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Intra-Adrenal Hepatic Heterotopia
0022-534 7/85 /1334-0652$02.00 /0 Vol. 133, April
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright © 1985 by The Williams & Wilkins Co.
Case Reports INTRA-ADRENAL HEPATIC HETEROTOPIA LOUIS H. HONORE From the Department of Patho/,ogy, University of Alberta and University of Alberta Hospitals, Edmonton, Alberta, Canada
ABSTRACT
The second case of intra-adrenal hepatic heterotopia is described in a normally structured male fetus stillborn at 26 weeks of gestation. The liver nodule, incidentally found in a random histological section of the right adrenal, was not encapsulated and blended with the adjacent fetal cortex. It consisted of cords of immature hepatocytes with abundant sinusoids and widespread hemopoiesis. Abnormalities included absence of a hexagonal pattern, incomplete portal tracts with dilated veins only, lack of bile ducts and canaliculi, and apparent failure of bile formation and glycogen deposition. The adrenal cortex is the most prone of all organs to the development of heterotopia. Aberrant adrenocortical rests are common in abdominal, pelvic and paragonadal connective tissues, 1• 2 and rare sites of occurrence include the gonads, 3- 5 1ung, 6 brain, 7 kidney8 and liver. 9 Exceptionally the misplaced adrenal tissue is the seat of neoplasia. 10 On the other hand, the presence of foreign tissue in the adrenal is unusual, and confined to gonadal and hepatic tissue. The gonadal elements concerned comprise metaplastic ovarian stroma,11 • 12 a theca granulosa cell tumor, 13 Leydig-like cells in the adrenal cortex of men with Buerger's disease14 and Leydig cells in a testosterone-secreting adrenomedullary ganglioneuroma. 15 Liver tissue within the adrenal, resulting from adrenohepatic fusion, is not an uncommon autopsy finding 16 but the existence of a separate intraglandular liver nodule has been recorded briefly only once. 17 The second case of this rare phenomenon is reported. CASE REPORT
A 26-year-old woman, gravida IV, para 2, had had a normal pregnancy until 26 weeks of gestation, when vaginal bleeding developed followed by spontaneous rupture of the membranes. Clinical and ultrasonic diagnosis was placental abruption. Despite bed rest and toco-lysis she went into spontaneous labor 4 days later. The fetal heart was heard before and during labor but the fetus was born dead. Post mortem the placenta showed an acute marginal basal hemorrhage consistent with abruption but no evidence of ascending infection. The male fetus, weighing 1,010 gm. and measuring 37 cm. crown to heel, was normally structured and exhibited changes associated with acute hypoxia. An incidental finding was the presence of a nodule of liver tissue in a random section of the grossly normal right adrenal. The ovoid nodule, measuring 2.28 x 0. 7 mm., was located in one of the wings of the gland normally devoid of adrenal medulla, and was wedged between the fetal cortex and the vascular connective tissue spur separating the superior and inferior layers of the gland (part A of figure). The nonencapsulated liver tissue blended imperceptibly with the cortical cells and consisted of thin unicellular or bicellular cords of small deeply basophilic immature hepatocytes, contrasting with the larger granular eosinophilic adrenocortical cells (part B of figure). The typical hexagonal pattern was absent with no cenbal veins and only scanty irregularly Accepted for publication December 14, 1984.
