Chondrosarcoma of the uterus: Report of a case and review of the literature

H U M A N P A T H O L O G Y - V O L U M E 9, NUMBER 6

CHONDROSARCOMA OF THE UTERUS: REPORT OF A CASE AND REVIEW OF THE LITERATURE PtIILIP B. CLEMENT, M.D.*

Abstract The clinical and pathologic features of a Case of primary chondrosarcoma of the uterus and 12 previously described similar cases are reviewed. Pathologically the tumors resemble chondrosarcoma of bone. The clinical features, including a higiz degree of malignancy, resemble those of other types of pure heterologous sarcomas and the typical miillerian mixed tumors of the uterus. Chondrosarcoma in the uterus most commonly takes the form o f a heterologous type o f m~llerian mixed tumor, in which the chondrosarcoma is admixed with a carcinomatous component. In such tumors other hbterologous stromal elements (rhabdomyosarcoma, osteosarcoma) or homologous stromal elements (endometrial stromal sarcoma, leiomyosarcoma) may also be present. A muclt rarer uterine tumor is one composed predominantly or entirely of chondrosarcoma without the presence o f epithelial or other heterologous mesenchymal elements. T h e purpose of this report is to describe the clinical and pathologic features o f a recently encountered case of uterine chondrosarcoma, and to review the world's literature relating to previously described sintilar tumors. CASE H I S T O R Y A 59 )'ear old white female (gravida two, para two), during the course o f investigation o f an enlarged thyroid, was found to have an abdominal mass. T h e patient had been aware o f the mass for an indefinite period o f time. Pelvic examinatiofi revealed a uterus enlarged to the size of a 20 week gestation, and the clinical diagnosis was uterine leiomyomas. A laparotomy revealed a massively enlarged uterus, but the other pelvic and abdominal organs were negative. No evidence o f extrauterine tumor was seen and a total abdominal hysterectomy with bilateral salpingooophorectomy was performed. Tile patient had an uneventful postoperative course. She remained well until six months later, when

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*Clinical Assistant Professor, Department of Pathology, Faculty of Medicine, University of British Columbia. Associate Pathologist, Vancouver General Hospital, Vancouver, British Columbia, Canada.

November 1978

she was readmitted to the hospital with syrup. toms and signs o f small bowel obstruction. A laparotomy revealed a large peMc tumor, which incorporated loops o f small bowel and a part of the sigmoid colon. A bypass side to side ileoileostomy and transverse colostomy were performed. Tile patient had a stormy postoperative course, developed gram negative septicemia, and expired 10 days later. An autopsy was performed. PATHOLOGY Tile hysterectomy specimen with attached tubes and ovaries weighed 1945 gin. The uterus was markedly enlarged and distorted by a spherical, poorly circumscribed mural mass 17 cm. in diameter replacing most of the myometrium, although focally a small rim of compressed myometrium was discernible around tile tumor. T h e endometrial cavity was displaced and compressed by the tnmor and was lined by an atrophic mucosa. Most of the cut surface o f the tumor tiad a cartilaginous appearance, being composed oflobules of hard gray translucent tissue with convoluted borders (Fig. 1). There were focal areas of cystic degeneration and calcification within the tnmor. T h e gross appearance o f the tumor was strikingly similar to that of chondrosarcoma o f bone. T h e small area o f myometrium uninvolved by tumor was unremarkable except for several well circumscribed nodules consistent with leiomyomas. T h e cen'ix, tubes, and ovaries were grossly unremarkable. Microscopically 25 sections revealed the tumor to be composed almost completely of chondrosarcoma, which varied from well to poorly differentiated. T h e c h o n d r o s a r c o m a generally grew in large lobules but focally formed trabeculae, which were calcified superficially so as to resemble the zone of provisional calcification at an epiphysis (Figs. 2, 3). In numerous areas the chondrosarcoma histologically merged with undifferentiated sarcoma composed of bizarre pleomorphic spindle-and giant cells (Fig. 4). In several sections areas of cllondrosarcoma were surrounded by foci of pleomorphic, mitotically active smooth muscle cells with the appearance o f leiomyosarcoma on both sections stained with hematoxylin and eosin and Masson's trichrome. At the periphery of the tumor there was infiltration of the surrounding myometrium and myometrial vascular and lymphatic ctmnnels, especially by the undifferentiated sarcomatous element. T h e r e was extensive tumor necrosis and hyalinization. No epithelial elements were present histologically. T h e other myometrial nodules were typical leiomyomas. T h e endometrium was atrophic and the cervix, tubes, and ovaries were unremarkable.

