MEDICAL t h e u n i l a t e r a l t u m o r s , it a p p e a r s t h a t b i l a t e r a l t u m o r s o c c u r at a s l i g h t l y e a r l i e r a g e , a r e associated with lower parity and higher abortion incidence and have a lower rate of malignancy. On the other band, nnilateral and bilateral Brenner tumors are similar in terms of symptomatology, laterality of tumor size and postmenopausally associated endometrial activity. ''6 The treatment of Brenner tumors is unilateral oophorectomy. In postmenopausal w o m e n t h e p r o c e d u r e o f c h o i c e is a h y s t e r ectomy with bilateral salpingo-oophorectomy) 3 I f m a l i g n a n t c h a n g e is e n c o u n t e r e d in t h e surgical specimen, a total abdominal hysterectomy with bilateral salpingo-ooplmrectomy is r e c o m m e n d e d as t h e i n i t i a l t r e a t m e n t in menopausal and postmenopausal women. If a m a l i g n a n t B r e n n e r t u m o r is e n c o u n t e r e d in a y o u n g e r w o m a n , t h e r a p y is m o r e likely to b e i n d i v i d u a l i z e d a n d c o n s e r v a t i v e , s u c h as a unilateral oophorectomy. The value of radiat i o n t h e r a p y as a t h e r a p e u t i c m o d a l i t y f o r r e s i d u a l o r r e c u r r e n t t u m o r is p r e s e n t l y u n determined.
References 1~ Badway, R. E., Jorgenson, O. it., and Cromer, J. K.: Bilateral Brenner tumors--review of literature and report of case. Med. Ann. D. C.,33:106, 1964. 2. Brenner, F.: Das Oophoroma Folliculare. Frankfurt. Z. Path., 1:150, 1907. 3. Christian, C. D., andJanovski, N. A.: Bilateral Brenner tumors. Ant. J. Obstet. Gynecol., 83:105, 1962. -4. Epple, tl. tl., and Bossert, L. J.: Three simultaneous neoplasms of the female genitalia: a Brenner tumor, a pseuclomucinous cystadenocarcinoma of the contralateral ovary, and a squamous cell carcinoma of the cervix. Obstet. Gynecol., 11:661, 1958. 5. Farrar, tt. K.,Jr., and Greene, R. R.: Bilateral Brenner tumors of tile ovary. Am. J. Obstet. Gynecol., 80: 1089, 1960. 6. Gifford, A. B.," and Birch, tt. W.: Bilateral Brenner tumors of the ovary. J. Med. Assoc. Georgia, 58:145, 1969. 7. tlamwi, G.J., et al.: Testosterone synthesis by a Brenner tumor, Part 1. Clinical evidence of masculinization during pregnanc). Part Ii. In ~itro biosynthetic steroid conversion of a Brenner tumor. Am. J. Obstet. Gynecol., 86:!015, 1963. 8. tlertig, A. T., and Gore, I1.: Tumors of the ovary and fallopiaxt tube. In Atlas of T u m o r Pathology, Sec. I X, Fasc. 33. Washington, D. C., Armed Forces Institute of Pathology, 1961, p. 124. 9. llughesdon, P. E.: Thecal and allied reactions in epithelial ovarian turnouts. ]. Obstet. Gynecol. Brit. Emp., 65:702, 1958. 10. tlnll, M. G. R., and Campbell, G. R.: The ntalignant Brenner tumor. Obstet. Gynecol., 42:527,, 1973. 11. Idelson, M. G.: Malignancy in Brenner tumors of the ovary, with comments on histogenesis and possible estrogen production. Obstet. Gynecol. Survey, 18: 246, 1963. 12. Kendall, B., and Bowers, P. A.: Bilateral Brenner tumor of the ovaries. Am. J. Ohstet. Gynecol., 80:439, 1960. 13. Kismer, R. W.: Gynecolo~" Principles attd Practice. Ed. 2. Chicago, Year Book Medical Publishers, Inc., 1972, p. 409. 14. Kraus, F. T.: Gynecologic Pathology. St. Louis, The C. V. Mosby Company, 1967, pp. 324,313.
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15. MacKinlay, C. J.: Brenner tumours of the ovary. J. Obstet. Gynecol. Brit. Emp., 65:58, 1056. 16. MacNaughtou-Jones, t1.: Uterine fibroid with an anomalous ovarian tnmour. Trails. Lond. Obstet. Soc., 40:154,213, 1898. 17. Meyer, R.: Uber verschiedene Erschlintmgsformen der als typus Brenner bekannten Eirstockageschwulst, ihre Zuordnung unter Andere Overialgerschwillste. Arch. G)naekol., 148:5tl, 1932. 18. Miles, 1'. A., Joj, M. C., and Norris, tt. J.: l'roliferative 9 and malignant Brenner tumors of the ovary. Cancer, 30:174, 1972. 19. Ming, S. C., and Goldman, tt4 tlormonal activity of Brenner tumors in postmenopausal women. Am. J. Obstet. Gynecol., 83:666, 1962. 20. Morris,J. M., and Scully, R. E.: Endocrine Pathology of the Ovary. St. Louis, Tile C. V. Mosby Co., 1958. 21. Novak, E. R., and Woodruff, J. D.: Novak's Gynecologic and Obstetric Pathotogy. Ed. 5. lqdladelphia. W. B. Saunders Company, 1962. 22. Novak, E. R., Woodruff, J. D., and Linthicum, J. M.: Evaluation of the unclassified tumors of the. Ovarian T u m o r Registry (1942-1952). Am. J. Ohstet. Gynecol., 87:999. 1963. 23. Schiflmann, J.: Postklimakterische Blutung und Brennerscher ovarial-tumor. Arch GynS.k.. 150:159, 1932. 24. Shay, M. D., and Janovs~, N. A.: Mangnant Brenner tumor associated with endometrial adeuocardinoma. Obstet. Gynecol., 22:246, 1963. 25. Silverberg, S. G.: Brenuer tumor of the ovary. Cancer, 28:588, 1971. 26. Silverberg. S. G., and Willson, M. A.: Uhrastructure of the Brenner tumor. Amer. J. Obstet. Gynecol., 112: 91, 1972. 27. Sternberg, W. I1.: Nonfunctioning Ovarian Neoplasms in the Ovary. Baltimore, Tile Williams & Wilkins Co., 1963, p. 209. 28. Teoh, T. B.: The histogenesis of Brenner tumors of the ovary, J. Path. Bact., 66:441, 1953. 29. Varden, L. C.: Bilateral Brenner tumors of the ovaries. *led. Ann. D. C., 33:70, 196t. 30. Von Numers, C.: A contribution to the case knowledge and histology of the Brenner tumor. Acta Obstet. Gynecol. Scand., 25(Suppl. 2):114, 1945.
