Tomographic Abnormalities Simulating Pituitary Microadenomas

Transcription

1 505 Tomographi bnormalities Simulating Pituitary Miroadenomas George Wortzman 1 N. B. Rewastle 2 False-positive and false-negative interpretations of sellar tomography were found in about one-fifth of ases in a reent autopsy study orrelating the presene of pituitary miroadenomas with abnormal sellar tomograms. n analysis of minor variations in the bony onfiguration of the sella dislosed variations due to posterior lobe asymmetry, interavernous venous hannels, bony asymmetry, and an empty sella in 27 of the 120 sellas examined. In some instanes, the asymmetry resulted from a ombination of these auses. further study of 50 pituitary glands in situ showed posterior lobe asymmetry to be a ommon anomaly (76% ) that an produe an obvious disparity between the two halves of the sella. Thus, the minor radiologi riteria of loal thinning of the anterior wall or floor, slant of the floor, or asymmetry of the two halves of the sella must be interpreted with aution as being indiative of the presene of pituitary miroadenoma. In the absene of linial or biohemial dysfuntion, the hanges more likely result from explainable anatomi auses. reent autopsy study orrelating th e presene of pituitary miroadenomas and abnormal sellar tomograms urged aution in diagnosin g a miroadenoma by sellar tomography [1]. False-positive and false-negative interpretation of tomographi findings were found in about one-fifth of 120 ases. The 27 ases of false-positive findings were reexamined as to origin of the minor variations in th e bony onfiguration of the sella. The results of this analysis plus a further study of 50 pituitary glands in situ are the subjet of this report. Materials and Methods Reeived November 4, 1981; aepted after revision February 11, Presented in part at the annual meeting of th e ssoiation of University Radiolog ists, New Orleans, pril ' Department of Rad iology, University of Toronto, Mt. Sin ai Hospital, 600 Universit y ve., Toronto, Ontario M5G 1 X5. ddress reprint requests to G. Wortzman. 2Department of Neuropathology, University of Toronto, Toronto, Ontario. Present address: Department of Pathology, Foothills Hospital, Calgary, lberta. JNR 3: , September/ Otober / 82/ $00.00 meri an Roentgen Ray Soiety The earli er report [1] ontain s a detailed desription of methods. Briefly, th is onsisted of an en blo removal of the pituitary and the sell a in an unseleted autopsy population only exluding ases with a liniall y apparent pituitary tumor. Hypoyloidal tomograms were done on th e speimens in anteroposteri or (P) and lateral projetions at 2 mm intervals. Interpretation was by three neuroradiologists independently and also togeth er. Criteria for se ll ar abnormali ty were the findings of a slanted se ll ar floor, loal ortial th inn ing of the lamina dura and erosion, or bu lging of th e anterior wall or floor of the sella. These riteria were based on earli er work by Vezina and Sutton [2] and MLahlan et al. [3]. Care was taken th at th e normal variations of sphenoid sinus development and septal attahments were not interpreted as abnormal. Cognizane was also taken of the normal vari ations of the dorsum, whih frequently has a onavity entrally with its lateral margins more anteriorl y situated. Following subsequent dealifiation of the blok of ti ssue, the speimens were imbedded in paraffin, ut in a midsagittal plane, and then setioned at 1 mm intervals. t eah level, sli des were stai ned with : (1) hematoxylin and eosin, (2) the Mann stain for aidophils and basophils, (3) periodi aid-shiff stain for arbohydrate residues, (4) Gordon stain for retiulum, and (5) immunoperoxidase for prolatin.