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November 1978

Figure 3. Sheets of chondrosarcoma merging with tumor growing in trabeculae, which are focally calcified, resembling the zone of provisional calcification at an epiphysis. (x ! 13,)

728

At necropsy, opening o f the peritoneal cavity revealed purulent ascitic fluid. T h e r e was a necrotic mass o f tumor 11 cm. in diameter in the pelvis to which several loops of small bowel and a portion o f the sigmoid colon were adherent, although no obvious site o f bowel perforation could be identified. T h e mass invaded anteriorly into the walls of tile bladder and vagina and compressed the distal portion of the left ureter. A 3 cm. necrotic nodule o f tumor was found subperitoneally in the anterior abdominal wall. The right lung contained two grossly cartilaginous subpleural nodules measuring 1.5 and 0.5 cm. Numerous similar smaller nodules were seeded subpleurally throughout both lungs. T h e right lobe of the thyroid was almost completely replaced by an encapsulated mass 6 cm. in diameter, which compressed a small rim o f normal thyroid tissue surrounding it. T h e cut surface of the mass was solid, homogeneous, fleshy, and red-brown, except for a grossly cartilaginous 0.3 cm. nodule in the center of the mass. Histologically the persistent tumor in the abdomen was ahnost completely necrotic, and viable tumor was composed o f poorly differentiated chondrosarcoma and undifferen-

tiated sarcoma. Metastatic tumor in tile lungs was composed of moderately well differentiated chondrosarcoma. T h e mass in the right lobe o f the thyroid proved to be an oxyphilic type of follicular adenoma, which contained in its center a metastatic n o d u l e of well differentiated chondrosarcoma. DISCUSSION Uterine sarcomas composed predominantly o f heterologous elements and lacking an epithelial component are extremely rare. 1 Such pure heterologous sarcomas include, in order of their, frequency, rhabdomyosarcoma, chondrosarcoma, and osteosarcoma. 2 No cases of uterine liposarcoma have yet been reported. T h e recently encountered case of uterine chondrosarcoma described in this report prompte d a search of the literature for similar tumors in an attempt to define their clinical and pathologic features. Only single case reports, mostly in the older literature, could be found, the most recent case being described in 1951. 3"14 Criteria for inclusion in this series included a predominant component of chondrosarcoma, an absence o f benign or malignant glandular elements (thus eliminating all

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Figure 4. Poorly differentiated chondrosarcoma (upper right) merging with areas of undifferentiated sarcoma composed of spindle and giant ceils. (x 206.)

types o f mixed miillerian tumors), and an absence o f other specific heterologous elements. T u m o r s that fulfilled tile foregoing criteria but contained in addition areas r e f e r r e d to as "fibrosarcoma," o r components described by such nonspecific terms as "spindle cell sarcoma, . . . . myxosarcoma," " r o u n d cell sarcoma," and "pleomorphic sarcoma" were not excluded, as these components could represent areas o f poorly differentiated o~' "dedifferentiated" chondrosarcoma. '~ No cases o f chondrosarcoma mixed with homologous sarcomatous elements (endometrial stromal sarcoma, leiomyosarcoma) were found. A n u m b e r o f tumors that were labeled and may have r e p r e s e n t e d examples o f uterine c h o n d r o s a r c o m a were not included in the study because o f inadequate descriptive o r p h o t o g r a p h i c d o c u m e n t a t i o n o f the histologic appearance, o r because the tumor was so extensively necrotic that the true histologic composition o f the t u m o r could not be d e t e r m i n e d . Including tile present case, 13 tumors fulfilling the foregoing criteria were found.