MUCOCELE OF THE APPENDIX SECONDARY TO OBSTRUCTION BY ENDOMETRIOSIS MARC R. HAI'KE, M . D . , * AND BRADLEY BIGELOW, M.D.'~
Abstract
A mucocele of the appendix secondaO' to obstruction by endometriosis is reported and the relevant literature reviewed. The theories of the pathogenesis of appeudiceal mucocele are reviewed *Medical Fellow, I ) e l m r t m c n t o1 Lal)or;.ttory Medicine atttl l'athology (Surgical P,tthology), University o f M i n n e s o t a School o f Medicine, Minneapolis, Minnesota. tAssociate l'rofessor o f Pathology, New York University School o f Medicine, New York, New York.
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H U M A N P A T H O L O G Y - V O L U M E 8, NUMBER 5 and discussed. To our knowledge, no similar, well documented case has been reported. Mucocele of the appendix and involvement of the appendix by endometriosis are both relatively rare. A h h o u g h the coincidence of these two conditions has been sporadically mentioned in the literature, the anatomically well defined occurrence of a mucocele secondary to obstructing endometriosis of tltat organ has not, to our knowledge, been well substantiated. It forms the basis for tltis report.
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trophied smooth muscle, wlticlt accotmted for ntost of the enlargelnent of the distal appendix (Figs. 3,4). In one area Otis process impinged u p o n the appendiceal naucosa, which showed superficial ulceration and was continuous with the ntucus filled cyst (Figs. 5, 6). No hyperplastic or neoplastic epithelitun was seen. Tile mucocele extended proxintally within the submucosa, producing a convex projection of the mucosa (Figs. I, 2). A giant cell reaction was noted in the ulcerated mncosa continuous witlt the mucus cyst; otherwise no inflammation, was present.
C L I N I C A L SUMMARY A 31 year old nulliparous woman complained of dysmenorrltea of about six months' duration. O n exantination she had a tender fixed left adnexal mass. At exploratory laparotomy a cystic area of endometriosis 5 cm. in dianteter was excised from the left ovary. Sintilar though smaller areas of endometriosis were rentoved from the right ovary and several areas involving the cul de sac were cauterized. Because enlargement of the tip of the appendix was discovered on routine exploration, an appendectomy was also performed. PATHOLOGIC FINDINGS Specimens from both ovaries revealed ovarian tissue containing typical endontetrial glands and stronta with fresh as well as organizing hemorrhage. T h e tip of tile a p p e n d i x was dilated up to 2 cm. in diameter. O n section a I cm. mucus filled cyst was noted proximal to the dilated tip of the appendix. This cyst was s u r r o u n d e d distally by irregularly thickened appendiceal wall (Figs. I, 2). Multiple foci of endontetrial glands and stroma were associated witit hyper-
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DISCUSSION Mucocele of the appendix is reported to occur in 0.07 to 0.3 per cent of surgically removed appendices. 1'' Most of the cases are asymptomatic, as was the present one, unless complicated by rupture, inflantmation, or neoplasia. Considerable controversy exists in the literature over the pathogenesis of the lesion. T h e role of proximal obstrnction versus prinmry ntucosal alteration has long been debated. Woodruff and McDonald, 2 in a review of 146 appendiceal mucoceles, found tltat they could be separated into two groups: tltose containing a primary adenocarcinonta, grade I (probably corresponding to what is now referred to as mucinous cystadenoma), and "simple mucoceles." Of their cases 136 were classified as "simple mucocele" and were thought to have resulted front proximal inflammatory stricture of the appendix with scarring secondary to repeated attacks of mild acute inflammation. Tlmt this does in fact occur was pointed out by Aschoff 3 in the mid-1930s. This theory of the pathogenesis of appendiceal mucocele was set forth by FraenkeP at the turn of the century.
Figure 1, Gross picture of the distal appendix, sectioned longitudinally, with i)roximal cut edge at top. Hypertropllied muscle forms all irregular mass extending to lower right. The mucocele extends up proximally from center, in the st~bmucosa. Figure 2. Whole mount histological section of Figure 1, showing hypertrol)hied muscle, which envelops tile distal portion of the mucocele.' Figure 3, Endometrial glands and stroma, surrounded by hypertrol~hied muscle, in tile distal appendix. Figure 4. Higher power view of ectopic endometrium with surrotmding hypertrot)hied smooth muscle. Figure 5. Distal portion of mucocele in area of Figure 2 marked "X." Mucus and cell debris occupy the cavity. Residual mucosa is at left. A giant cell reaction replaces the ulcerated mueosa at lower right and tOll. Hypertroplfied musctdaris mucosae appears at bottom. Figure 6. This area of Figure 2, marked "XX," is slightly more proximal than that in Figure 5. The distal portion of the mucocele, at left, is separated from the main mncous cyst, at this level, by a central band of submucost. This submucosal band disappeared in deeper levels of tile block, however, demonstrating that there was a single, albeit somewhat tortuotts, mtlcus filled cavity. A giant cell reaction lines the cavity at left, whereas the mucus at right is only enclosed by stroma.