2 506 WORTZMN ND REWCSTLE JNR:3, September/ Otober 1982 Pathologi study identified 43 adenomas in 32 of the 1 20 pituitaries so examined. These adenomas were mostly under 2 mm in size and distributed hi efly in the periphery of th e gland. High false-positive and fal se-negative interpretation rates of tomographi findings were found in th e orrelative study then done. Of the 27 ases onsidered abnormal on tomography, six had a oexisting adenoma, but in no ase was th e adenoma of su h size or position so as to onsider it to be the ause of the tomographi abnormality. The group of 27 ases was reexamined. The mirosopi struture of the pituitary gland and the bony sella were orrelated with the P and lateral tomographi studies. The results of this analysis are disussed below. further postmortem study of 50 pituitary glands in situ was arried out. This study onsisted of areful dissetion of the pituitary gland both before and after removal of the dorsum sell a to determine th e relative positions of the anterior and posterior lobes of the pituitary in relation to the midline of the sell a. Results Explanations for sellar variations in the 27 false-positive ases are summarized in table 1. In most ases, one ause for the misinterpretation was found; in four of the ases, more than one fator was instrumental in ausing the hanges onsidered ompatible with a miroadenoma. Posterior lobe asymmetry was the most ommon ause of the interpretati on of sellar abnormalities and was seen in 15 ases; in 13 of these, it was the only alteration present (figs. 1 and 2). This asymmetry, whih onsisted of a posterolateral rather than a midline relationship of the posterior lobe to the anterior lobe, instigated the seond part of this study, verifying this to be a true finding rather than a te hnial artifat. Interavernous venous hannels were always present, but, in eight of the ases, the size and position of the hannel was onsidered to be responsible for the abnormal onfiguration of bony ortex (figs. 3 and 4). In one of these ases, there was a oexisting adenoma; in another, there was bone asymmetry. n asymmetry of the bony walls of the sphenoid sinus that ould not be readily attributed to a vari ation in sinus development or of sinus septal attahment was found in four ases; in three of these, it was the only vari ation seen. The sellar onfiguration was onsidered due to a partially empty sella in two ases (fig. 5); in one, it was the sole explanati on. Instanes of minor degrees of empty sell a in the original study did not ause any signifiant deformity. Rathke pouh ysts were frequent findings, being seen in 29 of the original 120 subjets. They were present in four of 27 false-positives. In only one ase was the presene of the yst onsidered to be of signifiane, but, in that ase, there was also a oexisting posterior lobe asymmetry (fig. 6). The results of the in situ examination of the pituitary gland are summari zed in figure 7 with an example of an eentri posterior pituitary lobe shown in figure 8. The posterior lobe is frequently eentri in its relation to the anterior lobe and was midline in only 24% of ases. In 14% of ases, the TBLE 1: Explanations for False-Positive Sellar bnormalities in utopsy Speimens Explanation Posterior lobe asymmetry Bony wall asymmetry Venous hannel erosion Empty sella Venous hann el and adenoma Venous hannel and bone asymmetry Rath ke yst and posterior lobe asymmetry Empty sella and posterior lobe asymmetry Total No. Speimens posterior lobe was situated well laterally. The results of this seond study verify that the findings desribed above in 15 of the 27 ases studied were real rather than due to an artifat or an asymmetry developing in the preparation of the pathology setions. Disussion In 1936, Costello [4] found linially silent pituitary adenomas in 225 of 1,000 autopsies. Setions were done in the longest axis of the gland, either sagittally or transversely, ut by hand with thiknesses of mm. Most adenomas found were 1.5 mm or greater. MCormik and Halmi [5] reported 9.1 % adenomas in 1,600 onseutive autopsies. In our previous report [1], miroadenomas were found in 32 (27%) of 120 ases. The adenomas were usually under 2 mm in size. This higher inidene of adenomas is attributed to the greater number of setions taken. Criteria for identifiation of an adenoma were uniformity of ells, a stromal pattern different from the rest of the gland, and evidene of ompression of adjaent pituitary parenhyma. More than one adenoma was found in eight of the 32 ases. Immunoperoxidase staining identified 16 of 39 miroadenomas to be prolatinomas. s in the series of Costello [4], the adenomas were usually peripheral in loation with some projeting from the surfae of the gland under the apsule. Sine the early 1970s, an extensive body of literature pertaining to the sella and pituitary has appeared refleting advanes in the fields of neurosurgery, endorinology, pathology, gyneology, and radiology. These diagnosti advanes inlude the development of sensitive and speifi radioimmunoassays for blood prolatin, new staining tehniques to identify pituitary ell seretory produts, refinement of transphenoidal mirosurgery, and the medial treatment of the prolatinoma with bromoriptine [6-16]. M Lahlan [3] in 1970 and Vezina and Sutton [2] in 1974 showed that areful tomographi investigation of the sella turia allowed reognition of bony erosion due to aromegaly and also due to prolatin-sereting pituitary miroadenomas. The thinning of the ortex and the erosion or bulging of the wall or floor may be quite subtle and not