A variety o f c o m m o n clinical and pathologic features e m e r g e d from an analysis o f the 13 cases (Table 1). T h e patients generally presented in the fifth to seventh decades (average age, 53 years; range, 36 to 66 years). O f the 12 patients in whom symptoms are known, 10 presented with abnormal vaginal bleeding; in addition two o f these patients complained o f abdominal pain. O n e patient complained o f dysuria a n d vaginal discharge. Only the present patient was asymptomatic. Tlle obstetrical history was known ]n 11 cases; four patients were nulligravida, the r e m a i n d e r ranging from gravida three to 13. O f the three patients in whom the race was stated, two were white a n d one was black. Pelvic examination generally revealed an enlarged nterus, and in five cases t u m o r was visible p r o t r u d i n g t h r o u g h the external os into the vagina. Eleven patients underwent some form o f hysterectomy and two were treated only by curettage (Table 1). At the time o f surgery the uteri in almost all cases were enlarged, but in no case was there a p p a r e n t spread o f the

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t u m o r b e y o n d the uterus. Follow-up i n f o r m a tion was available in n i n e o f t h e 13 cases. With t h e e x c e p t i o n o f o n e patient w h o d i e d two days postoperatively a n d a n o t h e r w h o was alive a n d well eight m o n t h s postoperatively, the patients d i e d f r o m r e c u r r e n t o r metastatic t u m o r , o r both, at p o s t o p e r a t i v e intervals o f f o u r to 23 m o n t h s . Six o f the seven d e a t h s occ u r r e d within 13 m o n t h s following surgery. Grossly the t u m o r s a p p e a r e d to arise f r o m the e n d o m e t r i u m in 10 cases, generally f o r m i n g large p o l y p o i d masses, which projected into the e n d o m e t r i a l cavity but usually e x h i b i t e d invasion o f the u n d e r l y i n g m y o m e trium. I n t h r e e cases (cases 11, 12, a n d 13) the t u m o r s w e r e c o n s i d e r e d to be o f m y o m e t r i a l origin, b u t in two o f these t u m o r p r o t r u d e d into the e n d o m e t r i a l cavity. T h e p r e s e n t case was u n i q u e in that it a p p e a r e d to be c o n f i n e d to the m y o m e t r i u m . T h e t u m o r s w e r e usually grossly cartilaginous with areas o f calcification a n d cystic d e g e n e r a t i o n . In f o u r cases u n r e m a r k a b l e l e i o m y o m a s w e r e also present. Histologically the c h o n d r o s a r c o m a was usually well o r m o d e r a t e l y well d i f f e r e n t i a t e d , but generally m e r g e d with m o r e cellular, nonspecialized, mitotically active s a r c o m a in which the t u m o r cells w e r e s p i n d l e s h a p e d o r large a n d p o l y g o n a l with m u l t i p l e nuclei. Myxoid areas in which the t u m o r c e l l s w e r e stellate a n d m o r e sparsely distributed were c o m m o n l y described. T h e p r e s e n t t u m o r was the only o n e to contain areas o f h o m o l o g o u s s a r c o m a (leiomyosarcoma), but these foci w e r e so m i n o r quantitatively that a d e s i g n a t i o n o f mixed heterologous-homologous sarcoma seems u n w a r r a n t e d . T h e r e c u r r e n t o r metastatic t u m o r generally r e s e m b l e d the p r i m a r y t u m o r histologically. O f the six cases in which metastatic o r r e c u r r e n t t u m o r was available for histologic e x a m i n a t i o n , two w e r e c o m posed only of nonspecialized sarcoma, w h e r e a s in the r e m a i n i n g f o u r cases the rec u r r e n t o r metastatic t u m o r was c o m p o s e d o f both c h o n d r o s a r c o m a a n d nonspecialized sarcoma. U t e r i n e c h o n d r o s a r c o m a is a r a r e t u m o r r e p r e s e n t i n g a distinct type o f p u r e h e t e r o l o gnus s a r c o m a o f t h e uterus. Grossly a n d microscopically it resembles c h o n d r o s a r c o m a o f bone. Its p r e s e n t a t i o n in m i d d l e a g e d and elderly w o m e n with a b n o r m a l vaginal b l e e d i n g a n d its highly m a l i g n a n t b e h a v i o r d o not d i f f e r significantly f r o m t h e clinical f e a t u r e s of other forms of pure heterologous uterine sarcomas ( r h a b d o m y o s a r c o m a and osteosarcoma) o r f r o m typical mfillerian m i x e d t u m o r s o f the u t e r u s ? " tr-~_0T r e a t m e n t s h o u l d i n c l u d e surgical r e m o v a l o f the t u m o r in the f o r m o f total a b d o m i n a l h y s t e r e c t o m y and bilateral s a l p i n g o - o o p h o r e c t o m y . Conclusions as to the efficacy o f r a d i o t h e r a p y o r c h e m o t h e r a p y cannot be d r a w n on the basis o f this study.