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Figures 1 through 6.
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H U M A N P A T H O L O G Y - - V O L U M E 8, N U M B E R 5
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I n 10 o f tile cases studied by W o o d r u f f and McDonald a p r i m a r y ntucosal abnornmlity o f the a p p e n d i x was found, and the histological descriptions and illustrations c o r r e s p o n d to what is now r e f e r r e d to as naucinous cystadenoma, a benign lesion?'H These authors believed that tiffs lesion r e p r e s e n t e d a primary malignant change in the appendiceal mucosa engrafted u p o n a pre-existing mucocele, which had resulted front obstruction secondary to inflammatory stricture. This hypothesis was based on the a p p e a r a n c e o f several o f their cases, which they i n t e r p r e t e d as transitional forms between benign a n d malignant mucoceles. T h e y f o u n d no cases o f p r i m a r y infiltrating adenocarcinoma o f the appendix. In support o f their obstructive theory they cited experiments with newborn rabbits conducted by Naeslund 7 in which mucocele and pseudomyxoma peritonei were p r o d u c e d by ligation o f the base o f the a p p e n d i x and transection just distal to the ligature. T h e distal stump closed over by grantdation tissue, and subsequently overgrowth o f mucosa resulted in mucocele or p s e u d o m y x o m a peritonei. More recently Wellss and Cheng ~ were able to produce mucoceles in rabbits by ligating the proximal s t u m p and leaving the vascular pedicle intact. T h o s e authors, who proposed an obstructive etiology, t e n d e d to minimize the mncosal abnormalities or believed that they were a secondary p h e n o m e n o n engrafted u p o n a pre-existing mucocele. 2'I~ T h e purely inflammatory mucocele was by far the most c o m m o n lesion in their reports. On the o t h e r hand, in m o r e recent work a primary mucosal abnormality has been stressed in the pathogenesis o f the lesion. Any obstruction that may have been present in the appendix was discounted a n d the mucosal abnorntality was stressed. In the 73 cases r e p o r t e d by Higa et al? mucinous cystadenonm was causal i n 4 6 , with rnucosal hyperplasia accounting for 18 and frankly invasive adenocarcinoma for nine. Obstruction was rare in those with only mucosal hyperplasia but was regularly present in the o t h e r two groups. Qizilbash H did not give the incidence o f obstruction in Iris 64 cases, but since the m o r p h o l o g T and relative incidence o f the three basic lesions thought to be responsible for the mucoceles were essentially similar to those r e p o r t e d by Higa et al.,5 one might also assume the incidence o f obstruction to be similar. It is also o f interest that the lesion called adenocarcinoma o f the a p p e n d i x , grade I, which accounted for only 7 p e r cent o f the cases o f mucocele in W o o d r u f f a n d McDonald's series 2 in 1940, is a p p a r e n t l y biologically and histologically identical to that called mucinous cystadenoma by the recent authors and that
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accounted for 65 per cent o f tile 120 mucoceles in these two recent series, s' 11 This may reflect a true increase in the incidence o f this benign a d e n o m a t o u s proliferation o f the appendix, analogous to the colonic villous a d e n o m a , but m o r e likely it reflects simply an increased recognition o f this as a true lesion and not as a normal variant. Higa et al., 5 in c o m m e n t i n g on tlte presence o f obstruction in their cases o f mucocele caused by mucinous cystadenoma o r carcinoma, noted that ill the absence o f infection obstruction of the appendiceal lumen results in only a mild dilatation and not in true mucocele. However, Clteng 9 was regularly able to produce a mucocele in rabbits by ligation o f the base o f the a p p e n d i x with preservation o f the vascular pedicle, if the lumen o f the a p p e n d i x was tltoroughly washed and the animal was treated with antibiotics to prevent infection. In fact, he pointed out that if these two precautions were not taken, the animals regularly developed gangrenous appendicitis and died in septic shock front peritonitis. In addition, Wells,s in studying the pathogenesis o f acute appendicitis, was able to p r o d u c e mucocele o f the a p p e n d i x by obstruction o f the appendiceal lumen only if infection did not supervene, which it most often did. Wangensteen and Dennis ~ have shown that the obstructed a p p e n d i x o f man secretes mucin at a higher rate than normal and may generate an intraluminal pressure greater than, or eqtml to, the systolic blood pressure. In this study all the patients went on to develop acute appendicitis without mucocele. It is possible, however, that slowly developing, intermittent obstruction over the course o f many )'ears would have resulted in the production o f an obstructive mucocele, as several authors have postulated. 2" 4, n T h u s it seems that the last word has yet to be written r e g a r d i n g the pathogenesis o f the appendiceal naucocele. It seems reasonable to assume that malt)" cases will prove to have an obstructive etiology, and a n u m b e r o f them nmy be secondary to a hyperplastic o r neoplastic alteration o f the a p p e n d i x itself. Since the pathogenetic mechanism in tiffs latter group, especially those with only mucosal hyperplasia, is not absolutely clear, a combination o f obstruction and mncosal alteration seems likely. I f increased mucus production by a b n o r m a l mucosa is the basic mechanism, the a p p e n d i x can presumably .empty itself o f excessive mncus tmless obstructed by an inspissated ping. T h e present case showed no hyperplastic or neoplastic changes o f the epithelium and is considered to be o f purely obstructive origin, secondary to endometriosis. T h e sequence o f