652
disposed incomplete "portal tracts" containing dilated veins but no arteries or bile ducts. There was no cholestasis and no bile canaliculi could be recognized with routine and connective tissue stains. The liver cords were flanked by prominent sinusoids and there was widespread hemopoiesis. The occasional Kupffer cell was seen with an ovoid vesicular nucleus projecting into the sinusoid (part B of figure). Small amounts of glycogen were detected in the orthotopic liver with the use of the periodic acid, Schiff/ periodic acid, Schiff-diastase combination but none was found in the intra-adrenal liver nodule. Unfortunately, the tissue had been fixed in Bouin's fluid and embedded in paraffin, precluding ultrastructural, biochemical and enzymological studies. DISCUSSION
This is the second case reported of isolated hepatic heterotopia in the adrenal gland and the first case of this condition in a completely normal fetus. Cullen reported on a 6-week-old neonate who had lethal cardiac malformations (ostium primum defect and foramen ovale) and mongolian features, strongly suggestive of Down's syndrome. 17 Intra-adrenal hepatic heterotopia is not a recognized part of the Down phenotype 18 but this lack of association may simply reflect ignorance of Cullen's observation. In other words, thorough scrutiny of the adrenals in patients with Down's syndrome may well uncover further examples of such an anomaly. The etiology of this anomaly is unknown and one can only speculate on its pathogenesis. At least 2 factors must have contributed: 1) an aberrant segment of the hepatic diverticulum must have wandered into the adjacent adrenal anlage, and become cut off by the formation of the hepatic and adrenal capsules, 16 and 2) the adrenal mesenchyme investing the endodermal tissue must have been hepatogenic. Experiments show that although mesenchymdfof similar embryonic origin, that is mesenteric or peritoneal, can induce the prehepatic endoderm to differentiate into liver only the true hepatic mesenchyme of the septum transversum in close proximity to the cardiac fold can support complete structural and functional differentiation. 19 Thus, it is possible that the inductively imperfect adrenal mesenchyme is responsible for the abnormal structure and function of the liver nodule, that is failure of lobulation, absence of bile ducts and canaliculi, apparent failure of bile formation and the incomplete development of "portal tracts". The complete lack of tinctorially detectable glycogen
653
INTRA-ADRENA.L HEPATIC HETEROTOflA
A, heterotopic liver tissue (between arrows) in feta! adrenal cortex. Note absence of Hv,,u5 vm,>< capsule between liver and adrenal. H & E, reduced from X84. B, junction of adrenal h.,,..,w,".omr of hepatocytes, absence of cholestasis in liver, lack of artery and bile duct in Kupffer cell (short arrow). H & E, reduced from X525.
in the liver nodule must be ,nre>rnr,M.,,n with caution because of the low sensitivity and the unreliability of the method since hepatic glycogen formation is induced and stimulated corticoids, 19 one would have expected the liver nodule, ""'''"''"'r1 to high intraglandular corticoid levels, to contain more glycogen than the orthotopic liver. Its absence indicate that is enzymatic, inadequacy of the aberrant liver tissue. The functional significance, if any, of heterotopic liver tissue in the adrenal remains to be established. Since hepatic adenomas and carcinomas can be confused histologically with adrenocortical tumors 10 it remains possible that some nonfunctioning adrenocortical neoplasms may have arisen from heterotopic liver tissue. Only awareness of this possibility, coupled with the appropriate use of ultrastructural, immunocytochemical and biochemical methods will provide data to support or refute this suggestion.
tracts" and lack of
REFERENCES
1. Falls, J. L.: Accessm·y adrenal cortex in the brnad ligament. Incidence and uuva,•uw~, significance. Cancer, 8: 143, 1955. 2. Schechter, D. C.: Aberrant adrenal tissue. Ann. Surg., 167: 421, 1968.