3 JNR: 3, September / Otober 1982 FLSE-POSITIVE SELLR TOMOGRPHY 507 Fig. 1.-Eentri posteri or pituitary lobe., Lateral to mographi ut 4 mm to left of midline. Sloped anterior wall. B, Right-sided ut 4 mm from midline. Steeper anterior wall slope, inreased P diameter, and thinned dorsum. C, Histopathology orresponding to. D, Histopathology orresponding to B. Eentrially plaed posterior lobe of pituitary aounts for marked differene in sellar onfigurati on. 8 D 8 E D Fig. 2.-Eentri posterior pituitary lobe. Lateral tomog raphi uts on left () and right (B) of midline. Inreased P diameter evident on right. C and D, Histopathology orresponding to and B, respetively. s in fig. 1, sell ar onfigurati on is determined by eentri position of posterior lobe of pitui tary. E, P tomographi ut. Sell ar floor is slanted down on right. appreiated without the aid of pluridiretional tomography. The validity of these riteria has been verified both in radiologi and surgial literature [14, 17-21]. It has long been appreiated that there are, however, many asymmetries in the development of the sphenoid sinus, both as to the pattern of septati on and the degree of pneumatization [22-2 5]. With th e reent popularity of transsphenoidal neurosurgery, there has been again an interest

4 508 WORTZMN ND REWCSTLE JNR:3, September I Otober 1982 Fig. 3.- Venous hannels. Left () and right (B) tomographi uts. Deepened floor on B interpreted as ompatible with miroadenoma. C and D, Corresponding histopathology setions (to and B, respetively). Large rossing venous sinus beneath pi tuitary gland auses irregul arity of sellar fl oor. Low, small posterior lobe on D auses minor erosion of dorsum. B Fig. 4.-Venous hannels. Left () and right (B) tomographi uts. Erosion of dorsum and posterior sellar floor on right. C and D, Histopathology setions orresponding to and B, respetively. Large venous sinus posteroi nferior to pituitary gland auses asymmetry of two sides of sella. B o

5 JNR:3, September / Otober 1982 FLSE-POSITIVE SELLR TOMOGRPHY 509 B E /'" l' D '- Fig, 5. - Partiall y empty sella and eentri posteri or pituitary lobe. Lett () and right (B) lomographi uls. Inrease in P diameter of sell a on righl with Ihinned dorsum and some underutling of tu berulum. C and D, Histopalhology setions orresponding 10 and B, respetively. Parliall y empty se lla auses underutling of luberulum and eenlri posterior pituilary lobe thinning dorsum. E, P ui. Minor depression of se ll ar floor on righl side partl y allributable 10 septal lag. Fig Rathke pouh yst and eenlri posterior lobe of pituitary. Left () and righl (B) tomog raphi uls. Ball ooned onfiguration on lett when ompared with righl. C and D, Histopathology setions orresponding 10 and B, respetively. Large Rathke pou h yst and eenlri posteri or pitui tary lobe orrelate with tomographi hanges. B D