MEDICAL INTELLIGENCE events l e a d i n g to its p r o d u c t i o n is c o n s i d e r e d to be as follows: T h e e n d o m e t r i o s i s resulted in s m o o t h muscle h y p e r t r o p h y o f the a p p e n d i x , i n c l u d i n g the muscularis Inucosae, with obstruction o f s o m e o f the g l a n d crypts (Fig. 5). T h i s obstruction led to local i n c r e a s e d m u c i n p r o d u c t i o n with the p r o d u c t i o n o f m u l t i p l e small cysts. U h i m a t e l y coalescence o f these small cysts resulted in the single large one, which dissected t h r o u g h the s u b m u c o s a proximally (Figs. 1,2). E n d o m e t r i o s i s o f the a p p e n d i x is also a r a r e lesion. Most cases a r e associated with e n d o m e t r i o s i s in o t h e r pelvic a n d a b d o m i n a l structures. U o h a r a a n d K o b a r a ~a r e p o r t e d a 0.8 p e r cent i n c i d e n c e o f a p p e n d i c e a l e n d o metriosis in a p p r o x i m a t e l y 1500 a p p e n d e c tomies. T h i s figure m a y be artificially high, h o w e v e r , since the s u r g e r y was p e r f o r m e d in a hospital specializing in obstetrics a n d gynecology. Eight o f their 12 patients had e n d o metriosis d e m o n s t r a t e d elsewhere, usually in the ovaries. T h e f r e q u e n c y o f s y m p t o m a t o l o g y d u e to a p p e n d i c e a l e n d o m e t r i o s i s is a controversial m a t t e r in the literature, a n d is complicated by c o n f u s i o n with s y m p t o m s f r o m extraa p p e n d i c e a l endometriosis. T h e a p p e n d i x in t h e case u n d e r discussion was evidently asymptomatic. T w o r e p o r t s w e r e f o u n d that related appendiceal mucocele to endometriosis. 3 h e m i l t ~4 r e p o r t e d a m u c o c e l e that h e believed ,~as s e c o n d a r y to obstruction at the base o f the a p p e n d i x by fibrosis a n d e n d o m e t r i o s i s o f the cecnm. U n f o r t u n a t e l y his illustrations w e r e s o m e w h a t difficult to interpret. In his F i g u r e 170 he s h o w e d what was said to be t h e wall o f the c e c u m , at the base o f the a p p e n d i x , with two areas o f e n d o m e t r i o s i s within it. T h e l a r g e r o f the two glands was d e s c r i b e d as showing e n d o c e r v i c a l metaplasia, w h e r e a s the snmller was t h o u g h t to be typical e n d o m e t r i o s i s . T h e smaller g l a n d is acceptable as e n d o metriosis, for it s h o w e d what a p p e a r e d to be a small a m o u n t o f s t r o m a s u r r o u n d i n g it. However, the large g l a n d a p p e a r e d to us to be a colonic gland with changes consistent with hyperplasia o r neoplasia, as in a m u c i n o u s cystadenoma. It w o u l d seem, o n balance, that this m u c o c e l e may be related both to e n d o metriosis a n d to p r i m a r y mucosal alteration o f the cecum. Hilsabeck et al., 6 in s t u d y i n g a s~ries o f unusual mucoceles, m e n t i o n e d two cases associated with e n d o m e t r i o s i s . T h e y w e r e unable, h o w e v e r , to p r o v e that t h e e n d o m e triosis was pathogenetically i m p o r t a n t . T h u s , the p r e s e n t case a p p e a r s to us to be the only well d o c u m e n t e d e x a m p l e o f an obstructive m u c o c e l e s e c o n d a r y to e n d o m e t r i o s i s o f the a p p e n d i x . F u r t h e r m o r e , this m u c o c e l e
a p p e a r s to be p u r e l y obstrnctive a n d u n r e lated to any p r i m a r y mucosal a b n o r m a l i t y o f the a p p e n d i x .
References 1. Warren, S., and Warren, A. S.: A stud)' of 6797 surgically removed appendices. Ann. Surg., 83:222, 1926. 2. Woodruff, R., and McDonald,J. R.: Benign and malignant cystic tumors of the appendix. Surg. Gynecol. Obstet., 71:750, 19t0. 3. Aschoff, 1..: Appendicitis. Its Aeteriology and I'athology. (Translated by G. G. Pather.) London, Constable & Co., Ltd., 1932. 4. Fraeukel, E.: Ueber das sogennante pseudomyxoma peritonei. Munchen. Med. Wschr., 48:965, 1901. 5. ttiga, E., Rosai, J., Pizzimbono, C. A., and Wise, L.: Mucosal hyperplasia, mucinous cystadenoma, and mutinous cystadenocarcinoma of the appendix. A re-evaluation of appendiceal "'mucocele." Cancer, 32: 1525, 1973. 6. Hilsabeck, J. R., Woolner, I.. B., and Judd. E. S.: Some uncommon causes of appendiceal mucocele. Am. J. Surg.. 84:670. 1952. 7. Naesltmd, J.: Upsala Laekeref. Foerh., 34:1, 1928. (Quoted in Cheng, K. K., op. cit., and in Woodruff, R., and McDonald,J. R.,op. cit.). 8. Wells, A. Q.: Experimental lesions of the rabbit's appendix. Brit.J. Surg.,24:766, 1937. 9. Cheng, K. K.: An experimental stud)" of nmcocele of the appendix and pseudomyxoma peritonei. J. Pathol. Bacteriol., 61:217, 1949. 10. Woolner, L. B.: Carcinoma of the appendix. Comments on pathology. Proc. Staff Meet..Mayo Clin:, 28:17, 1953. 11. Qizilbasb, A. H.: Mucoceles of the appendix. Arch. Pathol., 99:548, 1975. 12. Wangensteen, O., and Dennis, C.: Experimental proof of the obstructive origin of appendicitis in man. Ann. Surg., 110:629, 1939. 13. Uohara, J. K., and Kobara, T. Y.: Endometriosis of the appendix. Amer. J. Obstet. Gynecol., 121~423, 1975. 14. Shemilt, P.: Endometrioma of the caecum causing muc~ cele of the appendix. Brit. J. Surg., 37:118, 1949.