3. Madhavan, M., Ramachandnm, P. C. and Chandra, K.: Adrenal rests in fetal testes. Report of three cases. Indian J. Ped., 38: 407, 1971. 4. Roosen-Runge, E. C. and Lund, J.: Abnormal sex cord formation and an intratesticular adrenal cortical nodule in a human fetus. Anat. Rec., 173: 57, 1972. 5. Symonds, D. A. and Driscoll, S. G.: An adrenal cortical rest within the fetal ovary: report of a case. Amer. J. Clin. Path., 60: 562, 1973. 6. Bozic, C.: Ectopic fetal adrenal cortex in the lung of a newborn. Virch. Arch. Path. Anat., 363: 371, 1974. 7. Wiener, M. F. and Dallgaard, S. A.: Intracranial adrenal gland: a
654
HONORE
case report. Arch. Path., 67: 228, 1959. 8. Honore, L. H. and O'Hara, K. E.: Combined adrenorenal fusion and adrenohepatic adhesion: a case report with review of the literature and discussion of pathogenesis. J. Urol., 115: 323, 1976. 9. Vestfrid, M. A.: Ectopic adrenal cortex in neonatal liver. Histopathology, 4: 669, 1980. 10. Wallace, E. Z., Leonidas, J.-R., Stanek, A. E. and Avramides, A.: Endocrine studies in a patient with functioning adrenal rest tumor of the liver. Amer. J. Med., 70: 1122, 1981. 11. Wong, T.-W. and Warner, N. E.: Ovarian thecal metaplasia in the adrenal gland. Arch. Path., 92: 319, 1971. 12. Fidler, W. J.: Ovarian thecal metaplasia in adrenal glands. Amer. J. Clin. Path., 67: 318, 1977. 13. Orselli, R. C. and Bassler, T. J.: Theca granuloma cell tumor arising in adrenal. Cancer, 31: 474, 1973. 14. Magalhaes, M. C.: A new crystal-containing cell in human adrenal
cortex. J. Cell Biol., 55: 126, 1972. 15. Aguirre, P. and Scully, R. E.: Testosterone-secreting adrenal ganglioneuroma containing Leydig cells. Amer. J. Surg. Path., 7: 699, 1983. 16. Dolan, M. F. and Janovski, N. A.: Adreno-hepatic union. Arch. Path., 86: 22, 1968. 17. Cullen, T. S.: Accessory lobes of the liver: an accessory hepatic lobe springing from the surface of the gallbladder. Arch. Surg., 11: 718, 1925. 18. Warkany, J.: Syndromes of chromosomal abnormalities. In: Congenital Malformations. Notes and Comments. Chicago: Year Book Medical Publishers, Inc., part IV, chapt. 37, pp. 324-331, 1971. 19. Croisille, Y. and Le Douarin, N. M.: Development and regeneration of the liver. In: Organogenesis. Edited by R. L. De Haan and H. Ursprung. New York: Holt, Rinehart and Winston, sect. V, chapt. 17,pp.421-466, 1965.
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright © 1985 by The Williams & Wilkins Co.
Case Reports INTRA-ADRENAL HEPATIC HETEROTOPIA LOUIS H. HONORE From the Department of Patho/,ogy, University of Alberta and University of Alberta Hospitals, Edmonton, Alberta, Canada
ABSTRACT
The second case of intra-adrenal hepatic heterotopia is described in a normally structured male fetus stillborn at 26 weeks of gestation. The liver nodule, incidentally found in a random histological section of the right adrenal, was not encapsulated and blended with the adjacent fetal cortex. It consisted of cords of immature hepatocytes with abundant sinusoids and widespread hemopoiesis. Abnormalities included absence of a hexagonal pattern, incomplete portal tracts with dilated veins only, lack of bile ducts and canaliculi, and apparent failure of bile formation and glycogen deposition. The adrenal cortex is the most prone of all organs to the development of heterotopia. Aberrant adrenocortical rests are common in abdominal, pelvic and paragonadal connective tissues, 1• 2 and rare sites of occurrence include the gonads, 3- 5 1ung, 6 brain, 7 kidney8 and liver. 9 Exceptionally the misplaced adrenal tissue is the seat of neoplasia. 10 On the other hand, the presence of foreign tissue in the adrenal is unusual, and confined to gonadal and hepatic tissue. The gonadal elements concerned comprise metaplastic ovarian stroma,11 • 12 a theca granulosa cell tumor, 13 Leydig-like cells in the adrenal cortex of men with Buerger's disease14 and Leydig cells in a testosterone-secreting adrenomedullary ganglioneuroma. 15 Liver tissue within the adrenal, resulting from adrenohepatic fusion, is not an uncommon autopsy finding 16 but the existence of a separate intraglandular liver nodule has been recorded briefly only once. 17 The second case of this rare phenomenon is reported. CASE REPORT