6 510 WORTZMN ND REWCSTLE JNR:3, September / Otober 1982 Left % 38% 42% Middle 12 24% Right % 10% 34% adjaent sell ar floor. The asymmetry reates diffiulties when omparing sequential lateral tomographi setions of the sell a, as the asymmetry, when due to the eentri nature of th e posterior lobe of the pituitary, is reognized as a unilateral in rease in the P diameter of the sella. defet and irregularity of the sell ar floor were seen in other ases of this seri es seondary to rossing venous sinuses. Cysts of the pouh of Rathke proved almost as ommon as mi roadenomas in the initial autopsy series, but were not shown to be responsible for any evident bony hange. In th e ase where the partially empty sella was the Fig. 7.- Posterior pituitary tobe asymmetry. Findings in 50 onseutive examinations o f pituitary glands in situ. Posterior lobe was entral in 24%, but eentri as depi ted in the rest. In 14%, the lateral margin o f the posteri or lobe was flush with the lateral margin of the an terior lobe; the other 62% o f less eentri plaed glands had their latera l margins as depited by th e broken line. in variations in anatomy of the sphenoid sinus and sell ar region with anomali es of th e bony walls of the sell a being identified [26-28]. Swanson and duboulay [29] examined 85 ases with no linial evidene of a pituitary lesion, yet the plain films in 3 1.7% demonstrated hanges that were idential with th ose desribed for a small intrasell ar lesion. The unanswered question, however, was whether these hanges were due to a oexisting but asymptomati adenoma. Other authors have pointed out normal variants in sellar onfigurations seondary to a sloped sellar floor, thinning of the sell ar ortex, the pattern of aeration and / or septation of the sphenoid sinus, or thikening of the muosal membrane of the sinus [30-32]. Earlier autopsy studies stressed either the inidene of miroadenomas or the variations of adjaent strutures suh as arotid vessels, arahnoid isterns, avernous sinuses, and the opti hi asm and nerves [33, 34]. More reent autopsy studies have dealt more with the histopathology of the pituitary gland and its relation to sellar tomographi abnormalities [1, 35-37] and have pointed out the nonspeifi ity of the sellar hanges previously onsidered due to a pituitary miroadenoma. The present study arries this a step further and reveals several reasons for apparent abnormalities. The most signifiant is an asymmetri position of the posterior lobe of the pituitary gland with its seondary effet on the dorsum sell a. This led to th e greatest number of errors of interpretation despite are being taken during the original study to avoid errors due to an asymmetry of the dorsum. In a omprehensive study, DiChiro and Nelson [38] pointed out the many irregularities in the appearane of the dorsum and desribed the depression of bone th at aommodates th e posteri or lobe of th e pituitary gland. This depression was alled " fossula hypophyseos" by Karlas, " impressio hypophysios" by Wegard, and " fossetta pituitaria" by Cardillo and Bossi (all ited in [38]). The resultant thinness of bone in the area of depression vari es and the entral part may be absent resulting in a ortiated " window" [39]. This depression of the anterior aspet of the dorsum may involve th e 8 Fig. 8.-, Pituitary gland in situ before removal (from the bak and above). The dorsum has been amputated. The blak thread runs in midline. B, Pituitary gland and stalk after removal, viewed from above, shows eentri position of posterior lobe.

7 JNR:3. September I Otober 1982 FLSE-POSITIVE SELLR TOMOGRPHY 511 sole abnormality, the hanges of the sella were onsidered to be due to an asymmetri invagination of subarahnoid spae. In addition to the anomalies and hanges of the sell a desribed above, there have been reports of other fators ausing hanges ompatible with an intrasell ar lesion. There is a report of an apparently eroded dorsum that at autopsy proved due to a ongenital lak of ossifiation [40]. Erosion of the floor of the sella simulating the hanges of a pituitary miroadenoma has also been reported in two ases of an anomalous arterial ommuniation between the intraavernous segments of internal arotid arteri es in assoiation with agenesis of one internal arotid [41]. Pluridiretional tomography is still of aid before transsphenoidal removal of a pituitary miroadenoma and usually reflets the side of the miroadenoma and will show the anatomy of sphenoid pneumatization and septation. However, there are many patients with hormonal dysfuntion where an adenoma has been found despite negative tomographi studies [12, 18]. In a reent radiologi-surgial orrelative study, good orrelation existed between the tomographi loalization and the loation of the tumor at su rgery in most ases [42]. In nearly 20% of 89 ases reported, however, the sell ar hanges suggestive of adenoma on tomography had no relation to the loation of the tumor as seen at surgery. This further indiates the need for aution in the interpretation of tomographi findings. Protools for the study of pituitary adenomas have hanged radiall y over the past 2-3 years as advanes in equipment and tehniques ontinue, and they are the subjet of reent review artiles [43,44]. Interpretation of plain films and tomographi studies of the sell a turia must be undertaken with aution. In addition to variations of sphenoid pneumatization and septation, one an be misled by a hange in the P diameter of the sell a seondary to eentri position of the posterior lobe of th e pituitary. n anatomi review shows the posterior lobe to be more frequently eentri in its relation to the anterior lobe than to being a truly midline attahment. In addition, bone defets simulating erosion of the sell ar floor may be seondary to interavernous venous hannels, bony wall asymmetry, or to anomalies of sphenoid sinus development and other explainable anatomi variations. CKNOWLEDGMENT We thank Christine Bobkowski for help in manusript preparation. REFERENCES 1. Burrow GN. Wortzman G, Rewastle NB, Holgate RC, Kovas K. Miroadenomas of the pituitary and abnormal sellar tomograms in an unseleted autopsy seri es. N Engl J Med 1981 ;304: Vezina JL, Sutton T J. Prolatin-sereting pituitary miroadenomas: roentgenologi d iagnosis. JR 1974; 120 : M Lahlan MSF, Wright D, Doyle FH. 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