NECROTIZlNG SlALOMETAPLASIA INVOLVING THE MUCOUS GLANDS OF THE NASAL CAVITY WILLIAM H. JOHNSTOX, M.D.*
Abstract
Necrotizing sialometaplasia was found in maxillary sitars mucous glamls of an 83 year old woman who had undergone a radical maxillectomy f o r basal cell carcinoma 10 days earlier. Previously recognized as an ulcerating lesion involving salivaly glands in the oral cavity, this ben~n reactive *Assistant Professor, Department of l'athology, School of Medicine, University of California, l.os Angeles, California.
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References 1~ Badway, R. E., Jorgenson, O. it., and Cromer, J. K.: Bilateral Brenner tumors--review of literature and report of case. Med. Ann. D. C.,33:106, 1964. 2. Brenner, F.: Das Oophoroma Folliculare. Frankfurt. Z. Path., 1:150, 1907. 3. Christian, C. D., andJanovski, N. A.: Bilateral Brenner tumors. Ant. J. Obstet. Gynecol., 83:105, 1962. -4. Epple, tl. tl., and Bossert, L. J.: Three simultaneous neoplasms of the female genitalia: a Brenner tumor, a pseuclomucinous cystadenocarcinoma of the contralateral ovary, and a squamous cell carcinoma of the cervix. Obstet. Gynecol., 11:661, 1958. 5. Farrar, tt. K.,Jr., and Greene, R. R.: Bilateral Brenner tumors of tile ovary. Am. J. Obstet. Gynecol., 80: 1089, 1960. 6. Gifford, A. B.," and Birch, tt. W.: Bilateral Brenner tumors of the ovary. J. Med. Assoc. Georgia, 58:145, 1969. 7. tlamwi, G.J., et al.: Testosterone synthesis by a Brenner tumor, Part 1. Clinical evidence of masculinization during pregnanc). Part Ii. In ~itro biosynthetic steroid conversion of a Brenner tumor. Am. J. Obstet. Gynecol., 86:!015, 1963. 8. tlertig, A. T., and Gore, I1.: Tumors of the ovary and fallopiaxt tube. In Atlas of T u m o r Pathology, Sec. I X, Fasc. 33. Washington, D. C., Armed Forces Institute of Pathology, 1961, p. 124. 9. llughesdon, P. E.: Thecal and allied reactions in epithelial ovarian turnouts. ]. Obstet. Gynecol. Brit. Emp., 65:702, 1958. 10. tlnll, M. G. R., and Campbell, G. R.: The ntalignant Brenner tumor. Obstet. Gynecol., 42:527,, 1973. 11. Idelson, M. G.: Malignancy in Brenner tumors of the ovary, with comments on histogenesis and possible estrogen production. Obstet. Gynecol. Survey, 18: 246, 1963. 12. Kendall, B., and Bowers, P. A.: Bilateral Brenner tumor of the ovaries. Am. J. Ohstet. Gynecol., 80:439, 1960. 13. Kismer, R. W.: Gynecolo~" Principles attd Practice. Ed. 2. Chicago, Year Book Medical Publishers, Inc., 1972, p. 409. 14. Kraus, F. T.: Gynecologic Pathology. St. Louis, The C. V. Mosby Company, 1967, pp. 324,313.
INTELLIGENCE
15. MacKinlay, C. J.: Brenner tumours of the ovary. J. Obstet. Gynecol. Brit. Emp., 65:58, 1056. 16. MacNaughtou-Jones, t1.: Uterine fibroid with an anomalous ovarian tnmour. Trails. Lond. Obstet. Soc., 40:154,213, 1898. 17. Meyer, R.: Uber verschiedene Erschlintmgsformen der als typus Brenner bekannten Eirstockageschwulst, ihre Zuordnung unter Andere Overialgerschwillste. Arch. G)naekol., 148:5tl, 1932. 18. Miles, 1'. A., Joj, M. C., and Norris, tt. J.: l'roliferative 9 and malignant Brenner tumors of the ovary. Cancer, 30:174, 1972. 19. Ming, S. C., and Goldman, tt4 tlormonal activity of Brenner tumors in postmenopausal women. Am. J. Obstet. Gynecol., 83:666, 1962. 20. Morris,J. M., and Scully, R. E.: Endocrine Pathology of the Ovary. St. Louis, Tile C. V. Mosby Co., 1958. 21. Novak, E. R., and Woodruff, J. D.: Novak's Gynecologic and Obstetric Pathotogy. Ed. 5. lqdladelphia. W. B. Saunders Company, 1962. 22. Novak, E. R., Woodruff, J. D., and Linthicum, J. M.: Evaluation of the unclassified tumors of the. Ovarian T u m o r Registry (1942-1952). Am. J. Ohstet. Gynecol., 87:999. 1963. 23. Schiflmann, J.: Postklimakterische Blutung und Brennerscher ovarial-tumor. Arch GynS.k.. 150:159, 1932. 24. Shay, M. D., and Janovs~, N. A.: Mangnant Brenner tumor associated with endometrial adeuocardinoma. Obstet. Gynecol., 22:246, 1963. 25. Silverberg, S. G.: Brenuer tumor of the ovary. Cancer, 28:588, 1971. 26. Silverberg. S. G., and Willson, M. A.: Uhrastructure of the Brenner tumor. Amer. J. Obstet. Gynecol., 112: 91, 1972. 27. Sternberg, W. I1.: Nonfunctioning Ovarian Neoplasms in the Ovary. Baltimore, Tile Williams & Wilkins Co., 1963, p. 209. 28. Teoh, T. B.: The histogenesis of Brenner tumors of the ovary, J. Path. Bact., 66:441, 1953. 29. Varden, L. C.: Bilateral Brenner tumors of the ovaries. *led. Ann. D. C., 33:70, 196t. 30. Von Numers, C.: A contribution to the case knowledge and histology of the Brenner tumor. Acta Obstet. Gynecol. Scand., 25(Suppl. 2):114, 1945.