A 26-year-old woman, gravida IV, para 2, had had a normal pregnancy until 26 weeks of gestation, when vaginal bleeding developed followed by spontaneous rupture of the membranes. Clinical and ultrasonic diagnosis was placental abruption. Despite bed rest and toco-lysis she went into spontaneous labor 4 days later. The fetal heart was heard before and during labor but the fetus was born dead. Post mortem the placenta showed an acute marginal basal hemorrhage consistent with abruption but no evidence of ascending infection. The male fetus, weighing 1,010 gm. and measuring 37 cm. crown to heel, was normally structured and exhibited changes associated with acute hypoxia. An incidental finding was the presence of a nodule of liver tissue in a random section of the grossly normal right adrenal. The ovoid nodule, measuring 2.28 x 0. 7 mm., was located in one of the wings of the gland normally devoid of adrenal medulla, and was wedged between the fetal cortex and the vascular connective tissue spur separating the superior and inferior layers of the gland (part A of figure). The nonencapsulated liver tissue blended imperceptibly with the cortical cells and consisted of thin unicellular or bicellular cords of small deeply basophilic immature hepatocytes, contrasting with the larger granular eosinophilic adrenocortical cells (part B of figure). The typical hexagonal pattern was absent with no cenbal veins and only scanty irregularly Accepted for publication December 14, 1984.
652
disposed incomplete "portal tracts" containing dilated veins but no arteries or bile ducts. There was no cholestasis and no bile canaliculi could be recognized with routine and connective tissue stains. The liver cords were flanked by prominent sinusoids and there was widespread hemopoiesis. The occasional Kupffer cell was seen with an ovoid vesicular nucleus projecting into the sinusoid (part B of figure). Small amounts of glycogen were detected in the orthotopic liver with the use of the periodic acid, Schiff/ periodic acid, Schiff-diastase combination but none was found in the intra-adrenal liver nodule. Unfortunately, the tissue had been fixed in Bouin's fluid and embedded in paraffin, precluding ultrastructural, biochemical and enzymological studies. DISCUSSION
This is the second case reported of isolated hepatic heterotopia in the adrenal gland and the first case of this condition in a completely normal fetus. Cullen reported on a 6-week-old neonate who had lethal cardiac malformations (ostium primum defect and foramen ovale) and mongolian features, strongly suggestive of Down's syndrome. 17 Intra-adrenal hepatic heterotopia is not a recognized part of the Down phenotype 18 but this lack of association may simply reflect ignorance of Cullen's observation. In other words, thorough scrutiny of the adrenals in patients with Down's syndrome may well uncover further examples of such an anomaly. The etiology of this anomaly is unknown and one can only speculate on its pathogenesis. At least 2 factors must have contributed: 1) an aberrant segment of the hepatic diverticulum must have wandered into the adjacent adrenal anlage, and become cut off by the formation of the hepatic and adrenal capsules, 16 and 2) the adrenal mesenchyme investing the endodermal tissue must have been hepatogenic. Experiments show that although mesenchymdfof similar embryonic origin, that is mesenteric or peritoneal, can induce the prehepatic endoderm to differentiate into liver only the true hepatic mesenchyme of the septum transversum in close proximity to the cardiac fold can support complete structural and functional differentiation. 19 Thus, it is possible that the inductively imperfect adrenal mesenchyme is responsible for the abnormal structure and function of the liver nodule, that is failure of lobulation, absence of bile ducts and canaliculi, apparent failure of bile formation and the incomplete development of "portal tracts". The complete lack of tinctorially detectable glycogen
653
INTRA-ADRENA.L HEPATIC HETEROTOflA
A, heterotopic liver tissue (between arrows) in feta! adrenal cortex. Note absence of Hv,,u5 vm,>< capsule between liver and adrenal. H & E, reduced from X84. B, junction of adrenal h.,,..,w,".omr of hepatocytes, absence of cholestasis in liver, lack of artery and bile duct in Kupffer cell (short arrow). H & E, reduced from X525.