Not,ember 1978

T h e histogenesis o f p u r e heterologous sarcomas a n d h e t e r o l o g o u s e l e m e n t s in mill. lerian m i x e d t u m o r s is u n k n o w n . T h e most p o p u l a r hypothesis is an o r i g i n f r o m rectaplastic e n d o m e t r i a l stromal cells, which are believed to be mutipotential. T h i s theory w o u l d account for the a p p a r e n t endometrial origin o f m o s t o f these t u m o r s ; the r a r e occ u r r e n c e o f such t u m o r s within the m y o m e . t r i u m (as in the p r e s e n t case) could b e exp l a i n e d by origin f r o m areas o f adenomyosis, s t r o m a l myosis, o r e n d o m e t r i o s i s o r from m u l t i p o t e n t i a l cells within the m y o m e t r i u m . References 1. Kempson, R. L., and Bari, W.: Uterine sarcomas. Classification, diagnosis and prognosis. Human Path., 1:331-349, 1970. 2. Ober, W. B.: Uterine sarcomas: histogenesis and taxonomy. Ann. N.Y. Acad. Sci., 75:568-585, 1959. 3. Wagner, E.: Verjauchende Enchondrome des Uterus, Lungenenchondrome, h~sche Peritonitis. Der GebSrmutterkrebs. Leipzig, 1854, p. 129. 4. Williams,J. W.: Contributions to the histology and histogenesis of sarcoma of the uterus. Am. J. Obstet. Gynec., 29:721-76.t, 189t. 5. Geisler, A.: 1]ber Sarkoma Uteri. Thesis, Breslau, 1892, pp. 10-12. 6. Seydel, O.: Ein enchondrom des Uterus. Ein Beitrag zur Genese der Mischtumoren des Uterus. Ztschr. Geburtsch. G)'nlik., 45:237-271, 1901. 7. Reid, W. L.: Notes on a case of chnndrosarcoma of the uterus. Glasgow Med. J., 57:371-374, 1902. 8. Malapert, P., and Morichau-Beauchant, R.: Tumeur conjonctive mixte (myxo-chondro-sarcome) de 1'uterus. Bull. Mrm. Soc. Anat. Paris, 80:391, 1905. 9. Perlstein, I.: The mesodermal mixed tumors of the uterus. Report of a case of botrioid chondrosarcoma of the endometrium. Surg. Gynec. Obstet., 28:43-55, 1919. 10. Van Akkeren, R.: Zwei seltene Falle yon Gebfirmuttergeschwulst. Zentralbl. Gynfik.,54:905--913, 1930. 11. Rankin, F. W., and Broders, A. C.: Primary fibromyxochondrosarcoma, of endometrial stroma. Am. J. Surg., 12:74-75, 1931. 12. Hartfall, S. J.: Chondro-sarcoma of the uterus. J. r Obst. Gynaec. Brit. Emp., 38:593-600, 1931. 13. Liebow, A. A., and Tennant, R.: Mesodermal mixed tumors of the body of the uterus. Am. J. Path., 17:130, 1941. 14. Pefia, E. F.: Primary chondrosarcoma of the uterus. Am.J. Obstet. Gynec., 61:461-464, 1951. 15. Sl!ittt. II..1.. Dorftnan, tl. D., Feclmer. R. E., and Ackerman, L. V.: Tumors of Bone and Cartilage. Atlas of Tumor Pathology, Second Series, Fascicle 5. Washington, D. C., Armed Forces Institute of Pathology, 1971. 16. Donkers, B., Kazzaz, B. A., and .Me~jering, J. H.: Rhabdomyosarcoma of the corpus uteri. Am. J. Obstet. Gynec., 114:1025-1030, 1972. 17. Scheffey, U C., Le~Snson, J., Herhut, P. A,, Hepler, T. K., and Gilmore, G. H.: Osteosarcoma of the uterus. Report of a case. Obstet. Gynec., 8:444-450, 1956. 18. Carleton, C. C., and Williamson, J. W.: Osteogenic sarcoma of the uterus. Arch. Path., 72:121-125 1961. 19. Amromin, G. C., and Gildenhorn, H. L.: Review of pathogenesis of primary osteogenic sarcoma of the uterus and adnexa. Am. J. Obstet. Gynec., 83:15741578, 1962. 20. Karpas, C. M., and Merendino, V.J.: Uterine osteogenic sarcoma: histochemical studies and report of a case. Obstet. Gynec., 24:629-633, 1964.