MUCOCELE OF THE APPENDIX SECONDARY TO OBSTRUCTION BY ENDOMETRIOSIS MARC R. HAI'KE, M . D . , * AND BRADLEY BIGELOW, M.D.'~
Abstract
A mucocele of the appendix secondaO' to obstruction by endometriosis is reported and the relevant literature reviewed. The theories of the pathogenesis of appeudiceal mucocele are reviewed *Medical Fellow, I ) e l m r t m c n t o1 Lal)or;.ttory Medicine atttl l'athology (Surgical P,tthology), University o f M i n n e s o t a School o f Medicine, Minneapolis, Minnesota. tAssociate l'rofessor o f Pathology, New York University School o f Medicine, New York, New York.
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H U M A N P A T H O L O G Y - V O L U M E 8, NUMBER 5 and discussed. To our knowledge, no similar, well documented case has been reported. Mucocele of the appendix and involvement of the appendix by endometriosis are both relatively rare. A h h o u g h the coincidence of these two conditions has been sporadically mentioned in the literature, the anatomically well defined occurrence of a mucocele secondary to obstructing endometriosis of tltat organ has not, to our knowledge, been well substantiated. It forms the basis for tltis report.
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trophied smooth muscle, wlticlt accotmted for ntost of the enlargelnent of the distal appendix (Figs. 3,4). In one area Otis process impinged u p o n the appendiceal naucosa, which showed superficial ulceration and was continuous with the ntucus filled cyst (Figs. 5, 6). No hyperplastic or neoplastic epithelitun was seen. Tile mucocele extended proxintally within the submucosa, producing a convex projection of the mucosa (Figs. I, 2). A giant cell reaction was noted in the ulcerated mncosa continuous witlt the mucus cyst; otherwise no inflammation, was present.
C L I N I C A L SUMMARY A 31 year old nulliparous woman complained of dysmenorrltea of about six months' duration. O n exantination she had a tender fixed left adnexal mass. At exploratory laparotomy a cystic area of endometriosis 5 cm. in dianteter was excised from the left ovary. Sintilar though smaller areas of endometriosis were rentoved from the right ovary and several areas involving the cul de sac were cauterized. Because enlargement of the tip of the appendix was discovered on routine exploration, an appendectomy was also performed. PATHOLOGIC FINDINGS Specimens from both ovaries revealed ovarian tissue containing typical endontetrial glands and stronta with fresh as well as organizing hemorrhage. T h e tip of tile a p p e n d i x was dilated up to 2 cm. in diameter. O n section a I cm. mucus filled cyst was noted proximal to the dilated tip of the appendix. This cyst was s u r r o u n d e d distally by irregularly thickened appendiceal wall (Figs. I, 2). Multiple foci of endontetrial glands and stroma were associated witit hyper-
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DISCUSSION Mucocele of the appendix is reported to occur in 0.07 to 0.3 per cent of surgically removed appendices. 1'' Most of the cases are asymptomatic, as was the present one, unless complicated by rupture, inflantmation, or neoplasia. Considerable controversy exists in the literature over the pathogenesis of the lesion. T h e role of proximal obstrnction versus prinmry ntucosal alteration has long been debated. Woodruff and McDonald, 2 in a review of 146 appendiceal mucoceles, found tltat they could be separated into two groups: tltose containing a primary adenocarcinonta, grade I (probably corresponding to what is now referred to as mucinous cystadenoma), and "simple mucoceles." Of their cases 136 were classified as "simple mucocele" and were thought to have resulted front proximal inflammatory stricture of the appendix with scarring secondary to repeated attacks of mild acute inflammation. Tlmt this does in fact occur was pointed out by Aschoff 3 in the mid-1930s. This theory of the pathogenesis of appendiceal mucocele was set forth by FraenkeP at the turn of the century.
Figure 1, Gross picture of the distal appendix, sectioned longitudinally, with i)roximal cut edge at top. Hypertropllied muscle forms all irregular mass extending to lower right. The mucocele extends up proximally from center, in the st~bmucosa. Figure 2. Whole mount histological section of Figure 1, showing hypertrol)hied muscle, which envelops tile distal portion of the mucocele.' Figure 3, Endometrial glands and stroma, surrounded by hypertrol~hied muscle, in tile distal appendix. Figure 4. Higher power view of ectopic endometrium with surrotmding hypertrot)hied smooth muscle. Figure 5. Distal portion of mucocele in area of Figure 2 marked "X." Mucus and cell debris occupy the cavity. Residual mucosa is at left. A giant cell reaction replaces the ulcerated mueosa at lower right and tOll. Hypertroplfied musctdaris mucosae appears at bottom. Figure 6. This area of Figure 2, marked "XX," is slightly more proximal than that in Figure 5. The distal portion of the mucocele, at left, is separated from the main mncous cyst, at this level, by a central band of submucost. This submucosal band disappeared in deeper levels of tile block, however, demonstrating that there was a single, albeit somewhat tortuotts, mtlcus filled cavity. A giant cell reaction lines the cavity at left, whereas the mucus at right is only enclosed by stroma.
MEDICAL I N T E L L I G E N C E
Figures 1 through 6.