in the liver nodule must be ,nre>rnr,M.,,n with caution because of the low sensitivity and the unreliability of the method since hepatic glycogen formation is induced and stimulated corticoids, 19 one would have expected the liver nodule, ""'''"''"'r1 to high intraglandular corticoid levels, to contain more glycogen than the orthotopic liver. Its absence indicate that is enzymatic, inadequacy of the aberrant liver tissue. The functional significance, if any, of heterotopic liver tissue in the adrenal remains to be established. Since hepatic adenomas and carcinomas can be confused histologically with adrenocortical tumors 10 it remains possible that some nonfunctioning adrenocortical neoplasms may have arisen from heterotopic liver tissue. Only awareness of this possibility, coupled with the appropriate use of ultrastructural, immunocytochemical and biochemical methods will provide data to support or refute this suggestion.
tracts" and lack of
REFERENCES
1. Falls, J. L.: Accessm·y adrenal cortex in the brnad ligament. Incidence and uuva,•uw~, significance. Cancer, 8: 143, 1955. 2. Schechter, D. C.: Aberrant adrenal tissue. Ann. Surg., 167: 421, 1968.
3. Madhavan, M., Ramachandnm, P. C. and Chandra, K.: Adrenal rests in fetal testes. Report of three cases. Indian J. Ped., 38: 407, 1971. 4. Roosen-Runge, E. C. and Lund, J.: Abnormal sex cord formation and an intratesticular adrenal cortical nodule in a human fetus. Anat. Rec., 173: 57, 1972. 5. Symonds, D. A. and Driscoll, S. G.: An adrenal cortical rest within the fetal ovary: report of a case. Amer. J. Clin. Path., 60: 562, 1973. 6. Bozic, C.: Ectopic fetal adrenal cortex in the lung of a newborn. Virch. Arch. Path. Anat., 363: 371, 1974. 7. Wiener, M. F. and Dallgaard, S. A.: Intracranial adrenal gland: a
654
HONORE
case report. Arch. Path., 67: 228, 1959. 8. Honore, L. H. and O'Hara, K. E.: Combined adrenorenal fusion and adrenohepatic adhesion: a case report with review of the literature and discussion of pathogenesis. J. Urol., 115: 323, 1976. 9. Vestfrid, M. A.: Ectopic adrenal cortex in neonatal liver. Histopathology, 4: 669, 1980. 10. Wallace, E. Z., Leonidas, J.-R., Stanek, A. E. and Avramides, A.: Endocrine studies in a patient with functioning adrenal rest tumor of the liver. Amer. J. Med., 70: 1122, 1981. 11. Wong, T.-W. and Warner, N. E.: Ovarian thecal metaplasia in the adrenal gland. Arch. Path., 92: 319, 1971. 12. Fidler, W. J.: Ovarian thecal metaplasia in adrenal glands. Amer. J. Clin. Path., 67: 318, 1977. 13. Orselli, R. C. and Bassler, T. J.: Theca granuloma cell tumor arising in adrenal. Cancer, 31: 474, 1973. 14. Magalhaes, M. C.: A new crystal-containing cell in human adrenal
cortex. J. Cell Biol., 55: 126, 1972. 15. Aguirre, P. and Scully, R. E.: Testosterone-secreting adrenal ganglioneuroma containing Leydig cells. Amer. J. Surg. Path., 7: 699, 1983. 16. Dolan, M. F. and Janovski, N. A.: Adreno-hepatic union. Arch. Path., 86: 22, 1968. 17. Cullen, T. S.: Accessory lobes of the liver: an accessory hepatic lobe springing from the surface of the gallbladder. Arch. Surg., 11: 718, 1925. 18. Warkany, J.: Syndromes of chromosomal abnormalities. In: Congenital Malformations. Notes and Comments. Chicago: Year Book Medical Publishers, Inc., part IV, chapt. 37, pp. 324-331, 1971. 19. Croisille, Y. and Le Douarin, N. M.: Development and regeneration of the liver. In: Organogenesis. Edited by R. L. De Haan and H. Ursprung. New York: Holt, Rinehart and Winston, sect. V, chapt. 17,pp.421-466, 1965.