these masses were mostly curved and they measured approximately 10 nm in diameter. Although most of the masses consisted of filaments only, in a few of them many randomly placed tubular structures and granules were also found (figs. 3 and 4). The tubules and the granules measured approximately 20-40 nm and 10-12 nm respectively in diameter and they were intimately mixed with the filaments described above. Some of the granules may represent cross sections of the filaments but others are probably ribosome particles. A definite association was often seen between the filamentous bodies and the RER (figs. 1-3). Prominent RER, free ribosomes and at times Golgi apparatus was conspicuous in the close proximity of many of the filamentous masses and also of the masses composed of both filaments and tubules (fig. 3). Not infrequently the cisternae of some of the RER appeared to be losing their continuity and “ disappearing ” in these spherical masses. DISCUSSION The occurrence of intracytoplasmic spherical masses composed of fine filaments was orginally reported by Racadot et al. (1964) in a pituitary adenoma associated with acromegaly. Subsequently, in a few more cases similar intracytoplasmic filamentous masses have been recorded (Cardell and Knighton ; Schochet et al., 1972; Kovacs et al., 1974; Horvath and Kovacs) and most of these cases of pituitary adenomas had acromegaly. Light microscopically, these tumours have shown features of either acidophil (Schochet et al.) or chromophobe (Cardell and Knighton; Horvath and Kovacs) or of mixed adenoma (Racadot et al, 1964). These filamentous masses are ultrastructurally quite different from microfilaments present in Crook’s hyalin (Kovacs et al.). Electron microscopically most of the reported cases with intracytoplasmic filamentous bodies showed sparsely granulated neoplastic cells with prominent rough endoplasmic reticulum. In the present study, intracytoplasmic filamentous masses were found in three out of five cases of chromophobe adenomas associated with acromegaly and they were not present in any of 13 cases of “non-functioning” chromophobe adenomas. In all the three cases showing filamentous masses, the neoplastic cells were sparsely granular and were well endowed with RER, free ribosomes and Golgi apparatus. Horvath and Kovacs found filamentous bodies in all the seven cases of sparsely granulated tumours they studied and also in two out of nine cases of well-granulated tumours. They did not find these structures in any adenoma not associated with acromegaly. It appears therefore that there is a strong association between the occurrence of the filamentous bodies and acromegaly and their presence is highly suggestive of a tumour arising from growth hormone-producing cells.

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It should be noted, however, that in a large series of 115 cases of acidophil adenomas, both well granulated and sparsely granulated, reported by Lewis and Van Noorden (1972), the authors did not describe the occurrence of similar structures. In the present study, although most of the spherical bodies were composed of fine filaments admixed with a few scattered small electron dense granules, a few of them also contained large numbers of tubular structures, morphologically closely similar to the cisternae of rough or smooth endoplasmic reticulum. The mechanism of formation of the intracytoplasmic filamentous masses is not known. Cardell and Knighton considered that they probably result from degeneration in the cytoplasm. A similar view has also been expressed by Schochet et al., but their formation has not been related to any particular type of cytoplasmic organelle. Since the filamentous masses in the present study were closely associated with rough endoplasmic reticulum and at times with Golgi apparatus it is tempting to speculate that these masses arise from degeneration of rough endoplasmic reticulum and Golgi apparatus. This contention is further supported by the fact that in some of the spherical masses many intact tubular structures and granules resembling ribosomes were present. It is possible that in the process of formation of the filamentous masses RER lose ribosomes from the cisternae followed by splitting and fragmentation of the cisternae,with the formation of filamentous structures from the walls of cisternae. The same process of degenerative change may also involve the cisternae of smooth endoplasmic reticulum including Golgi apparatus, with the resultant formation of filaments. Since the filamentous masses were generally seen in secretorily active adenomas it is considered likely that their formation may result from degeneration of rough and smooth endopkasmic reticulum following prolonged secretory activity. On the other hand, their occurrence only in the growth hormone-producing pituitary adenomas may suggest a special secretory role. Further studies to determine this aspect may help in establishing the true nature of the intracytoplasmic filamentous masses. SUMMARY The fine structure of filamentous masses in three cases of chromophobe adenoma of the pituitary gland is reported. These three were among 18 cases of chromophobe adenoma, 13 non-functioning and five with acromegaly, studied by electron microscopy. All the three cases with fine filamentous masses were adenomas with acromegaly and none of the non-functioning adenomas showed these structures. The cells containing filamentous masses were rich in rough endoplasmic reticulum and poor in secretory granules. These masses were composed of fine filaments and, in some, tubular structures and granules were also present. Prominent RER and sometimes an extensive Golgi system was seen in the adjacent cytoplasm. It is suggested that the filamentous masses arise as a result of degeneration and disintegration of RER and Golgi apparatus.

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I would like to thank my colleagues in the department of Neurosurgery for their help in collecting the specimens and Mr Achar Sin& for his technical assistance. Electron microscopy was performed in the E.M. Laboratory of the Department of Anatomy. REFERENCES CARDELL, R. R. JR., AND KNIGHTON, R. S. 1966. The cytology of a human pituitary tumour: an electron microscopic study. Trans. Aiizer. Micros. Soc., 85, 58. HORVATH, E., AND KOVACS, K. 1976. Ultrastructural classification of pituitary adenoma. Canad. J . Neurol. Sc., 3,9. KOVACS, K., HORVATH, E., STRATMANN, I. E., AND ESRIN,c. 1974. Cytoplasmic microfilaments in the anterior lobe of the human pituitary gland. Acta. Anat., 87, 414. LEWIS,P. D., AND VANNOORDEN, S. 1972. Pituitary abnormalities in acromegaly. Arch. Pathol., 94, 119. PEARSE, A. G. E. 1960. Histochemistry, 2nd ed., London, p. 831. RACADOT, J,, OLIVIER, L., AND PORCILE, E. 1964. Adenoma hypophysaire de type “mixte” avec symptomatologie acromegalique. Ann. Endocr., 25, 503. ROY, S. 1977. Ultrastructure of chromophobe adenoma of the human pituitary gland. J. Pathol., 122,219. SCHOCHET, S. S. JR., MCCORMICK, W. F., AND HALMI, N. S. 1972. Acidophil adenomas with intracytoplasrnic filamentous aggregates. A light and electron microscopic study. Arch. Pathol., 94, 16.

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FIG. 1.-Electron micrograph showing an intracytoplasmic filamentous mass (F) surrounded by many profiles, mostly circular, of rough endoplasmic reticulum. x 17,000.

FIG,2.-Filamentous mass with prominent RER and many free ribosomes around it. Note, mitochondria (m), smooth vesicles (V), secretory granules (g) and RER cisterns (R) entrapped in it. x 12,000.

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FIG. 3 . - Filamentous mass containing many tubular structures. scattered granules, a lipid vacuole (L), smooth vesicles (V), mitochondria (M) and secretory granule (G). Note prominent RER in the adjacent cytoplasm. x 20,500.

FIG. 4.-Part of a filamentous mass at higher magnification showing tubules, granules, filaments (arrow), mitochondria (M) and occasional RER cistern (arrow head). x 82,500.

Cytoplasmic filamentous masses in chromophobe adenoma of the human pituitary gland.

C Y T O P L A S M I C F I L A M E N T O U S MASSES I N C H R O M O PHOBE ADENOMA OF T H E H U M A N PITUITARY GLAND s. ROY Department of Patizology,...
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