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H U M A N P A T H O L O G Y - - V O L U M E 8, N U M B E R 5
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I n 10 o f tile cases studied by W o o d r u f f and McDonald a p r i m a r y ntucosal abnornmlity o f the a p p e n d i x was found, and the histological descriptions and illustrations c o r r e s p o n d to what is now r e f e r r e d to as naucinous cystadenoma, a benign lesion?'H These authors believed that tiffs lesion r e p r e s e n t e d a primary malignant change in the appendiceal mucosa engrafted u p o n a pre-existing mucocele, which had resulted front obstruction secondary to inflammatory stricture. This hypothesis was based on the a p p e a r a n c e o f several o f their cases, which they i n t e r p r e t e d as transitional forms between benign a n d malignant mucoceles. T h e y f o u n d no cases o f p r i m a r y infiltrating adenocarcinoma o f the appendix. In support o f their obstructive theory they cited experiments with newborn rabbits conducted by Naeslund 7 in which mucocele and pseudomyxoma peritonei were p r o d u c e d by ligation o f the base o f the a p p e n d i x and transection just distal to the ligature. T h e distal stump closed over by grantdation tissue, and subsequently overgrowth o f mucosa resulted in mucocele or p s e u d o m y x o m a peritonei. More recently Wellss and Cheng ~ were able to produce mucoceles in rabbits by ligating the proximal s t u m p and leaving the vascular pedicle intact. T h o s e authors, who proposed an obstructive etiology, t e n d e d to minimize the mncosal abnormalities or believed that they were a secondary p h e n o m e n o n engrafted u p o n a pre-existing mucocele. 2'I~ T h e purely inflammatory mucocele was by far the most c o m m o n lesion in their reports. On the o t h e r hand, in m o r e recent work a primary mucosal abnormality has been stressed in the pathogenesis o f the lesion. Any obstruction that may have been present in the appendix was discounted a n d the mucosal abnorntality was stressed. In the 73 cases r e p o r t e d by Higa et al? mucinous cystadenonm was causal i n 4 6 , with rnucosal hyperplasia accounting for 18 and frankly invasive adenocarcinoma for nine. Obstruction was rare in those with only mucosal hyperplasia but was regularly present in the o t h e r two groups. Qizilbash H did not give the incidence o f obstruction in Iris 64 cases, but since the m o r p h o l o g T and relative incidence o f the three basic lesions thought to be responsible for the mucoceles were essentially similar to those r e p o r t e d by Higa et al.,5 one might also assume the incidence o f obstruction to be similar. It is also o f interest that the lesion called adenocarcinoma o f the a p p e n d i x , grade I, which accounted for only 7 p e r cent o f the cases o f mucocele in W o o d r u f f a n d McDonald's series 2 in 1940, is a p p a r e n t l y biologically and histologically identical to that called mucinous cystadenoma by the recent authors and that
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accounted for 65 per cent o f tile 120 mucoceles in these two recent series, s' 11 This may reflect a true increase in the incidence o f this benign a d e n o m a t o u s proliferation o f the appendix, analogous to the colonic villous a d e n o m a , but m o r e likely it reflects simply an increased recognition o f this as a true lesion and not as a normal variant. Higa et al., 5 in c o m m e n t i n g on tlte presence o f obstruction in their cases o f mucocele caused by mucinous cystadenoma o r carcinoma, noted that ill the absence o f infection obstruction of the appendiceal lumen results in only a mild dilatation and not in true mucocele. However, Clteng 9 was regularly able to produce a mucocele in rabbits by ligation o f the base o f the a p p e n d i x with preservation o f the vascular pedicle, if the lumen o f the a p p e n d i x was tltoroughly washed and the animal was treated with antibiotics to prevent infection. In fact, he pointed out that if these two precautions were not taken, the animals regularly developed gangrenous appendicitis and died in septic shock front peritonitis. In addition, Wells,s in studying the pathogenesis o f acute appendicitis, was able to p r o d u c e mucocele o f the a p p e n d i x by obstruction o f the appendiceal lumen only if infection did not supervene, which it most often did. Wangensteen and Dennis ~ have shown that the obstructed a p p e n d i x o f man secretes mucin at a higher rate than normal and may generate an intraluminal pressure greater than, or eqtml to, the systolic blood pressure. In this study all the patients went on to develop acute appendicitis without mucocele. It is possible, however, that slowly developing, intermittent obstruction over the course o f many )'ears would have resulted in the production o f an obstructive mucocele, as several authors have postulated. 2" 4, n T h u s it seems that the last word has yet to be written r e g a r d i n g the pathogenesis o f the appendiceal naucocele. It seems reasonable to assume that malt)" cases will prove to have an obstructive etiology, and a n u m b e r o f them nmy be secondary to a hyperplastic o r neoplastic alteration o f the a p p e n d i x itself. Since the pathogenetic mechanism in tiffs latter group, especially those with only mucosal hyperplasia, is not absolutely clear, a combination o f obstruction and mncosal alteration seems likely. I f increased mucus production by a b n o r m a l mucosa is the basic mechanism, the a p p e n d i x can presumably .empty itself o f excessive mncus tmless obstructed by an inspissated ping. T h e present case showed no hyperplastic or neoplastic changes o f the epithelium and is considered to be o f purely obstructive origin, secondary to endometriosis. T h e sequence o f
MEDICAL INTELLIGENCE events l e a d i n g to its p r o d u c t i o n is c o n s i d e r e d to be as follows: T h e e n d o m e t r i o s i s resulted in s m o o t h muscle h y p e r t r o p h y o f the a p p e n d i x , i n c l u d i n g the muscularis Inucosae, with obstruction o f s o m e o f the g l a n d crypts (Fig. 5). T h i s obstruction led to local i n c r e a s e d m u c i n p r o d u c t i o n with the p r o d u c t i o n o f m u l t i p l e small cysts. U h i m a t e l y coalescence o f these small cysts resulted in the single large one, which dissected t h r o u g h the s u b m u c o s a proximally (Figs. 1,2). E n d o m e t r i o s i s o f the a p p e n d i x is also a r a r e lesion. Most cases a r e associated with e n d o m e t r i o s i s in o t h e r pelvic a n d a b d o m i n a l structures. U o h a r a a n d K o b a r a ~a r e p o r t e d a 0.8 p e r cent i n c i d e n c e o f a p p e n d i c e a l e n d o metriosis in a p p r o x i m a t e l y 1500 a p p e n d e c tomies. T h i s figure m a y be artificially high, h o w e v e r , since the s u r g e r y was p e r f o r m e d in a hospital specializing in obstetrics a n d gynecology. Eight o f their 12 patients had e n d o metriosis d e m o n s t r a t e d elsewhere, usually in the ovaries. T h e f r e q u e n c y o f s y m p t o m a t o l o g y d u e to a p p e n d i c e a l e n d o m e t r i o s i s is a controversial m a t t e r in the literature, a n d is complicated by c o n f u s i o n with s y m p t o m s f r o m extraa p p e n d i c e a l endometriosis. T h e a p p e n d i x in t h e case u n d e r discussion was evidently asymptomatic. T w o r e p o r t s w e r e f o u n d that related appendiceal mucocele to endometriosis. 3 h e m i l t ~4 r e p o r t e d a m u c o c e l e that h e believed ,~as s e c o n d a r y to obstruction at the base o f the a p p e n d i x by fibrosis a n d e n d o m e t r i o s i s o f the cecnm. U n f o r t u n a t e l y his illustrations w e r e s o m e w h a t difficult to interpret. In his F i g u r e 170 he s h o w e d what was said to be t h e wall o f the c e c u m , at the base o f the a p p e n d i x , with two areas o f e n d o m e t r i o s i s within it. T h e l a r g e r o f the two glands was d e s c r i b e d as showing e n d o c e r v i c a l metaplasia, w h e r e a s the snmller was t h o u g h t to be typical e n d o m e t r i o s i s . T h e smaller g l a n d is acceptable as e n d o metriosis, for it s h o w e d what a p p e a r e d to be a small a m o u n t o f s t r o m a s u r r o u n d i n g it. However, the large g l a n d a p p e a r e d to us to be a colonic gland with changes consistent with hyperplasia o r neoplasia, as in a m u c i n o u s cystadenoma. It w o u l d seem, o n balance, that this m u c o c e l e may be related both to e n d o metriosis a n d to p r i m a r y mucosal alteration o f the cecum. Hilsabeck et al., 6 in s t u d y i n g a s~ries o f unusual mucoceles, m e n t i o n e d two cases associated with e n d o m e t r i o s i s . T h e y w e r e unable, h o w e v e r , to p r o v e that t h e e n d o m e triosis was pathogenetically i m p o r t a n t . T h u s , the p r e s e n t case a p p e a r s to us to be the only well d o c u m e n t e d e x a m p l e o f an obstructive m u c o c e l e s e c o n d a r y to e n d o m e t r i o s i s o f the a p p e n d i x . F u r t h e r m o r e , this m u c o c e l e
a p p e a r s to be p u r e l y obstrnctive a n d u n r e lated to any p r i m a r y mucosal a b n o r m a l i t y o f the a p p e n d i x .
References 1. Warren, S., and Warren, A. S.: A stud)' of 6797 surgically removed appendices. Ann. Surg., 83:222, 1926. 2. Woodruff, R., and McDonald,J. R.: Benign and malignant cystic tumors of the appendix. Surg. Gynecol. Obstet., 71:750, 19t0. 3. Aschoff, 1..: Appendicitis. Its Aeteriology and I'athology. (Translated by G. G. Pather.) London, Constable & Co., Ltd., 1932. 4. Fraeukel, E.: Ueber das sogennante pseudomyxoma peritonei. Munchen. Med. Wschr., 48:965, 1901. 5. ttiga, E., Rosai, J., Pizzimbono, C. A., and Wise, L.: Mucosal hyperplasia, mucinous cystadenoma, and mutinous cystadenocarcinoma of the appendix. A re-evaluation of appendiceal "'mucocele." Cancer, 32: 1525, 1973. 6. Hilsabeck, J. R., Woolner, I.. B., and Judd. E. S.: Some uncommon causes of appendiceal mucocele. Am. J. Surg.. 84:670. 1952. 7. Naesltmd, J.: Upsala Laekeref. Foerh., 34:1, 1928. (Quoted in Cheng, K. K., op. cit., and in Woodruff, R., and McDonald,J. R.,op. cit.). 8. Wells, A. Q.: Experimental lesions of the rabbit's appendix. Brit.J. Surg.,24:766, 1937. 9. Cheng, K. K.: An experimental stud)" of nmcocele of the appendix and pseudomyxoma peritonei. J. Pathol. Bacteriol., 61:217, 1949. 10. Woolner, L. B.: Carcinoma of the appendix. Comments on pathology. Proc. Staff Meet..Mayo Clin:, 28:17, 1953. 11. Qizilbasb, A. H.: Mucoceles of the appendix. Arch. Pathol., 99:548, 1975. 12. Wangensteen, O., and Dennis, C.: Experimental proof of the obstructive origin of appendicitis in man. Ann. Surg., 110:629, 1939. 13. Uohara, J. K., and Kobara, T. Y.: Endometriosis of the appendix. Amer. J. Obstet. Gynecol., 121~423, 1975. 14. Shemilt, P.: Endometrioma of the caecum causing muc~ cele of the appendix. Brit. J. Surg., 37:118, 1949.
NECROTIZlNG SlALOMETAPLASIA INVOLVING THE MUCOUS GLANDS OF THE NASAL CAVITY WILLIAM H. JOHNSTOX, M.D.*
Abstract
Necrotizing sialometaplasia was found in maxillary sitars mucous glamls of an 83 year old woman who had undergone a radical maxillectomy f o r basal cell carcinoma 10 days earlier. Previously recognized as an ulcerating lesion involving salivaly glands in the oral cavity, this ben~n reactive *Assistant Professor, Department of l'athology, School of Medicine, University of California, l.os Angeles, California.
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